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REVIEW OF MBS COLONOSCOPY ITEMS

PREPARED BY DLA PIPER AUSTRALIAFOR THE DEPARTMENT OF HEALTH AND AGEING

Review of MBS Colonoscopy items

TABLE OF CONTENTS

Terms and abbreviations used in this review......................................................................................1

Summary of findings of the review..................................................................................................2

Background........................................................................................................................................7Guidance for colonoscopy in Australia......................................................................................7International guidance for colonoscopy......................................................................................8Justification for this review......................................................................................................10

Clinical and research questions addressed in this review............................................................11

Literature review methods..............................................................................................................12Types of studies considered for the review..............................................................................12Search strategies for identifying studies...................................................................................13Search terms for identifying studies.........................................................................................13Study selection..........................................................................................................................13Data extraction..........................................................................................................................14Quality assessment of studies...................................................................................................14Data analysis.............................................................................................................................14

Factors affecting rates of colonoscopy...........................................................................................15

Analysis of Medicare data...............................................................................................................17Key trends in MBS utilisation of colonoscopy and related items............................................17

Systematic review of the literature - results of search strategy...................................................22Introduction...............................................................................................................................22Findings for individual clinical and research questions...........................................................22

Question 1 - For patients with non-acute indications for colonoscopy, what is the appropriate timing between colonoscopies?....................................................................23

Question 1a: Patients with a family history of bowel cancer.................................24Question 1b: Patients with a genetic predisposition to bowel cancer....................26Question 1c: Patients with inflammatory bowel disease........................................28Question 1d: Older people.....................................................................................30Question 1e: Patients with a past history of bowel cancer.....................................31Question 1f: Patients with a past history of adenoma............................................36MBS data for timing of colonoscopy......................................................................39

Question 2 - What is the effectiveness of colonoscopy in improving outcomes in each target population?.............................................................................................................40

Question 2a: What is the effectiveness of colonoscopy in cancer prevention?.....41Question 2b: What is the effectiveness of colonoscopy in diagnosis of pathology in symptomatic patients?.............................................................................................45Question 2c: What is the likelihood of a single colonoscopy leading to the detection of an adenoma and / or colorectal cancer?..............................................................47Question 2d: What is the relationship between appropriateness criteria for colonoscopy and diagnostic yield?..........................................................................48

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Question 3: How do safety and quality outcomes of colonoscopy vary according to the procedural volumes of colonoscopists and with certification / re-certification processes?..........................................................................................................................................49

Question 3a: How do safety and quality outcomes of colonoscopy vary according to the procedural volumes of colonoscopists?.............................................................49Question 3b: How do safety and quality outcomes of colonoscopy vary according to certification / re-certification processes?............................................................52

Question 4 - How cost-effective is colonoscopy in each target population?...................53Question 5 - Are all patient groups in whom colonoscopy should be used able to access colonoscopy?....................................................................................................................55

Question 5a - What are the factors that influence access to colonoscopy?.............55Question 5b: What is the evidence for interventions that improve access to colonoscopy services?.............................................................................................58Question 5c: What is the impact of open access service configuration on access to colonoscopy services?.............................................................................................59

Consumer perspectives.............................................................................................................60

Discussion.........................................................................................................................................61General findings........................................................................................................................61Implications for the MBS - colonoscopy in individuals with no known risk factors and no relevant symptoms....................................................................................................................63Implications for the MBS - colonoscopy in individuals with known risk factors, established disease and/or relevant symptoms............................................................................................64

References........................................................................................................................................66Included studies........................................................................................................................66Excluded studies.......................................................................................................................79Other references........................................................................................................................81

Appendix 1 – Search terms for identifying studies.......................................................................84

Appendix 2 – Study assessment criteria........................................................................................86

Appendix 3 – Evidence hierarchy..................................................................................................90

Appendix 4 – Characteristics of excluded studies........................................................................91

Appendix 5 – Tables of included studies.......................................................................................93Review Question 1a: Appropriate timing of colonoscopy in patients with a family history of bowel cancer.............................................................................................................................93Review Question 1b: Appropriate timing of colonoscopy in patients with a genetic predisposition to bowel cancer.................................................................................................96Review Question 1c: Appropriate timing of colonoscopy in patients with inflammatory bowel disease.......................................................................................................................................99Review Question 1d: Appropriate timing of colonoscopy in older people............................106Review Question 1e: Appropriate timing of colonoscopy in patients with a past history of colorectal cancer.....................................................................................................................109Review Question 1f: Appropriate timing of colonoscopy in patients with a past history of adenoma..................................................................................................................................123Review Question 2a: Effectiveness of colonoscopy in cancer prevention.............................137

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Review Question 2b: Effectiveness of colonoscopy in diagnosis of pathology in symptomatic patients....................................................................................................................................154Review Question 2c: Likelihood of a single colonoscopy leading to the detection of an adenoma and / or colorectal cancer.......................................................................................160Review Question 2d: What is the relationship between appropriateness criteria for colonoscopy and diagnostic yield?..............................................................................................................165Review Question 3a: How do safety and quality outcomes of colonoscopy vary according to the procedural volumes of colonoscopists?............................................................................172Review Question 4: How cost-effective is colonoscopy in each target population?..............175Review Question 5a: Are all patient groups in whom colonoscopy should be used able to access colonoscopy?...............................................................................................................177Review Question 5b: What is the evidence for interventions that improve access to colonoscopy services?............................................................................................................178Review Question 5c: What is the impact of open access service configuration on access to colonoscopy services?............................................................................................................179

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TERMS AND ABBREVIATIONS USED IN THIS REVIEW

ABS Australian Bureau of Statistics

AFAP Attenuated familial adenomatous polyposis

AIHW Australian Institute of Health and Welfare

ASGE American Society for Gastrointestinal Endoscopy

CEA Carcinoembryonic antigen

CINAHL Cumulative Index of Nursing and Allied Health Literature

CT Computerised tomography

EPAGE European Panel for the Appropriateness of Gastrointestinal Endoscopy

FAP Familial adenomatous polyposis

FOBT Faecal occult blood test

GENCA Gastroenterological Nurses College of Australia

GESA Gastroenterological Society of Australia

HNPCC Hereditary non-polyposis colorectal carcinoma

ICER Incremental cost-effectiveness ratio

MBS Medicare Benefits Schedule

NHMRC National Health and Medical Research Council

QALY Quality-adjusted life year

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SUMMARY OF FINDINGS OF THE REVIEW

Clinical Research Questions

Findings

1. For patients with non-acute indications for colonoscopy, what is the appropriate timing between colonoscopies?

i. Family History: Risk of development of colorectal cancer in patients with a family history is categorised in currently endorsed guidelines as ‘at or slightly above’ (Category 1) risk, at ‘moderately increased’ (Category 2) risk and at ‘potentially high’ (Category 3) risk. According to these guidelines, patients with Category 1 risk require bowel cancer surveillance equivalent to that required by the general population. Studies included in this review demonstrate that decisions regarding commencement and frequency of surveillance colonoscopy in patients with Category 2 or Category 3 risk are based on the strength of family history and findings of index colonoscopy, particularly the presence and features of adenomas identified at index colonoscopy.

ii. Genetic predisposition: Patients with a genetic predisposition to bowel cancer are at increased risk of developing adenoma and colorectal carcinoma. Appropriate intervals between surveillance colonoscopies vary according to the type of genetic condition affecting the patient, the patient’s age, findings from preceding colonoscopies and the presence of other risk factors for colorectal cancer. As a result, recommended surveillance intervals for subsequent colonoscopies in this group of patients vary between several months and 5 years or longer. Published studies support the commencement of colonoscopic surveillance for patients with a defined genetic predisposition to bowel cancer at a younger age than for other groups of patients requiring surveillance colonoscopy.

iii. Inflammatory Bowel Disease: Patients with inflammatory bowel disease are at increased risk of colorectal cancer. Risk of development of colorectal cancer varies according to the patient’s individual risk factors. These include disease duration, disease extent as well as the presence of other risk factors for colorectal cancer such as primary sclerosing cholangitis, family history of sporadic colorectal cancer, the presence of strictures, pseudopolyps and mucosal dysplasia and the severity of endoscopic and histological inflammation, and factors that are independent of the patient’s inflammatory bowel disease status such as patient age and the presence of concurrent familial bowel cancer syndromes.

In patients without additional risk factors, included studies suggest that colonoscopic surveillance commenced from 8 to 10 years of diagnosis is warranted for pancolitis, and from 12 years in left sided colitis. In patients with additional risk factors for colorectal cancer, evidence suggests that surveillance may commence sooner, depending on the

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Findings

nature of the additional risk factors.

Empirical data are limited regarding the frequency with which surveillance colonoscopy should be performed in patients with inflammatory bowel disease. Available evidence suggests that ongoing colonoscopic surveillance should be performed at intervals of between ≤12 months and 5 years, depending on the endoscopic findings and clinical risk factors in the individual patient. The body of literature regarding the use of surveillance colonoscopy in inflammatory bowel disease is mostly related to the management of patients with ulcerative colitis.

iv. Older people: There was no direct evidence supporting cessation of colonoscopic screening based solely on the patient’s age. There were no trials identified in this review that assessed optimal intervals between colonoscopy examinations in older versus younger people for specific clinical conditions in which colonoscopic surveillance was indicated.

v. Patients with a past history of bowel cancer: Studies included in this review demonstrate a significant risk of synchronous and metachronous cancers and adenomas after resection of colorectal cancer. Colonoscopy is indicated pre- or peri-operatively to identify and manage synchronous lesions.

Studies included in this review suggest that post-operative colonoscopy performed within 12 months of surgery reduces the incidence of high-risk lesions at 1 year, including advanced adenomas, new cancer diagnoses and localised recurrence of malignancy.

Decisions regarding subsequent post-operative colonoscopies are determined according to the clinical features of the individual case. Five years is the maximum timeframe within which repeat colonoscopy is recommended in studies of patients with normal post-operative index colonoscopy. In patients with abnormal colonoscopy, repeat colonoscopy was performed at between 1 and 3 years, depending on the patients risk for subsequent neoplasia, in included studies.

vi. Patients with a past history of adenoma: The recommended timing of surveillance colonoscopy in patients with a past history of adenoma varies according to adenoma size, number and histological features. Surveillance intervals proposed across published studies vary between several months (in patients with incompletely removed adenomas) and 10 years (in patients with one or two lower risk adenomas and no other risk factors for colorectal cancer). In general, patients with larger adenomas, adenomas with higher grades of

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Findings

dysplasia, adenomas with villous components, patients with multiple adenomas and patients with other risk factors for development of colorectal neoplasia require more frequent surveillance. Patients with incomplete or inadequate colonoscopic examination require re-examination within 12 months of the prior examination.

MBS Data: The majority (68%) of patients receiving MBS-rebated colonoscopy have not had another MBS-rebated colonoscopy in the 10 years preceding the procedure. Patient aged between 50 and 74 years receive the majority of repeat MBS-rebated colonoscopies.

Approximately 1.5% of patients received 5 or more MBS-rebated colonoscopies over a 10-year period. Available MBS data do not provide information regarding the clinical indications for colonoscopies at this higher frequency.

2. What is the effectiveness of colonoscopy in improving outcomes in key target populations receiving colonoscopy?

What is the likelihood of a single colonoscopy leading to the detection of an adenoma and / or colorectal cancer?

Cancer prevention: Colonoscopy is a diagnostic and therapeutic tool that is used for the prevention and early identification of colorectal neoplasia in patients in whom the procedure is indicated. Colonoscopy appears to prevent colorectal cancer from developing in many at-risk patients through the identification and removal of pre-malignant tumours; appears to assist in the identification of malignant tumours at an earlier disease stage than would otherwise be detected; and may be colon-sparing in some patients with inflammatory bowel disease.

Diagnosis of pathology in symptomatic patients: The effectiveness of colonoscopy in the diagnosis of pathology in symptomatic patients varies according to the personal and clinical characteristics of the patient. Rates of diagnosis of significant pathology are higher in older compared with younger patients; and in patients whose symptoms include rectal bleeding or unexplained weight loss. Older compared with young patients with iron deficiency anaemia and patients with abnormal imaging and / or elevated carcinoembryonic antigen (CEA) levels also have higher rates of diagnosis of significant pathology at colonoscopy.

Detection of an adenoma and / or colorectal cancer: The likelihood of a single colonoscopy leading to the detection of an adenoma and / or carcinoma varied across studies according to the clinical and personal characteristics of the patient and according to the technical aspects of the colonoscopy itself. Colorectal carcinoma was detected in between 0.3% and 6% of patients in ‘usual’ colonoscopic practice in this review; and adenomas were diagnosed in up to 25% of patients.

Appropriateness criteria and diagnostic yield: Appropriateness

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Findings

criteria identify patients in whom the diagnostic yield from colonoscopy is greater. Patients in whom appropriateness criteria assess colonoscopy as ‘inappropriate’ may also have significant pathology present, although the diagnostic yield in this group is lower.

3. How do safety and quality outcomes of colonoscopy vary according to:

- the procedural volumes of providers performing colonoscopy?

- certification / re-certification processes for providers performing colonoscopy?

Procedural volume: Procedural volume is one of a range of factors affecting the procedural quality of colonoscopy. Included studies demonstrate a trend towards improved procedural quality with increasing numbers of procedures performed, provided the colonoscopist is appropriately trained.

Relationships between the procedural volume of the colonoscopist and detection of adenomas, development of subsequent colorectal cancer and adverse outcomes associated with colonoscopy have been observed. There is no clearly identifiable threshold volume of colonoscopy procedures below which procedural quality and safety declines noticeably in studies included within this review.

Medicare data indicate that the majority of providers performing MBS-rebated colonoscopy achieve procedural volumes above the minimum threshold recommended by the Quality Working Group of the National Bowel Cancer Screening Program. Medicare data are insufficient to determine the procedural volumes of all colonoscopists as procedures performed in public settings are not included in this dataset.

Certification / re-certification processes: No studies were identified that appraised the impact of certification or re-certification processes on the safety and quality outcomes of colonoscopy.

The Quality Working Group of the National Bowel Cancer Screening Program recommends that “compulsory certification by the Conjoint Committee should be introduced for all proceduralists performing colonoscopies as a prerequisite for making claims under the MBS and participating in the NBCSP”.

4. How cost-effective is colonoscopy in key target populations?

Cost-effectiveness of colonoscopy: Colonoscopy appears to be a cost-effective procedure across a broad range of clinical conditions. The personal and clinical characteristics of the patient, the skills and experience of the colonoscopist and the setting in which the colonoscopy is performed contribute to the cost-effectiveness of the procedure.

5. Are all patient groups in whom colonoscopy should be used able to

Access to colonoscopy: Analysis of Medicare data demonstrates a lower number of providers per 1,000 population for people in small rural and remote areas. However, access to colonoscopy services for

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Findings

access colonoscopy?

What is the impact of open access colonoscopy on access?

patients in remote and very remote areas may occur through the public sector and may not be MBS-rebated. No peer-reviewed studies were identified that examined whether all patient groups in whom colonoscopy should be used are able to access the procedure.

Interventions to improve access: Waiting list audit and the use of a patient navigator may improve access to colonoscopy services. Available published and unpublished data on the impact of waiting list audit on subsequent morbidity and mortality of patients whose colonoscopy was cancelled or delayed have not been assessed in studies included in this review.

Open access colonoscopy: Open access colonoscopy, where a patient is referred by a clinician for a colonoscopy without a prior consultation with the specialist performing the colonoscopy, may improve access to services. There is some evidence suggesting that open access colonoscopy is associated with reduced waiting times but not with an increase in the number of colonoscopies performed that are not clinically indicated. No studies were included that systematically addressed adverse outcomes from open access colonoscopy.

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BACKGROUND

Colonoscopy is an endoscopic procedure for examination of the terminal ileal, colonic and rectal mucosa. It is used in the diagnosis, management and ongoing follow-up of patients with a range of clinical conditions including neoplastic, inflammatory and familial conditions. Although colonoscopy services are predominantly provided to adult patients, the procedure is also performed in paediatric patients.

Colonoscopy is the gold standard for the examination of the bowel lining. It allows direct mucosal inspection to the terminal ileum and biopsy of or definitive treatment by polypectomy. Patients generally adopt a liquid diet one or more days prior to examination, followed by ingestion of oral lavage solutions and / or use of laxatives to stimulate bowel movements. Patients receive sedation or an anaesthetic to make the procedure more comfortable (Schroy 2007; Zubarik 2002).

A principal benefit of colonoscopy is that it allows for a full structural examination of the bowel in a single session and for the removal or biopsy of lesions identified during the procedure. Other forms of colon investigation, if positive, usually require colonoscopy as a follow up procedure (Winawer 2003).

Colonoscopy is widely available throughout both Australia’s public and private sectors. Services are provided predominantly in public and private hospital settings. However, settings such as stand-alone day units may also be utilised. Clinicians who perform colonoscopy may possess specialist gastroenterology, general medicine, surgical or primary care specialty qualifications. Approximately 75% of all colonoscopies performed on an admitted patient basis in Australia in 2008/09 were performed in the private sector, compared with 63% in 2001/02 (National Admitted Patient Care Dataset, 2001/02 to 2008/09).

There is an existing Australian process for formal recognition of training in colonoscopy by the Conjoint Committee for the Recognition of Training in Gastrointestinal Endoscopy, a conjoint committee of the Royal Australasian College of Surgeons, the Gastrointestinal Society of Australia and the Royal Australasian College of Physicians (Conjoint Committee 2011). Conjoint committee recognition is not a requirement for access to MBS items.

Guidance for colonoscopy in Australia

Clinicians access a variety of sources of guidance regarding the use of colonoscopy in specific disease states.

The Australian Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer (2005) relate only to indications for colonoscopy associated with bowel cancer. The guidelines currently make the following recommendations (Australian Cancer Network 2005):

organised screening for colorectal cancer with faecal occult blood testing (FOBT) performed at least once every 2 years is strongly recommended for the Australian population over 50 years of age;

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in persons at category 1 risk (those with a positive family history who are at or slightly above average risk) FOBT performed at least once every 2 years is recommended in combination with a sigmoidoscopy (preferably flexible) every 5 years; and

in persons at category 2 risk (those with a positive family history who are at moderately increased risk) colonoscopy every 5 years starting at age 50 or 10 years younger than the age of first diagnosis of bowel cancer in the family, whichever comes first, or sigmoidoscopy plus double contrast barium enema if colonoscopy is unavailable, is recommended.

Additional recommendations for gastrointestinal surveillance are made for persons with high risk familial colorectal cancer syndromes.

Draft national Clinical Guidelines for Surveillance Colonoscopy – in adenoma follow-up; following curative resection of colorectal cancer; and for cancer surveillance in inflammatory bowel disease (May 2011) are currently released for public consultation. This consultation period is expected to close in June 2011.

The Gastroenterological Society of Australia (GESA) and Gastroenterological Nurses College of Australia (GENCA) have published standards for endoscopic facilities and services that provide specifications for facilities, equipment, patient services, information, education and consent, organisation and administration, medical and nursing services, patient sedation, administrative services, medical records, environmental services, quality assurance and education (GESA / GENCA 2006; GESA 2008).

International guidance for colonoscopy

The American Society for Gastrointestinal Endoscopy (ASGE) and the European Panel for the Appropriateness of Gastrointestinal Endoscopy (EPAGE) have both developed criteria that describe indications for colonoscopy. These criteria have been evaluated in published studies and are discussed in more detail within this review. In summary, the main indications for colonoscopy according to the above criteria are as follows:

1 General indications for colonoscopy according to the ASGE criteria

evaluation of an abnormality on barium enema or other imaging study, which is likely to be clinically significant, such as a filling defect or stricture;

evaluation of unexplained gastrointestinal bleeding;

evaluation of unexplained iron deficiency anaemia;

screening and surveillance for colonic neoplasia;

evaluation of chronic inflammatory bowel disease of the colon if more precise diagnosis or determination of the extent of activity of disease will influence immediate management;

evaluation of clinically significant diarrhoea of unexplained origin;

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intraoperative identification of a lesion not apparent at surgery (e.g. polypectomy site, location of a bleeding site);

treatment of bleeding from such lesions as vascular malformation, ulceration, neoplasia, and polypectomy site (e.g., electrocoagulation, heater probe, laser or injection therapy);

foreign body removal;

excision of colonic polyp;

decompression of acute nontoxic megacolon or sigmoid volvulus;

balloon dilation of stenotic lesions (e.g., anastomotic strictures);

palliative treatment of stenosing or bleeding neoplasms (e.g. laser, electrocoagulation, stenting); and

marking a neoplasm for localization.

2 General indications for colonoscopy according to the EPAGE II criteria

iron-deficiency anaemia (malabsorption syndrome excluded);

haematochezia (without inflammatory bowel disease). Patient haemodynamically stable;

lower abdominal symptoms (chronic constipation / lower abdominal pain / bloating) of at least 3 months duration, without known inflammatory bowel disease, without anaemia and without FOBT positive stools, with or without empirical IBS therapy. No risk factors for colorectal cancer;

uncomplicated diarrhoea (infectious or malabsorption origin excluded and without known IBD). No anaemia. No bleeding. No risk factors for colorectal cancer. No HIV / AIDS. With or without empirical treatment;

evaluation of known ulcerative colitis, excluding surveillance for cancer;

evaluation of known Crohn's disease, excluding surveillance for cancer;

surveillance for colorectal cancer in patients with known inflammatory bowel diseases;

surveillance after colonic polypectomy; follow-up colonoscopy (complete colonoscopy, bowel preparation adequate, patient actually asymptomatic, life expectancy >10 years). Familial polyposis, HNPCC and hyperplastic polyposis syndrome excluded;

surveillance after curative intent resection of colorectal cancer;

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screening for colorectal cancer; and

miscellaneous indications.

Justification for this review

The delivery of evidence-based care is an important goal of the MBS and is articulated in Medicare Benefits Schedule – a quality framework for reviewing services. MBS item numbers relevant to colonoscopy services include:

32090: Fibreoptic colonoscopy examination of colon beyond the hepatic flexure with our without biopsy; and

32093: Endoscopic examination of the colon beyond the hepatic flexure by fibreoptic colonoscopy for the removal of 1 or more polyps, or the treatment of radiation proctitis, angiodysplasia or post-polypectomy bleeding by argon plasma coagulation.

There has been an increase in MBS utilisation between 2000/2001 and 2009/2010 financial years for both 32090 and 32093 item numbers. This increase has been observed in all States and Territories and for Australia as a whole. This has occurred in the context of an ageing population, an increasing prevalence of colorectal cancer in the population, the introduction of the National Bowel Cancer Screening Program, implementation of familial bowel cancer clinics associated with genetic diagnostic services nationwide and increased utilisation of private endoscopy services compared with public endoscopy services.

Consistency of the MBS with contemporary evidence is desirable in order to facilitate the provision of evidence-based care. The purpose of this review is to identify and appraise contemporary evidence regarding colonoscopy and its utilisation in Australia in order to consider whether MBS item numbers for colonoscopy are aligned with available evidence.

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CLINICAL AND RESEARCH QUESTIONS ADDRESSED IN THIS REVIEW

The specific clinical questions that are the focus of this review are as follows:

1 For patients with non-acute indications for colonoscopy, what is the appropriate timing between colonoscopies?

2 What is the effectiveness of colonoscopy in improving outcomes in key target populations receiving colonoscopy?

What is the likelihood of a single colonoscopy leading to the detection of an adenoma and / or colorectal cancer?

3 How do safety and quality outcomes of colonoscopy vary according to:

the procedural volumes of providers performing colonoscopy?

certification / re-certification processes for providers performing colonoscopy?

4 How cost-effective is colonoscopy in key target populations?

5 Are all patient groups in whom colonoscopy should be used able to access colonoscopy?

What is the impact of open access colonoscopy on access?

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LITERATURE REVIEW METHODS

Types of studies considered for the review

Studies involving adult patients (defined as persons aged > 16 years) who receive colonoscopy for any purpose relevant to the specific clinical questions outlined above were considered for inclusion.

The inclusion criteria for selection of specific studies included the following:

the publication presented original data or review of original data;

the publication included colonoscopy-specific data;

the publication addressed one or more of the specific research questions;

the publication described research that was conducted in humans;

the publication was in the English language;

the publication was published between 1999 and 2010; and

the publication described a study that was conducted in an appropriate population for the question being addressed.

Exclusion criteria for selection of relevant studies included the following:

the publication was an editorial, article or review which presented opinion rather than evidence;

for review articles, the publication was a non-systematic review;

the publication was of a study where methods were not sufficiently described to enable appraisal of quality according to NHMRC criteria;

the publication was a duplicate publication of the same research study;

the publication described a comparative study between colonoscopy and other colorectal diagnostic or management techniques;

the publication described research unrelated to the review questions;

the publication described the use of colonoscopy solely for population screening; and

the publication described research conducted in trainees.

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Search strategies for identifying studies

The search strategies used to identify studies were as follows:

1 Manuscripts were sought for the years 1999 to 2010 in order to identify relevant publications based on contemporary colonoscopy practice.

2 Searches were conducted in the MEDLINE, PsychINFO, CINAHL, EMBASE, Cochrane Library and were supplemented with searches of proprietary search engines (including Google® and Google Scholar®).

3 Direct analysis of output from known centres of excellence, international, national and state-based government agencies was conducted.

Search strategies were supplemented by approaching professional bodies for clinical guidelines, unpublished studies and reviews of relevance to this review. The National Health and Medical Research Council, the Australian Cancer Network, Cancer Australia and the National Bowel Cancer Screening Program Quality Working Group were approached to request additional materials relevant to this review.

Search terms for identifying studies

Relevant Medical Index Subject Heading (MeSH) terms and subject headings were combined with key words of relevance to enable databases to be searched.

An initial search strategy was used to identify materials of broad relevance to the review (Appendix 1). Results of the search that were relevant to the five specific review questions were identified by hand coding all abstracts and titles identified by the search strategy.

Study selection

Two reviewers independently sorted through search results by scanning lists of titles and abstracts generated by the electronic database search, highlighting potentially relevant articles. Full articles were retrieved if they addressed one or more of the specified review questions and could not be excluded based on the inclusion and exclusion criteria described above.

Abstracts that did not meet inclusion criteria were coded according to reason for rejection. If there was any doubt regarding the details of the study from the information given in the title and abstract, the full article was retrieved for clarification.

The two reviewers discussed results of the study selection process in order to address any differences of opinion. A third party was not required to resolve differences in opinion as the two reviewers were able to agree on studies that were selected.

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Data extraction

Data that were extracted include the following:

general information: the title of the publication, authors, country within which the study was conducted and the year of publication;

study design;

a description of the study methods;

the target group in whom the study was performed, the sampling method and sample size in study groups, relevant inclusion and exclusion criteria where provided;

interventions: purposes for which colonoscopy performed;

outcomes: primary outcomes assessed, secondary outcomes assessed.

Quality assessment of studies

Quality assessment was undertaken to enable publications of poorer quality to be identified and accounted for in data synthesis. The quality of reporting of each study was assessed by quality criteria based on the National Health and Medical Research Council’s “Levels of Evidence and Grades for Recommendations for Developers of Guidelines (NHMRC 2009)”. The study assessment criteria are described in Appendix 2.

Both reviewers independently undertook quality assessment of published materials. Differences of opinion were resolved through discussion between reviewers.

Data analysis

The search strategy (terms and limits) and yield were documented, including the number of publications identified by each database search, publications excluded and reasons for exclusion, the number of relevant publications identified through other search processes, the number of publications obtained for review, the level of evidence of relevant publications and the highest level of evidence found for each question.

Overall assessment of individual studies included, where appropriate, the level of evidence and quality rating according to NHMRC guidance. The evidence hierarchy that was applied to study assessment is described in Appendix 3.

Data from publications were summarised descriptively by chronicling and ordering the evidence in order to produce an account of the evidence and to enable integration of quantitative evidence of different levels and of qualitative evidence (Guyatt 2008).

Where objective outcomes data were provided, data were extracted and reported for relevant outcomes only.

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FACTORS AFFECTING RATES OF COLONOSCOPY

The primary focus of this review is the use of colonoscopy in the context of bowel cancer. Colorectal cancer is the second most common cancer (excluding non-melanoma skin cancer) and the second most common cause of cancer death reported to Australian cancer registries. In 2007, there were 14,234 new cases of colorectal cancer reported and 4, 047 deaths (AIHW 2010)

Data from the Australian Institute of Health and Welfare (AIHW) showing age-standardised bowel cancer incidence and mortality are reproduced in the tables below. They show some fluctuations in the age-standardised rate of incidence of bowel cancer within age groups (Figure 1), but an overall strong decline in the age-standardised rate of death from bowel cancer (Figure 2).

Figure 1: Bowel Cancer incidence by age group in Australia 1982 - 2007

Age-Standardised rates of bowel cancer incidence in Australia by age group

0.0

50.0

100.0

150.0

200.0

250.0

300.0

350.0

400.0

450.0

500.0

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

Year

Rat

e pe

r 100

,00

popu

latio

n

50–5455–5960–6465–6970–7475–7980–8485+

Source: the Australian Institute of Health and Welfare (AIHW) 2010 (Australian Cancer Incidence and Mortality Books, AIHW, using Australian population standard 2001 as the reference. year

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Figure 2: Rate of Death from bowel cancer per 100,000 population by age group, 1982-2007

Age-standardised rate per 100,000 population of death from bowel cancer by age group, 1982-2007

0.0

50.0

100.0

150.0

200.0

250.0

300.0

350.0

400.0

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

Year

Rate

per

100

,000

pop

ulat

ion 50–54

55–59

60–64

65–69

70–74

75–79

80–84

85+

Source: the Australian Institute of Health and Welfare (AIHW) 2010 (Australian Cancer Incidence and Mortality Books, AIHW, using Australian population standard 2001 for the reference year.

As the above data are age-standardised, they do not reflect changes in the overall burden of disease associated with bowel cancer in the population, contributed to by the increasing median age of the Australian population. As the occurrence of bowel cancer is strongly age-related, an ageing population is likely to increase the overall numbers of bowel cancers occurring in the population. In addition, the overall size of the population in Australia is increasing. This is also likely to contribute to a higher overall number of bowel cancers occurring in the population.

Data reported in Table 1 demonstrate that the crude number of new cases of bowel cancer occurring in the population increased from 9,861 cases in 1993 to 14,234 cases in 2007 and the incidence of bowel cancer increased from 0.56 to 0.68 per 1,000 population. The crude number of deaths from bowel cancer decreased from 4,398 deaths in 1993 to 4,047 deaths in 2007. Over the same time period, the number of large bowel investigations performed per 1,000 population and the number of colonoscopies performed per 1,000 population increased.

These data suggest that the recent growth in colonoscopy services has occurred in the context of rising crude numbers of bowel cancers occurring in the population, and a relative decline in large bowel procedures other than colonoscopy. In 1993/1994, colonoscopy accounted for 44% of all large bowel investigations, growing to 66% by 2000/2001. Over the same time period, the growth in overall large bowel investigative procedures grew by 15%, and there was a period of decline in the mid-1990s. As colonoscopy is the gold standard procedure for investigation of the large bowel,

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these data may reflect a change in investigative practice by health care providers with substitution of colonoscopy as the preferred investigation of the large bowel.

Table 1: Incidence and mortality rates of bowel cancer and investigations for bowel cancer in Australia 1993-2009

Year

Bowel cancer

incidence

Crude incidence per 1,000 population

Annual deaths from

bowel cancer

Annual deaths per

1,000 population

MBS large bowel

investig-ations per

1,000 population

MBS colon-oscopies per

1,000 population

1993 9,861 0.56 4,398 0.25 19 81994 10,284 0.58 4,587 0.26 19 91995 10,526 0.58 4,468 0.25 19 91996 10,876 0.59 4,560 0.25 19 101997 11,126 0.60 4,630 0.25 18 101998 11,157 0.60 4,599 0.25 18 101999 11,678 0.62 4,527 0.24 18 112000 12,264 0.64 4,659 0.24 20 132001 12,701 0.65 4,687 0.24 20 142002 12,479 0.64 4,538 0.23 20 152003 12,584 0.63 4,373 0.22 20 152004 13,014 0.65 4,070 0.20 20 162005 13,113 0.64 4,166 0.20 20 172006 13,639 0.66 3,809 0.18 21 182007 14,234 0.68 4,047 0.19 22 192008 n/a n/a n/a n/a 23 202009 n/a n/a n/a n/a 23 21

Table constructed with data from MBS statistics, from the Australian Institute of Health and Welfare (AIHW) 2010 (Australian Cancer Incidence and Mortality Books, AIHW, Canberra, and from Australian Bureau of Statistics (3105.0.65.001 Australian Historical Population Statistics, 2008)* Large bowel investigations consist of colonoscopy, flexible sigmoidoscopy, rigid sigmoidoscopy and barium enema.

ANALYSIS OF MEDICARE DATA

To complement the findings of the literature review, quantitative analysis of data obtained from Medicare Australia was performed. De-identified data for MBS items 32090 and 32093 for the years 1999/2000 to 2008/2009 were obtained through Medicare Australia and analysed. Results of these analyses are presented below.

Key trends in MBS utilisation of colonoscopy and related items

In the ten years between 2000/01 and 2009/10 the utilisation of MBS items for colonoscopy has increased in all States and Territories and for Australia as a whole (Figures 3 and 4).

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Figure 3: MBS Item 32090

Figure 4: MBS Item 32093

This increase was observed both in the overall numbers of colonoscopies performed (Figures 3 and 4) and the per capita rates of colonoscopies performed (Table 2). MBS data in Table 2 demonstrate that in 2009/10 there were 24.6 MBS-rebated colonoscopies performed per 1,000 population in Australia, an increase of 84% on the rate of 13.4 in 2000/01. The rate of increase varied across States and Territories from a 67% increase in Queensland to a 131% increase in Western Australia. The number of MBS-rebated colonoscopies performed per 1,000 population in the Northern Territory was significantly lower than other States and Territories for both financial years.

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Table 2: Number of MBS-rebated colonoscopies (MBS items 32090 and 32093) performed per 1,000 population by patients’ State and Territory for financial years 2000/01 and 2009/10

NSW VIC QLD SA WA TAS NT ACT Aust.

2000/01 12.8 14.6 16.0 11.9 10.2 11.2 4.6 10.0 13.4

2009/10 23.6 26.7 26.7 22.2 23.6 22.2 9.7 21.7 24.6

% change 2000/01 to 2009/10 84% 83% 67% 87% 131% 98% 111% 117% 84%

% Aust. average 2009/10 96% 109% 109% 90% 96% 90% 39% 88% 100%

The total number of MBS-rebatable colonoscopies performed between 2000/01 and 2009/10 was higher for item 32090 than for 32093. However the rate of increase in utilisation of the MBS item 32093 was 162% compared with a 59% increase in utilisation of the MBS item 32090 (Table 3). As a result, the MBS utilisation of 32090 relative to colonoscopy items as a whole decreased from 75% to 65% between 2000/01 and 2009/10.

Table 3: Total number and relative percentage of MBS utilisation of colonoscopy items for financial years 2000/01 and 2009/10

MBS items 2000/01 2009/10 % increase in item utilisationNumber Percentage Number Percentage

32090 189,023 75% 300,365 65% 59%

32093 61,858 25% 162,010 35% 162%

All 250,881 100% 462,375 100% 84%

MBS utilisation for colonoscopy item numbers varies according to age category. Utilisation rates (per 1,000 population) increase with increasing age category to a maximum in persons aged 65 to 69 years. Increases in MBS utilisation between 1999/2000 and 2008/2009 have occurred across all patient age groups (Figure 5).

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Figure 5: MBS utilisation for colonoscopy items according to age group

Available data from Casemix indicate that growth in colonoscopy has occurred predominantly in the private sector (Figure 6).

Figure 6: Colonoscopy separations in private and public settings, 2001/02 to 2008/09*

*A limitation of Casemix data is that it does not capture MBS-rebated colonoscopies that occur in non-inpatient settings, both public and private.

Colonoscopies comprised 66% of MBS-rebated investigations of the large bowel (colonoscopy, sigmoidoscopy, barium enema) in the 2000/01 financial year. By 2008/09 this proportion had increased to 88% (Table 4). There were significant decreases in the number of MBS-rebated rigid sigmoidoscopies and barium enemas performed and a small increase in the number of MBS-rebated

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flexible sigmoidoscopies performed, suggesting that colonoscopy has substituted increasingly for other large bowel investigative procedures. The number of MBS-rebated large bowel investigations as a whole increased by 39% between 2000/01 and 2009/10, largely due to the increase in MBS-rebated colonoscopies.

Table 4: Total number and relative percentage of large bowel investigations by type for financial years 2000/01 and 2009/10

MBS items 2000/2001 2009/10 % change in no. servicesNumber Percentage Number Percentage

Colonoscopy (32090, 32093)

250,881 66% 462,375 88% +84%

Rigid Sigmoidoscopy (32072, 32975, 32078, 32081)

63,100 17% 32,117 6% -51%

Flexible Sigmoidoscopy (32084, 32087)

19,478 5% 19,841 4% +2%

Barium Enema (58921) 43,922 12% 9,804 2% -78%

All 377,381 100% 524,137 100% +39%

MBS expenditure in rebates for colonoscopies has increased over the past ten years. The rate of increase was higher for item 32093 (5-year rate of increase of 96 to 97%) compared with item 32090 (5-year rate of increase of 50 to 51%), consistent with the greater increase in the number of 32093 procedures compared with 32090 procedures over this period (Table 5).

Table 5: Annual Medicare rebates items 32090 and 32093 (1999/00-2009/10)

Item 1999/2000 2004/2005 2009/10 % increase 5 years to 2004/05

% increase 5 years to 2009/10

32090 $31,623,784 $47,284,925 $71,203,293 50% 51%

32093 $13,979,297 $27,584,479 $54,022,879 97% 96%

Total $45,603,081 $74,869,404 $125,226,172 64% 67%

In summary, the key observations for the period 2000/01 to 2000/10 are:

in 2009/10, more than 2% of the population had a colonoscopy rebated through Medicare;

the rate of MBS-rebated colonoscopy increased between 2000/01 and 2009/10 in all States and Territories and Australia as a whole;

MBS utilisation for colonoscopy in the Northern Territory is significantly lower than other States and Territories;

most MBS-rebated colonoscopies do not include polypectomy; however colonoscopy with polypectomy (or argon plasma coagulation) has increased as a proportion of all MBS-rebated colonoscopies; and

numbers of MBS-rebated rigid sigmoidoscopy and barium enema have decreased over the same time period that MBS-rebated colonoscopy has increased.

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SYSTEMATIC REVIEW OF THE LITERATURE - RESULTS OF SEARCH STRATEGY

Introduction

The literature was searched using the methods outlined above. Our initial search identified 2,629 references to potential studies. A further reference to a potential additional study was obtained through contact with relevant professional bodies, making a total of 2,630 references (Figure 7).

Of these, we excluded 2,439 after initial independent title and abstract screening (kappa = 0.69) with 50 disagreements. The disagreements were resolved by consensus and all 25 were excluded while still at abstract screening stage.

Figure 7 – Search strategy results

The remaining 191 references required full-text review, from which 169 references were included. Reasons for excluding studies at full-text review are given in Appendix 4.

Data were extracted for all included studies and tabulated according to the review questions. Included studies and their characteristics are provided for each review question in Appendix 5.

Findings for individual clinical and research questions

Findings for each of the clinical and research questions are described below.

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Records identified through database searches (n=2,629)

Additional records identified through other sources (n=1)

Records screened (n=2,630) Records excluded (n=2,436)

Full text articles assessed for eligibility (n=194) Full text articles excluded

(n=32)

Studies included in systematic review (n=162)


Question 1 - For patients with non-acute indications for colonoscopy, what is the appropriate timing between colonoscopies?

The appropriate timing between colonoscopies for patients with non-acute indications who are at increased risk of bowel cancer is being comprehensively addressed by the Australian Cancer Network and the National Health and Medical Research Council. Draft national Clinical Practice Guidelines for Colonoscopy Surveillance are currently released for public consultation. In conjunction with the Clinical Practice Guidelines for the prevention, early detection and management of colorectal cancer 2005, these draft guidelines provide detailed advice regarding appropriate timing between surveillance colonoscopies in key population groups.

It is not the intention of this section of the review to provide clinical guidance regarding appropriate timing of colonoscopy. Rather, the review of included studies in this review was completed in order to consider whether MBS item numbers for colonoscopy are aligned with available evidence regarding appropriate timing between colonoscopies.

Consistent with the above caveat, the following observations are made. Appropriate timing of colonoscopy varied according to the clinical condition for which the procedure was being performed. Studies were identified that examined timing of colonoscopy in the following clinical groups:

a. patients with a family history of bowel cancer;

b. patients with a genetic predisposition to bowel cancer;

c. patients with inflammatory bowel disease;

d. older people;

e. patients with a past history of bowel cancer; and

f. patients with a past history of adenoma.

Caution is required in interpreting the association between timing of colonoscopy and colonoscopy outcomes where published studies are observational in nature or non-randomized, due to the inability of these study types to account for the effects of lead time and length time bias. Lead time bias is the bias that occurs when colonoscopy diagnoses bowel cancer earlier than it otherwise would have been detected but this does not result in prolonged survival. The appearance of prolonged survival is created by measuring survival time from the point at which the disease is diagnosed until death; as colonoscopy results in earlier detection of the cancer, survival time may appear to increase solely because it advances diagnosis of the condition, not because it improves the actual survival of the patient. Length time bias occurs in studies of surveillance colonoscopy because faster-growing bowel cancers generally have a shorter asymptomatic period than slower-growing tumours and are therefore less likely to be detected by surveillance colonoscopy performed over time. Faster-growing tumours are often associated with a poorer prognosis than slower-growing tumours. As a result of these factors, slower-growing tumours are likely to be over-represented in surveillance colonoscopy data. This means that surveillance colonoscopy may erroneously be associated with improved survival, even if it has no actual effect on mortality.

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Question 1a: Patients with a family history of bowel cancer

There were eight studies conducted across five countries and published since 1999 that addressed this question and were included in this review (Review Question 1a, Appendix 5). The Australian Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer also addressed this question and describe studies conducted prior to 1999 are relevant to this review question (Australian Cancer Network 2005). It is not the intention of this review to provide clinical guidance regarding timing of colonoscopy in patients with a family history of bowel cancer. Rather, the review of included studies in this review was completed in order to consider whether MBS item numbers for colonoscopy are aligned with available evidence regarding appropriate timing between colonoscopies for patients with a family history of bowel cancer.

The majority of included studies involved a retrospective analysis of procedural data of patients presenting for colonoscopy who had a family history. The highest level of evidence of studies was Level III-2. The sample size of included studies varied between 100 and 9,167 participants. The timeframes over which data were appraised varied between one and 18 years across studies. There were no randomised controlled clinical trials that addressed this review question.

The endorsed Australian guidelines categorise individuals with a family history of bowel cancer into at or slightly above average risk (Category 1), moderately increased (Category 2) and potentially high (Category 3) risk groups:

People at Category 1 risk are asymptomatic; have no personal history of bowel cancer, advanced adenoma or inflammatory bowel disease; and have either no close relatives with bowel cancer or have one first- or second-degree relative with bowel cancer diagnosed at age 55 years or older.

People at Category 2 risk are asymptomatic; and have one first-degree relative with bowel cancer diagnosed before the age of 55 years or two first-degree or one first- and one second-degree relative on the same side of the family with bowel cancer diagnosed at any age.

People at Category 3 risk have three or more first- or second-degree relatives on the same side with bowel cancer; or two or more first- or second-degree relatives on the same side with bowel cancer that have high risk features (multiple bowel cancers in one person, cancer before the age of 50 years, one relative with cancer of the endometrium, ovary, stomach, small bowel, renal pelvis, ureter, biliary tract or brain, at least one first-degree relative with a large number of adenomas throughout the large bowel, or a family member with an identified high-risk gene mutation) (Australian Cancer Network 2005).

Evidence regarding the association between family history of colorectal cancer and personal risk of developing the disease demonstrates that risk varies according to the presence of underlying genetic conditions that predispose to colorectal cancer.

Yeh et al. (1999), in a study of patients with one affected first degree relative, found that 15% over 40 years old and 6% under 40 years old had colorectal neoplasm (predominantly adenomas). Similarly Gilbert et al. (2001) demonstrated that, in patients with a family history of colorectal cancer in whom colonoscopy was commenced at 40 years of age or 10 years before the youngest affected relative, 19% of patients with second-degree relatives, 26% of patients with one first-degree

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relative and 39% of patients with two or more first-degree relatives developed colorectal neoplasia (predominantly adenomas). Nusko et al. (2002) found that the risk of developing advanced adenoma and / or carcinoma within three years of a previous colonoscopy was increased in people with a first-degree relative diagnosed with colorectal cancer.

Other studies have not found an association between family history and colorectal cancer risk over and above background population risk after other risk factors for colorectal cancer were controlled for. Martinez et al. (2009), in a pooled analysis of prospective studies, demonstrated that risk of developing advanced colorectal neoplasia within 4 years of a previously resected colorectal adenoma was 12% and was no different in patients with and without family history. Kahi et al. (2007), in a retrospective cohort of patients undergoing colonoscopy found no significant difference in advanced neoplasia rates between patients with a family history of colorectal cancer and patients with no family history. Beaudin et al. (2000), in a retrospective case control series in community gastroenterology practice found that, over a 10 year period of observation, there was no difference in development of subsequent adenoma in patients with and without family history. Schoenfeld et al. (2003), in patients with a family history of colorectal cancer who had received a normal screening colonoscopy 5 years earlier, found that 8% of patients had advanced adenomas at follow-up colonoscopy and 33% had adenomas. Odds of disease in patients with a family history were no higher than in patients with no family history.

Studies that specifically examined the risk of colorectal neoplasia in high-risk families (that meet criteria for familial cancer syndromes such as hereditary non-polyposis colorectal cancer - HNPCC) have demonstrated that this subgroup is at increased risk (Dove-Edwin 2005; Gilbert 2001). A prospective observational study by Dove-Edwin et al. (2005) found the risk of adenoma on follow-up colonoscopy performed within 3.3 years of index colonoscopy in high risk families was 26% compared with 13% in low risk families.

The endorsed Australian guidelines provide guidance regarding the frequency of screening colononscopy for patients with a family history of bowel cancer. According to the guidelines, screening recommendations for patients with Category 1 risk are equivalent to the general population (Australian Cancer Network 2005). For patients with a moderate family history risk, guidelines recommend that colonoscopic surveillance be performed at 5-yearly intervals commencing at age 50 years or 10 years before the age of the affected first-degree relative. For patient with high risk familial syndromes, recommendations vary according to the syndrome; colonoscopy is recommended at a earlier age and more frequently than for patients at moderate risk.

Summary statement

Risk of development of colorectal cancer in patients with a family history is categorised in currently endorsed guidelines as ‘at or slightly above’ (Category 1) risk, at ‘moderately increased’ (Category 2) risk and at ‘potentially high’ (Category 3) risk. According to these guidelines, patients with Category 1 risk require bowel cancer surveillance equivalent to that required by the general population. Studies included in this review demonstrate that decisions regarding commencement and frequency of surveillance colonoscopy in patients with Category 2 or Category 3 risk are based on the strength of family history and findings of index colonoscopy, particularly the presence and features of adenomas identified at index colonoscopy.

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Question 1b: Patients with a genetic predisposition to bowel cancer

Familial colorectal cancer includes syndromes in which there is a well-defined inherited genetic basis, as well as those families showing clustering of colorectal cancer in which no genetic cause has yet been found. The two best-characterised inherited syndromes are familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), (also known as Lynch syndrome). The risk of colorectal cancer is also increased in other familial syndromes, including Peutz-Jeghers syndrome, juvenile polyposis, hyperplastic polyposis and MSI-variable cancers (Australian Cancer Network 2005).

FAP and HNPCC have special significance because of their important contribution to colorectal cancer diagnosed before the age of 50 years. FAP and HNPCC are associated not only with an increased risk of colorectal cancer, but also with cancers in a variety of extracolonic sites. Other families have a family history of colorectal cancer that may indicate a potentially high risk, though not strictly meeting HNPCC criteria. Such families are more numerous than those matching classical diagnostic criteria for HNPCC and these form a significant proportion of the referrals for assessment (Australian Cancer Network 2005).

There were seven studies conducted across four countries and published since 1999 that addressed this question and were included in this review (Review Question 1b, Appendix 5). The Australian Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer (2005) also addressed this question and describe studies conducted prior to 1999 that are relevant to this review question (Australian Cancer Network 2005).

It is not the intention of this review to provide clinical guidance regarding appropriate timing of colonoscopy in patients with a genetic predisposition to bowel cancer. Rather, the review was completed in order to consider whether MBS item numbers for colonoscopy are aligned with available evidence regarding appropriate timing between colonoscopies for patients with a genetic predisposition to bowel cancer.

Four studies were prospective cohort studies; five were specifically conducted in patients with HNPCC. The highest level of evidence of studies was III-2. The sample size of included studies varied between 125 and 1,678 participants. Patients were followed for up to 23 years. There were no randomised controlled trials that addressed this review question.

Included studies conducted in people with a genetic predisposition to HNPCC and FAP demonstrated an increased risk of developing adenoma and colorectal carcinoma. The risk of colorectal neoplasia in patients with a genetic predisposition varied according to the patient’s age. In patients with a genetic predisposition to HNPCC who were aged between 20 and 34 years, 83% of patients had normal surveillance colonoscopies; this decreased to 56% of patients by age 65 years (Dove-Edwin 2005). In untreated patients with FAP the development of colorectal cancer approaches 100% by age 50 years (Australian Cancer Network 2005).

Across included studies the age at which colonoscopic surveillance commenced and the intervals between colonoscopies varied according to the genetic condition affecting the patient. The age of commencement of surveillance was not a specific focus of enquiry in included studies. Frequency of surveillance colonoscopy also varied across studies. Studies that included patients with HNPCC conducted surveillance colonoscopy at between one and five years (Dove Edwin 2005; Mecklin 2007). The significant heterogeneity between studies in study design, participants, settings and

26


patient groups prevented comparisons of diagnostic yield according to variations in surveillance intervals.

In patients with HNPCC and receiving colonoscopic surveillance every 2 to 3 years, 6% developed colorectal cancer over a 15 year period compared with 16% in non-screened non-randomized controls (Jarvinen 2000). The cumulative risk of adenoma by age 60 years varied between 50% and 70% across included studies and risk of developing colorectal cancer by age 60 years varied between 22% and 35% (Dove-Edwin 2005; Engel 2010; Mak 2007; Mecklin 2007). Those with HNPCC and a pathogenic germline mutation and with microsatellite instability were at further increased risk of tumour development than those with HNPCC but without microsatellite instability (18% to 23% versus 2%) (Engel 2010; Jarvinen 2000). Screening reduced the rate of colorectal cancer by between 62% compared with non-screened controls. The Australian Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer specify that patients with a genetic predisposition to HNPCC should receive surveillance colonoscopy annually or every two years, beginning at the age of 25 years or five years earlier than the age of diagnosis of the youngest affected member of the family (Australian Cancer Network 2005). More recent data indicate that relatives in families reaching HNPCC criteria but without mismatch repair deficiency (Family Syndrome X), do not need the frequent surveillance recommended for mutation carriers, not screening for extra colonic cancers (Lindor et al., 2005).

Patients with FAP have an autosomal disorder caused by a germline mutation in the APC gene. The causative APC gene mutation is identified in over 85% of affected families. It is estimated that there are approximately 2,000 affected and at-risk family members with FAP in Australia. Regular upper and lower gastrointestinal endoscopy is incorporated into protocols to prevent gastrointestinal malignancy in affected members of families with FAP. The recommended protocol for lower gastrointestinal screening is flexible sigmoidoscopy annually or biennially from age 12 to 15 years to 30 to 35 years until polyposis develops (Australian Cancer Network 2005). Depending on likely compliance, sigmoidoscopy is often done yearly to establish better rapport with the individual and continuity of care. If no family specific mutation has been identified and no adenomas have developed, sigmoidoscopy annually or biennially until 35 years and then every three years after the age of 35 years is currently recommended in The Australian Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer (Australian Cancer Network 2005).

The draft Clinical Practice Guidelines for Surveillance Colonoscopy are currently released for public consultation and address this review question.

Summary statement

Patients with a genetic predisposition to bowel cancer are at increased risk of developing adenoma and colorectal carcinoma. Appropriate intervals between surveillance colonoscopies vary according to the type of genetic condition affecting the patient, the patient’s age, findings from preceding colonoscopies and the presence of other risk factors for colorectal cancer. As a result, recommended surveillance intervals for subsequent colonoscopies in this group of patients vary between several months and 5 years or longer. Published studies support the commencement of colonoscopic surveillance for patients with a defined genetic predisposition to bowel cancer at a younger age than for other groups of patients requiring surveillance colonoscopy.

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Question 1c: Patients with inflammatory bowel disease

Patients with inflammatory bowel disease have an increased risk of colorectal cancer. Prophylactic proctocolectomy avoids colorectal cancer but is not justified in most patients. Prevention of colorectal cancer in patients with inflammatory bowel disease by surveillance colonoscopy has been explored in a number of studies. Colonoscopic surveillance has been advocated as an alternative means to reduce cancer-related mortality among individuals who wish to retain their colon. However, the development of advanced colorectal carcinoma is not always prevented by surveillance colonoscopy and there is no conclusive evidence that surveillance colonoscopy prolongs survival in patients with extensive colitis (Collins 2008).

Guidelines for colonoscopic surveillance of patients with inflammatory bowel disease are currently released for public consultation by the Australian Cancer Network.

It is not the intention of this review to provide clinical guidance regarding the frequency of surveillance colonoscopy in patients with inflammatory bowel disease, a complex and evolving area of research inquiry. Rather, the review of included studies in this review was completed in order to consider whether MBS item numbers for colonoscopy are aligned with available evidence regarding appropriate timing between colonoscopies for patients with inflammatory bowel disease.

There were 14 studies conducted across seven countries and published since 1999 that addressed this question and were included in this review (Review Question 1c, Appendix 5). There were two systematic reviews of the literature, two case control studies and a series of studies that were prospective or retrospective analyses of administrative data collected at colonoscopy performed for patients with inflammatory bowel disease. The highest level of evidence of studies was Level III-2. There were no randomised controlled trials that addressed this review question.

Patients with inflammatory bowel disease experienced increased risk of development of colorectal cancer over time across included studies. In patients with ulcerative colitis, the cumulative risk for the development of colorectal cancer at 10, 20, and 30 years was estimated as 0.5% to 4%, 2.5% to 8% and 6.1% to 18% respectively (Eaden 2001; Hata 2003; Odze 2004; Rutter 2006). Cumulative risk for development of colorectal cancer in patients with Crohn’s disease was less well defined (Collins 2008).

Risk of development of colorectal cancer varied according to the patient’s individual risk factors. These included disease duration, disease extent as well as the presence of other risk factors for colorectal cancer such as primary sclerosing cholangitis, family history of sporadic colorectal cancer, the presence of strictures, pseudopolyposis or mucosal dysplasia and the severity of endoscopic and histological inflammation, and factors that are independent of the patient’s inflammatory bowel disease status such as patient age and the presence of concurrent familial bowel cancer syndromes (Lutgens 2008; Rutter 2006; Shetty 1999). Risk factors therefore influenced decisions regarding timing of subsequent colonoscopy.

1 Ulcerative colitis

The overall prevalence of colorectal cancer in any patient with ulcerative colitis was estimated to be 3.7% (95% CI 3.2-4.2%) (Eaden 2001). Colonic dysplasia was detected after median disease duration of between 7 and 10 years in patients with pancolitis and 12 years in patients with left sided

28


colitis (Kottachchi 2009; Odze 2004). The average patient age at which dysplasia was detected was 56 years (Kottachchi 2009).

No randomised trials have been conducted to determine the efficacy of colonoscopic surveillance in patients with ulcerative colitis. As a result, indirect evidence from observational studies forms the basis for determining the efficacy of colonoscopic surveillance in colorectal cancer prevention for patients with ulcerative colitis. These studies have found that colonoscopic surveillance is associated with reduced death rates, increased cancer-related survival and earlier tumour stage at diagnosis in study populations with ulcerative colitis who receive surveillance colonoscopy compared with non screened populations. (Collins 2008; Hata 2003; Lutgens 2009; Velayos 2006). Without randomization, these studies are open to lead time and length time biases.

The time interval between repeat surveillance colonoscopies varies across studies from annually (or more frequently) to every five years. In patients with severe colitis or additional risk factors for developing colorectal cancer (including primary sclerosing cholangitis), surveillance annually or more frequently was associated with fewer ‘interval’ cases of malignancy than in patients receiving 2-yearly surveillance (Odze 2004; Shetty 1999). In patients with a macroscopically normal looking large bowel in two or more consecutive colonoscopies, cancer risk was equivalent to that of the general population. In these patients reducing surveillance frequency to five years was proposed (Rutter 2004; Rutter 2006). However, no long-term follow-up data regarding outcomes associated with 5-yearly surveillance were identified in this review.

2 Crohn’s disease

The risk of cancer in Crohn’s disease is estimated to be equivalent to the risk in ulcerative colitis when the extent and duration of disease are equivalent. Patients with disease confined to the colon have a higher relative risk of developing cancer compared with those who have ileocolonic disease. Patients with ileal disease alone do not have an increased relative risk of colon cancer. Further, compared with sporadic colon cancer or colon cancer associated with ulcerative colitis, tumours in Crohn’s disease are more frequently located in the proximal colon, reflecting the distribution of inflammation (Collins 2008).

There are fewer data published since 1999 regarding colonoscopic surveillance in patients with Crohn’s disease. Available evidence suggests that regular colonoscopy has a relatively low impact on clinical decisions regarding the medical management of participants’ Crohn’s disease; instead, the main benefit of colonoscopy is in the identification of dysplastic changes (Manes 2009). Randomized controlled trials in Australia and elsewhere are directly addressing this issue in the post operative setting and will be reported within 2 years.

One of the few published studies since 1999, Friedman et al. (2008) analysed data collected from colonoscopic surveillance within 7 years of diagnosis in a prospective observational cohort of patients with Crohn’s disease whose disease affected greater than 30% of their large bowel. Patients received repeat colonoscopy every 1 to 2 years (or sooner if dysplasia was found sooner). By the 10th surveillance examination, 25% of patients had definite dysplasia or cancer. Half of these participants were diagnosed with neoplasia at the time of initial surveillance colonoscopy. Siegel (2006) identified an association between colonoscopy and reduced risk of colorectal cancer in a case-control study involving 27 participants (OR 0.21; p=0.02).

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Summary statements

Patients with inflammatory bowel disease are at increased risk of colorectal cancer. Risk of development of colorectal cancer varies according to the patient’s individual risk factors. These include disease duration and disease extent as well as the presence of other risk factors for colorectal cancer such as primary sclerosing cholangitis, family history of sporadic colorectal cancer, the presence of strictures, pseudopolyps and mucosal dysplasia and the severity of endoscopic and histological inflammation, and factors that are independent of the patient’s inflammatory bowel disease status such as patient age and the presence of concurrent familial bowel cancer syndromes.

In patients without additional risk factors, included studies suggest that colonoscopic surveillance commenced from 8 to 10 years of diagnosis is warranted for pancolitis, and from 12 years in left sided colitis. In patients with additional risk factors for colorectal cancer, evidence suggests that surveillance may commence sooner, depending on the nature of the additional risk factors.

Empirical data are limited regarding the frequency with which surveillance colonoscopy should be performed in patients with inflammatory bowel disease. Available evidence suggests that ongoing colonoscopic surveillance should be performed at intervals of between ≤12 months and 5 years, depending on the endoscopic findings and clinical risk factors in the individual patient. The body of literature regarding the use of surveillance colonoscopy in inflammatory bowel disease is mostly related to the management of patients with ulcerative colitis.

Question 1d: Older people

The incidence of colorectal cancer is strongly influenced by patient age. As older people are at increased risk of developing colorectal cancer, the likelihood that a colonoscopy will yield a diagnosis of colorectal cancer (the positive predictive value) is increased in older age groups.

There were eight studies conducted across three countries that addressed this question and were included in this review (Review Question 1d, Appendix 5). The majority of studies were retrospective analyses of administrative data collected on patients undergoing colonoscopy in ‘usual’ clinical practice. The highest level of evidence of studies was III-2. The sample size of included studies varied between 157 and 915 participants. The age range of older participants was 65 to 96 years.

The diagnostic yield of colonoscopy in older people was dependent upon the indication for the procedure and was generally higher in patients who were symptomatic for colorectal disease compared with asymptomatic patients (Fontagnier 2000; Kirchgatterer 2002). Fontagnier et al. (2000), in a retrospective analysis of colonoscopy records of patients aged between 80 and 94 years, found that the main indication for colonoscopy was occult faecal blood or non-acute rectal bleeding (27%), which together indicated endoscopically significant findings in 76% of patients. Kirchgatterer et al. (2002), in a retrospective review of colonoscopy records of patients aged over 80 years found that over 70% had symptoms suggestive of colorectal disease. The most frequent indications for colonoscopy were abdominal pain, bleeding, constipation, anaemia and a past history of polyps.

The diagnostic yield of colonoscopy was higher in older people than in younger people matched for the same clinical indication (Largares-Garcia 2001).

30


Colonoscopy was well tolerated by older people. Complication rates associated with colonoscopy did not differ between older and younger people (approximately 0.6% across all age groups) (Kirchgatterer 2002; Largares-Garcia 2001; Lukens 2002). However, as older people are more likely to have significant co-morbid medical conditions, endoscopists will account for this in their clinical decisions regarding safe provision of colonoscopy services. This may confound results of observational studies that assess tolerability of colonoscopy in older age groups. Lukens et al. (2002) found that 86% of patients aged 80 years or older and 90% of patients aged less than 80 years tolerated bowel preparation. However, adverse events associated with phosphate bowel preparations are well documented in older people, including adverse renal, hepatic and cardiac effects (Wexner 2006). Therefore, the tolerability of bowel preparation by older people is strongly influenced by good clinical decisions regarding bowel preparation.

Summary statement

There was no direct evidence supporting cessation of colonoscopic screening based solely on the patient’s age. There were no trials identified in this review that assessed optimal intervals between colonoscopy examinations in older versus younger people for specific clinical conditions in which colonoscopic surveillance was indicated.

Question 1e: Patients with a past history of bowel cancer

Surveillance of patients with resected colon or rectal cancer is important to detect early recurrence of the primary malignancy if this occurs and to detect metachronous (occurring at a different time to the index tumour) and synchronous (occurring at the same time as the index tumour) colorectal neoplasms.

Guidelines for colonoscopic surveillance of patients after curative resection of colorectal cancer are currently released for public consultation by the Australian Cancer Network.

It is not the intention of this review to provide clinical guidance regarding the frequency of surveillance colonoscopy after curative resection of colorectal cancer. Rather, the review of included studies in this review was completed in order to consider whether MBS item numbers for colonoscopy are aligned with available evidence regarding appropriate timing between colonoscopies for patients with a past history of bowel cancer.

There were 29 studies conducted across 12 countries and published since 1999 that addressed this question and were included in this review (Review Question 1e, Appendix 5). There were three systematic reviews, one randomised controlled trial of intensive colonoscopic surveillance versus less intensive colonoscopic surveillance, two case control studies, four prospective observational studies and 15 retrospective ecological studies included in the review that appraised colonoscopic surveillance. There were an additional three studies, two meta-analyses of randomised controlled trials, and a single randomised controlled trial, that reported results from multi-interventional surveillance (e.g. combinations of clinical examination abdominal CT or ultrasound, serum carcinoembryonic antigen (CEA), colonoscopy, sigmoidoscopy) which included, but were not limited to, colonoscopic surveillance. In addition, national guidelines from three countries (including Australia) and a hypothetical decision analysis model (Hassan 2009) were identified and appraised. The highest level of evidence of studies was Level II for studies assessing colonoscopy (assessing more intensive versus less intensive colonoscopic surveillance) and Level I for multi-interventional studies of surveillance that included other surveillance modalities (e.g. CT, CEA

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testing). The sample size of included studies varied between 104 and 10,801 participants. The timeframe of included studies was up to 27 years in duration.

Included studies demonstrated that patients with colorectal cancer are at risk of synchronous and metachronous adenomas and carcinomas and may also experience recurrence of their resected colorectal tumour:

McFall et al. (2003), in a retrospective analysis of colonoscopic records of patients who received colonoscopy after colorectal cancer resection, found that 31% of patients had adenomatous polyps diagnosed after a mean time from operation of 21 months for advanced adenomas and 34 months for simple adenomas; and 3.5% developed metachronous cancers by 5 years post-operatively;

Yusoff et al. (2003) followed up over 600 Australian patients after colorectal cancer resection and demonstrated that at colonoscopy performed 1 year postoperatively, 9% of patients had adenoma detected, 1% had advanced adenoma and 1% had carcinoma;

Fukutomi et al. (2002), in a prospective study of patients after colonoscopic resection and followed on average yearly for 3 years, found that 32% of patients developed metachronous adenomas and 3.6% developed metachronous carcinoma;

Hyman et al. (2010), at colonoscopy 1 year after colorectal cancer resection, found 2.3% of patients had ‘new’ cancer diagnosed and 0.2% had a local recurrence;

Balleste et al. (2007) found that at two years of follow-up, colonoscopy revealed the presence of adenomas in 25% of patients and colorectal cancer in 3.9% patients, 50% of which was recurrent disease and 50% metachronous disease;

Cubiella Fernandez et al. (2003) performed endoscopic follow-up 6 months following surgery in patients without complete endoscopy prior to surgery and 12 months later in patients with complete endoscopy. Patients with synchronous polyps had higher risk of developing metachronous polyps;

Bouvier et al. (2008), in a search of case records of over 10,000 patients post-colorectal cancer resection, demonstrated that the cumulative rate of metachronous colorectal cancer was 1.8% at 5 years, 3.4% at 10 years and 7.2% at 20 years;

Risk of recurrent colorectal cancer varies according to a broad range of factors. Recurrence rates vary according to the stage of the primary tumour, from an estimated 3.7% in stage 1 disease to 13.3% in stage 2 and 30.8% in stage 3 disease (Kobayashi 2007). Risk factors for local recurrence include rectal cancer rather than colon cancer, a more advanced stage of the primary tumour, tumour ulceration, poor tumour differentiation, larger tumour size and location of the tumour in a less favourable position within the bowel, including distal versus proximal rectal cancer and rectal cancer on the anterior wall (Chan 2006; Gervaz 2005; Kobayashi 2007). In addition, the type of primary surgical intervention and the use of pre-operative neoadjuvant therapy influence rates of recurrence. The anastomosis is the most likely site of colorectal cancer recurrence (Australian Cancer Network 2005).

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Hyman (2010), in a review of tumour registry data, found that colonoscopy one year after colorectal cancer resection is associated with detection of ‘new’ colorectal cancers (2.3% of patients) and locally recurrent cancer (0.2% of patients). An Australian study by Platell (2005) identified a high prevalence of advanced adenomas in patients undergoing colonoscopy after colorectal cancer resection. Colonoscopy was performed three months postoperatively if not adequately performed prior to surgery and at twelve months postoperatively, then every three years. Polyps were identified at follow-up colonoscopy in 30% of patients. The majority were 1-4mm in size and were tubular adenomas. However, advanced adenomas were identified in 8% of patients. Another Australian study by Yusoff (2003) performed clearing colonoscopy examination in 161 patients who had colorectal cancer resected. Of the 89 patients who received a surveillance examination at one year postoperatively, 9% had non advanced adenoma, 1% had advanced adenoma and 1% had colorectal cancer.

It is estimated, based on a decision analysis model constructed to compare strategies of performing or not performing one-year endoscopic surveillance in 60 year old patients after colorectal cancer resection, that the number of 1-year colonoscopies required to find one colorectal cancer is 143 and the number needed to prevent one colorectal cancer-related death is 926 (Hassan 2009). The benefit of surveillance colonoscopy at 1 year post colorectal cancer resection in adenoma detection may be increased in patients with colorectal cancer and synchronous adenoma; the incidence of ‘missed’ adenoma, advanced ‘missed’ adenoma and metachronous adenoma was shown to be higher in the synchronous adenoma group (31% versus 6%; 4% versus 0% and 31% versus 9% respectively) in administrative data collected on 248 patients (Lee 2005). The association between surveillance colonoscopy 1 year after curative resection for cancer of the colon and rectum and overall survival is uncertain (Abu Nada 2003; Berman 2000).

Due to the increased risk of metachronous cancer in patients who have had a primary colorectal cancer, ongoing colorectal surveillance is required. The criteria for metachronous cancer can be defined as occurrence more than 12 months after curative surgery with preoperative complete colonoscopy or one negative postoperative colonoscopic follow-up to rule out synchronous tumour and tumour arising from mucosa at a site other than the anastomosis (Lan 2005). Indirect evidence suggests that new tumours may be more prominent in the right colon but are not different in tumour stage or histology. Bouvier (2008) found that the chances of developing metachronous cancer were higher in the right colon than elsewhere in the large bowel. The site of the index tumour also appears to influence metachronous tumour risk. Patients whose index tumour is in the left colon may be at greater risk of metachronous tumour development than those with rectal primary malignancy (Lan 2005).

Indirect evidence suggests that five-year survival appears to be higher in patients who have had at least one surveillance colonoscopy over the first 5 years after resection. Rulyak et al. (2007), in an analysis of administrative data, found an association between greater 5-year survival (76.8%) and at least one follow-up colonoscopy after colorectal cancer resection compared with patients who did not undergo follow-up (52.2%, p < 0.001).

Evidence supports tailoring decisions regarding intervals at which colonoscopic surveillance is performed in patients post-colorectal cancer resection to the patient’s other individual risk factors. The presence of multiple adenomas, synchronous adenomas and synchronous colorectal carcinoma indicate increased risk of development of metachronous tumours (Balleste 2007; Cubiella Fernandez 2003; Fukutomi 2002; Togashi 2000). In these patients, more frequent surveillance colonoscopy

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may be indicated (Togashi 2000). However, in other studies these predictive factors for development of metachronous cancer have not been confirmed (Bouvier 2008; Lan 2005).

A variably intense colonoscopy surveillance schedule, based on clinical features of the individual case, has been advocated for identifying local recurrence at an early stage when they are more likely to be treatable curatively (Platell 2005).

Wang (2009) reported the results of a randomised controlled trial of more compared with less intensive colonoscopy follow-up in patients undergoing surgery for colorectal cancer and randomised to either intensive colonoscopic surveillance (at 3 monthly intervals for 1 year, 6 monthly for the next 2 years and yearly thereafter) with less intensive surveillance (at 6 months, 30 months and 60 months). Findings associated with more intensive surveillance were higher detection of asymptomatic postoperative colorectal cancers and more re-operations with curative intent and a greater probability of survival but no significant difference in 5-year survival rate.

Multi-interventional studies, where colonoscopy was one of a range of investigations used in the ongoing surveillance of patients after bowel cancer resection, have been conducted. In a meta-analysis of five randomised controlled trials of multiple interventions by Renehan (2002), more intensive follow-up was associated with significantly earlier detection of all recurrences (difference in means was 8.5 months) and an increased detection rate for isolated local recurrences than less intensive follow-up. The effect was most pronounced in trials that used computed tomography and frequent measurement of serum carcinoembryonic antigen (CEA) as part of the intensive follow-up strategy. The impact of the colonoscopic component of surveillance on the overall results is uncertain. Rodriguez-Moranta (2006), in a randomised controlled trial comparing a simple surveillance strategy for patients with stage II or III colorectal cancer of clinical evaluation and serum CEA with a strategy of colonoscopy, abdominal CT or ultrasound and chest radiograph demonstrated higher overall survival in patients with Stage II colorectal cancer and rectal cancer; colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumour recurrences. Tjandra (2007) in a meta-analysis of eight randomised trials comparing different follow-up strategies and intensities, found a reduced overall mortality with more intensive follow-up (21.8% versus 25.7%) and improved chance of curative re-resection with more intensive follow-up (10.7% versus 5.7%).

Guidelines for surveillance need to balance the variation in risk factors for recurrence or development of a further tumour in the patient with resected colorectal cancer. Published guidelines vary in the post-discharge colonoscopy surveillance intervals (Table 6).

Table 6: Colonoscopy surveillance guidelines following colorectal cancer resection

Australian Cancer Network (2005)

Following colorectal cancer resection, patients require clinical review every 3 to 6 months for 2 years then 6 monthly.

Colonoscopy should be performed within 3 to 5 years of resection and repeated every 3 to 5 years.

American Cancer Society / US Multi-Society Task Force (Rex 2006)

Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stages II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. According to these guidelines:

The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In non-obstructed colons, colonoscopy should be performed

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preoperatively. In obstructed colons, double-contrast barium enema or computed tomography colonography should be performed preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease.

After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection.

If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that examination is normal, then the interval before the next subsequent examination should be 5 years.

Shorter intervals may be indicated by associated adenoma findings. Shorter intervals also are indicated if the patient's age, family history, or tumour testing indicate definite or probable hereditary non-polyposis colorectal cancer.

Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence compared with those with colon cancer and generally require surveillance at shorter intervals.

European Panel for the Appropriateness of Gastrointestinal Endoscopy (EPAGE II) (Arditi 2009)

In patients who have received a colon cancer resection and colon clearance, colonoscopy is recommended at 1 and 3 years.

If the colonoscopy performed after colon cancer resection reveals no abnormality, follow-up colonoscopy can be performed at 5 years.

If the colonoscopy performed after colon cancer resection reveals low risk adenomas, follow-up colonoscopy can be performed at 3 to 5 years.

If the colonoscopy performed after colon cancer resection reveals high risk adenomas, follow-up colonoscopy can be performed at 1 year.

Draft national Clinical Practice Guidelines for Surveillance Colonoscopy are currently released for public consultation. These guidelines provide detailed guidance regarding appropriate timing of colonoscopy in patients who have had curative resection of colorectal cancer.

No upper age threshold was identified in included studies in this review beyond which colonoscopic surveillance should cease (Bouvier 2008; Mathew 2006).

Summary statements

Studies included in this review demonstrate a significant risk of synchronous and metachronous cancers and adenomas after resection of colorectal cancer. Colonoscopy is indicated pre- or peri-operatively to identify and manage synchronous lesions.

Studies included in this review suggest that post-operative colonoscopy performed within 12 months of surgery reduces the incidence of high-risk lesions at 1 year, including advanced adenomas, new cancer diagnoses and localised recurrence of malignancy.

Decisions regarding subsequent post-operative colonoscopies are determined according to the clinical features of the individual case. Five years is the maximum timeframe within which repeat colonoscopy is recommended in studies of patients with normal post-operative index colonoscopy. In patients with abnormal colonoscopy, repeat colonoscopy was performed at between 1 and 3 years, depending on the patients risk for subsequent neoplasia, in included studies.

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Question 1f: Patients with a past history of adenoma

There were 29 studies conducted across 11 countries and published since 1999 that addressed this question and were included in this review (Review Question 1f, Appendix 5). There were three systematic reviews, two randomised controlled trials, one case control study, nine prospective observational studies and 13 retrospective ecological studies included in the review. In addition, national guidelines from three countries (including Australia) and a study that presented a hypothetical Markov model was included (Becker 2007). The highest level of evidence of studies was Level I (prognosis studies) and Level III-2 (diagnostic and intervention studies), as outlined in Appendix 3. The sample size of included studies varied between 34 and 9,167 participants. The timeframe of included studies was up to 24 years in duration.

In the Australian guidelines, colorectal polyps are described as circumscribed masses that project above the mucosal surface of the bowel. The principal types are adenomas, hyperplastic polyps, hamartomas and inflammatory polyps. The majority of polyps within the bowel are adenomas (Australian Cancer Network 2005).

Colorectal adenomas are a precursor to the development of the majority of colorectal carcinomas. Adenomas can be classified into subtypes based on histological criteria: tubular (the most common adenoma type), villous, tubulovillous or serrated. Adenomas are also described according to their shape and can be pedunculated, sessile, flat or depressed (Australian Cancer Network 2005). Levels of cytological dysplasia are also usually reported.

In studies included in this review adenomas were demonstrated to be more common with increasing age and in male patients (Schoenfeld 2003; Stevens 2003). The risk of metachronous malignancy or advanced neoplasia depends on the histology of the adenoma (villosity), level of dysplasia, its size and in some studies, its location, and the number of adenomas at index colonoscopy. Larger adenomas, more villous adenomas, more dysplastic adenomas and larger numbers of adenomas were indicators of higher malignant potential across studies. As a result, colonoscopic surveillance intervals vary according to the characteristics of the adenoma(s) detected (Chen 2003; Cordero 2001; Fukutomi 2002; Jorgensen 2007; Laiyemo 2009; Martinez 2009; Pinsky 2009; Rostirolla 2009; Saini 2006; Winawer 2006).

Becker et al. (2007) developed a Markov model based on time-dependent transition possibilities of adenoma to cancer. Modelling was based on the Erlangen Registry of Colorectal Polyps. Outcomes were calculated for a hypothetical 50 year old patient with 30 years of follow-up after initial polypectomy. Modelling estimated that 66 out of 1,000 patients would develop a colorectal cancer during 30 years without surveillance after clearing polypectomy compared with between 6 and 13 per 1,000 patients who received colonoscopic surveillance according to intervals specified in European guidelines.

No upper threshold in number of years post-polypectomy was identified across studies beyond which colonoscopic surveillance in patients with adenomas should cease (Becker 2007; Jorgensen 2007; Winawer 2006).

Lower risk adenomas

Patients with one or two tubular adenomas less than 10 mm are at lower risk of developing colorectal cancer than other patients with colorectal neoplasia (Australian Cancer Network 2005;

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Miller 2010; Pinsky 2009; Winawer 2006). The prevalence of any adenoma at second and third colonoscopy in patients with one or two tubular adenomas less than 10mm at baseline is approximately 35% and 30% respectively and prevalence of advanced adenoma is approximately 3.6% (Miller 2010).

Follow-up colonoscopy performed between 5 years and 10 years after baseline has been advocated (Robertson 2005; Laiyemo 2008; Lieberman 2007; Miller 2010; Winawer 2006). In patients with one to two tubular adenomas less than 10mm at baseline and no adenomas on follow-up colonoscopy, further follow-up colonoscopy at 10 years has been recommended (McFall 2003; Miller 2010; Robertson 2009).

High risk adenomas

Within a 1- to 5-year interval of baseline colonoscopy, up to 40% of patients will develop further adenomas (Avidan 2002; Blumberg 2000; Glazer 2008; Laiyemo 2008).

Risk of further adenomas within 1 to 5 years is particularly elevated in patients with multiple baseline adenomas (OR=4.5 to 5.3) and baseline adenomas larger than 1 cm (OR=2.6) (Avidan 2002; Bonithon Kopp 2004; Miller 2010). In patients with high risk adenomas at baseline, the probability of advanced adenomas occurring within 1 to 5 years is between 12% and 26% and of colorectal cancer is 0.5% (Laiyemo 2008; Martinez 2009; Matsuda 2009; Miller 2010).

Long-term colonoscopic surveillance (over 20 years) in patients with all types of adenomas, performed at intervals of between 6 months and 4 years, was estimated to result in the identification of colorectal cancer in approximately 1.5% of patients (Jorgensen 2007). Patients with high risk adenomas are at increased risk for development of colorectal cancer compared with patients with low risk adenoma (Martinez 2009). Features that indicate high risk include the following: adenomas ≥ 10 mm in size, ≥ 3 adenomas, adenomas with high grade dysplasia and / or adenomas with villous features (Lieberman 2007). Risk of malignant transformation is approximately 4 times greater in patients with adenomas larger than 1cm compared with patients with adenomas smaller than 1cm (Chen 2003).

Follow-up colonoscopy of patients with high risk adenomas has been recommended to be conducted every 3 years. This is based on data from the US National Polyp Study, a randomised controlled trial of surveillance in 1,418 patients with adenoma. Follow-up every 1 year was compared with follow-up every 3 years. In this study yearly follow-up was found to confer no additional benefit in advanced adenoma detection than 3 yearly (Winawer 1993). Studies of surveillance colonoscopy performed at 3 years in patients with high risk adenomas demonstrate further adenoma detection at 3 years with a prevalence of any adenoma of up to 37% and of advanced adenoma of up to 10.5% (Fukutomi 2002; Martinez 2009; Noshirwani 2000; Pinsky 2009; Saini 2006; Winawer 2006).

The percentages of patients identified with new high grade adenomas at follow up within 3 to 5 years increases with multiplicity of adenomas at baseline from 8.6% in patients with one adenoma at baseline colonoscopy to 24% in patients with ≥5 adenomas found at baseline colonoscopy (Martinez 2009). Endorsed national guidelines and the draft national Clinical Practice Guidelines for Surveillance Colonoscopy recommend more frequent surveillance in patients with 3 or more adenomas at baseline colonoscopy (synchronous). Detailed guidance regarding surveillance

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frequency in patients with multiple adenomas is included in the draft national Clinical Practice Guidelines for Surveillance Colonoscopy.

Serrated adenomas

Serrated adenomas are histologically defined by the presence of both hyperplastic and dysplastic features. They are thought to play a role in the development of sporadic colorectal cancers (Glazer 2008).

Limited data were identified in this review that described outcomes of varying follow-up intervals for patients with serrated adenomas. One study followed up patients with serrated adenoma with colonoscopic surveillance performed at an average of 29 months after initial colonoscopic examination. A total of 24% had developed adenomatous polyps in this timeframe (Glazer 2008).

Sessile adenomas

Sessile adenomas may be tubular, tubulovillous, villous or serrated. Unlike pedunculated polyps, which are attached to the surface of the bowel wall by a stalk (or peduncle), sessile adenomas sit on the surface of the mucous membrane and do not have a stalk. Their resection may be piecemeal, resulting in the adenoma not being totally removed and leaving residual adenoma behind. This increases the risk of development of carcinoma in the incompletely removed portion (Khashab 2009).

Data from included studies in this review of colonoscopy and polypectomy performed in patients with large sessile colorectal adenomas demonstrate that approximately 18% of patients will have macroscopically evident residual adenoma at follow-up, up to 13% of which will be evident within 3 to 6 months (Khashab 2009; Seitz 2003; Salama 2009).

Follow-up colonoscopy of patients with incomplete removal has been proposed within 3 to 6 months of the index colonoscopy and further follow-up performed at 12 months to ensure complete removal; if adenoma removal at index colonoscopy is complete, the subsequent surveillance intervals are determined according to the polyp features at the index colonoscopy (Khashab 2009; Salama 2009; Seitz 2003).

Techniques of removal and the experience of the colonoscopist and centre influence endoscopic resection success. Endoscopic resection can be successfully (95%) achieved when done by well trained specialists in specialized centres with the appropriate equipment (Swan 2009).

Detailed draft national guidelines for surveillance of patients with epithelial polyps are included in the draft national Clinical Practice Guidelines for Surveillance Colonoscopy (2011). The endorsed 2005 guidelines recommend the following (Australian Cancer Network 2005):

“Colonoscopic surveillance should occur according to the following protocols:

Within a year following incomplete or possible inadequate examination; for example, in a subject with multiple adenomas.

At three years for subjects with large adenomas (>1cm), adenomas with high-grade dysplasia, villous change in adenomas, three or more adenomas, or aged 60 or more with a first-degree relative with colorectal neoplasia.

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At four to six years in subjects without the risk factors outlined above”.

Summary statement

The recommended timing of surveillance colonoscopy in patients with a past history of adenoma varies according to adenoma size, number, histological features. Surveillance intervals proposed across published studies vary between several months (in patients with incompletely removed adenomas) and 10 years (in patients with one or two lower risk adenomas and no other risk factors for colorectal cancer). In general, patients with larger adenomas, adenomas with higher grades of dysplasia, adenomas with villous components, patients with multiple adenomas, and patients with other risk factors for development of colorectal neoplasia require more frequent surveillance. Patients with incomplete or inadequate colonoscopic examination require re-examination within 12 months of the prior examination.

MBS data for timing of colonoscopy

The frequency with which a patient has a colonoscopy can be determined from Medicare data but not the clinical indication for that repeat colonoscopy. In the ten year period up until 2008/09 there were 1.7 million 32090 colonoscopies and 694,000 32093 colonoscopies rebated by Medicare. Fifty-eight per cent were performed in patients aged between 50 and 74 years. A total of 68% of patients had only one colonoscopy between 1999/00 to 2008/09 (Table 7).

Table 7: Number of patients who had colonoscopies by procedure frequency (MBS items 32090 and/or 32093) from 1999/00 to 2008/09

Frequency of procedure 1999/00 to 2008/09

Number of patients

Proportion of patients by procedure frequency

Total number of colonoscopies

Number of repeatcolonoscopies

1 1,445,715 68% 1,445,715 -

2 428,587 20% 857,174 428,587

3 159,500 8% 478,500 319,000

4 56,273 3% 225,092 168,819

5 19,482 1% 97,410 77,928

6 6,954 0% 41,724 34,770

7 2,864 0% 20,048 17,184

8 1,172 0% 9,376 8,204

9 553 0% 4,977 4,424

10 or more 469 0% 4,690 4,221

Total 2,121,569 3,184,706 1,063,137

*2009/10 data not available at time of analysis

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There were over 170,000 MBS-rebated colonoscopies (approximately 5.6% of the total number rebated) performed in over 31,000 patients who received 5 or more colonoscopies over the 10 years between 1999/00 to 2008/09. The clinical indications for which these patients received colonoscopy at this high frequency are unknown as MBS data do not provide information regarding diagnosis. Further, patients in any of these frequency categories may have had additional colonoscopies if they also received the procedure as a public patient (not captured in MBS statistics).

Summary statement

The majority of patients (68%) receiving MBS-rebated colonoscopy have not had another MBS-rebated colonoscopy in the 10 years preceding the procedure. Patient aged between 50 and 74 years receive the majority of repeat MBS-rebated colonoscopies.

Approximately 1.5% of patients received 5 or more MBS-rebated colonoscopies over a 10-year period. Available MBS data do not provide information regarding the clinical indications for colonoscopies at this higher frequency.

Question 2 - What is the effectiveness of colonoscopy in improving outcomes in each target population?

Effectiveness of colonoscopy varies according to the clinical condition for which colonoscopy is being performed. Studies that were identified by the search strategy examined effectiveness of colonoscopy across the following clinical areas:

cancer prevention;

diagnosis of pathology in symptomatic patients; and

the likelihood of a single colonoscopy leading to the detection of adenoma and / or carcinoma.

A group of studies were also identified by the search strategy that specifically referred to the relationship between various published appropriateness criteria for colonoscopy and the diagnostic yield of colonoscopy. These are also discussed below.

Consistent with other diagnostic procedures, diagnostic colonoscopy is associated with a false negative rate for detecting adenoma and colorectal cancer; the sensitivity estimated at approximately 95%. Sensitivity for diagnosis of proximal colonic lesions is lower than for other colorectal regions (Abela 2009).

Caution in interpreting the impact of colonoscopy in reducing cancer incidence is needed as published studies are mainly observational in nature or non-randomized. As a result, lead time and length time biases may affect results of studies assessing the degree of effectiveness of colonoscopy.

As outlined above, lead time bias is the bias that occurs when colonoscopy enables diagnosis of bowel cancer earlier than it otherwise would have been detected but this does not result in prolonged survival. The appearance of prolonged survival is created by measuring survival time from the point at which the disease is diagnosed until death; as colonoscopy results in earlier detection of the cancer, survival time may appear to increase solely because it advances diagnosis of the condition, not because it improves the actual survival of the patient.

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Another type of bias that affects the interpretation of results of observational studies assessing the effectiveness of surveillance colonoscopy is length time bias. This type of bias occurs in studies of surveillance colonoscopy because faster-growing bowel cancers generally have a shorter asymptomatic period than slower-growing tumours and are therefore less likely to be detected by surveillance colonoscopy performed over time. Faster-growing tumours are often associated with a poorer prognosis than slower-growing tumours. As a result of these factors, slower-growing tumours are likely to be over-represented in surveillance colonoscopy data. This means that surveillance colonoscopy may erroneously associated with improved survival, even if it had no actual effect on mortality.

Question 2a: What is the effectiveness of colonoscopy in cancer prevention?

There were 36 studies conducted across 11 countries and published since 1999 that addressed this question and were included in this review (Review Question 2a, Appendix 5). There were two systematic reviews, three randomised controlled trials, four case control studies, seven prospective observational studies and 19 retrospective ecological studies included in the review. In addition, a study that presented a hypothetical Markov model was included (Becker 2007). The highest level of evidence of studies was Level I for effectiveness of surveillance in general and Level II for effectiveness of colonoscopy in cancer prevention in patients with a previous diagnosis of adenoma or colorectal carcinoma. However, randomised controlled trials compared colonoscopy performed at different intervals or with different combinations of other surveillance methods, rather than comparing colonoscopy with controls that received no surveillance. The sample size of included studies varied between 102 and 54,803 participants. The timeframe of included studies was up to 24 years in duration.

Studies examining the effectiveness of colonoscopy in cancer prevention were conducted in the following patient groups:

population screening for colorectal cancer;

cancer prevention in patients who have received previous colonoscopy;

patients with a past history of colorectal tumours (adenoma and / or carcinoma); and

patients with a high-risk familial condition that predisposes to colorectal cancer.

Population screening

Studies that specifically examined the effectiveness of colonoscopy in population screening were excluded from further analysis as this topic was specifically outside the scope of the review.

Cancer prevention in patients who have received previous colonoscopy

No randomised controlled trials of colonoscopy directly addressed the question of cancer prevention in patients without a past history of adenoma or colorectal carcinoma.

Indirect evidence from included studies supported the effectiveness of colonoscopy in preventing the development of cancer in adults who have ever received a previous colonoscopy. Case control studies conducted in patients who have been diagnosed with colorectal cancer and compared with population data or matched controls showed that patients who have ever received a previous

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colonoscopy are 37% to 88% less likely to develop colorectal cancer and 29% less likely to die from colorectal cancer than those who have not received a colonoscopy (Baxter 2009; Chen 2003; Singh 2006; Singh (1and 2) 2010). Several, but not all, studies have been unable to document protection afforded by colonoscopy for right sided cancer, though protection from left sided cancer is strong (Baxter 2009; Bressler 2007).

The strength of the association between colonoscopy and colorectal cancer risk was dependent on the age of the patient. In people aged 50 years and over the incidence of colorectal cancer was significantly lower among those who have had a previous colonoscopy (1.1 versus 2.3 diagnoses per 1,000 patient-years) compared with people aged 35 to 49 years (0.35 versus 0.31 diagnoses per 1,000 patient years) (Croese 1999).

Although colonoscopy was effective in preventing many colorectal cancers, the procedure was associated with varying rates of ‘missed’ or ‘interval’ cancer in some included studies, where patients were identified with colorectal cancer between colonoscopies (Pabby 2005). Approximately 22% of polyps are missed on colonoscopy, including 2% of adenomas ≥ 10 mm. Miss rates are higher for lesions in the proximal colon than distal colon and are operator-dependent (Heresbach 2008; van Rijn 2006).

Between 0.5% and 5% of adults who receive a complete colonoscopy in ‘usual’ colonoscopy practice will be identified with colorectal cancer within 3 to 5 years of their index procedure (Ee 2002; Farrar 2006; Seow 2006). Observational studies have shown that between 2% and 9% of patients diagnosed with colorectal cancer have had a colonoscopy within 6 to 36 months prior to diagnosis (Bressler 2007; Frenette 2007); 6% have had colonoscopy within the previous 43 months (Leaper 2004); and 5% have had a colonoscopy within 5 years of their diagnosis (Gorski 1999).

Patients with a past history of colorectal tumour (adenoma and / or carcinoma)

The majority of data regarding the effectiveness of colonoscopy in patients with a past history of colorectal tumour (either adenoma and / or carcinoma) are derived from observational studies. Where randomised controlled trials have been performed, patients in control groups have generally also received colonoscopy (usually at different intervals to patients in intervention groups) (e.g. Jorgensen 2007; Wang 2009) or colonoscopy has been combined with additional surveillance activities (including clinical examination, CT or ultrasound scans, CEA levels) (e.g. Rodriguez-Moranta 2006; Rulyak 2007).

Effectiveness of colonoscopy depends on the type of tumour for which surveillance is being conducted. Lieberman (2007) matched subjects with neoplasia to neoplasia-free controls and assigned them to colonoscopic surveillance within 5 years. The relative risk of advanced neoplasia (defined as tubular adenoma ≥10 mm, adenoma with villous histology, adenoma with high-grade dysplasia or invasive cancer) within 5.5 years was calculated. Relative risk in patients with baseline neoplasia was 1.9 (95%CI 0.8-4.4) with 1 or 2 tubular adenomas < 10mm, increasing to 6.9 (95%CI 2.6-18.1) for adenoma with high-grade dysplasia.

Included studies suggest that colonoscopy in patients with adenomas is associated with lower incidence of subsequent colorectal cancer and reduced colorectal cancer mortality. Jorgensen (2007) evaluated long-term surveillance in patients with all types of adenomas. Patients had initial colonoscopy then were randomised to surveillance at intervals that varied between 6 and 48 months.

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Colorectal cancer was found in 27 patients, the expected number being 41 (RR 0.65; 95% CI 0.43-0.95). Three of the 27 patients died from colorectal cancer, the expected number being 25 (RR 0.12; 95% CI 0.03-0.36). Leung (2010) conducted a prospective cohort study of patients with a prior history of polyp detection who were receiving ongoing surveillance colonoscopy. Patients were recruited from the US National Polyp Prevention Trial and followed for a median of 10.5 years. The ratio of colorectal cancers observed compared with that expected from US population data was 0.74 (95% CI 0.47-1.05). Patients in whom colorectal cancer was detected received an average of 3 colonoscopies over the surveillance period.

Indirect evidence also suggests that colonoscopy in patients with previous colorectal cancer is associated with detection of further tumours of the bowel and may improve survival compared with patients who receive no follow-up colonoscopy. Yusoff (2003) audited records of all patients who underwent colonoscopy following surgical resection of colorectal cancer between 1989 and 2001. The diagnostic yield of surveillance colonoscopy within 12 months of colorectal cancer resection was as follows: adenoma was identified in 9% of patients; advanced adenoma in 1%; and recurrent cancer in 1%. Rulyak (2007) analysed an organisational administrative database of patients with colorectal cancer. Results suggested that the 5-year survival was higher (77%) for patients who had at least one follow-up colonoscopy examination than for patients who did not undergo follow-up (52%). Fisher (2003) conducted a retrospective analysis of administrative data in patients with a new diagnosis of colorectal cancer. The primary outcome studied was 5-year mortality. Results suggested that the risk of death due to colorectal cancer was decreased by 43% (HR 0.57; 95% CI 0.51-0.64) in the group who had at least one follow-up colonoscopy compared with patients who had no follow-up colonoscopies after a diagnosis of non-metastatic colorectal cancer.

Becker et al. (2007) developed a Markov model based on time-dependent transition possibilities of adenoma to cancer. Modelling was based on the Erlangen Registry of Colorectal Polyps. Outcomes were calculated for a hypothetical 50 year old patient with 30 years of follow-up after initial polypectomy. Modelling estimated that patients under colonoscopic surveillance have an 84% to 94% reduction in risk from colorectal cancer compared with those who do not receive surveillance. Patients under colonoscopic surveillance were estimated to have a mean lifetime gain of between 98 and 110 days compared with patients who do not come for surveillance.

Multi-interventional studies, where colonoscopy was one of a range of investigations used in the ongoing surveillance of patients after bowel cancer resection, suggest that intervention strategies that include follow-up colonoscopy improve mortality outcomes. In a meta-analysis of five randomised controlled trials of multiple interventions by Renehan (2002), intensive follow-up, particularly where CT and serum CEA were incorporated into surveillance protocols, was associated with a reduction in all cause mortality (risk ratio 0.81; 95% CI 0.7 to 0.94). The impact of the colonoscopic component of surveillance on the overall results is uncertain. Rodriguez-Moranta (2006), in a randomised controlled trial comparing a simple surveillance strategy for patients with stage II or III colorectal cancer of clinical evaluation and serum CEA with a strategy of colonoscopy, abdominal CT or ultrasound and chest radiograph demonstrated no difference in the probability of survival after a median follow-up of 48 months. However, higher overall survival in patients with Stage II colorectal cancer and rectal cancer was observed in patients receiving more intensive surveillance and colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumour recurrences.

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Patients with high-risk familial and clinical conditions

Observational studies suggest surveillance colonoscopy may improve some colorectal cancer-related outcomes in patients with a genetic predisposition to colorectal cancer (Dove-Edwin 2005; Jarvinen 2000; Stupart 2009). A prospective cohort study conducted by Stupart et al. (2009) in patients with a gene mutation of MLH1 observed:

a lower incidence of colorectal cancer over a median follow-up of 5 years in patients undergoing surveillance (11% in patients who underwent surveillance colonoscopy versus 27% in patients who declined surveillance colonoscopy);

detection of cancer at a significantly earlier stage than in patients not undergoing surveillance; and

fewer deaths from colorectal cancer in patients undergoing surveillance (2% versus 12%).

Similarly, Dove-Edwin et al. (2005), in a prospective study of patients with HNPCC, found a lower incidence of colorectal cancer in patients under surveillance than in the absence of surveillance. Jarvinen (2000) found rates of colorectal cancer were reduced by 62% in at-risk family members of families with HNPCC who received 3-yearly colonoscopy compared with those who did not receive surveillance colonoscopy.

However, the impact of lead time bias on these results is uncertain. Randomised controlled trials are required in order to determine the association between survival time and surveillance colonoscopy in these population groups.

In contrast, uncontrolled studies in patients with a family history of colorectal cancer who do not also have an inherited condition that predisposes to colorectal cancer do not appear to derive benefit from surveillance colonoscopy that is over and above that of the general population in studies included in this review (Beaudin 2000; Kahi 2007; Martinez 2009; Schoenfeld 2003).

Included studies demonstrated the effectiveness of surveillance colonoscopy in improving disease-related outcomes in many patients with inflammatory bowel disease, particularly in patients with ulcerative colitis (Collins 2008; Lutgens 2009; Velayos 2006). Colectomy may be able to be delayed in patients undergoing surveillance (Collins 2008). Evidence from included studies suggests that cancers tend to be detected at an earlier stage in patients with inflammatory bowel disease who are undergoing surveillance, and these patients have a correspondingly better prognosis (Collins 2008). Surveillance colonoscopy has been found to decrease the risk of colorectal cancer in patients who had received 1 to 2 surveillance colonoscopies (OR=0.4 (95% CI 0.2 to 0.7) and in patients who had received > 2 surveillance colonoscopies (OR=0.3 (95% CI 0.1 to 0.8) over a 26 year study period (Velayos 2006).

Colonoscopic surveillance may reduce the risk of death from IBD-associated colorectal cancer. Collins et al. (2008), in a meta-analysis of observational studies, found a 19% reduction in colorectal cancer mortality in patients with inflammatory bowel disease who receive colonoscopic surveillance compared with patients who did not receive colonoscopic surveillance (Collins 2008). The 5-year survival from colorectal cancer in patients undergoing surveillance was 77% to 100%, compared with 36% to 74% in patients not undergoing surveillance (Collins 2008; Lutgens 2009).

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However, there is no clear evidence that surveillance colonoscopy prolongs survival in patients with extensive colitis (Collins 2008; Kottachchi 2009). These data, and data published by Velayos (2006) demonstrate the need for randomised controlled trials in order to determine the association between survival time and surveillance colonoscopy in patients with inflammatory bowel disease, and to account for lead time and length time bias inherent in observational study design.

Summary statement

Colonoscopy is a diagnostic and therapeutic tool that is used for the prevention and early identification of colorectal neoplasia in patients in whom the procedure is indicated. Colonoscopy appears to prevent colorectal cancer from developing in many at-risk patients through the identification and removal of pre-malignant tumours; appears to assist in the identification of malignant tumours at an earlier disease stage than would otherwise be detected; and may be colon-sparing in some patients with inflammatory bowel disease.

Question 2b: What is the effectiveness of colonoscopy in diagnosis of pathology in symptomatic patients?

There were 14 studies conducted across 10 countries and published since 1999 that addressed this question and were included in this review (Review Question 2b, Appendix 5). There were two case control studies, three prospective observational studies and 9 retrospective ecological studies included in the review. The highest level of evidence of studies was Level III-2. The sample size of included studies varied between 90 and 41,775 participants.

Significant heterogeneity was observed across included studies, reflecting that colonoscopy is indicated in the diagnosis of a broad range of colorectal conditions.

Retrospective analyses of data obtained from ‘usual’ clinical practice demonstrated that patients who are symptomatic for the presence of colorectal pathology form a significant proportion of colonoscopy caseloads; between 40% and 60% and of patients presenting for colonoscopy had symptoms suggestive of colorectal disease (Adler 2007; Keren 2008). In symptomatic patients colonoscopy results in positive findings in between 10% and 50% of patients; of these, 60% of patients have pathology diagnosed that is unrelated to the symptom that led to the colonoscopy being performed (Lasson 2008).

Across included studies the overall effectiveness of colonoscopy of diagnosing pathology (the ‘diagnostic yield’) varied according to the personal and clinical characteristics of the person receiving colonoscopy. Endoscopists whose clinical caseload includes a greater proportion of patients who are older, in at-risk cultural or social groups, who have a higher prevalence of familial and / or non-familial conditions or previous significant colorectal neoplasia had a higher diagnostic yield among their patients (Ang 2002; Carlo 2006).

Diagnostic yield increased significantly with increasing age (Ang 2002; Carlo 2006). An approximate doubling in the identification of overall pathology and of significant colonic neoplasia was observed in patients over the age of 45 to 50 years compared with younger patients (Carlo 2006; Keren 2008). The symptoms more commonly associated with significant colonic neoplasia included rectal pain, unexplained weight loss and rectal bleeding (Keren 2008). Diagnostic yield of colonoscopy for detection of significant colonic neoplasia was also increased in patients with abnormal imaging and / or elevated carcionembryonic antigen levels (Keren 2008).

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Diagnostic yield varied according to the specific symptoms under investigation. In patients with rectal bleeding the diagnostic yield of colonoscopy was between 31% and 66% of patients, with significant colonic neoplasia identified in between 13% and 17% of patients (Carlo 2006; Lasson 2008; Sanchez 2005). In patients with non-specific gastrointestinal symptoms, the diagnostic yield of colonoscopy was lower at approximately 13.2%, with adenomas detected in 6% of patients and significant colonic pathology identified in approximately 2.2% of patients (Ang 2002; Lasson 2008; Schoepfer 2005).

The effectiveness of colonoscopy in the diagnosis of pathology in patients with iron deficiency anaemia varied across studies. Colonoscopy revealed a bleeding source in 12% to 14% of patients with iron deficiency anaemia (Fireman 1999; Landy 2010; Park 2009). The most frequently detected abnormalities included diverticulosis and haemorrhoids (Park 2006; Stephens 2006). Between 5% and 9% of patients with iron deficiency anaemia and an identified bleeding source were shown to have suspected colorectal cancer (Landy 2010; Park 2009; Stephens 2006). The likelihood of association between iron deficiency anaemia and colorectal cancer was influenced by the patient’s age. Data collected from premenopausal women with iron deficiency anaemia demonstrated no differences in the frequency of clinically relevant lesions detected at colonoscopy between cases and controls; clinically relevant lower gastrointestinal lesions were found in approximately 5.6% of patients and 5.2% of controls (Park 2006). In contrast, in older patients with iron deficiency anaemia, up to 22% have polyps and / or colorectal cancer (Stephens 2006).

The diagnostic yield in patients with irritable bowel syndrome was not consistent across included studies. Patients with symptoms consistent with non-constipation irritable bowel syndrome did not have an increased risk of significant colonic pathology compared with healthy controls in a case control study conducted by Chey et al. (2010). However, retrospective review of colonoscopic procedures data by Keren et al. (2008) demonstrated a risk of significant colonic neoplasia in patients with irritable bowel syndrome of approximately 9% (Keren 2008). As patients in the study conducted by Chey (2010) were significantly younger than controls, this may account for the lack of association observed in study results.

Colonoscopy appears to be of limited effectiveness in diagnosing significant pathology in patients whose only symptom or risk factor is constipation (Gupta 2010; Pepin 2002). Constipation in conjunction with other symptoms had a higher diagnostic yield at colonoscopy than colonoscopy alone. Retrospective review of endoscopic databases from three hospitals, conducted by Pepin (2002) demonstrated that colorectal cancer was detected in 1.7% of patients with constipation, adenomas in 19.6% and advanced lesions in 5.9%. No case of colorectal cancer occurred in a patient whose sole symptom was constipation (Pepin 2002).

Summary statement

The effectiveness of colonoscopy in the diagnosis of pathology in symptomatic patients varies according to the personal and clinical characteristics of the patient. Rates of diagnosis of significant pathology are higher in older compared with younger patients; and in patients whose symptoms include rectal bleeding or unexplained weight loss. Older compared with young patients with iron deficiency anaemia and patients with abnormal imaging and / or elevated carcinoembryonic antigen levels also have higher rates of diagnosis of significant pathology at colonoscopy.

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Question 2c: What is the likelihood of a single colonoscopy leading to the detection of an adenoma and / or colorectal cancer?

The likelihood of a single colonoscopy leading to the detection of an adenoma and / or colorectal cancer varies considerably according to the many factors affecting individual risk, described in the preceding sections.

There were 13 studies conducted across 8 countries and published since 1999 that specifically addressed this question and were included in this review (Review Question 2c, Appendix 5). There were two case control studies, three prospective observational studies and 9 retrospective ecological studies included in the review. In addition, administrative data collected from participants of the Australian National Bowel Cancer Screening Program (NBCSP) were identified and reviewed. The highest level of evidence of studies was Level III-2. The sample size of included studies varied between 90 and 41,775 participants. The timeframes over which data were appraised varied between 12 months and 11 years between studies.

The likelihood of a single colonoscopy leading to the detection of an adenoma and / or carcinoma varied across studies according to the clinical and personal characteristics of the patient and according to the technical aspects of the colonoscopy itself. Multiple patient risk factors increased the prevalence of adenoma and / or carcinoma in participants, including patient age, gender, certain inherited conditions, inflammatory bowel disease, past history of adenoma and / or colorectal cancer and symptoms suggestive of colorectal pathology (Bradshaw 2003; Cottet 2007; Dowling 2000; Gilbert 2001; Keren 2008; Lee 2002; Menges 2006; Terhaar Sive Droste 2009).

The majority of studies were conducted in ‘usual’ colonoscopic practice and assessed the prevalence of colorectal neoplasia in consecutive patients that presented for colonoscopy for any indication. Overall, ‘significant colonic neoplasia’ (defined as a suspected malignant mass or polyp greater than 9 mm in diameter) was identified in between 7% and 13% of participants of studies included in this review (Keren 2008; Terhaar Sive Droste 2009):

colorectal cancer was diagnosed in between 0.3% and 6% of patients in whom colonoscopy was performed (Bowles 2004; Lee 2002; Loffeld 2005; Park 2006; Smith 1999; Terhaar Sive Droste 2009);

‘polyps’ were diagnosed in between 9% and 23% of patients in whom colonoscopy was performed (Bowles 2004; Lee 2002; Loffeld 2005; Menges 2006);

adenomas were diagnosed in approximately 7% to 8% of patients in whom colonoscopy was performed (Menges 2006; Park 2006; Terhaar Sive Droste 2009).

A subgroup of studies specifically examined the effectiveness of single colonoscopy in detecting adenoma / cancer in patients with a family history of colorectal cancer. Across these studies:

36% have ‘polyps’ (compared with 21% of controls);

4% to 25% have adenoma – risk is increased with increasing strength of family history and is significantly higher in patients aged over age 50 years compared with those less than 50 years (Bradshaw 2003; Cottet 2007; Dowling 2000; Gilbert 2001; Menges 2006; Syrigos 2002); and

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0.4% to 0.9% of patients have carcinoma (Dowling 2000; Gilbert 2001).

Data collected from participants of the NBCSP provide an estimate of the likelihood of a single colonoscopy detecting adenoma and / or carcinoma in people aged 50, 55 or 65 years with a positive faecal occult blood test (FOBT). Population-based colorectal cancer screening in Australia is available through the NBCSP. Approximately 40% of Australians in the target age groups participate in the Program. Of these, 6.6% return a positive FOBT, 76% of whom are recorded as having had a colonoscopy. Overall, 3.9% of participants with a positive FOBT are subsequently demonstrated to have suspected or confirmed cancer, 15.1% have confirmed adenomas, 32.3% have polyps and 48.7% have no cancer or adenoma (AIHW 2010).

Summary statement

The likelihood of a single colonoscopy leading to the detection of an adenoma and / or carcinoma varied across studies according to the clinical and personal characteristics of the patient and according to the technical aspects of the colonoscopy itself. Colorectal carcinoma was detected in between 0.3% and 6% of patients in ‘usual’ colonoscopic practice in this review; and adenomas were diagnosed in up to 25% of patients.

Question 2d: What is the relationship between appropriateness criteria for colonoscopy and diagnostic yield?

There were 14 studies conducted across 14 countries and published since 1999 that specifically addressed this question and were included in this review (Review Question 2d, Appendix 5). There were 13 included prospective studies that examined the relationship between appropriateness criteria and the diagnostic yield of colonoscopy and one study that evaluated compliance of clinicians with appropriateness criteria (Grassini 2008). Findings of studies were generated through comparison of patient cohorts with appropriateness criteria. The size of the case series that was analysed varied between 244 and 5,213 patients across studies. The timeframes over which data were appraised varied between 6 days and 4 years. The highest level of evidence was Level III-2.

Appropriateness criteria that were appraised across studies included the ASGE, EPAGE, Italian Society of Digestive Endoscopy (SIED) and criteria developed according Rand Corporation/University of California at Los Angeles (RAND/UCLA) panel method.

Across studies included in this review, the proportion of colonoscopies that were considered to be inappropriate relative to all colonoscopies performed was between 2% and 37% (Bersani 2005; Hughes-Anderson 2002).

However, the diagnostic yield of ‘inappropriate’ colonoscopy was substantial. Relevant findings were identified in between 14% and 48% of ‘inappropriate’ colonoscopies, depending on the case series and criteria used (Adler 2007; Gonvers 2007; Kmieciak 2003). Significant colonic neoplasia was identified in between 7% and 12% of ‘inappropriate’ colonoscopies (Adler 2007; Jabar 2004; Kmieciak 2003; Suriani 2009).

The diagnostic yield of colonoscopy was higher for ‘appropriate’ compared with ‘inappropriate’ colonoscopies across most studies (42% versus 21% in Balaguer 2005; 29% versus 20% in Bersani 2005; 26% versus 17% in De Bosset 2002; 48% versus 20% in Jabar 2004; 43% versus 16% in

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Morini 2001). In other studies, appropriateness of indication was not a predictive factor for positive findings or colorectal cancer (Chan 2006; Kmieciak 2003).

Different appropriateness criteria, when applied to the same case series, yielded different proportions of colonoscopies that were coded as ‘inappropriate’ in the two studies where this was appraised. In the first study the diagnostic yield of EPAGE criteria were higher than ASGE criteria (Adler 2007); and in the second study the diagnostic yield of ASGE criteria were higher than SIED criteria (Grassini 2007).

One included study assessed appropriateness of patient referral for colonoscopy before and after an educational intervention using ASGE / SIED criteria and designed to decrease inappropriate colonoscopy referrals by family physicians. The intervention was associated with a 15% reduction in inappropriate colonoscopy referrals (Grassini 2008). However, patient outcomes associated with non-referral in patients that otherwise may have been referred were not assessed.

Summary statement

Appropriateness criteria identify patients in whom the diagnostic yield from colonoscopy is greater. Patients in whom appropriateness criteria assess colonoscopy as ‘inappropriate’ may also have significant pathology present, although the diagnostic yield in this group is lower.

Question 3: How do safety and quality outcomes of colonoscopy vary according to the procedural volumes of colonoscopists and with certification / re-certification processes?

Studies were coded separately according to:

procedural volumes of colonoscopists; and

certification / re-certification processes.

Question 3a: How do safety and quality outcomes of colonoscopy vary according to the procedural volumes of colonoscopists?

There were 5 studies conducted across 3 countries and published since 1999 that specifically addressed this question and were included in this review (Review Question 3a, Appendix 5). There were four retrospective studies of colonoscopy case series and one prospective study among members of the Society of American Gastrointestinal Endoscopic Surgeons (Wexner 2001). The highest level of evidence of studies was Level III-2. The size of the case series that was analysed varied between 13,580 and 328,167 colonoscopies.

In addition, national guidance documents regarding procedural volumes of colonoscopists, certification and re-certification processes and colonoscopy were also identified and appraised. Significant heterogeneity was observed across the results of the five included studies that addressed this review question. Varying definitions of ‘low volume’ versus ‘high volume’ colonoscopists were applied across studies. ‘Low volume’ was defined (largely by quartile or quintile) as: <10, ≤33, ≤141, ≤154 and <591 colonoscopies a year; ‘high volume’ was defined (also by quartile or quintile) as ≥83, ≥100, ≥379, ≥508 and ≥1,301 colonoscopies a year.

Although heterogeneity between studies and the presence of multiple co-factors that also influence safety and quality outcomes of colonoscopy prevent a precise volume quality threshold being described, the following observations are made:

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the relationship between procedural volume and the detection of colorectal cancer, and detection and removal of polyps, was examined in two included studies. In one study the likelihood of detection of colorectal cancer and of detection and removal of polyps was shown to be higher for higher volume colonoscopists. In the other study that examined this outcome no association was found (Ko 2010; Rabeneck 2010);

the relationship between procedural volume and post-colonoscopy development of colorectal cancer was examined in one study. Results demonstrated that patients who have their colonoscopies performed by the lowest volume colonoscopists had an increased risk of developing colorectal cancer within 10 years of a negative endoscopy (Rabeneck 2010); and

the relationship between procedural volume and adverse outcomes of colonoscopy was examined in three included studies. Two studies demonstrated that the likelihood of complications associated with colonoscopy was between 1.4 and 3 times higher in endoscopists performing lower volumes of procedures (Lorenzo-Zuniga 2010; Rabeneck 2008). A third study failed to demonstrate an association between annual number of colonoscopies and rate of complications (Wexner 2001). However, this same study demonstrated that completion rates and time to completion increase as procedural volumes increase.

National guidance documents regarding procedural volumes of colonoscopists and quality outcomes provided the following:

according to guidelines on training and experience issued by GESA and the findings of a literature review conducted by the Quality Working Group of the National Bowel Cancer Screening Program, the procedural volume of colonoscopists is one of a range of measures of the proficiency of the colonoscopist (GESA 2006; NBCSP Quality Working Group 2009);

according to the findings of a systematic literature review conducted in the development of the Australian Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer (2005), the endoscopist’s training and overall experience, the quality of bowel preparation, sedation and a range of patient-specific factors influence procedural quality (Australian Cancer Network 2005); and

a range of other indicators that are used as measures of the procedural quality of colonoscopists include caecal intubation rates, instrument withdrawal times, adenoma detection rates and complication rates (Australian Cancer Network 2005; GESA 2006; NBCSP Quality Working Group 2009).

The Quality Working Group of the National Bowel Cancer Screening Program recommends that each colonoscopist performs more than 250 procedures per 5 years. This is within the range of procedural volumes associated with safe, high quality outcomes of colonoscopy identified in studies included in this review.

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Medicare data for procedural volumes

A high degree of variation in the procedural volumes of colonoscopists accessing MBS items for colonoscopy is observed in MBS data (Table 8). A significant limitation of the MBS data is that they do not capture the procedural volumes of colonoscopists who also provide services in health services where colonoscopy is not MBS-rebated, such as public hospitals, limiting the applicability of findings from MBS procedural volumes to describing the procedural volumes of practitioners.

There were 1,580 medical practitioners who performed colonoscopies that were rebated under Medicare in 2008/09. Of these, the majority were specialist gastroenterologists (N=449) or general / colorectal surgeons (N=685) (Table 8). The majority of specialist gastroenterologists perform greater than 300 MBS-rebated colonoscopies a year (Table 8).

The Quality Working Group of the National Bowel Cancer Screening Program recommends that each colonoscopist performs more than 250 procedures per 5 years. This represents an average of 50 colonoscopies a year. There were 625 providers (40%) who performed fewer than 50 MBS-rebated colonoscopies in 2008/09. However, as outlined above, the number of colonoscopies that providers perform in non-private settings is not included in this analysis. Therefore a proportion of these providers may be performing additional colonoscopies that result in the colonoscopist achieving greater than 50 colonoscopies for the 2008/09 financial year. The majority of general practitioners, other specialist medical practitioners and other specialist surgeons perform fewer than 10 MBS-rebated colonoscopies a year (Table 8).

Table 8: Number of providers performing MBS-rebated colonoscopies in 2008/09 by provider category*

Number of colonoscopies

Provider category <10 11-50 51-100 101-299 >300 Total

Gastroenterologist 16 4% 34 7% 34 7% 105 19% 260 58% 449

General / colorectal surgeon

92 13% 144 21% 108 16% 197 29% 144 21% 685

Other physician 44 29% 16 10% 7 5% 29 19% 58 38% 154

Other specialist surgeon

8 62% ≤5 ** ≤5 ** ≤5 ** ≤5 ** 13

General Practitioner 229 94% ≤5 ** ≤5 ** ≤5 ** ≤5 ** 244

Other specialist medical practitioner

35 100% 0 0% 0 0% 0 0% 0 0% 35

All Providers 424 27% 201 13% 153 10% 335 20% 467 30% 1,580

*2009/10 data not available at time of analysis; **small numbers suppressed

Table 9 describes the average number of services provided by colonoscopists performing >300 colonoscopies a year. In 2008/09, 90% and 87% of gastroenterologists and other physicians that perform colonoscopies were high volume providers (performed > 300 colonoscopies a year). Smaller proportions of each other specialty group were classified as high volume providers. In general their average number of services in 2008/09 was less than for gastroenterologists. The exception was for the high volume GP/Other Medical Practitioner category where the average

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number of colonoscopies in 2008/09 was 876. Overall the 30% of clinicians who are high volume providers perform 81% of all colonoscopies.

Table 9: Average number of services by providers performing > 300 procedures a year in 2008/09*

Provider category Number of providers

Average number of services

% of services for provider category

Gastroenterologist 260 856 90%

General/colorectal surgeon 144 557 62%

Other physician 58 754 87%

Other specialist surgeon ** ** **

General Practitioner ** ** **

Other specialist medical practitioner

0 0 0%

All 467 751 81%

*2009/10 data not available at time of analysis; **small numbers suppressed

Summary statements

Procedural volume is one of a range of factors affecting the procedural quality of colonoscopy. Included studies demonstrate a trend towards improved procedural quality with increasing numbers of procedures performed, provided the colonoscopist is appropriately trained.

Relationships between the procedural volume of the colonoscopist and detection of adenomas, development of subsequent colorectal cancer and adverse outcomes associated with colonoscopy have been observed. There is no clearly identifiable threshold volume of colonoscopy procedures below which procedural quality and safety declines noticeably in studies included within this review.

Medicare data indicate that the majority of providers performing MBS-rebated colonoscopy achieve procedural volumes above the minimum threshold recommended by the Quality Working Group of the National Bowel Cancer Screening Program. Medicare data are insufficient to determine the procedural volumes of all colonoscopists as procedures performed in public settings are not included in this dataset.

Question 3b: How do safety and quality outcomes of colonoscopy vary according to certification / re-certification processes?

The following definitions were used for the purposes of the review (from: “Improving Colonoscopy Services in Australia: A report from the National Bowel Cancer Screening Program Quality Working Group”):

“Certification refers to the process of recognition of training undertaken by medical trainees by a properly constituted and nationally recognised body. At present the Conjoint Committee for the Recognition of Training in Gastrointestinal Endoscopy (Conjoint Committee) performs this role with the approval of the professional bodies whose

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members undertake colonoscopy. The Conjoint Committee undertakes this role in an unofficial and voluntary capacity with the aim of promoting professional standards.

“Re-certification refers to the process of ongoing recognition of colonoscopists once they are certified, i.e. a regular re-certification process to ensure that skills and knowledge are maintained and up-to-date. At present there is no such process.

There were no studies identified by the search strategy that specifically addressed this review question. A significant body of research was identified that demonstrated a consistent and positive association between training and the delivery of safe, high quality colonoscopy services. However, no studies assessed the effectiveness of processes for recognising training, nor did studies appraise the effectiveness of processes for ongoing recognition of colonoscopists once they are certified.

The report “Improving Colonoscopy Services in Australia: A report from the National Bowel Cancer Screening Program Quality Working Group”, was identified by the search strategy. This report describes an extensive policy development process undertaken by The Quality Working Group of the National Bowel Cancer Screening Program in order to identify principles for certification and re-certification of colonoscopists in Australia (Quality Working Group, 2009).

The Quality Working Group recommends that “compulsory certification by the Conjoint Committee should be introduced for all proceduralists performing colonoscopies as a prerequisite for making claims under the MBS and participating in the NBCSP”.

According to the report, the Quality Working Group considers that a system of national accreditation for facilities and certification of individuals, supported by a strong education and training system will result in better health outcomes from colonoscopy services. Specifically the Quality Working Group considers that improvements in quality will be best served by development of a formal process to ensure the ongoing competency of proceduralists through a nationally recognised mandatory certification and eventual re-certification system; and through investigation of future training needs and delivery tools for colonoscopy training, especially the practicality and viability of establishing accelerated training programs for proceduralists who seek additional training.

Summary statement

No studies were identified that appraised the impact of certification or re-certification processes on the safety and quality outcomes of colonoscopy.

The Quality Working Group of the National Bowel Cancer Screening Program (NBCSP) recommends that “compulsory certification by the Conjoint Committee should be introduced for all proceduralists performing colonoscopies as a prerequisite for making claims under the MBS and participating in the NBCSP”.

Question 4 - How cost-effective is colonoscopy in each target population?

There were seven studies conducted across 4 countries (Italy, Norway, Germany and United States) published since 1999 that specifically addressed this question and were included in this review (Review Question 4, Appendix 5). There were three studies that utilised a decision analysis model to generate incremental cost-effectiveness ratios (ICERs), one micro-costing and time-and-motion study which generated estimated of median costs of colonoscopy (Henry 2007), two cost benefit analyses and one cost utility analysis (Saini 2010).

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The cost of an individual surveillance colonoscopy varied widely between studies, reflecting variation in clinical practice and models for funding healthcare between countries. The median direct health care cost of colonoscopy was estimated at between $200 USD and $379 (USD) per procedure; and the total societal cost at $923 (USD) per procedure (Henry 2007; Korner 2005; Menges 2006).

Hassan et al. (2008) evaluated the cost-effectiveness of appropriate versus inappropriate colonoscopy, based on both ASGE and EPAGE criteria. According to results, the numbers of appropriate and inappropriate colonoscopies that needed to be performed to detect one patient with cancer were 18 and 93 respectively. Similarly, 115 and 617 colonoscopies would be needed, respectively, to prevent one colorectal cancer-related death. However, colonoscopy performed for ‘appropriate’ and ‘inappropriate’ indications was more cost-effective than not performing colonoscopy at all in this study; the ICER for appropriate and inappropriate colonoscopies combined, compared with a policy of not referring patients to colonoscopy at all, was $6,154 versus $31,807 per life-year gained respectively.

Hassan et al. (2009(1)) applied the same methods to assess the cost-effectiveness of surveillance colonoscopy one year after polypectomy in 60-year-old patients with a history of endoscopic polypectomy and one year after colorectal cancer resection. In patients receiving post-polypectomy follow-up, colonoscopy at one year was relatively inefficient - the number of one year surveillance colonoscopies needed to detect one cancer and to prevent one cancer-related death was 354 and 1,437 respectively. Colonoscopic surveillance at one year after polypectomy was estimated to cost $66,136 (USD) per life-year gained. Saini et al. (2010) demonstrated that colonoscopy performed every 3 years in patients with high-risk adenomas and every 10 years in patients with low-risk adenomas was cost-effective compared with no surveillance (ICER of $5,743 (USD) per quality adjusted life year gained) and compared with a strategy of 3-yearly / 5-yearly surveillance in patients with high- and low-risk adenomas respectively (ICER of $296,266 (USD) per QALY).

In contrast, colonoscopic surveillance at one year in patients post-colorectal cancer resection was found to be more cost effective. The number of one year colonoscopies needed to detect one colorectal cancer and to prevent one cancer-related death was estimated by Hassan et al. (2009(2)) as 143 and 926 respectively; and the cost per life-year gained was estimated as $40,313 (USD). Korner et al. (2005) demonstrated that the number of colonoscopies that need to be performed to detect one patient with curable colorectal recurrence at 1 year post-operatively was 36 (95% CI 13-130) and at 5 years post-operatively was 27 (95% CI 8-143). The large confidence intervals highlight the great uncertainty associated with modelling, in part due to the low numbers of recurrences even in large patient series.

Menges et al. (2006) found that colonoscopic surveillance in 45-year old first-degree relatives of patients with colorectal cancer may be cost-effective. However, the authors concluded that this was difficult to establish with certainty due to the limitations of conducting economic evaluations for interventions where there is large variability in estimated patient compliance and the optimal screening schedule.

The draft national Clinical Practice Guidelines for Surveillance Colonoscopy include an analysis of data regarding cost-effectiveness of colonoscopy. These guidelines are currently released for public comment.

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Summary statement

Colonoscopy appears to be a cost-effective procedure across a broad range of clinical conditions. The personal and clinical characteristics of the patient, the skills and experience of the colonoscopist and the setting in which the colonoscopy is performed contribute to the cost-effectiveness of the procedure.

Question 5 - Are all patient groups in whom colonoscopy should be used able to access colonoscopy?

Studies were coded separately according to:

factors that influence access to colonoscopy;

evidence for interventions that improve access to colonoscopy services; and

the impact of open access service configuration on access to colonoscopy services.

Question 5a - What are the factors that influence access to colonoscopy?

There were 3 studies published since 1999 that specifically addressed this question and were included in this review (Review Question 5a, Appendix 5). Two systematic reviews and a retrospective analysis of administrative data were included. All were Level IV evidence. The size of the case series that was analysed varied between 13,580 and 328,167 colonoscopies.

A systematic review of the literature was conducted by the Agency for Healthcare Research and Quality that addressed this question (Holden 2010). Study findings demonstrated that people in the general population who are without health insurance, with no source of usual primary care, with no history of recent physician visits and with lower income status are less able to access colonoscopy.

Among patients who have had colorectal cancer that there is substantial variation in utilisation of colonoscopy. Rulyak et al. (2004), in an analysis of health services administrative data, found that the sociodemographic characteristics of these patients predict access to colonoscopy. Patients over 80 years of age and those with rectal cancer were less likely to undergo post-resection surveillance. Longer intervals between surveillance examinations were also associated with lower socioeconomic status. In contrast, patients who were married, of higher socioeconomic status or who belonged to some ethnic minority groups had increased utilisation (Rulyak 2004).

A review of studies of surveillance in inflammatory bowel disease demonstrated that patients with inflammatory bowel disease as a whole may be more likely to be of higher socioeconomic status and have reached higher levels of education, increasing the accessibility of colonoscopy in this patient group (Bernstein 2001).

The generalisability of the findings of the studies included in this section of the review, all conducted in North America, to the Australian setting is not known.

There were no studies identified in this review that specifically addressed the factors influencing access of patients to colonoscopy post-polypectomy.

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Data are available from the NBCSP regarding colonoscopy follow-up of patients after a positive FOBT was detected (AIHW 2010). Colonoscopy follow-up varied little according the age or gender of the participant. Participants with the lowest socio-economic status and with severe or profound activity limitations had significantly lower colonoscopy follow-up rates than participants as a whole. Colonoscopy follow-up rates did not vary according to rurality according to the AIHW report. Patients who spoke a language other than English at home had statistically higher colonoscopy follow-up rates. There were 44% of participants in whom FOBT was positive who did not proceed to colonoscopy as they had already received one in the previous 18 months.

Medicare data for access to MBS colonoscopy items

Table 10 describes the average caseload for each provider based on the rural, remote and metropolitan area classification. It shows that in capital cities and other metropolitan areas a higher concentration of providers is associated with a lower average number of colonoscopies performed per provider.

Table 10: Average number of services per provider and number of providers per 1,000 population by provider’s RRMA and state/territory (MBS items 32090 and 32093) for 2008/09*

RRMA Classification

NSW VIC QLD SA WA TAS NT ACT

Capital City 235

0.09

345

0.07

356

0.06

234

0.10

440

0.05

358

0.08

110

0.11

241

0.09

Other Metro 333

0.07

142

0.14

353

0.07

0

0

0

0

0

0

0

0

0

0

Large Rural 207

0.17

158

0.12

238

0.14

28

0.14

0

0

272

0.13

0

0

0

0

Small Rural 146

0.11

103

0.12

206

0.11

60

0.19

168

0.11

39

0.12

0

0

0

0

Other Rural 49

0.06

96

0.05

101

0.03

67

0.03

**

**

**

**

0

0

0

0

Remote 0

0

0

0

18

0.05

0

0

**

**

**

**

52

0.05

0

0

*Caution needs to be exercised in assessing the number of providers per 100,000 population in smaller centres because the low population may well mean there are in fact only 1 or 2 providers but a high ratio. However it is of note that in general the average caseload per provider is lower than in metropolitan areas. 2009/10 data not available at time of analysis; **small numbers suppressed

The number of services provided per 1,000 population is higher in capital cities, other metropolitan areas and large rural centres (except South Australia) than in other rural and remote areas (Table 11). Small rural centres have variable access to services.

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Table 11: Number of services provided per 1,000 population by provider’s RRMA and state/territory (MBS items 32090 and 32093) for 2008/9

RRMA Classification

NSW VIC QLD SA WA TAS NT ACT

Capital City 21.3 25.3 22.7 22.8 21.4 29.7 12.5 21.3

Other Metro 22.3 20.4 25.8 0 0 0 0 0

Large Rural 34.1 19.4 32.9 3.8 0 33.8 0 0

Small Rural 15.6 12.5 23.3 11.6 18.8 4.6 0 0

Other Rural 2.7 4.5 2.9 2.1 ** ** 0 0

Remote (2 categories) 0 0 0.8 0 ** ** 2.5 0

All 19.7 21.1 20.7 17.8 17.5 18.4 7.2 17.6

*2009/10 data not available at time of analysis; ** small numbers supporessed

A higher proportion of colonoscopies in remote and very remote areas are non-Medicare rebated compared with major cities and regional areas (Figure 8).

Figure 8: Rates of MBS-rebated colonoscopy as a proportion of all public and private hospital colonoscopies, 2008/09

0

0.2

0.4

0.6

0.8

1

Major cities Innerregional

Outerregional

Remote Very remote Total

Remoteness area of hospital

Prop

ortio

n of

sep

arat

ions

Private patients

Public patients

* National Admitted Patient Care dataset, 2008/09

Sustained increases in public hospital and private hospital colonoscopies were observed in urban and regional areas between 2003/04 and 2008/09. In remote and very remote areas, numbers were too small for trends over time to be statistically reliable over this time period.

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Summary statement

Analysis of Medicare data demonstrates a lower number of providers per 1,000 population for people in small rural and remote areas. However, access to colonoscopy services for patients in remote and very remote areas may occur through the public sector and may not be MBS-rebated.

No peer-reviewed studies were identified that examined whether all patient groups in whom colonoscopy should be used are able to access the procedure.

Question 5b: What is the evidence for interventions that improve access to colonoscopy services?

There were 2 studies published since 1999 that specifically addressed this question and were included in this review (Review Question 5b, Appendix 5). The first study was an analysis of the impact of a waiting list audit of 3,020 colonoscopy referrals where patients were re-listed for colonoscopy in accordance with UK guidelines for appropriate surveillance intervals (Chivers 2010). The second study was a randomised controlled trial involving 21 patients in order to determine whether a patient navigator can assist patients to overcome barriers to accessing colonoscopy (Christie 2008). The setting for the first study was seven UK hospitals; the second study was conducted in a US health service in patients referred for colonoscopy by their primary care physician.

Chivers et al. (2010) found that 22% of surveillance colonoscopy referrals were consistent with guidelines, 51% could be cancelled from the list and 27% could be given a new date for colonoscopy. Implementing the recommendations reduced the average wait for a diagnostic colonoscopy from 76.8 to 56.0 days (p<0.01). There was no follow-up conducted of patients whose colonoscopies were delayed or cancelled in order to assess patient outcomes.

Christie et al. (2008) demonstrated that 54% of patients assisted by a patient navigator accessed colonoscopy within the study period compared with 13% of patients who were not assisted by a patient navigator (p=0.058). All navigated patients were very satisfied with navigation services.

Queensland Health, in an evaluation of the pilot of the NBCSP, trialled Gastroenterology Nurse Coordinators (GENC) to assist patients to access NBCSP services, including colonoscopy services. Over 64% of respondents to the evaluation survey indicated that they were satisfied with the GENC care coordination with treatment services. Qualitative evaluation of the GENC pilot demonstrated that GENCs prior to and after their colonoscopy made the procedure less stressful.

Targeting clinician adherence with clinical practice guidelines is a strategy that may improve evidence-based delivery of colonoscopy services which may, in turn, result in improved access. Bampton (2002) conducted a prospective audit of colonoscopic surveillance decisions before and after dissemination of clinical practice guidelines to clinicians, and supervision of application of the guidelines by a nurse coordinator. After the intervention, adherence with guidelines increased for patient postpolypectomy (from 37% to 96%) and in patients with a family history of bowel cancer (from 63% to 96%). Bampton (2007) reviewed 1,794 colonoscopic surveillance decisions made by the coordinated colorectal screening program between 2000 and 2004 and demonstrated that adherence to evidence-based guidelines for colonoscopic surveillance was maintained over the 4 years of study.

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Cancer studies more generally suggest that patient navigators could play a role in helping individuals to overcome barriers to obtaining cancer care (Jandorf 2005; Peteriet 2008). Initial evaluation of a small Indigenous women's cancer support group established in regional Western Australia that helped to encourage screening, support families of those with cancer and help patients through their cancer journey provides qualified support for this model’s effectiveness in facilitating Indigenous participation in bowel cancer screening while also providing assistance with follow-up tests and treatment (Finn 2008).

Summary statement

Waiting list audit and the use of a patient navigator may improve access to colonoscopy services. Available published and unpublished data on the impact of waiting list audit on subsequent morbidity and mortality of patients whose colonoscopy was cancelled or delayed have not been assessed in studies included in this review.

Question 5c: What is the impact of open access service configuration on access to colonoscopy services?

Three studies published since 1999 that specifically addressed this question were included in this review (Review Question 5c, Appendix 5). One was a randomised controlled trial and two were prospective cohort studies. The sample size ranged from 360 to 1,131 patients.

An Australian study of an open access colonoscopy service provided as part of an outreach surgical services analysed results from colonoscopies performed on 360 patients, 75% of which were open access procedures (Hughes-Anderson 2002). The appropriateness of referrals was high; 90% were ‘appropriate’ according to ASGE criteria, 2% were ‘inappropriate’ and 8% were for unlisted indications. There was no difference in compliance with the ASGE guidelines according to the clinical specialty of the referring medical practitioner. Improved convenience and reduced costs for rural patients were identified as advantages of open access service configuration.

In the UK, a 21 month trial was conducted in patients with large bowel symptoms referred by their general practitioner to an open access endoscopy service. Patients were randomised to proceed directly to colonoscopy or to be assess prior to colonoscopy by a consultant endoscopist who was a surgeon with a colorectal interest. No difference was observed in the percentage of patients diagnosed with significant colonic pathology in either group. Open access service configuration was not associated with a shorter mean time to diagnosis of cancer in this study. In contrast, a UK prospective cohort study assessing the impact of open access service configuration on waiting times demonstrated a shorter time to definitive investigations (9 versus 52 days), shorter time to histological diagnosis (14 versus 42 days) and shorter time to treatment (55 versus 75 days) (Maruthachalam 2005).

Data were not provided regarding patient consent prior to bowel preparation, bowel preparation selection and how co-morbid clinical conditions including hepatic and renal impairment were assessed. Complexities of management of patient consent in open access services were not addressed. Adverse events that occurred prior to colonoscopy and as a result of the colonoscopy procedure (e.g. cardiac, renal and / or hepatic events) and those that occurred after discharge from the colonoscopy service were not described.

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Summary statement

Open access colonoscopy, where a patient is referred by a clinician for a colonoscopy without a prior consultation with the specialist performing the colonoscopy, may improve access to services. There is some evidence suggesting that open access colonoscopy is associated with reduced waiting times but not with an increase in the number of colonoscopies performed that are not clinically indicated. No studies were included that systematically addressed adverse outcomes from open access colonoscopy.

Consumer perspectives

No study that was included in this review specifically appraised the perspectives of consumers regarding appropriate timing of colonoscopy, its effectiveness or cost-effectiveness in key target populations, the impact of procedural volumes or certification / re-certification processes on safety and quality outcomes of colonoscopy or access to services in general.

Christie et al. (2008) assessed the satisfaction of study participants receiving patient navigator services to improve access to colonoscopy services. The authors found that all consumers were very satisfied with navigation services.

Maruthachalam et al. (2005) assessed consumer satisfaction with open access services for colonoscopy. The authors demonstrated that 98% of patients overall were satisfied with the services provided. Although satisfaction was high for consumers accessing open access services and services where colonoscopy was preceded by a colonoscopist specialist consultation, 7% of patients receiving open access services expressed a preference to be seen at the outpatient department before presenting for colonoscopy.

Data from the pilot study of the National Bowel Cancer Screening Program indicates that timely access to colonoscopy services is an important quality issue for consumers. Consumers reported that they do not want excessive waiting times for colonoscopy if they have a positive FOBT result and that services should be available to provide access to services for those at high risk, in order to allay anxiety associated with the presence of symptoms or a positive screening test (Department of Health and Ageing, 2004).

Summary statement

There is limited evidence from studies included in this review regarding consumer perspectives on appropriate timing of colonoscopy, its effectiveness or cost-effectiveness in key target populations, the impact of procedural volumes or certification / re-certification processes on safety and quality outcomes of colonoscopy or access to services in general. Available evidence demonstrates that consumer satisfaction with colonoscopy services is associated with timely access to services.

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DISCUSSION

General findings

The delivery of evidence-based care is an important goal of the MBS and is articulated in Medicare Benefits Schedule – a quality framework for reviewing services. Consistency of the MBS with contemporary evidence is desirable in order to facilitate the provision of evidence-based care. The purpose of this review was to identify and appraise contemporary evidence regarding colonoscopy and its utilisation in Australia in order to consider whether MBS item numbers for colonoscopy are aligned with available evidence.

The majority of included studies in this review appraised the role and appropriate use of colonoscopy for the prevention and early identification of colorectal neoplasia. Colonoscopy is associated with reduced risks associated with colorectal neoplasia; the degree of association dependent on a broad range of clinical factors. Appropriate timing of index and repeat colonoscopy in patients with or at risk of colorectal neoplasia is complex and relies on individualised clinical decisions by clinicians.

The draft national Clinical Practice Guidelines for Surveillance Colonoscopy include specific guidance regarding the commencement and frequency of surveillance colonoscopy in patients with or at risk of colorectal neoplasia. Once endorsed, these guidelines will assist clinicians in determining appropriate commencement and timing of colonoscopy across a range of clinical indications.

The purpose of this review is not to provide clinical advice. Rather, the following observations are made from this literature review for the purposes of considering alignment of MBS colonoscopy items with published evidence. A significant limitation of this review was the lack of randomised controlled clinical trial data relevant to each review question. This increases the likelihood that numerous sources of bias and confounding influence the reliability and precision of the results obtained from the largely observational data that was retrieved and analysed. Further, the year limit placed on this review resulted in studies published prior to 1999 being excluded from analysis. The impact of excluding these studies on interpretation of results is unknown.

In spite of these limitations, published evidence demonstrates that colonoscopy is a diagnostic and therapeutic tool that is utilised across a wide range of clinical conditions. Appropriate timing of colonoscopy is important to maximise the morbidity and mortality benefits associated with the procedure. There is considerable variation in when an index or follow-up colonoscopy should be performed as a large range of factors influence when colonoscopy is required. These factors need to be taken into account by the treating clinician in determining an appropriate colonoscopy surveillance schedule.

Because of the degree of variability in timing of colonoscopy and the complexity of factors that need to be taken into account in determining when follow-up colonoscopy is required, it is not feasible for the MBS colonoscopy items to incorporate specific recommendations regarding timing.

Analysis of MBS data demonstrates a pattern of increasing MBS utilisation of colonoscopy items since 1999/2000, observed in all States and Territories and Australia as a whole. Since 1993, utilisation of other MBS-rebated procedures for investigating the large bowel (sigmoidoscopy and

61


barium enema) has declined significantly, suggesting a change in clinical practice towards colonoscopy, the gold standard for investigation of the bowel. The majority of patients have not had more than one MBS-rebated colonoscopy within a 10-year period.

This increase in utilisation of colonoscopy has occurred in the context of significant population trends that explain much of the increase. These include an ageing population, an increasing population size within Australia and an increasing incidence of colorectal cancer in Australia. These factors, combined with the commencement of the National Bowel Cancer Screening Program, are important drivers of colonoscopy demand, a number of which are likely to further increase demand into the future.

The number of colonoscopies that also include polypectomy (or argon plasma coagulation) has increased in the past decade at a faster rate than colonoscopies without polypectomy. There may be a future decline in bowel cancer incidence from the current increase in polypectomy, but it is not possible to determine if this has had any impact to date.

Colonoscopy is a low risk procedure when performed by trained and experienced providers. Diagnostic colonoscopy is associated with a complication rate of approximately 0.1%. Major complications include colonic perforation and haemorrhage. Other occasional serious complications may occur with the use of sedation and with bowel preparation. The average number of colonoscopies performed by the colonoscopist is one of a range of factors that influence the procedural quality of colonoscopy and risk associated with the procedure. The endoscopist’s training and overall experience, as well as a range of setting- and patient-specific factors also influences procedural quality and safety. Numerous indicators are used as measures of the procedural quality and safety of colonoscopists including number of procedures performed over a specified timeframe, caecal intubation rates, instrument withdrawal times, adenoma detection rates and complication rates. There is no clear threshold volume of colonoscopy procedures identifiable from included studies below which procedural quality is not maintained. However, there is a strong trend towards improved procedural quality with increasing numbers of procedures performed, provided the colonoscopist is appropriately trained.

The majority of MBS-rebated colonoscopies are performed by high volume providers (averaging greater than 50 procedures in the 2008/09 financial year). As a provider group, gastroenterologists are the highest volume providers; the majority of colonoscopists who are gastroenterologists perform in excess of 300 MBS-rebated colonoscopies a year. It is not possible to infer from MBS data alone what proportion of colonoscopists perform fewer than 50 colonscopies a year as providers may also perform colonoscopies in public facilities.

Published economic analyses of colonoscopy suggest that colonoscopy is cost-effective in the majority of clinical situations, particularly colonoscopic surveillance post-polypectomy and post-colorectal cancer resection.

Access to colonoscopy is poorer for patients of lower socio-economic status and appears to be poorer for patients in small rural and remote areas.

Limited evidence demonstrates that access to colonoscopy may be improved through audit-based interventions of patient waiting lists and by assisting patients in high risk groups with the use of ‘patient navigators’. Further studies are needed to verify these findings. Open access colonoscopy

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has been evaluated in a number of studies. In some cases, open access colonoscopy improves access to services through reduced waiting times, without increasing numbers of colonoscopies performed that are not indicated. Data regarding the logistic and legal issues associated with open access colonoscopy, and pre- and post-colonoscopy adverse events associated with open access colonoscopy are limited.

Implications for the MBS - colonoscopy in individuals with no known risk factors and no relevant symptoms

This systematic review confirms that colonoscopy is substantially more likely to yield a clinically-relevant diagnosis when individuals have certain pre-existing conditions, symptoms or known familial or genetic risk. Although a colonoscopy in an individual without known risk factors or symptoms may yield a clinically-relevant diagnosis and may have a beneficial health effect, Endorsed Australian guidelines confirm that diagnostic colonoscopy is not specifically indicated in these circumstances.

A health screening service is defined as "a professional service that is a medical examination or test that is not reasonably required for the management of the medical condition of the patient".1 MBS rebates are not payable for health screening services unless the Minister otherwise directs. The Medicare Benefits Schedule states that Medicare benefits be paid for:

"A medical examination or test on a symptomless patient by that patient's own medical practitioner in the course of normal medical practice, to ensure the patient receives any medical advice or treatment necessary to maintain their state of health. Benefits would be payable for the attendance and tests which are considered reasonably necessary according to patients individual circumstances (such as age, physical condition, past personal and family history). For example, a Papanicolaou test in a woman (see General Explanatory note 13.6.4 for more information), blood lipid estimation where a person has a family history of lipid disorder. However, such routine check up should not necessarily be accompanied by an extensive battery of diagnostic investigations".2

Discussion with clinicians who were members of the clinical working group which assisted with this review suggests that clinicians appear to make a distinction (for MBS purposes) between 'screening colonoscopies' and colonoscopies performed on individuals who are asymptomatic and not at increased risk of bowel disease but who present to their doctor with concerns about their individual risk.

It is not possible to determine from MBS data how many MBS-rebated colonoscopies are currently being performed for screening purposes in asymptomatic patients at average or lower risk of colorectal pathology.

If national policy continues to specify FOBT screening with follow-up of patients with positive results by colonoscopy, consideration could be given to amending the MBS indication to make clear that colonoscopies are not intended to be performed on asymptomatic individuals with an average or below-average risk of bowel cancer. This would be consistent with MBS items for radiographic examination of the breast, which are introduced with the following note:

1 Section 19(5), Health Insurance Act 1973.

2 Australian Government Department of Health and Ageing Medicare Benefits Schedule Book, Operating from 01 November 2010, page 40.

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"Note: these items are intended for use in the investigation of a clinical abnormality of the breast/s and NOT for individual, group or opportunistic screening of asymptomatic patients."

A similar approach could be taken to qualifying the use of colonoscopy items in the MBS with the addition of the following note:

"Note: these items are intended for the investigation, management or follow up of patients with symptoms, signs (including a positive FOBT) or recent history suggestive of colorectal pathology and for the surveillance of patients at increased risk of colorectal cancer due to family history, genetic risk or pre-existing conditions. They are NOT intended for individual, group or opportunistic screening of asymptomatic patients who are not at increased risk of colorectal cancer".

Implications for the MBS - colonoscopy in individuals with known risk factors, established disease and/or relevant symptoms

An extensive range of variables influences the preferred frequency of colonoscopies in individuals with established bowel disease, symptoms of bowel disease and/or increased risk of clinically-relevant bowel disease. In individuals with a very high risk of bowel pathology or with some established diagnoses relatively short intervals between regular colonoscopies may be entirely appropriate. There are so many variables that must be taken into account in good clinical decision-making that it is neither possible nor appropriate to mirror evidence-based practice in item number descriptors.

Different MBS item numbers defined for colonoscopies performed for different purposes, however, could enhance application of evidence-based guidelines and provide a mechanism for improving future understanding of the reasons colonoscopy is performed.

For monitoring purposes, MBS item numbers 32090 and 32093 for colonoscopy could be categorised as follows:

1 Colonoscopy for the primary purpose of investigation, management or follow up of symptoms, signs (including a positive FOBT) or recent history suggestive of colorectal pathology.

2 Colonoscopy for the primary purpose of cancer surveillance in patients with:

2.1 a family history of or genetic predisposition to colorectal cancer;

2.2 a past history of inflammatory colorectal disease; and/or

2.3 a past history of colorectal adenoma or cancer.

3 Colonoscopy for other clinical indications.

Each category of colonoscopy would need to continue to be sub-categorised according to whether the colonoscopy involves removal of a polyp or other specified intervention, in accordance with the current categorisation of the MBS.

It would be expected that minimal numbers of procedures would be recorded in category 3 above.

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The consequence would be that almost all MBS rebates for colonoscopies would be claimed against one of six MBS item numbers.

This would provide information regarding the relative proportions of colonoscopies being performed for the purposes of diagnosis and management of colorectal pathology versus for cancer surveillance and address some of the MBS information gap which has become apparent in this review. It would also discourage colonoscopy for surveillance purposes in asymptomatic patients not at increased risk of cancer.

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REFERENCES

Included studies

1 Abu Nada MH, Johnson DRE, Buie WD, Heine JA, Jenken DA. The value of one year post-operative colonoscopy in the surveillance of cancer of the colon and rectum. Qatar Medical Journal. 2003;12(2):108-9.

2 Adler A, Roll S, Marowski B, Drossel R, Rehs HU, Willich SN, et al. Appropriateness of colonoscopy in the era of colorectal cancer screening: A prospective, multicenter study in a private-practice setting (Berlin Colonoscopy Project 1, BECOP 1). Diseases of the Colon and Rectum. 2007;50(10):1628-38.

3 AIHW / Australian Government Department of Health and Ageing. National Bowel Cancer Screening Program: Annual Monitoring Report 2009 (Data Supplement 2010). Canberra: AIHW2010.

4 Ang YS, Macaleenan N, Mahmud N, Keeling PWN, Kelleher DP, Weir DG. The yield of colonoscopy in average-risk patients with non-specific colonic symptoms. European Journal of Gastroenterology and Hepatology. 2002;14(10):1073-7.

5 Arditi C, Peytremann-Bridevaux I, Burnand B, Eckardt VF, Bytzer P, Agreus L, et al. Appropriateness of colonoscopy in Europe (EPAGE II): Screening for colorectal cancer. Endoscopy. 2009;41(3):200-8.

6 Avidan B, Sonnenberg A, Schnell TG, Leya J, Metz A, Sontag SJ. New occurrence and recurrence of neoplasms within 5 years of a screening colonoscopy. American Journal of Gastroenterology. 2002;97(6):1524-9.

7 Balaguer F, Llach J, Castells A, Bordas JM, Pellise M, Rodriguez-Moranta F, et al. The European Panel on the Appropriateness of Gastrointestinal Endoscopy guidelines colonoscopy in an open-access endoscopy unit: A prospective study. Alimentary Pharmacology and Therapeutics. 2005;21(5):609-13.

8 Balleste B, Bessa X, Pinol V, Csastellvi-Bel S, Castells A, Alenda C, et al. Detection of metachronous neoplasms in colorectal cancer patients: identification of risk factors. Diseases of the Colon and Rectum. 2007;50:971-80.

9 Baxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach DR, Rabeneck L. Association of colonoscopy and death from colorectal cancer. Annals of Internal Medicine. 2009;150(1):1-8.

10 Beaudin DJ. Results of screening first-degree relatives of patients with colorectal cancer: A community practice perspective. Canadian Journal of Gastroenterology. 2000;14(6):489-92.

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11 Becker F, Nusko G, Welke J, Hahn EG, Manasmann U. Follow-up after colorectal polypectomy: a benefit-risk analysis of German surveillance recommendations. International Journal of Colorectal Disease. 2007;22:929-39.

12 Berman J, Cheung R, Weinberg D. Surveillance after colorectal cancer resection. The Lancet. 2000;355:395-9.

13 Bernstein C, Kraut A, Blanchard J, Rawsthorne P, Yu N, Walld R. The relationship between inflammatory bowel disease and socioeconomic variables. American Journal of Gastroenterology. 2001;96(7):2117-25.

14 Bersani G, Rossi A, Ricci G, Pollino V, DeFabritiis G, Suzzi A, et al. Do ASGE guidelines for the appropriate use of colonoscopy enhance the probability of finding relevant pathologies in an open access service? Digestive and Liver Disease. 2005;37(8):609-14.

15 Blumberg D, Opelka FG, Hicks TC, Timmcke AE, Beck DE. Significance of a normal surveillance colonoscopy in patients with a history of adenomatous polyps. Diseases of the Colon and Rectum. 2000;43(8):1084-92.

16 Bonithon-Kopp C, Piard F, Fenger C, Cabeza E, O'Morain C, Kronborg O, et al. Colorectal adenoma characteristics as predictors of recurrence. Diseases of the Colon and Rectum. 2004;2004(47).

17 Bouvier AM, Latournerie M, Jooste V, Lepage C, Cottet V, Faivre J. The lifelong risk of metachronous colorectal cancer justifies long-term colonoscopic follow-up. European Journal of Cancer. 2008;44(4):522-7.

18 Bowles CJA, Leicester R, Romaya C, Swarbrick E, Williams CB, Epstein O. A prospective study of colonoscopy practice in the UK today: Are we adequately prepared for national colorectal cancer screening tomorrow? Gut. 2004;53(2):277-83.

19 Bradshaw N, Holloway S, Penman I, Dunlop MG, Porteous MEM. Colonoscopy surveillance of individuals at risk of familial colorectal cancer. Gut. 2003;52(12):1748-51.

20 Bressler B, Paszat LF, Chen Z, Rothwell DM, Vinden C, Rabeneck L. Rates of New or Missed Colorectal Cancers After Colonoscopy and Their Risk Factors: A Population-Based Analysis. Gastroenterology. 2007;132(1):96-102.

21 Brian Perry W, Opelka FG, Hicks TC, Timmcke AE, Beck DE. Geriatric colonoscopy. Perspectives in Colon and Rectal Surgery. 2000;13(2):93-100.

22 Carlo P, Paolo RF, Carmelo B, Salvatore I, Giuseppe A, Giacomo B, et al. Colonoscopic evaluation of hematochezia in low and average risk patients for colorectal cancer: A prospective study. World Journal of Gastroenterology. 2006;12(45):7304-8.

23 Chan C, Bokey E, Chapuis P, Renwick A, Dent O. Local recurrence after curative resection for rectal cancer is associated with anterior position of the tumour. British Journal of Surgery. 2006;93:1115-22.

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24 Chan TH, Goh KL. Appropriateness of colonoscopy using the ASGE guidelines: Experience in a large Asian hospital. Chinese Journal of Digestive Diseases. 2006;7(1):24-32.

25 Chen CD, Yen MF, Wang WM, Wong JM, Chen THH. A case-cohort study for the disease natural history of adenoma-carcinoma and de novo carcinoma and surveillance of colon and rectum after polypectomy: Implication for efficacy of colonoscopy. British Journal of Cancer. 2003;88(12):1866-73.

26 Chey WD, Nojkov B, Rubenstein JH, Dobhan RR, Greenson JK, Cash BD. The yield of colonoscopy in patients with non-constipated irritable bowel syndrome: Results from a prospective, controlled US trial. American Journal of Gastroenterology. 2010;105(4):859-65.

27 Chivers K, Basnyat P, Taffinder N. The impact of national guidelines on the waiting list for colonoscopy: A quantitative clinical audit. Colorectal Disease. 2010;12(7):632-9.

28 Christie J, Itzkowitz S, Lihau-Nkanza I, Castillo A, Redd W, Jandorf L. A randomized controlled trial using patient navigation to increase colonoscopy screening among low-income minorities. Journal of the National Medical Association. 2008;100(3):278-84.

29 Collins P, Mpofu C, Watson A, Rhodes J. Strategies for detecting colon cancer and / or dysplasia in patients with inflammatory bowel disease. Cochrane Database of Systematic Reviews. 2008;2:CD000279.

30 Cordero C, Leo E, Cayuela A, Bozada JM, Garcia E, Pizarro MA. Validity of early colonoscopy for the treatment of adenomas missed by initial endoscopic examination. Revista espa?ola de enfermedades digestivas : organo oficial de la Sociedad Espa?ola de Patolog?a Digestiva. 2001;93(8):519-28.

31 Cottet V, Pariente A, Nalet B, Lafon J, Milan C, Olschwang S, et al. Colonoscopic Screening of First-Degree Relatives of Patients With Large Adenomas: Increased Risk of Colorectal Tumors. Gastroenterology. 2007;133(4):1086-92.

32 Croese J. Colorectal cancer after open-access colonoscopy: A community and case survey. Medical Journal of Australia. 1999;170(6):251-4.

33 Cubiella Fernandez J, Gomez R, Sanhez E, Diez MS, Vega M. Endoscopic follow-up of patients after curative surgery for colorectal cancer: Results of a medical assistance protocol. Revista Espanola de Enfermedades Digestivas. 2003;95(4):278-81.

34 De Bosset V, Froehlich F, Rey JP, Thorens J, Schneider C, Wietlisbach V, et al. Do explicit appropriateness criteria enhance the diagnostic yield of colonoscopy? Endoscopy. 2002;34(5):360-8.

35 Dove-Edwin I, de Jong AE, Adams J, Mesher D, Lipton L, Sasieni P, et al. Prospective Results of Surveillance Colonoscopy in Dominant Familial Colorectal Cancer With and Without Lynch Syndrome. Gastroenterology. 2006;130(7):1995-2000.

68


36 Dove-Edwin I, Sasieni P, Adams J, Thomas HJW. Prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: 16 Year, prospective, follow-up study. British Medical Journal. 2005;331(7524):1047-9.

37 Dowling DJ, St. John DJB, Macrae FA, Hopper JL. Yield from colonoscopic screening in people with a strong family history of common colorectal cancer. Journal of Gastroenterology and Hepatology. 2000;15(8):939-44.

38 Eaden J, Abrams K, Mayberry J. The risk of colroectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48(4):526-35.

39 Ee HC, Semmens JB, Hoffman NE. Complete colonoscopy rarely misses cancer. Gastrointestinal Endoscopy. 2002;55(2):167-71.

40 Engel C, Rahner N, Schulmann K, Holinski-Feder E, Goecke TO, Schackert HK, et al. Efficacy of Annual Colonoscopic Surveillance in Individuals With Hereditary Nonpolyposis Colorectal Cancer. Clinical Gastroenterology and Hepatology. 2010;8(2):174-82.

41 Farrar WD, Sawhney MS, Nelson DB, Lederle FA, Bond JH. Colorectal Cancers Found After a Complete Colonoscopy. Clinical Gastroenterology and Hepatology. 2006;4(10):1259-64.

42 Feingold D, Forde KA. Colorectal cancer surveillance after age 65 years. American Journal of Surgery. 2003;185:297-300.

43 Fireman Z, Gurevich V, Coscas D, Kopelman Y, Segal A, Sternberg A. Results of gastrointestinal evaluation in 90 hospitalized iron deficiency anemia patients. The Israel Medical Association journal : IMAJ. 1999;1(4):232-5.

44 Fisher DA, Jeffreys A, Grambow SC, Provenzale D. Mortality and follow-up colonoscopy after colorectal cancer. American Journal of Gastroenterology. 2003;98(4):901-6.

45 Fontagnier EM, Manegold BC. Coloscopy in patients over 80 years: Indications, methods and results. Deutsche Medizinische Wochenschrift. 2000;125(44):1319-22.

46 Frenette CT, Strum WB. Relative rates of missed diagnosis for colonoscopy, barium enema, and flexible sigmoidoscopy in 379 patients with colorectal cancer. Journal of Gastrointestinal Cancer. 2007;38(2-4):148-53.

47 Friedman S, Rubin PH, Bodian C, Harpaz N, Present DH. Screening and Surveillance Colonoscopy in Chronic Crohn's Colitis: Results of a Surveillance Program Spanning 25 Years. Clinical Gastroenterology and Hepatology. 2008;6(9):993-8.

48 Fukutomi Y, Moriwaki H, Nagase S, Tajika M, Naito T, Miwa Y, et al. Metachronous colon tumors: Risk factors and rationale for the surveillance colonoscopy after initial polypectomy. Journal of Cancer Research and Clinical Oncology. 2002;128(10):569-74.

69


49 Gervaz P, Bucher P, Neyroud-Caspar I, Soravia C, Morel P. Proximal location of colon cancer is a risk factor for development of metachronous colorectal cancer: a population-based study. Diseases of the Colon and Rectum. 2005;48:227-32.

50 Gilbert JM, Vaizey CJ, Cassell PG, Holden J. Feasibility study of colonoscopy as the primary screening investigation in relatives of patients with colorectal cancer. Annals of the Royal College of Surgeons of England. 2001;83(6):415-9.

51 Glazer E, Golla V, Forman R, Zhu HQ, Levi G, Bodenheimer H. Serrated adenoma is a risk factor for sebsequent adenomatous polyps. Digestive Diseases and Sciences. 2008;53:2204-7.

52 Gonvers JJ, Harris JK, Wietlisbach V, Burnand B, Vader JP, Froehlich F, et al. A European view of diagnostic yield and appropriateness of colonoscopy. Hepato-Gastroenterology. 2007;54(75):729-35.

53 Gorski TF, Rosen L, Riether R, Stasik J, Khubchandani I. Colorectal cancer after surveillance colonoscopy: False-negative examination or fast growth? Diseases of the Colon and Rectum. 1999;42(7):877-80.

54 Grassini M, Verna C, Battaglia E, Niola P, Navino M, Bassotti G. Education improves colonoscopy appropriateness. Gastrointestinal Endoscopy. 2008;67(1):88-93.

55 Grassini M, Verna C, Niola P, Navino M, Battaglia E, Bassotti G. Appropriateness of colonoscopy: Diagnostic yield and safety in guidelines. World Journal of Gastroenterology. 2007;13(12):1816-9.

56 Gupta M, Holub J, Knigge K, Eisen G. Constipation is not associated with an increased rate of findings on colonoscopy: Results from a national endoscopy consortium. Endoscopy. 2010;42(3):208-12.

57 Hassan (1) C, Pickhardt PJ, Di Giulio E, Kim DH, Zullo A, Morini S. Cost-effectiveness of early one-year colonoscopy surveillance after polypectomy. Diseases of the Colon and Rectum. 2009;52(5):964-71.

58 Hassan (2) C, Pickhardt PJ, Zullo A, Di Giulio E, Laghi A, Kim DH, et al. Cost-effectiveness of early colonoscopy surveillance after cancer resection. Digestive and Liver Disease. 2009;41(12):881-5.

59 Hassan C, Di Giulio E, Pickhardt PJ, Zullo A, Laghi A, Kim DH, et al. Cost Effectiveness of Colonoscopy, Based on the Appropriateness of an Indication. Clinical Gastroenterology and Hepatology. 2008;6(11):1231-6.

60 Hata K, Watanabe T, Kazama S. Earlier surveillance colonoscopy programme improves survival in patients with ulcerative colitis associated colorectal cancer: results of a 23-year surveillance programme in the Japanese population. British Journal of Cancer. 2003;89(7):1232-6.

70


61 Henry SG, Ness RM, Stiles RA, Shintani AK, Dittus RS. A cost analysis of colonoscopy using microcosting and time-and-motion techniques. Journal of General Internal Medicine. 2007;22(10):1415-21.

62 Holden D, Harris R, Porterfield D, Jonas DE, Morgan L, Reuland D, et al. Enhancing the Use and Quality of Colorectal Cancer Screening. Evidence Report/Technology Assessment No.190. . Rockville, MD.2010.

63 Hughes-Anderson W, Rankin SL, House J, Aitken J, Heath D, House AK. Open access endoscopy in rural and remote Western Australia: Does it work? ANZ Journal of Surgery. 2002;72(10):699-703.

64 Hyman N, Moore J, Cataldo P, Osler T. The high yield of 1-year colonoscopy after resection: Is it the handoff? Surgical Endoscopy and Other Interventional Techniques. 2010;24(3):648-52.

65 Jabar MF, Abdul Halim ME, Gul YA. Appropriateness of Colonoscopy in a Tertiary Referral Centre. Asian Journal of Surgery. 2004;27(1):26-31.

66 Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P, De La Chapelle A, Mecklin JP. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000; 118: 829–34.

67 Jorgensen OD, Kronborg O, Fenger C, Rasmussen M. Influence of long-term colonoscopic surveillance on incidence of colorectal cancer and death from the disease in patients with precursors (adenomas). Acta Oncologica. 2007;46(3):355-60.

68 Kahi CJ, Azzouz F, Juliar BE, Imperiale TF. Survival of elderly persons undergoing colonoscopy: implications for colorectal cancer screening and surveillance. Gastrointestinal Endoscopy. 2007;66(3):544-50.

69 Keren D, Rainis T, Goldstein O, Stermer E, Lavy A. Significant colonic neoplasia prevalence and ASGE recommendations: Is it time for a change? Journal of Clinical Gastroenterology. 2008;42(8):886-91.

70 Khashab M, Eid E, Rusche M, Rex D. Incidence and predictors of 'late' recurrences after endoscopic piecemeal resection of large sessile adenomas. Gastrointestinal Endoscopy. 2009;70:344-9.

71 Kirchgatterer A, Hubner D, Aschl G, Hinterreiter M, Stadler B, Knoflach P. Colonoscopy and sigmoidoscopy in patients aged eighty years or older. Zeitschrift fur Gastroenterologie. 2002;40(12):951-6.

72 Kmieciak Le Corguille M, Gaudric M, Sogni P, Roche H, Brezault C, Dieumegard B, et al. Appropiateness of colonoscopy in a gastrointestinal unit in 2001: A prospective study using criteria established by a European panel of experts. Gastroenterologie Clinique et Biologique. 2003;27(2):213-8.

71


73 Ko CW, Dominitz JA, Green P, Kreuter W, Baldwin LM. Specialty Differences in Polyp Detection, Removal, and Biopsy during Colonoscopy. American Journal of Medicine. 2010;123(6):528-35.

74 Kobayashi H, Mochizuki H, Sugihara K, Morita T, Kotake K, Teramoto T, et al. Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery 2007;141:67-75.

75 Korner H, Soreide K, Stokkeland PJ, Soreide JA. Systematic follow-up after curative surgery for colorectal cancer in Norway: A population-based audit of effectiveness, costs, and compliance. Journal of Gastrointestinal Surgery. 2005;9(3):320-8.

76 Kottachchi D, Yung D, Marshall JK. Adherence to guidelines for surveillance colonoscopy in patients with ulcerative colitis at a Canadian quaternary care hospital. Canadian Journal of Gastroenterology. 2009;23(9):613-7.

77 Lagares-Garcia JA, Kurek S, Collier B, Diaz F, Schilli R, Richey J, et al. Colonoscopy in octogenarians and older patients. Surgical Endoscopy. 2001;15(3):262-5.

78 Laiyemo AO, Murphy G, Albert PS, Sansbury LB, Wang Z, Cross AJ, et al. Postpolypectomy colonoscopy surveillance guidelines: Predictive accuracy for advanced adenoma at 4 years. Annals of Internal Medicine. 2008;148(6):419-26.

79 Laiyemo AO, Pinsky PF, Marcus PM, Lanza E, Cross AJ, Schatzkin A, et al. Utilization and Yield of Surveillance Colonoscopy in the Continued Follow-Up Study of the Polyp Prevention Trial. Clinical Gastroenterology and Hepatology. 2009;7(5):562-7.

80 Lan Y, Lin JK, Li ACN, Lin TY, Chen W, Jiang J, et al. Metachronous colorectal cancer: necessity of post-operative colonoscopic surveillance. International Journal of Colorectal Disease. 2005;20(2):121-5.

81 Landy J, Macfarlane B. Synchronous bidirectional endoscopy for iron deficiency anaemia: Is it appropriate for patients under 50? Postgraduate Medical Journal. 2010;86(1016):338-40.

82 Lasson A, Kilander A, Stotzer PO. Diagnostic yield of colonoscopy based on symptoms. Scandinavian Journal of Gastroenterology. 2008;43(3):356-62.

83 Leaper M, Johnston MJ, Barclay M, Dobbs BR, Frizelle FA. Reasons for failure to diagnose colorectal carcinoma at colonoscopy. Endoscopy. 2004;36(6):499-503.

84 Lee JFY, Ng SSM, Yiu RYC, Leung KL, Lau JWY. Colonoscopy in adult patients: A review of its indications and its yield in detecting colorectal neoplasia. Annals of the College of Surgeons of Hong Kong. 2002;6(2):48-52.

85 Lee KH, Kim HC, Yu CS, Myung SJ, Yang SG, Kim JC. Colonoscopic surveillance after curative resection for colorectal cancer with synchronous adenoma. The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi. 2005;46(5):381-7.

72


86 Leung K, Pinsky P, Laiyemo AO, Lanza E, Schatzkin A, Schoen RE. Ongoing colorectal cancer risk despite surveillance colonoscopy: the Polyp Prevention Trial Continued Follow-up Study. Gastrointestinal Endoscopy. 2010;71(1):111-7.

87 Lieberman DA, Weiss DG, Harford WV, Ahnen DJ, Provenzale D, Sontag SJ, et al. Five-Year Colon Surveillance After Screening Colonoscopy. Gastroenterology. 2008;133(4):1077-85.

88 Loffeld RJ, Van Der Putten ABMM. the annual yield of diagnostic endoscopy of the lower digestive tract. European Journal of Internal Medicine. 2005;16(1):37-40.

89 Lorenzo-Zuniga V, Moreno de Vega V, Domenech E, Manosa M, Planas R, Boix J. Endoscopist experience as a risk factor for colonoscopic complications. Colorectal Disease. 2010;12(10):e273-e7.

90 Lukens FJ, Loeb DS, Machicao VI, Achem SR, Picco MF. Colonoscopy in octogenarians: A prospective outpatient study. American Journal of Gastroenterology. 2002;97(7):1722-5.

91 Lutgens MWMD, Oldenburg B, Siersema PD, Van Bodegraven AA, Dijkstra G, Hommes DW, et al. Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease. British Journal of Cancer. 2009;101(10):1671-5.

92 MacKenzie S, Norrie J, Vella M, Drummond I, Walker A, Molloy R, et al. Randomized clinical trial comparing consultant-led or open access investigation for large bowel symptoms. British Journal of Surgery. 2003;90(8):941-7.

93 Mak T, Senevrayar K, Lalloo F, Evans DGR, Hill J. The impact of new screening protocol on individuals at increased risk of colorectal cancer. Colorectal Disease. 2007;9(7):635-40.

94 Manes G, Imbesi V, Ardizzone S, Cassinotti A, Bosani M, Massari A, et al. Use of colonoscopy in the management of patients with Crohn's disease: Appropriateness and diagnostic yield. Digestive and Liver Disease. 2009;41(9):653-8.

95 Martinez ME, Baron JA, Lieberman DA, Schatzkin A, Lanza E, Winawer SJ, et al. A Pooled Analysis of Advanced Colorectal Neoplasia Diagnoses After Colonoscopic Polypectomy. Gastroenterology. 2009;136(3):832-41.

96 Maruthachalam K, Stoker E, Chaudhri S, Noblett S, Horgan AF. Evolution of the two-week rule pathway - Direct access colonoscopy vs outpatient appointments: One year's experience and patient satisfaction survey. Colorectal Disease. 2005;7(5):480-5.

97 Mathew J, Saklani AK, Borghol M. Surveillance colonoscopy in patients with colorectal cancer: How often should we be doing it? Surgeon. 2006;4(1):3-5.

98 Matsuda T, Fujii T, Sano Y, Kudo SE, Oda Y, Igarashi M, et al. Five-year incidence of advanced neoplasia after initial colonoscopy in Japan: A multicenter retrospective cohort study. Japanese Journal of Clinical Oncology. 2009;39(7):435-42.

73


99 McFall MR, Woods WGA, Miles WFA. Colonoscopic surveillance after curative colorectal resection: Results of an empirical surveillance programme. Colorectal Disease. 2003;5(3):233-40.

100 Mecklin J, Aarnio M, Laara E, Kairaluoma MV, Pylvanainen K, Peltomaki P, et al. Development of Colorectal Tumors in Colonoscopic Surveillance in Lynch Syndrome. Gastroenterology. 2007;133(4):1093-8.

101 Menges M, Fischinger J, Gartner B, Georg T, Woerdehoff D, Maier M, et al. Screening colonoscopy in 40- to 50-year-old first-degree relatives of patients with colorectal cancer is efficient: A controlled multicentre study. International Journal of Colorectal Disease. 2006;21(4):301-7.

102 Menges M, Gartner B, Georg T, Fischinger J, Zeitz M. Cost-benefit analysis of screening colonoscopy in 40- to 50-year-old first-degree relatives of patients with colorectal cancer. International Journal of Colorectal Disease. 2006;21(6):596-601.

103 Miller HL, Mukherjee R, Tian J, Nagar AB. Colonoscopy surveillance after polypectomy may be extended beyond five years. Journal of Clinical Gastroenterology. 2010;44(8):e162-e6.

104 Miller J, Mehta N, Feldman M, Furth E, Ginsberg GG, Yang YX, et al. Findings on serial surveillance colonoscopy in patients with low-risk polyps on initial colonoscopy. Journal of Clinical Gastroenterology. 2010;44(3):e46-e50.

105 Morini S, Hassan C, Meucci G, Toldi A, Zullo A, Minoli G. Diagnostic yield of open access colonoscopy according to appropriateness. Gastrointestinal endoscopy. 2001;54(2):175-9.

106 Moum B, Ekbom A, Vatn MH, Elgjo K. Change in the extent of colonoscopic and histological involvement in ulcerative colitis over time. American Journal of Gastroenterology. 1999;94(6):1564-9.

107 Noshirwani KC, Van Stolk RU, Rybicki LA, Beck GJ. Adenoma size and number are predictive of adenoma recurrence: Implications for surveillance colonoscopy. Gastrointestinal Endoscopy. 2000;51(4 I):433-7.

108 Nusko G, Mansmann U, Kirchner T, Hahn EG. Risk related surveillance following colorectal polypectomy. Gut. 2002;51(3):424-8.

109 Odze R, Farraye F, Hecht J, al. e. Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis. Clinical Gastroenterology and Hepatology. 2004;2(7):534-41.

110 Pabby A, Schoen RE, Weissfeld JL, Burt R, Kikendall JW, Lance P, et al. Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial. Gastrointestinal Endoscopy. 2005;61(3):385-91.

74


111 Park DI, Kim YH, Kim HS, Kim WH, Kim TI, Kim HJ, et al. Diagnostic yield of advanced colorectal neoplasia at colonoscopy, according to indications: An investigation from the Korean Association for the Study of Intestinal Diseases (KASID). Endoscopy. 2006;38(5):449-55.

112 Park DI, Ryu SH, Oh SJ, Yoo TW, Kim HJ, Cho YK, et al. Significance of endoscopy in asymptomatic premenopausal women with iron deficiency anemia. Digestive Diseases And Sciences. 2006;51(12):2372-6.

113 Park JS, Park DI, Park SK, Choi JS, Kim YH, Chang DK, et al. Endoscopic evaluation of significant gastrointestinal lesions in patients with iron deficiency with and without anaemia: A Korean Association for the Study of Intestinal Disease Study. Internal Medicine Journal. 2009;39(7):441-6.

114 Pepin C, Ladabaum U. The yield of lower endoscopy in patients with constipation: Survey of a university hospital, a public county hospital, and a Veterans Administration medical center. Gastrointestinal Endoscopy. 2002;56(3):325-32.

115 Pinsky PF, Schoen RE, Weissfeld JL, Church T, Yokochi LA, Doria-Rose VP, et al. The Yield of Surveillance Colonoscopy by Adenoma History and Time to Examination. Clinical Gastroenterology and Hepatology. 2009;7(1):86-92.

116 Platell C, Salama P, Barwood N, Makin G. Performing a colonoscopy 12 months after surgery for colorectal neoplasia. ANZ Journal of Surgery. 2005;75(5):282-5.

117 Postic G, Lewin D, Bickerstaff C, Wallace MB. Colonoscopic miss rates determined by direct comparison of colonoscopy with colon resection specimens. American Journal of Gastroenterology. 2002;97(12):3182-5.

118 Rabeneck L, Paszat LF, Hilsden RJ, Saskin R, Leddin D, Grunfeld E, et al. Bleeding and Perforation After Outpatient Colonoscopy and Their Risk Factors in Usual Clinical Practice. Gastroenterology. 2008;135(6):1899-906.e1.

119 Rabeneck L, Paszat LF, Saskin R. Endoscopist Specialty Is Associated With Incident Colorectal Cancer After a Negative Colonoscopy. Clinical Gastroenterology and Hepatology. 2010;8(3):275-9.

120 Ramsey SD, Howlader N, Etzioni R, Brown ML, Warren JL, Newcomb P. Surveillance endoscopy does not improve survival for patients with local and regional stage colorectal cancer. Cancer. 2007;109(11):2222-8.

121 Renehan AG, Egger MJ, Saunders M, O'Dwyer ST. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomized trials. British Medical Journal. 2002;324:1-8.

122 Rex DK, Kahi CJ, Levin B, Smith RA, Bond JH, Brooks D, et al. Guidelines for Colonoscopy Surveillance After Cancer Resection: A Consensus Update by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2006;130(6):1865-71.

75


123 Robertson DJ, Burke CA, Welch HG, Haile RW, Sandler RS, Greenberg ER, et al. Using the results of a baseline and a surveillance colonoscopy to predict recurrent adenomas with high-risk characteristics. Annals of Internal Medicine. 2009;151(2):103-9.

124 Robertson DJ, Greenberg ER, Beach M, Sandler RS, Ahnen D, Haile RW, et al. Colorectal cancer in patients under close colonoscopic surveillance. Gastroenterology. 2005;129(1):34-41.

125 Rodríguez-Moranta F, Saló J, Arcusa A, Boadas J, Piñol V, Bessa X, et al. Postoperative surveillance in patients with colorectal cancer who have undergone curative resection: a prospective, multicenter, randomized, controlled trial. Journal of Clinical Oncology. 2006;24(3):386-93.

126 Rostirolla RA, Pereira-Lima JC, Teixeira CR, Schuch AW, Perazzoli C, Saul C. Development of colorectal advanced neoplasia/adenomas in the long-term follow-up of patients submitted to colonoscopy with polipectomy. Arquivos de Gastroenterologia. 2009;46(3):167-72.

127 Rulyak S, Lieberman D, Wagner E, Mandelson M. Outcome of follow-up colon examination among a population-based cohort of colorectal cancer patients. Clinical Gastroenterology and Hepatology. 2007;5(4):470-6.

128 Rulyak S, Mandelson M, Brentnall TA, Rutter C, Wagner E. Clinical and sociodemographic factors associated with colon surveillance among patients with a history of coorectal cance. Gastrointestinal Endoscopy. 2004;59(2):239-47.

129 Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MA, et al. Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk. Gut. 2004;53(12):1813-6.

130 Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MA, et al. Thirty-Year Analysis of a Colonoscopic Surveillance Program for Neoplasia in Ulcerative Colitis. Gastroenterology. 2006;130(4):1030-8.

131 Saini SD, Kim H, Schoenfeld P. Incidence of advanced adenomas at surveillance colonoscopy in patients with a personal history of colon adenomas: a meta-analysis and systematic review. Gastrointestinal Endoscopy. 2006;64:614-26.

132 Saini SD, Schoenfeld P, Vijan S. Surveillance Colonoscopy Is Cost-Effective for Patients With Adenomas Who Are at High Risk of Colorectal Cancer. Gastroenterology. 2010;138(7):2292-9.e1.

133 Salama M, Ormonde DG, Quach T, Ee HC, Yusoff IF. Outcomes of endoscopic resection of large colorectal neoplasms: an Australian experience. Journal of Gastroenterology and Hepatology. 2009;25:84-9.

134 Sanchez A, Munoz C, Bujanda L, Iriondo C, Gil-Molet A, Cosme A, et al. The value of colonoscopy to assess rectal bleeding in patients referred from Primary Care Units. Revista Espanola de Enfermedades Digestivas. 2005;97(12):870-6.

76


135 Sardinha TC, Nogueras JJ, Ehrenpreis ED, Zeitman D, Estevez V, Weiss EG, et al. Colonoscopy in octogenarians: A review of 428 cases. International Journal of Colorectal Disease. 1999;14(3):172-6.

136 Schoenfeld PS, Fincher RK. Colonoscopic surveillance of patients with a family history of colon cancer and a history of normal colonoscopy: Is a five-year interval between colonoscopies appropriate? Clinical Gastroenterology and Hepatology. 2003;1(4):310-4.

137 Schoepfer A, Marbet UA. Colonoscopic findings of symptomatic patients aged 50 to 80 years suggest that work-up of tumour suspicious symptoms hardly reduces colorectal cancer-induced mortality. Swiss Medical Weekly. 2005;135(45-46):679-83.

138 Seitz U, Bohnacker S, Seewald S, Thonke F, Soehendra N. Long-term results of endoscopic removal of large colorectal adenomas. Endoscopy. 2003;35:s41-s4.

139 Seow CH, Ee HC, Willson AB, Yusoff IF. Repeat colonoscopy has a low yield even in symptomatic patients. Gastrointestinal Endoscopy. 2006;64(6):941-7.

140 Shetty K, Rybicki LA, Brzezinski A, Carey W, Lashner BA. The risk for cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis. American Journal of Gastroenterology. 1999;94(6):1643-9.

141 Siddique I, Mohan K, Hasan F, Memon A, Patty I, Al-Nakib B. Appropriateness of indication and diagnostic yield of colonoscopy: First report based on the 2000 guidelines of the American Society for Gastrointestinal Endoscopy. World Journal of Gastroenterology. 2005;11(44):7007-13.

142 Siegel CA, Sands BE. Risk factors for colorectal cancer in Crohn's colitis: A case-control study. Inflammatory Bowel Diseases. 2006;12(6):491-6.

143 Singh (1) H, Nugent Z, Demers AA, Kliewer EV, Mahmud SM, Bernstein CN. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Gastroenterology. 2010;139(4):1128-37.

144 Singh (2) H, Nugent Z, Mahmud SM, Demers AA, Bernstein CN. Predictors of colorectal cancer after negative colonoscopy: A population-based study. American Journal of Gastroenterology. 2010;105(3):663-73.

145 Singh H, Turner D, Xue L, Targownik LE, Bernstein CN. Risk of developing colorectal cancer following a negative colonoscopy examination: Evidence for a 10-year interval between colonoscopies. Journal of the American Medical Association. 2006;295(20):2366-73.

146 Smith GA, Oien KA, O'Dwyer PJ. Frequency of early colorectal cancer in patients undergoing colonoscopy. British Journal of Surgery. 1999;86(10):1328-31.

147 Stephens MR, Hopper AN, White SR, Jugool S, Stratford R, Lewis WG, et al. Colonoscopy first for iron-deficiency anaemia: A Numbers Needed to Investigate approach. QJM. 2006;99(6):389-95.

77


148 Stevens T, Burke CA. Colonoscopy screening in the elderly: When to stop? American Journal of Gastroenterology. 2003;98(8):1881-5.

149 Stigliano V, Fracasso P, Grassi A, Lapenta R, Citarda F, Tomaselli G, et al. Endoscopic follow-up in resected colorectal cancer patients. Journal of Experimental and Clinical Cancer Research. 2000;19(2):145-8.

150 Stupart DA, Goldberg PA, Algar U, Ramesar R. Surveillance colonoscopy improves survival in a cohort of subjects with a single mismatch repair gene mutation. Colorectal Disease. 2009;11(2):126-30.

151 Suriani R, Rizzetto M, Mazzucco D, Grosso S, Gastaldi P, Marino M, et al. Appropriateness of colonoscopy in a digestive endoscopy unit: A prospective study using ASGE guidelines. Journal of Evaluation in Clinical Practice. 2009;15(1):41-5.

152 Syrigos KN, Charalampopoulos A, Ho JL, Zbar A, Murday VA, Leicester RJ. Colonoscopy in asymptomatic individuals with a family history of colorectal cancer. Annals of Surgical Oncology. 2002;9(5):439-43.

153 Terhaar Sive Droste JS, Craanen ME, van der Hulst RWM, Bartelsman JF, Bezemer DP, Cappendijk KR, et al. Colonoscopic yield of colorectal neoplasia in daily clinical practice. World Journal of Gastroenterology. 2009;15(9):1085-92.

154 Tjandra J, Chan M. Follow-up after curative resection of colorectal cancer: a meta-analysis. Diseases of the Colon and Rectum. 2007;50(11):1783-99.

155 Togashi K, Konishi F, Ozawa A, Sato T, Shito K, Kashiwagi H, et al. Predictive factors for detecting colorectal carcinomas in surveillance colonoscopy after colorectal cancer surgery. Diseases of the Colon and Rectum. 2000;43(10 SUPPL.):S47-S53.

156 Velayos FS, Loftus J, Juess T, al. e. Predictive and protective factors associated with colorectal cancer in ulcerative colitis: a case-control study. Gastroenterology. 2006;130:1941-9.

157 Wang T, Cui Y, Huang WS, Deng YH, Gong W, Li Cj, et al. The role of postoperative colonoscopic surveillance after radical surgery for colorectal cancer: a prospective, randomized clinical study. Gastrointestinal Endoscopy. 2009;69(3 SUPPL.):609-15.

158 Wexner SD, Garbus JE, Singh JJ. A prospective analysis of 13,580 colonoscopies: Reevaluation of credentialing guidelines. Surgical Endoscopy. 2001;15(3):251-61.

159 Winawer SJ, Zauber AG, Fletcher RH, Stillman JS, O'Brien MJ, Levin B, et al. Guidelines for Colonoscopy Surveillance After Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. Gastroenterology. 2006;130(6):1872-85.

160 Yamaji Y, Mitsushima T, Ikuma H, Watabe H, Okamoto M, Kawabe T, et al. Incidence and recurrence rates of colorectal adenomas estimated by annually repeated colonoscopies on asymptomatic Japanese. Gut. 2004;53(4):568-72.

78


161 Yeh CY, Chiang JM, Wang JY, Chang KJ, Liang JT, Wang SM. Colonoscopic surveillance in asymptomatic persons with family history of colorectal cancer. Formosan Journal of Surgery. 1999;32(3):111-5.

162 Yusoff IF, Hoffman NE, Ee HC. Colonoscopic surveillance after surgery for colorectal cancer. ANZ Journal of Surgery. 2003;73(1-2):3-7.

Excluded studies

1 Abir F, Alva S, Longo W, Audiso R, Virgo K, Johnson F. The postoperative surveillance of patients wiht colon cancer and rectal cancer. American Journal of Surgery. 2006;192:100-8.

2 Bartram HP, Burgstaller M, Eller F, Eller U, Kellner R, Kerzel W, et al. Costs for endoscopic examinations in specialized gastroenterological practices - Members of the Bavarian BNG-group present their business management data for discussion. Verdauungskrankheiten. 2003;21(4):189-95.

3 Charalambopoulos A, Syrigos KN, Ho JL, Murday VA, Leicester RJ. Colonoscopy in symptomatic patients with positive family history of colorectal cancer. Anticancer Research. 2000;20(3 B):1991-4.

4 Dafnis G, Blomqvist P, Pahlman L, Ekbom A. The introduction and development of colonoscopy within a defined population in Sweden. Scandinavian Journal of Gastroenterology. 2000;35(7):765-71.

5 Ee HC, Yusoff IF. Colonoscopic surveillance after curative surgery for colorectal cancer. ANZ Journal of Surgery. 2005;75(5):257-8.

6 Farraye F, Odze R, Eaden J, Itzkowitz S. AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010;138(2):746-74.

7 Gado A, Ebeid B, Axon A. High quality colonoscopy in a low volume unit; is it achievable? Arab Journal of Gastroenterology. 2010;11(3):161-4.

8 Ge Z, Hu Y, Shi Y, Mo J, Zhang D, Xiao S. Evaluation of colonoscopic surveillance interval after removal of colonica adenomas. Chinese Journal of Gastroenterology. 2001;6(1):35-7.

9 Harris JK, Froehlich F, Gonvers JJ, Wietlisbach V, Burnand B, Vader JP. The appropriateness of colonoscopy: A multi-center, international, observational study. International Journal for Quality in Health Care. 2007;19(3):150-7.

10 Imperiale TF, Wagner DR, Lin CY, Larkin GN, Rogge JD, Ransohoff DF. Using Risk for Advanced Proximal Colonic Neoplasia to Tailor Endoscopic Screening for Colorectal Cancer. Annals of Internal Medicine. 2003;139(12):959-65+I10.

11 Imperiali G, Minoli G. Colonic neoplasm in asymptomatic patients with family history of colon cancer: results of a colonoscopic prospective and controlled study. Results of a pilot

79


study of endoscopic screening of first degree relatives of colorectal cancer patients in Italy. Gastrointestinal endoscopy. 1999;49(1):132-3.

12 Jeffery M, Hickey B, Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database of Systematic Reviews. 2007;Jan 24(1):CD002200.

13 John BJ, Irukulla S, Pilgrim G, Swift I, Abulafi AM. Surveillance colonoscopies for colorectal polyps - Too often, too many! An Audit at a Large District General Hospital. Colorectal Disease. 2008;10(9):898-900.

14 Keren D, Rainis T, Goldstein O, Stermer E, Lavy A. Significant colonic neoplasia prevalence and ASGE recommendations: Is it time for a change? Journal of Clinical Gastroenterology. 2008;42(8):886-91.

15 Khan IM, Karman Hassan M, Rahman S, Javed M, Khattak AK, Hameed K, et al. Frequency of organic pathologies in patients with Irritable bowel syndrome. JPMI - Journal of Postgraduate Medical Institute. 2009;23(4):341-6.

16 Khandker RK, Dulski JD, Kilpatrick JB, Ellis RP, Mitchell JB, Baine WB. A decision model and cost-effectiveness analysis of colorectal cancer screening and surveillance guidelines for average-risk adults. International Journal of Technology Assessment in Health Care. 2000;16(3):799-810.

17 Kim JB, Han DS, Lee HL, Kim JP, Jeon YC, Sohn JH, et al. The recurrence rate of colon polyp after polypectomy and the interval of surveillance colonoscopy: predictors of early development of advanced polyp. The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi. 2004;44(2):77-83.

18 Kula Z, Bala D, Piech J, Weishof A, Zegarski W, Dziki A. Retrospective colonoscopic evaluation in patients following colorectal carcinoma surgery. Polski Przeglad Chirurgiczny. 2004;76(5):473-82.

19 Lund JN, Scholefield JH, Grainge MJ, Smith SJ, Mangham C, Armitage NC, et al. Risks, costs, and compliance limit colorectal adenoma surveillance: Lessons from a randomised trial. Techniques in Coloproctology. 2002;6(1):63.

20 Macafee DAL, Whynes DK, Scholefield JH. Risk-stratified intensive follow up for treated colorectal cancer - Realistic and cost saving? Colorectal Disease. 2008;10(3):222-30.

21 Mulder SA, Van Soest EM, Dieleman JP, Van Rossum LGM, Ouwendijk RJT, Van Leerdam ME, et al. Exposure to colorectal examinations before a colorectal cancer diagnosis: A case-control study. European Journal of Gastroenterology and Hepatology. 2010;22(4):437-43.

22 Rabast U, Hartmann T, Kasper H. Colonoscopic diagnosis and treatment of colorectal neoplasias - Analysis of a 10 year period. Medizinische Welt. 2003;54(12):364-8.

80


23 Rabeneck L, Paszat LF, Saskin R. Endoscopist Specialty Is Associated With Incident Colorectal Cancer After a Negative Colonoscopy. Clinical Gastroenterology and Hepatology. 2010;8(3):275-9.

24 Ramsey SD, Howlader N, Etzioni R, Brown ML, Warren JL, Newcomb P. Surveillance endoscopy does not improve survival for patients with local and regional stage colorectal cancer. Cancer. 2007;109(11):2222-8.

25 Rex D. Quality in colonoscopy. American Journal of Gastroenterology. 2006;2006(101).

26 Romagnuolo J, Enns R, Ponich T, Springer J, Armstrong D, Barkun AN. Canadian credentialing guidelines for colonoscopy. Canadian Journal of Gastroenterology. 2008;22(1):17-22.

27 Scholefield JH, Steele RJ. Guidelines for follow up after resection of colorectal cancer. Gut. 2002;51(SUPPL. 5):v3-v5.

28 Sieg A. Objective criteria for the quality of colonoscopy. Verdauungskrankheiten. 2001;19(5):208-10.

29 Siegel CA, Sands BE. Risk factors for colorectal cancer in Crohn's colitis: A case-control study. Inflammatory Bowel Diseases. 2006;12(6):491-6.

30 Song J. Study on surveillance colonoscopy after endoscopic polypectomy of adenomatous lesions of large intestine. Journal of the Japan Society of Colo-Proctology. 1999;52(1):8-17.

31 Thomas-Gibson S, Thapar C, Shah SG, Saunders BP. Colonoscopy at a combined district general hospital and specialist endoscopy unit: Lessons from 505 consecutive examinations. Journal of the Royal Society of Medicine. 2002;95(4):194-7.

32 Vader JP, Pache I, Froehlich F, Burnand B, Schneider C, Dubois RW, et al. Overuse and underuse of colonoscopy in a European primary care setting. Gastrointestinal Endoscopy. 2000;52(5):593-9.

Other references

1 Abela J, Weir F, McGregor J, Diament R. Cancer of the proximal colon after a "normal" colonoscopy. Bioscience Trends. 2009; 3(4): 158-60.

2 American Society for Gastrointestinal Endoscopy. Appropriate Use of Gastrointestinal Endoscopy. A consensus statement from the American Society for Gastrointestinal Endoscopy. Available at: http://www.asge.org/WorkArea/showcontent.aspx?id=3394. Accessed: 15 January 2011.

3 Australian Cancer Network Colorectal Cancer Guidelines Revision Committee. Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer. Sydney2005.

81

http://www.asge.org/WorkArea/showcontent.aspx?id=3394

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Diament%20RH%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22McGregor%20JR%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Weir%20F%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Abela%20JE%22%5BAuthor%5D


4 Australian Institute of Health and Welfare, Australian Government Department of Health and Ageing. National Bowel Cancer Screening Program: annual monitoring report 2009 data supplement 2010. Canberra: AIHW2010.

5 Bampton P, Sandford J, Young G. Applying evidence-based guidelines improves use of colonoscopy resources in patients with a moderate risk of colorectal neoplasia. Medical Journal of Australia 2002; 176: 155-7.

6 Bampton P, Sandford J, Young G. Achieving long-term compliance with colonoscopic surveillance guidelines for patients at increased risk of colorectal cancer in Australia. International Journal of Clinical Practice 2007; 61: 510-13.

7 Conjoint Committee. 2011 [11 February 2011]; Available from: http://www.conjoint.org.au/.

8 Department of Health and Ageing. A qualitative evaluation of opinions, attitudes and behaviours influencing the bowel cancer screening pilot program: final report. August 2004. Available from: http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/content/eval-oct05-cnt

9 Finn L, Pepper A, Gregory P et al. Improving indigenous access to cancer screening and treatment services. Australasian Medical Journal 2008; 2: 1-21.

10 GESA. Guidelines on sedation and / or analgesia for diagnostic and interventional medical, dental or surgical procedures 2010.

11 GESA / GENCA. Standards for Endoscopic Facilities and Services. 3rd ed2007.

12 Guyatt G, Oxman A, Vist G, al. e. Rating quality of evidence and strength of recommendations GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. British Medical Journal. 2008;336:924-6.

13 Heresbach D, Barrioz T, Lapalus MG, Coumaros D, Bauret P, Potier P, et al. Miss rate for colorectal neoplastic polyps: A prospective multicenter study of back-to-back video colonoscopies. Endoscopy. 2008;40(4):284-90.

14 Jandorf L, Gutierrez Y, Lopez J et al. Use of a patient navigator to increase colorectal cancer screening in an urban neighbourhood health clinic. Journal of Urban Health 2005; 82: 216-24.

15 Lindor N, Rabe K, Petersen G et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA 2005; 293: 1979-85.

16 National Bowel Cancer Screening Program Quality Working Group. Improving Colonoscopy Services in Australia. Canberra: Australian Government Department of Health and Ageing 2009.

82

http://www.conjoint.org.au/


17 National Health and Medical Research Council. Levels of evidence and grades for recommendations for developers of guidelines. Canberra, December 2009.

18 Peteriet D, Molloy K, Reiner M et al. Establishing a patient navigator program to reduce cancer disparities in the American Indian communities of Western South Dakota. Cancer Control 2008; 15: 254-9.

19 Queensland Health. Queensland Bowel Cancer Screening Program. Phase 1 Evaluation. 7 August 2006-30 June 2008. Available at: http://www.health.qld.gov.au/bowelcancer/documents/qbcsp-phase1-eval.pdf

20 Schroy P, Lal S, Glick J, al. e. Patient preferences for colorectal cancer screening. American Journal of Managed Care. 2007;13:393-400.

21 Swan M, Bourke M, Alexander S, Moss A and Williams S. Large refractory colonic polyps: is it time to change our practice? A prospective study of the clinical and economic impact of a tertiary referral colonic mucosal resection and polypectomy service. Gastrointestinal Endoscopy 2009; 70: 1128-1136.

22 van Rijn J, Reitsma JB, Stoker J, Bossuyt PM, Van Deventer SJ, Dekker E. Polyp miss rate determined by tandem colonoscopy: systematic review. American Journal of Gastroenterology. 2006;101:343-50.

23 Wexner S, Beck D, Baron T et al. A consensus document on bowel preparation prior to colonoscopy. ASGE / ASCRS / SAGES Guidelines for Bowel Preparation Prior to Colonoscopy. 2006.

24 Wilson J, Hair C, Knight R et al. High incidence of inflammatory bowel disease in Australia: a prospective population-based Australian incidence study. Inflammatory Bowel Disease 2010; 16: 1550-6.

25 Winawer SJ, Fletcher RH, Rex D, al. e. Colorectal cancer screening and surveillance: clinical guidelines and rationale - Update based on new evidence. . Gastroenterology 2003;124:544-60.

26 Zubarik R, Ganguly E, Benway D, al. e. Procedure-related abdominal discomfort in patients undergoing colorectal cancer screening. American Journal of Gastroenterology. 2002;97:3056-61.

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APPENDIX 1 – SEARCH TERMS FOR IDENTIFYING STUDIES

1 colonoscopy [MeSH]

2 colonoscopy.tw

3 or/1 and 2

4 meta-analysis.pt.

5 (meta-anal$ or metaanal$).tw.

6 (uantitative$ review$ or uantitative$ overview$).tw.

7 (systematic$ review$ or systematic$ overview$).tw.

8 guideline.pt

9 randomized controlled trial.pt.

10 controlled clinical trial.pt.

11 random allocation/

12 double blind method/

13 single blind method/

14 clinical trial.pt.

15 cross-over studies/

16 ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).tw.

17 (randomi?ation or random allocation or random selection or random assignment or randomly allocated

18 randomly selected or randomly assigned or randomly divided or randomly distributed).tw.

19 cohort studies [MeSH]

20 case control studies [MeSH]

21 qualitative research [MeSH]

22 outcome assessment (health care) [MeSH]

23 quality assurance, health care [MeSH]

24 “costs and cost analysis”/ or cost-benefit analysis/ or “cost of illness”/ or exp health care costs/ or health

25 health status disparities [MeSH]

84


26 descriptive.sh

27 observational.sh

28 or/4-27

29 not (case report$ OR editorial$ OR comment$ or letter$)

30 animals/ not (animals/ and humans/)

31 28 and 29 and 30

32 3 and 31

85


APPENDIX 2 – STUDY ASSESSMENT CRITERIA

The following study assessment criteria were applied:

Systematic reviews

1 Were the questions and methods clearly stated?

2 Is the search procedure sufficiently rigorous to identify all relevant studies?

3 Does the review include all the potential benefits and harms of the intervention?

4 Does the review only include randomised controlled trials?

5 Was the methodological quality of primary studies assessed?

6 Are the data summarised to give a point estimate of effect and confidence intervals?

7 Were differences in individual study results adequately explained?

8 Is there an examination of which study population characteristics (disease subtypes, age/sex groups) determine the magnitude of effect of the intervention?

9 Were the reviewers’ conclusions supported by data cited?

10 Were sources of heterogeneity explored?

Randomised controlled trials

1 Were the setting and study subjects clearly described?

2 Is the method of allocation to intervention and control groups/sites independent of the decision to enter the individual or group in the study?

3 Was allocation to study groups adequately concealed from subjects, investigators and recruiters including blind assessment of outcome?

4 Are outcomes measured in a standard, valid and reliable way?

5 Are outcomes measured in the same way for both intervention and control groups?

6 Were all clinically relevant outcomes reported?

7 Are factors other than the intervention e.g. confounding factors, comparable between intervention and control groups and if not comparable, are they adjusted for in the analysis?

8 Were >80% of subjects who entered the study accounted for at its conclusion?

9 Is the analysis by intention to intervene (treat)?86


10 Were both statistical and clinical significance considered?

11 Are results homogeneous between sites? (Multi-centre/multi-site studies only).

Cohort studies

1 Are study participants well-defined in terms of time, place and person?

2 What percentage (%) of individuals or clusters refused to participate?

3 Are outcomes measured in a standard, valid and reliable way?

4 Are outcomes measured in the same way for both intervention and control groups?

5 Was outcome assessment blind to exposure status?

6 Are confounding factors, comparable between the groups and if not comparable, are they adjusted for in the analysis?

7 Were >80% of subjects entered accounted for in results and clinical status described?

8 Was follow-up long enough for the outcome to occur?

9 Was follow-up complete and were there exclusions from the analysis?

10 Are results homogeneous between sites? (Multicentre/multisite studies only).

Case-control studies

1 Was the definition of cases adequate?

2 Were the controls randomly selected from the source of population of the cases?

3 Were the non-response rates and reasons for non-response the same in both groups?

4 Is possible that over-matching has occurred in that cases and controls were matched on factors related to exposure?

5 Was ascertainment of exposure to the factor of interest blinded to case/control status?

6 Is exposure to the factor of interest measured in the same way for both case and control groups in a standard, valid and reliable way (avoidance of recall bias)?

7 Are outcomes measured in a standard, valid and reliable way for both case and control groups?

8 Are the two groups comparable on demographic characteristics and important potential confounders? And if not comparable, are they adjusted for in the analysis?

9 Were all selected subjects included in the analysis?

87


10 Was the appropriate statistical analysis used (matched or unmatched)?

11 Are results homogeneous between sites? (Multicentre/multisite studies only).

Diagnostic accuracy studies

1 Has selection bias been minimised?

2 Were patients selected consecutively?

3 Was follow-up for final outcomes adequate?

4 Is the decision to perform the reference standard independent of the test results (i.e. avoidance of verification bias)?

5 If not, what per cent were not verified?

6 Has measurement bias been minimised?

7 Was there a valid reference standard?

8 Are the test and reference standards measured independently (ie blind to each other)

9 Are tests measured independently of other clinical and test information?

10 If tests are being compared, have they been assessed independently (blind to each other) in the same patients or done in randomly allocated patients?

11 Has confounding been avoided?

12 If the reference standard is a later event that the test aims to predict, is any intervention decision blind to the test result?

88


Study quality – Rating

The following was used to rate the quality of each study against the study type criteria listed above.

A High: all or all but one of the criteria were met

B Medium: 2 or 3 of the criteria were not met

C Low: 4 or more of the criteria were not met

89


APPENDIX 3 – EVIDENCE HIERARCHY

The following evidence hierarchy was applied:

Level Intervention Diagnostic Prognosis

I A systematic review of level II studies

A systematic review of level II studies

A systematic review of level II studies

II A randomised controlled trial A study of test accuracy with: an independent, blinded comparison with a valid reference standard, among consecutive persons with a defined clinical presentation

A prospective cohort study

III-1 A pseudo-randomised controlled trial (i.e. alternate allocation or some other method)

A study of test accuracy with: an independent, blinded comparison with a valid reference standard, among non-consecutive persons with a defined clinical presentation

All or none of the people with the risk factor(s) experience the outcome; and the data arises from an unselected or representative case series which provides an unbiased representation of the prognostic effect

III-2 A comparative study with concurrent controls: non-randomised, experimental trial; cohort study; case-control study; interrupted time series with a control group

A comparison with reference standard that does not meet the criteria required for Level II and III-1 evidence

Analysis of prognostic factors amongst persons in a single arm of a randomised controlled trial

III-3 A comparative study without concurrent controls: historical controls, two or more single arm study, interrupted time series without a parallel control group

Diagnostic case-control study A retrospective cohort study

IV Case series with either post-test or pre-test/post-test outcomes

Study of diagnostic yield with no reference standard

Case series, or cohort study of persons at different stages of disease

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APPENDIX 4 – CHARACTERISTICS OF EXCLUDED STUDIES

Study Reason for exclusion

Abir 2006 Non-systematic review

Bartram 2003 Non-English language

Charalambopoulos 2000 Controls not appropriately matched on all relevant case criteria, insufficient details regarding family history

Dafnis 2000 Unable to separate data for paediatric colonoscopy from data for colonoscopy performed in adult patients

Ee 2005 Non-systematic review

Farraye 2010 Review methods not outlined

Gado 2010 All valid outcome measures were not included in the analysis; single colonoscopist

Ge 2001 Non-English language

Harris 2007 Duplicate publication of Gonvers 2007

Imperiale 2003 Unable to determine combined proximal and distal neoplasia rate for adenoma and / or carcinoma

Imperiali 1999 Comment on published studies

Jeffery 2007 Colonoscopy-specific data unable to be extracted

John 2008 Appropriateness criteria not used; 95% CI and p value for pre-test / post-test results not consistent; study limited to re-screening for patients undergoing adenoma surveillance

Keren 2008 Non-systematic review

Khan 2009 Not all subjects received colonoscopy

Khandker 2000 Screening study comparing costs of different colorectal cancer screening modalities

Kim 2004 Non-English language

Kula 2004 Non-English language

Lund 2002 Cost data not provided

Macafee 2008 Individual patient data for costs associated with colonoscopy surveillance alone not provided; intensive and routine group had same colonoscopy protocol

Mulder 2010 Colonoscopy-specific data unable to be extracted

Rabast 2003 Non-English language

Rabeneck 2010 Number of proceduralists not reported (only number of procedures)

Ramsey 2007 Colonoscopy-specific data unable to be extracted

Rex 2006 Non-systematic review

Romagnuolo 2008 Non-systematic review91


Scholefield 2002 Methods of guideline development not specified

Sieg 2001 Non-English language

Siegel 2006 Specific to patients with Crohn’s colitis

Song 1999 Non-English language

Thomas-Gibson 2002 Case numbers for individual proceduralists not reported

Vader 2000 The majority of patients who were eligible for colonoscopy did not receive it

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APPENDIX 5 – TABLES OF INCLUDED STUDIES

Review Question 1a: Appropriate timing of colonoscopy in patients with a family history of bowel cancerStudy ID and Level of Evidence

Country Sample size

Methods Key findings Quality score

Beaudin 2000

IV

Canada N=118 A retrospective case control study in a community-based gastroenterology practice of patients who have had screening by colonoscopy of asymptomatic first-degree relatives of patients with colorectal cancers.

Over the 10 years of the study, 1 advanced carcinoma and 22 adenomas in 15 patients were found across 118 individuals screened.

Sixteen patients had tubular adenomas and 6 had advanced lesions (carcinoma, tubulovillous adenomas or adenomas larger than 1 cm).

C

Dove-Edwin 20005

III-2

UK N=1,678 Prospective, observational study of high-risk families, followed up over 16 years in a tertiary referral family cancer clinic in London.

Median age at initial colonoscopy was 41 years. Colonoscopy was initially offered at five-yearly intervals and then three-yearly intervals if an adenoma was detected at index colonoscopy.

The incidence of adenomas with high risk pathological features or cancer was analysed according to the age, the extent of the family history, and findings on previous colonoscopies of participants.

Incidence of colorectal cancer and mortality during over 15,000 person years of follow-up were compared with those expected in the absence of surveillance.

Risk of adenoma or carcinoma increased with increasing age, from 2% in people younger than 35 years to 15% in those aged 65 years and older.

Risk of adenoma on follow-up colonoscopy in high-risk families was 26% compared with 13% in low-risk families.

High-risk adenomas and cancer were most common in families with hereditary non-polyposis colorectal cancer (on initial colonoscopy 5.7% and 0.9%, respectively), compared with 1.1% and 0.1% respectively for moderate and low risk families combined.

The incidence of colorectal cancer was substantially lower - 80% lower in families at moderate rather than high risk of colorectal cancer (p<0.001), and 43% lower in families with hereditary non-polyposis colorectal cancer (p=0.06) - than the expected incidence in the absence of surveillance.

C

Gilbert 2001

IV

UK N=449 Colonoscopy was performed in patients with one or more relatives with colorectal cancer; 212 were asymptomatic and 237 were symptomatic.

Colonoscopy commenced at 40 years of age or 10 years younger than the youngest affected relative.

Neoplastic change (benign and malignant) was found in 25.5% of the asymptomatic group and 24% of the symptomatic group; in 26% of those with one first degree relative, 39% with two or more first degree relatives and only 19% with second degree relatives.

A total of 38% of lesions were out of reach of a flexible

C

93


Study ID and Level of Evidence

Country Sample size


sigmoidoscope.

No known complications of colonoscopy occurred in participants.

Kahi 2007

IV

US N=163 Retrospective cohort study of persons aged ≥ 75 years who underwent colonoscopy between 1999 and 2000.

Advanced neoplasms were defined as colorectal cancer, polyp with high-grade dysplasia, villous histologic features, or tubular adenoma ≥1 cm.

No statistically significant difference in advanced neoplasm rate was observed between patients with a family history of colorectal cancer and patients with no family history.

C

Martinez 2009

III-2

US N=9,167 Individual data were pooled from 8 prospective studies comprising patients with previously resected colorectal adenomas.

Risk of developing subsequent advanced adenoma or cancer was quantified.

Median follow-up period was 47.2 months. Advanced colorectal neoplasia was diagnosed in 1,082 (11.8%) patients, 58 of whom (0.6%) had invasive cancer.

Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%) and those with an adenoma 20 mm in size or greater (19.3%).

The number and size of prior adenomas (p < 0.001 for trend) and the presence of villous features (OR 1.28; 95% CI 1.07-1.52) was associated with increased risk for metachronous advanced neoplasia.

B

Nusko 2002

IV

Germany N=1,159 Patients undergoing endoscopic removal of colorectal adenomas were prospectively recorded on the Erlangen Registry of Colorectal Polyps between 1978 and 1996.

A multivariate analysis of patients on long-term follow up was performed to identify risk factors determining surveillance intervals for patients with metachronous adenomas of advanced pathology (i.e. adenomas >10 mm or with high grade dysplasia or invasive carcinoma).

Follow-up colonoscopy was performed every 2 years for patients with multiple adenomas and 4 years for patients with single adenomas.

5 colorectal cancers occurred over 11 years of follow-up.

In patients with single adenomas it was estimated that 10% would develop advanced adenomas over 12.2 years; in patients with multiple adenomas it was estimated that 10% would develop advanced adenomas over 6.1 years.

On the basis of multivariate analysis, patients with parental history of colorectal carcinoma have an increased risk of metachronous

C

94



Country Sample size


adenomas of advanced pathology at follow up after three years.

Schoenfeld 2003

IV

US N=100 Consecutive patients with a family history of colorectal cancer and a normal screening colonoscopy 5 years earlier were offered a surveillance colonoscopy.

Patients also completed a questionnaire about potential risk factors for adenomas.

Multiple logistic regression analysis assessed associations between risk factors and adenomas.

Eight percent (8 of 100) of patients had advanced adenomas at surveillance colonoscopy, and 33% (33 of 100) had adenomas.

Among patients with adenomas, 39% (13 of 33) had no adenomas in the left side of the colon (i.e. distal to the splenic flexure). Among patients with advanced adenomas, 25% (2 of 8) had no adenomas in the left side of the colon.

Multiple logistic regression analysis showed a significant negative association between adenomas and NSAID use (OR 0.26 [95% CI 0.09-0.79]), and male gender had a positive association with adenomas (OR 2.79 [95% CI 1.017.74]).

C

Yeh 1999

IV

Taiwan N=409 The records of asymptomatic persons with one affected first-degree relative and who had received a colonoscopic examination between 1993 and 1996 were reviewed.

41 persons, including 3 with adenocarcinoma, 1 with a adenomatous polyposis, 7 multiple adenomas, and 30 single adenomas, were identified. 26 of the 178 older persons (> 40 years old) and 15 of the 231 younger persons (≤40 years old) had colorectaI neoplasm.

C

95


Review Question 1b: Appropriate timing of colonoscopy in patients with a genetic predisposition to bowel cancer Study ID and Level of Evidence

Country Sample size


Dove-Edwin 20005III-2

UK N=1,678 Prospective, observational study of high-risk families, followed up over 16 years in a tertiary referral family cancer clinic in London.Median age at initial colonoscopy was 41 years. Colonoscopy was initially offered at five-yearly intervals and then three-yearly intervals if an adenoma was detected at index colonoscopy.The incidence of adenomas with high risk pathological features or cancer was analysed according to the age, the extent of the family history, and findings on previous colonoscopies of participants. Incidence of colorectal cancer and mortality during over 15,000 person years of follow-up were compared with those expected in the absence of surveillance.

Risk of adenoma or carcinoma increased with increasing age, from 2% in people younger than 35 years to 15% in those aged 65 years and older.Risk of adenoma on follow-up colonoscopy in high-risk families was 26% compared with 13% in low-risk families.High-risk adenomas and cancer were most common in families with hereditary non-polyposis colorectal cancer (on initial colonoscopy 5.7% and 0.9%, respectively), compared with 1.1% and 0.1% respectively for moderate and low risk families combined. The incidence of colorectal cancer was substantially lower - 80% lower in families at moderate rather than high risk of colorectal cancer (p<0.001), and 43% lower in families with hereditary non-polyposis colorectal cancer (p=0.06) - than the expected incidence in the absence of surveillance.

C

Dove-Edwin 2006III-2

UK N=125 Prospective cohort study carried out at 2 tertiary centres on individuals from families with a dominant colorectal cancer history. Colonoscopy results in at-risk family members were compared.

Twenty-nine families were classified as having Lynch syndrome and 68 as not having Lynch syndrome. High-risk adenomas occurred in 7 of 91 (7.7%) individuals with Lynch syndrome and 15 of 197 (7.6%) individuals without Lynch syndrome. Cancer was observed only in individuals with Lynch syndrome (4/91; 4.4%). Multiple adenomas were only seen in non-Lynch syndrome individuals (13/197; 6.6%).

C

Engel 2010III-2

Germany N=1,126 A prospective, multicenter cohort study of individuals from 3 groups of HNPCC families: those with a pathogenic germline mutation in a mismatch repair gene (MUT group), those

Ninety-nine colorectal cancers were observed in 90 patients; 17 (17%) were detected through symptoms. 2 of 43 colorectal cancers detected by follow-up colonoscopy were

B

96



Country Sample size


without a mutation but with microsatellite instability (MSI group), and those who fufilled the Amsterdam criteria without microsatellite instability (MSS group).

regionally advanced. Tumour stages were significantly lower among tumours detected by follow-up colonoscopies compared with tumours detected by symptoms. Cumulative risk of colorectal cancer at the age of 60 years was similar in the MUT and MSI groups (23.0% combined; 95% CI 14.8%-31.2%) but considerably lower in the MSS group (1.8%; 95% CI 0.0%-5.1%).Adenomas at baseline colonoscopy predicted an earlier occurrence of subsequent adenoma (HR 2.6; 95% CI 1.7-4.0) and colorectal cancer (HR 3.9; 95% CI 1.7-8.5).

Jarvinen 2000III-2

Finland N=252 Prospective cohort study. Incidence of colorectal cancer and survival were compared in 2 cohorts of at-risk members of 22 families with HNPCC. Colonic screening at 3-year intervals was arranged for 133 subjects; 119 control subjects had no screening. Genetic testing was offered to subjects in whose families the causative mutation was known.

Colorectal cancer developed in 8 screened subjects (6%) compared with 19 control subjects (16 %; p = 0.014). The cancer rate was reduced by 62% in screened subjects. In mutation-positive subjects, the cancer rates were 18% in screened subjects and 41% in controls (p = 0.02). The decrease resulted from the removal of adenomas in 13 mutation-positive individuals (30%) and in 6 subjects with unknown mutation status (40%). All colorectal cancers in the study group were local, causing no deaths, compared with 9 deaths due to colorectal cancer in the controls. The overall death rates were 10 vs. 26 subjects in the study and control groups (p = 0.003), 4 vs. 12 in mutation-positive subjects (p = 0.05).

B

Mak 2007IV

UK N=244 Patients from HNPCC families and from intermediate risk families were referred for regular colonoscopic screening by

A total of three cancers, 39 adenomas and 41 hyperplastic polyps were found in the HNPCC group compared with one cancer, 22

C

97



Country Sample size


a Regional Genetics Service. Findings from colonoscopies performed between 1992 and 2003 were evaluated.

adenomas and 19 hyperplasic polyps in the intermediate risk group.

Mecklin 2007IV

Finland N=420 Data from the Finnish Hereditary Colorectal Cancer Registry electronic database on Lynch syndrome mutation carriers without previous colorectal tumours were reviewed. Between 1982 and 2005 patients underwent a total of 1,252 colonoscopies. The total follow-up time was 3,150 patient years.

The cumulative risk of adenoma by age 60 was estimated as 68% (95% CI 50%-80%) in men and 48% (95% CI 29%-62%) in women. The estimated cumulative risk up to age 60 years for the development of cancer found as a result of surveillance at an interval of 2 to 3 years was 35% (95% CI 16%-49%) in men and 22% (95% CI 7%-34%) in women. Half of the adenomas were located proximal to the splenic flexure. Extracolonic cancer was diagnosed in 73 patients (18%).

B

Stupart 2009III-2

South Africa

N=178 A prospective cohort study of patients who carry a mutation of the MLH1 gene in exon 13. Patients were offered surveillance colonoscopy between 1988 and 2006.

One hundred and twenty-nine subjects underwent surveillance colonoscopy, and 49 declined. After a median follow up of 5 years, colorectal cancer was diagnosed in 14/129 (11%) subjects in the surveillance group and 13/49 (27%) in the non-surveillance group (p = 0.019). Cancers in the surveillance group were at an earlier stage than in the non-surveillance group (p = 0.032). Death from colorectal cancer occurred in three of 129 (2%) subjects in the surveillance group, and six of 49 (12%) in the non-surveillance group (p = 0.021). The Kaplan-Meyer estimates for median survival from birth were 78 years in the surveillance group, and 55 years in the non-surveillance group (p = 0.024). The Kaplan-Meyer estimates for median colorectal cancer-free survival from birth were 73 years in the surveillance group and 47 years in the non-surveillance group (p = 0.0089).

C

98


Review Question 1c: Appropriate timing of colonoscopy in patients with inflammatory bowel diseaseStudy ID and Level of Evidence

Country Sample size


Collins 2008

III-2

UK N/A A systematic review of studies assessing disease outcomes in patients with inflammatory bowel disease who had received colonoscopic surveillance.

The proportion of patients dying from bowel cancer or other causes in the control and surveillance groups of each study was derived from life tables, survival curves or where possible, by calculating life tables from the data provided.

Data from the original research articles were converted into 2x2 tables (survival versus death x surveillance versus control) for each of the individual studies for comparable follow-up intervals.

The presence of significant heterogeneity among studies was tested by the chi-square test. Because this is a relatively insensitive test, a p value of less than 0.1 was considered statistically significant.

Provided statistical heterogeneity was not present, the fixed effects model was used for the pooling of data.

The 2x2 tables were combined into a summary test statistic using the pooled relative risk (RR) and 95% confidence intervals as described by Cochrane and Mantel and Haenszel.

For the pooled data analysis 8/110 patients in the surveillance group died from colorectal cancer compared to 13/117 patients in the non-surveillance group (RR 0.81; 95% CI 0.17 to 3.83).

Karlen 1998a in a nested case-control study comprising 142 patients from a study population of 4,664 patients with ulcerative colitis, found that 2/40 patients dying of colorectal cancer had undergone surveillance colonoscopy on at least one occasion compared with 18/102 controls (RR 0.28; 95% CI 0.07 to 1.17). One of 40 patients who died from colorectal cancer had undergone surveillance colonoscopies on two or more occasions compared with 12/102 controls (RR 0.22; 95% CI 0.03 to 1.74) in contrast to a more modest effect observed for patients who had only one colonoscopy (RR 0.43; 95% CI 0.05 to 3.76).

Choi 1993 found that carcinoma was detected at a significantly earlier stage in the surveilled patients; 15/19 had Duke’s A or B carcinoma in the surveilled group compared to 9/22 in the non-surveilled group (p = 0.039). The 5-year survival rate was 77.2% for cancers occurring in the surveillance group and 36.3% for the no-surveillance group (p= 0.026). Four of 19 patients in the surveillance group died from colorectal cancer compared to 11 of 22 patients in the non-surveillance group (RR 0.42; 95% CI 0.16 to 1.11).

Lashner (1990) found that four of 91 patients in a surveillance group died from colorectal cancer compared to 2 of 95 patients in a non-surveilled group (RR 2.09; 95% CI 0.39 to 11.12). Colectomy was less common in the surveillance group, 33 compared to 51 (p < 0.05) and was performed four years later (after 10 years of disease) in the surveillance group.

A

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Country Sample size


Eaden 2001

III-2

UK N=54,478 A systematic review and meta-analysis of studies to identify association between colorectal cancer and ulcerative colitis.

Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate.

There were 116 studies which met inclusion criteria and from which data could be extracted.

The overall prevalence of colorectal cancer in any patient with ulcerative colitis was estimated to be 3.7% (95% CI 3.2-4.2%). The overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000).

There were 19 studies that reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000).

These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years.

B

Friedman 2008

III-2

US N=259 A prospective observational study of patients with Crohn’s disease undergoing periodic colonoscopic surveillance.

All patients had at least 7 years of Crohn’s colitis affecting at least one third of the colon.

Patients were recalled every 1 to 2 years or sooner if dysplasia was found.

Pathology was classified as normal, dysplasia (indefinite, low-grade [LGD], or high-grade [HGD]) or carcinoma. Lesions were classified as flat, polyp, or mass.

Ninety percent of patients had extensive colitis. The median age at diagnosis was 22 years and the median disease duration was 18 years (range, 7-49 y).

On screening examination definite dysplasia or cancer was found in 18 patients (7%). Thirteen had LGD, 2 had HGD and 3 had cancer.

On surveillance examinations, a first finding of definite dysplasia or cancer was found in an additional 30 patients (14%). Twenty-two had LGD, 4 had HGD, and 4 had cancer.

The cumulative risk of detecting an initial finding of any definite dysplasia or cancer after a negative screening colonoscopy was 25% by the 10th surveillance examination. The cumulative risk of detecting an initial finding of flat HGD or cancer after a negative screening colonoscopy was 7% by the ninth surveillance examination.

C

100



Country Sample size


Hata 2003

IV

Japan N=217 Surveillance colonoscopies performed in patients with ulcerative colitis between 1979 and 2001 at a single institution were analysed.

Patients with invasive cancer found in the surveillance group were compared to those referred without surveillance colonoscopy.

Surveillance colonoscopy confirmed 15 patients with definite dysplasia. Of these, five were proved to have invasive cancer in the resected specimens.

The cumulative risk for the development of invasive cancer at 10, 20, and 30 years was 0.5, 4.1, and 6.1% respectively, while that for the development of definite dysplasia at 10, 20, and 30 years was 3.1, 10.0, and 15.6% respectively.

All the patients with invasive cancer in the surveillance group remained alive, while three out of four patients in the non-surveillance group died.

C

Kottachchi 2009

IV

Canada N=141 A retrospective chart review of all patients with ulcerative colitis undergoing colonoscopy screening and / or surveillance at a single institution between 1980 and 2005.

Patients were classified according to the extent of colonic disease: limited left-sided colitis (LSC), pancolitis and any disease extent with concurrent primary sclerosing cholangitis.

Colonic dysplasia was detected in 24 of 141 patients (17.0%), with 17 of 24 (70.8%) found at surveillance.

Two patients (8.3%) had colorectal cancer successfully treated.

The average age of patients with dysplasia was 56.1 years, with a mean disease duration of 10.9 years in LSC versus 11.8 years in pancolitis (p > 0.05).

No patients progressed to high-grade dysplasia or colorectal carcinoma.

Patients with pancolitis had a higher incidence of neoplasia (21% [18 of 86]) than patients with LSC (12% [6 of 49]; p=0.24).

Forty-one patients (29.5%) had at least one hyperplastic or inflammatory polyp.

C

Lutgens 2009

IV

The Netherlands

N=149 A nationwide pathology database was analysed to identify patients with inflammatory bowel disease with colorectal cancer who had been treated over the 15-year study period in one of eight study centres.

Patients were assigned to the surveillance group when

Twenty-three participants had had colonoscopic surveillance before their colorectal cancer was diagnosed.

The 5-year colorectal cancer-related survival rate of patients in the surveillance group was 100% compared with 74% in the non-

C

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Country Sample size


they had undergone one or more surveillance colonoscopies before a diagnosis of colorectal cancer.

Patients who had not undergone surveillance served as controls. Tumour stage and survival were compared between the two groups.

surveillance group (p=0.042).

Over the study period, 1 patient in the surveillance group died as a consequence of colorectal cancer compared with 29 patients in the control group (p=0.047).

Tumour stage was earlier overall in patients in the surveillance group (p=0.004).

Manes 2009

IV

Italy N=204 Patient records of consecutive patients with Crohn’s disease undergoing colonoscopy were appraised for appropriateness of colonoscopy indication and relevance of colonoscopy findings to the management of the patient.

There were 116 male and 88 female patients (mean age 41 years) included in the analysis. In 54% of patients, endoscopy revealed a significant lesion.

The endoscopic findings did not align with symptoms in 25% of cases.

C

Moum 1999IV

Norway N=496 All new cases of ulcerative colitis in a defined population were identified during a 4-yr period (496 patients). Of these, 384 patients (78%) were available for follow-up and were subjected to a second colonoscopy with representative biopsies taken from both normal and affected mucosa.

After 1 yr there were macroscopical signs of progression in 14%; 22% showed regression, and 30% had a normal colonoscopy.

The histological changes from diagnosis until follow-up showed progression in 20%, 24% showed regression, and 24% had normal histological findings.

Histological examination showed more extensive disease than did direct visualization in 4% of patients at diagnosis and in 28% at follow-up, whereas direct visualization showed more extensive disease than did histological examination in 18% of patients at diagnosis and 12% at follow-up.

The best correlation at both diagnosis and follow-up was seen in pancolitis (99% and 88%, respectively).

C

Odze 2004

IV

US N=83 Retrospective comparative study between patients with ulcerative colitis and controls without ulcerative colitis.

Patients were identified by a retrospective search of hospital administrative data.

The mean length of follow-up averaged 77 months. Controls underwent fewer colonoscopies (mean 1.6; range 1-4).

Of the 28 patients with ulcerative colitis who were followed-up by endoscopic surveillance (i.e. 6 patients had a colectomy), 39%

C

102



Country Sample size


underwent at least one endoscopic surveillance procedure per year, 43% had one procedure every second year, and 18% had 1 procedure every 3 years during the course of follow-up evaluation (mean number of endoscopies, 4.4; range, 1 -1 3).

Between 11% and 33% were identified with high grade dysplasia over the follow-up period.

There were 18 patients who had an initial polypectomy followed by endoscopic surveillance, with a mean follow-up period of 82.1 months (range 17-156 months). These patients had a mean of 4.4 colonoscopies per patient (range, 1-13 colonoscopies). Of these 18 patients under surveillance, 10 (56%) were followed-up for more than 7 years (84 mo), of which 7 (39%) were followed-up for more than 8 years.

Overall, 89% developed low-grade dysplasia, 11% developed high grade dysplasia and 4% developed cancer over the surveillance period.

Rutter 2004

III-2

UK N=204 A case control study in patients with ulcerative colitis who had neoplasia detected between 1988 and 2002. Cases were matched with two non-dysplastic colitic controls.

Data were collected on post-inflammatory polyps, scarring, strictures, backwash ileitis, a shortened, tubular, or featureless colon, severe inflammation and normal looking surveillance colonoscopies.

There were 68 cases and 136 controls.

On univariate analysis, cases were significantly more likely to have post-inflammatory polyps (OR 2.14; 95% CI 1.24-3.70), strictures (OR 4.22; 1.08-15.54), shortened colons (OR 10.0; 1.17-85.6), tubular colons (OR 2.03; 1.00-4.08) or segments of severe inflammation (OR 3.38; 1.41-10.13) and less likely to have had a macroscopically normal looking colonoscopy (OR 0.40; 0.21-0.74).

After multivariate analysis, a macroscopically normal looking colonoscopy (OR 0.38; 0.19-0.73), post-inflammatory polyps (2.29; 1.28-4.11), and strictures (4.62; 1.03-20.8) remained significant.

The five year risk of colorectal cancer following a normal looking colonoscopy was no different from that of matched general population

B

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Country Sample size


controls.

Rutter 2006

III-2

UK N=600 Data were obtained from a prospective surveillance database, medical records, and colonoscopy and histology reports of patients who were participants of a surveillance program for ulcerative colitis.

The primary end point was defined as death, colectomy, withdrawal from surveillance or census (January 1, 2001).

Follow-up information was obtained for patients who left the program.

Patients underwent 2,627 colonoscopies during 5932 patient-years of follow-up.

Seventy-four patients (12.3%) developed neoplasia, including 30 colorectal cancers. There was no difference in median age at onset of colitis for those with or without colorectal cancer (p = 0.8).

The cumulative incidence of colorectal cancer by colitis duration was 2.5% at 20 years, 7.6% at 30 years, and 10.8% at 40 years.

The 5-year survival rate was 73.3%.

Sixteen of 30 cancers were interval cancers.

B

Shetty 1999

III-2

US N=328 Patients with ulcerative colitis and primary sclerosing cholangitis were compared with a random sample of controls with ulcerative colitis but not primary sclerosing cholangitis.

Patient data were analysed for the period between inception of disease and outcome or censor.

Thirty-three (25%) of 132 patients with primary sclerosing cholangitis developed colorectal cancer or dysplasia compared with 11 (5.6%) of 196 controls (adjusted relative risk 3.15, 95% CI 1.37-7.27).

Six (4.5%) patients with primary sclerosing cholangitis and no controls died from colorectal cancer (p < 0.01).

B

Siegel 2006

III-2

US N=27 An administrative database was searched to identify cases and controls. Cases had a confirmed diagnosis of Crohn's disease involving at least one third of the colon and a confirmed diagnosis of colorectal adenocarcinoma.

Matched controls were randomly chosen from the same source population.

Paired univariate analysis was performed to develop an odds ratio (OR) for each exposure.

Colonoscopy performed for screening or surveillance was associated with an OR of 0.21 (95% CI 0.04-0.77).

C

Velayos 2006 US N=376 An administrative database was searched to identify Surveillance colonoscopy decreased the risk of colorectal cancer; C

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Country Sample size


III-2 cases and controls diagnosed between 1976 and 2002. Cases had chronic ulcerative colitis and colorectal cancer.

Matched controls with chronic ulcerative colitis were randomly chosen from the same source population.

patients who had received 1 to 2 surveillance colonoscopies OR=0.4 (95% CI 0.2 to 0.7); patients who had received > 2 surveillance colonoscopies OR=0.3 (95% CI 0.1 to 0.8).

105


Review Question 1d: Appropriate timing of colonoscopy in older peopleStudy ID and Level of Evidence

Country Sample size


Brian Perry 2000IV

US N=413 Analysis of a prospective database of colonoscopies performed from 1992 to 1996. Examination results were recorded by indication, which were divided into two groups - those with an independent indication such as bleeding or abnormal barium enema and those undergoing surveillance.

Patients were 80 years and older (range 80-96). The procedure was completed in 97%. In symptomatic patients, 33.3% had normal examinations or presence of diverticulosis, 15.3% had cancer, 45.9% had polyps, 4.1% had vascular malformations and 1.4% had other findings. In the surveillance patients, 55.0% had normal examinations or the presence of diverticulum, 0.8% had cancer, 43% had polyps, 0.3% had vascular malformations and 0.7% had other findings. One patient had a colon perforation requiring resection and one patient had a post-polypectomy haemorrhage requiring hospitalization.

C

Fontagnier 2000IV

Germany N=157 Clinical records of colonoscopies performed in patients aged over 80 years (average 83 years, oldest patient 94 years) were retrospectively analysed regarding indications, results and complications, with special reference to cancer of the colon.

The main indication for colonoscopy was occult faecal blood or non-acute rectal bleeding (27%), which together were important indicators of endoscopically significant findings (in 76%).

C

Kahi 2007IV

US N=404 Retrospective cohort study of persons aged ≥ 75 years who underwent colonoscopy between 1999 and 2000. Advanced neoplasms were defined as colorectal cancer, polyp with high-grade dysplasia, villous histologic features, or tubular adenoma (greater-than or equal to)1 cm.

Fifty-nine of 404 (15%) had an advanced neoplasm, including 8 (2%) with colorectal cancer. There were 167 deaths (41%); the mean overall survival was 4.1 ± 0.1 years (median 5.95 years). A symptomatic indication for colonoscopy was not predictive of death. Mortality was predicted by age (HR 1.16 for each year increase beyond age 75 years, 95% CI 1.07-1.3, p < 0.001) and Charlson score (HR 8.3 for each point increase, 95% CI 1.4-48.5, p = .02). The median survival of patients aged 75 to 79 years was >5 years if the Charlson score was ≤4. Among patients aged ≥80 years, the

C

106



Country Sample size


median survival was <5 years regardless of Charlson score. Kirchgatterer 2002IV

Austria N=781 Clinical records of patients aged over 80 years who had received colonoscopy between 1995 and 2000 were analysed. The indication, sedation, colonoscopy completion rate, endoscopic findings, therapeutic consequences and complications were evaluated.

The most frequent indications were: abdominal pain, bleeding, constipation, anaemia and history of polyps. Colonoscopy was completed successfully to the caecum in 71%. Common pathologic findings included diverticular disease, polyps and colorectal carcinoma. Curative surgery was possible in 55% and palliative surgery in 9% of patients with colorectal carcinoma, respectively. A complication was observed in six patients (0.6%), four bleedings following polypectomy, one perforation after dilatation of a stenotic tumour, and one transient neurologic deficit.

C

Largares-Garcia 2001IV

US N=803 A retrospective review of notes of patients who underwent colonoscopy in 1997. The patients were grouped by age: group A (17-49 years) had 166 patients (20%); group B (50-79 years) had 534 patients (67%); and group C (80 years and older) had 103 patients (13%).

Blood in the stool (84%) and history of colonic vascular disease (5.8%) were the most common indication for colonoscopy in older patients (84%). Completion of the colonoscopy to the caecum or anastomotic sites did not differ among the groups (p > 0.05), nor did complication rates among groups (p > 0.05).

C

Lukens 2002IV

US N=250 Prospective cohort study of consecutive outpatients (100 patients aged 80 years or older and 150 patients aged less than 80 years) referred for colonoscopy.

In octogenarians and non-octogenarians preparation tolerance (86% and 90%, respectively) was similar. No adverse outcomes occurred in either study group.

C

Sardinha 1999IV

US N=403 Patients 80 years of age or older who underwent colonoscopy between 1994 and 1996 were reviewed (median 84 years, range 80-95). Relevant parameters evaluated included indications for colonoscopy, significant endoscopic findings (biopsy-confirmed adenocarcinoma and adenomatous polyps (greater-than or equal to) 1 cm), complications and colonoscopy completion rate.

Post-polypectomy bleeding occurred in one patient. Indications for colonoscopy/number of cancers detected include: change in bowel habits, 78/2; blood/haemoccult positive, 69/8; abdominal pain, 12/0; constipation, 9/0; diarrhoea, 8/0; surveillance for history of polyps, 159/3; surveillance for history of cancer, 51/1; cancer or polyp on sigmoidoscopy, 42/4. The cancer detection rate in patients with bleeding was 11.5%, compared with 1.9% for all other symptoms.

C

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Country Sample size


Stevens 2003IV

US N=915 The endoscopic and pathology reports of all asymptomatic subjects undergoing colonoscopy for the purpose of colorectal cancer screening or an evaluation of abdominal pain or change in bowel habits between 1997 and 2000 were reviewed. A multivariate logistic regression analysis was used to assess the effect of age, gender, and indication for examination on the prevalence of neoplasia, as well as on having more than two adenomas, advanced adenomas (tubulovillous, villous, severe dysplasia, or size (greater-than or equal to) 1 cm), and invasive cancers

Mean age was 65 yr (range 50-100 years). Neoplasia peaked in the seventh decade, with a fall thereafter (p = 0.009). Prevalence of adenomas, advanced adenomas and invasive cancers increased with age.

C

108


Review Question 1e: Appropriate timing of colonoscopy in patients with a past history of colorectal cancerStudy ID and Level of Evidence

Country Sample size


Abu Nada 2003

IV

Qatar N=104 Clinical records of patients who had a diagnosis of colorectal cancer were randomly selected and reviewed. All had undergone peri-operative colonoscopy, resection for curative intent and follow-up colonoscopy approximately 1 year post-operatively.

There were 16 (15%) abnormal findings at the time of follow-up colonoscopy.

In 10 patients, the colon had not been "cleared" peri-operatively and the polyps identified were anticipated and removed.

In 6 (6%) there were new findings not previously documented: 3 hyperplastic polyps; 2 small (< 0.75cm) adenomatous polyps and 1 anastomotic recurrence of a rectal cancer.

C

Arditi 2009

I

Switzerland N/A A systematic search of guidelines, systematic reviews, and primary studies regarding colonoscopy for screening for colorectal cancer was performed.

The RAND/UCLA appropriateness method was applied to develop appropriateness criteria for colonoscopy in these circumstances.

Available evidence for colorectal cancer screening comes from small case-controlled studies, with heterogeneous results, and from indirect evidence from randomized controlled trials on faecal occult blood test screening and studies on flexible sigmoidoscopy screening.

Most guidelines recommend screening colonoscopy every 10 years starting at age 50 in average-risk individuals.

In individuals with a higher risk of colorectal cancer due to family history, there is a consensus that it is appropriate to offer screening colonoscopy at < 50 years.

EPAGE II considered screening colonoscopy appropriate above 50 years in average-risk individuals.

Panellists deemed screening colonoscopy appropriate for younger patients, with shorter surveillance intervals, where family or personal risk of colorectal cancer is higher.

A positive FOBT or the discovery of adenomas at sigmoidoscopy were considered appropriate indications.

Overall:

B

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Country Sample size


- In patients who have received a colon cancer resection and colon clearance, colonoscopy was recommended at 1 and 3 years.

- If the colonoscopy performed after colon cancer resection revealed no abnormality, follow-up colonoscopy was recommended at 5 years.

- If the colonoscopy performed after colon cancer resection revealed low risk adenomas, follow-up colonoscopy was recommended at 3 to 5 years.

- If the colonoscopy performed after colon cancer resection revealed high risk adenomas, follow-up colonoscopy was recommended at 1 year.

Balleste 2007

IV

Spain N=353 All patients with colorectal cancer attending one of ten study sites during a one-year period were included. Patients with familial adenomatous polyposis or inflammatory bowel disease were excluded.

All patients were monitored by colonoscopy within two years of their diagnosis.

Demographic, clinical, pathologic, molecular (microsatellite instability status and immunohistochemistry for MSH2 and MLH1), and familial characteristics (fulfilment of Amsterdam I or II criteria, and revised Bethesda guidelines) were analysed.

At two years of follow-up, colonoscopy revealed the presence of adenomas in 89 (25%) of patients and colorectal cancer in 14 (3.9%) of patients, in 7 cases restricted to anastomosis.

Univariate analysis demonstrated that development of metachronous neoplasm (adenoma or colorectal cancer) was associated with personal history of previous colorectal cancer (OR 5.58; 95% CI 1.01-31.01), and presence of previous or synchronous adenomas (OR 1.77; 95%CI 1.21-3.17).

Multivariate analysis identified previous or synchronous adenomas (OR 1.98; 95%CI 1.16-3.38) as independent predictive factor.

B

Berman 2000

I

US N/A A systematic review of studies assessing post-operative surveillance after colorectal cancer resection.

There was insufficient data to support the routine use of annual or more frequent colonoscopy to identify metachronous or recurrent colorectal cancer.

C

Bouvier France N=10,801 A patient database was interrogated to calculate the risk of metachronous colorectal cancers, to specify

Patients who had colorectal cancers totalled 61,879 person-years of follow- C

110



Country Sample size


2008

IV

their characteristics and potential risk factors in a geographically defined population over a 27-year period in patients with colorectal cancer.

The actuarial method was used to obtain crude metachronous colorectal cancer rates. Standardised incidence ratios (SIRs) were calculated.

up.

The cumulative rate of metachronous colorectal cancer was 1.8% at 5 years, 3.4% at 10 years and 7.2% at 20 years.

The SIR for metachronous colorectal cancer following a first colorectal cancer was 1.5; 95% CI 1.3-1.7. It remained greater throughout the study period between the first and the fifth years following diagnosis (SIR = 1.9; 95% CI 1.6-2.3).

Compared with solitary cancers, metachronous cancers were diagnosed at earlier stages (23.5% versus 40.9% were stage I, p < 0.001).

Chan 2006

IV

Australia N=308 Data were drawn from a prospective hospital registry of a single institution. All resections for rectal cancer between 1990 and 1998, with follow-up to 2003 were identified.

The 5-year local recurrence rate was 15.9% (95% CI 11.0 to 22.8) in patients with tumours that had an anterior component compared with 5.8% (95% CI 2.8 to 11.9) in patients with tumours without an anterior component (p=0.009). The association persisted after adjustment for other factors linked to local recurrence (HR 2.4; 95%CI 1.1 to 5.4). Similarly, anterior position had a significant negative independent association with survival (HR 1.4; 95%CI 1.0 to 2.00).

B

Cubiella Fernandez 2003

IV

Spain N=155 A retrospective analysis of follow-up outcomes and colonoscopic findings of patients with colorectal cancer who received curative surgery between 1994 and 1996.

Endoscopic follow-up was performed at six months following surgery in patients that did not have a complete endoscopy prior to surgery and one year after surgery if they did.

Subsequent colonoscopies were performed at two

A total of 74.2% of participants completed the surveillance protocol.

Three synchronous tumours, 4 anastomosis relapses and 2 metachronous tumours were detected.

There were 48.3% and 20.6% subjects who had synchronous and metachronous polyps respectively; 14.7% of the polyps were larger than 1 cm, 21.7% and 4.8% were tubulovillous and villous respectively, and 3.7% had severe dysplasia.

C

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Country Sample size


years and between the third and fifth year after surgery.

Fisher 2003

III-2

US N=3,546 A cohort of patients within a national database with a new diagnosis of colorectal cancer during fiscal year 1995 to 1996 was assessed.

Patients with inflammatory bowel disease, metastatic disease at presentation, or who died within 1 yr of initial diagnosis were excluded.

Demographics, comorbidities, colonoscopies, chemotherapy and radiation therapy data were collected.

The primary outcome was adjusted 5-yr mortality.

In the adjusted analysis, the risk of death was decreased by 43% (HR = 0.57, 95% CI = 0.51-0.64) in the group who had at least one follow-up colonoscopy compared with patients who had no follow-up colonoscopies.

B

Fukutomi 2002

III-2

Japan N=321 Patients were enrolled in a prospective observational study after colonoscopic resection of initial tumour between 1985 and 1999. Histology of initial tumours was adenoma in 214 patients and carcinoma in 107 patients.

Solitary tumour was observed in 196 patients and multiple tumours in 125 at initial endoscopy.

The median surveillance period was 39 (range 12-112) months, and the median frequency of surveillance colonoscopy was three (range 2-10) times.

Metachronous tumours were identified in 114 of 321 surveillance cases (36%). In the 114 cases, the number of patients with metachronous adenoma was 103 (90%) and that of carcinoma was 11 (10%).

Clinical characteristics at entry - including age, gender, multiplicity of polyp, histology of polyp, and site of polyp - were not different between patients with metachronous tumours and those without metachronous tumours.

Kaplan-Meier analysis revealed that patients with a histology of carcinoma and those with multiple polyps at entry developed metachronous tumours significantly earlier than did patients with initial adenomas and initial solitary polyp, respectively (p < 0.001, p < 0.001). However, other characteristics at entry did not produce significant differences in the rate of the development of metachronous tumours using Kaplan-Meier analysis.

Proportional hazards model analysis revealed that histology of the initial

B

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Country Sample size


tumour as carcinoma (relative risk, 1.690, 95% CI 1.118- 2.555) and multiplicity (1.472, 1011-2.143) were significant risk factors for metachronous colon tumours.

The 75%, 50%, and 25% metachronous tumour-free periods after initial polypectomy were 14, 21, and 39 months, respectively.

Gervaz 2005

IV

Switzerland N=5,006 A population-based study. A cancer registry database was used to identify patients diagnosed with colorectal adenocarcinoma between 1970 and 1999.

Patients with familial adenomatous polyposis and those with hereditary non-polyposis colorectal cancer syndrome were excluded from the study, as were patients with non-epithelial tumours.

There were 1,703 first primary tumours (34%) identified proximal to the splenic flexure. One hundred twenty occurrences of second primary colorectal cancer were observed in this population (2.4%).

The risk for developing a second incidence of primary colorectal cancer was higher in patients whose initial tumour was located in the proximal colon (3.4% versus 1.8%; OR 1.9; 95% CI 1.33-2.77).

B

Hassan 2009

Italy N/A Decision analysis model. Comparison of strategies of 1-year endoscopic surveillance versus no early endoscopy following surgical resection for colorectal cancer. A 2-year cancer upstaging was modelled in order to simulate cancer progression in patients with metachronous colorectal cancer who were not referred to early endoscopy.

The number of early 1-year colonoscopies needed to detect one colorectal cancer and to prevent one colorectal cancer-related death was 143 and 926, respectively. The incremental cost-effectiveness ratio of the early 1-year colonoscopy as compared to a policy of not performing it was $40,313 per life-year gained.

N/A

Hyman 2010

IV

US N=432 All patients undergoing surgery for colorectal cancer by two colon and rectal surgeons at a university hospital from 1991 to 2005 were identified from a tumour registry.

Patients with a complete preoperative colonoscopy by any physician and a 1-year follow-up examination by

Overall, 10 patients (2.3%) had a ''new'' cancer diagnosed at 1 year, and 1 patient (0.2%) had a local recurrence.

The index colonoscopy for 9 of the 10 of cancers found at 1 year was not performed by the operating surgeon.

C

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Country Sample size


the operating surgeon were selected for the study population.

Fisher's exact test was used to compare the probability of finding any adenoma, advanced adenoma, or invasive cancer based on the index endoscopist.

Kobayashi 2007

IV

Japan N=5,230 Consecutive patients (stage I, 1,367; stage II, 1,912; stage III, 1,951) who underwent curative resection of colorectal cancer at one of 14 study sites between 1991 and 1996 were included in the study.

Patient outcomes were investigated retrospectively.

There were 906 patients who developed recurrence of their colorectal cancer.

The recurrence rates of stage I, II, and III cancers were 3.7%, 13.3%, and 30.8%, respectively (p < 0.0001). The rate of recurrence in patients with stage II and III disease showed a rapid increase for the first 3 years. Recurrence after 5 years was less than 1% in each stage. The 5-year survival rates after primary colorectal surgery in patients who underwent resection for recurrence were better than in those without resection: 48% versus 22% in patients with local recurrence (p < 0.001).

B

Lan 2005

IV

Taiwan N=3,846 An administrative database of patients with colorectal cancer that occurred between 1981 and 2001 was reviewed. Cases of adenocarcinoma of the colon and rectum, which received curative resection during this period, were found.

The criteria of metachronous cancer were: occurrence more than 12 months after curative surgery; with pre-operative complete colonoscopy or one negative post-operative colonoscopic follow-up to rule out synchronous tumour; tumour arising from mucosa at a site other than anastomosis.

The age, gender of the patients, the location, pathological characteristics of the metachronous

In total, 43 cases of metachronous cancer were identified, giving an annual incidence of 0.18%.

The distribution of the location of the index tumour of metachronous cases was predominantly left-sided, which was not different from that of the control group.

The mean duration of occurrence of metachronous cancer after the primary operation was 71+/-46.6 months.

The association of adenomas had no relationship with the occurrence of the metachronous cancer.

No significant predicting factors for the development of metachronous tumours were found.

C

114



Country Sample size


tumours, occurrence of associated adenomas, the number of lesions, and the tumour stage were analysed and compared with the control group.

Lee 2005

III-3

Korea N=248 One hundred and twenty-four patients with colorectal cancer and synchronous adenoma and 124 patients with colorectal cancer without synchronous adenoma were selected from an administrative database.

Patients in the two groups were matched by the stage of colorectal cancer.

Median colonoscopic surveillance period was 55 months (range = 12-99 months).

The colonoscopic surveillance frequency and interval were similar between the two groups.

The incidence of missed adenoma, advanced missed adenoma and metachronous adenoma were higher in the synchronous adenoma group (30.8% versus 5.8%; 4.4% versus 0%; 31.1% versus 9.1% respectively) during the first consecutive two years of surveillance.

C

Lieberman 2007

III-3

US N=1,193 Subjects with neoplasia were matched with neoplasia-free controls and assigned to colonoscopic surveillance over 5 years.

Subjects were aged between 50 and 75 years and had screening colonoscopy between 1994 and 1997.

Relative risks for advanced neoplasia within 5.5 years were calculated.

Advanced neoplasia was defined as tubular adenoma ≥10 mm, adenoma with villous histology, adenoma with high-grade dysplasia or invasive cancer.

Eight hundred ninety-five (76.4%) patients with neoplasia and 298 subjects (59.5%) without neoplasia at baseline had colonoscopy within 5.5 years; 2.4% of patients with no neoplasia had interval advanced neoplasia.

The relative risk in patients with baseline neoplasia was 1.92 (95% CI: 0.83-4.42) with 1 or 2 tubular adenomas <10 mm, 5.01 (95% CI: 2.10-11.96) with 3 or more tubular adenomas <10 mm, 6.40 (95% CI: 2.74-14.94) with tubular adenoma ≥10 mm, 6.05 (95% CI: 2.48-14.71) for villous adenoma, and 6.87 (95% CI: 2.61-18.07) for adenoma with high-grade dysplasia.

C

Mathew 2006

IV

UK N=105 Colonoscopic records of patients who had surveillance colonoscopy following curative resection between 1998 and 2003 for cancer were available from an endoscopy department computer database.

The variables studied included the tumour site, Duke’s

Two patients were diagnosed with metachronous tumours and three with recurrence.

Adenomatous polyps were identified in 24 patients of which nine had multiple / advanced adenomas (≥ 1cm adenomatous polyps or adenomas with severe dysplasia).

C

115



Country Sample size


stage, number of recurrences, number of metachronous tumours, size and number of polyps and their biopsy results.

McFall 2003

IV

UK N=226 The colonoscopic records, biopsy results and follow-up details of patients diagnosed with colorectal cancer between 1990 and 1996 were reviewed.

The number and type of metachronous neoplastic lesions diagnosed was recorded. Rates of development of new neoplasms were estimated by calculating the time from operation to their first discovery.

Factors predictive of further development of polyps or cancer were sought.

Patients had one or more follow-up colonoscopies (mean time post resection 48.8 months).

In total 352 colonoscopies, encompassing 1437 patient years of surveillance, were performed.

Nine metachronous cancers in eight patients, five of which were asymptomatic, were diagnosed by colonoscopy at a mean of 63 months.

Three asymptomatic recurrences were diagnosed but all were inoperable.

70 (31%) patients had adenomatous polyps diagnosed after a mean time from operation of 34 months for simple adenomatous polyps and 21 months for those with advanced features.

Patients with multiple polyps or advanced polyps at the initial colonoscopy were more likely to form subsequent polyps; 5.8% of patients with a single adenoma or a normal colon formed an advanced adenoma over the next 36 months of surveillance.

C

Platell 2005

III-3

Australia N=253 Data linkage study of prospectively collected colonoscopy procedural data.

Patients were selected from a prospective colorectal database if they had undergone a curative resection for colorectal neoplasia and if they had had a completed colonoscopy prior to surgery. The selection criteria included patients who had: (i) presented with primary tumours of the colon or rectum; (ii) undergone elective resectional surgery for either stage I, II or III

The study group included patients of mean age 69.7 years (SD 11.6) and a male:female ratio of 1.4:1.0.

Colonoscopies were completed on 90% of patients at a mean of 1.1 years following surgery.

A total of 149 polyps were identified in 30% of patients. On histology, 42% were tubular adenomas, 6% tubulo-villous adenomas, 7% were villous adenomas, and 37% were hyperplastic.

Advanced adenomas were identified in 7.9% of patients (95% CI 4.8-

B

116



Country Sample size


colorectal cancer (Tumour Nodes Metastasis (TNM) classification) or for carcinoma in situ or severely dysplastic polyps; (iii) undergone a completed colonoscopy prior to surgery; (iv) undergone treatment before December 2002; and (v) free of metastatic disease at 12 months following surgery.

Patients were excluded if they (i) had stage IV disease; or (ii) presented to the colorectal unit with a recurrent tumour.

Study endpoints included: (i) compliance with follow up; (ii) the prevalence, total number, size, and histology of polyps; and (iii) identification of recurrent or metachronous cancer.

12.1%).

No recurrent or metachronous cancers were identified.

Postic 2002

IV

US N=156 A retrospective analysis was conducted of patients who had a portion of colon surgically removed and had lower endoscopy within 5 months. The focus of the review was to identify synchronous lesions in the portions of bowel that were removed.

Sensitivity was determined by counting the number of lesions detected at colonoscopy compared with those found in the surgically resected segment.

A total of 73 synchronous lesions were present in the resected segments of patients. Colonoscopy detected 56 of 73 lesions (sensitivity 76.7%: 95% CI = 67-86).

Of the 17 missed lesions, 14 of 17 (82%, 95% CI = 64-100) were <1-cm polyps. Endoscopy overlooked one 1-cm adenoma in the ascending colon. Two cancers were missed, both in the same patient in whom endoscopy detected a sigmoid cancer but missed synchronous lesions in the caecal and ascending colon.

C

Renehan 2002

I

UK N=1,342 Systematic review and meta-analysis of randomised controlled trials of intensive compared with control follow-up.

The main outcome measure was all cause mortality at five years (primary outcome).

Five trials, which included 1,342 patients, met the inclusion criteria.

Intensive follow up was associated with a reduction in all cause mortality (combined risk ratio 0.81, 95% CI 0.70 to 0.94, p=0.007). The effect was most pronounced in the four extramural detection trials that used computed tomography and frequent measurements of serum carcinoembryonic

A

117



Country Sample size


Rates of recurrence of intraluminal, local and metastatic disease and metachronous (second colorectal primary) cancers (secondary outcomes) were calculated.

antigen (risk ratio 0.73, 0.60 to 0.89, p=0.002).

Intensive follow up was associated with significantly earlier detection of all recurrences (difference in means 8.5 months, 7.6 to 9.4 months, p<0.001) and an increased detection rate for isolated local recurrences (risk ratio 1.61, 1.12 to 2.32, p=0.011).

Intraluminal recurrences and metachronous cancers were uncommon, irrespective of the intensity of follow up.

Intensive efforts directed at the detection of intraluminal disease (colonoscopy) were estimated to be of low benefit.

Rex 2006

IV

US N/A Joint update of guidelines by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer; addresses the use of endoscopy in the surveillance of patients with resected colorectal cancer.

Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stages II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance.

The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period.

In non-obstructed colons, colonoscopy should be performed preoperatively.

In obstructed colons, double-contrast barium enema or computed tomography colonography should be performed preoperatively, and colonoscopy should be performed 3 to 6 months after surgery.

These steps complete the process of clearing synchronous disease.

After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection.

If the examination at 1 year is normal, then the interval before the next

C

118



Country Sample size


subsequent examination should be 3 years. If that examination is normal, then the interval before the next subsequent examination should be 5 years.

Shorter intervals may be indicated by associated adenoma findings (see “Guidelines for Colonoscopy Surveillance After Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society”). Shorter intervals also are indicated if the patient’s age, family history, or tumour testing indicate definite or probable hereditary non-polyposis colorectal cancer.

Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence compared with those with colon cancer.

Although effectiveness is not proven, performance of endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6-month intervals for the first 2 years after resection can be considered for the purpose of detecting a surgically curable recurrence of the original rectal cancer.

Rodriguez-Moranta 2006

II

US N=259 Patients with stage II or III colorectal cancer were allocated randomly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring, or an intensive strategy in which abdominal computed tomography or ultrasonography, chest radiograph, and colonoscopy were added.

A total of 132 patients were included in the simple strategy arm and 127 were included in the intensive strategy arm. Both groups were similar with respect to baseline characteristics and rate and type of tumour recurrence.

After a median follow-up of 48 months, there was no difference in the probability of overall survival in the whole series (HR 0.87; 95% CI 0.49 to 1.54). However, the intensive strategy was associated with higher overall survival in patients with stage II tumours (HR 0.34; 95% CI 0.12 to 0.98) and in those with rectal lesions (HR 0.09; 95% CI 0.01 to 0.81), mainly due to higher rate of resectability for recurrent tumours.

Colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumour recurrence in the intensive arm.

B

119



Country Sample size


Rulyak 2007

IV

US N=1,002 An organisational administrative database of patients with colorectal cancer who underwent surgical resection was analysed.

Mortality was estimated by using survival analysis, and findings of colon examinations were determined by review of pathology reports.

The 5-year survival was higher (76.8%) for patients who had at least one follow-up examination than for patients who did not undergo follow-up (52.2%, p < 0.001).

In multivariate analysis, colon examination remained independently associated with improved survival (HR 0.58; 95% CI 0.44-0.75).

Twenty patients (3.1%) were diagnosed with a second colorectal cancer, including 9 cancers detected within 18 months of initial cancer diagnosis. Advanced neoplasia was more common (15.5%) among patients followed up between 36-60 months after diagnosis compared with patients followed up within 18 months (6.9%, p = 0.02).

History of adenomas was associated with advanced neoplasia on follow-up (p = 0.002). Patients with advanced neoplasia on initial follow-up were at high risk for advanced neoplasia on subsequent examinations (13/16, 81%).

C

Stigliano 2000

IV

Italy N=253 A retrospective study to identify the incidence of neoplasms of the colon, both metachronous or recurrent in patients who have received a resection for colorectal cancer between 1970 and 1988.

All the patients were submitted to colonoscopy once yearly for the first 5 years and then every 2 years.

Median follow-up was 105 months.

Anastomotic recurrence was observed in 22 of the 253 patients who underwent resection for rectal or sigmoid adenocarcinoma (8.7%).

Metachronous adenomas of the residual colon were found in 24 patients and metachronous cancers in 5 at Stage A, according to Dukes’ classification.

C

Tjandra 2007

I

Australia N=2,923 All randomized trials up to January 2007, comparing different follow-up intensities and strategies, were retrieved.

Meta-analysis of study results was performed.

Eight trials in patients with colorectal cancer undergoing curative resection were analysed.

There was a significant reduction in overall mortality in patients having intensive follow-up (intensive vs. less intensive follow-up: 21.8 versus 25.7%; p = 0.01).

Regular surveillance with colonoscopy (p = 0.04) was associated with a

A

120



Country Sample size


significant reduction in overall mortality but not cancer-specific mortality.

There was no significant difference in all-site recurrence and in local or distant metastasis. Detection of isolated local and hepatic recurrences was similar.

Intensive follow-up detected asymptomatic recurrence more frequently (18.9 versus 6.3%; p < 0.01) and 5.9 months earlier than less intensive follow-up protocol; these were demonstrated with all investigation strategies used. Intensive surveillance program detected recurrences that were significantly more amenable to surgical re-resection (10.7 versus 5.7%;p = 0.0002).

The chance of curative re-resection were significantly better with more intensive follow-up (24.3 versus 9.9 %; p = 0.0001), independent of the investigation strategies used.

Togashi 2000

IV

Japan N=341 A retrospective analysis of the clinical records of patients who had received colorectal cancer resection and who had undergone surveillance colonoscopy at least twice over a period of more than three years.

Metachronous colorectal carcinomas, defined as a new colorectal carcinoma detected by surveillance colonoscopy after surgery, were identified and analysed.

Surveillance colonoscopy was performed 4.6 times per patient during an average of 6.2 years.

Twenty-two metachronous colorectal carcinomas in 19 patients were detected, and 14 (64%) of 22 were detected within five years of surgery.

The cumulative incidence of developing colorectal carcinomas during a five-year period was 5.3%. Seventeen (77%) of 22 carcinomas were 10 mm or less in size. Ten (71%) of the 14 carcinomas in early stages showed a flat appearance.

Univariate analysis showed that extracolonic malignancy, coexistence of adenoma, and synchronous multiple colorectal carcinoma were significant predictive factors for detecting colorectal carcinomas in surveillance colonoscopy and that family history of colorectal carcinoma was a possible predictive factor.

C

121



Country Sample size


Multivariate analysis performed with Cox proportional hazards regression model showed that extracolonic malignancy and the coexistence of adenoma were significant predictive factors.

Wang 2009

II

China N=326 A prospective, randomised, controlled trial in a single health facility. Consecutive patients undergoing surgery for colorectal cancer were randomised to either an intensive colonoscopic surveillance group where colonoscopy was performed at 3-month intervals for 1 year, at 6-month intervals for the next 2 years and once a year thereafter or a routine colonoscopic surveillance group where colonoscopy was performed at 6 months, 30 months and 60 months postoperatively.

There were 165 subjects in the intensive surveillance group and 161 subjects in the routine surveillance group.

The 5-year survival rate was 77% in the intensive surveillance group and 73% in the routine surveillance group (p>0.05).

Postoperative colorectal cancer was detected in 13 patients (8.1%) in the intensive group and in 18 patients (11.4%) in the routine group.

In the intensive group there were more asymptomatic postoperative colorectal cancers (p=0.04) detected, more patients had re-operation with curative intent (p=0.048) and the probability of survival after postoperative colorectal cancer was higher (p=0.03).

B

Yusoff 2003

III-2

Australia N=606 An audit was performed of all patients who underwent colonoscopy following surgical resection of colorectal cancer between 1989 and 2001.

Two groups were assessed: (i) all patients undergoing surveillance colonoscopies; and (ii) all patients diagnosed with colorectal cancer at a single study centre who subsequently had postoperative colonoscopies.

Patients who had their index colonoscopy at the study centre and who subsequently underwent surveillance colonoscopies were studied in detail.

Yield for neoplasia, patterns of surveillance and concordance with clinical guidelines were determined.

There were 304 female and 302 male patients with a mean age of 67 years who underwent 990 colonoscopies for postoperative surveillance of colorectal cancer. Adenomatous polyps were detected in 184 examinations; intraluminal recurrence in 1 case; no metachronous cancers.

In a subgroup of 161 patients who had index and postoperative surveillance at the study centre, synchronous neoplasms were found in 32 patients (including four advanced adenomas and one colorectal cancer).

Of 89 patients who underwent a surveillance examination at 1 year postoperatively, the findings were: normal (80 cases; 90%); adenoma (eight cases; 9%); advanced adenoma (one case; 1%); and recurrent cancer (one case; 1%). No metachronous cancer was found.

C

122


Review Question 1f: Appropriate timing of colonoscopy in patients with a past history of adenomaStudy ID and Level of Evidence

Country Sample size


Avidan 2002

III-2

US N=484 A prospective observational study conducted in subjects who underwent a baseline screening colonoscopy and were re-assessed by a second colonoscopy performed 1 to 5 years later.

Multiple logistic regression was used to assess the influence of potential risk factors on the recurrence of colorectal adenomas, the strength of the influence being expressed as an OR with a 95% CI.

Within a 1- to 5-yr time interval, 37% of patients with adenomas at baseline had recurrent adenomas versus 19% recurrence in those with no adenoma at baseline.

Recurrence was associated with multiple baseline adenomas (OR=4.5; 95% CI 3.0-6.6) and baseline adenomas larger than 1 cm (OR=2.6; 95% CI 2.0-3.1).

There was a significant trend for adenomas to recur in the same proximal or distal segment as the baseline adenomas (p = 0.02).

15 colorectal cancers occurred in 484 patients with adenoma at baseline versus 2 colorectal cancers in 391 patients with no adenoma at baseline

B

Becker 2007

IV

Germany N=N/A A Markov model based on time-dependent transition possibilities was developed to perform a benefit-risk analysis of the risk-related surveillance recommendations based on the Erlangen Registry of Colorectal Polyps (ERCRP) in comparison with the recommendation of the German Society of Gastrointestinal Diseases and Nutrition (DGVS).

The outcome was calculated for a 50-year-old patient with 30 years of follow-up after initial polypectomy.

The data used in this model were taken from different sources, namely the ERCRP, the German Study Group of Colorectal Cancer, the German Statistical Yearbook, and from meta-analyses of studies reporting data on complications and sensitivity of

Patients under surveillance have a mean lifetime gain of 98 (ERCRP) and 110 (DGVS) days compared with those who do not come for surveillance.

84% and 94% of deaths from colorectal carcinoma could be prevented if patients were followed up according to the recommendations of the ERCRP and the DGVS, respectively.

Less colonoscopies are needed to prevent one death from colorectal cancer following the recommendations of the ERCRP (221) than those of the DGVS (283).

The risk of death due to colonoscopy for patients during follow-up is about 0.05% lifetime risk.

Sensitivity analysis showed the stability of the results under a wide range of reasonable variations of relevant parameters. In a pessimistic one-way sensitivity analysis regarding compliance, effectiveness was reduced to one

N/A

123



Country Sample size


colonoscopy. third.

Blumberg 2000

IV

US N=204 A retrospective review of a database of colonoscopies performed between 1990 and 1996. In patients under colonoscopic surveillance, cases of patients who had received three colonoscopies (an index (initial) colonoscopy positive for adenomas and 2 follow-up colonoscopies (interim and final)) were reviewed.

The risk of adenomas and cancers at final follow-up colonoscopy was compared between patients having a normal interim colonoscopy and those with a positive interim colonoscopy.

The risk at final colonoscopy was also stratified by time interval and the size and number of adenomas at the initial index colonoscopy

At index colonoscopy the median polyp size was 1 cm and median frequency was three polyps.

At all follow-up colonoscopies, 493 adenomas and one cancer (median follow-up, 55 months) were detected.

At 36 months patients with a normal interim colonoscopy (n = 91) had significantly fewer polyps than patients with a positive interim colonoscopy (n = 113; 15 vs. 40 percent; p = 0.0001).

By 40 months, adenomas were detected in more than 40 percent of patients in both groups.

The risk after a normal interim colonoscopy was not affected by time interval or number or size of polyps.

Adenomas found subsequent to a normal interim colonoscopy were dispersed throughout the colon in 28 patients and isolated to the rectosigmoid in 6 patients.

C

Bonithon-Kopp 2004

II

France, Denmark, Spain, Ireland

N=552 A secondary analysis of data from the European Fibre-Calcium Intervention trial – a randomised controlled trial of calcium and fibre supplementation in the prevention of adenoma recurrence.

The study population was comprised of patients with resected colorectal adenomas who had completed the trial.

At both baseline and three-year examinations, the

A three-year recurrence was observed in 122 patients (22.1%), and more than one-half of them had recurrent adenomas on the proximal colon.

After adjustment for patient characteristics and treatment allocation, the number of adenomas and their proximal location at baseline were the main predictors of recurrence.

In comparison with patients who had one or two adenomas on the distal colon, patients with three or more adenomas with at least one of them located on the proximal colon had a much higher risk of overall recurrence

B

124



Country Sample size


characteristics of adenomas detected at colonoscopy were recorded according to a standardised protocol.

The main outcomes measured were the three-year overall recurrence, recurrence of multiple adenomas, recurrence of advanced adenomas (size ≥ 1 cm or tubulovillous/villous architecture or moderate/severe dysplasia) and proximal and distal recurrence

(OR 5.3; 95 percent CI 2.7-10.3), proximal recurrence (8.5; 95 percent CI 4.1-18), and advanced adenoma recurrence (5.5; 95 percent CI 2.4-12.6).

Chen 2003

III-3

Taiwan N=2,652 A case-cohort design investigating time to carcinoma development in subjects with polyps who underwent their first colonoscopy between 1979 and 1998.

All subjects with polyps were linked to national cancer registry to ascertain 25 invasive carcinomas after polypectomy.

Compared to size less than 5 mm, patients with adenoma size between 6 and 10 mm and patients with adenoma size larger than 1 cm have 2.17-fold (0.67-10.74) and 4.25-fold (1.23-14.70), respectively, for the risk of malignant transformation.

C

Cordero 2001

III-2

Spain N=133 A prospective cohort study of patients with diagnosis of colonic adenomas who had undergone complete colonoscopy and endoscopic polypectomy.

All patients underwent colonoscopic follow-up at 3 years. Seventy-nine patients underwent colonoscopic follow-up both at 6 months and at 3 years, while 54 patients underwent just colonoscopic follow-up at 3 years and 47 just at 6 months.

Fifteen per cent of the patients analysed developed polyps with pathological features after 6 months.

The size and histological analysis of the polyps detected in the initial colonoscopic examination were independent of polyp development at 6 months (p < 0.05).

Patients with 3 or more polyps in the initial colonoscopic examination presented more polyps with pathological features after six months (25.8 versus 5.8%, p < 0.01).

Follow-up examination at 3 years did not reveal a higher occurrence of polyps with pathological features in either group of patients.

C

Feingold US N=56 A retrospective observational study. Data were obtained on asymptomatic patients 60 to 65 years of

56 out of 699 patients underwent a total of 123 colonoscopies after a C

125



Country Sample size


2003

IV

age with normal colonoscopies from retrospective review of an administrative database. Additional data were obtained from patients' medical records, office charts, and pathology reports.

normal colonoscopy performed between age 60 and 65 years.

Thirty-seven patients (66%) had surveillance colonoscopies that continued to be normal while 13 patients (23%) were diagnosed with colorectal adenomas and 6 patients (11%) were found to have hyperplastic polyps.

No cancers were identified.

Fukutomi 2002

III-2

Japan N=321 Patients were enrolled in a prospective observational study after colonoscopic resection of initial tumour between 1985 and 1999. Histology of initial tumours was adenoma in 214 patients and carcinoma in 107 patients. Solitary tumour was observed in 196 patients and multiple tumours in 125 at initial endoscopy.

The median surveillance period was 39 (range, 12-112) months, and the median frequency of surveillance colonoscopy was three (range, 2-10) times.

Metachronous tumours were identified in 114 of 321 surveillance cases (36%).

In the 114 cases, the number of patients with metachronous adenoma was 103 (90%) and that of carcinoma was 11 (10%).

Clinical characteristics at entry - including age, gender, multiplicity of polyp, histology of polyp, and site of polyp - were not different between patients with metachronous tumours and those without metachronous tumours.

Kaplan-Meier analysis revealed that patients with a histology of carcinoma and those with multiple polyps at entry developed metachronous tumours significantly earlier than did patients with initial adenomas and initial solitary polyp, respectively (p < 0.001, p < 0.001). However, other characteristics at entry did not produce significant differences in the rate of the development of metachronous tumours using Kaplan-Meier analysis.

Proportional hazards model analysis revealed that histology of the initial tumour as carcinoma (relative risk, 1.690, 95% CI 1.118- 2.555) and multiplicity (1.472, 1011-2.143) were significant risk factors for metachronous colon tumours.

The 75%, 50%, and 25% metachronous tumour-free periods after initial polypectomy were 14, 21, and 39 months, respectively.

B

126



Country Sample size


Glazer 2008

III-2

US N=34 Case control study.

Colonoscopic biopsies that contained a pathologic diagnosis of serrated adenoma performed between 1997 and 2005 were identified from a pathology database of a major urban academic medical centre. Those patients with absence of concomitant malignancy, complete colonoscopy, good or adequate bowel preparation and presence of at least one follow-up procedure were identified. These were matched to controls by age, sex, indication for colonoscopy, polyp type and number and duration of follow-up.

Outcomes of the follow-up procedures were compared.

The mean follow-up interval in the patient group was 29 months vs. 31 months in the control group (p = 0.82).

On follow-up examination four patients (24%) and no controls had adenomatous polyps (p = 0.01).

C

Jorgensen 2007

II

Denmark N=2,041 Evaluation of long-term surveillance of a patient population with all types of adenomas.

Patients had initial colonoscopy then were randomised to surveillance at intervals that varied between 6 and 48 months.

Prospective surveillance was performed between year 1978 and 2002.

Incidence of colorectal cancer and mortality from colorectal cancer was calculated, using age, sex, and calendar specific number of person years of follow-up for comparison with the standard Danish population.

New adenomas were removed in 736 patients; 144 had advanced adenomas at least once over the study period (28 with severe dysplasia, 9 with villous adenomas and 131 with adenomas > 10 mm).

Colorectal cancer was identified in 27 patients.

B

Khashab US N=136 Retrospective study of patients with large sessile Of 136 polyps with complete follow-up, 24 (17.6%) had macroscopically C

127



Country Sample size


2009

IV

colorectal adenomas identified through an endoscopic database who had polyps resected by piecemeal technique.

Follow-up was performed at 3 to 6 months and then 1 year after initial resection.

evident residual adenoma at follow-up, including 18 at the first follow-up and 6 (4.4%) with a "late" recurrence.

Among 94 polyps with no visible adenoma and with negative biopsy specimens of the scar at the first follow-up, 92 polyps (97.9%) were eradicated at late follow-up, compared with 36 of 42 (85.7%) of the remaining polyps (p = 0.005).

Laiyemo 2008

III-2

US N=1,905 Analysis of prospective data from the Polyp Prevention Trial in patients who had colorectal adenomas removed at baseline screening or diagnostic colonoscopy and completed the 4-year dietary intervention trial.

Baseline adenoma characteristics, risk-stratified according to definitions used in the guidelines, were examined as predictors for advanced adenoma recurrence

125 patients (6.6%) had advanced and 629 (33.0%) had non-advanced adenoma recurrence; 1151 (60.4%) had no recurrence within 4 years of follow-up.

The probability of advanced adenoma recurrence was 0.09 (95% CI 0.07 to 0.11) among patients with high-risk adenomas at baseline and 0.05 (CI 0.04 to 0.06) among those with low-risk adenomas at baseline.

B

Laiyemo 2009

III-2

US N=774 Analysis of prospective data from the Polyp Prevention Trial in patients who had colorectal adenomas removed at baseline screening or diagnostic colonoscopy and completed the 4-year dietary intervention trial.

A cohort of 1,297 participants were followed for a mean time of 5.9 years to examine the diagnostic yield of colonoscopy and predictive factors for adenoma and advanced adenoma recurrence.

Among 431 subjects with low-risk adenomas (1-2 non-advanced adenomas) at baseline colonoscopy and no adenoma recurrence at the end of the trial (lowest-risk category), 30.3% underwent a repeat colonoscopy within 4 years.

Among 55 subjects who had high-risk adenomas (advanced adenoma and/or ≥3 non-advanced adenomas) at baseline and again at the final trial colonoscopy (highest-risk category), 41.3% had a colonoscopy within 3 years and 63.5% had an examination within 5 years.

The cumulative yield of advanced adenoma through 6 years was 3.6% for the lowest-risk category, 38.9% for the highest-risk category, and ranged

B

128



Country Sample size


from 6.6% to 13.8% for intermediate-risk categories.

An advanced adenoma at the final trial colonoscopy was associated significantly with an advanced adenoma recurrence during surveillance (HR 6.2; 95% CI 2.5-15.4)

Lieberman 2008

IV

US N = 6,360 Retrospective analysis of health services colonoscopy data. Subjects included all asymptomatic adults receiving colonoscopy for screening during 2005 from 17 practice sites, which provide both colonoscopy and pathology reports to the Clinical Outcomes Research Initiative repository. Patients were classified by size of largest polyp.

Advanced histology was defined as an adenoma with villous or serrated histology, high-grade dysplasia, or an invasive cancer.

Risk factors for advanced histology were determined using Pearson chi(2) and Fisher exact tests.

The proportion with advanced histology was 1.7% in the 1- to 5-mm group, 6.6% in the 6- to 9-mm group, 30.6% in the greater than 10-mm group, and 72.1% in the tumour group.

Distal location was associated with advanced histology in the 6- to 9-mm group (p = .04) and in the greater than 10-mm group (p = .002).

C

Martinez 2009

III-2

US N=9,167 Individual data were pooled from 8 prospective studies, including randomised controlled trials, comprising patients with previously resected colorectal adenomas. Risk of developing subsequent advanced adenoma or cancer was quantified.

Median follow-up period was 47.2 months.

Advanced colorectal neoplasia was diagnosed in 1,082 (11.8%) of the patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%; standard error, 2.2) and those with an adenoma 20 mm in size or greater (19.3%; standard error, 1.5).

The number and size of prior adenomas (p < .0001 for trend) and the presence of villous features (OR, 1.28; 95% CI 1.07-1.52) was associated with increased risk for metachronous advanced neoplasia.

B

129



Country Sample size


Matsuda 2009

III-2

Japan N=5,309 Patients aged over 40 years who were referred for initial colonoscopy at six institutes were selected to participate in a prospective study of the relationship between colonoscopic surveillance and adenoma. They were classified into four groups based on the initial colonoscopy: A, patients without any adenoma; B, with adenomas of <6 mm only; C, with adenomas of ≥6 mm; D, with any intramucosal cancer and followed over time. The index lesion (IL) at follow-up colonoscopy was defined as large adenoma ≥10 mm, intramucosal/invasive cancer.

Overall, median follow-up period was 5.1 years.

A total of 379 ILs were newly diagnosed during follow-up colonoscopy.

The cumulative incidence of ILs in each group was A, 2.6%; B, 6.7%; C, 13.4%; and D, 12.6%

C

McFall 2003

III-3

UK N=226 A retrospective analysis of health services colonoscopy data. The colonoscopic records, biopsy results and follow-up details of patients diagnosed with colorectal cancer between 1990 and 1996 were reviewed. The number and type of metachronous neoplastic lesions diagnosed was recorded.

Rates of development of new neoplasms were estimated by calculating the time from operation to their first discovery.

Factors predictive of further development of polyps or cancer were sought.

Results were compared to published reports of intensive follow-up programmes.

Mean time of follow-up colonoscopy post resection was 48.8 months.

Nine metachronous cancers in eight patients, five of which were asymptomatic were diagnosed by colonoscopy at a mean of 63 months.

Three asymptomatic recurrences were diagnosed but all were inoperable.

70 (31%) patients had adenomatous polyps diagnosed after a mean time from operation of 34 months for simple adenomatous polyps and 21 months for those with advanced features.

Patients with multiple polyps or advanced polyps at the initial colonoscopy were more likely to form subsequent polyps.

5.8% of patients with a single adenoma or a normal colon formed an advanced adenoma over the next 36 months of surveillance.

C

Miller US N=399 A retrospective cohort study of patients with and Adenoma was identified at follow-up colonoscopy in 116 patients (29.1%) C

130



Country Sample size


2010

III-2

without adenomas on an index colonoscopy who returned at 5 to 10 years for a follow-up colonoscopy.

Multivariate logistic regression was used to identify variables that predict finding an adenoma on follow-up colonoscopy.

with 25 (6%) having advanced adenomas.

Patients with non-advanced adenomas on index colonoscopy had a risk of advanced adenoma on follow-up colonoscopy at 5 years of 5%.

The risk of advanced adenoma at 5 and 6 to 10 years in patients with a negative index colonoscopy was 7% and 3.6% respectively (p=0.15).

Patients with an advanced adenoma at index colonoscopy had the highest rate of advanced adenoma detection at 5 years at 26%.

Proximal polyp location (odds ratio 12.4, CI 2.7-56.7) predicted advanced adenoma occurrence at 5 years.

Miller 2010

III-2

US N=88 A retrospective cohort study of patients with 1 to 2 small tubular adenomas on an initial colonoscopy who underwent at least 2 additional surveillance examinations.

The primary outcome was any or advanced adenomas on the third colonoscopy.

At the second colonoscopy, 31 of 88 (35.2%) patients had at least one adenoma and at the third colonoscopy 26 of 88 (29.6%) patients had at least 1 adenoma.

Among patients with 1 to 2 small tubular adenomas on the second colonoscopy, the prevalence of any adenomas on the third colonoscopy was 39.3% [95% CI (CI): 21.5%-59.4%].

Among patients without adenomas at the second colonoscopy, the prevalence of any and advanced adenomas on the third colonoscopy was 25% (95% CI: 14.4%-38.4%), and 3.6% (95% CI: 0.4%-12.3%), respectively.

C

Noshirwani 2000

III-2

US N=697 A retrospective cohort study. From an Adenoma Registry the authors evaluated patient and adenoma characteristics in patients with an adenoma recurrence within 3 years of a positive baseline colonoscopy.

A significant outcome was defined as an adenoma

Having 3 or more adenomas on initial colonoscopy with at least 1 measuring 1 cm or larger greatly increased the chance of a significant finding on the first surveillance colonoscopy. Conversely, patients with 1 or 2 adenomas all measuring less than 1 cm were at low risk of an important outcome within 3 years.

C

131



Country Sample size


with a size of 1 cm or greater, tubulovillous or villous histology, high- grade dysplasia, carcinoma in situ, invasive cancer, or 4 or more adenomas.

Pinsky 2009

IV

US N=2,607 A retrospective observational study. A sample of subjects in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial with abnormal flexible sigmoidoscopy and follow-up colonoscopy were questioned about subsequent surveillance colonoscopy over a 10-year period.

Medical records were obtained to verify procedure dates and histologic findings.

Subjects with advanced adenomas, non-advanced adenoma, non-adenomatous polyps and no polyps at baseline were included.

At the first surveillance, 10.5% of participants had advanced adenoma and 37% had any adenoma in the advanced adenoma group (n = 1,057), compared with rates of 6.8% and 32% (non-advanced adenoma: n = 765), 4.9% and 22% (non-adenomatous polyps: n = 658), and 3.1% and 16% (no polyps: n = 127) in the other groups respectively (p < .0001).

Mean (SD) time intervals (years) from baseline colonoscopy to first surveillance were 3.4 (2.0) for advanced adenoma, 4.3 (2.0) for non-advanced adenoma, 4.5 (2.0) for non-adenomatous polyps, and 4.7 (2.0) for no polyps.

There were no increasing (or decreasing) trends in the observed rate of advanced adenoma or any adenoma with time to the initial surveillance examination in any baseline group.

Among subjects with a second surveillance examination, adenoma findings at both baseline and first surveillance influenced the rates of advanced adenoma and any adenoma at second surveillance.

B

Robertson 2005

IV

US N=2,915 An analysis of retrospective colonoscopy data from patients who were participants in one of three adenoma chemoprevention trials.

All participants underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions. The researchers identified patients subsequently diagnosed with invasive cancer

Mean follow-up was 3.7 years.

Seven patients were diagnosed with adenoma with high-grade dysplasia during follow-up.

Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high-grade dysplasia

B

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Country Sample size


or adenoma with high-grade dysplasia.

The timing, location, and outcome of all cases of cancer and high-grade dysplasia identified were described and risks associated with their development evaluated.

Robertson 2009

III-2

US N=564 Prospective cohort study performed in academic and private centres. All participants had 1 or more adenoma found on complete colonoscopy at study entry. Participants then underwent second and third study colonoscopies at 3-year intervals.

Proportion of patients with high-risk findings at the third study colonoscopy - either at least 1 advanced (> or = 1 cm or advanced histology) adenoma or multiple (> or = 3) adenomas were identified.

Fifty-eight of 564 participants (10.3%) had high-risk findings at the third study examination.

If the second examination showed high-risk findings, then results from the first examination added no significant information about the probability of high-risk findings on the third examination (18.2% for high-risk findings on the first examination vs. 20.0% for low-risk findings on the first examination; p = 0.78).

If the second examination showed no adenomas, then the results from the first examination added significant information about the probability of high-risk findings on the third examination (12.3% if the first examination had high-risk findings vs. 4.9% if the first examination had low-risk findings; p = 0.015).

B

Rostirolla 2009

IV

Brazil N=392 Retrospective observational study to determine the development rate of advanced neoplasia in patients receiving surveillance colonoscopy.

Patients who underwent two or more complete colonoscopies between 1995 and 2005, and who had at least one diagnosed colorectal adenoma were enrolled in the study. The endoscopic findings of the

The mean age of participants was 59 years.

A total of 28% of patients had advanced adenomas at index colonoscopy; 58% had low grade dysplasia and 14% had no adenoma at the first examination.

The mean period of surveillance was 123 months.

A total of 26% of participants in group 1 were identified with advanced

C

133



Country Sample size


first and subsequent colonoscopies of each patient were analysed.

The patients enrolled were divided according to the findings of the first colonoscopy: group 1 (high risk); 2 (low risk); and 3 (no adenoma) at the first colonoscopy. The development of advanced colorectal neoplasia was compared among groups.

neoplasia during the surveillance period; compared with 11% and 5% of participants in groups 2 and 3 respectively (p<0.05).

The mean time between the first colonoscopy and the colonoscopy where advanced neoplasia was detected was 104, 115 and 121 months in groups 1, 2 and 3 respectively.

Saini 2006

I

US N=15 studies

Computer searches of MEDLINE, PREMEDLINE, and EMBASE were performed to identify appropriate studies.

Study selection criteria were (1) study design--prospective or registry-based study, (2) study population - patients with a personal history of adenomas, and (3) intervention - completion of surveillance colonoscopy at an interval of > or =2 years.

Data were extracted on (1) incidence of advanced adenomas at surveillance colonoscopy, (2) interval between colonoscopies, and (3) risk factors associated with recurrent adenomas.

After the validity of study design was assessed and independent, duplicate data extraction was performed from selected trials, summary relative risks (RR) for the incidence of advanced adenomas at 3-year colonoscopy were calculated.

Patients with ≥3 adenomas at index colonoscopy were more likely to have recurrent advanced adenomas than were patients with 1 to 2 adenomas: RR 2.52, 95% CI 1.07-5.97.

Patients with adenomas with high-grade dysplasia at index colonoscopy were also at increased risk for recurrent advanced adenomas: RR 1.84, 95% CI 1.06-3.19.

In the individual studies, increasing size of adenomas and increasing number of adenomas at index colonoscopy were the most commonly reported risk factors associated with recurrent advanced adenomas.

A

Salama Australia N=140 Prospective observational study. Consecutive patients A total of 154 large neoplasms were identified in participants. The mean C

134



Country Sample size


2009

III-2

referred for endoscopic resection of large (≥20 mm) colorectal neoplasms between 2001 and 2008 were included. Resection details were recorded in a prospectively maintained database.

Data was collected on 30-day complication rates and follow-up colonoscopy findings.

age of participants was 68 years (range 22 – 94 years). Mean neoplasm size was 26 mm (range 20-80 mm) and 24 neoplasms were ≥40 mm.

Complete endoscopic removal was achieved in 95% of cases.

Twenty patients were referred for surgery (14%). In the endoscopy group, there were no deaths within 30 days. Twelve patients had a complication including two perforations.

Endoscopic follow-up data was available in 90% of cases and five patients (4%) were found to have residual adenoma that was treated endoscopically with subsequent clearance.

Seitz 2003

IV

Germany N=184 A retrospective evaluation of health services colonoscopy data collected over a period of 12 years. Over the period under examination, patients with polyps larger than 3 cm in diameter were treated endoscopically.

Patients with favourable histology were followed up at 3 - 6 month intervals in the first year and then every 1 - 2 years.

Recurrence rate of 166 benign polyps was 17 % (29/166). Two patients had malignant recurrence. 8 of 18 patients with malignant polyps underwent surgery while 10 were unfit for surgery. 8 of these patients remained free of recurrence.

C

Winawer 2006

III-2

US N/A Systematic review of the literature to delineate predictors of significant colonic neoplasia.

Update to US guidelines formulated based on consensus and findings of the review. The revised guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader

Risk factors for significant colonic neoplasia include the presence of 3 or more adenomas on index colonoscopy, high-grade dysplasia, villous features or an adenoma 1 cm or larger in size. A recommendation of 3-yearly follow-up colonoscopy was made for this patient group.

Patients at lower risk include those 1 or 2 small (<1 cm) tubular adenomas with no high-grade dysplasia. A recommendation of surveillance colonoscopy 5 to 10 years after index colonoscopy was made.

B

135



Country Sample size


consensus and thereby increase the use of the recommendations by endoscopists.

Patients with hyperplastic polyps were recommended to have 10-year follow-up colonoscopy.

There have been recent studies that have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians concerns.

Yamaji 2004

III-2

Japan N=6,225 Retrospective cohort study. A total of 4,659 men and 1,566 women participating in an annual colonoscopic screening programme and completing three or more colonoscopies were analysed during the 14 year study (period between 1988 and 2002).

Patients were divided into three groups according to the findings of two baseline colonoscopies: 4,084 subjects with no neoplasm, 1,818 with small adenomas (<10 mm) and 323 with advanced lesions, including carcinoma in situ, severe dysplasia or large adenomas ≥10 mm.

Colonoscopic surveillance interval was 2 baseline colonoscopies plus at least 1 or more colonoscopies over 14 years.

Mean age at the second colonoscopy was 48.8 years.

For all types of colorectal neoplasms, the incidence rate was 7.2% / year in subjects with no neoplasm at baseline, 19.3% / year in subjects with small adenomas and 22.9% / year in subjects with advanced lesions.

For advanced colorectal lesions, the incidence rate was 0.21% / year in subjects with no neoplasms at baseline, 0.6% / year in subjects with small adenomas and 1.9% / year in subjects with advance adenoma.

C

136


Review Question 2a: Effectiveness of colonoscopy in cancer preventionStudy ID and Level of Evidence

Country Sample size


Baxter 2009

III-2

Canada N = 5,750 Population-based, case-control study in persons aged 52 to 90 years who received a colorectal cancer diagnosis between 1996 and 2001 and died of colorectal cancer by 2003.

Five controls matched by age, sex, geographic location and socioeconomic status were randomly selected for each case.

Administrative claims data were used to detect exposure to any colonoscopy and complete colonoscopy (to the caecum) from 1992 to an index date 6 months before diagnosis in each case patient and the same assigned date in matched controls.

Exposures in case patients and controls were compared by using conditional logistic regression to control for co-morbid conditions. Secondary analyses were done to see whether associations differed by site of primary colorectal cancer, age or sex.

Compared with controls, case patients were less likely to have undergone any attempted colonoscopy (adjusted conditional odds ratio [OR], 0.69 [95% CI 0.63 to 0.74]) or complete colonoscopy (adjusted conditional OR, 0.63 [CI 0.57 to 0.69]).

Complete colonoscopy was strongly associated with fewer deaths from left-sided colorectal cancer (adjusted conditional OR, 0.33 [CI 0.28 to 0.39]) but not from right-sided colorectal cancer (adjusted conditional OR, 0.99 [CI 0.86 to 1.14]).

Patients who had received any previous colonoscopy were 37% less likely to develop colorectal cancer

B

Beaudin 2000

IV

Canada N=118 A retrospective analysis in a community-based referral gastroenterology practice of patients who have had screening by colonoscopy of asymptomatic first-degree relatives of patients with colorectal cancers.

Six per cent of those screened had advanced lesions (carcinoma, tubulovillous adenomas or adenomas larger than 1 cm).

C

Becker 2007

IV

Germany N=N/A A Markov model based on time-dependent transition possibilities was developed to perform a benefit-risk analysis of the risk-related surveillance recommendations based on the Erlangen Registry of Colorectal Polyps (ERCRP) in comparison with the recommendation of the German Society of Gastrointestinal Diseases and Nutrition

Patients under surveillance have a mean lifetime gain of 98 (ERCRP) and 110 (DGVS) days compared with those who do not come for surveillance.

84% and 94% of deaths from colorectal cancer could be prevented if patients were followed up according to the recommendations of the

N/A

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Country Sample size


(DGVS).

The outcome was calculated for a 50-year-old patient with 30 years of follow-up after initial polypectomy.

The data used in this model were taken from different sources, namely the ERCRP, the German Study Group of Colorectal Cancer, the German Statistical Yearbook, and from meta-analyses of studies reporting data on complications and sensitivity of colonoscopy.

ERCRP and the DGVS, respectively.

Less colonoscopies are needed to prevent one death from colorectal cancer following the recommendations of the ERCRP (221) than those of the DGVS (283).

The risk of death due to colonoscopy for patients during follow-up is about 0.05% lifetime risk.

Sensitivity analysis showed the stability of the results under a wide range of reasonable variations of relevant parameters. In a pessimistic one-way sensitivity analysis regarding compliance, effectiveness was reduced to one third.

Bressler 2007

IV

Canada N=12,487 Retrospective analysis of data from two administrative datasets and a cancer registry. All patients ≥ 20 years of age with a new diagnosis of right-sided, transverse, splenic flexure/descending, rectal or sigmoid colorectal cancer between 1997 and 2002 who had received a colonoscopy within the 3 years before their diagnosis were included.

Patients with new or missed cancers were defined as those whose most recent colonoscopy was 6 to 36 months before diagnosis.

Characteristics that might be risk factors for new or missed colorectal cancer were identified.

There were 3,288 patients with right sided, 777 with transverse, 710 with splenic flexure/descending and 7,712 with rectal or sigmoid cancer.

The rates of cancer identified within 6 to 36 months after a colonoscopy were 5.9%, 5.5%, 2.1%, and 2.3%, respectively.

Independent risk factors for these cancers in men and women were older age; diverticular disease; right-sided or transverse colorectal cancer; colonoscopy by an internist or family physician; and colonoscopy in an office.

C

Chen 2003

III-2

Taiwan N = 721 A case-cohort study, underpinning a cohort with 13,908 subjects (including 10,496 normal subjects, 2,652 polyps and 760 subjects with colorectal cancer) who underwent their first examination of colonoscopy between 1979 and 1998.

Participants were randomly selected from the cohort: 305

Subjects with polyps were linked to a national cancer registry to identify 25 patients with invasive carcinomas after polypectomy.

Compared to size less than 5 mm, patients with adenoma size between 6 and 10 mm and patients with adenoma size larger than 1 cm have 2.17-fold (0.67-10.74) and 4.25-fold (1.23-14.70), respectively, the risk of malignant transformation.

C

138



Country Sample size


normal subjects, 300 patients with polyps, and 116 patients with colorectal cancer.

Time to carcinoma development in subjects was estimated.

The estimates of overall efficacy of colonoscopy in reducing colorectal cancer was 73% for the model allowing for de novo carcinoma and 88% for the model without considering de novo carcinoma theory.

Collins 2008

III-2

UK N/A A systematic review of studies assessing disease outcomes in patients with inflammatory bowel disease who had received colonoscopic surveillance.

The proportion of patients dying from bowel cancer or other causes in the control and surveillance groups of each study was derived from life tables, survival curves or where possible, by calculating life tables from the data provided.

Data from the original research articles were converted into 2x2 tables (survival versus death x surveillance versus control) for each of the individual studies for comparable follow-up intervals.

The presence of significant heterogeneity among studies was tested by the chi-square test. Because this is a relatively insensitive test, a p value of less than 0.1 was considered statistically significant.

Provided statistical heterogeneity was not present, the fixed effects model was used for the pooling of data.

The 2x2 tables were combined into a summary test statistic using the pooled relative risk (RR) and 95% confidence intervals as described by Cochrane and Mantel and Haenszel.

For the pooled data analysis 8/110 patients in the surveillance group died from colorectal cancer compared to 13/117 patients in the non-surveillance group (RR 0.81; 95% CI 0.17 to 3.83).

Karlen 1998a in a nested case-control study comprising 142 patients from a study population of 4,664 patients with ulcerative colitis, found that 2/40 patients dying of colorectal cancer had undergone surveillance colonoscopy on at least one occasion compared with 18/102 controls (RR 0.28; 95% CI 0.07 to 1.17). One of 40 patients who died from colorectal cancer had undergone surveillance colonoscopies on two or more occasions compared with 12/102 controls (RR 0.22; 95% CI 0.03 to 1.74) in contrast to a more modest effect observed for patients who had only one colonoscopy (RR 0.43; 95% CI 0.05 to 3.76).

Choi 1993 found that carcinoma was detected at a significantly earlier stage in the surveilled patients; 15/19 had Duke’s A or B carcinoma in the surveilled group compared to 9/22 in the non-surveilled group (p = 0.039). The 5-year survival rate was 77.2% for cancers occurring in the surveillance group and 36.3% for the no-surveillance group (p= 0.026). Four of 19 patients in the surveillance group died from colorectal cancer compared to 11 of 22 patients in the non-surveillance group (RR 0.42; 95% CI 0.16 to 1.11).

Lashner (1990) found that four of 91 patients in a surveillance group died from colorectal cancer compared to 2 of 95 patients in a non-surveilled group (RR 2.09; 95% CI 0.39 to 11.12). Colectomy was

A

139



Country Sample size


less common in the surveillance group, 33 compared to 51 (p < 0.05) and was performed four years later (after 10 years of disease) in the surveillance group.

Croese 1999

IV

Australia N = 8,906 Case and population survey conducted between 1985 and 1998. Patients who underwent colonoscopies performed by the author between 1985 and 1996; those who were subsequently diagnosed with colorectal cancer to by 1998; and all 476 patients diagnosed with colorectal cancer between 1994 and 1997, regardless of prior colonoscopy status, were included.

Age-standardised incidence rates of colorectal cancer for patients who had had a previous colonoscopy and for the remaining community were calculated.

For people aged 50 years and over, the incidence of colorectal cancer was significantly lower among those who had had a previous colonoscopy than in the remaining community (1.14 versus 2.31 per 1000 patient-years; p = 0.0046).

For people aged 35 to 49 years, the incidence was 0.35 versus 0.31 per 1000 patient-years (p = 0.86).

Thirty-one colorectal cancers developed in 29 people who had had previous colonoscopy; five were graded Dukes C, none were graded Dukes D. In contrast, almost half the colorectal cancers in the rest of the community were graded Dukes C or D (p < 0.001).

All but one of those diagnosed with colorectal cancer on repeat colonoscopy had risk factors (personal or family history), and 23 of the colorectal cancers were subclinical, with 20 being diagnosed during surveillance colonoscopy.

C

Dove-Edwin 20005

III-2

UK N=1,678 Prospective, observational study of high-risk families, followed up over 16 years in a tertiary referral family cancer clinic in London.

Median age at initial colonoscopy was 41 years. Colonoscopy was initially offered at five-yearly intervals and then three-yearly intervals if an adenoma was detected at index colonoscopy.

The incidence of adenomas with high risk pathological features or cancer was analysed according to the age, the extent of the family history, and findings on previous

Risk of adenoma or carcinoma increased with increasing age, from 2% in people younger than 35 years to 15% in those aged 65 years and older.

Risk of adenoma on follow-up colonoscopy in high-risk families was 26% compared with 13% in low-risk families.

High-risk adenomas and cancer were most common in families with hereditary non-polyposis colorectal cancer (on initial colonoscopy 5.7% and 0.9%, respectively), compared with 1.1% and 0.1% respectively for moderate and low risk families combined.

The incidence of colorectal cancer was substantially lower - 80%

C

140



Country Sample size


colonoscopies of participants.

Incidence of colorectal cancer and mortality during over 15,000 person years of follow-up were compared with those expected in the absence of surveillance.

lower in families at moderate rather than high risk of colorectal cancer (p<0.001), and 43% lower in families with hereditary non-polyposis colorectal cancer (p=0.06) - than the expected incidence in the absence of surveillance.

Ee 2002

III-2

Australia N=9,533 Retrospective data linkage study. A multicenter endoscopy database was used to identify all reportedly normal colonoscopies. One cohort was assessed 5 years after colonoscopy with the use of a population-based health services-linked database to link patient morbidity, cancer, and mortality data. The second cohort was assessed by identifying patients who had cancer on repeat colonoscopy.

In the first cohort of 1,047 patients, 5 cancers (0.5%) were detected; not significantly different from that predicted by population statistics (risk = 1.0%) but significantly lower compared with that for all patients presenting for colonoscopy during the study period (risk = 5.2%).

In the second cohort of 8,486 patients with reportedly normal colonoscopies, 496 patients underwent repeat colonoscopies during an average follow-up of 3.1 years.

Cancer was diagnosed at the subsequent procedure in 3 patients (0.6%).

B

Farrar 2006

III-2

US N = 830 Case control study. An institutional cancer registry was searched in order to identify patients who had developed colorectal cancers within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio to patients with sporadic cancers, which were defined as colorectal cancers diagnosed on a patient’s first recorded colonoscopy.

Patient, colonoscopy, and tumour characteristics of interval and sporadic cancers were compared.

There were 45 patients who developed an interval cancer (5.4%; 95% CI 4.1%-7.2%).

Twenty-seven percent of interval cancers developed at previous polypectomy segments. Interval cancers were 3 times more likely to occur in the right colon and were smaller in size than sporadic cancers.

No difference in TNM stage at diagnosis, histologic type or grade, carcinoembryonic antigen level, or 5-year survival was found between interval and sporadic cancers.

B

Fisher 2003

IV

US N=3,546 Retrospective analysis of administrative data. Patients with a new diagnosis of colorectal cancer between 1995 and 1996 were identified in Veterans Affairs databases.

Demographics, co-morbidities, colonoscopies,

In the adjusted analysis the risk of death due to colorectal cancer was decreased by 43% (HR = 0.57, 95% CI = 0.51-0.64) in the group who had at least one follow-up colonoscopy compared with patients who had no follow-up colonoscopies after a diagnosis of

C

141



Country Sample size


chemotherapy, and radiation therapy were extracted from the database.

The primary outcome studied was adjusted 5-yr mortality.

non-metastatic colorectal cancer.

Frenette 2007

IV

US N = 282 Retrospective analysis of administrative data. Patients with colorectal cancer diagnosed between 2000 and 2005 were identified through a search of institutional administrative data.

Records were reviewed for the results of colonoscopy in the 3 years prior to diagnosis. An examination that was negative for cancer with no immediate follow-up was defined as a failure of diagnosis, either from inaccurate observation, failure to examine the entire colon, or failure of timely follow-up.

The diagnosis of colorectal cancer was not made in 25 of 282 colonoscopies (9%) performed in the 3 years prior to diagnosis.

C

Gorski 1999

IV

US N = 557 Retrospective analysis of administrative data. The records of patients with colorectal cancer that were diagnosed between 1990 and 1996 were reviewed to identify those patients who had prior colonoscopic surveillance within 60 months of their diagnosis.

There were 29 (5.2%) patients who had one or more colonoscopies before diagnosis of their colorectal cancer.

Mean interval between diagnosis and prior colonoscopy was 23 (range, 4-59) months.

The mean tumour size was 4.4 cm for the caecum and 2.4 cm for all other locations. Twenty tumours (69 percent) were well or moderately differentiated.

C

Jarvinen 2000III-2

Finland N=252 Prospective cohort study. Incidence of colorectal cancer and survival were compared in 2 cohorts of at-risk members of 22 families with HNPCC. Colonic screening at 3-year intervals was arranged for 133 subjects; 119 control subjects had no screening. Genetic testing was offered to subjects in whose families the causative mutation was known.

Colorectal cancer developed in 8 screened subjects (6%) compared with 19 control subjects (16 %; p = 0.014). The cancer rate was reduced by 62% in screened subjects. In mutation-positive subjects, the cancer rates were 18% in screened subjects and 41% in controls (p = 0.02). The decrease resulted from the removal of adenomas in 13 mutation-positive individuals (30%) and in 6 subjects with unknown mutation

B

142



Country Sample size


status (40%). All colorectal cancers in the study group were local, causing no deaths, compared with 9 deaths due to colorectal cancer in the controls. The overall death rates were 10 vs. 26 subjects in the study and control groups (p = 0.003), 4 vs. 12 in mutation-positive subjects (p = 0.05).

Jorgensen 2007

II

Denmark N = 2,041 Evaluation of long-term surveillance of a patient population with all types of adenomas.

Patients had initial colonoscopy then were randomised to surveillance at intervals that varied between 6 and 48 months.

Incomplete colonoscopies were followed-up by double contrasted barium enema.

Prospective surveillance was performed between year 1978 and 2002.

Incidence of colorectal cancer and mortality from colorectal cancer was calculated, using age, sex, and calendar specific number of person years of follow-up for comparison with the standard Danish population.

Relative risk of colorectal cancer and death from colorectal cancer in the total study population was calculated by dividing the observed number of cancers by the number expected in a standard Danish population the same age and sex distribution.

Complete colonoscopy was performed in 95% of male and 92% of female participants.

New adenomas were removed in 736 patients; 144 had advanced adenomas at least once over the study period (28 with severe dysplasia, 9 with villous adenomas and 131 with adenomas > 10 mm).

Colorectal cancer was identified in 27 patients.

Colorectal cancer was found in 27 patients, the expected number being 41 (RR 0.65, 95% CI 0.43_0.95). Three of the 27 patients died from CRC, the expected number being 25 (RR 0.12, 95% CI 0.03_0.36).

Compared with a standard population, patients with all types of adenomas, subjected to initial removal and following colonoscopic surveillance had a reduced incidence of colorectal cancer of 35% and a reduced mortality from colorectal cancer of 88%.

Reduction in mortality was assumed to be due to the more favourable stage of colorectal cancer; Dukes A occurred in 44% of participants compared with 10% of the Danish population.

B

Kahi 2007 US N=163 Retrospective cohort study of persons aged ≥ 75 years who No statistically significant difference in advanced neoplasm rate was C

143



Country Sample size


IV underwent colonoscopy between 1999 and 2000.

Advanced neoplasms were defined as colorectal cancer, polyp with high-grade dysplasia, villous histologic features, or tubular adenoma ≥1 cm.

observed between patients with a family history of colorectal cancer and patients with no family history.

Kottachchi 2009

IV

Canada N=141 A retrospective chart review of all patients with ulcerative colitis undergoing colonoscopy screening and / or surveillance at a single institution between 1980 and 2005.

Patients were classified according to the extent of colonic disease: limited left-sided colitis (LSC), pancolitis and any disease extent with concurrent primary sclerosing cholangitis.

Colonic dysplasia was detected in 24 of 141 patients (17.0%), with 17 of 24 (70.8%) found at surveillance.

Two patients (8.3%) had colorectal cancer successfully treated.

The average age of patients with dysplasia was 56.1 years, with a mean disease duration of 10.9 years in LSC versus 11.8 years in pancolitis (p > 0.05).

No patients progressed to high-grade dysplasia or colorectal carcinoma.

Patients with pancolitis had a higher incidence of neoplasia (21% [18 of 86]) than patients with LSC (12% [6 of 49]; p=0.24).

Forty-one patients (29.5%) had at least one hyperplastic or inflammatory polyp.

C

Leaper 2004

III-3

New Zealand

N = 4,598 Colonoscopies carried out in a single hospital facility over a 43-month period (1997 to 2001) were retrospectively analysed. All cases of colorectal carcinoma that occurred during the period were also identified. The data were then compared and all cases in which a colonoscopy had been performed more than 6 weeks before a colorectal carcinoma specimen being received by the pathology department were identified and analysed.

Over the study period there were 630 patients identified who were diagnosed with colorectal carcinoma.

6% of patients diagnosed with colorectal cancer had a colonoscopy within the previous 43 months.

C

Leung 2010

III-2

US N = 1,297 A prospective cohort study of patients with a prior history of polyp detection. Patients were recruited from those who had completed the US National Polyp Prevention Trial

Nine cases of colorectal cancer were diagnosed over 7,626 person-years of observation completed after the Polyp Prevention Trial had finished; this equated to an incidence rate of 1.2/1000 person years

B

144



Country Sample size


(PPT).

The PPT enrolled 2,079 patients who had a baseline enrollment colonoscopy (T0) with at least 1 adenomatous polyp but no history of colorectal cancer (CRC). Subjects were randomized to a dietary intervention to adopt a diet low in fat and high in fibre, fruits, and vegetables instead of their usual diet. A repeat colonoscopy was performed in 1 to 2 years (T1) to detect and remove lesions that may have been missed at the baseline colonoscopy. Subjects underwent a repeat colonoscopy in 4 years (T4) to examine the impact of dietary change on adenoma recurrence. Eligibility for the study required that subjects be 35 years and older and have 1 or more colorectal adenomas removed during a qualifying colonoscopy within 6 months before randomization. Exclusion criteria were history of CRC, surgical resection of adenomas, bowel resection, polyposis syndrome, inflammatory bowel disease, weight greater than 150% of recommended weight, lipid-lowering drug use, or a condition that would limit compliance with the diet protocol. The study was approved by the institutional review board of all participating centres.

After completion of the PPT, subjects were offered the option to continue in this observational study. Participants agreed to provide information to the researchers via annual health and lifestyle questionnaires that included questions about hospitalization, colonoscopy, and cancer diagnoses. Subsequent colonoscopy was performed at the discretion of the clinicians caring for the patients. Colonoscopy and pathology records were obtained, and the indications and

of observation.

The ratio of colorectal cancers observed compared with that expected was 0.64 (95% CI 0.28-1.06).

Including all colorectal cancers (N = 22) since the beginning of the Polyp Prevention Trial, the observed compared with expected rate of colorectal cancer was 0.74 (95% CI 0.47-1.05).

Of patients in whom colorectal cancer developed, 78% had a history of an advanced adenoma compared with 43% of patients who remained cancer free.

The patients in whom colorectal cancer was subsequently diagnosed had all undergone at least 3 colonoscopies before diagnosis since beginning the PPT. The average interval between the last colonoscopy and cancer diagnosis was 41 months (range 11 to 83 months).

145



Country Sample size


outcomes for the procedures were abstracted in a standardized manner. CRC cases were also identified from the annual questionnaires. Original medical records were obtained and reviewed for these cases including procedure, radiology, operative, and histopathology reports for information regarding the diagnosis, size, location, and stage of cancer.

Patients were followed for a median of 10.5 years; 4.3 years of median follow-up in the Polyp Prevention Trial and 6.2 years of median follow-up after the trial ended.

Lieberman 2007

III-3

US N=1,193 Subjects with neoplasia were matched with neoplasia-free controls and assigned to colonoscopic surveillance over 5 years.

Subjects were aged between 50 and 75 years and had screening colonoscopy between 1994 and 1997.

Relative risks for advanced neoplasia within 5.5 years were calculated.

Advanced neoplasia was defined as tubular adenoma ≥10 mm, adenoma with villous histology, adenoma with high-grade dysplasia or invasive cancer.

Eight hundred ninety-five (76.4%) patients with neoplasia and 298 subjects (59.5%) without neoplasia at baseline had colonoscopy within 5.5 years; 2.4% of patients with no neoplasia had interval advanced neoplasia.

The relative risk in patients with baseline neoplasia was 1.92 (95% CI: 0.83-4.42) with 1 or 2 tubular adenomas <10 mm, 5.01 (95% CI: 2.10-11.96) with 3 or more tubular adenomas <10 mm, 6.40 (95% CI: 2.74-14.94) with tubular adenoma ≥10 mm, 6.05 (95% CI: 2.48-14.71) for villous adenoma, and 6.87 (95% CI: 2.61-18.07) for adenoma with high-grade dysplasia.

C

Lutgens 2009

III-2

The Netherlands

N=149 A nationwide pathology database was analysed to identify patients with inflammatory bowel disease with colorectal cancer who had been treated over the 15-year study period in one of eight study centres.

Patients were assigned to the surveillance group when they had undergone one or more surveillance colonoscopies before a diagnosis of colorectal cancer.

Twenty-three participants had had colonoscopic surveillance before their colorectal cancer was diagnosed.

The 5-year colorectal cancer-related survival rate of patients in the surveillance group was 100% compared with 74% in the non-surveillance group (p=0.042).

Over the study period, 1 patient in the surveillance group died as a consequence of colorectal cancer compared with 29 patients in the

C

146



Country Sample size


Patients who had not undergone surveillance served as controls. Tumour stage and survival were compared between the two groups.

control group (p=0.047).

Tumour stage was earlier overall in patients in the surveillance group (p=0.004).

Martinez 2009

III-2

US N=9,167 Individual data were pooled from 8 prospective studies comprising patients with previously resected colorectal adenomas.

Risk of developing subsequent advanced adenoma or cancer was quantified.

Median follow-up period was 47.2 months. Advanced colorectal neoplasia was diagnosed in 1,082 (11.8%) patients, 58 of whom (0.6%) had invasive cancer.

Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%) and those with an adenoma 20 mm in size or greater (19.3%).

The number and size of prior adenomas (p < 0.001 for trend) and the presence of villous features (OR 1.28; 95% CI 1.07-1.52) was associated with increased risk for metachronous advanced neoplasia.

B

Pabby 2005

III-2

US N = 2,079 The study examined cancer diagnoses in the course of the US national Polyp Prevention Trial.

An algorithm was developed to classify each cancer into one of 4 aetiologies: (1) incomplete removal (cancer at the site of previous adenoma), (2) failed biopsy detection (cancer in an area of suspected neoplasia with negative biopsy specimens), (3) missed cancer (large, advanced stage cancer found at a short interval after colonoscopy), or (4) new cancer (small, early stage cancer after a long time interval).

There were 13 patients who had cancer detected over a total of 5,810 person years of observation (2.2 cases/1000 person years of observation).

The mean time between colonoscopy and carcinoma detection was 22 months (range 2 to 44 months).

There were 7 of 13 patients (53.8%) who had either a potentially “avoidable” cancer detectable at an earlier time interval because of incomplete removal (4/13) or missed cancer (3/13).

B

Postic 2002

IV

US N=158 A retrospective analysis was conducted of patients who had a portion of colon surgically removed and had lower endoscopy within 5 months. The focus of the review was to identify synchronous lesions in the portions of bowel that were removed.

A total of 73 synchronous lesions were present in the resected segments of patients.

Colonoscopy detected 56 of 73 the lesions (sensitivity 76.7%: 95% CI = 67-86). Of the 17 missed lesions, 14 of 17 (82%, 95% CI = 64-100) were <1-cm polyps.

C

147



Country Sample size


Sensitivity was determined by counting the number of lesions detected at colonoscopy compared with those found in the surgically resected segment.

Endoscopy overlooked one 1-cm adenoma in the ascending colon. Two cancers were missed, both in the same patient in whom endoscopy detected a sigmoid cancer but missed synchronous lesions in the caecal and ascending colon.

Renehan 2002

I

UK N=1,342 Systematic review and meta-analysis of randomised controlled trials of intensive compared with control follow-up.

The main outcome measure was all cause mortality at five years (primary outcome).

Rates of recurrence of intraluminal, local and metastatic disease and metachronous (second colorectal primary) cancers (secondary outcomes) were calculated.

Five trials, which included 1,342 patients, met the inclusion criteria.

Intensive follow up was associated with a reduction in all cause mortality (combined risk ratio 0.81, 95% CI 0.70 to 0.94, p=0.007). The effect was most pronounced in the four extramural detection trials that used computed tomography and frequent measurements of serum carcinoembryonic antigen (risk ratio 0.73, 0.60 to 0.89, p=0.002).

Intensive follow up was associated with significantly earlier detection of all recurrences (difference in means 8.5 months, 7.6 to 9.4 months, p<0.001) and an increased detection rate for isolated local recurrences (risk ratio 1.61, 1.12 to 2.32, p=0.011).

Intraluminal recurrences and metachronous cancers were uncommon, irrespective of the intensity of follow up.

Intensive efforts directed at the detection of intraluminal disease (colonoscopy) were estimated to be of low benefit.

A

Rodriguez-Moranta 2006

II

US N=259 Patients with stage II or III colorectal cancer were allocated randomly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring, or an intensive strategy in which abdominal computed tomography or ultrasonography, chest radiograph, and colonoscopy were added.

A total of 132 patients were included in the simple strategy arm and 127 were included in the intensive strategy arm. Both groups were similar with respect to baseline characteristics and rate and type of tumour recurrence.

After a median follow-up of 48 months, there was no difference in the probability of overall survival in the whole series (HR 0.87; 95% CI 0.49 to 1.54). However, the intensive strategy was associated with higher overall survival in patients with stage II tumours (HR

B

148



Country Sample size


0.34; 95% CI 0.12 to 0.98) and in those with rectal lesions (HR 0.09; 95% CI 0.01 to 0.81), mainly due to higher rate of resectability for recurrent tumours.

Colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumour recurrence in the intensive arm.

Rulyak 2007

IV

US N=1,002 An organisational administrative database of patients with colorectal cancer who underwent surgical resection was analysed.






C

Schoenfeld 2003

IV

US N=100 Consecutive patients with a family history of colorectal cancer and a normal screening colonoscopy 5 years earlier were offered a surveillance colonoscopy.

Patients also completed a questionnaire about potential risk factors for adenomas.

Multiple logistic regression analysis assessed associations

Eight percent (8 of 100) of patients had advanced adenomas at surveillance colonoscopy, and 33% (33 of 100) had adenomas.

Among patients with adenomas, 39% (13 of 33) had no adenomas in the left side of the colon (i.e. distal to the splenic flexure). Among patients with advanced adenomas, 25% (2 of 8) had no adenomas in the left side of the colon.

C

149



Country Sample size


between risk factors and adenomas. Multiple logistic regression analysis showed a significant negative association between adenomas and NSAID use (OR 0.26 [95% CI 0.09-0.79]), and male gender had a positive association with adenomas (OR 2.79 [95% CI 1.017.74]).

Seow 2006

IV

Australia N = 2,075 Retrospective analysis of administrative data. Adults who had ≥2 colonoscopies between 1992 and 2004 were identified from an endoscopic database of a tertiary referral hospital.

Patients were excluded if the repeat procedure was for completion or for high-risk surveillance.

The main outcome measures were yield for neoplasia by indication, interval to repeat examination and appropriateness for surveillance (determined by Australian guidelines).

The mean age of patients was 63.1 years (range, 19.2-92.4 years).

The mean number of examinations was 2.4 (range, 2-8), with a mean interval between examinations of 2.9 years.

Colorectal cancer was significantly more prevalent at initial colonoscopy compared with subsequent colonoscopies (7.9% versus 0.6%; prevalence ratio 14.2, 95% CI 8.5-23.7), as were advanced adenomas (15.3% versus 4.8%; prevalence ratio 3.2, 95% CI 2.6-3.9).

No colorectal cancers were detected in symptomatic patients undergoing polyp surveillance examinations performed before the recommended interval

C

Singh (1) 2010

III-2

Canada N = 54,803

Retrospective analysis of linked administrative data. Individuals were identified in a billings claims database who had received a colonoscopy as their first lower gastrointestinal endoscopy between 1987 and 2007.

Patients were followed until 2008, death or migration out of the province (310,718 person-years).

Individuals less than 50 years of age or more than 80 years of age at the index colonoscopy or those with prior sigmoidoscopy, inflammatory bowel disease, resective colorectal surgery or colorectal cancer were excluded.

Colorectal cancer mortality after the index colonoscopy was compared with that of the general population by

There was a 29% reduction in overall colorectal cancer mortality (SMR 0.71; 95% CI 0.61-0.82] among patients who had received a colonoscopy in the study period; a 47% reduction in mortality from distal colorectal cancer (SMR 0.53; 95% CI 0.42-0.67) and no reduction in mortality from proximal colorectal cancer (SMR 0.94; 95% CI 0.77-1.17).

B

150



Country Sample size


standardized mortality ratios (SMRs).

Stratified analyses were performed to determine colorectal cancer mortality for different sites of colorectal cancer.

Singh (2) 2010

III-2

Canada N = 45,985

Retrospective analysis of linked administrative data.

All individuals 40 years or older with negative colonoscopy were identified from a physicians billing claims database.

Colorectal cancer risk after negative colonoscopy was compared to that in the general population by standardized incidence ratios.

Patients were followed up for 229,090 person-years.

Risk of colorectal cancer diagnosis in patients with previous colonoscopy was reduced by between 40% and 50%.

B

Singh 2006

III-2

Canada N = 35,975

Population-based retrospective analysis of individuals whose colonoscopy evaluations did not result in a diagnosis of colorectal neoplasia.

Patients who had been evaluated between 1989 and 2003 were identified using a physician billing claims database.

Standardized incidence ratios (SIRs) were calculated to compare colorectal cancer incidence in our cohort with colorectal cancer incidence in the provincial population.

Cohort members were followed up from the time of the index colonoscopy until diagnosis of colorectal cancer, death, out-migration from the geographical area or end of the study period.

The main outcome measure was incidence of colorectal cancer.

A negative colonoscopy was associated with SIRs of 0.69 (95% CI 0.59-0.81) at 6 months, 0.66 (95% CI 0.56-0.78) at 1 year, 0.59 (95% CI 0.48-0.72) at 2 years, 0.55 (95% CI 0.41-0.73) at 5 years, and 0.28 (95% CI 0.09-0.65) at 10 years.

The proportion of colorectal cancer located in the right side of the colon was significantly higher in the colonoscopy cohort than the rate in the population as a whole (47% versus 28%; p<0.001).

B

Stupart 2009

III-2

South Africa

N=178 A prospective cohort study of patients who carry a mutation of the MLH1 gene in exon 13.

One hundred and twenty-nine subjects underwent surveillance colonoscopy, and 49 declined.

C

151



Country Sample size


Patients were offered surveillance colonoscopy between 1988 and 2006.

After a median follow up of 5 years, colorectal cancer was diagnosed in 14/129 (11%) subjects in the surveillance group and 13/49 (27%) in the non-surveillance group (p = 0.019).

Cancers in the surveillance group were at an earlier stage than in the non-surveillance group (p = 0.032).

Death from colorectal cancer occurred in three of 129 (2%) subjects in the surveillance group, and six of 49 (12%) in the non-surveillance group (p = 0.021).

The Kaplan-Meyer estimates for median survival from birth were 78 years in the surveillance group, and 55 years in the non-surveillance group (p = 0.024).

The Kaplan-Meyer estimates for median colorectal cancer-free survival from birth were 73 years in the surveillance group and 47 years in the non-surveillance group (p = 0.0089).

Velayos 2006

III-2

US N=376 An administrative database was searched to identify cases and controls diagnosed between 1976 and 2002. Cases had chronic ulcerative colitis and colorectal cancer.

Matched controls with chronic ulcerative colitis were randomly chosen from the same source population.

Surveillance colonoscopy decreased the risk of colorectal cancer; patients who had received 1 to 2 surveillance colonoscopies OR=0.4 (95% CI 0.2 to 0.7); patients who had received > 2 surveillance colonoscopies OR=0.3 (95% CI 0.1 to 0.8).

C

Wang 2009

II

China N=326 A prospective, randomised, controlled trial in a single health facility. Consecutive patients undergoing surgery for colorectal cancer were randomised to either an intensive colonoscopic surveillance group where colonoscopy was performed at 3-month intervals for 1 year, at 6-month intervals for the next 2 years and once a year thereafter or a routine colonoscopic surveillance group where colonoscopy was performed at 6 months, 30

There were 165 subjects in the intensive surveillance group and 161 subjects in the routine surveillance group.

The 5-year survival rate was 77% in the intensive surveillance group and 73% in the routine surveillance group (p>0.05).

Postoperative colorectal cancer was detected in 13 patients (8.1%) in the intensive group and in 18 patients (11.4%) in the routine group.

In the intensive group there were more asymptomatic postoperative colorectal cancers (p=0.04) detected, more patients had re-operation

B

152



Country Sample size


months and 60 months postoperatively. with curative intent (p=0.048) and the probability of survival after postoperative colorectal cancer was higher (p=0.03).

Yusoff 2003

III-2

Australia N=606 An audit was performed of all patients who underwent colonoscopy following surgical resection of colorectal cancer between 1989 and 2001.

Two groups were assessed: (i) all patients undergoing surveillance colonoscopies; and (ii) all patients diagnosed with colorectal cancer at a single study centre who subsequently had postoperative colonoscopies.

Patients who had their index colonoscopy at the study centre and who subsequently underwent surveillance colonoscopies were studied in detail.

Yield for neoplasia, patterns of surveillance and concordance with clinical guidelines were determined.

There were 304 female and 302 male patients with a mean age of 67 years who underwent 990 colonoscopies for postoperative surveillance of colorectal cancer. Adenomatous polyps were detected in 184 examinations; intraluminal recurrence in 1 case; no metachronous cancers.

In a subgroup of 161 patients who had index and postoperative surveillance at the study centre, synchronous neoplasms were found in 32 patients (including four advanced adenomas and one colorectal cancer).

Of 89 patients who underwent a surveillance examination at 1 year postoperatively, the findings were: normal (80 cases; 90%); adenoma (eight cases; 9%); advanced adenoma (one case; 1%); and recurrent cancer (one case; 1%). No metachronous cancer was found.

C

153


Review Question 2b: Effectiveness of colonoscopy in diagnosis of pathology in symptomatic patientsStudy ID and Level of Evidence

Country Sample size


Ang 2002

IV

UK N = 945 A retrospective analysis of administrative data. All patients who underwent a colonoscopy in a single endoscopy unit between 1996 and 1999 were included.

Patients were of average risk and had non-specific colonic symptoms (patients with significant risk factors were excluded).

The overall yield of adenomas was 5.8%.

The yield of distal adenomas in patients ≥ 50 years of age was 8.2% versus 0.2% in the < 50 years group.

The proximal adenoma yield in ≥ 50 year olds was 3.8% versus 0.2% in < 50 year olds.

C

Carlo 2006

IV

Italy N = 417 A prospective study in an open access endoscopy unit of patients with hematochaezia undergoing colonoscopy.

The final study group comprised 180 patients aged below 45 years and 237 over 45 years.

Main exclusion criteria were a 1st-degree family history of colorectal carcinoma, patients reporting blood mixed with stools and/or progressive colonic symptoms, or patients who had undergone colon surgery for neoplastic lesions.

Total colonoscopy was performed in 96% of patients.

Abnormal findings were observed in 34% of the younger and in 66% of the older patients. Findings included polyps in the distal colon (n = 2) and inflammatory bowel disease in the proximal colon (n = 29) in the group of the younger patients, and polyps (n = 15), inflammatory bowel disease (n = 13) and carcinoma (n = 6, 4 of the lesions were located proximal to the splenic flexure) in the older patients.

C

Chey 2010

III-3

US N = 917 A prospective, case-control study conducted at three sites in patients with suspected non-constipation-predominant irritable bowel syndrome.

All patients underwent colonoscopy with rectosigmoid biopsies.

Healthy persons undergoing colonoscopy for colorectal cancer screening or polyp surveillance comprised the control group.

Abnormalities identified at colonoscopy were compared between suspected irritable bowel syndrome and control groups.

There were 466 patients with suspected irritable bowel syndrome and 451 patients enrolled as controls.

The most common lesions identified in patients with suspected irritable bowel syndrome were haemorrhoids (18.2%), polyps (14.6%) and diverticulosis (8.8%).

Patients with irritable bowel syndrome had a lower prevalence of adenomas (7.7% vs. 26.1%) and diverticulosis (8.8% versus 21.3%) and higher prevalence of mucosal erythema or ulceration (4.9% versus 1.8%) compared with controls.

Logistic regression found the between-group differences in adenoma prevalence to be robust after correction for demographic factors.

B

154



Country Sample size


Fireman 1999

IV

Israel N = 90 A prospective, single-arm study of hospital inpatients identified with iron deficiency anaemia, defined as haemoglobin < 12.5 g/dl (men) and 11 g/dl (women), and serum iron < 50 g/dl, over the course of their admission.

Diagnostic colonoscopy was performed to identify diagnostic yield associated with iron deficiency anaemia.

The study group comprised patients (42% male) with a mean age of 65 +/- 15 years and mean haemoglobin of 8.1 g/dl.

A total of 49% of patients were discharged with iron deficiency of unknown origin.

Gastroscopy identified a bleeding source in 29% of patients.

Colonoscopy revealed a bleeding source in 14.4% of patients.

Gastrointestinal symptoms were found in 15% of patients with diseases of the lower gastrointestinal tract.

C

Gupta 2010

IV

US N = 41,775

A retrospective review of a colonoscopy research database of colonoscopies undertaken between 2000 and 2003.

Index colonoscopies performed for the indications of average-risk screening, constipation only or constipation with another indication were identified.

Logistic regression analyses were performed for constipation alone versus constipation with another indication, and for constipation alone versus average-risk screening.

Constipation alone did not show any increased risk of significant findings on colonoscopy.

Constipation and the presence of another indication had a statistically significant increased risk of a significant finding on colonoscopy.

The indication of constipation alone had a lower risk of significant findings on colonoscopy compared with average-risk screening.

C

Keren 2008

IV

Israel N = 13,517

Retrospective review of procedural data from colonoscopies conducted in ‘usual’ clinical practice over a 6 year period.

Procedural data were obtained from all consecutive patients who underwent colonoscopies in a single colonoscopy facility.

Indications were compared with American Society for Gastrointestinal Endoscopy guidelines.

Indications for colonoscopy were divided into 3 groups: screening (21.9% of the procedures), surveillance (17.6%) and symptoms/signs (60.5%).

A total of 2,867 patients (12.8%) had significant colonic neoplasia.

Significant colonic neoplasia occurred in 12.7% of the symptom/sign group (7.2% and 14.0% in the under 50 and over 50, age groups, respectively); screening 13.4% (5.5% and 15.1%, respectively); surveillance 12.6% (8.5% and 13.2%, respectively).

Among patients who had colonoscopy to investigate symptoms / signs, significant colonic neoplasia was identified in 9% of patients

C

155



Country Sample size


with irritable bowel syndrome, 11% of patients with hematochezia; 13% of patients with anaemia; 22% of patients with unexplained weight loss, 32% of patients with abnormal imaging; 14% of patients with inflammatory bowel disease, 31% of patients with elevated CEA and 30% of patients with rectal pain.

Landy 2010

IV

UK N = 558 Retrospective study. Analysis of administrative dataset.

An endoscopy database was searched for all synchronous bidirectional endoscopies that were undertaken for the indication of iron deficiency anaemia between 2003 and 2009.

Age, gender and endoscopic findings were retrieved for each procedure.

Significant findings were defined as cancer, grade 3 oesophagitis (Savory Miller classification), oesophageal stricture, Barrett's oesophagus, ulcer, arteriovenous malformation, colitis and colonic polyps >1 cm.

At colonoscopy 12% of patients had a significant finding; 5% had suspected cancer, 3% had a large polyp (>1cm), 2% had an arterio-venous malformation and 2% had colitis.

C

Lasson 2008

IV

Sweden N = 767 Retrospective study. Analysis of an administrative database of consecutive colonoscopies that were registered in a database over a 1 year period.

Asymptomatic subjects and patients with known inflammatory bowel disease were excluded.

Symptoms, colonoscopy findings and the endoscopists’ provisional diagnoses were recorded.

In patients with bleeding symptoms (n=405), serious colonic pathology - cancers and adenomas <1 cm, inflammatory bowel disease and angiodysplasia - were found in 54 (13.3%), 83 (20.5%) and 20 (4.9%) patients, respectively; 162 (40%) patients had findings that could be related to the symptom.

In 173 subjects with non-bloody diarrhoea, the diagnostic yield was 31.2%, i.e. mostly inflammatory bowel disease and microscopic colitis.

In 189 subjects with other gastrointestinal symptoms, the diagnostic yield was 13.2%.

Serious colonic pathology was found in 8 of 362 (2.2%) subjects

C

156



Country Sample size


examined because of non-bleeding symptoms.

Park 2006

III-3

Korea N = 243 A retrospective case-control study to evaluate the contribution of esophagogastroduodenoscopy (EGD) and colonoscopy to the aetiological diagnosis of a group of asymptomatic premenopausal women suffering from iron deficiency anaemia.

Consecutive asymptomatic premenopausal women were included in the patient group between 1998 and 2004.

There were 108 cases and 135 age-matched asymptomatic premenopausal women without anaemia who had undergone EGD and colonoscopy for medical checkups in the control group.

Clinically relevant lesions were detected in 7 of 108 (6.5%) of the cases and in 8 of 135 (5.9%) of the controls.

There were no differences with regard to the frequency of clinically relevant lesions between the two groups.

Concomitant upper and lower GI lesions were not detected in any patients.

In the upper GI tract, the only lesion found to be potentially causative of iron deficiency anaemia was a severe erosive gastritis, which was found in both the patient and the control groups.

A source consistent with chronic bleeding was detected in the lower gastrointestinal tract in 6 (5.6%) of the patients and 7 (5.2%) of the controls.

Bleeding haemorrhoids represented the most frequently detected lesions in both the patient and control groups. One case of colon cancer was detected in the case group and none in the controls.

C

Park 2009

IV

Korea N = 1,518

Patients with a ferritin value of ≤50 ng/mL and a total iron-binding capacity ≥300 mg/dL were retrospectively investigated using oesophagogastroduodenoscopy and colonoscopy between 2005 and 2006.

The lesions identified were classified as clinically important according to predetermined criteria.

Among study participants, 749 patients had anaemia and 769 had normal haemoglobin levels.

Clinically important lesions were identified in 24.6% of the patients with anaemia and in 22.8% of the patients without anaemia (p> 0.05).

The frequency of lower GI tract lesions (13.6 versus 11.4%) and upper GI tract lesions (11.9 versus 12.5%) was similar in the comparisons between the two groups. However, the frequency of malignant gastrointestinal lesions was higher in the patients with

C

157



Country Sample size


anaemia (5.1 versus 0.7%).

In addition, the patients without anaemia were significantly more likely to have early-stage neoplasia (adenoma, early gastric cancer and Dukes' A and B colon cancer) than were the patients with anaemia (98.4 versus 52.5%).

Pepin 2002

IV

US N = 358 Retrospective study. Endoscopic databases from 3 hospitals were searched for procedures with constipation as an indication.

Detection of neoplasia was the main outcome of interest.

In patients who underwent colonoscopy, cancer was detected in 1.7%, adenomas in 19.6%, and advanced lesions in 5.9%. Two patients with cancer were less than 50 years of age.

All patients in whom cancer was identified had symptoms in addition to constipation.

C

Sanchez 2005

IV

Spain N = 126 Patients referred from primary care units and complaining of rectal bleeding were included prospectively in a three-month follow-up study.

All patients underwent a colonoscopy.

Findings at colonoscopy were analysed according to demographic factors.

Patients had a mean age of 49.2 years (range: 19-80).

In total, 17% had significant abnormality identified at colonoscopy; 8% had polyps, 5% had colorectal cancer and 5% had inflammatory bowel disease.

C

Schoepfer 2005

IV

Switzerland N = 1,514

Findings from colonoscopies performed in symptomatic patients aged 50 to 80 between 1991 and 2000 were analysed retrospectively.

Symptoms leading to the endoscopy and the occurrence of neoplastic lesions were assessed.

Colorectal cancer was identified in 5.5% of all patients.

In 2.6% of patients a colorectal cancer was found before the age of 60.

In addition, 40% had diverticulosis, 32% had polyps, 3% had angiodysplasias and 1% had inflammatory bowel disease.

C

Stephens 2006

IV

UK N = 896 A retrospective review of case notes, endoscopy records and radiology reports was conducted in patients presenting to a single hospital with iron deficiency anaemia between 1995 and 2003.

Patients diagnosed with gastrointestinal malignancy were

The median age of patients was 71 years.

Lower gastrointestinal malignancy was detected in 111 patients; the median age of these patients was 73 years (range 31-94 years).

C

158



Country Sample size


identified and their outcomes determined. A total of 27% of patients had diverticulosis, 13% had polyps, 9% had colorectal cancer, 4% had inflammatory bowel disease and 3% had angiodysplasia.

159


Review Question 2c: Likelihood of a single colonoscopy leading to the detection of an adenoma and / or colorectal cancerStudy ID and Level of Evidence

Country Sample size


Bowles 2004

IV

UK N = 9,223

A prospective four month study of colonoscopies conducted in patients undergoing colonoscopy in one of 68 endoscopy units.

Patients undergoing colonoscopy for any indication were included.

The mean number of colonoscopies performed over the four month period was 142 in district general hospitals and 213 in teaching hospitals.

A normal colonoscopy was reported in 42.1%.

The most common diagnosis was polyps (22.5%) followed by diverticular disease (14.9%). Inflammatory bowel disease was recorded in 13.9% and carcinoma in 3.8%.

C

Bradshaw 2003

IV

UK N = 176 A prospective study of individuals seeking counselling about their family history of colorectal cancer.

Following pedigree tracing, verification, and risk assignment by genetic counsellors, colonoscopy was undertaken for those at a moderate or high risk of hereditary non-polyposis colorectal cancer.

Those classified as low risk were reassured and discharged without surveillance.

Asymptomatic individuals with first degree relatives affected with colorectal cancer at a young age, or more than one relative affected by do not fulfil the Amsterdam criteria for hereditary non-polyposis colorectal cancer were enrolled as participants.

Fifty-three individuals had a family history that met Amsterdam criteria (median age 43 years) and 123 individuals were classed as moderate risk (median age 43 years).

No cancers were detected at colonoscopy in any group.

Four individuals (8% (95% CI 0.4 -15%)) in the high risk group had an adenoma detected at a median age of 46 years. All were less than 50 years of age.

Five (4% (95% CI 0.6 - 8%)) of the moderate risk individuals had an adenoma at a median age of 54 years, two of whom were less than 50 years of age.

C

Cottet 2007

III-3

France N = 475 A case-control study performed in 18 endoscopic units of non-university hospitals.

A colonoscopy was offered to first-degree relatives of index cases with adenomas ≥10 mm if they were alive, aged 40 to 75 years and could be contacted by the index case.

The prevalence of large adenomas and cancers was 8.4% and 4.2%, in cases and controls, respectively.

Odds ratios (OR) associated with a history of large adenomas in relatives were 2.27 (95% CI 1.01-5.09) for cancers or large adenomas, 1.21 (95% CI 0.68-2.15) for small adenomas and 1.56

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Subjects were examined and matched for age, sex, and geographical area with two controls each.

Controls were randomly selected from 1,362 consecutive patients aged 40 to 75 years having undergone a colonoscopy for minor symptoms.

(95% CI 0.96-2.53) for all colorectal neoplasia.

The risk of large adenomas and cancers was higher in relatives of index cases younger than 60 years (OR 3.82; 95% CI 0.92-15.87) and when the index case had large distal adenomas (OR 3.14; 95% CI 1.27-7.73).

Dowling 2000

IV

Australia N = 232 A prospective audit of the outcome of screening colonoscopy was performed on a cohort of people with a strong family history of common colorectal cancer. All were registrants in a familial bowel cancer service solely because of their family medical history. They had no bowel symptoms and no prior endoscopic investigation of the large bowel.

Neoplastic lesions were detected at colonoscopy in 33 participants.

In 27 participants the major lesion was a small tubular adenoma; 4 had an advanced adenoma and 2 had cancer.

More neoplastic (p=0.02) and advanced neoplastic (p=0.03) lesions were found in those patients aged ≥50 years.

One advanced adenoma was detected in a participant < 50 years.

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Gilbert 2001

III-2

UK N = 212 Colonoscopy was performed in patients with one or more relatives with colorectal cancer; 212 were asymptomatic and 237 were symptomatic.

Colonoscopy commenced at 40 years of age or 10 years younger than the youngest affected relative.

Neoplastic change (benign and malignant) was found in 25.5% of the asymptomatic group and 24% of the symptomatic group; in 26% of those with one first degree relative, 39% with two or more first degree relatives and only 19% with second degree relatives.

A total of 38% of lesions were out of reach of a flexible sigmoidoscope.

No known complications of colonoscopy occurred in participants.

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Keren 2008

IV

Israel N = 22,341

Retrospective review of procedural data from colonoscopies conducted in ‘usual’ clinical practice over a 6 year period.

Procedural data were obtained from all consecutive patients who underwent colonoscopies in a single colonoscopy facility.

Indications were compared with American Society for Gastrointestinal Endoscopy guidelines.

Indications for colonoscopy were divided into 3 groups: screening (21.9% of the procedures), surveillance (17.6%) and symptoms/signs (60.5%).

A total of 2,867 patients (12.8%) had significant colonic neoplasia.

Significant colonic neoplasia occurred in 12.7% of the symptom/sign group (7.2% and 14.0% in the under 50 and over 50, age groups, respectively); screening 13.4% (5.5% and 15.1%, respectively); surveillance 12.6% (8.5% and 13.2%, respectively).

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Country Sample size


Among patients who had colonoscopy to investigate symptoms / signs, significant colonic neoplasia was identified in 9% of patients with irritable bowel syndrome, 11% of patients with hematochezia; 13% of patients with anaemia; 22% of patients with unexplained weight loss, 32% of patients with abnormal imaging; 14% of patients with inflammatory bowel disease, 31% of patients with elevated CEA and 30% of patients with rectal pain.

Lee 2002

IV

Hong Kong N = 869 The records of patients undergoing elective colonoscopy within an 18-month period at a single hospital were reviewed retrospectively.

Exclusion criteria included a personal history of colorectal malignancy or polyps, tumours or polyps detectable on rectal examination or rigid sigmoidoscopy, a positive physical examination suggestive of gastrointestinal malignancies, anaemia or positive faecal occult blood.

Per rectal bleeding was the most common indication for colonoscopy.

Complete colonoscopy rate was 93.7% and abnormalities were reported in 338 patients.

Forty-three patients (4.9%) were found to have cancer whereby age, duration of symptoms, blood mixed with stool and abdominal pain were identified as independent predictive factors.

Neoplastic polyps were confirmed in 200 patients (23%). Older age and being male were factors predictive of neoplastic polyps.

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Loffeld 2005

IV

The Netherlands

N = 10,836

Retrospective study. Patient records for all consecutive endoscopies performed over an 11-year period were analysed.

A standardized endoscopy data extraction tool was used.

Patients receiving follow-up after index colonoscopy were excluded.

Cancer was diagnosed in 4% to 6% of cases, inflammation in 9 to 15%, polyps in 9 to 16%, and diverticular disease in 21 to 37%.

The percentage of women undergoing the procedure each year ranged from 54% to 59%, that of men from 41% to 46%.

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Menges 2006

III-3

Germany N = 448 Patients with colorectal cancer were identified via a regional cancer registry, and their 40- to 50-year-old first-degree relatives (risk group) were invited for screening colonoscopy. Additional first-degree relatives and controls of the same age were recruited by newspaper articles and radio or television broadcastings.

Of 228 subjects in the risk group 36.4% had polypoid lesions compared to 20.9% of 220 controls (p<0.001).

Forty-three (18.9%) subjects in the risk group had adenomas compared to 18 (8.2%) in the control group (p=0.001).

High-risk adenomas (>10 mm and/or of villous type) were found in 12 persons in the risk group compared to 5 controls (not

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Country Sample size


Using high-resolution video colonoscopy, each detected polyp was removed and histopathologically assessed.

Each participant completed demographic and epidemiological questionnaires.

significant).

In the risk group most lesions (52%) were located proximal to the sigmoid colon compared to 29% in controls.

Park 2006

IV

Korea N = 17,307

A prospective multicentre study conducted in patients referred for colonoscopy.

Patients were enrolled between 2003 and 2004 from 11 tertiary medical centres and recruited according to 11 itemized colonoscopic indications.

Advanced colorectal neoplasia was found in 1,227/17,307 patients (1,176 (6.8%) advanced adenomas plus 51 (0.3%) carcinomas, 7.1%).

According to univariate and multivariate analysis, the factors associated with advanced colorectal neoplasia included age >60 years (OR 2.1; 95% CI 1.8 - 2.4), male gender (OR 2.1; 95% CI 1.7 - 2.7) and referral for colonoscopy from primary care physician (OR 3.1; 95% CI 2.5 - 3.7).

The yield of colonoscopy for advanced colorectal neoplasia was lower (2.2%) than expected in patients with iron-deficiency anaemia (OR 0.5; 95% CI 0.2 - 0.9).

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Smith 1999

IV

UK N = 2,198

A review of patient records of all colonoscopies performed by or under the supervision of a single endoscopist between 1990 and 1998.

Follow-up and outcome of all patients with early colorectal cancer was undertaken.

Ninety-five invasive colorectal cancers were identified from 2,198 colonoscopies (4.3%).

Eighteen were early colorectal cancers (0.8%). Macroscopically these were flat (9), villous (4) and pedunculated (5).

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Syrigos 2002

IV

UK N = 249 Retrospective analysis of administrative dataset. Analysis of findings from colonoscopies performed in asymptomatic individuals who had one or two first-degree relatives with colorectal cancer; individuals with three or more first-degree relatives with colorectal cancer were excluded.

Eighty-six colonic lesions were found in 51 individuals (51 of 249; 20.5%).

Among these 51 subjects, 27 had neoplastic polyps (10.8%) and 29 had metaplastic polyps (11.6%).

No invasive cancer was detected.

There were no statistically significant differences in the incidence of neoplastic polyps according to the number of affected first-

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Country Sample size


degree relatives.

Terhaar Sive Droste 2009

IV

The Netherlands

N = 4,623

A prospective multicenter colonoscopy survey of 18 hospitals.

Data of all colonoscopies performed during a three month period in 2005 were analysed.

The location and the histological features of all colonic neoplasms were recorded.

The prevalence and the distribution of advanced colorectal neoplasia and differences in yield between indication clusters were evaluated.

Advanced neoplasm was defined as adenoma > 10 mm in size, with > 25% villous features or with high-grade dysplasia or cancer.

A total of 90% of patients who underwent a total colonoscopy were symptomatic of colorectal disease.

The prevalence of advanced neoplasia was 13%, with 281 (6%) adenocarcinomas and 342 (7%) advanced adenomas; 67% and 33% of advanced neoplasia were located in the distal and proximal colon respectively.

B

164


Review Question 2d: What is the relationship between appropriateness criteria for colonoscopy and diagnostic yield?Study ID and Level of Evidence

Country Sample size


Adler 2007

III-2

Germany N = 605 A prospective cohort study conducted in 39 private-practice offices to collect data on consecutive colonoscopies performed during a 6-day study period.

A detailed questionnaire was developed to define indications and symptoms, and all findings at colonoscopy were recorded.

Colonoscopies were further analysed and stratified into a screening and a diagnostic group. In the diagnostic group, indications were assessed according to the current guidelines for appropriateness (American Society for Gastrointestinal Endoscopy (ASGE), European Panel for the Appropriateness of Gastrointestinal Endoscopy (EPAGE), and the results were correlated with the percentage of relevant findings.

During the study period, 1,397 colonoscopies (57 % screening, 43 % diagnostic) were analysed (male/female ratio = 39/61 %; mean age = 61 years).

There were 14% and 37% respectively of the 605 diagnostic colonoscopies that were coded as inappropriate relative to the criteria of the American Society for Gastrointestinal Endoscopy and the European Panel for the Appropriateness of Gastrointestinal Endoscopy.

Relevant findings were identified in between 14% (ASGE) and 18% (EPAGE) of ‘inappropriate’ colonoscopies (relevant findings were defined as cancer, polyps > 5 mm, inflammatory bowel disease, other inflammatory conditions, and benign stenoses).

Tumours were identified in between 7% (ASGE) and 12% (EPAGE) of ‘inappropriate’ colonoscopies (tumour findings were defined as cancer or polyps > 5 mm).

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Balaguer 2005

III-2

Spain N = 312 All consecutive patients referred for open-access colonoscopy in a single endoscopy unit were considered for inclusion in this prospective study.

Appropriateness of each colonoscopy was established according to the EPAGE criteria. In order to evaluate whether appropriateness of use correlated with the diagnostic yield of colonoscopy, relevant endoscopic findings were also recorded.

Open access colonoscopies for diagnostic purposes (72%), surveillance (21%) and colorectal cancer screening (7%) and assessed against EPAGE criteria.

The indication for the procedure was considered inappropriate in 73 (23%) patients.

Both referring doctor characteristics (specialty and health care setting) and patient data (age) correlated with appropriateness of endoscopy.

The diagnostic yield was significantly higher for appropriate colonoscopies (42%) than in those judged inappropriate

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Country Sample size


(21%) (p = 0.001).

Bersani 2005

III-2

Italy N = 2,221

In a cohort of consecutive patients referred for colonoscopy, the proportion of patients who underwent colonoscopy for appropriate indications was prospectively assessed.

The relationship between appropriateness and the presence of clinically relevant endoscopic diagnoses was assessed by calculating (1) the positive and negative likelihood ratio of the indications; and (2) the change in the probability of relevant endoscopic diagnoses in the presence of the ASGE criteria.

The rate for 'generally not indicated' colonoscopies was 37%.

Relevant endoscopic diagnoses were present in 28.5% of cases with ASGE indications versus 20.1% of patients without appropriate indications.

The risk of finding relevant diagnoses was significantly increased by ASGE criteria application (OR 1.58; 99% CI 1.20-2.07).

Positive and negative likelihood ratios did not vary significantly between appropriate and inappropriate indications.

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Chan 2006

IV

Malaysia N = 380 A prospective cross-sectional study of consecutive colonoscopies performed in a single open-access service.

Referrals were from endoscopists (gastroenterologists and surgeon-endoscopists), primary care physicians and other specialists.

The indication of a procedure referral was recorded and judged 'appropriate' or 'inappropriate' using the ASGE criteria.

The colonoscopic findings were recorded and classified as positive (endoscopies showing any pathology that had direct therapeutic or prognostic consequences) or negative findings (endoscopies showing no pathology or minor pathologies).

Of patients referred for colonoscopy, 220 (57.9%) were classified as appropriate according to the ASGE guidelines, and 49 (12.9%) as inappropriate. The remaining 111 patients (29.2%) presented with complaints and conditions that could not be categorised.

The rate of appropriate referral was similar for all three categories of physician (endoscopists: 59.8%, primary care physicians: 48.1%, others: 51.1%).

The most common appropriate indications were unexplained rectal bleeding (79 cases, 20.8%) and colorectal cancer surveillance (45 cases, 11.8%). The most common inappropriate indication was inappropriately timed colorectal cancer surveillance (32 cases, 8.4%). Chronic constipation in 36 cases (9.5%) was the most common 'unlisted' indication.

A positive colonoscopic finding was detected in 131 (34.5%) examinations and colorectal cancer was found in 36 patients

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Country Sample size


(9.5%).

Appropriateness of indication was not a predictive factor for positive findings or colorectal cancer and there was no difference in the proportion of cases with positive findings or colorectal cancer in the three 'appropriateness categories'.

De Bosset 2002

III-2

Switzerland N = 1,144

Consecutive patients referred for diagnostic colonoscopy at five centres and prospectively studied over a 17-month period.

The appropriateness of the indications for colonoscopy was assessed using criteria developed by the Rand Corporation/University of California at Los Angeles (RAND/UCLA) panel method, and the relationship between appropriateness of use and the presence of clinically relevant endoscopic lesions was analysed.

In total, 64.1% of the colonoscopies were judged appropriate, 13.3% uncertain and 22.6% inappropriate.

Significant endoscopic lesions were found in 23.8% of the colonoscopies.

Colonoscopies judged appropriate or uncertain yielded significantly more relevant lesions than did those judged to be inappropriate (25.6% versus 17.4%; p = 0.007).

Of 51 colon cancers, all but one were found in colonoscopies judged to be appropriate or uncertain.

In a multivariate analysis, the diagnostic yield of colonoscopy was significantly influenced by appropriateness, patient gender and treatment setting.

C

Gonvers 2007

III-2

Czech Republic, Denmark, France, Germany, UK, Italy, Poland, Spain, Sweden, Switzerland and Canada

N = 5,213

A prospective observational study that included consecutive patients referred for colonoscopy from 21 clinical centres in 11 countries.

Appropriateness of colonoscopy was assessed against EPAGE criteria. Determinants associated with a significant diagnosis were examined using multiple logistic regression.

A total of 20%, 26%, 27% and 27% of colonoscopies were judged to be ‘necessary’, ‘appropriate’, ‘uncertain’, or ‘inappropriate’ respectively.

There were 1,227 (24%) significant diagnoses made, including 218 (4%) cancers and 735 (14%) adenomatous polyps.

Among patients who had a significant diagnosis, 53% had an appropriate indication, 25% had an uncertain indication and 22% had an inappropriate indication.

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Country Sample size


Having an appropriate indication, increasing age and male sex increased the odds of finding a significant diagnosis at colonoscopy.

Grassini 2007

III-2

Italy N = 1,017

Consecutive patients (560 men and 457 women; mean age 64.4 ± 16 years) referred to an open-access endoscopy unit for colonoscopy between 2004 and 2006 were evaluated according to ASGE and Italian Society of Digestive Endoscopy (SIED) guidelines for appropriateness of colonoscopy.

Diagnostic yield was defined as the percentage of relevant colonic pathologies of the total number of colonoscopies performed.

There were 85.2% patients who underwent colonoscopy that was considered appropriate based on at least one ASGE or SIED criterion; colonoscopy was considered inappropriate for 14.8% of patients.

The diagnostic yield of colonoscopy was significantly higher for appropriate colonoscopies (26.9% ASGE versus 10.6% SIED, p < 0.001) than for inappropriate colonoscopies (5.3%).

There was no missed colorectal cancer following the ASGE/SIED criteria.

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Grassini 2008

III-2

Italy N = 1,017

A prospective study conducted in a single endoscopy unit. Consecutive outpatients were referred to an endoscopy unit by family physicians for diagnostic colonoscopy before and after an educational intervention using ASGE / SIED criteria and designed to decrease inappropriate colonoscopy referrals by family physicians.

Reduction rates, cost savings, and reduction of waiting lists were evaluated.

The post-intervention rate of inappropriate referrals was significantly lower than pre-intervention rate (p ≤0.001).

The intervention was associated with a 15% reduction in inappropriate colonoscopy referrals.

C

Hughes-Anderson 2002

III-2

Australia N = 360 Prospective data were collected and analysed from all patients undergoing upper and lower endoscopy procedures in an outreach surgical service offering open access endoscopy in rural areas between 1996 and 2000.

Indications for referral between the general practitioners and the visiting surgeons were reviewed in patient records

A total of 75% of endoscopies were booked as open access services.

A total of 90% of colonoscopies were judged ‘appropriate’, 2% were ‘inappropriate’ and 8% were for unlisted indications.

There was no difference in compliance with the ASGE

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Country Sample size


and assessed for compliance with the ASGE guidelines.

The groups were analysed for appropriateness of referrals and frequency of positive pathology investigations.

guidelines between general practitioners and surgeon referrals.

Diagnostic yield for ‘appropriate’ and ‘inappropriate’ groups was not reported.

Jabar 2004

III-2

Malaysia N = 244 A prospective 90-day audit was performed at a tertiary referral centre to examine the appropriateness of colonoscopy by indication.

Consecutive patients were included and their indications for colonoscopy were assessed against ASGE criteria.

The predominant indications for colonoscopy were altered bowel habit (37%) and rectal bleeding (18%).

A total of 84% of colonoscopies were judged to be appropriate by ASGE guidelines.

In 43% of colonoscopies there were positive findings. Diagnostic yield was 48% in ‘appropriate’ and 20% in ‘inappropriate’ colonoscopies. Neoplasia was diagnosed in 29% of ‘appropriate’ and 10% of ‘inappropriate’ colonoscopies.

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Kmieciak 2003

III-2

France N = 406 Consecutive patients receiving colonoscopy were included in the study. The referral indication was judged for appropriateness using a scoring system on the basis of the EPAGE criteria.

Appropriateness was able to be assessed in 94% of the colonoscopies.

A total of 54% were judged appropriate, 40% equivocal, and 6% inappropriate.

Rate of abnormal colonoscopy was not different between the 3 groups; diagnostic yield was 46% in ‘appropriate’ and 48% in ‘inappropriate’ colonoscopies.

In the appropriate group, adenomatous polyps were more frequent (24%) than in the two other groups (13% and 12%; p < 0.05) and tended to be larger in size. In the inappropriate group, patients were significantly younger and no cancer was found.

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Country Sample size


There were 5 colonic cancers in the inappropriate group and 12 in the appropriate group.

Morini 2001

III-2

Italy N = 1,123

Consecutive patients referred for open-access colonoscopy were prospectively enrolled in the study.

The ASGE guidelines were used to assess the relationship between the appropriate use of colonoscopy and the presence of relevant endoscopic findings.

The rate of colonoscopies "generally not indicated" according to ASGE guidelines was 29% (39% for primary care physicians and 23% for specialists; p < 0.0001).

A relevant endoscopic finding was detected in 338 examinations (35%).

The diagnostic yield was significantly higher for "generally indicated" colonoscopies (43%) compared with "generally not indicated" procedures (16%) (p < 0.001).

C

Siddique 2005

III-2

Kuwait N = 736 Consecutive patients (415 males, 321 females; mean age 43.6±16.6 years) undergoing colonoscopy between 2001 and 2002 were prospectively enrolled in the study.

ASGE guidelines were used to assess the appropriateness of the indications for the procedure.

Diagnostic yield was defined as the ratio between significant findings detected on colonoscopy and the total number of procedures performed for that indication.

A total of 64% of patients had colonoscopy that was "generally indicated", 20% had "generally not indicated" colonoscopy and 16% had colonoscopy for an indication that was "not listed".

The diagnostic yield of colonoscopy was highest for the "generally indicated" (38%) followed by "not listed" (13%) and "generally not indicated" (5%) categories.

In the multivariable analysis, the diagnostic yield was independently associated with the appropriateness of indication that was "generally indicated" (odds ratio=12.3).

C

Suriani 2009

III-2

Italy N = 677 Consecutive colonoscopies performed over an 11-month period in a digestive endoscopy unit with an open access system were appraised.

The rate of 'generally indicated' colonoscopy was 77% and 'generally not indicated' colonoscopy was 18%. The rate of indication not listed in the ASGE guidelines was 5%.

Cancer and polyps > 5mm were found in 7.3% and in 21.3% respectively of patients with appropriate colonoscopy indications.

Cancer and polyps > 5 mm were detected in 0.8% and 12%

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Country Sample size


respectively of patients with ‘generally not indicated’ colonoscopy.

Polyps > 5 mm were found in 12% of patients receiving colonoscopy for an indication not listed in ASGE guidelines; no cancer was detected in the ‘not listed’ group.

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Review Question 3a: How do safety and quality outcomes of colonoscopy vary according to the procedural volumes of colonoscopists?Study ID and Level of Evidence

Country Sample size Methods Key findings Quality score

Ko 2010

IV

US N = 328,167 colonoscopies

A retrospective cross-sectional study using an administrative database of reimbursement claims.

Primary outcome measures were use of diagnostic biopsy, polyp detection, and polyp removal.

Generalized estimating equations were used to identify independent predictors of the outcomes, adjusting for patient and provider characteristics.

A total of 24% of providers performed ≤ 33 colonoscopies, 25% performed 34 to 55 colonoscopies, 25% performed 58 to 82 colonoscopies and 26% performed 83 to 367 colonoscopies annually.

Polyp detection and removal rates were significantly lower for non-gastroenterologists than gastroenterologists, with adjusted relative risk for polyp detection between 0.80 (95% CI 0.77-0.83) for general surgeons and 0.93 (95% CI 0.89-0.98) for internists.

Compared with gastroenterologists, diagnostic biopsy was significantly less likely for general (RR 0.69; 95% CI 0.65-0.74) or colorectal surgeons (RR 0.58; 95% CI 0.52-0.65).

The likelihood of polyp detection and removal was higher for physicians in the middle 2 quartiles of annual colonoscopy volume, but similar for physicians in the highest and lowest volume quartiles.

Polyp detection and removal were significantly less likely for examinations in ambulatory surgery centres or offices than hospital outpatient settings, while diagnostic biopsy was significantly less likely in office settings.

C

Lorenzo-Zuniga 2010

IV

Spain N = 25,214 colonoscopies

All colonoscopies performed between 1995 and 2008 in a single institution were reviewed. Demographic data, endoscopic procedure information, incidence of colonic perforation and post-polypectomy bleeding and endoscopist experience were recorded.

In the 14-year period there were 5 providers who performed 76 to 591 procedures a year (low volume), 3 who performed 592 to 1300 procedures a year (medium volume) and 2 who performed 1301 to 1824 procedures a year (high volume).

The overall colonic perforation risk was 0.51/1000 procedures; and post-polypectomy bleeding was 14.7/1000 procedures.

The relative risk (RR) of complications was 2.8/1000 procedures. Risk of complications increased from 0.2% in high volume proceduralists to 0.4% in low volume proceduralists. The RR was

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highest for endoscopists performing less than 591 procedures per year (4.0/1000 [95% CI 3.7-4.3] versus 2.9/1000 [95% CI 2.6-3.2]).

Post-polypectomy bleeding and colonic perforations were 1.6 times more likely to occur with colonoscopies performed by low volume proceduralists.

Rabeneck 2008

IV

Canada N = 97,091 colonoscopies

Individuals 50 to 75 years old who underwent an outpatient colonoscopy between 2002 and 2003 were included in the study population.

Using administrative data, all individuals who were admitted to hospital with bleeding or perforation within 30 days following the colonoscopy were identified.

Pooled rates of bleeding and perforation were calculated. Generalized estimating equations were used to evaluate factors associated with bleeding and perforation.

A total of 20% of providers performed 1 to 141 procedures, 20% performed 142 to 209 procedures, 20% performed 210 to 283 procedures, 20% performed 284 to 378 procedures and 20% performed 379 to 1,225 procedures annually.

The pooled rates of colonoscopy-related bleeding and perforation were 1.64/1000 and 0.85/1000 respectively. The death rate was 0.074/1000 or approximately 1/14,000.

Older age, male sex, having a polypectomy, and having the colonoscopy performed by a low-volume endoscopist were associated with increased odds of bleeding or perforation.

Compared with the highest volume quintile, patients who had their colonoscopies performed by endoscopists in the lowest volume quintile had a 3-fold higher risk of bleeding or perforation.

C

Rabeneck 2010

IV

Canada N = 110,402 patients

A cohort of patients aged 50 to 80 years who had a negative complete colonoscopy between 1992 and 1997 was identified by using linked administrative databases.

Cohort members had no history of colorectal cancer or inflammatory bowel disease or a recent colonic resection. Each individual was followed and those with a new diagnosis of colorectal cancer were identified.

Multivariable analysis was used to evaluate the

A total of 20% of providers performed 1 to 154 procedures, 20% performed 155 to 256 procedures, 20% performed 257 to 370 procedures, 20% performed 371 to 507 and 20% performed 508 to 1,102 procedures annually.

There was no association between endoscopist colonoscopy volume and incident colorectal cancer.

Compared with the highest volume quintile, patients who had their colonoscopies performed by endoscopists in the lowest volume quintile had a 1.6-fold higher odds of developing colorectal cancer

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association of patient, endoscopist, and procedure setting characteristics with incident colorectal cancer.

within 10 years of a negative colonoscopy.

Wexner 2001

III-2

US N = 13,580 colonoscopies

A prospective study of efficacy and safety endpoints of colonoscopy.

Members of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) prospectively entered data into a common database.

In total, 22% of providers performed < 10 procedures, 37% performed 10 to 49 procedures, 19% performed 50 to 99 procedures and 22% performed 100 or more colonoscopy procedures annually.

Rate of complications ranged between 0.12% and 0.29%. There was no relationship between annual number of colonoscopies performed and rate of complications.

Completion rate and time to completion improved as annual colonoscopies performed increased from – 73% and 30 minutes for proceduralists who performed < 10 colonoscopies a year to 97% and 16 minutes in those who performed > 500 colonoscopies a year.

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174


Review Question 4: How cost-effective is colonoscopy in each target population?Study ID and Level of Evidence

Country Purpose Methods Key findings

Hassan 2008

Italy To assess the clinical and economic impact of American Society for Gastrointestinal Endoscopy and the European Panel on the appropriateness of Gastrointestinal Endoscopy appropriateness guidelines in selecting patients who are referred for colonoscopy, in relation to colorectal cancer detection

Decision analysis model. The number of colonoscopies needed to detect one case of cancer and to prevent one cancer-related death and incremental cost-effectiveness ratios (ICER), according to appropriateness categories, were computed in a simulated population of patients that were 60 years of age and referred for colonoscopy

The numbers of appropriate and inappropriate colonoscopies that needed to be performed to detect one patient with cancer were 18 and 93 respectively. 115 and 617 colonoscopies would be needed to prevent one colorectal cancer-related death. The ICER for appropriate and inappropriate colonoscopies was $6,154 and $31,807 per life-year gained respectively.

Hassan 2009

Italy To assess the clinical and economic impact of early surveillance colonoscopy one year after polypectomy in relation to detection of colorectal cancer

Decision analysis model. Comparison of strategies of performing or not performing one-year endoscopic surveillance in 60-year-old patients who underwent an initial endoscopic polypectomy.

The number of early one-year colonoscopies needed to detect one cancer and to prevent one cancer-related death was 354 and 1,437, respectively. The incremental cost-effectiveness ratio of performing early one-year colonoscopy as compared with not performing it was $66,136 per life-year gained.

Hassan 2009

Italy To assess the clinical and economic impact of early surveillance post-surgical colonoscopy at 1 year in relation to the detection of metachronous colorectal cancer

Decision analysis model. Comparison of strategies of 1-year endoscopic surveillance versus no early endoscopy following surgical resection for colorectal cancer. A 2-year cancer upstaging was modelled in order to simulate cancer progression in patients with metachronous colorectal cancer who were not referred to early endoscopy.

The number of early 1-year colonoscopies needed to detect one colorectal cancer and to prevent one colorectal cancer-related death was 143 and 926, respectively. The incremental cost-effectiveness ratio of the early 1-year colonoscopy as compared to a policy of not performing it was $40,313 per life-year gained.

Henry 2007 US To determine the direct health care costs, direct non-health care costs and costs related to patients' time associated with colonoscopy.

Micro-costing and time-and-motion study with 276 participants who had undergone colonoscopy.

The median direct health care cost, median direct non-health care and patient time costs were $379, $226 and $274 respectively. The median total societal cost of colonoscopy was $923.

Korner 2005

Norway To determine the relative costs associated with different methods of follow-up of patients post curative colorectal cancer resection.

314 consecutive patients undergoing curative surgery for colorectal cancer were studied with regard to cost of follow-up modalities.

The median cost of colonoscopy performed 5 years after surgery was $214. 27 colonoscopies (range 8 to 143 colonoscopies) needed to be performed to detect

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Country Purpose Methods Key findings

one patient with curable disease.

Menges 2006

Germany Detailed cost-benefit analysis of index and repeat endoscopies

Screening colonoscopy in 45- to 55-year-old first-degree relatives of patients with colorectal cancer

Estimate of (euro) 20,000 for diagnosis and treatment of one cancer case when participation is high. Estimate of (euro)40,000 per cancer case for ‘usual’ participation rates

Saini 2010 US To estimate the cost-effectiveness of periodic surveillance colonoscopy in patients with colonic adenomas

Markov model. A cohort of 50-year-old patients with newly diagnosed adenomas, followed until death was modelled. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated

Colonoscopy every 3 years in high-risk patients and every 10 years in low-risk patients (3/10 strategy) was more costly but also more effective than no surveillance (ICER of $5,743 per QALY gained). In comparison a 3/5 strategy was more costly but only marginally more effective (ICER of $296,266 per QALY).

176


Review Question 5a: Are all patient groups in whom colonoscopy should be used able to access colonoscopy?


Country Sample size


Bernstein 2001

IV

Canada N = 14 studies

Systematic literature review describing the relationship between inflammatory bowel disease and employment, income, disability, education and marital status.

Patients with inflammatory bowel disease are generally of higher socioeconomic status and have reached higher levels of education.

Results of the author’s analysis of administrative data demonstrated that patients were more likely to be unemployed than the general population and were not of higher socioeconomic status, in contrast to other published studies.

C

Holden 2010

I

US N = 21 studies

Systematic review of studies assessing access to colonoscopy for colorectal cancer screening.

People without health insurance, people with no source of usual care, people with no recent physician visits, and people with lower income status have low colorectal cancer screening rates.

A

Rulyak 2004

IV

US N = 1,002 patients

An organisational administrative database of patients with colorectal cancer who underwent surgical resection was analysed.






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177


Review Question 5b: What is the evidence for interventions that improve access to colonoscopy services?Study ID and Level of Evidence

Country Sample size


Chivers 2010

IV

UK N = 3,020

A quantitative five-stage clinical audit cycle involving a large patient cohort which included seven hospitals across four geographical areas.

Participants were consecutive patients waiting for a surveillance colonoscopy. Their notes were reviewed and the indications for colonoscopy were compared with the Association of Coloproctology of Great Britain and Ireland (ACPGBI) /British Society of Gastroenterology (BSG) guidelines.

Those patients whose referral to the surveillance colonoscopy waiting list was not found to be compliant were adjusted to be in line with the guidelines.

Main outcome measures were the impact of adjusting the surveillance colonoscopy waiting list on the diagnostic colonoscopy service, assessed by measuring the average waiting times for a colonoscopy before and after the intervention.

A total of 22% (n = 664) of surveillance colonoscopy referrals were in line with the guidelines, 51% (n = 1,540) could be cancelled from the list and 27% (n = 816) could be given a new date for colonoscopy.

Implementing the recommendations reduced the average wait for a diagnostic colonoscopy from 76.8 to 56.0 days (p<0.01).

N/A

Christie 2008

II

US N = 21 A prospective, randomized trial to determine whether a patient navigator (PN) can help overcome the organizational barriers to colonoscopy experienced by patients in low-income minority groups.

Patients of average risk for colorectal cancer were referred by their primary care physician for screening colonoscopy.

After the PN received the referral, patients were randomly assigned to either receive navigation (PN+) to screening colonoscopy or not receive navigation (PN-).

A total of 54% of navigated patients completed screening colonoscopy versus 13% of non-navigated patients (p=0.058).

One-hundred percent of navigated patients were very satisfied with navigation services.

C

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Review Question 5c: What is the impact of open access service configuration on access to colonoscopy services?Study ID and Level of Evidence

Country Sample size


Hughes-Anderson 2002

III-2

Australia N = 360 Prospective data were collected and analysed from all patients undergoing upper and lower endoscopy procedures in an outreach surgical service offering open access endoscopy in rural areas between 1996 and 2000.

Indications for referral between the general practitioners and the visiting surgeons were reviewed in patient records and assessed for compliance with the ASGE guidelines.

The groups were analysed for appropriateness of referrals and frequency of positive pathology investigations.

A total of 75% of endoscopies were booked as open access services.

A total of 90% of colonoscopies were judged ‘appropriate’, 2% were ‘inappropriate’ and 8% were for unlisted indications.

There was no difference in compliance with the ASGE guidelines between general practitioners and surgeon referrals.

Diagnostic yield for ‘appropriate’ and ‘inappropriate’ groups was not reported.

C

MacKenzie 2003

II

UK N = 1,131

Over 21 months, patients with large bowel symptoms referred by their general practitioner to an open access endoscopy service were randomised to proceed directly to colonoscopy or to be assess prior to colonoscopy by a consultant endoscopist who was a surgeon with a colorectal interest.

Assessment of utilisation and rate of unnecessary procedures by patients accessing colonoscopy via open access versus those attending a specialist outpatient-clinic was compared.

The most common symptom among referred patients was rectal bleeding (69.1%) followed by change in bowel habit (48.8%) and abdominal pain (32.3%).

The percentage of patients with colonic or other pathology diagnosed was the same in both groups, 63.6 per cent in the consultant-led group compared with 61.8 per cent in the open access group (p = 0.558).

Likewise the percentage of patients with cancer or other significant pathology was similar in both groups (13.9 versus 15.4 per cent; p = 0.532).

The mean (SD) time to diagnose cancer or other significant pathology was 55.1 (39.2) days in the consultant-led group compared with 57.4 (33.6) days in the open access group (p = 0.514).

C

Maruthachalam 2005

UK N = 639 Data were collected prospectively on patients who were referred for direct access colonoscopy or outpatient appointments at the discretion of the referring general

There were 188 patients who underwent colonoscopy at their initial hospital visit and 19 (10.1%) colorectal cancers were diagnosed; 442 patients had an outpatient appointment and 32

C

179



Country Sample size


III-2 practitioner.

A postal questionnaire was used to survey patient satisfaction.

(7.2%) colorectal cancers were diagnosed.

All outcome parameters measured were reduced for patients referred directly for colonoscopy including time to definitive investigations (Median 9 versus 52 days p < 0.0001), time to histological diagnosis (Median 14 versus 42 days p < 0.0001) and time to treatment (Median 55 versus 75 days p < 0.0483).

One hundred and seventy patients were surveyed by the postal questionnaire of whom 127 (75%) responded.

Ninety-eight percent of patients were satisfied with the service provided. Four (6.6%) of 60 patients who had undergone direct access colonoscopy expressed a desire to be seen at the outpatient department initially.

180

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