crc lecture 2011
TRANSCRIPT
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Surgery of Colorectal Cancer
By
Professor Ahmed Hussein
Chairman of Unit of Colon and Rectal SurgeryUniversity of Alexandria
Incidence
In Egypt, colorectal cancer is the fourth most commonly diagnosed cancer in both men
and women.
World Age-adjusted Incidence Rates by GenderMales Females M/F Ratio
World 20.1 14.6 1.2
More Developed Countries 40.0 26.6 1.2Less Developed Countries 10.2 7.7 1.2
Incidence Rates/100,000
The Incidence of CRC in Egypt
EgyptianNew CRC
CasesIncidence/100,000
MedianAge
M/FRatio
Number ofDeaths
Males 2263 6.3 48.0 1.1 1426
Females 2057 5.3 48.8 1.0 1295
Total 4320 5.8 48.4 1.1 2721
Middle East Cancer Consortium (MECC), Egypt
Risk Factors for Colorectal Cancer:
1. Hereditary CRC Syndromesa. Adenomatous polyposis syndromes
i. Familial adenoamtous polyposis (FAP)ii. MYH-associated polyposis (MAP)
b. Nonpolyposis syndrome
i. Hereditary nonpolyposis CRC (HNPCC)c. Hamartomatous polyp syndromes
i. Peutz-Jeghers syndrome (PJS)ii. Juvenile polyposis syndrome (JPS)
iii. Cowden disease (Bannayan-Ruvalcaba-Riley)2. Inflammatory Bowel Disease: Ulcerative Colitis3. Personal History of CRC4. Family History of CRC5. Ethnic background: Ashkenazi Jews6. Age: above 50 years in the western community.
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a. In Egypt the median age of CRC less than 50 yearsEnvironmental Factors
Increased risk of CRC with a diet high in:
1. Red meat and animal fat
2. Low-fiber diet: low overall intake of fruits and vegetables
Lifestyle choices that are associated with increased risk for CRC:
1. Alcohol and tobacco consumption
2. Obesity
3. Sedentary habits
Factors associated with lower risk include:
1. Folate intake
2. Calcium intake
3. Estrogen replacement therapy
Genetics of Colorectal Cancer
Genetics does not mean inherited, genetics means pathogenesis. Genetically, colorectal
cancer represents a complex disease, and accumulation of genetic alterations is associated
with progression from normal epithelial cells or premalignant lesion (adenoma) to
invasive adenocarcinoma. Colorectal cancers have several gene expression profiles with
different pathogenic (genetic) pathways.
Types of Colorectal Cancer
Type %Sporadic 75%
Family History of CRC 18%HNPCC 5%
FAP 1%
MAP 1%PJS & JP
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Pathway I CIN (Chromosomal Instability)
Acquired (somatic) or inherited (germline) macrogenetic alterations at chromosomal
level either in the form of abnormal number (aneuploidy) or gross changes i.e. loss of
heterozygosity (LOH).
The important genes involved in these chromosome losses are APC (5q), DCC (18q), and
TP53 (17p).
This pathway is seen in Familial Adenomatous Polyposis (FAP) and adenoma-carcinoma
model.
Pathway II Microsatellite Instability (MSI) Mismatch Repair Pathway (MMR)
Germline or somatic microgenetic (intragenic) mutations of DNA damage-repair genes
result in Microsatellite Instability (MSI) i.e. insertion or deletion of nucleotides in one ormore alleles. MSI means alterations in repeating units of DNA that occur normally
throughout the genome.
The important genes involved in this MSI are MMR genes (hMSH2, hMSH6, hMLH1,
hMLH3, hPMS1, hPMS2)
This pathway is seen in 95% of HNPCC and 18% of sporadic colorectal cancer.
Alternative Pathways
1. Flat & depressed adenoma2. De Novo CRC
3. Colitis induced CRC
4. Serrated Pathway
Alternative pathways are involved in up to 30% of CRC, precursors not easily seen with
rapid evolution following genetic instability.
Normal
Epithelium
APC
Early
Adenoma
K-ras
Intermediate
Adenoma
DCC
Late
Adenoma
p53
Cancer
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Colitis induced CRC
This pathway is seen in ulcerative colitis and schistosomiasis Japonicum. Chronic
inflammation results in free O2 radicals cause DNA damage. Dysplasia-carcinoma
model.
Serrated Pathway: CpG I sland Methylator Phenotype (CIMP)
Epigenetic factors are mechanisms outside the gene such as a cells exposure to
carcinogens or hormones, or genetic variations that modify a gene or its protein by
methylation, demethylation, phosphorylation, or dephosphorylation. Genes that must be
expressed in all tissues have unmethylated regions, called CpG islands. On the other
hand, genes that must be turned off in differentiated tissues have these islands
methylated.
In this pathway type C tumor suppressor genes silenced by promoter region CpG
methylation.
This pathway is seen in Juvenile Polyposis, Peutz-Jeghers Syndrome and Serrated
adenomas
Normal
Epithelium
Aneuploidy
p53
IndefiniteDysplasia
p53
Low GradeDysplasia
K-ras
MSI
High GradeDysplasia
DCC
Cancer
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Clinical Picture of Colorectal Cancer
1. Asymptomatic by screening program
2. Primary Lesion
3. Metastases
4. Complications
Screening for Colorectal Cancer
Life-Time Risk of CRC
Group Life Time Risk of CRCGeneral Population 5%Ashkenazi Jews 6-10%
Family History of CRC 10-15%
Personal History of CRC 15-20%IBD 15-40%
PJS 50%
JP 50%HNPCC 70-80%
FAP >95%
High Risk Group
1. 10-100% lifetime risk according to:a. Family history criteria
b. Pathological criteria
c. Pathogenic gene mutation
2. Screening Method: in Genetics Centre for formal counseling & mutation analysis
Moderate Risk Group
1. First degree relative (FDR) with CRC aged
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b. Flexible Sigmoidoscpy / 5 years
c. Colonoscopy / 10 years
Clinical Picture of Primary Colorectal Cancer
The most common presenting symptoms associated with colon cancer are abdominal
pain, followed by change in bowel habits, rectal bleeding, and occult blood in the stool.
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Cancer Right Colon
1. Change in Bowel Habits
a. Diarrhea
2. Pain
a. Vague upper abdominal
3. Iron Deficiency Anemia
4. Weight Loss
5. Mass (advanced )
6. Obstruction Rare
Cancer Left Colon
1. Change in Bowel Habitsa. Increasing Constipation
2. Pain
a. Colicky with distension
3. Weight Loss
4. Mass (advanced or fecal matter)
5. Obstruction common or 1st presentation
6. Bleeding /Rectum
7. Mucous/ Rectum
Cancer Rectum
1. Bleeding /Rectum
2. Mucous/ Rectum
3. Tensmus (Sense of incomplete evacuation)
4. Change in Bowel Habits
a. Spurious morning diarrhea
5. Pain
a. Colicky in rectosigmoid lesions
b. Severe pelvic ( advanced due to infiltration)
6. Weight Loss7. Rare Obstruction in rectosigmoid lesions
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Symptom Rt. Side Lt. Side Rectum
Change in Bowel Habits Diarrhea ConstipationConstipation
spurious morning
diarrhea
Bleeding /Rectum Altered Dark FreshColicky Pain + ++++ upper 1/3
Mass +++ ++ -
Mucous/ Rectum - + ++++Tensmus
Incomplete Evacuation- - +++++
Weight Loss +++ + ++Iron Deficiency Anemia ++++ + +
Spread of Colorectal Cancer
1. Direct spread
a. Intramural
i. Circumferential
ii. Longitudinal
b. Transmural
2. Lymphatic spread
3. Venous spread: Liver & Lung metastases
4. Transperitoneal spread
a. Malignant ascites
b. Krukenbergs tumor
Complications of Colorectal Cancer
1. Intestinal obstruction
2. Penetration (fistula)
3. Bleeding (anemia or hypovolemia)
4. Intussusception: incomplete obstruction
5. Perforation
a. Tumor perforationb. Caecal perforation caused by a left-sided colon cancer
Diagnosis
An individualized approach to the diagnosis considers:
1- The patients symptoms
2- Age
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3- Personal history of inflammatory bowel disease, colon polyps, or colorectal
cancer
4- Family history of colon cancer or predisposing genetic syndromes (e.g., familialadenomatous polyposis or hereditary nonpolyposis colorectal cancer)
Diagnostic Evaluation
1- Colonoscopy: A crucial part of this evaluation is to ensure that the patients entire
colon and rectum have been assessed with colonoscopy for the presence of
synchronous neoplasms. Colonoscopy allows biopsy and histologic confirmation
of the diagnosis. It also allows for identification and endoscopic removal of
synchronous polyps. Pre-operative histology should be done in all rectal tumors.
2- Depending on the patients age and health status, a variety of laboratory,
radiologic, and cardiorespiratory tests may be appropriate to assess the patients
operative risk.
Preoperative Assessment
1- Preoperative, carcinoembryonic antigen level:
Is beneficial for two reasons:
a. Postoperative return to normal of an elevated preoperative CEA is associated with
complete tumor resection, whereas persistently elevated values indicate the
presence of visible or occult residual disease.
b. Elevated preoperative CEA levels have been found to be an independent
prognosticator of poor outcome.
CEA has never been useful as a screening tool as it is elevated in a variety of
conditions, including colorectal cancer, proximal gastrointestinal cancers, lung and
breast cancers, benign inflammatory conditions of the gastrointestinal tract, and
smoking.
2- Preoperative CT scanning
CT scans can be used to evaluate local extension of the tumor and regionallymphadenopathy, as well as for the presence of hepatic metastases.
3- Preoperative chest x-rays or chest CT scanning: to evaluate the lungs for evidence of
metastatic disease.
4- PET CT scan is not routinely indicated.
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TNM Staging
T
Tx: Incomplete informationTis: It involves only the mucosa
T1: Extends into the submucosa
T2: Extends into the muscularis propria
T3: Extends into subserosa
T4a: Penetrates visceral peritoneum
T4b: Tumor invades other organs or structures
NNx: Incomplete information
N0: No LN involvement
N1: In 1- 3 regional LNs.
N1a: in 1 regional LNs
N1b: in 2- 3 regional LNsN1c: Tumor Deposits in subserosa, mesentry, nonperitonealized pericolic or
perirectal tissues without regional LNs metastasis
N2: In 4 or more regional LNsN2a: in 4-6 regional LNs
N2b: in 7 or more regional LNs
MM0: No distant Metastasis
M1: Distant MetastasisM1a: Metastasis confined to one organ or site (Liver, lung, ovary, non-regional LNs)
M1b: Metastasis in more than one organ/site or peritonium
5-years Survival
Stage I 92%
Stage II 73%IIA 85%
IIB 72%
Stage III 56%IIIA 83%
IIIB 64%
IIIC 44%
Stage IV 8%
TNM Dukes
Stage 0 Tis N0 M0 -
Stage I T1 N0 M0 AT2 N0 M0 A
Stage IIA T3 N0 M0 BIIB T4a N0 M0 BIIC T4b N0 M0 B
Stage IIIA T1-2 N1/N1c M0 CT1 N2a M0 C
IIIB T3-4 N1/N1c M0 C
T2-T3 N2a M0 CT1-T2 N2b M0 C
IIIC T4a N2a M0 CT3-T4a N2b M0 C
T4b N1-N2 M0 C
Stage IVA Any T Any N M1a -IVB Any T Any N M1b -
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Preparation for Operation
A. Informed Consent
All patients who are to undergo surgery for colon cancer need to be clearly informed of
the reasons for and the extent of the proposed resection, the likely outcome of the
surgery, the pertinent complications and their likelihood of occurring, expected length of
hospitalization and recovery, alternatives to the proposed surgery, and prognosis.
B. Mechanical Bowel Preparation
Mechanical bowel preparation is nearly universally used in elective surgery. Despite its
nearly universal use, the literature does not support a defined benefit for preoperative
mechanical preparation of the bowel. The persistence in using a preoperative bowel
preparation may be justified simply on the basis of the advantages it affords in ease of
handling the prepared colon, the proven safety of the methods used for bowel cleansing,
and the relatively low cost. Outpatient bowel preparation (the day before surgery) is
generally safe and cost effective.
C. Prophylactic Antibiotics
Prophylactic antibiotics have proven effectiveness in decreasing the rate of infection,
mortality, and cost of hospitalization after colonic resection. There are a wide variety of
antibiotic regimens that are effective. Regardless which parenteral antibiotic regimen is
selected, it is agreed that it must be given before the start of the operation to be effective.
D. Blood Cross Match and Transfusion
Blood transfusion should be based on physiologic need. The need for transfusion is
primarily based on the starting hemoglobin, the patients physiologic status, and extent of
intraoperative blood loss.
The immunosuppressive effect of transfusion is well established. Patients who receive
perioperative blood transfusions have a greater incidence of infection. However, recently
it was found that the immunosuppressive effect of transfusion does not increase the rate
of cancer recurrence. Other factors (extent of resection required, location of tumor, and
experience of surgeon) in patients requiring transfusion may actually be the cause for the
increased recurrence rate.
E. Thromboembolism Prophylaxis
All patients undergoing surgery for colon cancer should receive prophylaxis against
thromboembolic disease. Patients undergoing colon resection for cancer have a high
incidence of venous thromboembolism, including deep venous thrombosis and
pulmonary embolism.
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Operative Issues
A. Operative Technique
The extent of resection of the colon should correspond to the lymphovascular drainage of
the site of the colon cancer. The determinant of adequate bowel resection for colon
cancer is removal of the primary feeding arterial vessel and its corresponding lymphatics.
Tumors located in border zones should be resected with the neighboring lymphatic
regions to encompass both possible directions of spread. The length of bowel resected is
usually governed by the blood supply to that segment. Ligation of the origin of the
primary feeding vessel ensures the inclusion of the apical nodes, which may convey
prognostic significance for the patient. There is much concern regarding intraoperative
manipulation of the tumor with shedding of cancer cells into the portal circulation.
However, the value of the no touch technique has not been proven, although there is a
theoretic basis for its use.
Arterial Supply of the Colon and Rectum
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Site of the Lesion Operation Vessels Excised Parts
AppendixCecum
Ascending Colon
Right Hemicolectomywith ileotransverse
anastomosis
IleocolicRight Colic
Rt. branch of middle
colic
Cecum, appendix,ascending colon and
the right third of the
transverse colon
Hepatic Flexure Extended Right
Hemicolectomy
with ileotransverse
anastomosis
Ileocolic
Right Colic
Middle Colic
Cecum, appendix,
ascending colon and
the right two thirds of
the transverse colon
Transverse Colon Transverse colectomy
with anastomosis
between the ascending
and descending colons
Middle Colic Transverse colon
including both hepatic
and splenic flexures
greater omentum in
T4 lesionsSplenic Flexure Extended Left
Hemicolectomy with
anastomosis between
transverse and sigmoid
colons
Inferior Mesenteric
Left branch of the
middle colic
Descending Colon
and Left half of the
transverse colon
Descending Colon Left Hemicolectomy
with anastomosis
between transverse
and sigmoid colons or
(Rectum)
Inferior Mesenteric Descending Colon
and Left third of the
transverse colon
sigmoid colon
Sigmoid Colon Sigmoidectomy
With anastomosisbetween left colon and
upper rectum
Inferior Mesenteric Sigmoid Colon
Upper Third Rectum Tumor Specific
Mesorectal Excision
With anastomosis
between descending
colon and middle third
rectum
If the anastomosis
above the peritoneal
reflection = Anterior
ResectionIf the anastomosis
below the peritoneal
reflection = Low
Anterior Resection
Inferior Mesenteric Sigmoid Colon and
upper third Rectum
with distal safety
margin of 5 cm
Middle and lower
Third Rectum down
to > 2 cm from the
dentate line
Total Mesorectal
Excision
With anastomosis
between descending
colon and anal canal
(coloanal anastomosis)
Inferior Mesenteric
Middle Rectal
Sigmoid Colon and
total proctectomy with
distal safety margin at
least 2 cm
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= Ultra-Low Anterior
Resection
< 2 cm from the
dentate line or lesioninfiltrating the anal
sphincter or the pelvic
floor muscles
Total Mesorectal
Excision withAbdominoperineal
Excision of the
Rectum (APER) with
permanent colostomy
Inferior Mesenteric
Middle RectalInferior Rectal
Sigmoid Colon, total
proctectomy, analcanal, anal sphincters
and pelvic floor
muscles
Right Hemicolectomy
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Left Hemicolectomy
Total Colectomy & Ileorectal Anastomosis
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Sigmoid Colectomy
Sigmoid Colectomy with End colostomy and Hartmanns pouch
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Laparoscopic resection of colon cancer is feasible but requires specific surgical expertise.
Adherence to oncologic principles is possible and adequate lymphadenectomy with
disease-free margins can be achieved comparable to open surgery.
Operative IssuesEmergency
A. Obstructing Colon Cancer
a.Patients with an obstructing right or transverse colon cancer should undergo a right
or extended right colectomy. A primary ileocolic anastomosis can be performed in
the appropriate clinical setting.
b.Patient with a left-sided colonic obstruction, the procedure selected should be
individualized from a variety of appropriate operative approaches.
i.Resection with end colostomy and Hartmanns pouchii.Resection with on-table colonic lavage and primary anastomosis
iii.Subtotal colectomy with ileorectal anastomosis.
iv.Insertion of colonic Stent to relieve the acute obstruction thereby permitting
an elective colonic oral lavage, colonoscopy, and subsequent resection with
primary anastomosis.
The three-stage approach of performing proximal diversion, then resection, then
colostomy closure is generally thought to be less advantageous because of its high
mortality and morbidity rates.
B. Colonic Perforation
The site of a colonic perforation caused by colon cancer should be resected, if at all
possible.
a. Right-sided colon perforation from a right colon cancer should be resected. If
there is a free perforation with peritonitis, an anastomosis may be unwise and the
patient is probably best left with an end ileostomy. The distal end may be brought
out as a mucous fistula or stapled off as a Hartmanns pouch. Alternatively, if
there is limited fecal spillage, the surgeon may choose to reanastomose the bowel
with or without fecal diversion.
b. When a left colon cancer perforates resulting in peritonitis, a Hartmanns
resection is the indicated operation in most settings. In cases in which there is
massive proximal colonic distention and/or ischemia, a subtotal colectomy may
be the best choice. If there is a limited degree of peritoneal contamination, the
surgeon may choose to perform an ileorectal or ileosigmoid anastomosis with a
diverting loop ileostomy.
c. In the case of a right colon perforation caused by a left-sided colon cancer, most
experts advocate a subtotal colectomy. Whether an anastomosis or a loop
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ileostomy to protect the anastomosis are performed is dependent on the surgeons
judgment about the degree of contamination and the patients clinical status.
C. Massive Colonic Bleeding
Acutely bleeding colon cancers that require emergent resection should be removed
following the same principles as in elective resection. Because of the cathartic effect of
the bleeding, the bowel has been effectively cleansed of the bulk of fecal matter and a
primary anastomosis can be considered. Whether to proceed with an anastomosis or elect
to perform an end stoma and mucous fistula (or Hartmanns pouch) is based on the
surgeons judgment about the current clinical condition of the patient.
In cases in which the site of the bleeding cannot be identified, a subtotal colectomy is the
preferred procedure.
POSTOPERATIVE STAGING OF COLON CANCER
a. Colon cancers should be staged using the TNM staging system.
b. It is important that accurate pathologic evaluation of the radial margin of resection
be performed. Each operation is given a resection code to denote completeness of
resection:
R0: Complete tumor resection with all margins negative
R1: Incomplete tumor resection with microscopic involvement of the margin
R2: Incomplete tumor resection with gross residual tumor that was not resected.
c. Other factors that have an impact on the patients risk of recurrence and survival.
i. Microscopic venous or lymphatic invasion within the specimen worsen the
prognosis for every stage.
ii. Histologic grade and histologic type
iii. Serum CEA
Lymph node numbers:
To be properly evaluated, one should strive to have a minimum of 15 lymph nodes
examined microscopically.
The accuracy of colon cancer staging improves with increasing the number of lymph
nodes evaluated microscopically. Ten or more lymph nodes can be found in 98 percent of
colon specimens and 13 or more lymph nodes can be found in 91 percent of specimens
without using fat-clearing techniques.
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Adjuvant Therapy
A. Chemotherapy
Postoperative adjuvant systemic chemotherapy has a proven benefit in Stage III colon
cancer and may be beneficial in certain high risk Stage II patients.
Patients with Stage III colon cancer are recognized to be at high risk for recurrence, and
administration of 5-fluorouracil (5-FU)/leucovorin for six months postoperatively has
proven benefit in decreasing recurrence and improving survival.
Patients with Stage II colon cancer who are considered at higher risk for recurrence
include those with one or more of the following characteristics: tumor perforation,
adherence, or invasion of adjacent organs; nondiploidy by flow cytometry; poorlydifferentiated tumor; or venous, lymphatic, and perineural invasion. It may be
advantageous for these patients to receive adjuvant chemotherapy.
The oral chemotherapy agent, capecitabine:
Capecitabine is an oral fluoropyrimidine carbamate preferentially converted to 5-FU in
tumor cells.
B. Immunotherapy
The value of immunotherapy for colon cancer is undetermined. Its use is recommendedwithin the setting of a clinical trial.
C. Intraperitoneal/Intraportal Chemotherapy
Intraperitoneal and intraportal infusions of chemotherapy are recommended only in the
confines of a clinical trial.
D. Radiation Therapy
The role for radiation therapy in colon cancer is limited.
Radiation is rarely used in the treatment of colon cancer. Radiations potential for injuryto the abdominal viscera limits its usefulness.
Surveillance
1. History & Physical Examination: Every 3-6 m for 2 y then every 6 m for a total of 5 yrs
2. Serum CEA: Every 3-6 m for 2 y then every 6 m for a total of 5 yrs
3. CT scan of abdomen & pelvis: Annually for 3 years
4. Colonoscopy: At 1 year then as clinically indicated
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Rectal Cancer
Any cancer whose distal margin is 15 cm or less from the anal verge using a rigid
sigmoidoscope should be classified as rectal.
Rectal cancer comprises approximately 25 percent of the malignancies arising in the large
bowel. Anatomically, the rectum is the distal 15-cm of the large bowel leading to the anal
canal. Cancers of the intraperitoneal rectum behave like colon cancers with regard to
recurrence patterns and prognosis. By contrast, the extraperitoneal rectum resides within
the confines of the bony pelvis; it is this distal 10 to 12 cm that constitutes the rectum
from the oncologic standpoint.
Rectal Cancer is a challenging disease because:
1. Common malignancy
2. Difficult dissection
3. Treatment not infrequently entails a permanent stoma
4. Sexual and urinary morbidity
5. Local recurrence
PREOPERATIVE ASSESSMENT
An individualized approach to the diagnosis considers:
1- The patients symptoms2- Age
3- Personal history of inflammatory bowel disease, colon polyps, or colorectal
cancer
4- Family history of colon cancer or predisposing genetic syndromes (e.g., familial
adenomatous polyposis or hereditary nonpolyposis colorectal cancer)
I. DIAGNOSTIC EVALUATION
1- Colonoscopy: A crucial part of this evaluation is to ensure that the patients entire
colon and rectum have been assessed with colonoscopy for the presence ofsynchronous neoplasms. Colonoscopy allows biopsy and histologic confirmation of
the diagnosis. It also allows for identification and endoscopic removal of synchronous
polyps.
2- Depending on the patients age and health status, a variety of laboratory, radiologic,
and cardiorespiratory tests may be appropriate to assess the patients operative risk.
3- When an ostomy is a consideration, preoperative counseling with an enterostomal
therapist should be offered when available.
4- Digital rectal examination and rigid proctosigmoidoscopy
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a. Digital rectal examination enables detection and assessment of the size
and degree of fixation of mid and low rectal tumors.
b. Rigid proctosigmoidoscopy and digital rectal examination allow the mostprecise assessment of tumor location and the distance of the lesions from
the anal verge. These issues are critical in optimizing preoperative
planning.
5- Abdominal and pelvic CT scans often used to evaluate local extension of the tumor
and regional lymphadenopathy, as well as for the presence of hepatic metastases.
However, its role in local staging is limited.
6- Transrectal ultrasound (TRUS) is the diagnostic modality of choice for preoperative
local staging of mid and distal rectal cancers. TRUS may be more accurate in
defining earlier-stage lesions (T1, T2).
7- Pelvic Magnetic Resonance Imaging: MRI is more accurate in assessing T3 and T4lesions. MRI has the added advantage of a multiplanar and larger field of view of the
mesorectal fascia and more accurately predicts the likelihood of obtaining a tumor-
free circumferential resection margin.
8- Preoperative routine chest radiographs or chest CT scanning: Rectal cancer is more
likely than colon cancer to be associated with lung metastases without liver
metastases.
9- Carcinoembryonic antigen (CEA) level is most useful when found to be elevated
preoperatively and then normalizes after resection of the tumor. Subsequent
elevations suggest recurrence or metastatic disease. Because of a lack of sensitivity
and specificity, it is not used as a screening test.
10-PET CT scan is not routinely indicated
TREATMENT CONSIDERATIONS
Informed opinion of the (MDT) Multidisciplinary Team (Radiologist, Pathologist,
Medical Oncologist and Colorectal Surgeon). The patient and family should have the
opportunity to ask questions and to have important information repeated. The patient
should have an access to treatment within 31 days of discussion with MDT.
Surgery is the mainstay of treatment for rectal cancer. The risk of recurrence is dependenton the TNM stage. Early stage cancer can be treated by surgical resection alone. More
advanced lesions require adjuvant therapy to increase the probability of cure.
The surgeon is a critical variable with respect to morbidity, sphincter preservation rate,
and local recurrence.
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SURGICAL THERAPY
Resection Margin
The proximal resection margin is determined by blood supply considerations. For upper
third rectal cancers both the rectum and mesorectum are divided not less than 5 cm below
the lower margin of the tumor. A 2-cm distal margin is adequate for most low rectal
cancers. In smaller cancers of the low rectum without adverse histologic features, a 1-cm
distal margin is acceptable.
Site of the Lesion Operation Vessels Excised Parts
Upper Third Rectum Tumor Specific
Mesorectal Excision
With anastomosis
between descendingcolon and middle third
rectum
If the anastomosis
above the peritoneal
reflection = Anterior
Resection
If the anastomosis
below the peritoneal
reflection = Low
Anterior Resection
Inferior Mesenteric Sigmoid Colon and
upper third Rectum
with distal safety
margin of 5 cm
Middle and lower
Third Rectum downto > 2 cm from the
dentate line
Total Mesorectal
ExcisionWith anastomosis
between descending
colon and anal canal
(coloanal anastomosis)
= Ultra-Low Anterior
Resection
Inferior Mesenteric
Middle Rectal
Sigmoid Colon and
total proctectomy withdistal safety margin at
least 2 cm
< 2 cm from the
dentate line or lesion
infiltrating the anal
sphincter or the pelvic
floor muscles
Total Mesorectal
Excision with
Abdominoperineal
Excision of the
Rectum (APER) with
permanent colostomy
Inferior Mesenteric
Middle Rectal
Inferior Rectal
Sigmoid Colon, total
proctectomy, anal
canal, anal sphincters
and pelvic floor
muscles
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Tu
Total Me
or Specifi
T
25
orectal E
Mesorect
ME with
cision (T
l Excision
PER
Prof
E)
(TSME)
Surger
ssorAhmedyofCRCHussein
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Level of Proximal Vascular Ligation
Proximal lymphovascular ligation at the origin of the superior rectal artery is adequate for
most rectal cancers. There is no demonstrable survival advantage for a high ligation of
the inferior mesenteric artery at its origin. In patients with lymph nodes thought to be
involved clinically, removal of all suspicious nodal disease up to the origin of inferior
mesenteric artery is recommended. High ligation of the inferior mesenteric vessels may
be helpful to provide additional mobility of the left colon, as often is required for a low
colorectal anastomosis.
Circumferential Resection Margin
For distal rectal cancers, total mesorectal excision (TME) is recommended. For upper
rectal cancers, a tumor-specific mesorectal resection is adequate.
The mesorectum is the fatty tissue that encompasses the rectum. It contains
lymphovascular and neural elements. Surgical excision of the mesorectum is
accomplished by sharp dissection in the plane between the fascia propria of the rectum
and the presacral fascia. Radial clearance of mesorectal tissue enables the en bloc
removal of the primary rectal cancer with any associated lymphatic, vascular, or
perineural tumor deposits. Total mesorectal excision is associated with the lowest
reported local recurrence rates.
Pathologic assessment of rectal cancer specimens suggests that distal mesorectal spread
may occur up to 4 cm away from the primary tumor. Thus, a cancer in the distal rectum
should be treated with a total mesorectal excision in most cases. Upper rectal cancers
may be treated with a tumor-specific mesorectal resection with distal safety margin of 5
cm.
Circumferential margin involvement in the presence of an intact mesorectal specimen is a
strong predictor for local recurrence. A margin of 2 mm between tumor and the
mesorectal fascia was considered positive and was associated with a higher local
recurrence rate. Furthermore, patients who had a margin 1 mm had an increased risk of
distant metastases
En Bloc Resection of Adherent (T4) Tumors
Rectal cancers with adjacent organ involvement should be treated by en bloc resection.
Tumors may be adherent to adjacent organs by malignant invasion or inflammatory
adhesions. Locally invasive rectal cancer (T4) is removed by an en bloc resection to
include any adherent tissues. If a tumor is transected at the site of local adherence,
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resection is deemed incomplete, because it is associated with a higher incidence of local
recurrence.
Inadvertent Perforation
Inadvertent perforation of the rectum worsens oncologic outcome and should be
documented. This should be considered in postoperative adjuvant treatment decisions and
outcome measurements.
Other Operative Considerations
1. Role of Oophorectomy
Bilateral oophorectomy is advised when one or both ovaries are grossly abnormal or
involved with contiguous extension of the colon cancer. However, prophylactic
oophorectomy is not recommended..
2. Laparoscopic-assisted resection of rectal cancer is feasible but requires specific
surgical expertise.
3. Emergency intervention:
Hemorrhage, obstruction, and bowel perforation are the most common indications for
emergency intervention for rectal cancer. Appropriate management must be
individualized with options, including resection with anastomosis and proximal
diversion, or diversion alone followed by radiation. Self-expandable metallic stents can
be used to relieve obstruction by a proximal rectal cancer.
Preoperative Clinical Staging
1. T1-2,N0
2. T3, N0 OR T any, N1-2
3. T4 and/or locally unresectable primary
4. T any, N any, M1 resectable metastases
5. T any, N any, M1 unresectable metastases or medically in operable
Treatment of T1-2, N0, M0
Transanal Resection
1. Conventional resection or Transanal Microsurgery
2. Full thickness excision through the bowel wall into the perirectal fat
3. T1N0
4. Small (
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6. within 8 cm of AV
7. < 30% of rectal circumference
8. Negative (> 3 mm) deep & mucosal margins9. No Tumor fragmentation
According to histopathology of the resected specimen, either Surveillance would be
sufficient or further radical surgery might be indicated
Transabdominal Radical Resection is indicated if Unfavorable histological features:
1. LVI + PNI+
2. Grade 3-4
3. Positive Margins
4. T2
Transabdominal Radical Resection:
1. Mid to upper rectum
a. TSME (LAR) 5 cm below distal edge of Tumor + colorectal anastomosis.
2. Low rectal lesions
a. Tumor Within 2 cm above the dentate line
i. APER
ii. ISRR If T1 & T2
b. Tumor Above 2 cm from the dentate line
i. TME with coloanal anastomosis
ii. Spare autonomic nerves
Adjuvant Chemotherapy
If the pathology review after transabdominal resection revealed
1. T3N0
2. T1-3 N1-2
Regimens over 6 months
1. 5-FU +/- LV or FOLFOX or Capecitabine ( 1 Cycle)
2. Concurrent 5-FU/RT or capecitabine/RT
3. 5-FU +/-LV or FOLFOX or capecitabine (2 Cycles)
T3, N0 / T any, N1-2, M0
Preoperative (NeoAdjuvant) Therapy is a MUST
1. Continuous 5-FU/RT
2. Alternatives : bolus 5-FU/LV/RT or Capecitabine/RT
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Operative
Transabdominal approach only, performed 5-10 weeks after completion of neoadjuvant
therapy
Postoperative Adjuvant Therapy
1. 5-FU +/- LV
2. Alternatives : FOLFOX or Capecitabine
All patients receiving preoperative (Neoadjuvant) therapy should receive postoperative
adjuvant therapy for 6 months
T4 and/or locally unresectable primary
Resectable case = anticipated negative (R0) microscopic circumferential resection margin
Preoperative (NeoAdjuvant) Therapy
1. Continuous 5-FU/RT
2. Alternatives : bolus 5-FU/LV/RT or Capecitabine/RT
Operative
More Radical (multi-organ) approach, complete removal of tumor and involved viscera
with R0 margins.
Postoperative Adjuvant Therapy
1. 5-FU +/- LV
2. Alternatives : FOLFOX or Capecitabine
3. All patients receiving preoperative (Neoadjuvant) therapy should receive
postoperative adjuvant therapy for 6 months
T any, N any, M1 resectable metastases
1. Combination chemotherapy:a. FOLFOX/FOLFIRI/capeOX +/- Bevacizumab
b. FOLFIRI/FOLFOX +/- cetuximab (KRAS wild-type gene only)
2. Staged or synchronous resection of metastases and rectal lesion
3. Adjuvant Therapy:
a. Continuous IV 5FU/ RT
b. Bolus 5FU+leucovorin/ RT
c. Capecitabine/RT
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T any, N any, M1 unresectable metastases or medically inoperable
1. Role of palliative surgery
a. Only If Obstruction, Perforation or Bleeding
2. Symptomatic Treatment
a. Chemotherapy alone
b. Combind modality
i. 5FU/RT or Capecitabine /RT.
c. Resection of involved rectal segment + CT
d. Intraluminal Stent + CT
e. Diverting colostomy + CT
Pathologic Evaluation of Rectal Cancer
1. Gross: Tumor & Specimen
2. Grade
3. LVI & PNI
4. T Stage
5. Number of regional LNs evaluated
6. N Stage: Number of +ve LNs
7. M Stage
a. Other organs
b. Peritoneum
c. Nonregional lymph nodes
8. Proximal, distal, & CRM
9. p = pathologic staging
10.yp = pathologic staging following neoadjuvant therapy
Surveillance
1. History & Physical Examination
a. Every 3-6 months for 2 years
b. Then every 6 months for a total of 5 years
2. CT scan of abdomen & pelvis Annually for 3 years3. Colonoscopy At 1 yearthen as clinically indicated
ADJ UVANT THERAPY
Neoadjuvant Therapy (Preoperative chemoradiation) should be offered to patients with
Stage II and III rectal cancers.
1- It is given as long course (45-50 Gy in 25-28 fractions)
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2- 5-FU based chemotherapy should delivered concurrently with radiation
3- All patients receiving preoperative (Neoadjuvant) therapy should receive
postoperative adjuvant therapy for 6 months
Rationale for Neoadjuvant Therapy
1. Avoids irradiation of neorectum & small bowel
2. Systemic Therapy early
a. Less burden of disease
b. Better drug perfusion
i. Nonsurgically manipulated tumor
ii. Well vascularized oxygenated tissue
3. As Radiosensitizers
a. Enhanced rates of downstaging & pathologic complete response (ypCR)
Site AtDL 2cmDL MidRectum UpperRectum
PedunculatedPolyp
LVI,G12
Polypectomy&Observe
SessilePolyporLVI+,
G34
RadicalSurgery
T1,LVI,G12 SCRT
+APR
APR/
CRT+ISRR
Local
Excision
Local
Excision/TME
TSME
T1,LVI+,G34,orT2 SCRT+
APR
APR/
CRT+ISRR
TME TME TSME
GoodT3 CRT+
APR
CRT+APR TME TME TSME
BadT3 CRT+APR CRT+APR CRT+TME CRT+TME CRT+TSME
T4a CRT+APR CRT+APR CRT+TME CRT+TME CRT+TSME
T4b
CRT+APR
CRT+APR CRT+TME CRT+TME CRT+TSME