Colitis IndeterminateColitis IndeterminateNajib HaboubiNajib Haboubi

Professor of Health Sciences, Liver and Professor of Health Sciences, Liver and Gastrointestinal PathologyGastrointestinal Pathology

Head of Surgical pathologyHead of Surgical pathologyTrafford Healthcare Centre.Trafford Healthcare Centre.

UKUK

Overlap in the spectrum of Overlap in the spectrum of non-specific IBD ;non-specific IBD ;

colitis indeterminate (CI)colitis indeterminate (CI)

Ashley PriceAshley Price

J.Clin Path 1978J.Clin Path 1978

Material & MethodsMaterial & Methods330 consecutive cases of 330 consecutive cases of

colectomy or proctocolectomycolectomy or proctocolectomy for UC or CD between for UC or CD between 1960-1973.1960-1973.

30 cases of IBD which could 30 cases of IBD which could not be categorised further and not be categorised further and therefore classified as C1therefore classified as C1

27 out of 30 cases (90%) 27 out of 30 cases (90%)

Were presented as Were presented as acute acute severesevere disease in comparison disease in comparison to (30%) in UC and CD in to (30%) in UC and CD in the same hospital for the the same hospital for the same period.same period.

Indeterminate Colitis in the Indeterminate Colitis in the Spectrum of Inflammatory Spectrum of Inflammatory

Bowel DiseaseBowel Disease

Ken Lee, Alan Medline & Stanley ShockeyKen Lee, Alan Medline & Stanley Shockey

Arch. Path & Lab Med, 1979Arch. Path & Lab Med, 1979

Confirm Price’s observation.Confirm Price’s observation.

ClassicallyClassically CI CI

5-15% of colonic 5-15% of colonic resectates resectates in in IBD.IBD. Mostly seen in the Mostly seen in the severe activesevere active

phase.phase. There is There is histological overlap between histological overlap between

UC and CDUC and CD..

CI CI Not a specific Not a specific pathological entitypathological entity

A condition that ‘awaits final A condition that ‘awaits final diagnosis’ which we may never diagnosis’ which we may never arrive to.arrive to.

Has no specific distinguishing Has no specific distinguishing pathological feature.pathological feature.

Dilated segment (transverse), Dilated segment (transverse), relative rectal sparing, thin wall, relative rectal sparing, thin wall,

severe mucosal ulceration severe mucosal ulceration

HistologyHistology

Severe inflammation.Severe inflammation. In most the process In most the process

is continuous and is continuous and diffuse.diffuse.

Islands of relatively Islands of relatively intact mucosa.intact mucosa.

CI is has no diagnostic CI is has no diagnostic histological featureshistological features

Knife like Knife like ‘stab’ or V ‘stab’ or V types fissures types fissures that may extend that may extend to superficial to superficial muscularis. muscularis.

MyocytolysisMyocytolysis. .

ProblemsProblems Terminology.Terminology. DiagnosisDiagnosis Definitions.Definitions. OutcomeOutcome..

Indeterminate Colitis Indeterminate Colitis

Colitis IndeterminateColitis Indeterminate Fulminant ColitisFulminant Colitis Toxic Mega colonToxic Mega colon Disintegrative ColitisDisintegrative Colitis Acute Severe ColitisAcute Severe Colitis

ProblemsProblems TerminologyTerminology.. DiagnosisDiagnosis Definitions.Definitions. OutcomeOutcome..

Shared features of CD and ICShared features of CD and IC

CDCD Rectal sparing Rectal sparing Deep FissuresDeep Fissures True True

Transmural Transmural inflammationinflammation

ICIC Rectal sparingRectal sparing.. Superficial FissuresSuperficial Fissures False Transmural False Transmural

Inflammation (in Inflammation (in areas of ulcerationareas of ulceration).).

Rectal sparing in Rectal sparing in genuine UCgenuine UC

After topical or systemic After topical or systemic treatment.treatment.

Children at initial presentation.Children at initial presentation.

ProblemsProblems TerminologyTerminology.. DiagnosisDiagnosis DefinitionsDefinitions.. OutcomeOutcome..

Definition 1 (Price 1978)Definition 1 (Price 1978)

AcuteAcute clinical situation. clinical situation. Overlap of histological features of Overlap of histological features of

CD and UCCD and UC . . Surgical Resectates.Surgical Resectates.

Definition 2 St. Marks 1991Definition 2 St. Marks 1991 Cleveland Clinic 1992 Cleveland Clinic 1992

Typically fulminant.Typically fulminant. Resectates. Resectates. Overlapping features.Overlapping features. Further sub classify into Further sub classify into

CI probably UCCI probably UC

CI probably CD CI probably CD

CI ‘unspecified’CI ‘unspecified’

Definition 3 (Kangas 1994)Definition 3 (Kangas 1994)

Patients who had the Patients who had the clinical and clinical and macroscopical features of either CD or UC macroscopical features of either CD or UC both pre and intra operativelyboth pre and intra operatively

AND AND The histology remained indertermined.The histology remained indertermined. They included cases in which the They included cases in which the

diagnosis was based on mucosal biopsiesdiagnosis was based on mucosal biopsies. .

RecommendationRecommendation Mucosal biopsies Mucosal biopsies

CIBD with no distinguishing CIBD with no distinguishing histological features.histological features.

IBD unclassified.IBD unclassified.

Definition 4 (Mayo Clinic 1995)Definition 4 (Mayo Clinic 1995)

Unequivocal diagnosis of chronic Unequivocal diagnosis of chronic UC preoperativelyUC preoperatively but but

inconclusiveinconclusive histology on examiation of histology on examiation of the pathologic specimens the pathologic specimens intra operativelyintra operatively..

Definition 5 (Price 2 1996)Definition 5 (Price 2 1996)

‘‘The inability to make a confident The inability to make a confident diagnosis of the pattern of colitis despite diagnosis of the pattern of colitis despite an adequate surgical resectates or an adequate surgical resectates or adequate mucosal biopsies from the adequate mucosal biopsies from the colon and rectum’colon and rectum’

Resectates and mucosal biopsiesResectates and mucosal biopsies

Not necessarily a surgical acute condition.Not necessarily a surgical acute condition.

Not necessarily cases of IBD.Not necessarily cases of IBD.

Definition 6 Indeterminate colitis,Definition 6 Indeterminate colitis, Montreal Working Party 2005Montreal Working Party 2005

Returned to original definition by PriceReturned to original definition by Price

‘‘should be reserved only for those cases should be reserved only for those cases where colectomy has been performed and where colectomy has been performed and pathologists are unable to make a definitive pathologists are unable to make a definitive diagnosis of either Crohn’s disease or diagnosis of either Crohn’s disease or ulcerative colitis after full examination’ulcerative colitis after full examination’

Satangi J, Silverberg MS, Vermeire S and J-F Colombel. The Montreal classification Satangi J, Silverberg MS, Vermeire S and J-F Colombel. The Montreal classification of inflammatory bowel disease: controversies, consensus and implications. of inflammatory bowel disease: controversies, consensus and implications.

Gut 2006;55:749-753Gut 2006;55:749-753..

ProblemsProblems TerminologyTerminology.. Diagnosis.Diagnosis. Definitions.Definitions. OutcomeOutcome..

Natural History, Variable. Natural History, Variable.

87% will end up with either CD or UC 87% will end up with either CD or UC (Swan et al) after time and careful review.(Swan et al) after time and careful review.

Most polarise into UC. Meucci et al Most polarise into UC. Meucci et al 80% UC.80% UC.

10-40% CD.10-40% CD. Still there is a group of patients who after Still there is a group of patients who after

long term follow up the pathologist and long term follow up the pathologist and the clinician can not put it into either the clinician can not put it into either CD or UC.CD or UC.

Natural History of Natural History of Indeterminate ColitisIndeterminate Colitis

Wells, McMillen, Price, Ritchie & Nicholls.Wells, McMillen, Price, Ritchie & Nicholls.

Br. J. Surgery 1991.Br. J. Surgery 1991.

After mean follow up of 108 months After mean follow up of 108 months and review of histological and review of histological

radiological and clinical dataradiological and clinical data

Group 1Group 1 1919 Probable CD -Probable CD - UC (1)UC (1)

Group 2Group 2 1111 Probable UC - Probable UC - No changeNo change

Group 3Group 3 1616 Indeterminate - Indeterminate - UC (3) UC (3) CD CD

(1)(1)

ConclusionConclusion

Patients continuing with a Patients continuing with a diagnosis of IC are unlikely diagnosis of IC are unlikely to show features of CD on to show features of CD on long term follow-up.long term follow-up.

Current Research and Current Research and Development Development

Serology: ASCA/ANCASerology: ASCA/ANCA Genetics.Genetics. Gastric biopsies.Gastric biopsies. RANTESRANTES

Ansari et al J Clin Path Ansari et al J Clin Path 2006 Bahrain2006 Bahrain

Comparison of RANTES expression in Comparison of RANTES expression in CD and UC: an aid in the differential CD and UC: an aid in the differential diagnosis.diagnosis.

Mucosal biopsies from patients with Mucosal biopsies from patients with UC have a significantly more staining UC have a significantly more staining of lymphocytes and histiocytes in of lymphocytes and histiocytes in UC than CD.UC than CD.

Outcome after IAP ; Varies Outcome after IAP ; Varies

UC like (UC like (St MarksSt Marks) ) CD like CD like ( Kangas et al 1994)( Kangas et al 1994)

BetweenBetween ( Yu et al Mayo 2000)( Yu et al Mayo 2000)

Indeterminate Colitis – Pouch SurgeryIndeterminate Colitis – Pouch Surgery

Yu et al 2000 Mayo ClinicYu et al 2000 Mayo Clinic82 IC patients82 IC patientsPouch failure 27% IC vs. 11% UCPouch failure 27% IC vs. 11% UCPelvic sepsis 13% IC vs. 7% UCPelvic sepsis 13% IC vs. 7% UCPouch Fistula 31% IC vs. 9% UCPouch Fistula 31% IC vs. 9% UC15% of IC evolved into CD.15% of IC evolved into CD.Removal of converted cases = outcome Removal of converted cases = outcome

identical between IC and UCidentical between IC and UC

SUMMARYSUMMARY CI constitutes a small but important subgroup of CI constitutes a small but important subgroup of

IBDIBD Mostly in fulminant state.Mostly in fulminant state. Most patients will polarize to either CD or UC Most patients will polarize to either CD or UC

after:after:1.1. Good clinico-pathological correlation Good clinico-pathological correlation ANDAND2.2. Long term follow-up.Long term follow-up.

Standardisation of definition is important for Standardisation of definition is important for meaningful comparison between various studies meaningful comparison between various studies and treatment options.and treatment options.

ACGBIACGBI

Glasgow 2-5Glasgow 2-5thth July July

ESCP Annual General MeetingESCP Annual General MeetingMalta September 26-29Malta September 26-29

Pre-meeting coursePre-meeting course

Core Subject UpdateCore Subject UpdateWednesday 26 September 14:00 – 17:00Wednesday 26 September 14:00 – 17:00

ESCP Annual General MeetingESCP Annual General MeetingMalta September 26-29Malta September 26-29

SymposiaSymposiaImaging in Colorectal CancerImaging in Colorectal Cancer

Pelvic Floor DisordersPelvic Floor DisordersLaparoscopyLaparoscopy

Pouches in Ulcerative ColitisPouches in Ulcerative Colitis

DebatesDebatesHaemorrhoidectomyHaemorrhoidectomy

Rectal ProlapseRectal ProlapseLaparoscopyLaparoscopy

ESCP Annual General MeetingESCP Annual General MeetingMalta September 26-29Malta September 26-29

Keynote LecturesKeynote LecturesManagement of Large WoundsManagement of Large Wounds

LaparoscopyLaparoscopyUpdate on Familial Adenomatous PolyposisUpdate on Familial Adenomatous Polyposis

Sacral Nerve Stimulation for Fecal IncontinenceSacral Nerve Stimulation for Fecal IncontinenceInterpretation of Endpoints in Cancer TrialsInterpretation of Endpoints in Cancer Trials

Management of the Advanced Pelvic MalignancyManagement of the Advanced Pelvic Malignancy

Consultants’ CornerConsultants’ Corner

Free Paper and Oral Poster PresentationsFree Paper and Oral Poster Presentations

Six Best PapersSix Best Papers

Abstract deadline date Abstract deadline date SundaySunday 20 20 May 2007 May 2007

Submissions open at Submissions open at www.escp.eu.comwww.escp.eu.com

Future ESCP Scientific MeetingsFuture ESCP Scientific Meetings 2008: 24 – 27 September: 2008: 24 – 27 September: Nantes, FranceNantes, France2009: 23 – 26 September 2009: 23 – 26 September 2010: 22 – 25 September2010: 22 – 25 September

Is ‘Indeterminate Colitis’ Is ‘Indeterminate Colitis’ Crohn’s Disease in Long-Term Crohn’s Disease in Long-Term

Follow-Up?Follow-Up?

Kangas, Matikainen & Matila.Kangas, Matikainen & Matila.

Int. Surg. 1994.Int. Surg. 1994.

Tampere, Finland.Tampere, Finland.

ConclusionConclusion

Cases labelled for IC show Cases labelled for IC show tendency to develop CD after tendency to develop CD after a long follow-up.a long follow-up.

Fulminant Colitis in IBDFulminant Colitis in IBDDetailed Pathologic and Clinical Detailed Pathologic and Clinical

AnalysisAnalysis

Swan, Geogehan, O’Donoghue, Hyland Swan, Geogehan, O’Donoghue, Hyland and Sheahanand Sheahan

Dis Col and Rectum 1998Dis Col and Rectum 1998

67 FC of IBD67 FC of IBD

DiseaseDisease Original DxOriginal Dx After Path After Path reviewreview

CP CP correlationcorrelation

UCUC 4040 4545 4545

CDCD 1616 1313 1616

ICIC 1111 99 66

Can the pathologist come off the Can the pathologist come off the fence?fence?

Yes , after a long follow Yes , after a long follow up .up .

Definition 6 Montreal Definition 6 Montreal Classification 2005Classification 2005

Satangi J et al The Montreal classification of inflammatory bowel disease: Satangi J et al The Montreal classification of inflammatory bowel disease: controversies, consensus and implications. Gut 2006;55:749-753.controversies, consensus and implications. Gut 2006;55:749-753.

Back to original Price 1978 classification.Back to original Price 1978 classification. Acute phaseAcute phase ResectateResectate IBD but cannot be further categorised IBD but cannot be further categorised

histologicallyhistologically