1. Colitis Indeterminate Najib Haboubi Professor of Health Sciences, Liver and Gastrointestinal Pathology Head of Surgical pathology Trafford Healthcare Centre. UK

2. Overlap in the spectrum of non-specific IBD ; colitis indeterminate (CI) Ashley Price J.Clin Path 1978

3. Material & Methods 330 consecutive cases of colectomy or proctocolectomy for UC or CD between 1960-1973. 330 consecutive cases of colectomy or proctocolectomy for UC or CD between 1960-1973. 30 cases of IBD which could not be categorised further and therefore classified as C1 30 cases of IBD which could not be categorised further and therefore classified as C1

4. 27 out of 30 cases (90%) Were presented as acute severe disease in comparison to (30%) in UC and CD in the same hospital for the same period. Were presented as acute severe disease in comparison to (30%) in UC and CD in the same hospital for the same period.

5. Indeterminate Colitis in the Spectrum of Inflammatory Bowel Disease Ken Lee, Alan Medline & Stanley Shockey Arch. Path & Lab Med, 1979 Confirm Price’s observation.

6. Classically CI 5-15% of colonic resectates in IBD. 5-15% of colonic resectates in IBD. Mostly seen in the severe active phase. Mostly seen in the severe active phase. There is histological overlap between UC and CD. There is histological overlap between UC and CD.

7. CI Not a specific pathological entity A condition that ‘awaits final diagnosis’ which we may never arrive to. A condition that ‘awaits final diagnosis’ which we may never arrive to. Has no specific distinguishing pathological feature. Has no specific distinguishing pathological feature.

8. Dilated segment (transverse), relative rectal sparing, thin wall, severe mucosal ulceration

9. Histology Severe inflammation. In most the process is continuous and diffuse. Islands of relatively intact mucosa.

10. CI is has no diagnostic histological features Knife like ‘stab’ or V types fissures that may extend to superficial muscularis. Myocytolysis.

11. Problems Terminology. Terminology. Diagnosis Diagnosis Definitions. Definitions. Outcome. Outcome.

12. Indeterminate Colitis Colitis Indeterminate Colitis Indeterminate Fulminant Colitis Fulminant Colitis Toxic Mega colon Toxic Mega colon Disintegrative Colitis Disintegrative Colitis Acute Severe Colitis Acute Severe Colitis

13. Problems Terminology. Terminology. Diagnosis Diagnosis Definitions. Definitions. Outcome. Outcome.

14. Shared features of CD and IC CD CD Rectal sparing Rectal sparing Deep Fissures Deep Fissures True Transmural inflammation True Transmural inflammation IC Rectal sparing. Superficial Fissures False Transmural Inflammation (in areas of ulceration ).

15. Rectal sparing in genuine UC After topical or systemic treatment. After topical or systemic treatment. Children at initial presentation. Children at initial presentation.

16. Problems Terminology. Terminology. Diagnosis Diagnosis Definitions. Definitions. Outcome. Outcome.

17. Definition 1 (Price 1978) Acute clinical situation. Acute clinical situation. Overlap of histological features of CD and UC. Overlap of histological features of CD and UC. Surgical Resectates. Surgical Resectates.

18. Definition 2 St. Marks 1991 Cleveland Clinic 1992 Typically fulminant. Typically fulminant. Resectates. Resectates. Overlapping features. Overlapping features. Further sub classify into Further sub classify into CI probably UC CI probably UC CI probably CD CI probably CD CI ‘unspecified’ CI ‘unspecified’

19. Definition 3 (Kangas 1994) Patients who had the clinical and macroscopical features of either CD or UC both pre and intra operatively Patients who had the clinical and macroscopical features of either CD or UC both pre and intra operativelyAND The histology remained indertermined. The histology remained indertermined. They included cases in which the diagnosis was based on mucosal biopsies. They included cases in which the diagnosis was based on mucosal biopsies.

20. Recommendation Mucosal biopsies CIBD with no distinguishing histological features. CIBD with no distinguishing histological features. IBD unclassified. IBD unclassified.

21. Definition 4 (Mayo Clinic 1995) Unequivocal diagnosis of chronic UC preoperatively but Unequivocal diagnosis of chronic UC preoperatively but inconclusive histology on examiation of the pathologic specimens intra operatively. inconclusive histology on examiation of the pathologic specimens intra operatively.

22. Definition 5 (Price 2 1996) ‘The inability to make a confident diagnosis of the pattern of colitis despite an adequate surgical resectates or adequate mucosal biopsies from the colon and rectum’ ‘The inability to make a confident diagnosis of the pattern of colitis despite an adequate surgical resectates or adequate mucosal biopsies from the colon and rectum’ Resectates and mucosal biopsies Not necessarily a surgical acute condition. Not necessarily cases of IBD.

23. Definition 6 Indeterminate colitis, Montreal Working Party 2005 Returned to original definition by Price Returned to original definition by Price ‘should be reserved only for those cases where colectomy has been performed and pathologists are unable to make a definitive diagnosis of either Crohn’s disease or ulcerative colitis after full examination’ Satangi J, Silverberg MS, Vermeire S and J-F Colombel. The Montreal classification of inflammatory bowel disease: controversies, consensus and implications. Gut 2006;55:749-753.

24. Problems Terminology. Terminology. Diagnosis. Diagnosis. Definitions. Definitions. Outcome. Outcome.

25. Natural History, Variable. 87% will end up with either CD or UC (Swan et al) after time and careful review. 87% will end up with either CD or UC (Swan et al) after time and careful review. Most polarise into UC. Meucci et al 80% UC. Most polarise into UC. Meucci et al 80% UC. 10-40% CD. 10-40% CD. Still there is a group of patients who after long term follow up the pathologist and the clinician can not put it into either CD or UC. Still there is a group of patients who after long term follow up the pathologist and the clinician can not put it into either CD or UC.

26. Natural History of Indeterminate Colitis Wells, McMillen, Price, Ritchie & Nicholls. Br. J. Surgery 1991.

27. After mean follow up of 108 months and review of histological radiological and clinical data Group 119Probable CD -UC (1) Group 211Probable UC - No change Group 316Indeterminate - UC (3) CD (1)

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

29. Current Research and Development Serology: ASCA/ANCA Serology: ASCA/ANCA Genetics. Genetics. Gastric biopsies. Gastric biopsies. RANTES RANTES

30. Ansari et al J Clin Path 2006 Bahrain Comparison of RANTES expression in CD and UC: an aid in the differential diagnosis. Comparison of RANTES expression in CD and UC: an aid in the differential diagnosis. Mucosal biopsies from patients with UC have a significantly more staining of lymphocytes and histiocytes in UC than CD. Mucosal biopsies from patients with UC have a significantly more staining of lymphocytes and histiocytes in UC than CD.

31. Outcome after IAP ; Varies UC like ( St Marks ) UC like ( St Marks ) CD like ( Kangas et al 1994) CD like ( Kangas et al 1994) Between ( Yu et al Mayo 2000) Between ( Yu et al Mayo 2000)

32. Indeterminate Colitis – Pouch Surgery Yu et al 2000 Mayo Clinic 82 IC patients Pouch failure 27% IC vs. 11% UC Pelvic sepsis 13% IC vs. 7% UC Pouch Fistula 31% IC vs. 9% UC 15% of IC evolved into CD. Removal of converted cases = outcome identical between IC and UC

33. SUMMARY CI constitutes a small but important subgroup of IBD CI constitutes a small but important subgroup of IBD Mostly in fulminant state. Mostly in fulminant state. Most patients will polarize to either CD or UC after: Most patients will polarize to either CD or UC after: 1.Good clinico-pathological correlation AND 2.Long term follow-up. Standardisation of definition is important for meaningful comparison between various studies and treatment options. Standardisation of definition is important for meaningful comparison between various studies and treatment options.

34. ACGBI Glasgow 2-5 th July Glasgow 2-5 th July

35. ESCP Annual General Meeting Malta September 26-29 Pre-meeting course Core Subject Update Wednesday 26 September 14:00 – 17:00

36. ESCP Annual General Meeting Malta September 26-29 Symposia Imaging in Colorectal Cancer Pelvic Floor Disorders Laparoscopy Pouches in Ulcerative Colitis DebatesHaemorrhoidectomy Rectal Prolapse Laparoscopy

37. ESCP Annual General Meeting Malta September 26-29 Keynote Lectures Management of Large Wounds Laparoscopy Update on Familial Adenomatous Polyposis Sacral Nerve Stimulation for Fecal Incontinence Interpretation of Endpoints in Cancer Trials Management of the Advanced Pelvic Malignancy Consultants’ Corner Free Paper and Oral Poster Presentations Six Best Papers

38. Abstract deadline date Sunday 20 May 2007 Submissions open at www.escp.eu.com www.escp.eu.com Future ESCP Scientific Meetings 2008: 24 – 27 September: Nantes, France 2009: 23 – 26 September 2010: 22 – 25 September

40. Is ‘Indeterminate Colitis’ Crohn’s Disease in Long-Term Follow-Up? Kangas, Matikainen & Matila. Int. Surg. 1994. Tampere, Finland.

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

42. Fulminant Colitis in IBD Detailed Pathologic and Clinical Analysis Swan, Geogehan, O’Donoghue, Hyland and Sheahan Dis Col and Rectum 1998

43. 67 FC of IBD Disease Original Dx After Path review After Path review CP correlation UC404545 CD161316 IC1196

44. Can the pathologist come off the fence? Can the pathologist come off the fence? Yes, after a long follow up. Yes, after a long follow up.

46. Definition 6 Montreal Classification 2005 Satangi J et al The Montreal classification of inflammatory bowel disease: controversies, consensus and implications. Gut 2006;55:749-753. Definition 6 Montreal Classification 2005 Satangi J et al The Montreal classification of inflammatory bowel disease: controversies, consensus and implications. Gut 2006;55:749-753. Back to original Price 1978 classification. Back to original Price 1978 classification. Acute phase Acute phase Resectate Resectate IBD but cannot be further categorised histologically IBD but cannot be further categorised histologically