Histological healing favors lower risk of colon carcinoma in extensive ulcerative colitis.

AIM To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer (CC) or high grade dysplasia (HGD). METHODS This is a single center (Lenox Hill Hospital) retrospective cohort and descriptive study of extensive ulcerative colitis (UC) for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis. Data analyzed included: duration of UC, date of diagnosis of (CC) or (HGD), number of surveillance colonoscopies, and biopsies showing histological inflammation and its severity in each of 6 segments when endoscopic appearance is normal. Two subgroups of patients were compared: group 1 patients who developed CC/HGD and group 2 patients who did not develop CC/HGD. RESULTS Of 115 patients with longstanding UC reviewed, 68 patients met the inclusion criteria. Twenty patients were in group 1 and 48 in group 2. We identified the number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed inflammation. Overall, histological disease activity in the absence of gross/endoscopic disease was found in 31.2% (95%CI: 28%-35%) of colonoscopies performed on the entire cohort of 68 patients. Histological disease activity when the colonoscopy showed an absence of gross disease activity was more common in group 1 than group 2 patients, 88% (95%CI: 72%-97%) vs 59% (95%CI: 53%-64%). Only 3/20 (15%) of patients in group 1 ever had a colonoscopy completely without demonstrated disease activity (i.e., no endoscopic or histological activity) as compared to 37/48 (77%) of patients in group 2, and only 3.3% (95%CI: 0.09%-8.3%) of colonoscopies in group 1 had no histological inflammation compared to 23% (95%CI: 20%-27%) in group 2. CONCLUSION Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among those patients who demonstrate persistent histological inflammation in the absence of gross mucosal disease. Our findings support including the elimination of histological inflammation in the definition of mucosal healing, and support this endpoint as an appropriate goal of therapy because of its risk of increasing dysplasia and colon cancer.

[1]  F. Carrat,et al.  Risk of colorectal high-grade dysplasia and cancer in a prospective observational cohort of patients with inflammatory bowel disease. , 2013, Gastroenterology.

[2]  B. Korelitz,et al.  Is Treatment with 6-Mercaptopurine for Colitis Associated with the Development of Colorectal Cancer? , 2013, Inflammatory bowel diseases.

[3]  P. Rutgeerts,et al.  Prognostic Value of Serologic and Histologic Markers on Clinical Relapse in Ulcerative Colitis Patients With Mucosal Healing , 2012, The American Journal of Gastroenterology.

[4]  Robert L. Goldstone,et al.  Dysplasia is more common in the distal than proximal colon in ulcerative colitis surveillance , 2012, Inflammatory Bowel Diseases.

[5]  P. Rutgeerts,et al.  Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. , 2011, Gastroenterology.

[6]  S. Kane,et al.  Mucosal healing in Crohn's disease and ulcerative colitis: what does it tell us? , 2011, Current opinion in gastroenterology.

[7]  E. Kuipers,et al.  Majority of patients with inflammatory bowel disease in clinical remission have mucosal inflammation , 2011, Inflammatory bowel diseases.

[8]  B. Sands,et al.  Can endoscopy be avoided in the assessment of ulcerative colitis in clinical trials? , 2011, Inflammatory bowel diseases.

[9]  M. Regueiro,et al.  Physician assessment of ulcerative colitis activity correlates poorly with endoscopic disease activity , 2011, Inflammatory bowel diseases.

[10]  B. Korelitz Mucosal healing as an index of colitis activity: back to histological healing for future indices. , 2010, Inflammatory bowel diseases.

[11]  A. Kornbluth,et al.  Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee , 2010, The American Journal of Gastroenterology.

[12]  P. Rutgeerts,et al.  Mucosal healing predicts long‐term outcome of maintenance therapy with infliximab in Crohn's disease , 2009, Inflammatory bowel diseases.

[13]  P. Higgins,et al.  Controversies in mucosal healing in ulcerative colitis. , 2009, Inflammatory bowel diseases.

[14]  N. Harpaz,et al.  Progression to colorectal neoplasia in ulcerative colitis: effect of mesalamine. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[15]  N. Harpaz,et al.  Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. , 2007, Gastroenterology.

[16]  M. Vatn,et al.  Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. , 2007, Gastroenterology.

[17]  P. Rutgeerts,et al.  Mucosal healing in inflammatory bowel disease: impossible ideal or therapeutic target? , 2007, Gut.

[18]  A. Forbes,et al.  Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. , 2006, Gastroenterology.

[19]  L. Melton,et al.  Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota. , 2006, Gastroenterology.

[20]  J. Terdiman,et al.  Effect of 5-Aminosalicylate Use on Colorectal Cancer and Dysplasia Risk: A Systematic Review and Metaanalysis of Observational Studies , 2005, The American Journal of Gastroenterology.

[21]  M. Schwartz,et al.  Is Endoscopy Necessary for the Measurement of Disease Activity in Ulcerative Colitis? , 2005, The American Journal of Gastroenterology.

[22]  A. Forbes,et al.  Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk , 2004, Gut.

[23]  Alastair Forbes,et al.  Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. , 2004, Gastroenterology.

[24]  Yunni-Yi Chen,et al.  Gross Versus Microscopic Pancolitis and the Occurrence of Neoplasia in Ulcerative Colitis , 2003, Inflammatory bowel diseases.

[25]  K. Abrams,et al.  The risk of colorectal cancer in ulcerative colitis: a meta-analysis , 2001, Gut.

[26]  A. Öst,et al.  A reproducible grading scale for histological assessment of inflammation in ulcerative colitis , 2000, Gut.

[27]  S. Riley,et al.  Microscopic activity in ulcerative colitis: what does it mean? , 1991, Gut.

[28]  H. Adami,et al.  Ulcerative colitis and colorectal cancer. A population-based study. , 1990, The New England journal of medicine.

[29]  S. Geller,et al.  Cancer in universal and left-sided ulcerative colitis: factors determining risk. , 1979, Gastroenterology.

[30]  Sommers Sc,et al.  Responses to drug therapy in ulcerative colitis. Evaluation by rectal biopsy and histopathological changes. , 1975 .

[31]  B. Korelitz,et al.  Mucosal-cell counts in ulcerative and granulomatous colitis. , 1975, American journal of clinical pathology.

[32]  B. Morson Rectal biopsy in inflammatory bowel disease. , 1972, The New England journal of medicine.

[33]  A. Dick,et al.  Persistence of mucosal abnormality in ulcerative colitis. , 1966, Gut.

[34]  Matts Sg,et al.  THE VALUE OF RECTAL BIOPSY IN THE DIAGNOSIS OF ULCERATIVE COLITIS1 , 1961 .

[35]  Gray Mj,et al.  Ulcerative colitis. A follow-up investigation with mucosal biopsy studies. , 1961 .

[36]  S. Truelove,et al.  Biopsy Studies in Ulcerative Colitis , 1956, British medical journal.

[37]  L. Peyrin-Biroulet,et al.  Clinical implications of mucosal healing for the management of IBD , 2010, Nature Reviews Gastroenterology &Hepatology.

[38]  M. Picco Decreasing Time-Trends of Colorectal Cancer in a Large Cohort of Patients With Inflammatory Bowel Disease , 2009 .

[39]  A. Cohen,et al.  Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. , 2001, Gastroenterology.

[40]  B. Korelitz,et al.  Responses to drug therapy in ulcerative colitis. Evaluation by rectal biopsy and histopathological changes. , 1975, The American journal of gastroenterology.

[41]  S G MATTS,et al.  The value of rectal biopsy in the diagnosis of ulcerative colitis. , 1961, The Quarterly journal of medicine.

[42]  A. Dick,et al.  Ulcerative colitis. A follow-up investigation with mucosal biopsy studies. , 1961, British medical journal.

[43]  G PLACITELLI,et al.  [Ulcerative colitis]. , 1958, La Riforma medica.