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 to23%(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. 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 with the inclusion criteria .wenty patients were in group 1 and 48 in group 2.We identified th E number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed pain. 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 (ie, no endoscopic or histological activity) as compared to 37/48 %) 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% CONCLUSION: Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among those patients who demonstrated persistent histological inflaM findings in the absence of gross mucosal disease. Our findings support the elimination of histological inflammation in the definition of mucosal healing, and support this endpoint as a suitable goal of therapy because of its risk of increasing dysplasia and colon cancer.