Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis

BACKGROUND & AIMS: The value of colonoscopic surveillance for neoplasia in long-standing extensive ulcerative colitis remains controversial. This study reports on prospectively collected data from a surveillance program over a 30-year period. METHODS: Data were obtained from the prospective surveillance database, medical records, colonoscopy, and histology reports. The primary end point was defined as death, colectomy, withdrawal from surveillance, or census date (January 1, 2001). Follow-up information was obtained for patients who left the program. RESULTS: Six hundred patients underwent 2627 colonoscopies during 5932 patient-years of follow-up. The cecal intubation rate was 98.7%, with no significant complications. Seventy-four patients (12.3%) developed neoplasia, including 30 colorectal cancers (CRCs). There was no difference in median age at onset of colitis for those with or without CRC (P = .8, Mann-Whitney). The cumulative incidence of CRC by colitis duration was 2.5% at 20 years, 7.6% at 30 years, and 10.8% at 40 years. The 5-year survival rate was 73.3%. Sixteen of 30 cancers were interval cancers. CRC incidence decreased over time (r = -.40, P = .04; linear regression). CONCLUSIONS: Colonoscopic surveillance is safe and allows the vast majority of patients to retain their colon. Although two thirds of patients with potentially life-threatening neoplasia benefited from surveillance, the program was not wholly effective in cancer prevention. The cancer incidence, however, was considerably lower than in the majority of other studies, and was constant for up to 40 years of colitis duration, suggesting there is no need to intensify surveillance over time.     

Diagnosis and management of dysplasia in patients with inflammatory bowel diseases

Patients with ulcerative colitis and Crohn's colitis face an increased lifetime risk of developing colorectal cancer. Factors associated with increased risk include long duration of colitis, extensive colonic involvement, primary sclerosing cholangitis, a family history of colorectal cancer, and, according to some studies, early disease onset and more severely active inflammation. Although prophylactic proctocolectomy can essentially eliminate the risk of cancer, most patients and their physicians opt instead for a lifelong program of surveillance. This entails regular medical follow-up, management with antiinflammatory and putative chemopreventive agents, and periodic colonoscopic examinations combined with extensive biopsy sampling throughout the colon. The main objective of regular colonoscopy is to detect neoplasia at a surgically curative and preferably preinvasive stage, i.e., dysplasia. An initial screening colonoscopy should be performed 7-8 years from disease onset or immediately in patients with primary sclerosing cholangitis. Surveillance should then continue annually or biennially so long as no dysplasia is found or suspected. Biopsy specimens are graded pathologically as negative, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, or invasive cancer. The diagnosis and grading of dysplasia can be very challenging and should be confirmed by an expert pathologist whenever intervention or a change in management is contemplated. If 1 or more biopsy specimens are indefinite for dysplasia, colonoscopy intervals should be reduced. A patient with low- or high-grade dysplasia found in a discrete adenoma-like polyp, but nowhere else, can be safely managed with polypectomy and accelerated surveillance. However, dysplasia of any grade found in an endoscopically nonresectable polyp and high-grade dysplasia found in flat mucosa are both strong indications for proctocolectomy. Evidence further suggests that the same may be true even of low-grade dysplasia in flat mucosa. Chromoendoscopy holds promise for facilitating the endoscopic detection of neoplasia. The clinical application of newer molecular methods to detect neoplasia, particularly gene microarrays and stool DNA testing, also deserve further study.     

Magnifying colonoscopy with narrow band imaging system for the diagnosis of dysplasia in ulcerative colitis: a pilot study

BACKGROUND: Narrow-band imaging (NBI) is a novel illumination technology for endoscopy that enhances vasculature of the GI tract. OBJECTIVE: The aim was to elucidate whether NBI colonoscopy can identify dysplasia in patients with ulcerative colitis (UC). DESIGN: Cross-sectional study of eligible patients. SETTING: Single center. PATIENTS: 46 patients with UC. INTERVENTIONS: Apparently flat mucosa at each segment and visible protruding lesions were observed by magnifying NBI colonoscopy. The surface structure was classified into honeycomb-like, villous, or tortuous pattern. The grade of dysplasia was determined in the specimens obtained from protrusions and from flat mucosa. MAIN OUTCOME MEASUREMENTS: The positive predictive value of conventional and NBI colonoscopy for the diagnosis of dysplasia. RESULTS: A total of 296 sites (20 protruding lesions and 276 flat areas) were examined by NBI colonoscopy. The surface pattern was determined to be honeycomb like in 161 sites, villous in 85 sites, and tortuous in 50 sites. Five dysplastic lesions were detected in 3 patients. A patient had 3 dysplastic lesions and the other 2 had a dysplastic lesion each. The positive rate of dysplasia was higher in protrusions (2/20 sites, 10%) than in flat mucosa (3/276 sites, 1.1%, P = .038; however, correction for the multiple testing of data removes this significance). When the surface pattern was taken into account, the rate of positive dysplasia was higher in the tortuous pattern (4/50 sites, 8%) than in the honeycomb-like or villous patterns (1/246 sites, 0.4%, P = .003). LIMITATIONS: Uncontrolled study. CONCLUSIONS: The tortuous pattern determined by NBI colonoscopy may be a clue for the identification of dysplasia during surveillance for UC.     

Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study

BACKGROUND & AIMS: Although inflammation is presumed to contribute to colonic neoplasia in ulcerative colitis (UC), few studies have directly examined this relationship. Our aim was to determine whether severity of microscopic inflammation over time is an independent risk factor for neoplastic progression in UC. METHODS: A cohort of patients with UC undergoing regular endoscopic surveillance for dysplasia was studied. Degree of inflammation at each biopsy site had been graded as part of routine clinical care using a highly reproducible histologic activity index. Progression to neoplasia was analyzed in proportional hazards models with inflammation summarized in 3 different ways and each included as a time-changing covariate: (1) mean inflammatory score (IS-mean), (2) binary inflammatory score (IS-bin), and (3) maximum inflammatory score (IS-max). Potential confounders were analyzed in univariate testing and, when significant, in a multivariable model. RESULTS: Of 418 patients who met inclusion criteria, 15 progressed to advanced neoplasia (high-grade dysplasia or colorectal cancer), and 65 progressed to any neoplasia (low-grade dysplasia, high-grade dysplasia, or colorectal cancer). Univariate analysis demonstrated significant relationships between histologic inflammation over time and progression to advanced neoplasia (hazard ration (HR), 3.0; 95% CI: 1.4-6.3 for IS-mean; HR, 3.4; 95% CI: 1.1-10.4 for IS-bin; and HR, 2.2; 95% CI: 1.2-4.2 for IS-max). This association was maintained in multivariable proportional hazards analysis. CONCLUSIONS: The severity of microscopic inflammation over time is an independent risk factor for developing advanced colorectal neoplasia among patients with long-standing UC.     

High-grade dysplastic adenoma-like mass lesions are not an indication for colectomy in patients with ulcerative colitis

Objective. The management of high-grade dysplasia (HGD) in polypoid lesions in patients with ulcerative colitis (UC) is not well characterized. The purpose of this study was to characterize the clinical course of patients with HGD in adenoma-like dysplasia-associated lesion or masses (DALMs) in the absence of any synchronous flat dysplasia. We hypothesize that colectomy is not warranted in patients who undergo complete excision of adenoma-like DALMs with HGD in UC. Material and methods. Pathology and clinical databases were systematically searched for the presence of dysplastic lesions in inflammatory bowel disease from 1997 to 2004. Patients with UC who had adenoma-like DALMs were identified, and a subset with HGD lesions was defined as our study cohort. Results. A total of 102 patients with UC were identified. Thirty of them (29%) had adenoma-like DALMs without synchronous flat dysplasia; 9 of these patients (30%) had HGD in these lesions. Thirty-two surveillance colonoscopies were performed in this cohort (mean 3.6 colonoscopies/patient). The patients were followed for a mean of 76.5 months (52–99 months). Three out of 9 patients (33%) had colectomy. None of the patients in this cohort was detected to have carcinoma in surveillance biopsies and/or in the resection specimens. Conclusions. Our data suggest that the presence of HGD in DALMs does not warrant colectomy. Continued close observation is suggested in this patient cohort after complete excision of polyps. Further prospective evaluation of this patient population is merited.     

Survival and cause-specific mortality in ulcerative colitis: follow-up of a population-based cohort in Copenhagen County

BACKGROUND & AIMS: A population-based cohort from Copenhagen County comprising 1160 patients diagnosed with ulcerative colitis between 1962 and 1987 was followed-up until 1997 to describe survival and cause-specific mortality. METHODS: Observed vs. expected deaths were presented as standardized mortality ratio (SMR) with exact 95% confidence intervals (CI) calculated by using individually registered person-years at risk and Danish 1995 mortality rates. Cumulative survival curves were calculated. RESULTS: A total of 261 deaths occurred, not significantly different from the expected number of 249 (SMR, 1.05; 95% CI, 0.92-1.19). The median age at death among men was 70 years (range, 6-96 years) and among women 74 years (range, 25-96 years). Twenty-five deaths (9.6%) were caused by complications to ulcerative colitis, mostly infectious and cardiovascular postoperative complications. Patients older than 50 years of age at diagnosis and with extensive colitis showed an increased mortality within the first 2 years because of ulcerative colitis-associated causes. The mortality from colorectal cancer was not increased and that of cancer in general was significantly lower than expected: 50 vs. 71 (SMR, 0.70; 95% CI, 0.52-0.93). A significantly increased mortality from pulmonary embolism and pneumonia was found. Among women only, death from genitourinary tract diseases and suicide was significantly increased. CONCLUSIONS: Despite an overall normal life expectancy for patients with ulcerative colitis, patients >50 years of age and with extensive colitis at diagnosis had increased mortality within the first 2 years after diagnosis, owing to colitis-associated postoperative complications and comorbidity.     

Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration

Colonoscopic screening for neoplasia was performed in a regional group of ulcerative colitis patients with a disease duration of greater than or equal to 15 years. A total of 121 patients, aged less than 80 years, were invited to participate, of whom 100 (83%) accepted colonoscopy, including biopsies in 15 standard locations of the entire colon, plus additional biopsies from all visible lesions. Unequivocal dysplasia was found in one patient with extensive colitis and a disease duration of 31 years. A polyp with highly differentiated adenocarcinoma was found in the sigmoid colon of a patient with intermittent rectum involvement, 37 years after the ulcerative colitis diagnosis had been made. Biopsy specimens from the remaining 98 patients showed no signs of dysplasia or cancer. Thus the frequency of pre-malignant or malignant changes is very low compared with the results of similar studies, and the rationale for general colonoscopic surveillance programmes for such patients is open to question.     

Cancer surveillance in ulcerative colitis: critical analysis of long-term prospective programme

BACKGROUND: Patients with longstanding ulcerative colitis are at increased risk of colorectal cancer. In the literature, no agreement has yet been reached regarding prevention strategies. Our report sums up a prospective study started in 1980. METHODS: A total of 65 patients affected by ulcerative colitis for more than seven years were admitted to a regular colonoscopic and biopsy follow-up programme. RESULTS: Some 20 years after the beginning of the study, 23 (35.3%) patients have been operated upon, 2 patients have died but not from cancer 29 (44.66%) patients have abandoned the programme. Only 11 (16.9%) patients have remained under colonoscopic surveillance. CONCLUSION: These results cast some doubts on the significance of such a programme and on its long-term feasibility.