Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine.

BACKGROUND & AIMS: Evidence suggests that mesalamine-based anti-inflammatory medicines may prevent colorectal cancer (CRC) in ulcerative colitis (UC). If mesalamine exerts its chemopreventive effect by its anti-inflammatory activity, then other medications that reduce colitis activity also should possess chemopreventive properties. Our aim was to determine the effect of the immunomodulators 6-mercaptopurine (6MP) and azathioprine (AZA) in preventing the development of dysplasia or CRC in UC. METHODS: Patients with UC who underwent a surveillance colonoscopy in 1996-1997 were identified from a gastrointestinal pathology database. A proportional hazards analysis assessing 6MP/AZA use as a time-changing covariate was performed to evaluate the effect of 6MP/AZA on: (1) progression to any neoplasia (low-grade dysplasia, high-grade dysplasia, or CRC), and (2) progression to advanced neoplasia (high-grade dysplasia or CRC). RESULTS: A total of 315 subjects met inclusion criteria and were followed for an average of 8 years from their first surveillance examination. There were no significant differences in rates of progression to advanced neoplasia or to any neoplasia between 6MP/AZA users and never-users by log-rank testing. The proportional hazards analysis resulted in hazard ratios of 1.06 (95% confidence interval, .59-1.93) and 1.30 (95% confidence interval, .45-3.75) when considering the effect of exposure to 6MP/AZA on progression to any or to advanced neoplasia, respectively. The results were unaffected by known potential confounders. CONCLUSIONS: In UC patients with no initial history of dysplasia, 6MP/AZA use appears to have little or no effect on the rate of neoplastic transformation in the colon. Importantly, the use of 6MP/AZA did not increase malignant transformation in UC.     

Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis

BACKGROUND & AIMS: Long-standing ulcerative colitis has long been recognized as a risk factor for colorectal cancer, but there is still no universal consensus on the optimal management of ulcerative colitis patients with low-grade dysplasia in flat mucosa. Some authorities favor prompt colectomy, whereas others recommend continued surveillance. The purpose of our study was to determine the frequency with which flat low-grade dysplasia in ulcerative colitis progresses to advanced neoplasia (high-grade dysplasia or colorectal cancer) and whether specific variables could predict such progression. METHODS: We reviewed the medical histories, colonoscopic findings, and surgical and pathology reports of 46 patients with ulcerative colitis diagnosed with flat low-grade dysplasia on a surveillance colonoscopy. The rates of neoplastic progression, as well as the frequency of advanced neoplasia, were tabulated. We correlated progression with several clinical and colonoscopic variables: the number of biopsy samples positive for flat low-grade dysplasia, the duration and anatomic extent of disease, patient age, and medication use. RESULTS: Among these 46 patients, there were 7 cases of colorectal cancer, 5 of which were stage II or higher. Unexpected advanced neoplasia occurred in 4 of 17 (23.5%) patients who underwent colectomy for flat low-grade dysplasia. On an actuarial basis, the rate of neoplastic progression was 53% at 5 years. No clinical features predicted progression to advanced neoplasia. Cancers, including 2 at advanced stages, developed despite frequent follow-up surveillance examinations. CONCLUSIONS: A finding of flat low-grade dysplasia during ulcerative colitis surveillance is a strong predictor of progression to advanced neoplasia. Early colectomy should be recommended for such patients.     

Ki-ras proto-oncogene mutations in sporadic colorectal adenomas: relationship to histologic and clinical characteristics

BACXKGROUND & AIMS: The goal of this study was to examine the relationship between Ki-ras mutations in colorectal adenomas and characteristics of both the subject (age, gender, and family/personal history of colonic neoplasia) and the adenoma (multiplicity, size, location, and histologic features). METHODS: Ki-ras mutations were detected by direct sequencing in 738 adenomatous polyps removed at baseline from 639 participants in a nutritional trial of adenoma recurrence. RESULTS: Ki-ras mutations were detected in 17.2% of the adenomas. Ki-ras mutations were unrelated to gender, family, or personal history of colonic neoplasia, location within the colorectum, or adenoma multiplicity, but were more common in older subjects (P = 0.01 for trend), in larger adenomas (P < 0.0001 for trend), in adenomas with villous histology (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.1-4.9 vs. tubular), and in adenomas with high-grade dysplasia (32.0% vs. 13.6%; OR, 3.0; 95% CI, 1.9-4.6 vs. low-grade dysplasia). Multivariate analysis showed Ki-ras mutations to be independently associated with subject age (P = 0.01 for trend), tubulovillous/villous histology (OR, 2.3; 95% CI, 1.5-3.7), and high-grade dysplasia (OR, 1.9; 95% CI, 1.2-3.1). Adenoma size was not independently related to Ki-ras mutation. CONCLUSIONS: Ki-ras mutations are associated with the histologic features of adenoma progression (villous histology and high-grade dysplasia) rather than with adenoma growth.     

Flat adenomas in the National Polyp Study: is there increased risk for high-grade dysplasia initially or during surveillance?

BACKGROUND & AIMS: The flat adenoma may be a more aggressive pathway in colorectal carcinogenesis. Sessile adenomas from the National Polyp Study cohort were reclassified histopathologically as flat or polypoid and compared with initial and surveillance pathology. METHODS: A total of 933 sessile adenomas detected during 1980-1990 were reclassified as follows: (1) adenoma thickness (AT): < or =1.3 mm, and (2) adenoma ratio (AR): adenoma thickness <2x normal mucosa thickness. Logistic regression was used to assess whether flat adenomas had an effect on risk for high-grade dysplasia initially, and a Cox proportional hazards model assessed the risk for advanced adenomas at surveillance. RESULTS: The analysis encompassed 8401 person-years of follow-up evaluation. AT and AR measures of adenoma flatness were 95% concordant. By the AT measure, flat adenomas (n = 474) represented 27% of all baseline adenomas. Flat adenomas were found to be no more likely to exhibit high-grade dysplasia than sessile (polypoid) or pedunculated adenomas, the odds ratio for high-grade dysplasia was 1.91 (95% confidence interval [CI], 0.66-5.47; P = 0.23) for sessile (polypoid) vs. flat adenomas and 1.78 (95% CI, 0.63-5.02; P = 0.28) for pedunculated vs. flat adenomas adjusted for size, villous component, and location, and corrected for correlation of risk within an individual patient. Patients with flat adenomas at initial colonoscopy were not at greater risk for advanced adenomas at surveillance compared with those with polypoid adenomas only, the odds ratio was 0.76 (95% CI, 0.4-1.42; P = .39), adjusted for multiplicity, age, and family history of colorectal cancer. CONCLUSIONS: Flat adenomas identified in the National Polyp Study cohort at baseline were not associated with a higher risk for high-grade dysplasia initially, or for advanced adenomas at surveillance.     

Five-year colon surveillance after screening colonoscopy

BACKGROUND & AIMS: Outcomes of colon surveillance after colorectal cancer screening with colonoscopy are uncertain. We conducted a prospective study to measure incidence of advanced neoplasia in patients within 5.5 years of screening colonoscopy. METHODS: Three thousand one hundred twenty-one asymptomatic subjects, age 50 to 75 years, had screening colonoscopy between 1994 and 1997 in the Department of Veterans Affairs. One thousand one hundred seventy-one subjects with neoplasia and 501 neoplasia-free controls were assigned to colonoscopic surveillance over 5 years. Cohorts were defined by baseline findings. Relative risks for advanced neoplasia within 5.5 years were calculated. Advanced neoplasia was defined as tubular adenoma greater than > or =10 mm, adenoma with villous histology, adenoma with high-grade dysplasia, or invasive cancer. RESULTS: Eight hundred ninety-five (76.4%) patients with neoplasia and 298 subjects (59.5%) without neoplasia at baseline had colonoscopy within 5.5 years; 2.4% of patients with no neoplasia had interval advanced neoplasia. The relative risk in patients with baseline neoplasia was 1.92 (95% CI: 0.83-4.42) with 1 or 2 tubular adenomas <10 mm, 5.01 (95% CI: 2.10-11.96) with 3 or more tubular adenomas <10 mm, 6.40 (95% CI: 2.74-14.94) with tubular adenoma > or =10 mm, 6.05 (95% CI: 2.48-14.71) for villous adenoma, and 6.87 (95% CI: 2.61-18.07) for adenoma with high-grade dysplasia. CONCLUSIONS: There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance. Patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia.     

Barrett's esophagus: Macroscopic markers and the prediction of dysplasia and adenocarcinoma

BACKGROUND AND AIMS: Surveillance endoscopy has been advocated for patients with Barrett's esophagus but the cost-effectiveness of this has been questioned. The aim of this study is to identify an optimum surveillance protocol by examining if macroscopic markers at diagnosis predict the development of dysplasia. METHODS: The sample was 353 patients with Barrett's esophagus undergoing surveillance by a community-based group of gastroenterologists between 1981 and 2001. At diagnosis the presence of macroscopic and microscopic markers was noted. The presence and pattern of dysplasia and development of adenocarcinoma was documented during subsequent surveillance. RESULTS: Three hundred and fifty-three patients (71% male) underwent regular surveillance over 19 056 patient-months (median 42 months), having a median number of three surveillance endoscopies (range 1-40). Nine patients (seven male) developed adenocarcinoma (1/176 patient years) and four male patients developed high-grade dysplasia (1/397 patient years). Twelve of these 13 patients entered with one or more macroscopic markers: severe esophagitis, nodularity, Barrett's ulcer or stricture. Dysplasia risk was associated with macroscopic markers. Patients who entered with one marker were 6.7 times more likely to develop high-grade dysplasia/adenocarcinoma (HR = 6.7, 95% CI = 1.3, 35). Patients who entered with two or more markers were 14 times more likely to develop high-grade dysplasia/adenocarcinoma (HR = 14.1, 95% CI = 2.02, 102). CONCLUSIONS: The presence of severe esophagitis, Barrett's ulcer, nodularity or stricture at entry indicates a high-risk group for Barrett's esophagus. Cost-effectiveness of surveillance for these patients and those with dysplasia at entry would thus improve.     

Increased Risk of Both Ulcerative Colitis and Crohn’s Disease in a Population Suffering from COPD

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways. In the majority of cases, the inflammation is triggered by tobacco smoke. Smoking also affects the pathogenesis of inflammatory bowel disease (IBD), protecting against ulcerative colitis (UC) and promoting development of Crohn's disease (CD). The present study was undertaken to investigate occurrence of IBD among COPD patients, indicating common inflammatory pathways and shared vulnerability on a genetic basis. The study was designed as a population-based cohort study. All individuals discharged with a diagnosis of COPD from 1987 to 2002 were identified in the Swedish Inpatient Register (n=180,239). Controls and first-degree relatives of both cases and controls were identified using the Multi-Generation Register. Finally, all individuals (n=1,174,557) were compared with the Inpatient Register, identifying discharges with a diagnosis of UC or CD. Hazard ratios (HR) for IBD were determined by Cox proportional hazards regression analysis. COPD patients had a significantly higher risk of both UC (HR 1.83; 95% CI 1.61-2.09) and CD (HR 2.72; 95% CI 2.33-3.18). Among first-degree relatives of COPD patients, there was also an overall increased risk of CD (HR 1.25; 95% CI 1.09-1.43) but not of UC (HR 1.09; 95% CI 0.96-1.23). The kinship of first-degree relatives displayed an increased risk of both UC and CD among siblings (HR 1.49; 95% CI 1.15-1.91 and HR 1.46; 95% CI 1.12-1.89, respectively). The results suggest that COPD and IBD may have inflammatory pathways in common, including genetic variants of genes predisposing for disease.     

Survival of elderly persons undergoing colonoscopy: implications for colorectal cancer screening and surveillance

BACKGROUND: In the elderly, the increased prevalence of colorectal neoplasia and the protective effect of colonoscopy may be offset by advancing age and comorbidity. OBJECTIVE: To describe and quantify the endoscopic findings, survival, and predictors of mortality of elderly persons after colonoscopy. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of persons aged>or=75 years who underwent colonoscopy in 1999 and 2000 at a U.S. Veterans Affairs facility and urban county hospital. MAIN OUTCOME MEASURES: Advanced neoplasms were defined as colorectal cancer (CRC), polyp with high-grade dysplasia, villous histologic features, or tubular adenoma>or=1 cm. Comorbidity was measured with the Charlson comorbidity index. Subjects were followed until death or study closure. RESULTS: Of 469 eligible subjects, 65 were excluded and 404 were included in the study. Fifty-nine of 404 (15%) had an advanced neoplasm, including 8 (2%) with CRC. There were 167 deaths (41%); the mean overall survival was 4.1+/-0.1 years (median 5.95 years). A symptomatic indication for colonoscopy was not predictive of death. Mortality was predicted by age (hazard ratio 1.16 for each year increase beyond age 75 years, 95% CI 1.07-1.3, P=.0003) and Charlson score (hazard ratio 8.3 for each point increase, 95% CI 1.4-48.5, P=.02). The median survival of patients aged 75 to 79 years was >5 years if the Charlson score was or=80 years, the median survival was <5 years regardless of Charlson score. LIMITATIONS: Retrospective design. CONCLUSIONS: In this cohort of elders, age and comorbidity were predictors of death. The protective effect of younger age lessens as comorbidity increases. These findings may have important implications for CRC screening and surveillance in elders.     

EMR for Barrett's esophagus-related superficial neoplasms offers better diagnostic reproducibility than mucosal biopsy

BACKGROUND: EMR of Barrett's esophagus (BE)-related superficial neoplasms represents an efficacious staging modality. It also allows for better pathologic grading compared with mucosal biopsy specimens. However, the interobserver variation in the interpretation of EMR specimens has not been tested. OBJECTIVE: To evaluate consistency in the diagnosis of BE-related neoplasia on EMR specimens. DESIGN: Nine pathologists reviewed 25 esophageal EMR specimens and corresponding biopsy specimens independently. Each pathologist classified the cases as either non-neoplastic BE, low-grade dysplasia, high-grade dysplasia, intramucosal adenocarcinoma, or invasive adenocarcinoma. Interobserver concordance for both specimens from EMRs and biopsies was measured by intraclass correlation and Kendall's coefficient of concordance. The proportion of agreement was also calculated for each specimen and compared for EMR and biopsy by using the Wilcoxon signed rank test. SETTING: Teaching hospitals. PATIENTS: Twenty-five patients who underwent EMR for BE-related neoplasia. RESULTS: The intraclass correlation and the Kendall's coefficient for the 25 biopsy specimens was 0.938 (95% CI 0.880-0.965) and 0.677, respectively; for the 25 EMRs, these were significantly improved, at 0.977 (95% CI 0.957-0.987) and 0.831, respectively. In addition, the proportion of agreement for EMR specimens was significantly better compared with biopsy specimens (P = .015). CONCLUSIONS: Interobserver agreement of BE-related neoplasia on EMR specimens is significantly higher compared with biopsy specimens. The results may relate to the larger tissue sampling compared with biopsy specimens and the ability to evaluate mucosal landmarks, such as double muscularis mucosae. Thus, we suggest that EMRs, in addition to being a staging and therapeutic procedure, improve diagnostic consistency.     

Predictors of proximal neoplasia in patients without distal adenomatous pathology

BACKGROUND: Previous colorectal cancer screening studies have observed that some patients may have advanced proximal neoplasia without distal findings. Since these studies have included only gender, age, and family history as risk factors, they are limited in their ability to identify predictors of isolated proximal neoplasia. METHODS: Data were collected from the charts of 1,988 patients who presented for colonoscopy. Information gathered included endoscopic findings, histology, known risk factors for colorectal neoplasia, and smoking pattern. Our main outcome was the presence of proximal adenomatous neoplasia in patients who had no distal adenomas. We defined significant neoplasia as adenocarcinoma, high-grade dysplasia, villous polyps, adenomas 1 cm or greater or more than two adenomas of any size. RESULTS: Fifty-five patients had isolated significant proximal neoplasia that would have been missed on a flexible sigmoidoscopy. While patients older than 60 yr had a greater risk for this neoplasia (odds ratio = 3.01: 95% CI = 1.66-4.23; p < 0.001), those who took a daily aspirin had a reduced risk (OR = 0.60; 95% CI = 0.30-0.88; p < 0.05). A family history of colorectal cancer increased the patient's risk of having any adenomas (OR = 2.01; 95% CI = 1.33-3.40; p < 0.01) or villous tissue (OR = 2.03; 95% CI = 1.27-3.51; p < 0.05) in the proximal colon without distal findings. Smoking was associated with an increased risk of large (> 1 cm) isolated proximal tubular polyps (OR = 2.71; 95% CI = 1.64-4.46; p < 0.01) as well as isolated significant proximal neoplasia (OR = 2.30; 95% CI = 1.59-3.31; p < 0.01). CONCLUSIONS: Age greater than 60 yr, a history of at least 10 pack-years of smoking, and a family history of colorectal cancer increased the risk of finding significant proximal polyps in patients without distal pathology.     

Childhood growth and risk of inflammatory bowel disease: a population-based study of 317,030 children

Background: Growth in childhood is associated with later development of autoimmune diseases and cancer, but the impact of growth on risk of inflammatory bowel disease (IBD) remains unknown. We conducted a population-based cohort study to examine whether birth weight, childhood height, or changes in height associated with later risk of IBD.

Methods: Our cohort consisted of 317,030 children from the Copenhagen School Health Records Register (born 1930–1989) with height repeatedly measured from age 7 to 13 and with data on birth weight on a subset. Through linkage to the Danish National Patients Register, cases of IBD were identified. Cox proportional hazard regression was used to examine associations between measures of childhood growth and risk of IBD.

Results: During more than 9 million years of follow-up, 1612 individuals were diagnosed with Crohn’s disease (CD) and 2,640 with ulcerative colitis (UC). Birth weight and childhood heights were not associated with subsequent risk of CD or UC (HRs close to 1.00). Childhood growth from 7 to 10 years (CD: HR, 1.00; 95% CI, 0.85–1.18; UC: HR, 0.92; 95% CI, 0.81–1.05) and 10 to 13 years (CD: HR, 1.02; 95% CI, 0.89–1.17; UC: HR, 0.95; 0.85–1.05) did not associate with risk of IBD either.

Conclusion: In this large population-based cohort study, birth weight and childhood growth did not influence risk of IBD, which contrasts with observations in other chronic diseases. Thereby, the study also suggests that pre-clinical effects of adult IBD are not measurable in childhood and that childhood risk factors for IBD do not influence growth.     

Neoplasia in the ileoanal pouch following colectomy in patients with ulcerative colitis and primary sclerosing cholangitis

Background & AimsPrimary sclerosing cholangitis (PSC) is typically associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). PSC–IBD patients are at an increased risk for colorectal neoplasia. The ileal pouch-anal anastomosis (IPAA) is a treatment option for patients with medically refractory UC or neoplasia. However, little is known about the development of pouch neoplasia in PSC–UC patients following an IPAA. We aim to describe the incidence of pouch neoplasia in PSC–UC patients after an IPAA.MethodsWe conducted a retrospective chart review of patients with a confirmed diagnosis of PSC and IBD who underwent colectomy with IPAA followed by pouch surveillance between 1995 and 2012.ResultsSixty-five patients were included in the cohort and were followed up from the time of colectomy/IPAA for a median of 6 years. The most common indications for surgery were low-grade dysplasia (LGD) and refractory colitis. Only 3 patients developed evidence of neoplasia (LGD n = 1, high-grade dysplasia n = 1, adenocarcinoma n = 1). The cumulative 5-year incidence of pouch neoplasia was 5.6% (95% confidence intervals [CI], 1.8%–16.1%).ConclusionBased on our short-term follow-up, surveying the pouch frequently appears to be an unnecessary practice in PSC–IBD patients. Longer follow-up will be needed to develop an optimal surveillance strategy for the development of dysplasia and cancer in such patients.     

Skip inflammation of the appendiceal orifice: A prospective endoscopic study

Objective. The purpose of the study was to evaluate the incidence of discontinuous inflammation of the appendiceal orifice in patients undergoing colonoscopy for diagnosis or surveillance of colonic disease. Material and methods. Consecutive and unselected patients subjected to colonoscopy over a 3-year period were included in a prospective study. Biopsies were taken within 2 cm of the orifice of the appendix, from the caecum and from predefined colonic segments. Discontinuous inflammation of the appendiceal orifice was defined as an area of macroscopic inflammatory changes distinct from a normal caecum of ascending colon. The biopsies were graded histologically for the presence and severity of inflammation by a pathologist without knowledge of the endoscopic findings. Results. A total of 271 patients were included. The final diagnoses were: ulcerative colitis (UC) (83 patients), Crohn's disease (CD) (54), indeterminate colitis (12), irritable bowel syndrome (IBS) (54), microscopic colitis (15) and other disease (53). Endoscopic discontinuous inflammation of the appendiceal orifice was found in 27% (95% CI: 17–38%) of patients with UC, 24% (95% CI: 13–39%) with CD, 40% (95% CI: 12–74%) with indeterminate colitis, 8% (95% CI: 0–36%) with microscopic colitis, 10% (95% CI: 3–24%) of patients with IBS and in 9% (95% CI: 2–21%) of other diseases (p?Conclusions. Discontinuous inflammation of the appendiceal orifice is common in patients with IBD irrespective of clinical activity. However, patients with otherwise normal colon may also show congestion of this area without or with minimal microscopic inflammation.     

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.     

Risk of colectomy in patients with ulcerative colitis under thiopurine treatment

Background and AimsLittle is known about the risk factors of colectomy in patients with ulcerative colitis (UC) under thiopurine treatment. The aim of the study was to determine the prevalence and the predictive risk factors of colectomy in an extensive cohort of patients with UC treated with thiopurines in Spain.MethodsAmong 5753 UC patients, we identified those diagnosed between 1980 and 2009 and treated with azathioprine or mercaptopurine (AZA/MP). We analyzed the age at diagnosis, familial history of IBD, extraintestinal manifestations (EIMs), disease extent, smoking status and treatment requirements (AZA/MP, cyclosporine (CsA) or anti-TNFα). Colectomies for dysplasia or cancer were excluded. Survival analysis and Cox proportional hazard regression were performed. Results were reported as hazard ratios (HR) with 95% CI.ResultsAmong the 1334 cases included, 119 patients (8.9%) required colectomy after a median time of 26 months (IQR 12–42) after AZA/MP initiation. Independent predictors of colectomy were: Extensive UC (HR 1.7, 95% CI: 1.1–2.6), EIMs (HR 1.5, 95% CI: 1.0–2.4), need for antiTNFα (HR 2.3, 95% CI: 1.5–3.4) and need for CsA (HR 2.4, 95% CI: 1.6–3.7). Patients requiring early introduction of AZA/MP had an increased risk of colectomy with a HR of 4.9 (95% CI: 3.2–7.8) when AZA/MP started in the first 33 months after UC diagnosis.ConclusionsNearly one-tenth of patients with UC under thiopurines require colectomy. Extensive UC, EIMs, need for CsA or anti-TNFα ever and an early need for AZA/MP treatment were associated with a higher risk of colectomy. These risk factors of colectomy could help to stratify risk in further controlled studies in UC.     

Evaluation of a risk score based on dietary and lifestyle factors to target a population at risk in colorectal cancer screening

BackgroundThe aim of our study was to assess three risk scores to predict lesions, advanced neoplasia (high-risk adenomas and colorectal cancer (CRC)) and CRC in individuals who participate to colorectal cancer screening.MethodsThe data of dietary and lifestyle risk factors were carried out during 2 mass screening campaigns in France (2013–2016) and the FOBT result was collected until December 2018. The colonoscopy result in positive FOBT was recovered. Three risk scores (Betés score, Kaminski score and adapted-HLI) were calculated to detect individuals at risk of lesions.ResultsThe Betés score had an AUROC of 0.63 (95% CI, [0.61–0.66]) for lesions, 0.65 (95% CI, [0.61–0.68]) for advanced neoplasia and 0.65 (95% CI, [0.58–0.72]) for predicting screen-detected CRC.The adapted HLI score had an AUROC of 0.61 (95% CI, [0.58–0.65]) for lesions, 0.61 (95% CI, [0.56–0.65]) for advanced neoplasia and 0.55 (95% CI, [0.45–0.65]) for predicting screen-detected CRC.The Kaminski score had an AUROC of 0.65 (95% CI, [0.63–0.68]) for lesions, 0.65 (95% CI, [0.61–0.68]) for advanced neoplasia and 0.69 (95% CI, [0.62–0.76]) for predicting screen-detected CRC.ConclusionA simple questionnaire based on CRC risk factors could help general practitioners to identify participants with higher risk of significant colorectal lesions and incite them to perform the fecal occult blood test.     

Progression of low-grade dysplasia to advanced neoplasia based on the location and morphology of dysplasia in ulcerative colitis patients with extensive colitis under colonoscopic surveillance

BackgroundThe management of low-grade dysplasia (LGD) in ulcerative colitis (UC) patients remains unclear.AimThe aim of our study was to study the risk of progression of LGD to advanced neoplasia (AN), defined as high-grade dysplasia (HGD) or colorectal cancer (CRC) for UC patients undergoing surveillance based on location and morphology of LGD.Methods997 UC patients underwent 3152 surveillance colonoscopies from 1998 to 2011. Kaplan–Meier estimates and incidence rates calculated.ResultsOf the 102 patients with LGD (65 raised and 37 flat), 5 (4.9%) patients progressed to AN (3 HGD and 2 CRC) after a median follow-up of 36 months (interquartile range 18–71 months). Initial location of dysplasia was in the proximal colon in 47, distal colon in 55 patients. Four of the 5 (80%) patients with AN had initial dysplasia in the distal colon. Distal colonic LGD had an incidence rate for AN of 2.1 cases per 100 person years at risk, while proximal LGD had an incidence of 0.5 cases per 100 person years. Flat LGD in the distal colon was more likely to progress to AN [hazard ratio = 3.6; 95% confidence interval, CI (1.3–10.6)]. Twenty of the 102 patients (15 flat and 5 raised) underwent colectomy: 2 (10%) had evidence of AN in colectomy (1 HGD and 1 CRC), 9 had LGD and remaining 9 did not have dysplasia.ConclusionsThe frequency of progression of LGD to AN is low. Flat dysplasia located in the distal colon is associated with a greater risk of progression to AN.     

Immunosuppressant medications and mortality in inflammatory bowel disease

OBJECTIVE: This study examined whether treatment of Crohn's disease (CD) and ulcerative colitis (UC) with immunosuppressant medications was associated with an increased risk of death in the era prior to antitumor necrosis factor (TNF) therapies.
DESIGN: This retrospective cohort study used data from the General Practice Research Database from 1987 to 1997. CD and UC patients were matched to controls on age, sex, and primary care practice. CD and UC patients were stratified according to whether they used immunosuppressant medications during follow-up. Cox proportional hazards models adjusted for comorbidities were used to define the relative hazard of death. Additional models examined the relative hazard of death with current use of corticosteroids or thiopurines.
RESULTS: The cohort included 5,539 patients with CD, 8,910 patients with UC, and 41,624 controls. Patients with CD had an increased mortality (not immunosuppressant-treated CD hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.07–1.51; immunosuppressant-treated CD HR 2.44, 95% CI 1.84–3.25). Increased mortality was only observed among UC patients treated with immunosuppressant medications (HR 1.67, 95% CI 1.34–2.09). In both CD and UC, current corticosteroid therapy was associated with increased mortality (CD HR 2.48, 95% CI 1.85–3.31; UC HR 2.81, 95% CI 2.26–3.50). Current use of thiopurines was not associated with increased mortality (CD HR 0.83, 95% CI 0.37–1.86; UC HR 0.70, 95% CI 0.29–1.70).
CONCLUSIONS: Patients treated with corticosteroids, but not thiopurines, are at increased risk of death, although this study could not clarify whether this was as a result of the medication or the underlying disease severity.     

Gastric dysplasia may be an independent risk factor of an advanced colorectal neoplasm

AIM: To evaluate the relationship between gastric dysplasia and Helicobacter pylori ( H pylori) and the occurrence of colorectal adenoma, and to define the necessity for colonoscopy in patients with gastric dysplasia or H pylori infection.METHODS: From May 2005 to February 2008, 133 patients with established gastric dysplasia by gastroduodenoscopy (EGD) were additionally investigated by colonoscopy. The authors compared results with those of 213 subjects who underwent both EGD and colonoscopy during the same period at the author's Health Promotion Center as a control group. H pylori infection was evaluated in both the gastric dysplasia and control groups.RESULTS: The mean age of all 346 study subjects was 54.1 ± 10.5 years, and there were 258 (73%) men and 87 (27%) women. No significant difference was found between the H pylori positive and negative subjects in terms of the prevalence of colorectal adenoma and advanced colorectal adenoma ( P = 0.261). Patients with gastric dysplasia showed no elevated risk of colorectal adenoma (OR = 0.910, 95% CI: 0.5871.411,P = 0.738),but had a significantly higher risk of having advanced colorectal adenoma (OR = 3.382, 95% CI: 1.7006.342,P = 0.000).CONCLUSION: The study emphasizes the need for colon surveillance in patients with gastric dysplasia,regardless of H pylori infection.     

Prevalence and risk of colorectal neoplasia in consumers of alcohol in a screening population

BACKGROUND AND AIMS: Although studies suggest a positive association between alcohol consumption and risk for colorectal neoplasia, the impact on screening has not been fully examined. It is also unclear whether all types of alcohol are associated with an increased risk. We performed a cross-sectional study to examine the impact of regular alcohol consumption on the detection of significant colorectal neoplasia in a screening population. METHODS: Data collected for 2,291 patients presenting for screening colonoscopy: known risk factors for colorectal neoplasia and alcohol drinking pattern. Our outcome was the endoscopic detection of significant colorectal neoplasia, which included adenocarcinoma, high-grade dysplasia, villous tissue, adenomas 1 cm or greater and multiple (>2) adenomas of any size. RESULTS: When compared to abstainers, we found an increased risk for significant neoplasia in those patients who consumed more than eight drinks of spirits alcohol (26.3%; OR = 2.53; 95% CI = 1.10-4.28; p < 0.01) and those who drank more than eight servings of beer per week (21.7%; OR = 2.43; 95% CI = 1.11-5.32; p= 0.02). Consuming one to eight glasses of wine per week was associated with a decreased risk for significant neoplasia (OR = 0.55; 95% CI = 0.34-0.87; p < 0.01). CONCLUSIONS: While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.