Fernando S. Velayos

Effect of 5-Aminosalicylate Use on Colorectal Cancer and Dysplasia Risk: A Systematic Review and Metaanalysis of Observational Studies

OBJECTIVES:We performed a systematic review with metaanalysis of observational studies evaluating the association between 5-ASA use and colorectal cancer (CRC) or dysplasia among patients with ulcerative colitis.METHODS:We conducted a search of Medline Embase Biosis, Web of Science, Cochrane Collaboration, manually reviewed the literature, and consulted with experts. Studies were included if they 1) evaluated and clearly defined exposure to 5-aminosalicylates in patients with ulcerative colitis, 2) reported CRC or dysplasia outcomes, 3) reported relative risks or odds ratio or provided data for their calculations. Quantitative analysis using a random-effects model is presented.RESULTS:Nine studies (3 cohort, 6 case–control) containing 334 cases of CRC, 140 cases of dysplasia, and a total of 1,932 subjects satisfied all inclusion criteria. Five studies reported CRC outcomes alone, two studies reported separate cancer and dysplasia outcomes, and two studies reported a combined outcome of CRC or dysplasia. All primary estimates are homogenous. Pooled analysis showed a protective association between use of 5-aminosalicylates and CRC (OR = 0.51; 95% confidence interval (CI): 0.37–0.69) or a combined endpoint of CRC/dysplasia (OR 0.51; 95% CI: 0.38–0.69). 5-ASA use was not associated with a lower risk of dysplasia, although only two studies evaluated this outcome (OR = 1.18; 95% CI: 0.41–3.43).CONCLUSION:Pooled results of observational studies support a protective association between 5-aminosalicylates and CRC or a combined endpoint of CRC/dysplasia in patients with ulcerative colitis. Additional studies analyzing the effect of 5-ASA on risk of dysplasia are needed.

SCENIC International Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease

Patients with ulcerative colitis or Crohn’s colitis have an increased risk of colorectal cancer (CRC). Most cases are believed to arise from dysplasia, and surveillance colonoscopy therefore is recommended to detect dysplasia. Detection of dysplasia traditionally has relied on both examination of the mucosa with targeted biopsies of visible lesions and extensive random biopsies to identify invisible dysplasia. Current U.S. guidelines recommend obtaining at least 32 random biopsy specimens from all segments of the colon as the foundation of endoscopic surveillance. However, much of the evidence that provides a basis for these recommendations is from older literature, when most dysplasia was diagnosed on random biopsies of colon mucosa. With the advent of video endoscopy and newer endoscopic technologies, investigators now report that most dysplasia discovered in patients with inflammatory bowel disease (IBD) is visible. Such a paradigm shift may have important implications for the surveillance and management of dysplasia. The evolving evidence regarding newer endoscopic methods to detect dysplasia has resulted in variation among guideline recommendations from organizations around the world. We therefore sought to develop unifying consensus recommendations addressing 2 issues: (1) How should surveillance colonoscopy for detection of dysplasia be performed? (2) How should dysplasia identified at colonoscopy be managed?

Incidence and Mortality of Colorectal Adenocarcinoma in Persons With Inflammatory Bowel Disease From 1998 to 2010

BACKGROUND & AIMS The relationship between inflammatory bowel disease (IBD) and the incidence and mortality of colorectal adenocarcinoma (CRC) has not been evaluated recently. METHODS We calculated the incidence and standardized incidence and mortality rate ratios of CRC among adult individuals with intact colons using Kaiser Permanente of Northern Californias database of members with IBD and general membership data for the period of 1998 to June 2010 (data through 2008 were used to calculate mortality). We also evaluated trends in medication use and rates of cancer detection over time. RESULTS We identified 29 cancers among persons with Crohns disease (CD) and 53 among persons with ulcerative colitis (UC). Overall, the incidence rates of cancer among individuals with CD, UC, or in the general membership were 75.0, 76.0, and 47.1, respectively, per 100,000 person-years. In the general population, the incidence of CRC was 21% higher in 2007-2010 than in 1998-2001 (P for trend, <.0001), coincident with the growth of CRC screening programs. The incidence of CRC among individuals with CD or UC was 60% higher than in the general population (95% confidence interval [CI] for CD, 20%-200%; 95% CI for UC, 30%-200%) and was stable over time (P for trend was as follows: CD, .98; UC, .40). During 1998-2008, the standardized mortality ratio for CRC in individuals with CD was 2.3 (95% CI, 1.6-3.0) and 2.0 in those with UC (95% CI, 1.3-2.7). Over the study period, anti-tumor necrosis factor agents replaced other therapies for CD and UC; the rate of colonoscopy increased by 33% among patients with CD and decreased by 9% in those with UC. CONCLUSIONS From 1998 to 2010, the incidence of CRC in patients with IBD was 60% higher than in the general population and essentially stable over time.

Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease

Background:Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed a systematic review and meta-analysis to evaluate the effects of thiopurine exposure during pregnancy or at the time of conception on three measures of fetal risk in women and men with IBD. Methods:A systematic search of PubMed and Web of Science using a combination of Mesh and text terms was performed to identify studies reporting birth outcomes from IBD women and men exposed to thiopurines within 3 months of conception and/or during pregnancy. A meta-analysis was performed using the random effects model to pool estimates and report odds ratio (OR) for three outcomes in women: low birth weight (LBW), preterm birth, and congenital abnormalities and one in men: congenital abnormalities. Results:In women with IBD exposed to thiopurines, the pooled ORs for LBW, preterm birth, and congenital abnormalities were 1.01 (95% confidence interval [CI] 0.96, 1.06), 1.67 (95% CI 1.26, 2.20), and 1.45 (95% CI 0.99, 2.13), respectively. In men, the pooled OR for congenital abnormality was 1.87 (95% CI 0.67, 5.25). Conclusions:Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.

A Test-based Strategy Is More Cost Effective Than Empiric Dose Escalation for Patients With Crohn's Disease Who Lose Responsiveness to Infliximab

BACKGROUND & AIMS Patients with Crohns disease who become unresponsive to therapy with tumor necrosis factor antagonists are managed initially with either empiric dose escalation or testing-based strategies. The comparative cost effectiveness of these 2 strategies is unknown. We investigated whether a testing-based strategy is more cost effective than an empiric dose-escalation strategy. METHODS A decision analytic model that simulated 2 cohorts of patients with Crohns disease compared outcomes for the 2 strategies over a 1-year time period. The incremental cost-effectiveness ratio of the empiric strategy was expressed as cost per quality-adjusted life-year (QALY) gained, compared with the testing-based strategy. We performed 1-way, probabilistic, and prespecified secondary analyses. RESULTS The testing strategy yielded similar QALYs compared with the empiric strategy (0.801 vs 0.800, respectively) but was less expensive (

Risk factors for colorectal neoplasia in inflammatory bowel disease: a nested case-control study from Copenhagen county, Denmark and Olmsted county, Minnesota.

31,870 vs

SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.

37,266, respectively). In sensitivity analyses, the incremental cost-effectiveness ratio of the empiric strategy ranged from

Incidence and prognosis of colorectal dysplasia in inflammatory bowel disease : A population-based study from Olmsted County, Minnesota

500,000 to more than

Early predictors of severe lower gastrointestinal bleeding and adverse outcomes: a prospective study.

5 million per QALY gained. Similar rates of remission (63% vs 66%) and response (28% vs 26%) were achieved through differential use of available interventions. The testing-based strategy resulted in a higher percentage of surgeries (48% vs 34%) and lower percentage use of high-dose biological therapy (41% vs 54%). CONCLUSIONS A testing-based strategy is a cost-effective alternative to the current strategy of empiric dose escalation for managing patients with Crohns disease who have lost responsiveness to infliximab. The basis for this difference is lower cost at similar outcomes.

Time Trends in Therapies and Outcomes for Adult Inflammatory Bowel Disease, Northern California, 1998–2005

OBJECTIVES:Population-based data on risk factors and protective factors for colorectal dysplasia and cancer in patients with inflammatory bowel disease (IBD) are sparse. We conducted a nested case–control study of such factors in two well-described IBD cohorts from Copenhagen County, Denmark and Olmsted County, Minnesota.METHODS:Forty-three neoplasia cases were matched on six criteria to 1–3 controls (N = 102). Medical records were scrutinized for demographic and clinical data. For each variable, the odds of neoplasia were estimated using conditional logistic regression.RESULTS:Primary sclerosing cholangitis (PSC) (odds ratio [OR] 6.9, 95% confidence interval [CI] 1.2–40), percentage of disease course with clinically active disease (OR [per 5% increase] 1.2, 95% CI 0.996–1.4), and ≥1 yr of continuous symptoms (OR 3.2, 95% CI 1.2–8.6) were associated with neoplasia, whereas a borderline association with median number of small-bowel x-rays (OR 1.3, 95% CI 0.96–1.6) was observed. We did not observe a protective effect of frequency of physician visits (OR 1.4, 95% CI 0.96–2.0), number of colonoscopies (OR 1.4, 95% CI 1.0–2.1), cumulative dose of sulfasalazine (OR [per 1,000 g] 1.1, 95% CI 1.0–1.3) and mesalamine (OR [per 1,000 g] 1.3, 95% CI 0.9–1.9), or partial intestinal resections (OR 1.5, 95% CI 0.3–7.1).CONCLUSIONS:Subgroups of IBD patients—those with PSC, severe long-standing disease, and exposure to x-ray—were at greater risk of colorectal neoplasia. The protective effect of close follow-up, colonoscopy, and treatment with 5-aminosalicylates was questionable.