Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15–40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research.

BackgroundElevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature identified in 60% of sporadic colon cancers and may be linked with heterogeneous expression of the DNA mismatch repair (MMR) protein hMSH3. Unlike microsatellite instability-high (MSI-H) in which hypermethylation of hMLH1 occurs followed by multiple susceptible gene mutations, EMAST may be associated with inflammation and subsequent relaxation of MMR function with the biological consequences not known. We evaluated the prevalence of EMAST and MSI in a population-based cohort of rectal cancers, as EMAST has not been previously determined in rectal cancers.MethodsWe analyzed 147 sporadic cases of rectal cancer using five tetranucleotide microsatellite markers and National-Cancer-Institute-recommended MSI (mononucleotide and dinucleotide) markers. EMAST and MSI determinations were made on analysis of DNA sequences of the polymerase chain reaction products and determined positive if at least two loci were found to have frame-shifted repeats upon comparison between normal and cancer samples from the same patient. We correlated EMAST data with race, gender, and tumor stage and examined the samples for lymphocyte infiltration.ResultsAmong this cohort of patients with rectal cancer (mean age 62.2 ± 10.3 years, 36% female, 24% African American), 3/147 (2%) showed MSI (three males, two African American) and 49/147 (33%) demonstrated EMAST. Rectal tumors from African Americans were more likely to show EMAST than Caucasians (18/37, 49% vs. 27/104, 26%, p = 0.014) and were associated with advanced stage (18/29, 62% EMAST vs. 18/53, 37%, non-EMAST p = 0.02). There was no association between EMAST and gender. EMAST was more prevalent in rectal tumors that showed peri-tumoral infiltration compared to those without (30/49, 60% EMAST vs. 24/98, 25% non-EMAST, p = 0.0001).ConclusionsEMAST in rectal cancer is common and MSI is rare. EMAST is associated with African-American race and may be more commonly seen with metastatic disease. The etiology and consequences of EMAST are under investigation, but its association with immune cell infiltration suggests that inflammation may play a role for its development.

BackgroundNutritional status is an important factor in predicting the risk associated with surgery for cancer patients. This is especially true in colorectal cancer. Many nutritional assessments are used in clinical practice, but those assessments are rarely evaluated for their ability to predict postoperative outcome.MethodsThis is a retrospective, multi-institutional study of the ACS-NSQIP database, investigating preoperative nutrition status and its association with postoperative mortality and morbidity.ResultsThe prevalence of malnutrition is higher in colorectal cancer, when compared with other most common cancers. Among 42,483 colorectal cancer patients postoperative mortality was significantly associated with hypoalbuminemia (hazard ratio = 3.064, p < 0.001), body weight loss (hazard ratio = 1.229, p = 0.033) and body mass index of <18.5 kg/m2 (hazard ratio = 1.797, p < 0.001). Only hypoalbuminemia significantly predicted all postoperative complications, even in further multivariate logistic regression analyses (p < 0.001). Multiple regression analysis showed that the hypoalbuminemia group had the highest coefficient in significant association with length of total hospital stay (B = 3.585, p < 0.001) and overall complication (B = 0.119, p < 0.001).ConclusionsIn colorectal cancer, malnutrition significantly contributes to postoperative mortality, morbidity and length of total hospital stay. Hypoalbuminemia, with levels below 3.5 g/dl, serves as an excellent assessment tool and preoperative predictor of postoperative outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12937-015-0081-5) contains supplementary material, which is available to authorized users.

Background & Aims Little is known about outcomes of patients with ulcerative colitis with low-grade dysplasia (UC-LGD). We estimated the incidence of and risk factors for progression to colorectal cancer (CRC) in cohorts of patients with UC-LGD who underwent surveillance (surveillance cohort), and the prevalence of dysplasia-related findings among patients who underwent colectomy for UC-LGD (surgical cohort). Methods We performed a systematic literature review through June 1, 2016 to identify cohort studies of adults with UC-LGD. We estimated pooled incidence rates of CRC and risk factors associated with dysplasia progression in surveillance cohorts, and prevalence of synchronous advanced neoplasia (CRC and/or high-grade dysplasia) in surgical cohorts. Results In 14 surveillance cohort studies of 671 patients with UC-LGD (52 developed CRC), the pooled annual incidence of CRC was 0.8% (95% CI, 0.4–1.3); the pooled annual incidence of advanced neoplasia was 1.8% (95% CI, 0.9–2.7). Risk of CRC was higher when LGD was diagnosed by expert gastrointestinal pathologist (1.5%) than by community pathologists (0.2%). Factors significantly associated with dysplasia progression were concomitant primary sclerosing cholangitis (OR, 3.4; 95% CI, 1.5–7.8), invisible dysplasia (vs visible dysplasia; OR, 1.9; 95% CI, 1.0–3.4), distal location (vs proximal location; OR, 2.0; 95% CI, 1.1–3.7) and multifocal dysplasia (vs unifocal dysplasia; OR, 3.5; 95% CI, 1.5– 8.5). In 12 surgical cohort studies of 450 patients who underwent colectomy for UC-LGD, 34 patients had synchronous CRC (pooled prevalence, 17%; 95% CI, 8–33). Conclusion In a systematic review of the literature, we found that among patients with UC-LGD under surveillance, the annual incidence of progression to CRC was 0.8%; differences in rates of LGD diagnosis varied with pathologists' level of expertise. Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD are high-risk features associated with dysplasia progression.