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Excess body weight (EBW) is an independent risk factor for many human malignancies, including cancers throughout the gastrointestinal and hepatobiliary tract from the esophagus to the colorectum. The relative risk of gastrointestinal cancer in obese individuals is approximately 1.5-2.0 times that for normal weight individuals, with organ-specific and gender-specific differences for specific cancers. The association between EBW and risk of premalignant stages of gastrointestinal carcinogenesis, such as colorectal adenoma and Barrett esophagus, is similar, implying a role for EBW during the early stages of carcinogenesis that could be relevant to preventative strategies. EBW also impacts negatively on gastrointestinal cancer outcomes. The mechanistic basis of the association between EBW and carcinogenesis remains incompletely understood. Postulated mechanisms include increased insulin and insulin-like growth factor signaling and chronic inflammation (both linked to the metabolic syndrome), as well as signaling via adipokines, such as leptin. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention. Whether weight loss leads to reduced future gastrointestinal and liver cancer risk has yet to be fully explored. There is some support for the idea that weight loss negatively regulates colorectal carcinogenesis. In addition, data suggest a reduction in risk of several cancers in the first 10 years after bariatric surgery.

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Mucosal abnormalities persist 3 years after RYGB and include elevation of the protumorigenic cytokine MIF, which is upregulated following Apc loss and which contributes to intestinal epithelial cell homeostasis. These observations should prompt clinical studies of colorectal neoplastic risk after RYGB.

Faecal calprotectin (FCP) is a non-invasive biomarker of intestinal inflammation, levels of which are reported to be elevated in individuals with increased body mass index (BMI). We investigated whether weight loss (WL), induced by dietary and behavioural change in a community weight loss programme (Slimming World), was associated with a reduction in FCP in a longitudinal cohort study. We obtained paired stool samples at the start and 11-15 weeks into the weight loss programme in 40 individuals with a BMI >25 kg m(-2) and no known colorectal or systemic inflammatory condition. Eight of 40 (20%) 'healthy' participants had a baseline FCP greater than 50 μg g(-1) (the accepted adult cutoff value for FCP), termed FCP(high). Although the degree (%) of WL was similar (5.1 FCP(high) versus 6.1 FCP(normal); P=0.63), only FCP(high) individuals, but not FCP(normal) participants, demonstrated a reduction in FCP level (median 0.3-fold versus 1.0-fold (that is, no change) during the study period (P=0.065). A large prospective cohort study of FCP(high) and FCP(normal) obese individuals is now required to determine the relationship between local mucosal inflammation and the systemic inflammatory state associated with obesity, as well as understand the relationship between FCP levels, WL and future risk of colorectal neoplasia.

We describe an unusual case of visceral Leishmaniasis affecting the gastrointestinal tract in a young immunocompetent patient whose only recent foreign travel was a trip to Mexico 9 months previously. She presented insidiously with diarrhoea, weight loss and developed subacute intestinal failure. Interestingly, she lacked most of the typical features of acute infection, including visceromegaly, fevers and hypergammaglobulinaemia. Atypical visceral involvement involving the gastrointestinal tract is well recognized in HIV coinfection, but very rare in immunocompetent patients. Repeated microscopy and culture of endoscopic biopsies failed to identify Leishmania parasites. Serological tests - direct agglutination test and anti-K39 antibody tests - were negative. This case highlights a very rare presentation of the condition with the absence of other visceral involvement and diagnosis being eventually made solely on polymerase chain reaction of rectal tissue, with a subsequent excellent response to therapy with intravenous liposomal amphotericin.

Objective: The hypothesis that sleeve gastrectomy (SG) is not associated with an increase in mucosal colorectal cancer (CRC) biomarkers, unlike Roux-en-Y gastric bypass (RYGB), was tested. Design and Methods: Rectal mucosa, blood, and urine were obtained from morbidly obese patients (n 5 23) before and after (median 28 months) SG, as well as from nonobese controls (n 5 20). Rectal epithelial cell mitosis and apoptosis, crypt size=fission, and pro-inflammatory gene expression were measured, as well as systemic inflammatory biomarkers, including C-reactive protein (CRP). Results: The mean pre-operative body mass index in SG patients was 65.7 kg=m 2 (24.7 kg=m 2 in controls). Mean excess weight loss post-SG was 38.2%. There was a significant increase in mitosis frequency, crypt size, and crypt fission (all P < 0.01) in SG patients versus controls, as well as evidence of a chronic inflammatory state (raised CRP and mononuclear cell p65 NFjB binding), but there was no significant change in these biomarkers after SG, except CRP reduction. Macrophage migration inhibitory factor mRNA levels were increased by 39% post-SG (P 5 0.038). Conclusions: Mucosal biomarkers of CRC risk do not increase at 6 months following SG, unlike RYGB. Biomarkers of rectal crypt proliferation and systemic inflammation are increased in morbidly obese patients compared with controls.

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