Inflammatory bowel diseases (IBD) increase the risk of developing colorectal cancer. Dietary components that reduce inflammation are associated with lower cancer risk. The long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is present in fish oil and has potent anti-inflammatory properties. The objective of this study is to determine whether dietary fish oil enriched with DHA (DFO) could reduce experimentally induced colitis and colon cancer risk in a mouse model. When SMAD3−/− mice are exposed to Helicobacter hepaticus, mild colitis is observed 4 weeks postinfection. Mice were fed isocaloric diets modified to include corn oil, safflower oil, or DFO (doses ranging from 0.75% to 6.00%) as the fatty acid source for 8 weeks. Mice were gavaged with H. hepaticus; DFO feeding was continued; and mice were sacrificed 4 weeks after infection. The colon and cecum were collected for histopathology. Spleens and mesenteric lymph nodes were collected and analyzed for T-cell populations using flow cytometry. Contrary to expectations, DFO induced severe colitis and adenocarcinoma formation. DFO consumption was associated with decreased CD8 + cell frequency and diminished CD69 expression on CD4 + and CD8 + T-cell populations. Mice consuming DFO also exhibited higher FoxP3 + CD25 + CD4 + T regulatory cell frequency, FoxP3 expression, and altered L-selectin expression during infection. We concluded that DFO-fed mice may be less equipped to mount a successful response to H. hepaticus infection, increasing colon cancer risk. These results support the need to establish a tolerable upper limit for DHA intake particularly in the context of chronic inflammatory conditions such as IBD.

BackgroundObesity increases the risk of colon cancer. It is also known that most colorectal cancers develop from adenomatous polyps. However, the effects of obesity and adipokines on colonic polyp formation are unknown.MethodsTo determine if BMI, waist circumference or adipokines are associated with colon polyps in males, 126 asymptomatic men (48–65 yr) were recruited at time of colonoscopy, and anthropometric measures as well as blood were collected. Odds ratios were determined using polytomous logistic regression for polyp number (0 or ≥3) and polyp type (no polyp, hyperplastic polyp, tubular adenoma).Results41% of the men in our study were obese (BMI ≥30). The odds of an obese individual having ≥3 polyps was 6.5 (CI: 1.3–33.0) times greater than those of a lean (BMI<25) individual. Additionally, relative to lean individuals, obese individuals were 7.8 (CI: 2.0–30.8) times more likely to have a tubular adenoma than no polyp. As BMI category increased, participants were 2.9 (CI: 1.5–5.4) times more likely to have a tubular adenoma than no polyps. Serum leptin, IP-10 and TNF-α were significantly associated with tubular adenoma presence. Serum leptin and IP-10 were significantly associated with increased likelihood of ≥3 polyps, and TNF-α showed a trend (p = 0.09).ConclusionsObese men are more likely to have at least three polyps and adenomas. This cross-sectional study provides evidence that colonoscopy should be recommended for obese, white males.

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Background Dysregulated insulin signaling is thought to contribute to cancer risk. Methods To determine if insulin-related serum factors are associated with colon polyps, 126 asymptomatic men (48–65yr) were recruited at colonoscopy. Blood was collected. Odds ratios were determined using polytomous logistic regression for polyp number and type. Results Males with serum C-peptide concentration >3.3 ng/ml were 3.8 times more likely to have an adenoma relative to no polyp than those with C-peptide ≤1.8 ng/ml. As C-peptide tertile increased, an individual was 2 times more likely to have an adenoma (p=0.01) than no polyp. There were no associations between insulin-like growth factor or its binding proteins with polyp number or type. Males with soluble receptor for advanced glycation end products (sRAGE) concentration >120.4 pg/ml were 0.25 times less likely to have ≥3 polyps relative to no polyps compared to males with sRAGE ≤94.5 pg/ml. For each increase in sRAGE tertile, a man was 0.5 times less likely to have ≥3 polyps than no polyps (p=0.03). Compared to males with a serum vascular endothelial growth factor (VEGF) concentration ≤104.7 pg/ml, males with a serum VEGF concentration >184.2 pg/ml were 3.4 times more likely to have ≥3 polyps relative to no polyps. As the VEGF tertile increased, a man was 1.9 times more likely to have ≥3 polyps than no polyps (p=0.049). Conclusions Serum concentrations of C-peptide, sRAGE, and VEGF may indicate which men could benefit most from colonoscopy. Impact Identification of biomarkers could reduce medical costs through the elimination of colonoscopies on low-risk individuals.

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Increased adiposity does not influence colitis severity in SMAD3-/- mice. Importantly, caloric restriction negatively impacts survival following pathogen challenge, potentially due to an impaired immune response.

Chronic inflammation contributes to colorectal carcinogenesis. To determine if serum cytokines are associated with colon polyps, 126 asymptomatic men (48–65yr) were recruited at colonoscopy. Serum cytokine concentrations were measured. Odds ratios were determined using polytomous logistic regression for polyp number and type. Males with serum monocyte chemotactic protein-3 (MCP-3) or soluble interleukin-4 receptor (sIL-4R) concentrations in the highest tertile were 0.2 times less likely to have ≥3 polyps relative to no polyps. For each increase in serum MCP-3 or sIL-4R tertile a man was about 0.4 times less likely to have ≥3 polyps than no polyps. Males with serum concentrations of interferon-α2 (IFN-α2) or interleukin (IL)-7 in the highest tertile were 3 times more likely to have an adenoma relative to no polyps. Those with serum IL-8 concentrations in the highest tertile were 4 times more likely to have an adenoma relative to no polyps. For each increase in serum IFN-α2, IL-7 or IL-8 tertile an individual was 1.8 times more likely to have an adenoma than no polyp. Serum concentrations of MCP-3, sIL-4R, IFN-α2, IL-7 and IL-8 may indicate which men are more likely to have colorectal polyps.

PURPOSE: Malignant bowel obstruction (MBO) is common in advanced GI cancer, and MBO management, including drainage percutaneous endoscopic gastrostomy (dPEG), is palliative. How patients understand the goals of dPEG and its impact on disease is inadequately understood in the literature. Therefore, we analyzed these issues in patients with GI cancer. METHODS: Demographics, clinical variables, and patient outcomes were abstracted from the medical record. Illness understanding and future expectations were retrieved from palliative care notes. We described additional treatment and outcomes after dPEG and estimated overall survival (OS). RESULTS: From January 2015 to June 2017, 125 admitted patients with metastatic GI cancer underwent dPEG for MBO. Cancers were most commonly colorectal (34%) and pancreatic/ampullary (25%). During the dPEG admission, 32% (40 of 125) of patients had a palliative care consultation, and 22% (28 of 125) were asked about illness understanding and future expectations. All (28 of 28) reported good understanding of the advanced nature of their disease, but few were accurate about prognosis given their stage IV disease (10 of 28). Of the 117 (94%) discharged, 13% (15 of 117) received additional chemotherapy, which rarely prevented progression; half (63 of 117) had a do-not-resuscitate order; and most (101 of 117) were enrolled in hospice at death. Median time to death was 37 days (95% CI, 29 to 45 days); 6-month OS was 3.7% (95% CI, 1.2% to 8.4%). CONCLUSION: dPEGs are placed close to end of life in patients with advanced GI cancer. A minority of patients receive additional chemotherapy post-dPEG. Many have adequate disease understanding, but chemotherapy benefit is low, and future expectations vary. This may be an opportunity for improved communication regarding palliative procedures in advanced cancer.