The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc Min/+ mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc Min/+ mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.

Background: Obesity and metabolic syndrome are considered the risk factors of colorectal adenoma (CRA) and colorectal cancer (CRC). Chemerin is a novel adipocytokine associated with the development of gastric cancer, esophageal cancer, hepatocellular carcinoma, and CRC. However, the relationship between chemerin levels and CRA remains unclear. Objective: This study is aimed at investigating the association between serum chemerin levels and the development of CRA. Methods: We conducted a total colonoscopy-based cross-sectional case-control study of 80 male patients with CRA and 80 male age-matched control individuals without CRA, according to their endoscopic findings. Serum chemerin concentrations were measured using a sandwich enzyme-linked immunosorbent assay kit, and the OR of CRA was calculated via logistic regression analysis. Results: The mean serum chemerin level of the CRA group was significantly higher than that of the control group (7.9 ± 0.41 vs. 5.16 ± 0.34 ng/mL, p < 0.001). Serum chemerin level was positively correlated to the development of CRA (r = 0.34). Multivariate logistic regression analysis revealed that a high chemerin level was independently associated with the development of CRA (OR 2.82, 95% CI 1.39-5.72). Conclusions: Our findings indicated that increased serum chemerin levels are positively associated with the presence of CRA in men. Chemerin may play an important role in the development of CRA.

The risk of developing metachronous gastric cancer (MGC) following curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) remains even after eradicating Helicobacter pylori (HP) successfully. We screened initial EGC and adjacent non-cancerous mucosa ESD-resected specimens for somatic variants of 409 cancer-related genes, assessing their mutational burden (MB) to predict molecular markers for metachronous post-ESD development. We compared variants between ten patients diagnosed with MGC more than 3 years after ESD and ten age-matched patients who did not have MGC developments after successful HP eradication. We found no significant background differences between the two groups. In adjacent non-cancerous mucosa, the MB tended to be higher in the patients with metachronous developments than in the others. Somatic genomic alterations of RECQL4, JAK3, ARID1A, and MAGI1 genes were significantly associated with MGC development. The criteria including both the MB and their variants, which had potential significant values for predicting MGC. In conclusion, combined of assessing specific somatic variants and MB may be useful for predicting MGC development. This study included a limited number of subjects; however, our novel findings may encourage further exploration of the significance of the molecular features of EGC that predict MGC development, thereby promoting focused follow-up strategies and helping elucidate the mechanisms.

The present report describes a rare case of esophageal carcinoid tumor that was treated by endoscopic resection. A 43-year-old woman underwent esophagogastroduodenoscopy at her family clinic for screening of the upper digestive tract and a small lesion resembling a submucosal tumor was detected in the lower esophagus. A biopsy sample from the lesion was diagnosed as esophageal carcinoid tumor and the patient visited our hospital for detailed examination. The tumor was approximately 3 mm in diameter and its surface appeared to be covered with normal squamous epithelium. The tumor had a shiny reddish surface without ulceration or erosion. Magnifying endoscopy with narrow-band imaging showed structures resembling reticular vessels under the epithelium. Endoscopic ultrasonography depicted the tumor as a low-echoic mass within the lamina propria. Computed tomography did not detect the tumor and no metastatic lesions were evident in other organs. With the patient's informed consent, the tumor was resected using endoscopic submucosal dissection, with a sufficient free margin in both the vertical and horizontal directions. Magnifying endoscopic examination showed the resected tumor to have abundant reticular vessels. Finally, the tumor was diagnosed immunopathologically as an esophageal carcinoid tumor (neuroendocrine cell tumor, grade 1), without lymphatic or vascular invasion.

Background/Aims: Obesity and insulin resistance are associated with an increased risk of colorectal adenoma (CRA). Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis through its amplification of insulin secretion in response to oral nutrients; however, its role in human CRA remains unknown. We investigated oral glucose-mediated GLP-1 secretion in patients with adenoma. Methods: We performed a case-control study of 15 nondiabetic patients with pathologically diagnosed CRA and 10 age-matched healthy controls without adenoma. Plasma concentrations of active GLP-1 were measured during a 75 g oral glucose tolerance test. Results: Mean waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR) values, the total areas under the curve (AUC) of glucose and insulin were significantly higher in patients with CRA than in controls. The total AUC of GLP-1 (p = 0.01) was lower in patients with CRA than in controls. Moreover, the total AUC of GLP-1 showed a negative correlation with WC, total AUC of glucose, and HOMA-IR. Multiple linear regression analyses revealed that the total AUC of GLP-1 was independently correlated with the number and maximum size of CRAs. Conclusion: GLP-1 could actively participate in the development of CRA in humans, particularly in patients with metabolic syndrome.