Kazuhiro Sakuta

Effect of Cellulose Acetate Beads on Interleukin-23 Release

Interleukin (IL)‐23, which is released by activated monocytes and neutrophils, promotes production of high levels of IL‐17 by T‐helper 17 cells. Cellulose acetate (CA) beads are used as carriers for granulocyte and monocyte (GM) adsorptive apheresis using Adacolumn. Contact between blood and CA beads induces cytokine release; however, their inflammatory effects on IL‐23 release are unclear. We aimed to clarify the effect of CA beads on IL‐23 release in vitro. We incubated peripheral blood with and without CA beads and measured IL‐23. Compared to blood samples incubated without CA beads, blood samples incubated with CA beads had significantly decreased amounts of IL‐23. In conclusion, CA beads inhibited IL‐23 release from adsorbed GMs. The biological effects of this decrease in IL‐23 release during GM adsorption to CA beads need further clarification.

Effect of Cellulose Acetate Beads on the Release of Transforming Growth Factor‐β

Transforming growth factor‐β (TGF‐β) is released by activated platelets and induces the differentiation of T‐helper 17 from naïve T cells. Contact between blood and cellulose acetate (CA) beads induces cytokine release, although their inflammatory effects on TGF‐β release are unclear. We aimed to clarify the effect of CA beads on the release of TGF‐β in vitro. We incubated peripheral blood with and without CA beads and measured platelets and TGF‐β. Compared with blood samples incubated without beads, the platelet count and amount of TGF‐β significantly decreased in blood samples incubated with CA beads. In conclusion, CA beads inhibited the release of TGF‐β from adsorbed platelets. The biological effects of this reduction of TGF‐β release during platelet adsorption to CA beads need further clarification.

Esophageal carcinoid tumor treated by endoscopic resection.

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 patients 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.

Treatment with Anti-Interleukin-6 Receptor Antibody Ameliorates Intestinal Polyposis in Apc Min/+ Mice under High-Fat Diet Conditions

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.

Characteristics of Small Bowel Polyps Detected in Cowden Syndrome by Capsule Endoscopy

Cowden syndrome is an uncommon, autosomal dominant disease characterized by multiple hamartomas and hyperplastic lesions in the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. About 30% of Cowden syndrome cases are reportedly complicated by malignant diseases. Hamartomatous polyps occur throughout the gastrointestinal tract, the most common sites being the stomach, colon, esophagus, and duodenum. Small bowel polyps can occur in Cowden syndrome; however, they are difficult to detect by conventional examination, including double-contrast X-ray study. Here, we report three cases of Cowden syndrome with small bowel polyps, which were detected by capsule endoscopy. The small bowel polyps of Cowden syndrome frequently occur at the oral end of the small bowel, especially in the duodenum and jejunum, and their color is similar to that of the surrounding mucosa; additionally, the polyps are relatively small (2–5 mm). Capsule endoscopy is useful for detecting small bowel polyps in Cowden syndrome.

Impaired Secretion of Glucagon-Like Peptide 1 in Patients with Colorectal Adenoma after an Oral Glucose Load

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.

Mo1937 Chemerin As a Risk Factor for Human Colorectal Adenoma

Growing evidence suggests that metabolic syndrome is not only a cluster of risk factors for cardiovascular disease and type 2 diabetes, but also for some cancer including a colorectal cancer. We have previously shown that insulin resistance, an increased visceral fat, hypoadiponectinemia and low-grade systemic inflammation assessed by serum IL-6 levels are linked to the risk of colorectal adenoma. Recently, it has been reported that chemerin, as a novel adipokine, can act as a chemoattractant for immune cells. And obesity, insulin resistance and inflammation have shown to have elevated serum levels of chemerin. However, the role of chemerin in human colorectal adenoma is still unknown. Therefore, we investigated the relationship between serum chemerin levels and the incidence of colorectal adenoma. Methods: We conducted a total colonoscopy-based cross-sectional case-control study. 76 male individuals with an endoscopically diagnosed colorectal adenoma were enrolled along with 72 age-matched male for our control group. Both cohort groups underwent health checkups, between 2007 and 2009, at Tohoku Central Hospital. Serum levels of chemerin were measured in samples of venous blood obtained from the participants after an overnight fast. The risk for colorectal adenoma was evaluated by logistic regression analysis. Results: In the colorectal adenoma group, the mean levels of serum insulin, fasting, plasma glucose, value of HOMA-IR and HbA1c were higher than those in the control group. There were no differences between the groups in the proportions of current smokers, alcohol consumers, mean BMI, bold pressure and serum triglyceride. The mean concentration of serum chemerin was significantly higher in the colorectal adenoma group than in the control group (791±354 ng/ml vs. 538±401 ng/ml, p<0.001). In multivariate analysis, high chemerin level (above the median) was associated with the incidence of colorectal adenoma (OR 2.9, 95%CI; 1.456.09) after adjustment for age, blood pressure, BMI, triglyceride, HOMA-IR and HbA1c. In conclusion, the present study suggests that increased serum levels of chemerin are positively associated with the incidence of colorectal adenoma in men. Our study indicates that chemerin may play an important role in the development of human colorectal adenoma. To confirm our findings in this study, further replication and research are required to elucidate the underlying the mechanisms. This will enable us to gain a better understanding of the link between metabolic syndrome and colorectal adenoma.