Makoto Yagi

A multicenter prospective study on the prevalence of Helicobacter pylori-negative and nonsteroidal anti-inflammatory drugs-negative idiopathic peptic ulcers in Japan.

The prevalence of Helicobacter pylori‐negative and nonsteroidal anti‐inflammatory drug‐negative peptic ulcers, commonly known as idiopathic peptic ulcers (IPUs), has been reported to be very low (0.9–2.6%) in Japan based on data from the 1990s. However, recent trends have yet to be been reported. Herein, we present a multicenter prospective analysis between 2012 and 2013 investigating current trends in the prevalence and characteristics of IPUs in Japan.

Diagnosis and treatment of eosinophilic esophagitis in clinical practice

Eosinophilic esophagitis (EoE) is a chronic and abnormal Th2 type immunological response characterized by intense eosinophilic inflammation localized within the esophagus. This leads to esophageal dysfunction and remodeling accompanied by subepithelial fibrosis. Recently, EoE has been recognized as one of the major causes of dysphagia or food impaction in adults. The prevalence of EoE has been increasing over the past several decades, particularly in Western countries. EoE should be differentiated from secondary esophageal eosinophilia (EE) in gastroesophageal reflux disease (GERD) and eosinophilic gastroenteritis, involving the entire gastrointestinal tract. EoE is an uncommon condition in Asia compared with Western countries. With the growing interest and awareness of this condition during the past decade, reports of this disease are increasingly emerging in Asian countries including Japan. Typical EoE does not respond to proton pump inhibitor (PPI) therapy according to the current Western diagnostic guidelines. However, some cases of EE exhibit symptomatic relief and histological improvement in response to PPI [i.e., PPI-responsive esophageal eosinophilia (PPI-REE)]. The understanding of the clinical manifestations and unique endoscopic images of EoE, differences and similarities between GERD, PPI-REE, and EoE will all serve as the differential diagnosis. Further knowledge of the indications and efficacy of PPI therapy and topical steroid therapy will also aid in the management of these diseases. In this article, we will review the current diagnosis and treatment of EoE in clinical practice.

Helicobacter pylori-negative and non-steroidal anti-inflammatory drugs-negative idiopathic peptic ulcers show refractoriness and high recurrence incidence: Multicenter follow-up study of peptic ulcers in Japan.

Helicobacter pylori‐negative and non‐steroidal anti‐inflammatory drugs (NSAIDs)‐negative idiopathic peptic ulcers (IPU) have attracted attention in Japan and other developed countries. The aim of the present study was to clarify the healing rate of IPU and the risk of recurrence.

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.

Relationship Between Tumor Necrosis Factor-α Release and Granulocyte and Monocyte Adsorption to Cellulose Acetate Beads

Tumor necrosis factor‐α, (TNF)‐α, a proinflammatory cytokine, is produced by activated granulocytes and monocytes (GMs) and implicated as a major factor in inflammatory bowel disease (IBD) pathogenesis. Reduction of TNF‐α should improve IBD pathology. GM adsorptive apheresis (GMA) is an effective therapy for inflammatory disorders including IBD. GM adsorption to cellulose acetate (CA) beads induces anti‐inflammatory cytokine release, although these effects on TNF‐α release are not clarified. We hypothesized that GMA may inhibit TNF‐α release. The aim of the present study was to clarify the effects of GM adsorption to CA beads on TNF‐α release in vitro. Peripheral blood was incubated with and without CA beads and TNF‐α was measured. For comparison, TNF‐α was measured in another lipopolysaccharide (LPS)‐containing peripheral blood sample incubated similarly. The amount of TNF‐α in blood samples incubated with CA beads was significantly higher than in those incubated without beads, although it was significantly lower than TNF‐α incubated with LPS‐containing sample without beads. The amount of TNF‐α after incubation with CA beads positively correlated with GM adsorption ratio. GM adsorption to CA beads induced a small amount of TNF‐α release. This is the first report on TNF‐α release induced via GM adsorption stimuli. The biological effects of TNF‐α release during GM adsorption need to be clarified.

Preferential location of idiopathic peptic ulcers

Abstract Objective: Helicobacter pylori infection-negative, nonsteroidal antiinflammatory drugs (NSAIDs)-negative peptic ulcers, which are termed idiopathic peptic ulcers (IPUs), have been increasing worldwide. In this study, we investigated the preferential locations of gastric ulcers according to their cause (e.g., H. pylori and NSAIDs), with special attention to IPUs. Material and methods: A total of 361 patients consecutively diagnosed with a peptic ulcer over a period of one year were classified into four groups according to H. pylori-infection status and NSAIDs usage. The ulcer location was divided into the antrum, angularis, and body, and was compared among the four ulcer groups. Results: The ulcers of 43 patients were classified as IPUs. Compared with simple H. pylori ulcers, IPUs more preferentially located in the antrum (14% vs. 52%, p < 0.01). The difference was more pronounced in the analysis of IPUs in which patients with a history of H. pylori eradication or those with severe atrophic gastritis were excluded, and 79% of these IPUs were located in the antrum. With duodenal ulcers taken together, the vast majority of (86%) these IPUs occurred in the duodenal bulb or the antrum. The proportion of antral ulcers in NSAISs users also differed depending on the presence of concomitant H. pylori infection (positive: 22% vs. negative: 62%, p < 0.01). Conclusion: There was a striking difference in the ulcer location within the stomach depending on the cause of the ulcer, and IPUs predominantly occurred in the antrum. This information on the preferential locations of ulceration should provide endoscopists with some hints concerning the etiology of ulcers.

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.