Nobuyuki Matsuhashi

Obesity-associated autoantibody production requires AIM to retain the immunoglobulin M immune complex on follicular dendritic cells.

Natural immunoglobulin M (IgM) is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC) that contains various elements, including apoptosis inhibitor of macrophage (AIM). Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM(-/-)) mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

Endoscopic tissue shielding method with polyglycolic acid sheets and fibrin glue to cover wounds after colorectal endoscopic submucosal dissection (with video).

BACKGROUND Colorectal endoscopic submucosal dissection (ESD) has made it possible to resect large specimens in an en bloc fashion. However, this can lead to postoperative adverse events, such as perforation and bleeding. Prevention of adverse events after colorectal ESD is therefore an important goal. OBJECTIVE To evaluate the utility of a shielding method using polyglycolic acid (PGA) sheets and fibrin glue to manage ulcers after colorectal ESD. DESIGN Prospective, single-arm, pilot study. SETTING Single tertiary care center for colorectal ESD in Japan. PATIENTS Ten patients with 10 colorectal tumors scheduled for ESD were enrolled between September and November 2012. INTERVENTIONS Just after ESD, we placed PGA sheets on the mucosal defect with biopsy forceps. After the whole defect was covered, we sprayed fibrin glue through a special double-lumen spraying tube. We sprayed fibrinogen through 1 lumen and then thrombin through the other lumen. MAIN OUTCOME MEASUREMENTS Success rate, mean procedure time, and adverse events associated with the covering technique and the persistence of PGA sheets at follow-up colonoscopy. RESULTS All 10 tumors were successfully resected. Mean tumor size was 39.7 ± 15.2 mm. All mucosal defects were successfully covered with PGA sheets. Mean procedure time was 18.7 ± 15.9 minutes. No procedure-related adverse events occurred. Upon colonoscopy 9 to 12 days after ESD, the PGA sheets were still fixed on the whole defect in 8 patients. LIMITATIONS Small sample size. CONCLUSIONS Our technique, which uses PGA sheets and fibrin glue, appears to shield mucosal defects, and it may be effective in reducing postoperative adverse events.

Effective training system in colorectal endoscopic submucosal dissection.

Although colorectal endoscopic submucosal dissection (ESD) is superior to endoscopic mucosal resection (EMR) in en bloc resection rate, it is technically quite difficult because of the anatomical and histological characteristics of the colorectal wall. This difficulty prevents wide spread of the technique. Establishment of the training system for colorectal ESD is necessary to standardize training and to achieve wider acceptance of this technique. Herein, we describe our training system for colorectal ESD, and assess the validity of the training system for colorectal ESD, based on the clinical outcomes and learning curve of trainees. Our training system for colorectal ESD would help the spread of this procedure.

An effective training system for endoscopic submucosal dissection of gastric neoplasm.

BACKGROUND AND STUDY AIMS A standard training system for endoscopic submucosal dissection (ESD) remains to be established. In this study, we evaluated the validity of our training program for gastric ESD. PATIENTS AND METHODS Four trainees performed gastric ESD for a total of 117 lesions in 107 patients (27 to 30 consecutive lesions per trainee) at a tertiary referral center during 2 years in the training program. Trainees, who already had the fundamental skills and knowledge needed for ESD, each assisted at 40 gastric ESD procedures, then in 20 cases applied post-ESD coagulation (PEC) to gastric mucosal defects; they then began to perform ESD, starting with gastric antral lesions. Treatment outcomes, including mean procedure time, and rates of en bloc resection, en bloc plus R0 resections, complications, and self-completion, were evaluated, for the initial 15 and subsequent 12 to 15 cases. RESULTS Overall rates of en bloc resection and en bloc plus R0 resection were as high as 100 % and 96.6 %, respectively. Regarding complications, seven cases of delayed hemorrhage (6.0 %) and three cases of perforation (2.6 %) occurred; all complications were solved endoscopically. The most frequent reason for operator change was lack of submucosal dissection skill. The self-completion rate was more than 80 % even in the early period, and did not increase for later cases. CONCLUSIONS Our training system enabled novice operators to perform gastric ESD without a decline in clinical outcomes. Key features of this training are prior intensive learning and actual ESD during the learning period under expert supervision.

Usefulness of training using animal models for colorectal endoscopic submucosal dissection: is experience performing gastric ESD really needed?

Background and study aims: Despite the clinical advantages of colorectal endoscopic submucosal dissection (ESD), an effective training system, especially for Western endoscopists, has been challenging to establish. Herein, we propose a novel training program using ex vivo animal models and evaluate the learning curve of colorectal ESD trainees without gastric ESD experience. Patients and methods: A total of 80 colorectal lesions were prospectively collected and removed by two novice operators. Before human ESD procedures, they received ESD training using an ex vivo porcine “proximal colon” model, which simulates a lumen with many folds and flexions. To assess the validity of our training system, the self-completion and en bloc R0 resection rates, the operation time, and prevalence of complications were compared between the first and latter period. Moreover the factors associated with prolonged operation time were evaluated. Results: The overall rates of self-completion and en bloc R0 resection were 98 % (78/80) and 100 % (80/80), respectively. The operation time during the first period was significantly longer than that during the latter period (86 ± 50 minutes vs. 60 ± 36 minutes, P = 0.01). Regarding complications, only two cases of perforations and delayed hemorrhage were observed during the first period; however, all of the complications were successfully managed endoscopically. The presence of fibrosis was identified as a significant independent predictor of a prolonged operation time during the first period (coefficient, 5.90; 95 %CI, 2.36 – 9.44, P = 0.002). Conclusions: Our trainees achieved high rates of self-completion and R0 resection without severe complications even during the first 20 cases, suggesting that our training programs using ex vivo animal models are useful for trainees without gastric ESD experience. Study registration: UMIN000013566

Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan

Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271)

Is narrow-band imaging useful for histological evaluation of gastric mucosa-associated lymphoid tissue lymphoma after treatment?

Endoscopic diagnosis of stomach mucosa‐associated lymphoid tissue (MALT) lymphoma is often difficult because few specific findings are indicated. Even when MALT lymphoma is suspected by endoscopy, it is still difficult to make a definitive diagnosis by biopsy because lymphoma cells sometimes distribute unevenly. We previously reported that a tree‐like appearance (TLA) is a characteristic finding of MALT lymphoma by narrow‐band imaging (NBI) magnifying endoscopy and it is valuable in the selection of an optimal biopsy site in MALT lymphoma. Here, we study the frequency of TLA and evaluate the relationship between the response to eradication therapy and TLA in MALT lymphoma.

Endoscopic papillary large‐balloon dilation versus endoscopic papillary regular‐balloon dilation for removal of large bile‐duct stones

Endoscopic papillary large‐balloon dilation (EPLBD) became popular for the treatment of large common bile‐duct stones (CBDS), and its feasibility has been reported in comparison to endoscopic sphincterotomy. However, the comparison between EPLBD and endoscopic papillary regular‐balloon dilation (EPBD) has not been reported. In the present study, the efficacy and complications of EPLBD were compared with those of EPBD.

Plasma free choline is a novel non-invasive biomarker for early-stage non-alcoholic steatohepatitis: A multi-center validation study.

Aim:  Choline is a dietary component that is crucial for normal cellular function. Choline is predominantly absorbed from the small intestine and completely metabolized in the liver. We recently demonstrated that free choline (fCh) levels in blood reflect the level of phosphatidylcholine synthesis in the liver and is correlated with the onset of non‐alcoholic steatohepatitis (NASH). Our aim here was to validate the utility of this biomarker for NASH diagnosis.

Development of a new classification for in vivo diagnosis of duodenal epithelial tumors with confocal laser endomicroscopy: A pilot study

Confocal laser endomicroscopy (CLE) has been established for in vivo diagnosis of various gastrointestinal diseases. However, validated criteria for confocal diagnosis of duodenal tumors do not exist. Therefore, the aim of the present pilot study was to develop a novel classification for in vivo optical diagnosis of duodenal tumors using CLE.