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Proton pump inhibitor (PPI) therapy causes hypergastrinemia, which could promote the development and progression of neuroendocrine tumors (NETs). Concerns have been raised about the safety of long-term PPI use due to a possible increased risk of NETs. This study aimed to investigate the association between hypergastrinemia and the risk of NETs. Twenty outpatients presenting with serum gastrin levels greater than 400 pg/mL after long-term PPI treatment were registered in this study. Immunohistochemical analyses for chromogranin A (CgA), Ki67, gastrin and CCK/B gastrin receptor (CCKBR) were performed, and positive cell numbers were counted. There were no NET or gastric epithelial neoplasia cases observed among any of the 20 patients examined throughout the PPI treatment period. Histologically, ECL cell hyperplasia were shown in all patients. However, no relationship was found between serum gastrin levels and the number of CgA positive ECL cells. There was also no relationship between serum gastrin levels and the proportion of Ki67 positive cells or the density of CCKBR positive cells. The data indicate no relationship may exist between NETs and hypergastrinemia secondary to PPI treatment in patients having no, or mild, atrophic gastritis.

Background Endoscopic submucosal dissection (ESD) is more invasive than other common endoscopic procedures and may increase the risk for deep vein thrombosis (DVT)/pulmonary embolism. The incidence of DVT/pulmonary embolism after ESD has not been adequately studied. Objective To evaluate DVT incidence and disease-specific features of D-dimer levels in ESD patients. Design Prospective cohort study. Setting Single academic center. Patients This study involved 60 patients with superficial gastric neoplasms indicated for ESD. Intervention For all patients who underwent ESD, ultrasonography of the lower limbs was performed to detect DVT the day after ESD. D-dimer levels were measured 3 times: before ESD, immediately after ESD, and the day after ESD. Main Outcome Measurements DVT incidence after ESD. Results The DVT incidence was 10.0% (6/60). At all 3 time points, D-dimer measurements were higher in patients with DVT than in patients without DVT. According to receiver operating characteristic curve analysis, the resulting cut-off value of the D-dimer level the day after ESD was 1.9 μg/mL (sensitivity 83.3%; specificity 79.6%) for ESD patients, with superior association to pre-ESD or immediately after ESD. In univariate analyses, high D-dimer levels the day after ESD and the presence of comorbidities were significantly associated with DVT development. Limitations Single center and small number of patients. Conclusion ESD procedures have a moderate risk for venous thromboembolism. In patients undergoing ESD, D-dimer levels, especially on the day after ESD, may have specific features associated with DVT development.

Background There is no known preventive agent against nonsteroidal anti-inflammatory drug (NSAID) induced small-intestinal injury. Objective To evaluate by capsule endoscopy whether coadministration of prostaglandin (PG) can prevent small-intestinal damage induced by short-term NSAID treatment. Design Single-blind, randomized, controlled trial. Setting All procedures were performed at Nippon Medical School. Subjects Thirty-four healthy male volunteers. Methods All subjects were randomly assigned to 2 groups: an NSAID-control group, who underwent NSAID (diclofenac sodium, 25 mg 3 times daily) and omeprazole (20 mg once daily) treatment, and an NSAID-PG group, who received PG (misoprostol, 200 μg 3 times daily) in addition to the same NSAID-omeprazole treatment. Eligible subjects, 15 per group, underwent capsule endoscopy before and 14 days after treatment. Main Outcome Measurements The number of mucosal breaks at capsule endoscopy. Results NSAID treatment significantly increased the mean (SD) number of mucosal breaks per subject, from a basal level of 0.1 ± 0.3 up to 2.9 ± 6.3 lesions in the NSAID-control group ( P = .012). In contrast, there was no significant change in the mean number of mucosal breaks before and after PG cotreatment ( P = 0.42). Thus, the mean number of posttreatment mucosal breaks per subject was significantly higher in the NSAID-control group than in the NSAID-PG group ( P = .028). There was a significant increase in the percentage of subjects in the NSAID-control group, with at least 1 mucosal break after treatment (from 6.7% to 53.3%), whereas there was no change in the incidence of mucosal breaks in the NSAID-PG group, which remained at 13.3%. ( P = .002). Limitations Single-center, open-label study. Conclusions PG cotherapy reduced the incidence of small-intestinal lesions induced by a 2-week administration of diclofenac sodium.

Background Double-balloon endoscopy (DBE) is a new method that allows visualization, tissue sampling, and therapeutic intervention of a variety of pathologies throughout the small-intestinal tract. Objective In the present study, we evaluated the diagnostic yield of DBE and its impact on the final diagnosis, treatment, and clinical outcome of patients with obscure GI bleeding (OGIB). Design and Setting A hospital-based cross-sectional, follow-up study. Patients We studied 108 consecutive patients (66 men and 42 women) referred to our hospital from July 2003 to February 2007 for the evaluation of OGIB: 13 patients with overt-ongoing bleeding, 76 with overt-previous bleeding, and 19 with occult OGIB. Main Outcome Measurements Diagnostic yield, a final diagnosis, treatment, and clinical outcome were all analyzed in each group. Results DBE diagnostic rates for patients with overt-ongoing, overt-previous, and occult bleeding were 100.0%, 48.4% and 42.1%, respectively. The difference in diagnostic yields between the overt-ongoing group and the 2 other groups was statistically significant ( P Conclusions DBE was proven to be a very useful diagnostic tool and had a therapeutic impact in the majority of patients with OGIB. The best candidates for the procedure were patients with overt-ongoing bleeding.

Recent studies have reported that expression of MCP-1 and its receptor, CCR2; and CD40-CD40 ligand (CD40L) interaction on mesenchymal cells play important roles in tumor development. Studies have also connected MCP-1, CCR2, and CD40L to COX-2 expression. The aim of this study was to examine the effect of MCP-1/CCR2 and CD40-CD40L interaction on COX-2 and VEGF expression in endothelial cells. We also investigated the localization of these proteins in gastric cancer tissue. COX-2 and CCR2 levels were evaluated in CD40L-stimulated HUVECs by Western blot and real-time PCR. VEGF secreted in the culture media was quantified by ELISA. Localizations of MCP-1, CD40L, CD34, CD40 and CCR2 in 34 gastric cancer tissue specimens were evaluated by immunohistochemistry. CD40-CD40L interaction-induced COX-2 production and subsequently, upregulated COX-2 production contributed to elevated VEGF and CCR2 levels in CD40L-stimulated HUVECs. CD40L-stimulated VEGF production was COX-2 but not COX-1 dependent. RS-102895, a CCR2-specific antagonist, significantly reduced VEGF production in CD40L- and MCP-1-stimulated HUVECs. MCP-1 had a synergistic effect on COX-2, CCR2 and VEGF levels in CD40L-stimulated HUVECs. In gastric cancer tissue, there was significant correlation between microvessel density and scores for CD40L, MCP-1 and CCR2 protein expression. Thus, MCP-1 had a synergistic effect on COX-2 and CCR2 protein expression in CD40L-stimulated HUVECs and thereby stimulated VEGF production in these cells.

Background The recent development of double balloon endoscopy (DBE) has revolutionized enteroscopy. This system allows for endoscopic scrutiny and treatment of the entire small bowel, but general consensus has not yet been reached regarding procedural guidelines. Methods We have been using the DBE system since June 2003, at Nippon Medical School Hospital, Tokyo, Japan, where 163 patients have undergone 265 DBE examinations. This study presents a detailed analysis of the current status of DBE examination at our institution, with particular focus on indications, contraindications, sedation, choice of insertion route, complications, and relevant technical points. Observations The most common indication for DBE was obscure GI bleeding. Patients were placed under conscious or deep sedation and their vital signs were monitored throughout the examination. The choice of either an oral or anal insertion route was determined on the basis of clinical symptoms or any previous examination data. When analyzing the entire small bowel, we began via the anal route and marked the intestine with India ink at the furthest insertion point lying closest to the oral route. We then switched our approach to the oral route, and confirmed total enteroscopy when the enteroscope reached the India-ink mark. With regard to complications, we encountered 1 case of acute pancreatitis and 2 cases of aspiration pneumonia after examination. Conclusions The DBE system allows for full investigation of the pathology of the small intestine and timely endoscopic treatment. However, for the DBE system to achieve more widespread acceptance, it is critical that we establish a universal method for its safe and efficient use.

Usefulness of Double-Balloon Endoscopy for Diagnosis and Treatment of the Post-Operative Gastrointestinal Tract Shu Tanaka, Keigo Mitsui, Atsushi Tatsuguchi, Akihito Ehara, Tsuyoshi Kobayashi, Tsuguhiko Seo, Masaoki Yonezawa, Kazuhiro Nagata, Yoshiaki Shibata, Shunji Fujimori, Teruyuki Kishida, Katya Gudis, Choitsu Sakamoto Backgrounds and Aims: Endoscopic examination of the afferent limb, or choledocho-jejunostomy, in patients with various surgical reconstructions of the gastrointestinal tract, such as Roux-en-Y anastomosis or Billroth II gastrojejunostomy, is often extremely difficult due to anatomical characteristics and intestinal adhesion. Although the advent of video capsule endoscopy facilitated the observation of the entire small bowel, one of the limitations of this new technology includes the difficulty of accessing the surgically reconstructed gastrointestinal tract. Double-balloon endoscopy (DBE) (Fujinon, EN-450P5/20, EN-450T5/20, Fuji Photo Optical Co., Ltd., Saitama, Japan) facilitates the selective inspection of discrete intestinal regions, and allows for timely endoscopic treatment of disorders heretofore requiring surgical intervention. In this study, we evaluated the efficacy of double-balloon endoscopy in patients with surgically reconstructed gastrointestinal tracts. Patients: A total of 130 patients underwent 200 DBE examinations between Jun. 2003 and Nov. 2005 at Nippon Medical School Hospital, Tokyo, Japan. Among them, 12 consecutive patients with surgically reconstructed gastrointestinal tracts were enrolled. The median age of these 12 patients was 65.3 (30-81); 6 men and 6 women. The surgical procedures of these patients included Billroth II gastrojejunostomy in 5 patients, Roux-en-Y anastomosis in 3 patients, pancreatoduodenectomy in 3 patients, and blind loop with side to side anastomosis in 1 patient. Results: DBE could reach the cecum of the afferent loop in 10 of 12 patients (83.3%), with endoscopic access and direct observation successfully carried out in all these 10 patients. Cholangiocellular carcinomas were found in 2 patients, choledocholithiasis in 2 patients, and 4 patients underwent the procedure for endoscopic retrograde cholangiography (ERC). Anastomotic stricture after Rouxen-Y anastomosis was found in 1 patient who had been suffering from symptoms of ileus. A detachable stent was placed at the stricture, and clinical symptoms improved. No complications were encountered during and after any of these procedures. Conclusions: DBE is a very useful and safe tool for the diagnosis and treatment of lesions in the surgically reconstructed gastrointestinal tract. It may also preclude unnecessary surgical intervention in certain cases.

Double-Balloon Endoscopy: A Novel Endoscopic Technique for the Treatment of Small Intestinal Diseases Shu Tanaka, Keigo Mitsui, Atsushi Tatsuguchi, Akihito Ehara, Tsuyoshi Kobayashi, Tsuguhiko Seo, Masaoki Yonezawa, Kazuhiro Nagata, Yoshiaki Shibata, Shunji Fujimori, Teruyuki Kishida, Katya Gudis, Choitsu Sakamoto Background and Aims: Endoscopic observation and treatment of the small bowel has been limited by its inaccessibility. Recently, Yamamoto et al. have reported a new insertion method of enteroscopy, double-balloon endoscopy (Fujinon EN-450P5/20, EN-450T5/20, Fuji Photo Optical Co., Ltd., Tokyo, Japan), which allows endoscopic scrutiny and treatment of the entire small bowel, with intervention capabilities; using two balloons to alternately grip the intestinal wall. This method enables us to investigate the pathophysiology of the small intestine, and allows for timely endoscopic treatment of disorders heretofore requiring surgical intervention. In this study we evaluated the efficacy of the double-balloon enteroscopy system in the endoscopic treatment of the small bowel. Results: 65 patients underwent a total of 90 double-balloon enteroscopies; between June 2003 and October 2004 at Nippon Medical School, Tokyo, Japan. The median age was 60.9 (range, 33-81) years. In all, 9 patients were successfully treated in the process of endoscopic examination. Electrocoagulation for hemostasis at the bleeding source, such as regions of angiodysplasia deep in the small bowel, was conducted in 4 patients. Direct observation of surgically bypassed tract or afferent loop of the Roux-en-Y or Billroth II anastomosis, and scrutiny of the bile duct after gastrointestinal reconstruction, were performed endoscopically in 3 patients. Endoscopic balloon dilatation of a stricture in the small intestine was carried out in 1 patient with delayed stenosis following abdominal blunt trauma, and a foreign body trapped by ileal stenosis was retrieved successfully in another patient. The extent of lesions ranged over the whole small intestine, with inclusion of a blind loop not accessible by capsule endoscopy. All these treatments were outside the scope of conventional methods, but were made possible by this innovative system, which improved access to previously inaccessible areas of the small intestine. We encountered no complications during and after any procedure. Conclusions: Double-balloon enteroscopy is being proven to be a safe and valuable method, with high diagnostic yield offering a wide range of therapeutic capabilities. Our results suggest that double-balloon enteroscopy can dramatically increase the range of endoscopic treatment and may in certain cases preclude unnecessary surgical intervention. Abstracts