Hideharu Ogiyama

Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer : A prospective randomized controlled trial

OBJECTIVES:With conventional methods of endoscopic mucosal resection for early gastric cancer (EGC), proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) have a similar effect on preventing bleeding from artificial ulcers. An objective of this study is to investigate whether a stronger acid suppressant (i.e., PPI) more effectively prevents bleeding after the recent advanced technique of endoscopic submucosal dissection (ESD) for EGC.METHODS:This was a prospective randomized controlled trial performed in a referral cancer center. A total of 143 patients with EGC who underwent ESD were randomly assigned to the treatment groups. They received either rabeprazole 20 mg (PPI group) or cimetidine 800 mg (H2RA group) on the day before ESD and continued for 8 wk. The primary end point was the incidence of bleeding that was defined as hematemesis or melena that required endoscopic hemostasis and decreased the hemoglobin count by more than 2 g/dL.RESULTS:In baseline data, the endoscopists who performed the ESD were significantly different between the groups. Finally, 66 of 73 patients in the PPI group and 64 of 70 in the H2RA group were analyzed. Bleeding occurred in four patients in the PPI group and 11 in the H2RA group (P = 0.057). Multivariate analysis revealed that treatment with the PPI significantly reduced the risk of bleeding: adjusted hazard ratio 0.47, 95% confidence interval 0.22–0.92, P = 0.028. One delayed perforation was experienced in the H2RA group.CONCLUSIONS:PPI therapy more effectively prevented delayed bleeding from the ulcer created after ESD than did H2RA treatment.

Endoscopic submucosal dissection for early gastric cancer performed by supervised residents: assessment of feasibility and learning curve *

BACKGROUND AND AIM Endoscopic submucosal dissection (ESD) is feasible as a treatment for early gastric cancer (EGC) when it is performed by an experienced endoscopist. We investigated whether it was feasible for novice endoscopists to perform ESD for EGC, and how difficult it was to learn the procedure. METHODS This case series study was performed in a cancer referral center. Three resident endoscopists, who had already learned basic procedures, performed ESD under supervision for 30 consecutive lesions, and their procedures were analyzed. The procedure was divided for assessment into (i) mucosal incision and (ii) submucosal dissection by completion of the circumferential mucosal cut. An insulated-tip knife was used for mucosal incision and submucosal dissection. A total of 90 mucosal EGCs (< or = 2 cm) without ulcers or scars in 87 patients were included. Outcomes were: rates of complete resection, complications, and self-completion; operation time; learning curve; and reasons for change of supervisor as an indicator of difficulty. RESULTS Among the 90 procedures, there was a good overall complete resection rate of 93 %, with an acceptable complication rate of 4.4 %; the complications were delayed hemorrhage in two patients, and perforations in another two patients that were repaired successfully by endoscopic clipping. The self-completion rate and operation time were significantly worse for submucosal dissection than for mucosal incision. Two of the three operators showed a flat learning curve for submucosal dissection. Difficulty with the procedure was related mainly to uncontrollable hemorrhage. CONCLUSIONS With appropriate supervision, gastric ESD by residents is feasible, with equivalent complete resection rates and acceptable complication rates compared with those of experienced endoscopists, although there was difficulty in achieving sufficient self-completion rates in submucosal dissection. Better control of bleeding during submucosal dissection may be a key to improving the procedure.

Scheduled endoscopic surveillance controls secondary cancer after curative endoscopic resection for early gastric cancer: a multicentre retrospective cohort study by Osaka University ESD study group

Background After endoscopic submucosal dissection (ESD) of early gastric cancer (EGC), patients are at high risk for synchronous or metachronous multiple gastric cancers. Objective To elucidate the time at which multiple cancers develop and to determine whether scheduled endoscopic surveillance might control their development. Design A multicentre retrospective cohort study from 12 hospitals was conducted. Patients with EGC who underwent ESD with en bloc margin-negative curative resection were included. Synchronous cancer was classified as concomitant cancer or missed cancer. The cumulative incidence of metachronous cancers and overall survival rate were calculated using the Kaplan–Meier method. Results From April 1999 to December 2010, 1258 patients met the inclusion criteria. Synchronous or metachronous multiple cancers were detected in 175 patients (13.9%) during a mean of 26.8 months. Among the 110 synchronous cancers, 21 were missed at the time of the initial ESD. Many of the missed lesions existed in the upper third of the stomach and the miss rate was associated with the endoscopists inexperience (<500 oesophagogastroduodenoscopy cases). The cumulative incidence of metachronous cancers increased linearly and the mean annual incidence rate was 3.5%. The incidence rate did not differ between patients with or without Helicobacter pylori eradication. Four lesions (0.32%) were detected as massively invading cancers during the follow-up. Conclusions Nineteen per cent of synchronous cancers were not detected until the initial ESD. The incidence rate of metachronous cancer after ESD was constant. Scheduled endoscopic surveillance showed that almost all recurrent lesions were treatable by endoscopic resection.

SHORT-TERM OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR EARLY GASTRIC NEOPLASM: MULTICENTER SURVEY BY OSAKA UNIVERSITY ESD STUDY GROUP

Background:  Endoscopic submucosal dissection (ESD) was developed for en bloc removal of large and flat gastrointestinal tract neoplasms. In Japan, ESD is performed under conscious sedation. The risks for sedation‐related complications of ESD, such as postoperative pneumonia, have not been evaluated. The aim of this study was to evaluate the incidence of postoperative pneumonia after ESD in a multicenter survey.

Disturbed gastrointestinal motility and decreased interstitial cells of Cajal in diabetic db/db mice

Background and Aim:  Diabetes mellitus (DM) often causes gastrointestinal dysmotility. Interstitial cells of Cajal (ICC), which express c‐kit receptor tyrosine kinase (KIT), are considered the pacemaker cells for gastrointestinal movement. The present study was designed to determine the role of ICC in the pathogenesis of gastroenteropathy in type 2 DM.

Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms: a multicenter retrospective cohort study

BACKGROUND AND STUDY AIMS The safety and efficacy of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms (SENs) have not been evaluated in a multicenter survey. The aim of this study was to investigate the clinical outcomes in a multicenter study that included municipal hospitals. PATIENTS AND METHODS Of 312 consecutive patients with 373 esophageal lesions treated by ESD at 11 hospitals from May 2005 to December 2012, a total of 368 SENs in 307 patients were retrospectively analyzed. RESULTS The median tumor size was 18 mm (range 2 - 85 mm). The median procedure time was 90 minutes (range 12 - 450 minutes). The en bloc resection and complete resection rates were 96.7 % (95 % confidence interval [CI] 94.4 % - 98.1 %) and 84.5 % (95 %CI 80.5 % - 87.8 %), respectively. Perforation (including mediastinal emphysema), postoperative pneumonia, bleeding, and esophageal stricture, occurred in 5.2 % (95 %CI 3.3 % - 7.9 %), 1.6 % (95 %CI 0.7 % - 3.5 %), 0 %, and 7.1 % (95 %CI 4.9 % - 10.2 %) of patients, respectively. All of these complications were cured conservatively. No procedure-related mortality occurred. Early treatment periods (odds ratio [OR] = 4.04; P < 0.01) and low volume institutions (OR = 3.03; P  = 0.045) were significantly independent risk factors for perforation. The circumference of the lesion was significantly associated with postoperative stricture (OR = 32.3; P < 0.01). The procedure times significantly decreased in the later period of the study (P < 0.01). Follow-up data (median 35 months; range 4 - 98 months) showed significant differences in overall survival (P = 0.03) and recurrence-free survival (P < 0.01) rates between patients with curative and noncurative resections. CONCLUSIONS Esophageal ESD has become feasible with acceptable complication risks and favorable long term outcomes.

Local Resection by Combined Laparoendoscopic Surgery for Duodenal Gastrointestinal Stromal Tumor

Combined laparoendoscopic surgery is a novel surgical method which consists of both endoscopic surgery from inside the gastrointestinal tract and laparoscopic surgery from the outside. We report a case of duodenal GIST, in which combined laparoendoscopic local resection was attempted. The lesion was resected endoscopically using endoscopic submucosal dissection technique under laparoscopic assistance. Laparoscope was used for originating the orientation of the tumor, intra-operative EUS, and monitoring serosal injury from the peritoneal cavity. Postoperative hemorrhage occurred; however, precise orientation of the lesion helped us to manage the patient with minimal invasive reoperation. And thus, the bowel integrity was completely preserved, by avoiding segmental duodenal resection and pancreaticoduodenectomy. This novel, less invasive surgical procedure may become an attractive option for the lesions originating in the anatomically challenging portion of the GI tract for endoscopic or laparoscopic surgery alone.

Lack of adiponectin promotes formation of cholesterol gallstones in mice.

Plasma adiponectin levels are reduced in obese people, and hypoadiponectinemia is recently reported to associate with cholesterol gallstone formation in human. The aim of this study was to examine the role of adiponectin in gallstone formation using adiponectin knockout mice. We analyzed male knockout and C57BL6J mice fed normal or lithogenic diet for 6 weeks. On lithogenic diet, the prevalence rate of gallstone was significantly greater in knockout mice than C57BL6J mice. The molar percentages of beta and omega-muricholic acid were significantly higher and hepatic sterol 12 alpha-hydroxylase expression (cyp8b1) was significantly lower in knockout mice than C57BL6J mice fed normal diet. The bile apolipoprotein A-I protein levels were decreased in knockout mice. Histological examination showed gallbladder wall thickening and accumulation of glycoprotein in the gallbladder of knockout mice. Gallbladder phospholipase A2-IVA expression was significantly higher in knockout mice than in C57BL6J mice fed lithogenic diet. Our results indicate that lack of adiponectin promotes gallstone formation in mice.

Renal dysfunction is an independent risk factor for bleeding after gastric ESD

Background and study aims: The number of patients with chronic kidney disease (CKD) is increasing worldwide and gastric cancer sometimes occurs with CKD. However, the safety and feasibility of endoscopic submucosal dissection (ESD) for patients with CKD are not clear. The aim of this study is to clarify the feasibility and safety of gastric ESD for patients with CKD. Patients and methods: This was a multicenter retrospective cohort study. In total, 144 patients with CKD who underwent gastric ESD between May 2003 and October 2012 were enrolled. The patients were divided into three groups: stage 3 (estimated glomerular filtration rate [eGFR]: 30 – 59 mL/min), stage 4 (eGFR: 15 – 29 mL/min), and stage 5 (eGFR: < 15 mL/min) according to the Kidney Disease Improving Global Outcomes Guidelines. The en bloc and curative resection rates and complications were assessed as short-term outcomes. Overall survival was analyzed using Kaplan – Meier methods. Results: In total, 92 patients were in stage 3 CKD; 23 in stage 4; and 29 in stage 5, including 19 patients in hemodialysis. The en bloc resection rate was 95.8 %. Post-ESD bleeding was observed in four patients with stage 5 CKD (13.8 %), three with stage 4 (13.0 %), and one with stage 3 (1.1 %). All bleeding could be controlled by endoscopic hemostasis, but five patients required blood transfusion. Perforation occurred in two patients (6.9 %) with stage 5 CKD, none (0 %) with stage 4, and two (4.3 %) with stage 3. Multivariate Poisson regression analysis revealed CKD stage 4 was a critical factor related to bleeding, whereas diabetes mellitus and CKD stage 5, which largely consist of patients receiving hemodialysis, were not. The median observation period of patients who achieved curative resection was 25.9 months (range 0.8—112.7 months) and the 3-year overall survival rate was 92.5 %. Conclusions: Estimated GFR is a significant independent predictive factor of post-ESD bleeding in patients with CKD.

Incidence of gastric adenocarcinoma among lesions diagnosed as low‐grade adenoma/dysplasia on endoscopic biopsy: A multicenter, prospective, observational study

Differentiation between gastric adenocarcinoma and low‐grade adenoma/dysplasia (LGA) on endoscopic forceps biopsy is difficult. We aim to clarify the incidence of carcinoma in specimens, obtained by endoscopic resection (ER), from cases that had been diagnosed as LGA (Vienna category 3) on endoscopic biopsy.