Published papers

microRNAs (miRNAs) are small non-coding RNAs that can function as endogenous silencers of target genes and play critical roles in human malignancies. To investigate the molecular pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the miRNA expression profile was analyzed. miRNA microarray analysis with tissue specimens from gastric MALT lymphomas and surrounding non-tumor mucosae revealed that a hematopoietic-specific miRNA miR-142 and an oncogenic miRNA miR-155 were overexpressed in MALT lymphoma lesions. The expression levels of miR-142-5p and miR-155 were significantly increased in MALT lymphomas which do not respond to Helicobacter pylori (H. pylori) eradication. The expression levels of miR-142-5p and miR-155 were associated with the clinical courses of gastric MALT lymphoma cases. Overexpression of miR-142-5p and miR-155 was also observed in Helicobacter heilmannii-infected C57BL/6 mice, an animal model of gastric MALT lymphoma. In addition, miR-142-5p and miR-155 suppress the proapoptotic gene TP53INP1 as their target. The results of this study indicate that overexpression of miR-142-5p and miR-155 plays a critical role in the pathogenesis of gastric MALT lymphoma. These miRNAs might have potential application as therapeutic targets and novel biomarkers for gastric MALT lymphoma.

BACKGROUND AND AIM: In Japan, patient acceptance of bowel preparation methods before colonoscopy remains unknown. This study was conducted to evaluate the patient acceptance of sodium phosphate (NaP) tablets and polyethylene glycol solution (PEG) with sodium picosulfate. METHODS: One hundred patients were randomized into one of the following two groups: the NaP tablet first-use group or the PEG with sodium picosulfate first-use group in a crossover design trial. Patient acceptance and incidence of adverse events were evaluated using a questionnaire. Colon-cleansing effectiveness was also evaluated. RESULTS: Patients' overall impressions of the preparations were significantly different between the NaP tablet (77.9%, 67/86) and PEG with sodium picosulfate (60.5%, 52/86; P = 0.001). Nausea incidence as an adverse event was significantly different between the two regimens (P = 0.03). Colon-cleansing effectiveness was not significantly different between the two regimens. CONCLUSIONS: The results of this crossover study showed that patient acceptance was similar to those previously reported in a parallel-group comparison. In Japanese patients, preference for and acceptance of NaP tablets was significantly higher than that for PEG with sodium picosulfate solution.

BACKGROUND/AIMS: In capsule endoscopy (CE), the capsule does not always reach the cecum within its battery life, which may reduce its diagnostic yield. We evaluated the effect of mosapride citrate, a 5-hydroxytryptamine-4 agonist that increases gastrointestinal motility, on CE completion. METHODS: In a retrospective study, we performed univariate and multivariate analyses for 232 CE procedures performed at our hospital. To identify factors that affect CE completion, the following data were systematically collected: gender, age, gastric transit time (GTT), nonsteroidal anti-inflammatory drug administration, previous abdominal surgery, hospitalization, use of a polyethylene glycol solution, use of mosapride citrate (10 mg), body mass index (BMI), and total recording time. RESULTS: The univariate analysis showed that oral mosapride citrate, GTT, and BMI were associated with improved CE completion. Multivariate analyses showed that oral mosapride citrate (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.01 to 3.91) and GTT (OR, 2.34; 95% CI, 1.13 to 4.87) were significant factors for improving the CE completion. Oral mosapride citrate significantly shortened the GTT and small bowel transit time (SBTT). CONCLUSIONS: Oral mosapride citrate reduced the GTT and SBTT during CE and improved the CE completion rate.

A 58-year-old man was transferred to us from his local hospital because of failure to control his gastrointestinal bleeding by endoscopic hemostasis. Abdominal imaging suggested a hypervascular tumor of the pancreatic head (36 mm diameter), and laboratory testing showed an elevated serum gastrin level (17,800 pg/mL). Gastroduodenal endoscopy revealed multiple duodenal ulcers and active bleeding from the ampulla of Vater. The selective arterial secretagogue injection test suggested a gastrinoma in the pancreatic head, but no gastrinoma in the pancreatic tail. The patient was diagnosed with solitary pancreatic head gastrinoma complicated by hemosuccus pancreaticus, and pancreaticoduodenectomy was performed. Intraoperatively, the diagnosis was changed to primary peripancreatic lymph node gastrinoma without pancreatic involvement. The gastrointestinal bleeding stopped postoperatively and serum gastrin levels returned to normal. Histological examination of the surgical specimens revealed a small submucosal gastrinoma in the duodenum (7 mm diameter). The final diagnosis was microgastrinoma of the duodenum with peripancreatic lymph node metastasis. The cause of bleeding from the ampulla of Vater was initially obscure, but eventually a hemorrhagic erosion with moderate atypia was found in the common bile duct, indicating biliary intraepithelial neoplasia (BilIN). This is the first report of hemobilia due to BilIN with gastrinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) is more difficult for rectal cancer than for gastric cancer. OBJECTIVE: To evaluate the feasibility and safety of an ESD procedure by using external forceps for early rectal cancer. DESIGN: A case series. SETTING: A tertiary medical center. PATIENTS: Thirteen patients with early-stage rectal cancer were enrolled. Twelve of the 13 lesions were granular-type laterally spreading tumors and 1 was a protruding tumor. INTERVENTIONS: After circumferential incision around the lesion with a dual-knife or a flex-knife, bendable external forceps were introduced with the help of grasping forceps inserted through the accessory channel and anchored at the anal margin of the lesion. After the forceps were bent, they were locked. With gentle anal traction and bending applied with the forceps, the lesion was elevated, the submucosal layer was opened, and the submucosal layer was dissected from the grasped side, facilitating dissection of the submucosal layer under direct vision. MAIN OUTCOME MEASUREMENTS: Technical success, complication rates. RESULTS: The mean lesion size was 33.0 mm (range 20-80 mm), and the mean operating time was 60 minutes (range 20-150 minutes). All lesions could be resected en bloc with tumor-free margins. Major bleeding after ESD occurred in only 1 patient (7.7%), who did not require blood transfusion. Perforation did not occur in any patient. LIMITATIONS: Single-center experience, small number of patients. CONCLUSION: This ESD procedure using external forceps for early-stage rectal cancers is feasible and safe.

BACKGROUND/AIMS: A flexible spectral imaging color enhancement system was installed in new capsule software for video capsule endoscopy. Contrast image capsule endoscopy (CICE) is a novel technology using light-emitting diodes selected for the main absorption range of hemoglobin. We assessed the feasibility and diagnostic effi cacy for small bowel surveillance in patients with polyposis syndromes. METHODS: Six patients with polyposis syndromes, four with familial adenomatous polyposis and one each with Cowden syndrome (CS) and Cronkhite-Canada syndrome (CCS) were examined using CICE. We conducted three evaluations to assess the effect on the numbers of the detected polyps; compare polyp diagnostic rates between adenoma and hamartoma; and assess polyp visibility. RESULTS: The numbers of detected polyps and diagnostic accuracy did not differ signifi cantly between pre-contrast and contrast images. However, 50% of the adenomatous polyps displayed enhanced visibility on contrast images. CICE contrast images exhibited clearly demarcated lesions and improved the visibility of minute structures of adenomatous polyps. Hamartomatous polyp micro-structures in patients with CS and CCS were more clearly visualized on contrast than pre-contrast images. CONCLUSIONS: CICE is an effective tool for enhancing the visibility of polyps in patients with polyposis syndrome.

BACKGROUND AND OBJECTIVE: Capsule endoscopy (CE) is a comfortable for the patients; however, CE review is time-consuming. The aim of this study was (1) to evaluate the effectiveness of the CE software in reducing the CE reading time and the number of false negatives by beginners, and (2) to determine the learning curve for reading CE images. METHODS: Capsule endoscopic images were captured by Pillcam SB (Given Imaging Ltd, Tokyo, Japan), and analyzed using the proprietary RAPID 5 software. Comparison of CE reading using different software modes: manual mode, automatic mode, and QuickView (QV) mode. Three trainee endoscopists participated as CE readers. Each participant watched CE videos in which positive findings had been predefined by trained endoscopists. Each participant read the same CE record by using one of three different software modes. These were blinded on clinical history of patients. CE reading time was recorded, and the number of false negatives was counted. Each trainee endoscopist read a total of 45 CE videos, in five steps divided into nine videos per step. RESULTS: There was no significant reader associated difference between the results for the different modes. The QV software did miss some positive findings. Therefore, the total number of instances of FN by the software plus the reader in the QV mode was significantly higher than the others. The reading times in the automatic mode and the QV mode were significantly shorter than that in the manual mode. After the second step, the number of instances of false negatives significantly decreased. CONCLUSIONS: CE software is useful for reducing the reading time. Experience of approximately 20 CE readings can be considered as the first step to becoming an expert.

BACKGROUND: Passive video capsule endoscopy is the criterion standard for small-bowel exploration but cannot be used for the large gastric cavity. We report the first blinded comparative clinical trial in humans comparing a magnetically guided capsule endoscope (MGCE) and a conventional high-definition gastroscope. OBJECTIVE: To assess the potential of gastric examination with a guided capsule. DESIGN: Blinded, nonrandomized comparative study. SETTING: Single endoscopy center. METHODS: The trial involved 61 patients included in a blinded capsule and gastroscopy comparative study. MGCE examination was performed 24 hours after patients had undergone gastroscopy. To remove food residue or mucus, patients drank 900 mL of water in 2 portions. Then to provide the air-water interface required by the guidance system, they drank 400 mL of water at 35 degrees C. RESULTS: Visualization of the gastric pylorus, antrum, body, fundus, and cardia was evaluated as complete in 88.5%, 86.9%, 93.4%, 85.2%, and 88.5% of patients, respectively. Of gastric lesions, 58.3% were detected by both gastroscopy and MGCE at immediate assessment and review of recorded data. Capsule examination missed 14 findings and gastroscopy missed 31 findings seen with MGCE. Overall diagnostic yield was similar for both modalities. LIMITATION: Pilot study. CONCLUSIONS: Diagnostic results were similar for the 2 methods. After some technical difficulties related to gastric expansion or presence of mucus had been overcome, this study opened a new field for noninvasive gastric examination in countries where high gastric cancer incidence demands a screening tool.

BACKGROUND: Proton pump inhibitors have been reported to be more useful than histamine-2 receptor antagonists for the prevention of bleeding after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia. The aim of this study was to assess the effects of the proton pump inhibitor lansoprazole and the histamine-2 receptor antagonist roxatidine for the prevention of bleeding and the promotion of ulcer healing after ESD and to compare the cost-effectiveness of these two drugs. METHODS: The study subjects were 129 patients who underwent ESD for superficial gastric neoplasia. The patients were randomly assigned to the lansoprazole group (L group) or the roxatidine group (R group). Either drug was administered intravenously from the morning of the ESD day to the day after the ESD, followed by oral treatment for an additional 8 weeks. A second-look endoscopy was performed on the day after the ESD, and a repeat endoscopy was performed at 8 weeks after the ESD. The incidence of bleeding and the ulcer-healing rate at 8 weeks after the ESD were analyzed, as well as the total cost of treatment with these antisecretory agents. RESULTS: Three patients in each group were excluded from the analysis, leaving 62 patients in L group and 61 in R group. Two of the 62 patients (3.2%) in L group and three of the 61 patients (4.9%) in R group showed bleeding after ESD ; there was no significant difference between the two groups (P = 0.68). The ulcer-healing rate was 93.5% (58/62) in L group and 93.4% (57/61) in R group (P = 1). The total cost of treatment with the antisecretory agent from the day of the ESD to day 56 after the ESD was Yen 13,212 for lansoprazole and Yen 5,841 for roxatidine. CONCLUSIONS: Roxatidine appears to have high cost-effectiveness in the prevention of bleeding and in the promotion of ulcer healing after ESD for superficial gastric neoplasia.

BACKGROUND: Routine diagnosis of the histopathological activity of ulcerative colitis (UC) requires multiple biopsy samples, and an endocytoscopy system (ECS) provides real-time ultra-magnifying microscopic imaging in vivo. METHODS: We have established an ECS score (ECSS) to determine a histopathological activity index of UC. Fifty-five UC patients (mean age 40.7 years; 67% men) were enrolled. A super-magnifying ECS with magnification 450x was used, and sample biopsies were obtained. Matts' histopathological grade was determined, to evaluate disease severity, by two pathologists, with consensus. The ECSS of UC was independently determined by at least two investigators, with consensus. In total, 76 pairs of ECSS and Matts' histopathological grades were independently acquired. To validate the ECSS, inter-observer agreement between three endoscopists, with consensus, and another endoscopist, was calculated as the kappa value. We also evaluated the correlation between the ECSS and Matts' histopathological grade, and between the conventional Matts' endoscopic grade and Matts' histopathological grade. RESULTS: The ECSS of UC intestinal mucosa, i.e., the sum of the indices for shape (0-3) and distance between crypts (0-2), and the visibility of superficial microvessels (0-1), showed a strong correlation with Matts' histopathological grades (rho = 0.713, P < 0.001); as well, there was a strong correlation between the conventional Matts' endoscopic grade and Matts' histopathological grade (rho = 0.694, P < 0.001). Furthermore, the ECSS showed high reproducibility (kappa = 0.79, 95% confidence interval [CI] 0.71-0.87). CONCLUSIONS: Our novel ECSS has good predictive value for the histopathological activity of UC.

Here, we report an adult patient with IgA-related enteropathy complicated with massive intestinal bleeding and acute renal failure, but without skin lesions. Surgical resection of the small intestine and steroid pulse therapy was performed. Histopathology revealed significant deposition of IgA and C3 in the small vessels of the intestine and the kidney mesangium. Although skin purpura was absent, the histopathology and clinical manifestations suggested that the pathophysiology was similar to Henoch-Schonlein purpura (HSP), implying IgA-related enteropathy as a subclass of HSP. Retrospective analysis indicates that terminal ileum lesions may be a poor prognostic indicator.

BACKGROUND AND AIM: Esophagogastroduodenoscopy through the oral cavity of patients who have undergone percutaneous endoscopic gastrostomy (PEG) causes some distress and puts these patients at risk of aspiration pneumonia. The aim of this study was to evaluate results for the upper gastrointestinal tract by transgastrostomic endoscopy using an ultrathin endoscope. METHODS: The study subjects were 43 patients, who underwent exchange of a PEG button or tube, 20-French or more in diameter. After PEG buttons or tubes were extracted from the gastrostomy tract, an ultrathin endoscope was inserted through the gastrostomy tract. The stomach and the duodenal bulb were observed and the esophagus was observed in retrograde passage. A new PEG button or tube was then inserted. The rate of successful insertion into the esophagus and duodenal bulb, the observation of the gastrostomy site in retroversion in the stomach, and the endoscopic findings were analyzed. RESULTS: Ninety-nine examinations were carried out. The esophagus could be observed in 95 (96.0%), the duodenum in 92 (92.9%) and the gastrostomy site in the stomach in all. Gastric polyps were detected in four patients, gastric erosions in two, reflux esophagitis in two, polypoid lesion at the gastrostomy tract in two, gastric ulcer scar in one, duodenal ulcer scar in one, early gastric cancer in one and recurrent esophageal cancer in one. Neither discomfort nor complications occurred during transgastrostomic endoscopy. CONCLUSIONS: Observation of the upper gastrointestinal tract by transgastrostomic endoscopy using an ultrathin endoscope during a gastrostomy button or tube replacement may be useful and safe.

A 51-year-old man was referred to our hospital because of duodenal lesions of lymphoma. Endoscopy showed multiple tiny smooth whitish granules in the second portion of the duodenum including the papilla of Vater. Biopsy specimens showed medium-sized centrocyte-like cells forming lymphoid follicles, and immunohistology showed positive staining for bcl-2 and CD10. A small bowel series showed multiple granular lesions extending from the second portion of the duodenum to the proximal jejunum and the proximal ileum. On the basis of these findings, the tumor was diagnosed as stage I follicular lymphoma (FL). Although the patient was negative for Helicobacter pylori, he underwent antibiotic treatment. The lesions improved 3 months after antibiotic treatment, but biopsy specimens showed residual lymphoma cells. The patient therefore received combination chemotherapy with rituximab. Endoscopy 4 months later showed regression of FL, and there was no evidence of recurrence during 3 years of follow up. The partial regression of duodenal lesions of intestinal FL may be due to the effect of antibiotic treatment.

BACKGROUND: The endocytoscopy system (ECS) is a new method to provide real-time super-magnifying microscopic imaging in vivo. Routine diagnosis of amebic colitis requires multiple tests that are both time consuming and costly. OBJECTIVE: To determine the feasibility of ECS to directly detect the amebic parasites in vivo. DESIGN: Prospective, single-center, pilot study. SETTING: Tertiary-care university hospital. PATIENTS: This study involved 5 patients who were suspected to have amebic colitis by conventional colonoscopy in our institute. INTERVENTIONS: A super-magnifying ECS with 450 x magnification. MAIN OUTCOME MEASUREMENTS: We compared ECS findings with those of conventional methods-serum antibody tests and histology of colon biopsy specimens. RESULTS: We successfully visualized the amebic trophozoites in all 5 cases. In contrast, 3 specimens had positive results on serology, and 3 had positive histology results on hematoxylin and eosin staining. LIMITATIONS: Pilot study with a limited number of patients. Findings were compared only with serology and histology findings. CONCLUSIONS: ECS would be a useful tool for the prompt diagnosis of amebic colitis via the real-time in vivo visualization of amebic trophozoites.

BACKGROUND AND STUDY AIMS: Video capsule endoscopy has been established in diagnosis of small-bowel disease and has been evaluated for esophageal pathology and recently for colorectal diagnostics. Gastric capsule endoscopy has not hitherto been feasible due to the stomach's large surface area and volume. We present the first application of a magnetically navigated capsule in the human stomach. PATIENTS AND METHODS: 29 volunteers and 24 patients (men 42, women 11; mean age 47.5 years) were included in a feasibility study. Low-level magnetic fields were used to maneuver the double-sensor video capsule within the human stomach with an air-water interface provided by ingestion of 1300 ml water within 1 hour before examination. Visualization of all parts of the stomach was attempted; time for visualization was recorded, and a subjective assessment of completeness of visualization was documented. RESULTS: There was technical failure in one individual; thus technical success rate was 98 %. In the 52 remaining cases, examiners assessed that the antrum, body, fundus, and cardia were fully visualized in 98 %, 96 %, 73 % and 75 %, respectively. Mean duration of examinations was 30 minutes (range 8 - 50), with a longer time (mean 37 minutes) for volunteers for study reasons. In total, 30 findings were identified: 14 were detected by both gastroscopy and capsule, 10 lesions were identified by guided capsule examination only, 6 by gastroscopy only. No significant capsule-related adverse events occurred. CONCLUSION: Magnetically navigated video capsule endoscopy appears to be feasible and sufficiently accurate for gastric examination. It may permit endoscopic examinations that are more patient-friendly and without sedation. Comparative studies are under way.

BACKGROUND: Autofluorescence (AF) videoendoscopy has an advantage over ordinary videoendoscopy in the diagnosis of gastric neoplasias, and the aim of the present study was to evaluate the effectiveness of using the SAFE-3000 videoendoscopy system to diagnose superficial gastric neoplasias. METHODS: Ordinary videoendoscopy, AF videoendoscopy, and chromoendoscopy (CE) were used to diagnose the tumor existence and extent in 14 patients with gastric adenoma, 40 patients with intestinal-type early gastric cancer (EGC) (10 protruded, and 30 depressed), and nine patients with diffuse-type EGC. The diagnostic accuracies of the three kinds of images were evaluated by comparison with the results of histopathological assessment of resected specimens. RESULTS: For gastric adenomas the diagnostic accuracy between the AF images and white light (WL) images did not differ significantly, and for protruded intestinal-type EGCs and diffuse-type EGCs the diagnostic accuracy did not differ significantly between any of the types of images. For depressed intestinal-type EGCs, the diagnostic accuracy of AF images tended to be higher than that of the WL images (P < 0.05) and it was not significantly different from that of the CE images. The detection rate of pink or orange color in AF images was significantly higher for protruded intestinal-type EGCs than gastric adenomas (P = 0.005), depressed intestinal-type EGCs (P < 0.001), and diffuse-type EGCs (P = 0.027). CONCLUSIONS: Autofluorescence videoendoscopy using the SAFE-3000 system for gastric neoplasias might be useful for diagnosing depressed intestinal-type early gastric cancers. The detection of orange or pink color in AF images may be efficacious in discriminating protruded intestinal-type early gastric cancers from gastric adenomas.