Impact of mixed-infection rate of clarithromycin-susceptible and clarithromycin-resistant Helicobacter pylori strains on the success rate of clarithromycin-based eradication treatment.

BACKGROUND: Clarithromycin (CAM) resistance is a major contributor to the failure to eradicate Helicobacter pylori (H. pylori). The mixed-infection ratio of CAM-susceptible and CAM-resistant H. pylori strains differs among individuals. Pyrosequencing analysis can be used to quantify gene mutations at position each 2142 and 2143 of the H. pylori 23S rRNA gene in intragastric fluid samples. Herein, we aimed to clarify the impact of the rate of mixed infection with CAM-susceptible and CAM-resistant H. pylori strains on the success rate of CAM-containing eradication therapy. MATERIALS AND METHODS: Sixty-four H. pylori-positive participants who received CAM-based eradication therapy, also comprising vonoprazan and amoxicillin, were enrolled in this prospective cohort study. Biopsy and intragastric fluid samples were collected during esophagogastroduodenoscopy. H. pylori culture and CAM-susceptibility tests were performed on the biopsy samples, and real-time PCR and pyrosequencing analyses were performed on the intragastric fluid samples. The mutation rates and eradication success rates were compared. RESULTS: The overall CAM-based eradication success rate was 84% (54/64): 62% (13/21) for CAM-resistant strains, and 95% (39/41) for CAM-sensitive strains. When the mutation rate of the 23S rRNA gene was 20% or lower for both positions (2142 and 2143), the eradication success rate was 90% or more. However, when the mutation rate was 20% or higher, the eradication success rate was lower (60%). CONCLUSIONS: The mutation rate of the CAM-resistance gene was related to the success of eradication therapy, as determined via pyrosequencing analysis.

Diagnostic performance of linked color imaging for gastric cancer by Helicobacter pylori infection status: A subanalysis of the large-scale, multicenter randomized controlled trial LCI-FIND.

BACKGROUND: Linked color imaging (LCI) is a new image enhancement technology that facilitates the recognition of subtle differences in mucosal color. In the large-scale, multicenter randomized controlled trial LCI-FIND, LCI demonstrated good diagnostic performance for the detection of tumor lesions in the upper gastrointestinal tract. The aim of the present study was to exploratively evaluate the diagnostic performance of LCI according to H. pylori infection status as a subanalysis of LCI-FIND trial. METHODS: The patients were randomly allocated to receive white light imaging (WLI) first, followed by LCI (WLI group), or vice versa (LCI group), and the two groups were compared for the detection of tumors. Data from this trial were analyzed by the presence/absence of H. pylori infection and further analyzed by successful or unsuccessful eradication in the H. pylori infection group. RESULTS: The 752 patients in the WLI group and 750 patients in the LCI group who had participated in the LCI-FIND trial were included. In the successful eradication group, more gastric lesions were detected by primary mode in the LCI group than in the WLI group, indicating that more lesions were missed by WLI. Fisher's exact probability test for the comparison of the WLI and LCI groups yielded a p-value of 0.0068, with missed gastric lesions being detected 0.136 times (95% confidence interval: 0.020-0.923), significantly less with LCI than with WLI. CONCLUSION: The current study suggests that LCI should be used for gastric cancer screening, particularly in patients with successful H. pylori eradication.

Surveillance esophagogastroduodenoscopy using linked color imaging and narrow-band imaging: A multicenter randomized controlled trial.

BACKGROUND AND AIM: There has been no report on a direct comparison between linked color imaging (LCI) and second-generation narrow-band imaging (2G-NBI) for surveillance of epithelial neoplasms in the upper gastrointestinal tract (UGIT). The aim of this study was to verify the superiority of LCI to 2G-NBI for surveillance esophagogastroduodenoscopy and to clarify how each endoscopic system should be used. METHODS: This study was conducted as an open-label, two-arm-parallel (1:1), multicenter, randomized controlled trial at six institutions. Patients aged 20-85 years with a treatment history of epithelial neoplasms in the UGIT were recruited. Patients were assigned to a 2G-NBI group and an LCI group, and esophagogastroduodenoscopy was performed with primary image-enhanced endoscopy followed by white light imaging (WLI). The primary endpoint was the detection rate of one or more epithelial neoplasms in the primary image-enhanced endoscopy. A WLI-detected epithelial neoplasm was defined as a lesion that was detected in only WLI. RESULTS: A total of 372 patients in the 2G-NBI group and 378 patients in the LCI group were analyzed. Epithelial neoplasms in the UGIT were detected by 2G-NBI in 18 patients (4.6%) and were detected by LCI in 20 patients (5.3%) (P = 0.87). WLI-detected epithelial neoplasms were in 11 patients in the 2G-NBI group (3.0%) and in 1 patient in the LCI group (0.27%) (P = 0.003). CONCLUSIONS: Linked color imaging did not show superiority to 2G-NBI for the detection of epithelial neoplasms. Also, the percentage of WLI-detected epithelial neoplasms in primary NBI was significantly higher than that in primary LCI.

Linked color imaging provides enhanced visibility with a high color difference in upper gastrointestinal neoplasms.

BACKGROUND AND AIM: The aim of this post-hoc analysis in a randomized, controlled, multicenter trial was to evaluate the visibility of upper gastrointestinal (UGI) neoplasms detected using linked color imaging (LCI) compared with those detected using white light imaging (WLI). METHODS: The visibility of the detected UGI neoplasm images obtained using both WLI and LCI was subjectively reviewed, and the median color difference (ΔE) between each lesion and the surrounding mucosa according to the CIE L*a*b* color space was evaluated objectively. Multivariate logistic regression analysis was performed to identify factors associated with neoplasms that were missed under WLI and detected under LCI. RESULTS: A total of 120 neoplasms, including 10, 32, and 78 neoplasms in the pharynx, esophagus, and stomach, respectively, were analyzed in this study. LCI enhanced the visibility 80.9% and 93.6% of neoplasms in pharynx/esophagus and stomach compared with WLI, respectively. LCI also achieved a higher ΔE of enhanced neoplasms compared with WLI in the pharynx/esophagus and stomach. The median WLI ΔE values for gastric neoplasms missed under WLI and later detected under LCI were significantly lower than those for gastric neoplasms detected under WLI (8.2 vs 9.6, respectively). Furthermore, low levels of WLI ΔE (odds ratio [OR], 7.215) and high levels of LCI ΔE (OR, 22.202) were significantly associated with gastric neoplasms missed under WLI and later detected under LCI. CONCLUSION: Color differences were independently associated with missing gastric neoplasms under WLI, suggesting that LCI has an obvious advantage over WLI in enhancing neoplastic visibility.

Clinical evaluation of a novel molecular diagnosis kit for detecting Helicobacter pylori and clarithromycin-resistant using intragastric fluid.

BACKGROUND: Although there are many Helicobacter pylori (H. pylori) diagnostic methods, the culture and antibiotic susceptibility test is an important method for selecting the most effective H. pylori eradication regimen. However, this diagnostic method is complicated and takes several days; therefore, the development of a rapid and simple diagnostic method is required. Eradication failure due to clarithromycin (CAM) resistance should also be considered. In this study, we report the clinical evaluation of point-of-care testing (POCT) kit using intragastric fluid, a novel kit for detecting H. pylori and CAM resistance. MATERIALS AND METHODS: The study participants were 143 patients suspected of H. pylori infection and had an endoscopic examination. The novel diagnostic kit diagnosed H. pylori infection and CAM resistance-associated mutation using intragastric fluid. To diagnose H. pylori infection, the relationship between the diagnostic kit and conventional diagnostic methods (urea breath test, stool antigen test, culture test, and real-time polymerase chain reaction [PCR]) was evaluated. For CAM resistance-associated mutation detection, the concordance between the diagnostic kit and antibiotic susceptibility test was evaluated. RESULTS: The diagnosis of H. pylori infection with the novel molecular diagnostic kit using intragastric fluid showed significant relationship with conventional diagnostic methods. Especially when the culture was control, the sensitivity was 100% (67/67), the specificity was 95.9% (71/74), and the overall concordance was 97.9% (138/141). The detection of CAM resistance-associated mutations had a concordance rate of 97.0% (65/67) when compared with the antibiotic susceptibility test. CONCLUSIONS: The H. pylori molecular POCT kit uses intragastric fluid as a sample and can diagnose H. pylori infection and detect CAM resistance-associated mutations within an hour. This novel kit is expected to prove useful in selecting the most effective eradication regimen for H. pylori.

Linked Color Imaging Focused on Neoplasm Detection in the Upper Gastrointestinal Tract : A Randomized Trial.

BACKGROUND: Linked color imaging (LCI) is a new image-enhanced endoscopy technique that allows users to recognize slight differences in mucosal color. OBJECTIVE: To compare the performance of LCI with white light imaging (WLI) in detecting neoplastic lesions in the upper gastrointestinal tract. DESIGN: A controlled, multicenter trial with randomization using minimization. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000023863). SETTING: 16 university hospitals and 3 tertiary care hospitals in Japan. PATIENTS: 1502 patients with known previous or current cancer of the gastrointestinal tract and undergoing surveillance for gastrointestinal cancer. INTERVENTION: WLI followed by LCI examination (WLI group) or LCI followed by WLI examination (LCI group). MEASUREMENTS: Diagnosis of 1 or more neoplastic lesions in the pharynx, esophagus, or stomach in the first examination (primary outcome) and 1 or more neoplastic lesions overlooked in the first examination (secondary outcome). RESULTS: 752 patients were assigned to the WLI group and 750 to the LCI group. The percentage of patients with 1 or more neoplastic lesions diagnosed in the first examination was higher with LCI than with WLI (60 of 750 patients or 8.0% [95% CI, 6.2% to 10.2%] vs. 36 of 752 patients or 4.8% [CI, 3.4% to 6.6%]; risk ratio, 1.67 [CI, 1.12 to 2.50; P = 0.011]). The proportion with overlooked neoplasms was lower in the LCI group than in the WLI group (5 of 750 patients or 0.67% [CI, 0.2% to 1.6%] vs. 26 of 752 patients or 3.5% [CI, 2.3% to 5.0%]; risk ratio, 0.19 [CI, 0.07 to 0.50]). LIMITATION: Endoscopists were not blinded. CONCLUSION: LCI is more effective than WLI for detecting neoplastic lesions in the pharynx, esophagus, and stomach. PRIMARY FUNDING SOURCE: Fujifilm Corporation.

Eradication of Helicobacter pylori may improve dyspepsia in the elderly for the long term.

BACKGROUND: Therapy for eradication of Helicobacter pylori (H. pylori) improves symptoms of H. pylori-associated dyspepsia (HPD), but the effects of eradication in elderly patients are unclear. The aim of our study was to investigate dyspepsia symptoms and long-term effects of eradication in elderly patients. METHODS: This retrospective study included 496 patients who received H. pylori eradication therapy. The patients were divided into a group of elderly patients (group E: ≧ 65 years old) and a group of non-elderly patients (group N: < 65 years old). Abdominal symptoms were evaluated using a questionnaire about abdominal symptoms before eradication and after eradication (1-2 months and more than one year). Dyspepsia was defined as a score of 4 points or more for at least one of 4 items (postprandial fullness, early satiety, epigastric pain, and hunger pain). Improvement of symptoms was defined on the basis of changes in Global Overall Systems scores. RESULTS: There were no differences in abdominal symptoms before eradication between the two groups. Successful eradication improved symptoms in patients with dyspepsia within 2 months (in 75.6% (56/74) of the patients in group N and in 64.5% (20/31) of the patients in group E). The questionnaire showed that 80% (32/40) of the patients in group N and 60% (12/20) of the patients in group E had long-term relief of dyspepsia. The scores for abdominal symptoms in group E continued to improve for a mean period of 54.8 months after eradication. CONCLUSIONS: Eradication of H. pylori age-independently improved dyspepsia symptoms for the long term.

Histological and magnified endoscopic evaluation of villous atrophy in gastrointestinal graft-versus-host disease.

AIM:  To measure histological villous atrophy and to clarify the diagnostic accuracy of endoscopic villous atrophy in gastrointestinal graft-versus-host disease. METHODS:  Data for patients who underwent upper and/or lower endoscopic examinations after hematopoietic stem cell transplantation were retrospectively collected. In study 1, group A included 56 patients in whom GI-GVHD was histologically confirmed and group B included 60 patients in whom GI-GVHD was not histologically confirmed. Group C included 59 patients before HSCT. The lengths of villi and crypts in the duodenum and terminal ileum were histologically measured. In study 2, the diagnostic accuracies of villous atrophy of the duodenum and of the terminal ileum using magnifying endoscopy were evaluated. RESULTS:  In study 1, the lengths of villi and the villi/crypt (V/C) ratios of the duodenum and terminal ileum in group A were significantly smaller than those in the other groups (p < 0.05). V/C ratio was moderately correlated with clinical severity, histological grades, and endoscopic grades in the terminal ileum. In study 2, the diagnostic accuracies of magnified images for villous atrophy were 83.8% in the duodenum and 94.9% in the terminal ileum. CONCLUSION:  Magnifying endoscopy enables evaluation of villous atrophy and is useful for optical biopsy of GVHD.

Changes of Dyspeptic Symptom after Successful Eradication in Helicobacter pylori-Associated Dyspepsia.

BACKGROUND: Helicobacter pylori (H. pylori) gastritis could cause dyspepsia, and eradication is recommended as the first-line treatment. Patients who continuously have their symptoms under control > 6 months after eradication are defined as having H. pylori-associated dyspepsia (HPD), whereas patients who do not benefit from successful eradication are defined as having functional dyspepsia. OBJECTIVES: We assessed changes in dyspeptic symptoms after successful eradication of H. pylori by using a questionnaire. METHODS: We studied H. pylori-infected dyspeptic participants with abdominal symptom scores > 4 points on the Global Overall Symptom (GOS) scoring items and received eradication therapy. We evaluated their symptoms using the GOS questionnaire before their eradications, at 1-month and at 1-year check-ups after eradication therapy. RESULTS: Thirty dyspeptic participants (mean age 59.6 ± 15.3 years) answered every questionnaire. Fourteen participants (46.7%) had HPD, whereas 16 participants (53.3%) were non-HPD patients. The questionnaire at 1 month showed sensitivity of 64.3% (9/14) and specificity of 56.3% (9/16) for HPD. Approximately 60% of H. pylori-infected dyspepsia participants were identified as having HPD or non-HPD within 1 month after their eradications. CONCLUSIONS: Approximately 60% of HPD participants improved at 1 month after eradication. The questionnaire at 1 month helped diagnose HPD in advance and guided next treatment choice.

Clinical impact of the perioperative management of oral anticoagulants in bleeding after colonic endoscopic mucosal resection.

BACKGROUND: Heparin bridging therapy (HBT) is indeed related to a high frequency of bleeding after endoscopic mucosal resection (EMR). In this study, our aim was to investigate clinical impact of management of oral anticoagulants without HBT in bleeding after colonic EMR. METHODS: From data for patients who underwent consecutive colonic EMR, the relationships of patient factors and procedural factors with the risk of bleeding were analysed. Our management of antithrombotic agents was based on the shortest cessation as follows: the administration of warfarin was generally continued within the therapeutic range, and direct oral anticoagulants (DOACs) were not administered on the day of the procedure. We calculated bleeding risks after EMR in patients who used antithrombotic agents and evaluated whether perioperative management of anticoagulants without HBT was beneficial for bleeding. RESULTS: A total of 1734 polyps in 825 EMRs were analysed. Bleeding occurred in 4.0% of the patients and 1.9% of the polyps. The odds ratios for bleeding using multivariate logistic regression analysis were 3.67 in patients who used anticoagulants and 4.95 in patients who used both anticoagulants and antiplatelet agents. In patients with one-day skip of DOACs, bleeding occurred in 6.5% of the polyps, and there were no significant differences in bleeding risk between HBT and continuous warfarin or one-day skip DOACs. CONCLUSIONS: The use of oral anticoagulants was related to bleeding after colonic EMR, and perioperative management of oral anticoagulants based on the shortest cessation without HBT would be clinically acceptable.

Evaluation of gastric acid suppression with vonoprazan using calcium carbonate breath test.

Vonoprazan, a potassium-competitive acid blocker, is a new class of acid-suppressing agent. The acid-inhibitory effect of vonoprazan has been well-documented. However, there is no report on the extent to which the amount of gastric acid secretion is suppressed, not pH measurement, by the use of vonoprazan. The aim of this study was to evaluate this suppression effect. This was a single-arm, interventional pilot study involving 7 healthy Japanese men. The subjects were administered 20 mg vonoprazan for 6 days. The amount of gastric acid secretion was determined using the calcium carbonate breath test. The acid outputs were defined as the maximum Δ13C‰ (Δ13C max) and area under the curve (AUC) during the 30 min sampling period. The Δ13C max and AUC values significantly decreased on the administration of 20 mg vonoprazan. The AUC dropped by approximately 78% on day 1 and by 84% on day 6 and subsequently returned to the control level after cessation of vonoprazan therapy (reduction by 68% on day 7 and by 42% on day 8). In conclusion, the amount of gastric acid secretion rapidly decreased by the administration of vonoprazan; this inhibitory effect was found to be potent and long-lasting. (UMIN ID: UMIN000025469).

Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis concomitant with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Although graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), cytomegalovirus (CMV) reactivation also occurs in patients after allo-HSCT and these conditions often clinically overlap. The aim of this study was to determine reliable endoscopic findings of CMV colitis in patients with gastrointestinal graft-versus-host-disease (GI-GVHD). Patients after allo-HSCT who were histologically confirmed to have GI-GVHD with or without CMV colitis and patients with an immunosuppressive condition were retrospectively analyzed. We divided the patients into three groups: GI-GVHD with CMV colitis (group A), GI-GVHD without CMV colitis (group B), and CMV colitis without undergoing allo-HSCT (group C). From medical records, the involved colorectal areas and endoscopic findings according to the groups were compared. A total of 70 patients were divided into three groups (group A: n = 19, group B: n = 28, group C: n = 23). Mucosal injuries in groups A and C frequently occurred in the cecum including ileocecal valves. On the other hand, there were no abnormal lesions on ileocecal valves in group B. Furthermore, ulcer lesions were more frequently observed in groups A and C than in group B (p < 0.001). The sensitivity and specificity of mucosal injuries in the cecum for prediction of CMV colitis were 89.5 and 76.5%, respectively, and mucosal injuries in the cecum were more reliable findings than CMV antigenemia. Ulcer lesions in the cecum are reliable endoscopic findings for CMV colitis in patients with GI-GVHD after allo-HSCT.

Preventive effect of mesenchymal stem cell culture supernatant on luminal stricture after endoscopic submucosal dissection in the rectum of pigs.

BACKGROUND: Mesenchymal stem cells (MSCs) are valuable in regenerative medicine, and MSC culture supernatant (MSC-CS) reportedly inhibits inflammation and fibrosis. We investigated whether colorectal luminal stricture develops after circumferential endoscopic submucosal dissection (ESD) in the colorectum, and whether the development of luminal stricture could be prevented by using MSC-CS enema. METHODS: In the first experiment, we performed circumferential ESD in the rectums or distal colons of pigs (n = 4 in each group). We sacrificed the pigs on Day 22 and measured the degree of luminal stricture. In the second experiment, we performed circumferential ESD in the rectums of pigs and administered an MSC-CS gel or a control gel enema after ESD for 4 days. We sacrificed the pigs on Day 8 (n = 3 in each group) or 22 (n = 3 in each group) to measure the degree of luminal stricture, and performed histological analysis. RESULTS: Severe luminal stricture was observed in the rectum but not in the distal colon. Moreover, fiber accumulation in the submucosa and hypertrophy of the muscularis propria were observed in the rectum but not in the distal colon. The degree of luminal stricture in the rectum was significantly lower in the MSC-CS group than in the control group. Furthermore, MSC-CS attenuated myofibroblast activation and hypertrophy of the muscularis propria on Day 22, and reduced inflammatory cell infiltration on Day 8. CONCLUSIONS: Luminal stricture after ESD developed only in the rectum because of the difference in myofibroblast activation and fiber accumulation. In addition, MSC-CS enema prevented luminal stricture after ESD, possibly by inhibiting the inflammatory reaction and fibrosis.

Lavender Color in Linked Color Imaging Enables Noninvasive Detection of Gastric Intestinal Metaplasia.

BACKGROUND AND AIMS: Recently, there have been some reports that image-enhanced endoscopy may improve detection of gastric intestinal metaplasia (GIM). Our aim was to determine the usefulness of linked color imaging (LCI) for detection of GIM. METHODS: In prospectively recruited patients, the whole antrum was observed by white light imaging (WLI) followed by LCI. When a whitish flat elevation (WFE) in WLI and a lavender color sign (LCS) in LCI were detected, target biopsies were performed after LCI. Random biopsies were performed in patients who had neither WFE nor LCS. The primary endpoint was the diagnostic accuracy of GIM per patient in WLI and LCI and the secondary endpoints were that of GIM per biopsy and interobserver agreement. RESULTS: Data from 128 patients were analyzed and 58 patients (45.3%) had histological GIM in the antrum. The per-patient yields of WLI and LCI to detect GIM were 19.0% (11/58) and 91.4% (53/58) respectively. Diagnostic accuracies of target biopsies for GIM were 23.7% in WLI and 84.2% in LCI. Kappa values among 3 doctors were 0.60 for WFE and 0.78 for LCS respectively. CONCLUSION: LCI could be a new diagnostic tool for detecting GIM during routine endoscopy.

Oral administration of conditioned medium obtained from mesenchymal stem cell culture prevents subsequent stricture formation after esophageal submucosal dissection in pigs.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for esophageal cancer often causes postoperative stricture when more than three fourths of the circumference of the esophagus is dissected. Mesenchymal stem cells are a valuable cell source in regenerative medicine, and conditioned medium (CM) obtained from mesenchymal stem cells reportedly inhibits inflammation. In this study we evaluated whether CM could prevent esophageal stricture after ESD. METHODS: We resected a semi-circumference of pig esophagus by ESD. We prepared CM gel by mixing with 5% carboxymethyl cellulose and endoscopically applied it onto the wound bed immediately after ESD and on days 8 and 15 (weekly CM group) or administered it orally from days 1 to 4 (daily CM group). We also injected triamcinolone acetonide into the remaining submucosa immediately after ESD (steroid group). We killed the pigs on day 8 or day 22 to measure the stricture rate and to perform histologic analysis. RESULTS: Stricture rate in weekly and daily CM groups and steroid groups were significantly lower than in the control group on day 22. Moreover, CM significantly attenuated the number of activated myofibroblasts and fiber thickness on day 22. CM also significantly decreased the infiltration of neutrophils and macrophages compared with the control group on day 8. CONCLUSIONS: CM gel prevents esophageal stricture formation by suppressing myofibroblast activation and fibrosis after the infiltration of neutrophils and macrophages. Oral administration of CM gel is a promising treatment for the prevention of post-ESD stricture.

Effect on Helicobacter pylori eradication therapy against gastric cancer in Japan.

BACKGROUND: In Japan, there have been approximately 50 000 deaths from gastric cancer annually for over 40 years with little variation. It has been reported that most gastric cancers in Japan are caused by Helicobacter pylori infection. H. pylori eradication therapy was approved for patients with chronic gastritis by the Japanese national health insurance scheme in February 2013 for patients with an endoscopic diagnosis of chronic gastritis is positive for H. pylori. We examined the effect on gastric cancer death rate 4 years after expansion of health insurance coverage. AIM: We conducted an epidemiological study and analyzed trends in prescription for H. pylori eradication therapy. We used the electronic medical claims database from Hokkaido, Japan to evaluate the impact of expansion of national health insurance coverage for H. pylori eradication therapy on deaths from gastric cancer. METHODS: Data on deaths from gastric cancer were obtained from the Japanese Ministry of Health, Labour and Welfare and the Cancer Statistics in Japan (2015). Analysis of electronic claims records was performed using the National Database, mainly focusing on Hokkaido. Prescriptions for H. pylori eradication therapy and the number of patients treated for gastric cancer were also extracted from the Hokkaido database. RESULTS: Approximately 1.5 million prescriptions for H. pylori eradication therapy were written annually. Gastric cancer deaths fell each year: 48 427 in 2013, 47 903 in 2014, 46 659 in 2015, and 45 509 in 2016, showing a significant decrease after expansion of insurance coverage for H. pylori eradication therapy (P<.0001). CONCLUSIONS: Prescriptions for H. pylori eradication therapy increased markedly after approval of the gastritis indication by the national health insurance scheme and was associated with a significant decrease in gastric cancer deaths.

Gastric mucosal cracked and cobblestone-like changes resulting from proton pump inhibitor use.

BACKGROUND AND AIM: Use of proton pump inhibitors (PPI) is histologically associated with oxyntic gland dilatations. Two interesting mucosal changes are often detected endoscopically in patients who use PPI: gastric cracked mucosa (GCM) and gastric cobblestone-like mucosa (GCSM). The aim of the present study was to clarify the relationship between PPI use and these mucosal changes. METHODS: This was a single-center observational study. All successive subjects who underwent a routine esophagogastroduodenoscopy (EGD) between August and November 2014 in Hokkaido University Hospital were enrolled. Endoscopists carried out the assessment blinded to the use of PPI and checked for GCSM and GCM using original diagnostic criteria for GCM and GCSM. Subjects were divided into two groups: those who used PPI (PPI group) and those who did not (control group). Endoscopic findings and backgrounds were compared between the two groups. RESULTS: A total of 538 patients were analyzed (control group: 374 patients, men/women: 204/170, median age: 65.2 years; PPI group: 164 patients, men/women: 89/75, median age: 67.1 years). GCM was detected in 54 (10.0%) subjects, and GCSM was detected in 18 (3.3%) subjects. There was a significant difference in the prevalence rate of GCM between the control group (14/374, 3.7%) and the PPI group (40/164, 24.4%) (P < 0.01). GCSM was significantly more prevalent in the PPI group (15/164, 9.1%) than in the control group (3/374, 0.8%) (P < 0.01). CONCLUSION: Novel GCM and GCSM endoscopic findings in the corpus area seem to be strongly associated with PPI use.

Multicenter randomized controlled study to assess the effect of prophylactic clipping on post-polypectomy delayed bleeding.

BACKGROUND AND AIM: Prophylactic clipping has been widely used to prevent post-procedural bleeding in colon polypctomy. However, its efficiency has not been confirmed and there is no consensus on the usefulness of prophylactic clipping. The aim of the present study was to evaluate the preventive effect of prophylactic clipping on post-polypectomy bleeding. METHODS: A multicenter randomized controlled study was conducted from January 2012 to July 2013 in Japan. Patients who had polyps <2 cm in diameter were divided into a clipping group and a non-clipping group by cluster randomization. After endoscopic polypectomy, patients allocated to the clipping group underwent prophylactic clipping, whereas the procedure was completed without clipping in patients allocated to the non-clipping group. Occurrence of post-polypectomy bleeding was compared between the two groups. RESULTS: Seven hospitals participated in this study. A total of 3365 polyps in 1499 patients were evaluated. The clipping group consisted of 1636 polyps in 752 patients, and the non-clipping group consisted of 1729 polyps in 747 patients. Post-polypectomy bleeding occurred in 1.10% (18/1636) of the cases in the clipping group, and in 0.87% (15/1729) of those in the non-clipping group. The difference was -0.22% (95% confidence interval [CI]: -0.96, 0.53). Upper limit of the 95% CI was lower than the non-inferiority margin (1.5%), and we could thus prove non-inferiority of non-clipping against clipping. CONCLUSION: Prophylactic clipping is not necessary to prevent post-polypectomy bleeding for polyps <2 cm in diameter.

Multicenter study on hemorrhagic risk of heparin bridging therapy for periendoscopic thromboprophylaxis.

BACKGROUND: For endoscopic interventions, heparin bridging therapy is recommended in patients who are at high risk from interruption of antithrombotic therapy. Although heparin bridging has been reported to be effective in preventing thrombosis, several reports have raised concerns about increased risk of bleeding. The aim of this study was to clarify complications of hepari bridging therapy in therapeutic endoscopy. METHODS: A nationwide multicenter survey using questionnaire was performed about patients undergoing therapeutic endoscopy with heparin bridging. Patients who underwent therapeutic endoscopy without heparin bridging therapy were considered as controls. Compliance scores of heparin bridging therapy guideline were employed, and association was analyzed between the score and occurrence of post-procedural bleeding. RESULTS: The incidence of post-procedural bleeding was significantly higher (13.5%, 33/245) in the heparin group compared with the control group (2.7%, 299/11102)(p < 0.001). Thrombosis occurred in 1 patient each in the two groups. In the heparin group, post-procedural bleeding was more likely to be delayed bleeding. Dose adjustment of heparin was a significant factor contributing to bleeding. The compliance score of heparin bridging therapy guideline was significantly higher in those who suffered bleeding. CONCLUSIONS: Heparin bridging therapy significantly increased the risk of post-procedural bleeding compared with the control. The bleeding risk was associated with greater adherence with guidelines for heparin bridging therapy.