Successful Eradication of Helicobacter pylori Could Prevent Metachronous Gastric Cancer: A Propensity Matching Analysis.

BACKGROUND AND AIM: Helicobacter pylori is the leading cause of gastric cancer, but it is still uncertain whether eradicating H. pylori in early gastric cancer (EGC) patients who underwent endoscopic resection can prevent metachronous gastric cancer (MGC). This study aimed to investigate the effect of H. pylori eradication to prevent MGC after endoscopic submucosal dissection (ESD). METHODS: In this propensity-matched retrospective observational study, 770 patients with EGC who received ESD were enrolled. The outcome was the incidence of MGC; this was compared between the persistent and eradicated groups. RESULTS: MGC was detected in 27 patients (7.8%) during a median period of 39.0 months (range 26.0-64.0). After propensity matching, 126 pairs of patients in each group were analyzed. The 5-year cumulative incidence rates of MGC were 13.2 and 3.9% in the persistent and eradicated groups, respectively (p= 0.021, log-rank test). On multivariate analysis, H. pylori eradication prevented MGC significantly (hazard ratio [HR] 0.32; p = 0.029). The results remained robust after inverse probability of treatment weighting analysis (HR 0.30; p = 0.020). CONCLUSIONS: Successful H. pylori eradication could prevent MGC after ESD for EGC.

Safety of Endoscopic Mucosal Resection Using a Bipolar Snare for Superficial Nonampullary Duodenal Epithelial Tumors and the Predictive Factors of Piecemeal Resection.

INTRODUCTION: Endoscopic mucosal resection for small superficial nonampullary duodenal epithelial tumors is a noninvasive treatment; however, perforations can occur. Bipolar snares can reduce the risk of perforation due to small tissue damage. Currently, only few studies have reported endoscopic mucosal resection for small superficial nonampullary duodenal epithelial tumors using a bipolar snare and the effect of preoperative findings. OBJECTIVE: To investigate (1) resectability and adverse events of endoscopic mucosal resection using a bipolar snare for small superficial nonampullary duodenal epithelial tumors and (2) the predictions of piecemeal resection. METHODS: Between 2007 and 2017, 89 patients with 107 lesions underwent endoscopic mucosal resection using a bipolar snare. Among them, 88 lesions of 77 patients were evaluated. The primary outcome was the incidence of en bloc resection and R0 resection and adverse events. Risk factors associated with piecemeal resection, including preoperative lesion findings, were also examined. RESULTS: The incidence rates of en bloc and R0 resections were 85.2 and 48.9%, respectively. Neither intraoperative or delayed perforations nor procedure-related mortality was noted. The nonlifting sign after submucosal injection was associated with an increase in piecemeal resection (odds ratio: 20.3, 95% confidence interval: 2.53-162; p = 0.005). CONCLUSION: Endoscopic resection for small superficial nonampullary duodenal epithelial tumors can cause perforation; however, endoscopic mucosal resection using a bipolar snare can be a safe treatment option as it does not cause perforations. The nonlifting sign after submucosal injection is a predictive factor for piecemeal resection.

Non-adherence to Medications in Pregnant Ulcerative Colitis Patients Contributes to Disease Flares and Adverse Pregnancy Outcomes.

BACKGROUND: Adherence to medications is important to maintain disease under control and to prevent complications in pregnant patients with ulcerative colitis (UC). To evaluate the incidence of non-adherence during pregnancy and its effect on relapse and pregnancy outcomes, we conducted a multicenter prospective study using a patient self-reporting system without physician interference. METHODS: Sixty-eight pregnant UC women were recruited from 17 institutions between 2013 and 2019. During the course of pregnancy, questionnaires were collected separately from patients and physicians, to investigate the true adherence to medications, disease activity, and birth outcomes. Multivariable logistic regression analysis was performed to identify the risk factors for the relapse or adverse pregnancy outcomes. RESULTS: Of 68 pregnancy, 15 adverse pregnancy outcomes occurred in 13 patients. The rate of self-reported non-adherence was the greatest to mesalamines in the first trimester, which was significantly higher than physicians' estimate (p = 0.0116), and discontinuation was observed in 42.1% of non-adherent group. Logistic regression analysis revealed non-adherence as an independent risk factor for relapse [odds ratio (OR) 7.659, 95% CI 1.928-30.427, p = 0.038], and possibly for adverse pregnancy outcome (OR 8.378, 95% CI 1.350-51.994, p = 0.023). Among the subgroup of patients treated with oral mesalamine alone, the non-adherence was confirmed to be an independent risk factor for relapse (p = 0.002). CONCLUSION: Non-adherence to mesalamine was underestimated by physicians in pregnant UC patients and contributed to disease relapse and possibly on pregnancy outcomes. Preconceptional education regarding safety of medications and risk of self-discontinuation is warranted.

Positive correlation between pancreatic volume and post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND AND AIM: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most common and serious adverse event associated with ERCP. Risk factors for PEP have been described in various reports. However, risk factors have not been quantified to date. The aim of this study was to investigate the risk factors for PEP by quantification of pancreatic volume using pre-ERCP images. METHODS: Overall, 800 patients were recruited from April 2012 to February 2015 for this study. There were 168 patients who satisfied the inclusion criteria. Measurement of pancreatic volume was achieved using the volume analyzer SYNAPSE VINCENT in all cases and was used to evaluate the risk factors for PEP. RESULTS: According to the criteria established by the consensus guidelines (Cotton classification), 17 patients (10.1%) were classified as having mild disease, 4 (2.4%) as having moderate disease, and 5 (3.0%) as having severe disease. Multivariate model analysis showed that a large pancreatic volume was a significant risk factor for PEP (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.06-1.13; P < 0.001). In addition, the association between the pancreatic volume and the severity of PEP was positively correlated (the effect of volume [per 1 mL]; OR 1.09, 95% CI 1.07-1.12; P < 0.001, the effect of volume [per 10 mL]; OR 2.27, 95% CI 1.72-3.00; P < 0.001). A larger pancreatic volume was significantly associated with a higher incidence of PEP. CONCLUSIONS: A large pancreatic volume was identified as a risk factor for PEP. The results of this study suggest that pre-ERCP images might be useful for predicting PEP.

Effect of EP1 Receptor Antagonist on Transient Lower Esophageal Sphincter Relaxations in Humans.

BACKGROUND/AIMS: Transient lower esophageal sphincter relaxations (TLESRs) are the major cause of gastroesophageal reflux. Recently, an EP1 receptor antagonist, ONO-8539, showed the reduction of TLESRs in monkeys. However, its effect on TLESRs in humans remains unclear. This study investigated the effect of ONO-8539 on postprandial TLESRs in healthy male subjects. METHODS: Twenty-seven subjects participated in this placebo-controlled, cross-over study. The subjects received either placebo or ONO-8539 (450 mg) after a standardized breakfast. A 30-min basal recording was performed 4 h after drug administration. Subsequently, TLESR recordings were performed after a high-fat test meal for 3 h. The examination was repeated at least 7 days from the first evaluation for washout. RESULTS: Thirteen patients were ultimately analyzed. The basal lower esophageal sphincter pressure was not different between the 2 groups (16.3 and 18.0 mm Hg for placebo and ONO-8539, respectively; p = 0.88). ONO-8539 significantly reduced the number of TLESRs from 15.0 to 12.0 for 3 h (p < 0.05). The proportion of terminating events of TLESRs was significantly different between the 2 groups (p < 0.05). No events and swallowing terminated more TLESRs with ONO-8539 than with placebo. CONCLUSIONS: ONO-8539 suppressed TLESRs mildly. EP1 receptor may be involved with the mechanism of human TLESRs.

Impact of preoperative biopsy sampling on severe submucosal fibrosis on endoscopic submucosal dissection for colorectal laterally spreading tumors: a propensity score analysis.

BACKGROUND AND AIMS: It is believed that preoperative biopsy sampling for superficial-type colorectal tumors should be avoided because submucosal fibrosis caused by biopsy sampling makes EMR impossible. However, few studies have reported the influence of biopsy sampling on colorectal endoscopic submucosal dissection (ESD). This study aimed to examine the effect of biopsy sampling on submucosal fibrosis and treatment outcomes of ESD for laterally spreading tumors (LSTs). METHODS: Between April 2005 and September 2015, 441 consecutive patients underwent colorectal ESD in Osaka City University Hospital. Using propensity score matching and inverse probability of treatment weighting (IPTW), we retrospectively evaluated risk factors for severe submucosal fibrosis and treatment outcomes for patients with LSTs, with or without preoperative biopsy sampling. RESULTS: A total of 428 LSTs resected using ESD were enrolled. After matching, there were 136 matched pairs of lesions that did or did not undergo biopsy sampling. Preoperative biopsy sampling increased severe fibrosis compared with that in the non-biopsy sampling group (20.6% vs 11.0%; P = .03) and was significantly associated with severe fibrosis after matching (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.07-4.10; P = .03). After adjustment with IPTW, biopsy sampling also increased the risk of severe fibrosis (OR, 2.33; 95% CI, 1.17-4.63; P = .02). However, no significant differences were observed between the 2 groups in treatment outcomes. CONCLUSIONS: Preoperative biopsy sampling for colorectal LSTs might cause severe submucosal fibrosis but has no adverse influence on clinical outcomes of ESD.

Long-term outcome of endoscopic submucosal dissection for early gastric cancer in patients with severe comorbidities: a comparative propensity score analysis.

BACKGROUND: Recently, endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) has been performed on patients with severe comorbidities because it is less invasive, although little is known regarding long-term outcomes. This study aimed to assess the long-term outcomes of ESD for patients with severe and non-severe comorbidities. METHODS: We enrolled 1081 patients who underwent ESD for EGC between February 2004 and June 2013. Based on the American Society of Anesthesiologists Physical Status (ASA-PS) classification, we defined patients with severe and non-severe comorbidities as ASA-PS 3 and 1/2, respectively. We retrospectively compared the overall survival, risk factors for mortality, and adverse events between these two groups using propensity score matching and inverse probability of treatment weighting. RESULTS: A total of 488 patients met the eligibility criteria. After matching, the ASA-PS 3 group showed a significantly shorter survival than the ASA-PS 1/2 group (5-year overall survival rate, 79.1 vs. 87.7%; p < 0.01). In addition, only the ASA-PS 3 group had a significant risk factor for mortality using both the Cox analysis [hazard ratio (HR), 2.56; 95% confidence interval (CI) 1.18-5.52; p = 0.02] and the IPTW method (HR, 3.14; 95% CI 1.91-5.14; p < 0.01). There was no significant difference in adverse events after matching between the two groups (p = 0.21). CONCLUSIONS: The long-term outcome of gastric ESD for patients with severe comorbidities was worse than for those with non-severe comorbidities. Further studies will be necessary to determine if ESD is truly warranted in these patients.

Association between dietary iron and zinc intake and development of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: The prevalence of ulcerative colitis (UC) has been increasing in Japan. Trace elements, such as iron, zinc, magnesium, and copper, can cause digestive symptoms where there is a deficiency or excess. We focused on the dietary intake of trace elements and their associations with UC development. METHODS: A multicenter, hospital-based case-control study was conducted in Japan. Cases were 127 newly diagnosed UC patients, and 171 age-matched and sex-matched hospital controls were recruited. We considered that UC patients had potentially changed their dietary habits due to disease symptoms. The dietary habits were investigated using a self-administered diet history questionnaire to analyze the dietary intakes and frequencies at two points, the previous 1 month and 1 year before. RESULTS: In the assessment of dietary habits 1 year before, the highest intake of iron showed an increased odds ratio (OR) for UC on multivariate analysis (OR = 4.05, 95% confidence interval, 1.46-11.2, P < 0.01). The highest intake of zinc 1 year before showed a decreased OR for UC (OR = 0.39, 95% confidence interval, 0.18-0.85, P = 0.01). Intakes of magnesium and copper had no significant association with UC. Because most UC cases had experienced the first symptom of UC within the previous 11 months, these intakes at 1 year before represented an association with pre-illness dietary habits. CONCLUSION: A high intake of iron has some effect on the development of UC. In contrast, a high intake of zinc has a protective effect on the development of UC.

Optimal Biopsy Protocol to Evaluate Histological Effectiveness of Proton Pump Inhibitor Therapy in Patients with Eosinophilic Esophagitis.

OBJECTIVE: Recent guidelines propose that both proton pump inhibitor (PPI) responders and nonresponders are included in eosinophilic esophagitis (EoE). Although multiple biopsies should be required to diagnose EoE because of patchy distribution of esophageal eosinophils, it is unclear whether multiple biopsies are required to evaluate histological effectiveness of PPI therapy. This study aimed to determine the optimal biopsy protocol after PPI therapy in patients with EoE. METHODS: Of 110 EoE patients, 22 PPI nonresponders were enrolled. Intraepithelial eosinophils were counted in areas of high density in multiple biopsy specimens after PPI therapy. The prevalence of esophageal eosinophilia and peak eosinophil counts after PPI therapy was analyzed according to the biopsy sites and endoscopic findings. Positive predictive value (PPV) was calculated according to the number of biopsies. RESULTS: Of 124 biopsies, 59 (47.6%) specimens showed esophageal eosinophilia (≥15 per high-power field). Eosinophil counts were significantly higher in specimens from the lower esophagus than in those from the upper esophagus but not in those from the middle esophagus. Prevalence of esophageal eosinophilia was 76.2, 40.9, and 24.3% in the lower, middle, and upper esophagus respectively. PPI nonresponders were diagnosed in all cases with 4 biopsy specimens obtained from the lower and middle esophagus, showing that PPV for non-effectiveness of PPI therapy was 0.910 (95% CI 0.773-1.000). The prevalence of esophageal eosinophilia and peak eosinophil counts was higher in cases with white plaques and linear furrows. CONCLUSION: Multiple biopsies should be required to evaluate histological effectiveness of PPI therapy in patients with EoE. Four biopsies from the lower and middle esophagus may be sufficient.

Changes in Clock Genes Expression in Esophagus in Rat Reflux Esophagitis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Clock genes harmonize circadian rhythms by their periodic expression and regulate several physiological functions. However, the association between clock genes and GERD is still unknown. AIMS: We investigated whether reflux esophagitis affects circadian variability of clock genes in the esophagus and other organs using a rat reflux esophagitis model. METHODS: Reflux esophagitis was induced in 7-week-old male Wistar rats. Sham-operated rats were used as controls. Rats were killed at 09:00 (light period) and 21:00 (dark period) 3 days (acute phase) and 21 days (chronic phase) after induction of esophagitis. The expression levels of clock gene mRNAs such as Per1, Per2, Per3, Cry1, Cry2, Arntl, and Clock in the esophagus were investigated by qPCR. Arntl expression was examined in stomach, small intestine, colon, and liver tissues. Serum melatonin and IL-6 levels were measured by ELISA. RESULTS: Histological examination of reflux esophagitis mainly revealed epithelial defects with marked inflammatory cell infiltration in the acute phase and mucosal thickening with basal cell hyperplasia in the chronic phase. Circadian variability of clock genes, except Cry1, was present in the normal esophagus and was completely disrupted in reflux esophagitis during the acute phase. The circadian variability of Per2, Per3, and Arntl returned to normal, but disruption of Per1, Cry2, and Clock was present in the chronic phase. Disruption of circadian variability of Arntl was observed in the esophagus, as well as in the stomach, small intestine, and liver tissues in reflux esophagitis during the acute phase. There were no significant differences in serum melatonin and IL-6 levels between control and reflux esophagitis animals in both acute and chronic phases. CONCLUSIONS: Disruption to circadian variability of clock genes may play a role in the pathogenesis of GERD.

Barrett's esophagus is negatively associated with eosinophilic esophagitis in Japanese subjects.

BACKGROUND: Although both eosinophilic esophagitis (EoE) and Barrett's esophagus (BE) are considered to be associated with T helper (Th) 2-mediated immune responses, the association between EoE and BE is unclear. We investigated the clinical relationship between EoE and BE. METHODS: We conducted a single-center retrospective observational study. The study included 95 patients with EoE and randomly selected age- and sex-matched controls who underwent esophagogastroduodenoscopy during a medical health check-up at Osaka City University in a ratio of 1:2 for comparison. We compared the clinical characteristics and the prevalence rate of BE, reflux esophagitis (RE), hiatal hernia, and atrophic gastritis between EoE patients and controls by univariate analysis. Furthermore, we performed multivariate logistic regression analysis to investigate the association of these factors with EoE. RESULTS: On univariate analysis, the prevalence rate of BE was significantly lower in patients with EoE than in controls (2.1% vs. 13.2%; p = 0.00528). In contrast, the prevalence rate of RE was higher in EoE patients than in controls, but it was not statistically significant (absence and Grades A, B, and C: 74.7%, 18.9%, 5.3%, and 1.1% vs. 83.7%, 12.6%, 3.7%, and 0%; p = 0.193, respectively). Multivariate analysis showed that BE was negatively associated with EoE (odds ratio: 0.132; 95% confidence interval: 0.0302-0.573; p = 0.00686). CONCLUSIONS: BE is negatively associated with EoE in Japanese subjects. The mechanism behind the inverse relationship between EoE and BE should be examined.

Obesity and hiatal hernia may be non-allergic risk factors for esophageal eosinophilia in Japanese adults.

BACKGROUND: Esophageal eosinophilia (EE) is a basal condition of eosinophilic esophageal disorders including eosinophilic esophagitis (EoE) and asymptomatic EE. EoE is considered as an allergic disorder, while it is unclear whether other non-allergic conditions are involved in the pathophysiology of EE. The aim of this study is to investigate the non-allergic risk factors for EE. METHODS: This cross-sectional study included subjects who underwent esophagogastroduodenoscopy on a medical health check-up. We compared clinical characteristics between subjects with EE (n = 27) and those without EE (n = 5937). RESULTS: The detection rate of EE was 0.45% (27/5964 persons). Of 27 subjects with EE, 20 subjects were symptomatic and 7 were asymptomatic. On univariate analysis, subjects with EE significantly had higher body mass index (BMI) compared to those without EE; 23.4 (4.4) vs 22.3 (4.5) kg/m2, median (interquartile range), p = 0.005. Endoscopic findings revealed that subjects with EE had significantly higher proportion of hiatal hernia (29.6% vs 14.7%; p = 0.049). Subjects with EE were significantly younger and had higher proportion of bronchial asthma; 45 (11.5) vs 51 (18) years, p = 0.013; 25.9% vs 5.2%, p < 0.001, respectively. Multivariate analysis showed that subjects with EE were positively associated with BMI [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.03-1.20; p = 0.010) and hiatal hernia (OR 2.63; 95% CI 1.12-6.18; p = 0.026) compared to those without EE. On trend test, advanced BMI classification had significant trend for increased prevalence of EE (p = 0.002). CONCLUSIONS: Obesity and hiatal hernia may be non-allergic risk factors for EE in Japanese adults.

Serum interleukin-6 level is associated with response to infliximab in ulcerative colitis.

OBJECTIVES: Infliximab is effective in patients with ulcerative colitis (UC); however, one-third of patients do not respond and require additional therapies such as other biologic agents. Therefore, the aim of this study was to analyze the association between pro-inflammatory molecules and clinical efficacy to elucidate possible mechanisms for the non-response to infliximab to aid in treatment selection. MATERIALS AND METHOD: Patients with moderate-to-severe active UC receiving infliximab in our hospital between 2010 and 2016 for whom pre-treatment serum samples were available were retrospectively evaluated. We analyzed the association between serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) and the clinical efficacy of infliximab. The primary endpoint was clinical response at the end of the induction period. RESULTS: Forty-one patients were included in this study. After induction therapy, 27 patients (65.9%) showed a clinical response. Serum IL-6 levels were significantly lower in responders than in non-responders (p = .012), whereas no significant differences were noted in other factors including sMAdCAM-1 and TNF-α. Multivariate analysis identified that serum IL-6 level (odds ratio = 0.72; 95% confidence interval, 0.54-0.96; p = .027) was independently associated with response to infliximab. CONCLUSIONS: Serum IL-6 level is associated with response to infliximab in UC. Elevated concentrations of IL-6 may provide insight to the mechanism of non-response to infliximab.

Heparin-bridging therapy is associated with post-colorectal polypectomy bleeding in patients whose oral anticoagulation therapy is interrupted.

OBJECTIVES: The American and Japanese Societies for Gastrointestinal Endoscopy Guidelines recommend heparin-bridging therapy for patients whose oral anticoagulants are interrupted for endoscopic procedures. However, little is known about the potential association between heparin-bridging therapy and post-polypectomy bleeding (PPB). The aim was to investigate the incidence of PPB associated with heparin-bridging therapy administered to patients whose anticoagulants were interrupted. MATERIALS AND METHODS: This was a retrospective observational study using inverse propensity analysis. Between 2013 and 2015, 1004 patients with 2863 lesions were included. The primary outcomes were the rates of PPB and thromboembolism associated with heparin-bridging therapy. The risk factors associated with PPB were identified using multivariate logistic regression analysis involving probability of treatment weighting (IPTW). RESULTS: The patients were categorized into a heparin-bridging therapy group (78 patients with 255 lesions) or a control group (926 patients with 2608 lesions). The PPB rate in the heparin-bridging therapy group (10.2%, 8/78) was significantly higher than in the control group (1.1%, 11/926) (p <.01). Thromboembolism occurred in one patient in the control group. The multivariate analysis revealed that heparin-bridging therapy was an independent risk factor associated with PPB (odds ratio [OR], 8.21; 95% confidence interval [95% CI], 2.32-29.10; p <.01). IPTW showed heparin-bridging therapy increased PPB (OR, 7.68; 95% CI, 1.83-32.28; p <.01). CONCLUSIONS: Heparin-bridging therapy administered to patients whose oral anticoagulants were interrupted was associated with an increased PPB risk.

Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease.

BACKGROUND AND AIM: Secondary loss of response to adalimumab (ADA-LOR) commonly occurs in patients with Crohn's disease (CD) treated with adalimumab (ADA). We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA-LOR in adult CD patients. METHODS: Patients were divided into either an ED (≥900 kcal/day) or a non-ED group (<900 kcal/day). Cumulative non-ADA-LOR rates were compared between groups. The effects of ED intake to reduce ADA-LOR were also assessed in antitumor necrosis factor-alpha (TNF-α)-naïve and infliximab (IFX)-intolerant or refractory CD patients. Serum ADA and TNF-α levels were measured. RESULTS: We enrolled 117 CD patients into the ED (n = 25) or non-ED (n = 92) groups. Although the cumulative non-ADA-LOR rate was higher in the ED group than in the non-ED group, ED intake was not an independent reducing factor for ADA-LOR (adjusted hazard ratio = 0.725; 95% confidence interval: 0.448-1.180; P = 0.196) in all patients. ED intake was significantly more effective in reducing ADA-LOR in IFX-intolerant or refractory patients than in anti-TNF-α-naïve patients in a dose-related manner (P for interaction <0.20). Serum ADA levels did not differ between the groups. Serum TNF-α levels were significantly lower in the ED group than in the non-ED group at week 28 (P = 0.044) and week 52 (P = 0.043). CONCLUSIONS: Concomitant ED therapy reduced ADA-LOR in IFX-intolerant or refractory patients in a dose-related manner. Reductions in the TNF-α levels by concomitant ED intake may contribute to reduce ADA-LOR in CD patients.

Endoscopic Submucosal Dissection for Adenocarcinomas of the Esophagogastric Junction.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (EGJ) is uncommon in Eastern countries, including Japan, but it is believed that the incidence of EGJ adenocarcinoma will increase in Asia in the future due to the decreasing incidence of Helicobacter pylori infection. Endoscopic submucosal dissection (ESD) is a minimally invasive and curative treatment that allows precise pathological assessment. SUMMARY: Magnifying endoscopy with narrow-band imaging may be useful for differential diagnoses and for delineating the cancer margin of EGJ adenocarcinoma, but subsquamous carcinoma extension, which is the invasion of EGJ adenocarcinoma beneath the normal esophageal squamous epithelium, makes it difficult to detect cancer margins of the oral side in ESD for EGJ adenocarcinoma. Since subsquamous carcinoma extension was reported to be less than 1 cm in most cases, the oral safety margin that is placed 1 cm from the squamocolumnar junction is useful for negative cancerous horizontal margin. A multicenter retrospective study of esophageal adenocarcinoma including EGJ adenocarcinoma showed that mucosal and submucosal cancer within 500 µm from the muscularis mucosa without lymphovascular involvement, a poorly differentiated component, and lesion size over 3 cm were not associated with metastasis. Several retrospective studies about ESD for EGJ adenocarcinoma have suggested feasible short-term and long-term outcomes using curative criteria based on gastric cancer guidelines. Key Messages: ESD would be a good first-line treatment for superficial EGJ adenocarcinoma, including Barrett's adenocarcinoma. Additional information about the incidence of metastasis would help confirm the indication of ESD for EGJ adenocarcinoma.

Clinical Utility of Capsule Endoscopy and Double-Balloon Enteroscopy in the Management of Obscure Gastrointestinal Bleeding.

BACKGROUND: Obscure gastrointestinal bleeding (OGIB) is a common but embarrassing problem for gastroenterologists. Most bleeding lesions associated with OGIB are present in the small intestine and sometimes cannot be identified due to the difficulty associated with physical accessibility. Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) have enabled in the process of diagnosing and have evolved to become approaches to treating OGIB. SUMMARY: CE is a minimally invasive procedure and has a high diagnostic yield in patients with OGIB. DBE offers additional advantage of biopsy collection for pathological diagnosis and therapeutic intervention, but it should be noted that it sometimes causes severe adverse events such as acute pancreatitis, intestinal bleeding, and intestinal perforation. CE should be performed early in the workup course of OGIB. Positive CE findings enhance the diagnostic yield of subsequent DBE, and the effective therapeutic intervention improves the clinical outcomes of OGIB patients. On the contrary, there are no clear guidelines for further investigation of patients with negative CE findings at the present. Although patients in stable general condition may only require follow-up, repeated CE is useful to detect positive findings in patients with evidence of sustained bleeding and progressing anemia. We have revealed that repeated CE has higher positive finding rate than DBE in OGIB patients with negative CE findings in a preliminary study. Key Messages: CE and DBE have complementary roles in the management of OGIB, and the precise timing and proper sequence may be important for the approach to treating OGIB.

The feasibility and short-term clinical outcomes of single-incision laparoscopic surgery for patients with complex Crohn's disease.

PURPOSE: Single-incision laparoscopic surgery (SILS) offers excellent cosmetic results compared with conventional multi-port laparoscopic surgery. Recently, this technique has been applied to Crohn's disease (CD) with primary ileocolic strictures; however, the application of a laparoscopic approach for complex CD, which involves abscess formation, fistula formation, and recurrent CD, is controversial. The aim of this study was to investigate the safety and feasibility of SILS for patients with complex disease and to compare its clinical results in patients with complex disease vs. those with simple stricture disease. METHODS: Fifty patients who underwent SILS for CD were divided into two groups: those with complex disease (complex group, n = 25), and those with simple strictures (simple group, n = 25). The preoperative data and clinical outcomes were analyzed and compared between the groups. RESULTS: The operative time, blood loss and length of laparotomy incision were not significantly different between the groups. Although the rate of conversion and need for an additional port tended to be higher in the complex group, the rate of postoperative complications and length of hospital stay did not differ significantly between the groups. CONCLUSION: SILS may be feasible for carefully selected patients with complex CD.

Prediction of esophageal stricture in patients given locoregional triamcinolone injections immediately after endoscopic submucosal dissection.

BACKGROUND AND AIM: Esophageal endoscopic submucosal dissection (ESD) to resect widespread lesions has increased the incidence of strictures, and some patients develop strictures despite receiving prophylactic locoregional triamcinolone injections. The present study evaluated the predictive factors for esophageal stricture formation in patients given prophylactic triamcinolone injections after ESD. METHODS: This was a retrospective observational study. Of 552 consecutive patients who underwent ESD, those who received prophylactic triamcinolone injections immediately after ESD were enrolled. Primary outcome was predictive factors for esophageal stricture formation in patients given prophylactic triamcinolone injections. RESULTS: We evaluated 101 en bloc resections involving 144 lesions in 96 patients. Strictures occurred following 17 (16.8%) resections. Wider circumferential mucosal defect (odds ratio [OR] 2.42, 95% confidence interval [CI]: 1.01-5.80; P = 0.048) was an independent predictive factor for stricture development. Cut-off value associated with stricture formation was five-sixths of the circumferential mucosal defect. Propensity analysis determined that frequency of esophageal strictures increased in patients with circumferential mucosal defects of more than five-sixths compared with those less than five-sixths (OR = 5.70, 95% CI: 1.61-20.18; P = 0.007). CONCLUSION: Resections involving circumferential mucosal defects of more than five-sixths increased the likelihood of stricture formation in patients given prophylactic locoregional triamcinolone injections after esophageal ESD.

Long-term prognosis of expanded-indication differentiated-type early gastric cancer treated with endoscopic submucosal dissection or surgery using propensity score analysis.

BACKGROUND AND AIMS: Although endoscopic submucosal dissection (ESD) for expanded-indication lesions of differentiated-type early gastric cancer (EGC) has been widely accepted, no prospective randomized study has been conducted on this subject. This study aimed to evaluate the long-term outcomes of ESD and surgery for expanded-indication lesions of differentiated-type EGC. METHODS: Between 1997 and 2012, 1500 consecutive patients with EGC were treated in Osaka City University Hospital. Using propensity score matching and inverse probability of treatment weighting (IPTW), we retrospectively evaluated the long-term outcomes, risk factors for mortality, and adverse events for patients with expanded-indication lesions of differentiated-type EGC who underwent ESD or surgical treatments. RESULTS: A total of 308 patients with expanded-indication lesions of differentiated-type EGC confirmed by pathologic examination after ESD or surgery met the eligibility criteria. After matching, the 5-year overall survival rate was higher in the ESD group than in the surgery group (97.1% vs 85.8%; P = .01). We also found that surgery was significantly associated with mortality using both the IPTW method (hazard ratio [HR], 10.89; 95% confidence interval [CI], 1.37-86.6; P < .01), and Cox analysis (HR, 8.60; 95% CI, 1.11-66.52; P = .04) after matching. Significantly fewer adverse events were associated with ESD than with surgery (6.8% vs 28.4%; P < .01). No cause-specific mortality was observed in either group. CONCLUSIONS: Our results indicate that ESD might be an alternative treatment modality for expanded-indication lesions of differentiated-type EGC.