Search

Introduction: Fishbone (FB) ingestion is a rare cause of gastrointestinal perforation. Herein, we report a case of FB-induced colonic perforation, in which the presence of a penile colonic carcinoma may have contributed to the development of the perforation. Case Presentation: An 83-year-old man was admitted to our hospital with severe abdominal pain during bowel movement. Computed tomography (CT) yielded a diagnosis of sigmoid colonic perforation due to FB and secondary peritonitis. Preoperative endoscopic examination suggested that the perforation was associated with a stalked colon tumor in the vicinity. After undergoing low anterior resection and sigmoid colostomy, the patient is currently doing well. Conclusion: The incidence of FB-induced colorectal-cancer-related perforation is expected to increase in the future owing to an aging society, the increase in the rates of colorectal cancer, and increase in fish consumption. This rare case suggests that preoperative examinations are important and that even relatively small polyps can contribute to gastrointestinal perforation caused by FBs. Older individuals should exercise caution during fish ingestion.

Abstract Background Although proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) are useful in peptic ulcer prevention, their efficacy in preventing other gastrointestinal bleeding remains unclear. This study aimed to identify the status of gastrointestinal bleeding in the modern era when PPIs are widely used. Methods This study included patients who underwent percutaneous coronary intervention (PCI) between 2018 and 2019 at two high-volume centers. Patients were categorized based on whether they experienced gastrointestinal bleeding within 2 years of PCI into groups A (patients who experienced gastrointestinal bleeding within 2 years after PCI) and B (patients who did not experience gastrointestinal bleeding). Results Groups A and B included 21 (4.1%) and 494 (95.9%) patients, respectively (a total of 515 patients). Age at the initial PCI (77.8±2.4 and 72.0±0.5 years in groups A and B, respectively; p = 0.02), weight (53.8±3.2 and 61.8±0.7 kg in groups A and B, respectively; p = 0.01), and concomitant warfarin use (14.3% and 2.0% in groups A and B, respectively; p = 0.0005) were significantly different between the groups. The high bleeding risk rate (90.5% and 47.6% in groups A and B, respectively; p = 0.0001) was significantly different between the groups. A total of 95.9% of patients were taking PPIs or PCAB without significant differences between the groups. However, only one patient, who was taking steroids, had a gastric ulcer during PCAB treatment. Conclusions Acid-related upper gastrointestinal bleeding is largely controlled by PPIs in post-PCI patients. Furthermore, the risk factors for non-acid-related bleeding include older age, lower weight, and concomitant warfarin use.

Abstract Background/aims The natural history of pancreatic branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) is still unknown. This retrospective study aims to determine the morphological changes of BD-IPMNs with attention to the history of surgical resection for extrapancreatic malignancies. Methods and materials This study included 427 subjects with BD-IPMN at the Osaka Medical College from January 2001 to December 2019; 134 patients were included. The predictive factors for the progression of BD-IPMN based on morphological changes were evaluated by univariate as well as multivariate analyses. Furthermore, the clinical features of BD-IPMNs with progressive lesions during follow-up were investigated. Results The average interval of follow-up was 35.8 months (with a range between 12.1 and 157 months). Disease progression occurred in 6 subjects (4.5%). In two of them (1.5%), IPMN-related invasive carcinoma was found. Multivariate analysis demonstrated that surgical resection for extrapancreatic malignancies was a significant predictor of BD-IPMN progression. Conclusion The history of resection of extrapancreatic malignancies should be considered during the follow-up of BD-IPMN.

Background and aimUstekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. Predicting treatment efficacy in advance would be useful for selecting a therapeutic agent. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment.Materials and methodsWe retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at Osaka Medical and Pharmaceutical University Hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment.ResultsOf the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. Baseline C-reactive protein-to-lymphocyte ratio values were significantly higher in the non-remission than in the remission group. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6-62.4, p = 0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (odds ratio: 10, confidence interval: 1.78-56.1, p = 0.009) and that at week 8 (odds ratio: 12, confidence interval: 2.16-66.5, p = 0.005) were significantly associated with clinical remission at week 48.ConclusionsThe baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.

Abstract Background and Aim Patients with gastroesophageal reflux disease (GERD) frequently also have functional dyspepsia (FD) symptoms, which impair their quality of life. However, the magnitude and characteristics of the effects of each symptom on daily life have been unclarified. Using multiple regression analysis, we aimed to clarify these questions. Methods We enrolled 290 patients from 29 institutions across Japan, in this prospective, observational study. Patients responded to three questionnaires (Gastroesophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test [GERD‐TEST], Hospital Anxiety and Depression Scale [HADS], and 8‐item Short‐Form Health Survey [SF‐8]) before and after 4 weeks of proton pump inhibitor treatment. Pearson correlation and multiple regression analyses were conducted between symptoms such as typical GERD, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) of FD, and aspects of daily life, namely, level of satisfaction with the daily life of GERD‐TEST, anxiety and depression score of HADS, and physical and mental component summary of SF‐8. Results Pearson correlation analysis showed a significant correlation in all combinations between GERD/FD‐EPS/FD‐PDS symptoms and the nine aspects of daily life. However, multiple regression analysis results deviated from these results, with the most significant effects seen in the PDS‐symptom subscale (SS) on the five aspects of daily life, that is, dissatisfaction with eating, daily life‐SS, anxiety, depression, and mental component summary (MCS) whereas the significant effects in GERD‐SS on five aspects of daily life, that is, dissatisfaction for eating, anxiety, depression, physical component summary, and MCS, disappeared. Conclusion Dealing with co‐existing FD symptoms without overlooking them may be important in the management of GERD.

Abstract Non-erosive reflux disease (NERD) is classified into grade N (no minimal change) and grade M (minimal change) based on the Los Angeles classification. However, few reports have described the clinical characteristics of grade M. This study was performed to clarify the clinical characteristics of grade M. Among 290 consecutive patients with gastroesophageal reflux disease (GERD), 45 patients with grade M, 62 patients with grade N, and 94 patients with grade A were compared with respect to clinical differences. The degree of symptom improvement after 4 weeks of proton pump inhibitor administration was also prospectively compared among the three groups. Grades N and M showed no or little difference in the patients’ backgrounds (including sex and body mass index), GERD/functional dyspepsia symptom scores, life dissatisfaction (diet, sleep, work, and mood), Short Form-8 (mental component summary) scores, and symptom improvement. In contrast, significant differences were present between grades M and A as well as between grades N and A. The overall results of our study suggest that the distinction between grade M and grade N is of little clinical significance from the viewpoint of clinical characteristics.

We report a case of delayed perforation following esophageal endoscopic submucosal dissection (ESD). A patient with Parkinson’s disease presented with two superficial carcinomatous lesions in the middle third of the esophagus. ESD was performed, and 4/5 of the esophageal circumference was resected, including the adjacent lesion area. Immediately post-ESD, triamcinolone acetonide was injected into the submucosa underlying the ulcer to prevent scarring and stenosis. Histopathological examination of the resected specimen revealed squamous cell carcinoma limited to the lamina propria with negative margins. Seventeen days post-ESD, the patient experienced sudden-onset chest pain during a meal. Computed tomography showed pneumomediastinum, which indicated a delayed perforation. We immediately performed subtotal esophagectomy. A sharply torn longitudinal perforation was present in the post-ESD ulcer. Delayed perforation after esophageal ESD is extremely rare. In this case, the perforation might have been caused by food impaction and delayed ulcer healing due to triamcinolone injection.

Introduction: Liver cirrhosis is the ultimate condition of chronic liver diseases. Non-alcoholic steatohepatitis and fatty liver diseases are emerging in association with metabolic syndrome largely due to excess nutrition. Stromal cells of adipose tissue are enriched mesenchymal stem cells which are pluripotent and immunomodulatory, which are expected to be applied for repairing/regenerative therapy of the impaired organs. Methods: We conducted the multi-institutional clinical trial (Japanese UMIN Clinical Trial Registry: UMIN000022601) of cell therapy using freshly isolated autologous adipose tissue-derived regenerative (stem) cells (ADRCs), which are obtained by the investigational trial device, adipose tissue dissociation device, for liver cirrhosis patients due to non-alcoholic steatohepatitis or fatty liver disease, to exploratory assess efficacy as well as safety of this trial. We completed treatment and 24 weeks follow-up for 7 patients. Results: We observed that 6 out of 7 patients' serum albumin concentration was improved. As for prothrombin activity, 5 out of 7 patients showed improvement. No trial-related adverse events, which were serious or non-serious, was observed. Besides, no malfunction of the investigational trial device was encountered. Conclusion: Thus, treatment with autologous ADRCs obtained with the investigational trial device in steatohepatitis-related cirrhosis was confirmed to be safely conductible and potentially promising for the retaining or improving the impaired hepatic reserve.

Abstract Background Although some kinds of endoluminal surgery for patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) have been reported, there are few reports on their long-term outcomes. In 2014, we reported the effectiveness of endoscopic surgery for PPI-refractory GERD, which we invented and named endoscopic submucosal dissection for GERD (ESD-G) in 2008. Thereafter, we accumulated more cases and monitored the patients’ condition postoperatively and describe the outcomes herein. Patients and methods This single-center, single-arm trial was conducted at the Osaka Medical and Pharmaceutical University Hospital. We compared outcomes between before and 3–6 months after ESD-G. Additionally, we investigated the outcomes of patients 5 or more years after ESD-G. Results We performed 42 ESD-G procedures in 35 patients between 2008 and 2020. In seven patients, ESD-G was performed twice for various reasons. The frequency scale for the symptoms of GERD score was significantly improved 3–6 months after ESD-G (22 → 10, p

Endoscopic ultrasound-guided biliary drainage has been developed as an alternative method for biliary drainage. EUS-guided hepaticogastrostomy (EUS-HGS) can be attempted via the trans-gastric route. These procedures are technically complex for two reasons. First, puncture of the intrahepatic bile duct via the trans-gastric route can be more difficult than that by other approaches because of the small diameter of the target site, and guidewire insertion or manipulation is challenging during EUS-HGS. Second, critical adverse events, such as stent migration into the abdominal cavity, could occur because of the greater mobility of the stomach compared to the duodenum. Therefore, endoscopists should be cautious when performing EUS-HGS. An advantage of EUS-HGS is that it can be performed in patients with complications such as duodenal bulb obstruction or surgically altered anatomy. Recent advances in technique and improvements in devices and stents for EUS-HGS have shown promise for improving the technical success rate of EUS-HGS and reducing the rate of adverse events. However, endoscopists should remain aware of the possibility of critical adverse events such as stent migration.

Most patients who require biliary drainage can be treated by endoscopic retrograde cholangiopancreatography (ERCP)-guided procedures. However, ERCP can be challenging in patients with complications, such as malignant duodenal obstruction, or a surgically-altered anatomy, such as a Roux-en-Y anastomosis, which prevent advancement of the duodenoscope into the ampulla of Vater. Recently, endoscopic ultrasound (EUS)-guided biliary drainage via transhepatic or transduodenal approaches has emerged as an alternative means of biliary drainage. Typically, EUS-guided gallbladder drainage or choledochoduodenostomy can be performed via both approaches, as can EUS-guided hepaticogastrostomy (HGS). EUS-HGS, because of its transgastric approach, can be performed in patients with malignant duodenal obstruction. Technical tips for EUS-HGS have reached maturity due to device and technical developments. Although the technical success rates of EUS-HGS are high, the rate of adverse events is not low, with stent migration still being reported despite many preventive efforts. In this review, we described technical tips for EUS-HGS related to bile duct puncture, guidewire insertion, fistula dilation, and stent deployment, along with a literature review. Additionally, we provided technical tips to improve the technical success of EUS-HGS.

Abstract Background and Aim In patients with severe erosive reflux disease (ERD; Los Angeles classification grade C/D) who do not undergo endoscopic examination, insufficient strength and duration of proton pump inhibitor (PPI) therapy may lead to complications such as esophageal bleeding and stenosis. Therefore, to provide a safe and effective treatment for gastroesophageal reflux disease (GERD), we investigated the clinical features of patients with severe ERD and their responses to PPI therapy. Methods Patients with GERD symptoms received PPI therapy for 4 weeks after endoscopic examination. The patients completed the Gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test questionnaire before and 2 or 4 weeks after PPI treatment. Patient characteristics, presence/absence of coexisting atrophic gastritis (AG) and hiatus hernia (HH), and responses to PPI therapy were compared in patients with GERD among three groups (nonerosive reflux disease, mild ERD [grade A/B], and severe ERD). Results The severe ERD group had a significantly higher proportion of males, higher body mass index, and longer duration of GERD morbidity. Furthermore, the severe ERD group also had a significantly lower incidence of coexisting AG and higher incidence of HH. There was no difference in the severity of GERD before PPI treatment among the three groups. Unexpectedly, the response to PPI therapy was the best in the severe ERD group. Conclusion Sufficient strength and period of PPI therapy are required, even if the symptoms show early improvement, when treating GERD patients without performing endoscopy, considering the possibility of severe ERD.

Background: Several studies have suggested that elderly patients, as well as younger patients, can be safely treated using endoscopic retrograde cholangiopancreatography (ERCP). However, endoscopic ultrasound-guided biliary drainage (EUS-BD) has not been clinically evaluated for very elderly patients. The present multicenter, retrospective study aimed to determine the safety of EUS-BD for advanced elderly patients. Method: Patients who underwent EUS-BD during this period were retrospectively enrolled, and they were divided into two groups based on age: group A (age

Abstract Whipple's disease is a systemic chronic bacterial infection caused by Tropheryma whipplei, a gram‐positive bacillus. T. whipplei infection in the small intestine often causes malabsorption and is often accompanied by gastrointestinal symptoms such as diarrhea and abdominal pain. In this report, we describe our experience with a case of Whipple's disease in which the affected patient did not have the typical gastrointestinal symptoms. The patient was an 80‐year‐old male who presented with complaints of weight loss and lower leg edema due to malabsorption and shortness of breath during exertion. A blood test revealed a decreased albumin level and an elevated C‐reactive protein level. Endoscopic images revealed diffuse white villi, the presence of which extended from the duodenum to the upper jejunum. We made a diagnosis of Whipple's disease based on pathological findings associated with the duodenum, electron microscopic findings, and findings of polymerase chain reaction (PCR) tests (performed using mucosal tissue). Clinical symptoms and endoscopic findings improved with antibiotics. Real‐time PCR tests were performed for a quantitative evaluation of the effect of treatment. Endoscopy is useful for diagnosing Whipple's disease when there is an absence of gastrointestinal symptoms, and hypoalbuminemia of unknown etiology is observed.

Abstract Background The current virtual chromoendoscopy equipment cannot completely detect superficial squamous cell carcinoma (SCC) in the esophagus, despite its development in the recent years. Thus, in this study, we aimed to elucidate the appropriate air volume during endoscopic observation to improve the visibility of esophageal SCC. Methods This retrospective study included a total of 101 flat type esophageal SCCs identified between April 2017 and January 2019 at the Department of Gastrointestinal Oncology, Osaka International Cancer Institute. Video images of narrow band imaging (NBI) under both less-air and standard-air conditions were recorded digitally. Videos were evaluated by five endoscopists. Relative visibility between less-air and standard-air conditions of the brownish area, brownish color change of the epithelium, and dilated intrapapillary capillary loop (IPCL) were graded as 5 (definitely better under less-air condition) to 1 (definitely worse under less-air condition), with 3 indicating average visibility (equivalent to standard-air observation). Results The mean (standard deviation) visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs under less-air condition were 3.94 (0.58), 3.73 (0.57), and 4.13 (0.60), respectively, which were significantly better than that under standard-air condition (p

Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD) has emerged as an option in patients with failure of retrograde access to the pancreatic duct (PD) because of difficulty in cannulation or surgically altered anatomy. This article provides a comprehensive review of the techniques and outcomes of EUS-PD, especially EUS-guided pancreatic transmural stenting. The clinical data derived from a total of 401 patients were reviewed in which the overall technical and clinical success rates were 339/401 (85%, range 63%–100%) and 328/372 (88%, range 76%–100%), respectively. Short-term adverse events occurred in 25% (102/401) of the cases, which included abdominal pain (n=45), acute pancreatitis (n=17), bleeding (n=10), and issues associated with pancreatic juice leakage such as perigastric or peripancreatic fluid collection (n=9). In conclusion, although EUS-PD remains a challenging procedure with a high risk of adverse events such as pancreatic juice leakage, perforation, and severe acute pancreatitis, the procedure seems to be a promising alternative for PD drainage in patients with altered anatomy or unsuccessful endoscopic retrograde pancreatography.

Endoscopic ultrasound (EUS)-guided pancreatic access is an emergent method that can be divided into the two main techniques of EUS-guided rendezvous and pancreatic transmural stenting (PTS). While many reports have described EUS-guided procedures, the indications, technical tips, clinical effects, and safety of EUS-guided pancreatic duct drainage (EUS-PD) remain controversial. This review describes the current status of and problems associated with EUS-PD, particularly PTS. We reviewed clinical data derived from a total of 334 patients. Rates of technical and clinical success ranged from 63% to 100% and 76% to 100%, respectively. In contrast, the rate of procedure-related adverse events was high at 26.7% (89/334). The most frequent adverse events comprised abdominal pain (n=38), acute pancreatitis (n=15), bleeding (n=9), and issues associated with pancreatic juice leakage such as perigastric fluid, pancreatic fluid collection, or pancreatic juice leaks (n=8). In conclusion, indications for EUS-PTS are limited, as is the evidence of its viability, due to the scarcity of expert operators. Despite improvements made to various devices, EUS-PTS remains technically challenging. Therefore, a long-term, large-scale, multicenter study is required to establish this technique as a viable alternative drainage method.

Background and study aims Stent migration into the abdominal cavity, which can occur due to stent shortening or stomach mobility, is a critical adverse event (AE) in EUS-HGS. To prevent this AE due to stent shortening, a novel, partially covered self-expandable metal stent with an antimigratory single flange has recently become available in Japan. The present study evaluated the clinical feasibility and safety of EUS-HGS using this novel stent. Patients and methods We measured stent length in the abdominal cavity and the luminal portion after EUS-HGS using computed tomography (CT) performed 1 day after EUS-HGS (early phase). To evaluate stent shortening and the influence of stomach mobility, we also measured stent length at the same sites on CT performed at least 7 days after EUS-HGS (late phase). Results Thirty-one patients successfully underwent EUS-HGS using this stent. According to CT in the early phase, stent length in the abdominal cavity was 7.13 ± 2.11 mm and the length of the luminal portion was 53.3 ± 6.27 mm. Conversely, according to CT in the late phase, stent length in the abdominal cavity was 8.55 ± 2.36 mm and the length of the luminal portion was 50.0 ± 8.36 mm. Stent shortening in the luminal portion was significantly greater in the late phase than in the early phase (P = 0.04). Conclusions CT showed that stent migration can occur even with successful stent deployment, due to various factors such as stent shortening. The antimigratory single flange may be helpful to prevent stent migration, but further prospective comparative studies are needed to confirm our results.

BackgroundAutonomic dysfunction is a factor in irritable bowel syndrome (IBS). However, there are no reports of autonomic nervous system (ANS) activity during natural defecation in patients with IBS. We aimed to clarify the relationship between ANS activity and life events, such as defecation and abdominal symptoms, using real-time recording.MethodsSix patients with IBS and 14 healthy controls were enrolled in this prospective multicenter study. ANS activity was recorded for 24 h using a T-shirt wearable device, and life events were recorded simultaneously in real time using a smartphone application software. Low frequency/high frequency (LF/HF) and HF calculated by power spectrum analysis were defined as activity indicators of the sympathetic and parasympathetic nerves, respectively.ResultsThe means of LF/HF and HF in the period with positive symptoms were comparable between the groups; however, the sum of LF/HF, sum of ΔLF/HF, and the maximum variation in ΔLF/HF were significantly higher in the IBS group. In the IBS group, the sum of ΔLF/HF and LF/HF increased significantly from 2 min before defecation, and the sum of LF/HF remained significantly higher until 9 min after defecation. The sum of ΔLF/HF at 2 min before defecation was significantly positively correlated with the intensity of abdominal pain and diarrhea and constipation scores. In contrast, it was significantly negatively correlated with defecation satisfaction and health-related quality of life.ConclusionsIn patients with IBS, sympathetic nerve activity was activated 2 min before defecation, which was correlated with abdominal symptoms and lower QOL.

Background: After multiple uncovered self-expandable metal stent (UCSEMS) deployments, endoscopic revision becomes complex and potentially challenging. A novel stent delivery system with a dilation function has recently been developed in Japan. This study evaluated the technical feasibility of this device for patients with unresectable malignant hilar biliary obstruction (MHO) after multiple UCSEMS deployments. Method: Participants comprised consecutive patients with unresectable MHO who had undergone multiple UCSEMS deployments and required endoscopic revision for the right or left hepatic bile ducts, as decided by cholangiography under endoscopic retrograde cholangiopancreatography (ERCP) guidance. Results: A total of 14 patients requiring endoscopic revision of right and left hepatic bile ducts were enrolled in this study. Among these 14 patients, guidewire insertion through the mesh of previously placed stents failed in 2 patients. As a result, these two patients underwent only unilateral UCSEMS deployment. Because clinical success was not obtained, transmural placement of the UCSEMS under Endoscopic Ultrasound (EUS) guidance to the segment of the liver not being drained was performed in those patients. The molting technique was attempted in 12 patients, proving successful in all patients. The technical success rate was therefore 92.8% (12/14). Mean procedure time was 23.2 min. Conclusion: This novel stent delivery system with a dilation function may be useful in endoscopic revision techniques for bilateral UCSEMS deployment.

Background and study aims We developed a self-propelled capsule endoscope that can be controlled from outside the body with real-time observation. To improve the device, we conducted a clinical trial of total gastrointestinal capsule endoscopy in healthy subjects to ascertain whether our first-generation, self-propelled capsule endoscope was safe and effective for observing the entire human gastrointestinal tract. Patients and methods After adequate gastrointestinal pretreatment, five healthy subjects were instructed to swallow a self-propelling capsule endoscope and the safety of a complete gastrointestinal capsule endoscopy with this device was assessed. We also investigated basic problems associated with complete gastrointestinal capsule endoscopy. Results No adverse effects of the magnetic field were identified in any of the subjects. No mucosal damage was noted in any of the subjects with the use of our first-generation, self-propelling capsule endoscope. We found that it took longer than expected to observe the stomach; the view was compromised by the swallowed saliva. The pylorus was extremely difficult to navigate, and the endoscope’s fin sometimes got caught in the folds of the small intestine and colon. Conclusions To resolve the problems associated with the existing self-propelling capsule endoscope, it may be necessary to not only improve the capsule endoscopes, but also to control the environment within the gastrointestinal tract with medications and other means. Our results could guide other researchers in developing capsule endoscopes controllable from outside the body, thus allowing real-time observation.

ABSTRACT Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat deposition in the liver unrelated to alcohol consumption, is highly prevalent worldwide. However, effective therapeutic agents approved for NAFLD treatment are lacking. An ileal bile acid transporter inhibitor (IBATi), which represents a new mode of treatment of chronic idiopathic constipation, leads to increased delivery of bile acids to the colon. We investigated the effect of IBATi against NAFLD through modification of the gut microbiota in mice. IBATi treatment significantly suppressed body weight gain, liver dysfunction, and serum low-density lipoprotein levels and significantly decreased NAFLD activity scores in high-fat diet (HFD) mice. Treatment with IBATi ameliorated the decreased hepatic cholesterol 7-a-monooxygenase (Cyp7a1) and increased ileal fibroblast growth factor 15 (Fgf15) mRNA expression in HFD mice. Further, IBATi treatment changed the α-diversity in the gut microbiota reduced by HFD, which was analyzed in feces using 16S rRNA sequencing. To establish the mechanism underlying improvement in NAFLD induced by IBATi, we recolonized antibiotic solution-treated mice by fecal microbiome transplantation (FMT) using stool from HFD or HFD plus IBATi mice. This is the first report that fecally transplanted gut microbiota from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. In conclusion, IBATi improved hepatic steatosis by ameliorating gut microbiota dysbiosis in NAFLD model mice, suggesting a potential therapeutic agent for NAFLD treatment. IMPORTANCE NAFLD is an increasingly recognized condition that may progress to liver cirrhosis and hepatocellular carcinoma, and community surveys have assessed that the prevalence is 14 to 32% worldwide. The first line of treatment for NAFLD is lifestyle modification to achieve weight reduction, particularly through diet and exercise. However, weight reduction is difficult to achieve and maintain, and pharmacological agents approved for the treatment of NAFLD are lacking. This study investigated the influence of the gut microbiota and the effect of an IBATi on NAFLD using a murine model. Treatment with IBATi significantly improved NAFLD in HFD mice. Further, fecal microbiome transplantation using stool from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. Our study makes a significant contribution to the literature because the study findings suggest a potential treatment strategy for NAFLD patients by ameliorating gut microbiota dysbiosis.

Eosinophilic gastroenteritis is an eosinophilic inflammatory disease that responds well to steroids but often relapses upon their discontinuation, necessitating maintenance treatment. The anti–interleukin-5 antibody mepolizumab is useful for treating bronchial asthma and eosinophilic polyangiitis granulomatosa, and its efficacy in eosinophilic esophagitis has also been investigated. However, there are few reports of cases of eosinophilic gastroenteritis treated with mepolizumab. Here we report a case of steroid-dependent eosinophilic enteritis associated with asthma treated with mepolizumab that was maintained in steroid-free remission.

Abstract Background Metachronous cancer in patients with head and neck cancer (HNC) is common and is associated with a poor prognosis. We aimed to evaluate the incidence of metachronous cancer at different sites according to age at diagnosis of index HNC. Methods We collected data on 2011 patients with oral cancer, oropharynx cancer, hypopharyngeal cancer, and laryngeal cancer as index cancers using the Osaka International Cancer Institute Cancer Registry database between 2005 and 2016. Among these, we analyzed 1953 patients after excluding 5 patients who were not followed-up and 53 patients with simultaneous multiple index cancers. We evaluated the cumulative incidence of metachronous cancer in the esophagus, lung, and other sites according to age at diagnosis of the index HNC using the Kaplan–Meier method. Multivariate logistic regression analysis was performed to identify factors that influenced the incidence of metachronous cancers following HNC. Results The cumulative incidence of metachronous esophageal cancer in young patients (

Abstract Background We aimed to investigate how high-dose ecabet sodium affects low-dose aspirin-induced small intestinal mucosal injury in healthy volunteers. Methods Healthy volunteers were enrolled randomly into one of two groups with the following drug regimens for 2 weeks: group A, low-dose aspirin once per day and group B, low-dose aspirin and 4.0 g of ecabet sodium. Small bowel capsule endoscopy was performed before and 2 weeks after low-dose aspirin administration. Results A significant difference was found in the median number [range] of small intestinal lesions between baseline and two weeks after low-dose aspirin administration in group A (baseline: 1 [0–5], after: 5 [1–11]; p = 0.0059) but not in group B (baseline: 0.5 [0–9], after: 3 [0–23]; p = 0.0586). In group B, although the median number [range] of lesions in the first tertile of the small intestine did not increase two weeks after low-dose aspirin administration (baseline: 0 [0–4], after: 1.5 [0–8]; p = 0.2969), the number of lesions in the second and third tertiles of the small intestine increased significantly (baseline: 0 [0–5], after: 2 [0–15]; p = 0.0469). Conclusions Ecabet sodium had a preventive effect on low-dose aspirin-induced small intestinal mucosal injury in the upper part of the small intestine. Trial registration ISRCTN 99322160, 01/10/2018.

M2b monocytes commonly isolated from patients with unhealthy alcohol use (Alc) have been described as cells that make the host susceptible to opportunistic infections. CD34+CD10+CD19− cells are multilineage progenitors of CD19+ cells, and we show that the effect of these cells from the peripheral blood on M2b monocyte polarization differed between healthy donors and Alc in this study. In healthy donors, these cells consistently differentiated into high-mobility group box-1 (HMGB1)-nonproducing cells (CD19+ cells) in response to retinoic acid (RA). However, owing to the lack of expression of RA receptor (RAR), these cells from Alc failed to differentiate into CD19+ cells under the same RA stimulation. Conditioned medium (CM) of these cells from Alc induced the polarization of M2b monocytes, which increases the susceptibility of hosts to opportunistic infections in Alc. When the alcoholic individuals were subjected to 2 weeks of abstinence from alcohol, these cells from Alc recovered their RAR expression and differentiated into CD19+ cells. Moreover, the CM of these cells from Alc after abstinence lost its ability to induce M2b monocyte polarization. These results indicate that these cells from Alc have different properties from those of healthy donors. In Alc, these cells without RAR stimulate M2b monocyte polarization through the production of HMGB1.

Background and study aims Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) may be most complex because of the EUS-guided biliary drainage procedure and variations in the course of the intrahepatic bile duct compared with the common bile duct (CBD). Appropriate guidewire insertion is essential. Physician-controlled guidewire manipulation (PCGW) might improve technical success rates of bile duct cannulation. The present study aimed to determine the technical feasibility and safety of PCGW during EUS-HGS. Patients and methods A total of 122 consecutive patients who were scheduled to undergo EUS-HGS between October 2017 and April 2019 were prospectively registered. The primary endpoint was the technical success rate of guidewire insertion into the CBD or hepatic hilum. Guidewire insertion was considered to have failed if the HGS assistant failed to achieve manipulation. Results The intrahepatic bile duct was successfully punctured in 120 of 122 patients. During guidewire insertion by the HGS assistant, guidewire fracture was observed in one patient. The guidewire was successfully inserted into the biliary tract and manipulated by the HGS assistant in 96 patients. PCGW was thus attempted for the remaining 23 patients. The guidewire was inserted by PCGW in all 23 patients, improving the technical success rate for guidewire insertion from 80 % to 100 %. After tract dilation, we deployed covered metal stents and plastic stents in 117 and two patients, respectively. The overall technical success rate for EUS-HGS was 97.5 % (119/122). Adverse events comprising bile peritonitis or leakage developed in five patients. Conclusion PCGW might contribute to improving the success rate of EUS-HGS.

Background and study aims Duct penetration by the guidewire sometimes occurs during endoscopic retrograde cholangiography, which might lead to adverse events such as acute pancreatitis. To prevent duct penetration, making a loop shape with the guidewire might provide a useful technique. The aim of this experimental study was thus to evaluate which types of guidewire can most easily form a loop shape. Methods This experimental study evaluated six guidewires (0.025-inch, angle type): MICHISUJI; VisiGlide 2; Jagwire; Pathcorse; RevoWave-α UltraHard 2; and M-through. Flexibility of the tip, shaft stiffness, and the ability to form a loop were evaluated for each type in an ex vivo model. Deformation behavior was also recorded on video, and factors suitable for making a loop shape in each guidewire were evaluated. Results Flexibility and stiffness of each guidewire differed significantly. During an experimental study regrading deformation behavior before forming a loop shape, maximum load was lower for MICHISUJI (6.8 g) than for other guidewires (Jagwire [11.3 g], M-through [12.9 g], VisiGlide 2 [12.9 g], Revowave [21 g], and Pathcorse [25.4 g]). Mean time required to achieve a loop shape was as follows: MICHISUJI, 6.2 seconds; M-through, 8.7 seconds; VisiGlide 2, 11.0 seconds; and Revowave, 7.1 seconds. Conclusion In conclusion, characteristics of flexibility and stiffness among guidewires were significantly different in the ex-vivo study. In the experimental study regrading deformation behavior until achieving a loop shape, maximum load also differed. To evaluate whether guidewires easily form a loop shape, clinical study is needed.

Background: Little is known about the efficacy of proton-pump inhibitor (PPI) therapy in the management of esophageal ulcers after endoscopic submucosal dissection (ESD). Therefore, the objective of this study was to investigate the efficacy of PPI in ulcer healing following ESD for superficial esophageal neoplasms, using a propensity score analytic approach. Methods: This retrospective cohort study was conducted at a single referral center. Between April 2005 and August 2015, 199 consecutive patients with superficial esophageal cancer and esophageal dysplasia underwent ESD. For patients with PPI administration, intravenous PPI therapy was commenced immediately after ESD, and oral PPI was administered daily from post-operative day 3, until ulcer healing was identified. We compared the remnant-ulcer rate at 4 weeks after esophageal ESD between the PPI administration and non-PPI groups, using propensity scores and the inverse probability of treatment weighting (IPTW) method. Results: After exclusions, a total of 88 patients were analyzed. The remnant-ulcer rate at 4 weeks after ESD was 25.5% (12/47) and 14.6% (6/41) in the PPI administration and non-PPI groups ( p = 0.21). After adjusting for background factors using IPTW, the risk of a remnant ulcer in the PPI administration group was not decreased significantly compared with that in the non-PPI group [odds ratio (OR) = 2.42, 95% confidence interval (CI): 0.73–7.97, p = 0.15]. Furthermore, PPI therapy did not decrease significantly the remnant-ulcer rate on logistic regression analysis after adjusting for the propensity score (OR = 2.40, 95% CI: 0.69–8.32, p = 0.15). Conclusion: PPI administration does not promote ulcer healing after ESD for superficial esophageal squamous cell carcinoma.

Background: Endoscopic treatment for malignant biliary obstruction (MBO) in patients bearing surgically altered anatomy (SAA) is not well-established. Although endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as a new treatment option for MBO, limited data are available regarding the efficacy and safety of EUS-BD in patients with SAA. We conducted a multicenter prospective registration study to evaluate the efficacy and safety of EUS-BD in this population. Methods: This study involved 10 referral centers in Japan. Patients with SAA who were scheduled to receive EUS-BD for unresectable MBO between May 2016 and September 2018 were prospectively registered. The primary endpoint was technical success and the secondary outcomes were clinical success, procedure time, procedure-related adverse events (AEs), stent patency, and overall survival. Results: In total, 40 patients were prospectively enrolled. The surgical reconstruction methods were gastrectomy with Roux-en-Y reconstruction (47.5%), gastrectomy with Billroth-II reconstruction (15%), pancreaticoduodenectomy (27.5%), and hepaticojejunostomy with Roux-en-Y reconstruction (10%). EUS-BD was performed for primary biliary drainage in 31 patients and for rescue biliary drainage in nine patients. Transmural stenting alone (60%), antegrade stenting alone (5%), and a combination of the two techniques (35%) were selected for patients treated with EUS-BD. Technical and clinical success rates were 100% (95% confidence interval, 91.2–100.0%) and 95% (95% confidence interval, 83.1–99.4%), respectively. Mean procedure time was 36.5 min. Early AEs were noted in six patients (15%): three self-limited bile leak, one bile peritonitis, and two pneumoperitonea. Late AEs occurred in six patients (15%): one jejunal ulcer and five stent occlusions. Stent patency rate after 3 months of survival was 95.7% (22/23). Median overall survival was 96 days. Conclusion: EUS-BD for MBO in patients with SAA appears to be effective and safe not only as a rescue drainage technique after failed endoscopic retrograde cholangiography but also as a primary drainage technique. Clinical Trial Registration: UMIN000022101

Background and study aims A novel fine-gauge electrocautery dilator (ED) has recently become available in Japan. The current study evaluated the safety and feasibility of transluminal antegrade dilation for hepaticojejunal stricture (HJS) using this novel ED. Patients and methods Patients who with complicated HJS were retrospectively enrolled. The primary and secondary endpoints of this study were rates of technical success defined as functional antegrade HJS dilation using the novel ED and types of adverse events, respectively. A total of 22 patients were enrolled. Among them, six were treated using an enteroscopic approach due to the absence of bile duct dilation or patient refusal to undergo EUS-HGS. Therefore, 16 patients underwent EUS-HGS. Results The procedure was successful in 15 of 16 patients (93.8 %). The contrast medium flowed from the intrahepatic bile duct to the intestine of 14 of 15 patients (93.3 %). The resolution rate of HJS was 13 of 14 (92.9 %) at 6 months. Conclusion Our technique might offer a new option with which to treat HJS, although a prospective study with long-term follow-up is needed.

Background and aims Treatment of biliary neoplasms often involves multiple endoscopic retrograde cholangiopancreatography (ERCP)-related procedures. Endoscopic sphincterotomy (ES) may prevent post-ERCP pancreatitis (PEP). This retrospective, multicenter cohort study aimed to investigate the effectiveness of ES for prevention of PEP in patients with biliary neoplasm. Methods Patients with biliary duct neoplasm who underwent ERCP between January 2006 and December 2016 were enrolled. The frequency of PEP was compared between the ES and non-ES groups using propensity score analysis. The effectiveness of ES in subgroups of patients who underwent biliary duct stent placement, intraductal ultrasound (IDUS), and transpapillary biliary duct biopsy was analyzed by logistic regression. Results Of the 362 patients enrolled, 84 (23.2 %) developed PEP. Propensity score matching for PEP risk factors in 172 ERCP procedures showed that the frequency of PEP in the ES group was lower than that in the non-ES group (19.7 % vs. 33.7 %). Non-ES was also an independent risk factor for PEP in patients who underwent intraductal ultrasound and transpapillary biliary duct biopsy (RR = 4.54 and 5.26), but was not an independent risk factor for PEP in patients with biliary duct stents. In addition, there was no evidence that the frequency of PEP was statistically different between patients with plastic stents and metal stents in the ES and non-ES groups (P = 0.14 and 0.10). Conclusions ES is an effective technique to prevent PEP in patients with biliary neoplasms. In particular, ES is a safe technique to prevent PEP when performing IDUS and transpapillary biliary duct biopsy.

Background/AimsElectrohydraulic lithotripsy (EHL) under endoscopic retrograde cholangiopancreatography (ERCP) guidance can be an option to treat difficult stones. Recently, a digital, single-operator cholangioscope (SPY-DS) has become available. Peroral transluminal cholangioscopy (PTLC) using SPY-DS has also been reported. In this retrospective study, the technical feasibility and clinical effectiveness of EHL for difficult bile duct stones under ERCP guidance and under PTLC guidance was examined.Methods : In this pilot study, patients with difficult bile duct stones between July 2016 and July 2017 were retrospectively enrolled.Results : Forty-two consecutive patients underwent EHL using a SPY-DS; 34 patients underwent EHL under ERCP guidance, and the other 8 patients underwent EHL under PTLC guidance. Median procedure time was 31 minutes (range, 19 to 66 minutes). The median number of EHL sessions was 1 (range, 1 to 2), and that of ERCP sessions was also 1 (range, 1 to 3). The rate of complete stone clearance was 98% (41/42). Adverse events such as cholangitis and acute pancreatitis were seen in 14% (6/42), which could be treated conservatively.Conclusion : sEHL using SPY-DS was technically feasible, not only under ERCP guidance, but also PTLC guidance. A prospective clinical study of EHL using SPY-DS is needed.

Background/AimsRecently, recombinant human soluble thrombomodulin (rTM) has been developed as a new drug for disseminated intravascular coagulation (DIC). This study aims to evaluate the clinical benefit of rTM in patients with sepsis-induced DIC caused by acute cholangitis who underwent biliary drainage.Methods : Patients were divided into two groups: the rTM therapy group and the non-rTM therapy group. The primary outcome was the DIC resolution rate at 7 days, and the secondary outcome was 28-day mortality rate.Results : Thirty-five patients were treated by rTM, and 36 patients were treated without rTM for DIC. The rate of resolution of DIC at day 7 was significantly higher in the rTM group than in the non-rTM group (82.9% vs 55.6%, p=0.0012). Compared with the non-rTM group, the 28-day survival rate of the r-TM group was significantly higher (rTM vs non-rTM, 91.4% vs 69.4%, p=0.014). According to multivariate analysis, non-rTM (hazard ratio [HR], 2.681) and CRP (HR, 2.370) were factors related to decreased survival.Conclusion : srTM treatment may have a positive impact on improving DIC and survival rates in patients with severe acute cholangitis.

Abstract Background Laparoscopic and endoscopic cooperative surgery (LECS) was performed for the local resection of gastrointestinal stromal tumors (GIST). LECS enables less resection of the lesion area and preserves function. Furthermore, LECS can be safely performed and independent of tumor location. However, LECS is not usually used for cases involving gastric carcinoma because it may seed tumor cells into the peritoneal cavity when the gastric wall is perforated. Here, we report seven cases of LECS for intra-mucosal gastric carcinoma, which were difficult to carry out by endoscopic submucosal dissection (ESD) because of ulcer scars. Methods We performed LECS (classical LECS and inverted LECS) in seven cases of intra-mucosal gastric carcinoma. All cases had ulcer scars beside the tumor. LECS was chosen because ESD was thought to be difficult because of the ulcer scars. We only selected cases in which the patients did not prefer gastrectomy and endoscopic examination was indicative of intra-mucosal gastric carcinoma. Results In all cases, LECS was performed without severe complications including postoperative stenosis. Histopathology findings proved that the tumors were intra-mucosal carcinoma and had been resected completely. Furthermore, there were ulcer scars (Ul IIIs-IVs) beside the tumor. Currently, dissemination and recurrence have not been apparent. Conclusions LECS for intra-mucosal gastric carcinoma is an efficient procedure, but strict observation is necessary because of the possibility of peritoneal dissemination. Results suggest that LECS is likely to be effective for cases involving intra-mucosal gastric carcinoma that are difficult to treat by ESD due to ulcer scars.

Background/Aim: Recently, endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has emerged using a self-expandable metallic stent (SEMS). The aim of the study was to evaluate the long-term outcomes of this procedure. In addition, the efficacy and safety of EUS-GBD with SEMS were assessed. Patients and Methods: Thirteen consecutive patients who underwent EUS-GBD for acute cholecystitis between February 2014 and September 2016 were included in this retrospective study. EUS-GBD was performed under the guidance of EUS and fluoroscopy, through puncturing the gallbladder with a needle, inserting a guidewire, dilating the puncture hole, and placing a SEMS. Results: The rates of technical success, functional success, and adverse events were 100%, 92.3% and 7.7%, respectively. The median procedure time was 26.9 min (range 19–42 min). The median follow-up time was 240 days (range 14–945 days) and during this follow-up period recurrence of cholecystitis was observed in one patient (7.7%). Conclusion: EUS-GBD with a SEMS is a possible alternative treatment for acute cholecystitis in high surgical risk patients. Long-term outcomes after EUS-GBD were promising.

Skeletal muscle is a major organ of insulin-induced glucose metabolism. In addition, loss of muscle mass is closely linked to insulin resistance (IR) and metabolic syndrome (Met-S). Skeletal muscle loss and accumulation of intramuscular fat are associated with a variety of pathologies through a combination of factors, including oxidative stress, inflammatory cytokines, mitochondrial dysfunction, IR, and inactivity. Sarcopenia, defined by a loss of muscle mass and a decline in muscle quality and muscle function, is common in the elderly and is also often seen in patients with acute or chronic muscle-wasting diseases. The relationship between Met-S and sarcopenia has been attracting a great deal of attention these days. Persistent inflammation, fat deposition, and IR are thought to play a complex role in the association between Met-S and sarcopenia. Met-S and sarcopenia adversely affect QOL and contribute to increased frailty, weakness, dependence, and morbidity and mortality. Patients with Met-S and sarcopenia at the same time have a higher risk of several adverse health events than those with either Met-S or sarcopenia. Met-S can also be associated with sarcopenic obesity. In this review, the relationship between Met-S and sarcopenia will be outlined from the viewpoints of molecular mechanism and clinical impact.

The term “cachexia” is derived from the Greek words kakos (bad) and hexis (habit). Cachexia is a malnutrition associated with chronic diseases such as cancer, chronic heart failure, chronic renal failure, and autoimmune diseases, and is characterized by decreased skeletal muscle mass. Cancer cachexia is quite common in patients with advanced cancer. Weight loss is also a characteristic symptom of cancer cachexia, along with decreased skeletal muscle mass. As nutritional supplementation alone cannot improve cachexia, cytokines and tumor-derived substances have been attracting attention as its relevant factors. Cancer cachexia can be also associated with reduced chemotherapeutic effects, increased side effects and treatment interruptions, and even poorer survival. In 2011, a consensus definition of cachexia has been proposed, and the number of relevant research reports has increased significantly. However, the pathogenesis of cachexia is not fully understood, and there are currently few regulatory-approved standard treatments for cachexia. The main reason for this is that multiple etiologies are involved in the development of cachexia. In this review, we will outline the current status of cachexia, the mechanisms of which have been elucidated in recent years, especially from the perspective of advanced cancer.