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.

Risk of Pancreatitis Following Biliary Stenting With/Without Endoscopic Sphincterotomy: A Randomized Controlled Trial.

BACKGROUND & AIMS: The efficacy of endoscopic sphincterotomy (ES) before endoscopic transpapillary biliary drainage in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been established. The aim of this study was to evaluate the effect of performing ES before biliary stent/tube placement on the occurrence of PEP. METHODS: Three hundred seventy patients with biliary stricture requiring endoscopic biliary stenting were enrolled and randomly allocated to the ES group (n = 185) or non-ES group (n = 185). All participants were followed up for 30 days after the procedure. The data and occurrence of adverse events were prospectively collected. The primary outcome measure of this study was the incidence of PEP within 2 days of initial transpapillary biliary drainage. Secondary outcome measures were the incidence of other adverse events related to biliary stent/tube placement. RESULTS: PEP occurred in 36 patients (20.6%) in the non-ES group and in 7 patients (3.9%) in the ES group (P < .001). The difference in the incidence of PEP between the 2 groups in the per-protocol population was 16.7% (95% confidence interval, 10.1%-23.3%), which was not within the noninferiority margin of 6%. Except for bleeding, the incidences of other adverse events were not significantly different between the groups. CONCLUSION: ES before endoscopic biliary stenting could have the preventive effect on the occurrence of PEP in patients with biliary stricture. University Hospital Medical Information Network Number, UMIN000025727.University Hospital Medical Information Network Clinical Trial Registry URL: https://www.umin.ac.jp/ctr/index.htm.

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.

Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. METHODS: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. RESULTS: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. CONCLUSION: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

Inutility of endoscopic sphincterotomy to prevent pancreatitis after biliary metal stent placement in the patients without pancreatic duct obstruction.

Background: The incidence of post-ERCP pancreatitis (PEP) has been reported to be significantly higher in patients without main pancreatic duct (MPD) obstruction who undergo transpapillary biliary metal stent (MS) placement than in those with ordinary ERCP setting.Objective: To evaluate the benefit of endoscopic sphincterotomy (ES) prior to MS placement in preventing PEP in patients with distal malignant biliary obstruction (MBO) without MPD obstruction.Materials and methods: In total, 160 patients who underwent initial MS placement for MBO were enrolled. Eighty-two patients underwent ES immediately prior to MS placement, whereas 78 underwent MS placement without ES. An inverse probability of treatment weighting method was adopted to adjust the differences of the patients' characteristics. The primary outcome was the incidence of PEP. The secondary outcomes included the incidence of other adverse events (bleeding, cholangitis, perforation and stent dislocation) and time to recurrent biliary obstruction.Results: The incidence of PEP was 26.8% in the ES and 23.1% in the non-ES (unadjusted odds ratio [OR] [95%CI]: 1.22, [0.60-2.51], adjusted OR [95%CI]: 1.23, [0.53-2.81], p = .63). Logistic-regression analysis revealed no factors that could be attributed to the occurrence of PEP. The incidence of other adverse events was not different between the groups. The median time to recurrent biliary obstruction was 131 (2-465) days and 200 (4-864) days in the ES and non-ES, respectively (p = .215).Conclusions: ES prior to MS placement for patients with distal MBO without MPD obstruction does not reduce the incidence of PEP.

Endoscopic ultrasound-guided choledochoduodenostomy vs. transpapillary stenting for distal biliary obstruction.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has gained popularity as an alternative to percutaneous biliary drainage for patients in whom endoscopic retrograde cholangiopancreatography has failed. There are no previous studies comparing EUS-CDS with endoscopic transpapillary stenting (ETS) as first-line treatment for distal malignant obstruction. The aim of this study was to compare the clinical efficacy and safety of EUS-CDS and ETS as first-line treatment in patients with distal malignant biliary obstruction. PATIENTS AND METHODS: A total of 82 patients with distal malignant biliary obstruction underwent initial biliary drainage using self-expandable metal stents at a tertiary care university hospital. ETS was performed between June 2009 and May 2012, and EUS-CDS was performed between May 2012 and March 2014. Clinical success rates, adverse event rates, and reintervention rates were retrospectively evaluated for EUS-CDS and ETS. RESULTS: A total of 26 patients underwent EUS-CDS and 56 underwent ETS. Clinical success rates were equivalent between the groups (EUS-CDS 96.2 %, ETS 98.2 %; P = 0.54). The mean procedure time was significantly shorter with EUS-CDS than with ETS (19.7 vs. 30.2 minutes; P < 0.01). The rate of overall adverse events was not significantly different between the groups (EUS-CDS 26.9 %, ETS 35.7 %; P = 0.46). Post-procedural pancreatitis was only observed in the ETS group (0 % vs. 16.1 %; P = 0.03). The reintervention rate at 1 year was 16.6 % and 13.6 % for EUS-CDS and ETS, respectively (P = 0.50). CONCLUSIONS: EUS-CDS performed by expert endoscopists was associated with a short procedure time and no risk of pancreatitis, and would therefore be feasible as a first-line treatment for patients with distal malignant biliary obstruction.

Liver elasticity measurement before and after biliary drainage in patients with obstructive jaundice: a prospective cohort studya prospective cohort study.

BACKGROUND: Obstructive jaundice has been reported to influence liver elasticity, independent of liver fibrosis. The aim of our prospective study was to evaluate the changes in liver elasticity, before and after biliary drainage, in patients with obstructive jaundice, and to evaluate the correlation between elasticity measures and serum markers of liver fibrosis. METHODS: This is a prospective cohort study of 20 patients with obstructive jaundice. Liver elasticity was assessed by Transient Elastography (TE) and Virtual Touch™ Quantification (VTQ). Serum total bilirubin (T-Bil) level was measured before biliary drainage (Day 0), with measures repeated at 2 days (Day 2) and 7 days (Day 7) after biliary drainage. Serum levels of the following markers of liver fibrosis were also obtained on Day 0 and Day 7: hyaluronic acid (HA), procollagen-III-peptide (P-III-P). RESULTS: T-Bil, TE, and VTQ for the left (VTQ-L) and right (VTQ-R) lobes of the liver were all elevated before biliary drainage, with respective levels, measured at Day 0, of 11.9 ± 1.5 mg/dl, 12.1 ± 0.9 kPa, 2.23 ± 0.10 m/s, and 1.85 ± 0.10 m/s. All values decreased on Day 7 after drainage: T-Bil, 4.7 ± 1.0 mg/dl (P < 0.001); TE, 7.6 ± 0.6 kPa (P < 0.001); VTQ-L, 1.53 ± 0.08 m/s (P < 0.001); and VTQ-R, 1.30 ± 0.05 m/s (P < 0.001). Similar changes were observed in serum markers of liver fibrosis. Liver elasticity measures correlated with serum levels of T-Bil, P-III-P, and HA (r = 0.35-0.67, P < 0.001). CONCLUSIONS: This study confirmed decreases in liver elasticity, measured by TE and VTQ, after biliary drainage. Measures of liver elasticity correlated to levels of T-Bil and serum markers of liver fibrosis. (UMIN ID: UMIN00001284313). REGISTRATION NUMBER: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN00001284313 ); Registration date: 2014-01-14.

Transpapillary selective bile duct cannulation technique: Review of Japanese randomized controlled trials since 2010 and an overview of clinical results in precut sphincterotomy since 2004.

In 1970, a Japanese group reported the first use of endoscopic retrograde cholangiopancreatography (ERCP), which is now carried out worldwide. Selective bile duct cannulation is a mandatory technique for diagnostic and therapeutic ERCP. Development of the endoscope and other devices has contributed to the extended use of ERCP, which has become a basic procedure to diagnose and treat pancreaticobiliary diseases. Various techniques related to selective bile duct cannulation have been widely applied. Although the classical contrast medium injection cannulation technique remains valuable, use of wire-guided cannulation has expanded since the early 2000s, and the technique is now widely carried out in the USA and Europe. Endoscopists must pay particular attention to a patient's condition and make an attendant choice about the most effective technique for selective bile duct cannulation. Some techniques have the potential to shorten procedure time and reduce the incidence of adverse events, particularly post-ERCP pancreatitis. However, a great deal of experience is required and endoscopists must be skilled in a variety of techniques. Although the development of the transpapillary biliary cannulation approach is remarkable, it is important to note that, to date, there have been no reports of transpapillary cannulation preventing post-ERCP pancreatitis. In the present article, selective bile duct cannulation techniques in the context of recent Japanese randomized controlled trials and cases of precut sphincterotomy are reviewed and discussed.

Technical difficulty according to location, and risk factors for perforation, in endoscopic submucosal dissection of colorectal tumors.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is a widely accepted treatment for colorectal tumors, but is technically more difficult and has a higher risk of complications such as perforation than gastric ESD. Few studies have investigated the factors associated with technical difficulty and perforation in colorectal ESD. This study aimed to evaluate the technical difficulty according to location, and the risk factors for perforation, in colorectal ESD. METHODS: This retrospective study included 134 consecutive colorectal tumors treated by ESD in 122 patients at the Division of Endoscopy of Hokkaido University Hospital and the Department of Gastroenterology of Kitami Red Cross Hospital from November 2011 to February 2013. To evaluate the technical difficulty of performing ESD for colorectal tumors at specific locations, the en bloc R0 resection rate, specimen diameter, procedure speed, and procedure time were compared among tumor locations using the χ (2) test or analysis of variance. Risk factors for perforation were identified by multiple logistic regression analysis. RESULTS: The en bloc R0 resection rate was 86.6 % (116/134), the mean tumor diameter was 27.1 mm, and the mean procedure time was 63.5 min. The mean speed of procedures was significantly slower in the sigmoid colon (24.7 min/cm(2)) than in other areas. Perforation occurred in nine cases (6.7 %). Submucosal fibrosis was the only factor independently associated with perforation (odds ratio 5.684, 95 % confidence interval 1.307-24.727). CONCLUSIONS: ESD was slower for sigmoid colon tumors than for tumors in other areas, suggesting that ESD was technically more difficult in the sigmoid colon than in other colorectal areas. Submucosal fibrosis was independently associated with perforation during colorectal ESD.

Difference from bile duct cancer and relationship between bile duct wall thickness and serum IgG/IgG4 levels in IgG4-related sclerosing cholangitis.

BACKGROUND/AIMS: IgG4-related sclerosing cholangitis (IgG4-SC) is a newly established entity. The purpose of this study was to investigate the differences in intraductal ultrasonography (IDUS) findings between IgG4-SC and bile duct (BD) cancer (BDC) as well as the relationship among BD wall thickness, serological and pathological findings in IgG4-SC. METHODOLOGY: Based on the diagnostic criteria of IgG4-SC, we reviewed patients in our hospital between April 2005 and June 2013, and analyzed the data obtained from 32 patients with IgG4-SC and 40 patients with BDC. RESULTS: Regarding IDUS findings, significantly more cases in BDC indicated rigid/papillary inner margin than in IgG4-SC, while biopsy was more efficient. There were no significant correlations between BD wall thickness and serum IgG/IgG4 levels or the number of IgG4-positive cells of the BD specimens. All the IgG4-SC patients without steroid treatment revealed discordant results in the shifts of IgG, IgG4 and BD wall thickness between the 1st and 2nd examinations, while all patients with steroid had completely concordant results of the shifts. CONCLUSIONS: IDUS findings alone are insufficient for differentiation between IgG4-SC and BDC. BD wall thickness, serum IgG and IgG4 proportionally shift and reflect the effect of steroid on IgG4-SC after steroid treatment, not before it.

Endoscopic Hemostatic Treatment with a Novel Self-Assembling Peptide Gel for Precut Fistulotomy-Related Bleeding.

Introduction: Precut fistulotomy is of interest as one of the salvage techniques for selective bile duct cannulation using endoscopic retrograde cholangiopancreatography. Of the various endoscopic treatments reported to date for bleeding associated with papillotomy incision, endoscopic hemostasis treatment with a novel self-assembling peptide (SAP) matrix-forming gel (TDM-621) (3-D Matrix Ltd., Tokyo, Japan) remains only insufficiently reported in the literature. Case Presentation: We herein report 6 cases of precut fistulotomy-related bleeding successfully treated with endoscopic hemostasis treatment with TDM-621, i.e., 5 and 1 cases during and after precut fistulotomy, respectively, in 2 males and 4 females aged 68-96 years (mean age, 85 years), 3 of whom had been on antithrombotic drugs. Types of bleeding treated included oozing bleeding (n = 5) and oozing bleeding from a visible vessel (n = 1). In all cases, complete hemostasis was achieved with TDM-621 without causing rebleeding. Conclusion: Endoscopic hemostasis with TDM-621 may prove effective for precut fistulotomy-related bleeding and represent a potential modality of first choice in hemostasis. In addition, endoscopic hemostasis with combined modality therapy using TDM-621 and endoscopic hemoclips may prove effective for bleeding from visible vessels.

Potassium-competitive acid blocker-associated gastric mucosal lesions.

Since the introduction of vonoprazan, a potassium-competitive acid blocker (P-CAB), it has been demonstrated to reversibly inhibit gastric acid secretion by engaging in potassium-competitive ionic binding to H+/K+-ATPase. In contrast, proton pump inhibitors (PPIs) achieve H+/K+-ATPase inhibition through covalent binding to cysteine residues of the proton pump. Reported cases have indicated an emerging trend of P-CAB-related gastropathies, similar to those associated with PPIs, as well as unique gastropathies specific to P-CAB use, such as the identification of web-like mucus. Pathologically, parietal cell profusions, which show a positively correlated with hypergastrinemia, have a higher incidence in P-CAB users compared to PPI users. Thus, this review aims to summarize the endoscopic and pathological findings reported to date concerning P-CAB-related gastric mucosal lesions. Additionally, it seeks to discuss the differences between the PPIs and P-CABs in terms of the formation and frequency of associated gastropathies. This review highlights the evident differences in the mechanism of action and potency of acid inhibition between P-CABs and PPIs, notably contributing to differences in the formation and frequency of associated gastropathies. It emphasizes the necessity to distinguish between P-CAB-related and PPI-related gastropathies in the clinical setting.

Ulcerated Stenosis of the Small Intestine Associated With Hepatic Portal Venous Gas After Treatment for Cytomegalovirus Enteritis: A Case Report.

Due to its rarity, cytomegalovirus (CMV) enteritis remains poorly described with regard to its endoscopic and radiological findings. A 75-year-old woman was admitted to our hospital with abdominal pain and was treated with an antiviral agent for CMV enteritis. She was readmitted to our hospital 10 days after discharge due to a recurrence of abdominal pain. Emergency computed tomography revealed hepatic portal venous gas (HPVG) and ileal dilatation involving focal stenosis of the ileum. The patient underwent laparoscopic partial resection of the small intestine and was finally diagnosed with ulcered stenosis of the small intestine after treatment for CMV enteritis. This report represents a valuable addition to the literature describing a rare case of ulcerated stenosis of the small intestine associated with HPVG after treatment for CMV enteritis.

A Case of Duodenal Adenocarcinoma Effectively Highlighted by Linked Color Imaging and Confirmed by Histopathology.

While the differential diagnosis of duodenal adenocarcinoma versus adenoma remains the key to determining treatment strategies in patients with suspected duodenal adenocarcinoma, the role of linked color imaging (LCI) in their differential diagnosis remains insufficiently documented. In this case, esophagogastroduodenoscopy (EGD) was performed on a 67-year-old man for anemia, which revealed a 20-mm-sized, whitish, partially reddish, pedunculated lesion located in the duodenal bulb on white light imaging. Using LCI, the lesion was highlighted as a whitish, pedunculated lesion with its central and inferior areas depicted as orangish and reddish, respectively. Endoscopic mucosal resection was performed on the suspicion of an adenocarcinoma for biopsy and endoscopic diagnosis. Histological examination revealed the lesion to be an adenocarcinoma contained in an adenoma: papillary, type 0-Ip, measuring 20x20 mm, pTis (M), involving no lymphovascular invasion. This case appears to underpin the usefulness of LCI in the differential diagnosis of duodenal adenocarcinoma.