A novel self-assembling peptide hemostatic gel as rescue therapy for fistula bleeding after endoscopic ultrasound-guided hepaticogastrostomy.

The novel synthetic self-assembling peptide PuraStat has been approved for hemostasis in endoscopic procedures. Nakahara and colleagues describe their application of PuraStat for hemostasis of refractory fistula bleeding after endoscopic ultrasound-guided hepaticogastrostomy. The effective and technically easy procedure is a useful option when hemostasis cannot be achieved by other means.

Significant association between HLA-B*35:01 and onset of drug-induced liver injury caused by Kampo medicines in Japanese patients.

AIM: Drug-induced liver injury (DILI) is a severe and life-threatening immune-mediated adverse effect, occurring rarely among treated patients. We examined genomic biomarkers in the Japanese population that predict the onset of DILI after using a certain class of drugs, such as Kampo products (Japanese traditional medicines). METHODS: A total of 287 patients diagnosed as DILI by hepatology specialists were recruited after written informed consent was obtained. A genome-wide association analysis and human leukocyte antigen (HLA) typing in four digits were performed. RESULTS: We found a significant association (p = 9.41 × 10-10 ) of rs146644517 (G > A) with Kampo product-related DILI. As this polymorphism is located in the HLA region, we evaluated the association of HLA types and found that 12 (63.2%) of 19 Kampo-DILI patients contained HLA-B*35:01, whereas only 15.2% were positive for this HLA among healthy volunteers. The odds ratio was 9.56 (95% confidence interval 3.75-24.46; p = 2.98 × 10-6 , corrected p = 4.17 × 10-5 ), and it increased to 13.55 compared with the DILI patients not exposed to Kampo products. The individual crude drug components in the Kampo products, including Scutellaria root (ougon in Japanese), rhubarb (daiou), Gardenia fruit (sanshishi), and Glycyrrhiza (kanzou), were significantly associated with HLA-B*35:01. CONCLUSIONS: HLA-B*35:01 is a genetic risk factor and a potential predictive biomarker for Kampo-induced DILI in the Japanese population.

Three Cases of Unprovoked Venous Thromboembolism with Prothrombin p.Arg596Gln Variant and a Literature Review of Antithrombin Resistance.

Antithrombin resistance (ATR) is a newly identified strong genetic predisposition to venous thromboembolism (VTE) caused by genetic variations in prothrombin with substitutions of Arg at position 596 with either Leu, Gln, or Trp. In the present report, we identified a missense variant p.Arg596Gln in 3 patients from 2 families with unprovoked VTE who each experienced their first VTE event at 19, 67, and 19 years old. The three patients did not show any positive markers for thrombophilia on routine testing, suggesting that patients with unprovoked VTE who have negative findings on thrombophilia tests may carry a prothrombin variant with ATR.

Clinical outcomes and predictors of technical failure of endoscopic transpapillary gallbladder drainage in acute cholecystitis.

BACKGROUND AND AIMS: Endoscopic transpapillary gallbladder drainage (ETGBD) has been performed as an alternative therapy against cholecystectomy in patients with acute cholecystitis. To date, few studies have reported the safety, efficacy, and factors affecting ETGBD. We evaluated the clinical outcomes and predictors of technical failure of ETGBD. METHODS: Patients with acute cholecystitis who underwent ETGBD were retrospectively reviewed, and consecutive patients were included in the study. The technical success rate, clinical success rate, adverse events, and the predictors associated with the technical failure of ETGBD were investigated. RESULTS: A total of 242 patients were enrolled in the study. The technical success rate of ETGBD and clinical success rate of technically successful ETGBD cases were 87% and 93%, respectively. We experienced cystic duct injury in 24 patients as an ETGBD-related adverse event, and pancreatitis in 12 patients as an endoscopic retrograde cholangiopancreatography-related adverse event. Multivariate analysis indicated that cystic duct injury was the independent predictor associated with the technical failure of ETGBD (odds ratio, 11; 95% confidence interval, 3.9-29; p < 0.001). CONCLUSIONS: ETGBD was a safe and effective treatment method for acute cholecystitis with acceptable adverse events. There was no predictor based on the information from patient characteristics; however, cystic duct injury was associated with the technical failure of ETGBD.

Targeted deep sequencing analyses of long QT syndrome in a Japanese population.

Long QT syndrome (LQTS) is one of the most common inherited arrhythmias and multiple genes have been reported as causative. Presently, genetic diagnosis for LQTS patients is becoming widespread and contributing to implementation of therapies. However, causative genetic mutations cannot be detected in about 20% of patients. To elucidate additional genetic mutations in LQTS, we performed deep-sequencing of previously reported 15 causative and 85 candidate genes for this disorder in 556 Japanese LQTS patients. We performed in-silico filtering of the sequencing data and found 48 novel variants in 33 genes of 53 cases. These variants were predicted to be damaging to coding proteins or to alter the binding affinity of several transcription factors. Notably, we found that most of the LQTS-related variants in the RYR2 gene were in the large cytoplasmic domain of the N-terminus side. They might be useful for screening of LQTS patients who had no known genetic factors. In addition, when the mechanisms of these variants in the development of LQTS are revealed, it will be useful for early diagnosis, risk stratification, and selection of treatment.

Long-term outcomes of endoscopic transpapillary gallbladder drainage using a novel spiral plastic stent in acute calculus cholecystitis.

BACKGROUND: Endoscopic transpapillary gallbladder stenting (EGBS) is considered for patients with contraindications to early surgery for acute calculus cholecystitis. However, evidence regarding the long-term outcomes of EGBS is insufficient to date. The aim of the study was to evaluate the feasibility of EGBS as a bridge to or alternative to surgery when there are contraindications. METHODS: We reviewed the cases of patients who underwent EGBS using a novel spiral-shaped plastic stent for acute calculus cholecystitis between January 2011 and December 2019. We retrospectively evaluated the long-term outcomes of EGBS using a novel spiral-shaped plastic stent. RESULTS: Forty-nine patients were included. The clinical success rate of EGBS was 97%. After EGBS, 25 patients (surgery group) underwent elective cholecystectomy and 24 patients did not (follow-up group). In the surgery group, the median period from EGBS to surgery was 93 days. There was a single late adverse event with cholecystitis recurrence. In the follow-up group, the median follow-up period was 236 days. Late adverse events were observed in eight patients, including recurrence of cholecystitis (four patients), duodenal penetration by the distal stent end (two patients), and distal stent migration (two patient). In the follow-up group, the time to recurrence of biliary obstruction was 527 days. CONCLUSIONS: EGBS with a novel spiral-shaped plastic stent is safe and effective for long-term acute calculus cholecystitis. There is a possibility of EGBS to be a bridge to surgery and a surgical alternative for acute calculus cholecystitis in patients with contraindications to early cholecystectomy.

Mutational spectrum of hepatitis C virus in patients with chronic hepatitis C determined by single molecule real-time sequencing.

The emergence of hepatitis C virus (HCV) with resistance-associated substitution (RAS), produced by mutations in the HCV genome, is a major problem in direct acting antivirals (DAA) treatment. This study aimed to clarify the mutational spectrum in HCV-RNA and the substitution pattern for the emergence of RASs in patients with chronic HCV infection. HCV-RNA from two HCV replicon cell lines and the serum HCV-RNA of four non-liver transplant and four post-liver transplant patients with unsuccessful DAA treatment were analyzed using high-accuracy single-molecule real-time long-read sequencing. Transition substitutions, especially A>G and U>C, occurred prominently under DAAs in both non-transplant and post-transplant patients, with a mutational bias identical to that occurring in HCV replicon cell lines during 10-year culturing. These mutational biases were reproduced in natural courses after DAA treatment. RASs emerged via both transition and transversion substitutions. NS3-D168 and NS5A-L31 RASs resulted from transversion mutations, while NS5A-Y93 RASs was caused by transition substitutions. The fidelity of the RNA-dependent RNA polymerase, HCV-NS5B, produces mutational bias in the HCV genome, characterized by dominant transition mutations, notably A>G and U>C substitutions. However, RASs are acquired by both transition and transversion substitutions, and the RASs-positive HCV clones are selected and proliferated under DAA treatment pressure.

Technique of straightening the guidewire using a balloon catheter for successful endoscopic transpapillary gallbladder stenting.

Video 1The technique of straightening the guidewire, looped in the neck of the gallbladder because of segmental adenomyomatosis, using a balloon catheter during endoscopic transpapillary gallbladder stent placement.

Gender Differences in Smoking Initiation and Cessation Associated with the Intergenerational Transfer of Smoking across Three Generations: The Nagahama Study.

Global tobacco policies lowered overall and male smoking rates, but female smoking rates have remained unchanged. Parent-child studies revealed the effects of parental smoking, but gender differences had mixed results. We investigated the effects of long-term smoking behavior in families over three generations in order to clarify gender differences. A cross-sectional study in a community-based genome cohort was conducted using a self-reported questionnaire. A total of 8652 respondents were stratified by gender regarding smoking initiation. A logistic regression analysis was performed to analyze the family smoking history. A total of 2987 current smokers and ever-smokers were compared regarding smoking cessation. With respect to smoking initiation, women were affected by their smoking mothers (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.8-3.2) and grandmothers (OR, 1.7; CI, 1.1-2.4). Women who continued smoking were affected only by their smoking mothers (OR, 1.6; CI, 1.05-2.49). In conclusion, gender differences in smoking initiation and cessation are possibly associated with family smoking history. Mothers and grandmothers were shown to have a strong influence on women with respect to both smoking initiation and cessation. Future research should focus on providing evidence for effective gender-specific intervention programs to curb long-term smoking in women.

Double-guidewire technique for endoscopic transpapillary gallbladder stenting.

Highlight Endoscopic transpapillary gallbladder stenting is effective for acute cholecystitis with high surgical risk. However, looping of the guidewire in the cystic duct sometimes impedes placement of the stent. Nakahara and colleagues present a case of successful endoscopic transpapillary gallbladder stenting after straightening the looped guidewire using a double-guidewire technique.

Incidence and management of cystic duct perforation during endoscopic transpapillary gallbladder drainage for acute cholecystitis.

BACKGROUND AND AIM: Evidence regarding the incidence and clinical outcome of cystic duct perforation (CDP) during endoscopic transpapillary gallbladder drainage (ETGBD) is inadequate. The present study aimed to evaluate the incidence and management of CDP during ETGBD. METHODS: Between March 2011 and December 2019, 249 patients underwent initial ETGBD for acute cholecystitis. The incidence of CDP was retrospectively examined and the outcomes between the CDP and non-CDP groups were compared. RESULTS: CDP during ETGBD occurred in 23 (9.2%) of 249 patients (caused by guidewire in 15 and cannula in 8). ETGBD was successful in 10 patients following CDP. In 13 patients who failed ETGBD, 11 underwent bile duct drainage during the same session; nine patients underwent gallbladder decompression by other methods, such as percutaneous drainage. Clinical resolution for acute cholecystitis was achieved in 20 patients, and no bile peritonitis was noted. ETGBD technical success rates (45.3% vs. 91.2%, p < 0.001), ETGBD procedure times (66.5 vs. 54.8 min, p = 0.041), and hospitalization periods (24.5 vs. 18.7 days, p = 0.028) were significantly inferior in the CDP group (n = 23) compared with the non-CDP group (n = 216). There were no differences in clinical success and adverse events other than CDP between both groups. CONCLUSIONS: Cystic duct perforation reduced the ETGBD technical success rate. However, even in patients with cystic duct perforation, an improvement of acute cholecystitis was achieved by subsequent successful ETGBD or additional procedures, such as percutaneous drainage.

Efficacy of endoscopic large balloon dilation extended for 2 minutes in bile duct stone removal: A multicenter retrospective study.

BACKGROUND/PURPOSE: There is no evidence regarding the optimal balloon dilation time during endoscopic papillary large balloon dilation (EPLBD). The study aim was to evaluate the efficacy of 2-minute extended balloon dilation for EPLBD. METHODS: Two hundred and five patients who underwent EPLBD during endoscopic retrograde cholangiopancreatography (ERCP) for bile duct stones at three tertiary centers were included in the analysis. Clinical outcomes and the adverse events were compared between the 0-minute group (n = 94, balloon deflated immediately after waist disappearance) and the 2-minute group (n = 111, balloon dilation maintained for 2 minutes after waist disappearance). The risk factors of post-ERCP pancreatitis (PEP) after EPLBD were assessed. RESULTS: There were no significant differences in the stone removal rates and hospitalization periods between the two groups. However, the total ERCP procedure time was significantly shorter in the 2-minute group (40.6 vs 48.9 min, P = .03). The incidence of PEP was 7.4% in the 0-minute group and significantly lower at 0.9% in the 2-minute group (P = .04). Multivariate analysis identified without 2-minute extended EPLBD as a significant risk factor of PEP (OR: 9.9, P = .045). CONCLUSIONS: Extension of EPLBD for 2 minutes helped prevent PEP and shortened the procedure time.

The Influence of Pre-Procedural Imaging and Cystic Duct Cholangiography on Endoscopic Transpapillary Gallbladder Drainage in Acute Cholecystitis.

Endoscopic transpapillary gallbladder drainage (ETGBD) for acute cholecystitis is challenging. We evaluated the influence of pre-procedural imaging and cystic duct cholangiography on ETGBD. Patients who underwent ETGBD for acute cholecystitis were retrospectively examined. The rate of gallbladder contrast on cholangiography, the accuracy of cystic duct direction and location by computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP), and the relationship between pre-procedural imaging and the technical success of ETGBD were investigated. A total of 145 patients were enrolled in this study. Gallbladder contrast on cholangiography was observed in 29 patients. The accuracy of cystic duct direction and location (proximal or distal, right or left, and cranial or caudal) by CT were, respectively, 79%, 60%, and 58% by CT and 68%, 55%, and 58% by MRCP. Patients showing gallbladder contrast on cholangiography underwent ETGBD with a significantly shorter procedure time and a lower rate of cystic duct injury. No other factors affecting procedure time, technical success, and cystic duct injury were identified. Pre-procedural evaluation of cystic duct direction and location by CT or MRCP was difficult in patients with acute cholecystitis. Patients who showed gallbladder contrast on cholangiography showed a shorter procedure time and a lower rate of cystic duct injury.

Clinical Outcomes of Early Endoscopic Transpapillary Biliary Drainage for Acute Cholangitis Associated with Disseminated Intravascular Coagulation.

Acute cholangitis (AC) is often associated with disseminated intravascular coagulation (DIC), and endoscopic transpapillary biliary drainage (EBD) under endoscopic retrograde cholangiopancreatography (ERCP) is a treatment of choice. However, no evidence exists on the outcomes of EBD for AC associated with DIC. Therefore, we retrospectively evaluated the treatment outcomes of early EBD and compared endoscopic biliary stenting (EBS) and endoscopic nasobiliary drainage (ENBD). We included 62 patients who received early EBD (EBS: 30, ENBD: 32) for AC, associated with DIC. The rates of clinical success for AC and DIC resolution at 7 days after EBD were 90.3% and 88.7%, respectively. Mean hospitalization period was 31.7 days, and in-hospital mortality rate was 4.8%. ERCP-related adverse events developed in 3.2% of patients (bleeding in two patients). Comparison between EBS and ENBD groups showed that the ENBD group included patients with more severe cholangitis, and acute physiology and chronic health evaluation II score, systemic inflammatory response syndrome score, and serum bilirubin level were significantly higher in this group. However, no significant difference was observed in clinical outcomes between the two groups; both EBS and ENBD were effective. In conclusion, early EBD is effective and safe for patients with AC associated with DIC.