TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage.

The consensus-based TOKYO criteria were proposed as a standardized reporting system for endoscopic transpapillary biliary drainage. The primary objective was to address issues arising from the inconsistent reporting of stent outcomes across studies, which has complicated the comparability and interpretation of study results. However, the original TOKYO criteria were not readily applicable to recent modalities of endoscopic biliary drainage such as biliary drainage based on endoscopic ultrasound or device-assisted endoscopy. There are increasing opportunities for managing hilar biliary obstruction and benign biliary strictures through endoscopic drainage. Biliary ablation has been introduced to manage benign and malignant biliary strictures. In addition, the prolonged survival times of cancer patients have increased the importance of evaluating overall outcomes during the period requiring endoscopic biliary drainage rather than solely focusing on the patency of the initial stent. Recognizing these unmet needs, a committee has been established within the Japan Gastroenterological Endoscopy Society to revise the TOKYO criteria for current clinical practice. The revised criteria propose not only common reporting items for endoscopic biliary drainage overall, but also items specific to various conditions and interventions. The term "stent-demanding time" has been defined to encompass the entire duration of endoscopic biliary drainage, during which the overall stent-related outcomes are evaluated. The revised TOKYO criteria 2024 are expected to facilitate the design and reporting of clinical studies, providing a goal-oriented approach to the evaluation of endoscopic biliary drainage.

Dedicated Echoendoscope for Interventional Endoscopic Ultrasound: Comparison with a Conventional Echoendoscope.

Background/Objective: Interventional endoscopic ultrasound (I-EUS) is technically difficult and has risks of severe adverse events due to the scarcity of dedicated endoscopes and tools. A new EUS scope was developed for I-EUS and was modified to increase the puncture range, reduce the blind area, and overcome guidewire difficulties. We evaluated the usefulness and safety of a new EUS scope compared to a conventional EUS scope. Methods: All I-EUS procedures were performed at Juntendo University Hospital from April 2020 to April 2022. The primary outcomes included the procedure time and fluoroscopy time. The secondary outcomes included the technical success rate and the rates of procedure-related adverse events. Clinical data were retrospectively reviewed and statistically analyzed between the new and conventional EUS scopes. Results: In total, 143 procedures in 120 patients were analyzed. The procedure time was significantly shorter with the new EUS scope, but the fluoroscopy time was not different. Among the patients only undergoing EUS-guided biliary drainage (EUS-BD), 79 procedures in 74 patients were analyzed. Both the procedure time and fluoroscopy time were significantly shorter with the new EUS scope. Multivariate analysis revealed that a new EUS scope and use of covered metal stents could reduce the fluoroscopy time. The technical success rate and the adverse event rate were not significantly different between the total I-EUS and the EUS-BD only groups. However, the conventional scope showed stent deviation during stent placement, which did not happen with the new scope. Conclusions: The new EUS scope reduced procedure time for total I-EUS and fluoroscopy time for EUS-BD compared to a conventional EUS scope because of the improvement suitable for I-EUS.

Liver biopsy as a useful diagnostic tool for hepatic sarcoidosis: A case report.

In certain cases, it is difficult to distinguish hepatic sarcoidosis from malignant lymphoma or drug-induced liver injury and to select the proper treatment for this condition. The present study describes the case of a female patient in her 30s who was referred to the hospital due to fever, arthralgia, myalgia and abnormal liver function test results for 4 months. A laboratory examination revealed elevated levels of serum angiotensin-converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R), as well as an increase in serum hepatic and biliary tract enzymes. Gallium scintigraphy revealed a marked uptake in the liver, as well as an uptake in the mediastinal, inguinal and external iliac lymph nodes. Magnetic resonance imaging revealed extensive hepatosplenomegaly with multiple non-enhancing splenic nodules. Hepatic sarcoidosis was diagnosed by a liver biopsy as non-caseating hepatic granulomas, and multinucleated giant cells were observed. The patient responded to treatment with 20 mg prednisolone daily, and exhibited an improvement in her symptoms. An improvement was also observed in her serum levels of ACE, sIL-2R, and serum hepatic and biliary tract enzymes; decreased gallium uptake in the liver was also observed. On the whole, the present case report reconfirms that liver biopsy is a useful diagnostic tool for hepatic sarcoidosis.

Elderly patient with unresectable advanced­stage hepatocellular carcinoma who received atezolizumab plus bevacizumab and achieved a complete response: A case report.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis, particularly in patients with advanced-stage disease, elderly individuals and/or in those with poor liver function. Immune checkpoint inhibitor-containing therapies, such as atezolizumab, an anti-programmed death ligand-1 monoclonal antibody, plus bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, may be effective and safe therapeutic options for elderly patients with advanced-stage HCC. The present study reports the case of a male patient his 80s who consumed alcohol with unresectable advanced-stage HCC who received combination therapy comprising atezolizumab plus bevacizumab for 6 months. The patient achieved a complete response despite the discontinuation of treatment due to nephrotoxicity. It is critical for patients with HCC and a Child-Pugh A grade to continue therapy for HCC, even if they are older. The development of more effective therapies is required for patients with advanced-stage HCC with a worse liver function than those with a Child-Pugh A grade. The case described in the present study demonstrates the need for obtaining further evidence regarding the efficacy and safety of the combination therapy including atezolizumab plus bevacizumab for elderly patients with advanced-stage HCC.

Assessment of drainage vein of focal nodular hyperplasia using contrast-enhanced ultrasound.

PURPOSE: Identification of drainage vessels is useful for differential diagnosis of hepatic tumors. Direct drainage to the hepatic vein has been reported to occur in focal nodular hyperplasia (FNH), but studies evaluating the drainage veins of FNH are limited. We aimed to investigate the detection rate of the FNH drainage vein and the factors related to visualization of the drainage vein on contrast-enhanced ultrasound (CEUS). METHODS: Fifty consecutive patients with 50 FNH lesions were retrospectively evaluated in this study. We calculated and compared the detection rate of the FNH drainage vein on CEUS, contrast-enhanced magnetic resonance imaging (CEMRI), and contrast-enhanced computed tomography (CECT), and identified the factors correlated with visualization of the FNH drainage vein on CEUS by using multivariate logistic regression analyses. RESULTS: Visualization of the drainage vein was confirmed in 31 of 50 lesions (62%) using CEUS, three of 44 lesions (6.8%) using CEMRI, and one of 18 lesions (5.6%) using CECT. The detection rate of the FNH drainage vein on CEUS was significantly higher than that on CEMRI and CECT (p < 0.001). Multivariate analysis identified lesion size (≥ 25 mm) and detection of the spoke-wheel pattern on Doppler US as independent factors for drainage vein detection in FNH. CONCLUSION: Our study showed that rapid FNH drainage to the hepatic vein was observed at a relatively high rate on CEUS, suggesting that CEUS focusing on detection of drainage veins is important for diagnosing FNH.

Severe hepatitis E virus genotype 3b in a patient with alcohol­associated liver disease: A case report.

Hepatitis E virus (HEV) infection occasionally causes acute-on-chronic liver failure in patients with alcohol-associated cirrhosis. These reports have been published mainly from highly HEV genotype 1-endemic countries. The present study describes the case of a patient with severe HEV genotype 3b infection and alcohol-associated liver disease. A male patient in his 70s who consumed alcohol, and who had begun consuming alcohol at the age of 12, had high levels of alanine aminotransferase (ALT) and total bilirubin. The peak levels of ALT and total bilirubin were 1,067 IU/l and 26.3 mg/dl, respectively. A computed tomography scan revealed an atrophic liver. Upon admission, both anti-HEV immunoglobulin A and HEV RNA were positive, and his HEV was genotype 3b. He also had chronic kidney disease, as his estimated glomerular filtration rate was <45 ml/min/1.73 m2, and ribavirin could not be used. The abnormal levels of the liver function parameters of the patient gradually improved due to conservative treatment, and he was discharged on day 43. On the whole, the present study demonstrates that careful attention should be paid to patients with viral hepatitis, including hepatitis E, when alcohol-associated liver disease is present. Novel anti-HEV drugs need to be developed for severe HEV infections with chronic kidney disease.

Balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography for hepatolithiasis in patients with hepaticojejunostomy.

BACKGROUND AND AIM: Balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is an emerging procedure for pancreatobiliary diseases in patients with surgically altered anatomy. However, data on BE-ERCP for hepatolithiasis after hepaticojejunostomy (HJS) are still limited. METHODS: Stone removal success, adverse events and recurrence were retrospectively studied in consecutive patients who underwent BE-ERCP for hepatolithiasis after HJS between January 2011 and October 2022. Subgroup analysis was performed to compare clinical outcomes between patients who had undergone HJS over 10 years before (past HJS group) and within 10 years (recent HJS group). RESULTS: A total of 131 patients were included; 39% had undergone HJS for malignancy and 32% for congenital biliary dilation. Scope insertion and complete stone removal were successful in 89% and 73%, respectively. Early adverse events were observed in 9.9%. Four patients (3.1%) developed gastrointestinal perforation but could be managed conservatively. Hepatolithiasis recurrence rate was 17%, 20% and 31% in 1-year, 3-year, and 5-year after complete stone removal. The past HJS group was the only risk factor for failed stone removal (odds ratio 10.4, 95% confidence interval 2.99-36.5) in the multivariable analysis. Failed scope insertion (20%) and failed guidewire or device insertion to the bile duct (22%) were two major reasons for failed stone removal in the past HJS group. CONCLUSIONS: BE-ERCP for hepatolithiasis was effective and safe in cases with HJS but the complete stone removal rate was low in the past HJS group. Recurrent hepatolithiasis was common and careful follow up study is needed even after complete stone removal.

Daily Diet and Nutrition Risk Factors for Gastric Cancer Incidence in a Japanese Population.

Background/Aims: : Nutritional factors associated with gastric cancer (GC) are not completely understood. We aimed to determine the effect of nutrient intake on the incidence of GC. Methods: : This was a post hoc analysis of a prospective trial that evaluated modalities for GC screening in participants aged 30 to 74 years living in high-risk areas for GC in Japan between June 2011 and March 2013. The patients were followed up for GC incidence for 6 years. All participants completed a self-administered food frequency questionnaire (FFQ) upon enrollment before GC screening. Daily nutrient intake was calculated from the FFQ and dichotomized at each cutoff value using receiver operating characteristic analysis. Risk factors associated with GC incidence were investigated in terms of nutrient intake and participant characteristics using Cox proportional hazards regression analysis. Results: : Overall, 1,147 participants were included in this analysis. The median age was 62 years, and 50.7% of the participants were men. The median follow-up period was 2,184 days. GC was detected in 25 participants during the follow-up. Multivariate Cox proportional hazards regression analysis revealed that the intake of sodium (adjusted hazards ratio [aHR], 3.905; 95% confidence interval [CI], 1.520 to 10.035; p=0.005) and vitamin D (aHR, 2.747; 95% CI, 1.111 to 6.788, p=0.029) were positively associated with GC incidence, whereas the intake of soluble dietary fiber (aHR, 0.104; 95% CI, 0.012 to 0.905; p=0.040) was inversely associated with GC incidence. Conclusions: : Daily high intake of sodium and vitamin D and low soluble dietary fiber intake are associated with GC incidence.

Correlation between pathology and quantitative ultrasonographic evaluation of pancreatic fat with ultrasonographic classification.

PURPOSE: No studies of the relationship between grayscale sonographic findings and pancreatic fat content have been reported to date. This study aimed to investigate the correlation between echogenicity and fat content of resected specimens using quantitative analysis. METHODS: Forty-two consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy for pancreatic tumors were enrolled in this study. Ultrasonographic images were compared with quantitative pathological analysis. Subjective evaluation of echogenicity was classified as hypoechoic, isoechoic, hyperechoic, and super hyperechoic. The total and intralobular fat areas were measured. RESULTS: The mean, median, modal, minimum, and maximum ultrasound gray values correlated with the proportion of total fat area (r = 0.349; 0.357, 0.486, 0.466, and 0.347; p = 0.024, 0.020, 0.014, 0.019, and 0.089, respectively), but did not correlate with the proportion of intralobular fat area. Subjective classification was correlated with median gray value (p < 0.001), intralobular fat area (p = 0.118), and total fat area (p = 0.011). Cases were classified as hypoechoic (n = 3), isoechoic (n = 7), hyperechoic (n = 30), and super hyperechoic (n = 2). The subjective classification was correlated with the median gray value (p < 0.001) and total fat area (p = 0.005), and not correlated with the intralobular fat area (p = 0.118). Hyperechoic or super hyperechoic pancreatic parenchyma contains over 19.7% fat. Computed tomography values correlated with the proportion of intralobular fat area (r = - 0.479, p = 0.004) and total fat area (r = - 0.541, p < 0.001). CONCLUSION: Echogenicity classified based on subjective evaluation and image analysis were correlated with the proportion of fat in the pancreas.

A comparison of diagnostic utility of new endoscopic scraper combined cell block method and conventional brush catheter for biliary tract cancer.

Background/Aims: The sensitivities of endoscopic trans-papillary pathologic diagnosis of biliary tract cancer (BTC) are unsatisfactory. Recently, the diagnostic utility of the endoscopic scraper device, Trefle for biliary stricture has been reported. The Trefle can be guided to the target biliary stricture over the guidewire and is as easy to use as the conventional brush catheter (CBC). This study evaluated the efficacy and safety of Trefle-assisted tissue acquisition combined cell block method and CBC cytology for biliary strictures due to BTCs. Methods: We retrospectively reviewed consecutive patients with biliary strictures in whom CBC cytology or Trefle-assisted tissue acquisition under endoscopic retrograde cholangiopancreatography was performed for suspected BTCs from January 2015 to June 2022 at our institution. Results: 173 patients (CBC group; n = 55, Trefle group; n = 118) were enrolled in this study. The sensitivity, specificity, and accuracy of CBC cytology for BTC were 68.3%/100%/76.4%. On the other hand, the sensitivity, specificity, and accuracy of Trefle-assisted tissue acquisition for BTC were 93.7%/95.7%/94.1%, showing superior sensitivity (p < 0.001) and accuracy (p = 0.002) compared to that of CBC. Conclusions: Compared to CBC cytology, Trefle-assisted tissue acquisition has superior diagnostic performance while maintaining procedural simplicity and is considered useful for diagnosing malignant biliary stricture.

ERCP using balloon-assisted endoscopes versus EUS-guided treatment for common bile duct stones in Roux-en-Y gastrectomy.

BACKGROUND AND AIMS: We compared ERCP using a balloon-assisted endoscope (BE-ERCP) with EUS-guided antegrade treatment (EUS-AG) for removal of common bile duct (CBD) stones in patients with Roux-en-Y (R-Y) gastrectomy. METHODS: Consecutive patients who had previous R-Y gastrectomy undergoing BE-ERCP or EUS-AG for CBD stones in 16 centers were retrospectively analyzed. RESULTS: BE-ERCP and EUS-AG were performed in 588 and 59 patients, respectively. Baseline characteristics were similar, except for CBD diameter and angle. The technical success rate was 83.7% versus 83.1% (P = .956), complete stone removal rate was 78.1% versus 67.8% (P = .102), and early adverse event rate was 10.2% versus 18.6% (P = .076) in BE-ERCP and EUS-AG, respectively. The mean number of endoscopic sessions was smaller in BE-ERCP (1.5 ± .8 vs 1.9 ± 1.0 sessions, P = .01), whereas the median total treatment time was longer (90 vs 61.5 minutes, P = .001). Among patients with biliary access, the complete stone removal rate was significantly higher in BE-ERCP (93.3% vs 81.6%, P = .009). Negative predictive factors were CBD diameter ≥15 mm (odds ratio [OR], .41) and an angle of CBD <90 degrees (OR, .39) in BE-ERCP and a stone size ≥10 mm (OR, .07) and an angle of CBD <90 degrees (OR, .07) in EUS-AG. The 1-year recurrence rate was 8.3% in both groups. CONCLUSIONS: Effectiveness and safety of BE-ERCP and EUS-AG were comparable in CBD stone removal for patients after R-Y gastrectomy, but complete stone removal after technical success was superior in BE-ERCP.

Retrospective comparative study of new slim-delivery and conventional large-cell stents for stent-in-stent methods for hilar malignant biliary obstruction.

OBJECTIVES: Endoscopic management of unresectable hilar malignant biliary obstruction (HMBO) is technically challenging, and effectiveness of stent-in-stent using large-cell, metal stents was reported. A new, large-cell stent with a 6F tapered delivery system was recently developed. The aim of this study was to compare clinical outcomes of slim-delivery and conventional large-cell stents. METHODS: This was a multicenter retrospective comparative study of stent-in-stent methods using slim-delivery stents (Niti-S Large Cell SR Slim Delivery [LC slim-delivery]) and conventional stents (Niti-S large-cell D-type; LCD) for unresectable HMBO. RESULTS: Eighty-three patients with HMBO were included; 31 LC slim-delivery and 52 LCD. Overall technical and clinical success rates were 100% and 90% in LC slim-delivery group and 98% and 88% in LCD group. Use of the LC slim-delivery was associated with shorter stent placement time in the multiple regression analysis, with a stent placement time of 18 and 23 min in LC slim-delivery and LCD groups, respectively. The early adverse event (AE) rate of LC slim-delivery was 10%, with no cholangitis or cholecystitis as compared to 23% in the LCD group. Recurrent biliary obstruction (RBO) rates and time to RBO were comparable between the two groups: 35% and 44%, and 8.5 and 8.0 months in LC slim-delivery and LCD groups, respectively. The major cause of RBO was tumor ingrowth (82%) in the LC slim-delivery group and sludge (43%) and ingrowth (48%) in LCD group. CONCLUSION: Stent-in-stent methods using LC slim-delivery shortened stent placement time with low early AE rates and comparable time to RBO in patients with HMBO.

Development and external validation of a nomogram for prediction of post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is widely performed for management of pancreatobiliary diseases; however, post-ERCP pancreatitis (PEP) remains as an unsolved problem. Although various risk factors for PEP have been reported, the prediction of PEP remains controversial. This study aimed to develop a predictive model for PEP. METHODS: Consecutive patients undergoing ERCP for biliary indications at two centers were retrospectively studied. Using data from a training cohort, we utilized a multivariable model to select five variables to construct a nomogram. The predictive model was internally and externally validated. Based on the nomogram, the patients were categorized into low-, moderate-, and high-risk groups. RESULTS: Using the data of 2224 patients in the training cohort, five variables were selected to generate a nomogram: 1) sex, 2) indication for ERCP, 3) difficult cannulation, 4) guidewire insertion into the pancreatic duct, and 5) endoscopic sphincterotomy or sphincteroplasty. The most significant risk factor was endoscopic papillary balloon dilation such as endoscopic sphincterotomy or sphincteroplasty. The bias-corrected concordance index was 0.72 in the training cohort and 0.72 in the validation cohort. Calibration curves for both cohorts demonstrated good agreement between the predicted and observed frequencies of the actual outcome. In the validation cohort, PEP developed in 5.0% and 14% of patients in the moderate- and high-risk groups, respectively. CONCLUSIONS: We successfully developed a good predictive model for PEP. The prevention of PEP in high risk patients should be investigated further.

Involvement of proliferation of atypical hepatocytes and CDT 1 in the liver cancer of rats administered the diethylnitrosamine.

We have reported that extent of proliferation of atypical hepatocytes (POAH) in non-cancerous liver in hepatocellular carcinoma and chromatin licensing and DNA replication factor 1 (CDT1) are associated with postoperative recurrence. Here, we investigated whether extent of POAH and expression of CDT1 in liver are also associated with chemically induced liver cancer in rats. Male Fisher strain rats were orally administered diethylnitrosamine (DEN) in their drinking water and sacrificed at 6, 8, 12, or 14 weeks after start of DEN administration. We serially monitored changes in extent of POAH, CDT1 expression by immunohistochemistry (IHC), and CDT1 mRNA expression in liver by real-time quantitative PCR. The extent of POAH in liver progressed in a time-dependent manner after start of DEN administration. CDT1 expression was higher at 8 weeks than at 6 weeks by IHC, suggesting that CDT1 expression may be a marker of POAH severity. CDT1 mRNA expression in liver was significantly higher at 12 weeks than at 6 weeks (p<0.0001). We found that extent of POAH and the expression of CDT1 are also important factors in the development of chemical carcinogen-induced hepatocarcinogenesis. Furthermore, the association with POAH and CDT1 expression in carcinogenic process is important regardless of the cause of hepatocarcinogenesis.

A single-center prospective study on pain alleviation during peroral upper endoscopy with an ultrathin endoscope.

BACKGROUND: The efficacy of transnasal endoscopy using an ultrathin endoscope has been reported in several studies. However, few studies regarding peroral endoscopy with ultrathin endoscopes with high resolution have been reported. This study investigates the pain alleviation of peroral endoscopy with an ultrathin endoscope. METHODS: Patients with a history of peroral endoscopy using a conventional, normal-diameter scope with no sedation who underwent peroral esophagogastroduodenoscopy (EGD) using a thin scope between April-July 2022 were included in this study. After the procedure, the patients completed a questionnaire evaluating pain during the examination and willingness to repeat the procedure. The physicians were surveyed regarding their level of satisfaction. The primary endpoint was patient satisfaction, which corresponded to the rate of patients who rated the thin endoscope as more comfortable or somewhat more comfortable than the previously-used, conventional endoscope. RESULTS: One hundred and forty-five patients were included in the analyses. Patient satisfaction was achieved in 86.2% (125/145) of patients. The median visual analog scale pain score was 3 (0-7) points in this study, which is significantly lower than the pain score after the previous endoscopy (5 (0-10) points; p < 0.001). In addition, 96% (24/25) of patients who underwent EGD by an expert and 95.8% (115/120) who underwent EGD by a non-expert were willing to repeat endoscopy using the thin scope (p = 0.69). CONCLUSION: Peroral endoscopy using a thin scope reduces patient pain regardless of the endoscopist's experience.

Muscle Cramps in Outpatients with Liver Diseases in Tokyo, Japan.

Background and Objectives: Muscle cramps are often observed in patients with liver diseases, especially advanced liver fibrosis. The exact prevalence of muscle cramps in outpatients with liver diseases in Japan is unknown. Patients and Methods: This study examined the prevalence of, and therapies for, muscle cramps in outpatients with liver diseases in Tokyo, Japan. A total of 238 outpatients with liver diseases were retrospectively examined. We investigated whether they had muscle cramps using a visual analog scale (VAS) (from 0, none, to 10, strongest), and also investigated their therapies. Results: Muscle cramps were observed in 34 outpatients with liver diseases (14.3%); their mean VAS score was 5.53. A multivariate analysis demonstrated that older age (equal to or older than 66 years) was the only significant factor as-sociated with muscle cramps. The prevalence of muscle cramps among patients with liver diseases seemed not to be higher. The problem was that only 11 (32.4%) of 34 outpatients received therapy for their muscle cramps. Conclusions: Only age is related to muscle cramps, which is rather weak, and it is possible that this common symptom may not be limited to liver disease patients.

Diagnostic utility of quantitative analysis of microRNA in bile samples obtained during endoscopic retrograde cholangiopancreatography for malignant biliary strictures.

BACKGROUND: The sensitivity of bile cytology for malignant biliary strictures is not adequate. To overcome this limitation, we evaluated whether quantitative analysis of microRNAs (miRNAs) in bile can provide a precise diagnosis of malignant biliary strictures due to pancreatic cancer (PC) and biliary tract cancer (BTC). METHODS: This was a retrospective evaluation of miRNA levels in stored bile samples of patients with PC, BTC or benign biliary stricture obtained during biliary drainage from April 2019 to December 2021 at our institution. A total of 113 patients (PC; n = 40, BTC; n = 38, control; n = 35) were enrolled. The miRNA candidates to be quantified were determined with microarray analysis from each 3 patients with PC, BTC and controls. RESULTS: Using microarray analysis, we confirmed four significantly up-regulated miRNAs (miR-1275, miR-6891-5p, miR-7107-5p, miR-3197) in patients with PC and BTC compared to control patients. Quantitative PCR was then performed in 113 bile samples for these miRNAs. miR-1275 was significantly upregulated in PC (p = 0.003) and BTC (p = 0.049) compared to controls, miR-6891-5p was significantly upregulated in PC compared to controls (p = 0.025). In particular, a combination of bile cytology and miR-1275 in bile showed a sensitivity of 77.5% (95% CI, 70.7-77.5%), specificity of 100% (95% CI, 92.2-100%) and an area under the curve (AUC) of 0.93, and provided a significantly greater additional diagnostic effect than bile cytology alone (p = 0.014). CONCLUSIONS: This study suggest that bile miRNAs could be potential biomarkers for pancreato-biliary diseases, particularly miR-1275 and miR-6891-5p may be helpful in the diagnosis of PC and BTC.

The Usefulness of the Alpha-Retroflex Position in Biliary Cannulation on Single-Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography in Patients with Roux-en-Y Gastrectomy: A Retrospective Study.

Introduction: Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is a useful therapeutic procedure that provides promising results in patients with surgically altered anatomy. However, biliary cannulation in BE-ERCP remains challenging. Therefore, in patients with Roux-en-Y gastrectomy, this study aimed to evaluate a BE-ERCP cannulation strategy that includes the newly developed alpha-retroflex scope position. Methods: This was a retrospective review of 52 patients with Roux-en-Y gastrectomy who underwent BE-ERCP at two centers between April 2017 and December 2022. In these patients, three types of scope position had been used for biliary cannulation: straight (S-position), J-retroflex (J-position), and alpha-retroflex (A-position). First, the S-position was used for biliary cannulation. Then, if biliary cannulation was difficult with this position, the J-position was used, followed by the A-position, if necessary. Results: The biliary cannulation success rate was 96.6% (50/52). The S-, J-, and A-positions achieved successful biliary cannulation in 24 (48%), 14 (28%), and 12 patients (24%), respectively. No adverse events, including post-ERCP pancreatitis and perforation, occurred. Conclusion: This was the first study of a cannulation strategy that included the A-position in addition to the S- and J-positions. The study showed that the A-position is feasible and safe in BE-ERCP in patients with Roux-en-Y gastrectomy.

Masitinib Inhibits Hepatitis A Virus Replication.

The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs are currently available in clinical situations. For anti-HAV drug screening, more convenient and useful models that mimic HAV replication are needed. In the present study, we established HuhT7-HAV/Luc cells, which are HuhT7 cells stably expressing the HAV HM175-18f genotype IB subgenomic replicon RNA harboring the firefly luciferase gene. This system was made by using a PiggyBac-based gene transfer system that introduces nonviral transposon DNA into mammalian cells. Then, we investigated whether 1134 US Food and Drug Administration (FDA)-approved drugs exhibited in vitro anti-HAV activity. We further demonstrated that treatment with tyrosine kinase inhibitor masitinib significantly reduced both HAV HM175-18f genotype IB replication and HAV HA11-1299 genotype IIIA replication. Masitinib also significantly inhibited HAV HM175 internal ribosomal entry-site (IRES) activity. In conclusion, HuhT7-HAV/Luc cells are adequate for anti-HAV drug screening, and masitinib may be useful for the treatment of severe HAV infection.