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The torque and fanning techniques allow for multiple areas within pancreatic lesions to be targeted using different maneuvers and can, hence, enhance diagnostic outcomes. We compared the diagnostic performance of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for pancreatic masses using the torque and fanning techniques.This multicenter randomized trial enrolled a total of 160 consecutive patients who underwent EUS-FNB for solid pancreatic tumors using either the torque or fanning technique. Three passes were permitted for each lesion, and the technique sequence was randomly assigned as either torque first or fanning first with the standard technique as a reference.The median quality score of the histological samples was significantly higher in the torque and fanning group than in the standard group (p .001). Furthermore, the torque technique provided improved sensitivity of 93.38% and accuracy of 94.30%. The standard technique provided diagnostic sensitivity of 68.84% and accuracy of 72.96%, while the fanning technique showed sensitivity of 91.85% and accuracy of 93.04%.The new torque technique enables the acquisition of better-quality samples and can potentially increase the diagnostic outcomes in the EUS-FNB of pancreatic solid masses, with the same recommendations as those for the fanning technique.

Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) may be a feasible and useful alternative in patients with malignant biliary obstruction (MBO) after failed endoscopic retrograde cholangiopancreatography (ERCP). To date, the risk factors for adverse events (AEs) and long-term outcomes of EUS-HGS have not been fully explored according to stent type. Therefore, we evaluated potential risk factors for AEs and long-term outcomes of EUS-HGS.In total, 120 patients who underwent EUS-HGS were retrospectively reviewed. A multivariate analysis through Cox proportional hazard and logistic regression model was used to identify the risk factors for stent dysfunction and AEs, respectively. Stent patency and patient survival were evaluated using Kaplan-Meier plots with a log-rank test for each stent.The technical and clinical success rates were 96.2% (102/106) and 83.0% (88/106). The median duration of stent patency was longer in self-expandable metal stents (SEMS) compared to plastic stents (PS) (158 vs. 108 days). Kaplan-Meier analysis indicated that the type of stent was not associated with stent patency (Hazard ratios [HR] 0.997, 95% confidence interval [CI] [0.525-1.896]) or overall survival. In addition, multivariate analysis indicated that hilar MBO significantly associated with stent dysfunction (HR, 2.340; 95% CI, 1.028-5.326, p = 0.043) and late AEs.Given the lower incidence of AEs and better long-term outcomes of EUS-HGS, it can be considered a safe alternative to ERCP or percutaneous approaches regardless of which stent is used. Furthermore, hilar MBO was established as a potential risk factor for stent dysfunction and late AEs.

Background Endoscopic clip placement is technically challenging using a duodenoscope, limiting their application for treatment of bleeding after endoscopic papillectomy. This study evaluated the efficacy of newly designed clips to prevent bleeding after endoscopic papillectomy. Methods Patients (n = 80) with suspected benign adenomas on the major papilla who were scheduled for endoscopic papillectomy with or without clipping were randomized. A new duodenoscope-compatible clip capable of being rotated, reopened, and repeatedly repositioned was used. The primary end point was incidence of delayed bleeding. Results The clipping procedure was successful in all patients. The incidence of delayed bleeding was nonsignificantly higher in the no-clipping group than in the clipping group (31.6 % [95 % confidence interval (CI) 19.1–47.5] vs. 15.0 % [95 %CI 7.1–29.1]). The incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis did not differ significantly between the groups (clipping vs. no-clipping: 17.5 % [95 %CI 8.7–31.9] vs. 5.3 % [95 %CI 1.5–17.3]), and all cases were mild. Conclusions Placement of the newly designed rotatable clip was technically feasible and tended to have a protective effect by preventing delayed bleeding after endoscopic papillectomy, although statistical significance was not reached.

Background/Aims The appropriate number of band ligations during the first endoscopic session for acute variceal bleeding is debatable. We aimed to compare the technical aspects of endoscopic variceal ligation (EVL) in patients with variceal bleeding according to the number of bands placed per session. Methods We retrospectively reviewed multicenter data from patients who underwent EVL for acute variceal bleeding. Patients were classified into minimal EVL (targeting only the foci with active bleeding or stigmata of recent bleeding) and maximal EVL (targeting potential bleeding sources in addition to the aforementioned targets) groups. The primary endpoint was 5-day treatment failure. The secondary endpoints were 30-day rebleeding, 30-day mortality, and intraprocedural adverse events. Results Minimal EVL was associated with lower rates of hypoxia and shock during EVL than maximal EVL (hypoxia, 0.9% vs 2.9%; shock, 1.3% vs 3.4%). However, treatment failure was higher in the minimal EVL group than in the maximal EVL group (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.41). Age ≥60 years, Model for End-Stage Liver Disease score ≥15, Child-Turcotte-Pugh classification C, presence of hepatocellular carcinoma, and systolic blood pressure

Endoscopic retrograde cholangiopancreatography (ERCP) is challenging in patients undergoing Roux-en-Y (REY) reconstruction; although balloon-assisted enteroscopy is the first-line treatment, it is not always available considering equipment and expertise. We aimed to evaluate the feasibility of using a cap-assisted colonoscope as the primary approach for ERCP in REY reconstruction. We included 47 patients with REY who underwent ERCP using a cap-assisted colonoscope between January 2017 and February 2022. The primary outcome was intubation success for ERCP using a cap-assisted colonoscope during REY reconstruction. The secondary outcomes were cannulation success, procedure-related adverse events, and variables affecting successful intubation. Comparing side-to-side jejunojejunostomy (SS-JJ) and side-to-end jejunojejunostomy (SE-JJ) groups, the intubation success rate using a cap-assisted colonoscope in the SS-JJ group was higher than that in the SE-JJ group (34 of 38 (89.5%) vs. 1 of 9 (11.1%), p < 0.001). Successful intubation was achieved in 37 (97.4%) and 8 (88.9%) patients in the SS-JJ and SE-JJ groups, respectively, after applying the rescue technique using a balloon-assisted enteroscope for failed ERCP using only a colonoscope. No perforation occurred. Multivariable analysis showed that SS-JJ was a predictive factor for successful intubation (odds ratio [95% confidence interval] = 37.06 [3.91–925.56], p = 0.005). Usage of a cap-assisted colonoscope can be crucial for ERCP in patients undergoing REY reconstruction. Anatomically, SS-JJ can facilitate easy and accurate identification of the afferent limb and a highly successful ERCP using a cap-assisted colonoscope.

Background/aims The endoscopic step-up approach is accepted as the preferred treatment for complicated or symptomatic walled-off necrosis (WON). Direct endoscopic necrosectomy (DEN) is an effective therapeutic option, but few reports describe long-term follow-up in this patient population. Thus, we aim to assess the long-term outcomes of DEN following severe necrotizing pancreatitis. Methods The data of all acute pancreatitis patients who underwent DEN following endoscopic transmural drainage from six referral centers between 2007 and 2017 were retrospectively collected. Results Sixty patients (76.7% male, mean age 48.3 years) underwent a median of 4 sessions of DEN starting at a median of 45.5 days after the onset of acute pancreatitis. Clinical success was achieved in 51 patients (85%), with a 35% complication rate and a 5% mortality rate. Using multivariate analysis, the risk factor associated with DEN failure or major DEN complications requiring intervention or surgery was an identified bacterial/fungal WON infection (odds ratio, 19.3; 95% confidence interval, 1.5 to 261.7). During the median follow-up period of 27 months, complicated WON recurrence was observed in 5.3% of patients, and long-term complications occurred in 24.6% of patients (four exocrine insufficiency, nine newly developed diabetes mellitus, one recurrent small bowel obstruction, one chylous ascites). Conclusions Considering that long-term complications are similar to those observed after pancreatectomy, DEN should be performed meticulously while minimizing damage to the viable pancreatic parenchyma with adequate antibiotic escalation.

Unlike in normal cells, ursodeoxycholic acid (UDCA) causes apoptosis rather than protection in cancer cells. Aim of this study was to demonstrate whether UDCA actually inhibits proliferation and induces apoptosis in bile duct cancer cells; the effect of UDCA on the expression of COX-2, PI3K/AKT, ERK, and EGFR; how UDCA affects cancer cell invasiveness and metastasis, since these effects are not established in bile duct cancer cells. SNU-245 cells (human extrahepatic bile duct cancer cells) were cultured. MTT assays were performed to evaluate the effect of UDCA on the cell proliferation. A cell death detection enzyme-linked immunosorbent assay and a caspase-3 activity assay were used to determine apoptosis. Western blot analysis measured expression levels of various proteins. The invasiveness of the cancer cells was evaluated by invasion assay. In cultured bile duct cancer cells, UDCA suppressed cell proliferation in bile duct cancer cells by inducing apoptosis and p53 activation, blocking deoxycholic acid (DCA)-induced activated EGFR-ERK signaling and COX-2, inhibiting DCA-induced activated PI3K-AKT signaling, and suppressing the invasiveness of bile duct cancer cells. In addition, a MEK inhibitor impaired UDCA-induced apoptosis in bile duct cancer cells. UDCA has antineoplastic and apoptotic effects in bile duct cancer cells. Thus, UDCA could be a chemopreventive agent in patients with a high risk of cancer, and/or a therapeutic option that enhances other chemotherapeutics.

Laparoscopic cholecystectomy remains the standard treatment for acute cholecystitis (AC) although it is always not suitable for patients who are poor candidates for surgery. Recently, endoscopic gallbladder (GB) drainage was found to be a potentially revolutionary alternative for cholecystectomy for the control of symptoms, definitive treatment, or bridging therapy until surgery is possible. Two endoscopic methods have been established using either the trans-mural or trans-papillary drainage approach. Endoscopic ultrasound-guided GB drainage (EUS-GBD) (trans-mural approach) is a novel technique that allows stent placement between the GB and duodenum or stomach via fistula track, effectively enabling GB drainage. For endoscopic trans-papillary GB drainage (ETGBD) (trans-papillary approach), attempts of selective cannulation to the cystic duct should be made to place the stent in the same manner as an endoscopic retrograde cholangiopancreatography. In comparison, EUS-GBD has higher clinical success and lower recurrence rates than ETGBD due to the use of larger-caliber stents, which allows for effective drainage when performed by skilled practitioners at high-volume centers. Advantages of ETGBD over EUS-GBD include more affordable costs and physiologic drainage, which preserves naive anatomy for possible future cholecystectomy. Although the field of endoscopic treatment for AC is rapidly advancing, important questions regarding which method improves clinical outcomes and safety more effectively remain unaddressed. Herein, the current status of endoscopic treatment for AC, including a technical review on clinical outcomes, adverse events, and advantages and disadvantages of each technique are reviewed, as well as other future prospects.

Endoscopic access to the targeted site is a major challenge for the endoscopic retrograde cholangiopancreatography (ERCP) in patients undergoing Roux-en-Y (R-Y) reconstruction after total or subtotal gastrectomy. We aimed to evaluate the feasibility, reproducibility, and safety of mechanistic loop resolution strategies using a short-type single-balloon enteroscopy (short SBE) system.Between February 2020 and March 2022, consecutive patients with a previous R-Y gastrectomy requiring ERCP were prospectively enrolled. Different mechanistic loop resolution strategies for two-dimensional loops, three-dimensionally rotated loops, and loops making a cane or S-shape were applied during the SBE approach.Forty-three short SBE-ERCP procedures were performed on 37 patients, with an approach success rate of 100.0% (43/43). The mean time to reach the jejunojejunal anastomosis and target site were 8.0 (6.0-11.0) minutes and 26.0 (16.0-36.0) minutes, respectively. The major challenges for the approach were the cane or S-shaped loop in the jejunojejunal anastomosis or Treitz ligament. The retroflex positioning of a SBE in front of the papilla was achieved in 86.0% (37/43), and the cannulation success rate in patients with an intact papilla was 90.9% (30/33). The initial, overall therapeutic successes, median total procedure time, and adverse event rate were 87.8%, 92.7%, 77.0 (IQR 56-100.5) minutes, and 11.6%, respectively.Short SBE-ERCP using standardized mechanistic loop resolution strategies is effective and reproducible in patients with R-Y reconstruction after gastrectomy.ClinicalTrial.gov (NCT04847167).

Backgrounds/aims PPARγ, farnesoid X receptor (FXR) and CYP7A1 are associated with solubility of bile. This study was performed to understand a mechanism and interactions of statin-induced PPARγ, PGC-1α and HNF-4α related to the statin-induced activation of FXR and CYP7A1, and verify whether the mevalonate pathway is involved in the mechanism. Methods MTT assays were performed using cultured human Hep3B cells to determine the effect of atorvastatin on the cell proliferation. Expression levels of indicated proteins were measured using Western blotting assays by inhibiting the protein expression or not. Results Atorvastatin increased expression of PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. PPARγ ligand of troglitazone upregulated the expression of PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. Silencing of PPARγ, PGC1α, and HNF4α using respective siRNA demonstrated that atorvastatin-induced FXR and CYP7A1 activation required sequential action of PPARγ /PGC-1α/HNF-4α. The silencing of PPARγ completely inhibited atorvastatin-induced PGC-1α expression, and the PGC1α silencing partially inhibited atorvastatin-induced PPARγ expression. The inhibition of HNF4α did not affect atorvastatin-induced PPARγ expression, but partially inhibited atorvastatin-induced PGC-1α expression. Besides, mevalonate completely reversed the effect of atorvastatin on PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1. Conclusions Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.

Epithelial-mesenchymal transition (EMT) features are associated with pathological severity in the progression and metastasis of various cancer types, including bile duct cancer (BDC). Our previous study demonstrated that ursodeoxycholic acid (UDCA) blocked the EGFR-MAPK signaling pathway and inhibited the invasion of BDC cells. The present study was performed to determine whether UDCA inhibits EMT and promotes the expression of E-cadherin to inhibit the invasion and aggressiveness of BDC. In addition, the present study aimed to confirm that the primary mechanism of inhibition of EMT by UDCA is related to the EGFR axis. Human extrahepatic BDC cells were cultured. The effect of UDCA on cell proliferation was evaluated using MTT assays. A cell death ELISA kit was used to measure apoptosis, and western blot assays or immunofluorescence staining assays measured the expression levels of various target proteins. The mRNA expression of Slug and ZEB1 was evaluated via reverse transcription-quantitative PCR. The invasiveness of BDC cells was estimated by invasion assays and western blot assays for focal adhesion kinase (FAK). UDCA inhibited the proliferation of BDC cells as effectively as gefitinib (an EGFR inhibitor), and the combination of UDCA and gefitinib revealed an additive effect on the proliferation of cells. UDCA and gefitinib induced apoptosis, and the combination of UDCA and gefitinib demonstrated an additive effect on apoptosis in BDC cells. UDCA restored the E-cadherin expression inhibited by EGF and suppressed N-cadherin expression increased by EGF as effectively as gefitinib. UDCA suppressed the Slug and ZEB1 mRNA expression induced by EGF in BDC cells. UDCA suppressed the invasiveness of BDC cells and FAK expression linked to the invasiveness of BDC. In conclusion, UDCA enhanced E-cadherin expression and suppressed N-cadherin expression through inhibition of the EGF-EGFR axis, contributing to the inhibition of EMT and invasiveness in BDC cells. Therefore, UDCA may be applied as an adjuvant or palliative antineoplastic agent and as a therapeutic option to enhance the effect of other chemotherapeutics.

Background Although many studies have reported the efficacy of different stents for endoscopic ultrasonography (EUS)-guided peripancreatic fluid collection (PFC) drainage, they have not completely determined which stent is superior. This network meta-analysis comprehensively evaluated the comparative efficacy of stents used in EUS-guided PFC. Methods We searched all relevant studies published up to February 2019 that examined the efficacy of double pigtail plastic stent (DPPS), fully covered self-expanding metal stent (FCSEMS), and lumen-apposing metal stent (LAMS) in EUS-guided PFC drainage. We performed a Bayesian network meta-analysis for clinical efficacy and adverse events. Results Fifteen studies comprising 1746 patients were included in the meta-analysis. In terms of clinical success, no significant differences were noted in LAMS versus DPPS or LAMS versus FCSEMS (risk ratio [RR] 1.04 [95% credible interval (CrI) 0.99-1.11] and RR 0.96 [95% CrI 0.91-1.03]), respectively). FCSEMS was superior in terms of clinical success to DPPS (RR 1.09, 95% CrI 1.02-1.15). There was no significant difference in the recurrence of PFC among groups. Regarding adverse events, LAMS had a higher bleeding risk than FCSEMS (RR 6.70, 95% CrI 1.77-36.27) and tended to have a higher risk of bleeding than DPPS (RR 2.67, 95% CI 0.71-9.28). In terms of stent migration, there was no significant difference between any two groups compared. Conclusions FCSEMS had superior efficacy in terms of clinical success compared with DPPS stents. Significant superiority of LAMS to DPPS was not identified. Additionally, LAMS had the higher risk of bleeding than FCSEMS.

OBJECTIVES Successful biliary cannulation is a prerequisite and important component of endoscopic retrograde cholangiopancreatography, but conventional cannulation methods (CCMs) have a postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) rate of 14.1% in patients at high risk for PEP. The aim of this study was to evaluate the effectiveness and safety of needle-knife fistulotomy (NKF), compared with a CCM, when used for primary biliary access in patients at high risk for developing PEP. METHODS A total of 207 patients with one or more risk factors for PEP were prospectively enrolled. The patients were randomly allocated to one of 2 groups according to the primary biliary cannulation technique (NKF or CCM). We compared biliary cannulation success rates, cannulation and procedure times, and the incidence of adverse events, including PEP, between the groups. RESULTS The mean number of PEP risk factors was similar between the groups (NKF, 2.2 ± 1.0; CCM, 2.2 ± 0.9). PEP occurred in 8 patients in the CCM group and in no patients in the NKF group (9.2% vs 0%, P < 0.001). The rates of other adverse events did not differ between the groups. The biliary cannulation success rate was high in the NKF group, but relatively low in the CCM group, possibly because of the stringent failure criteria aimed at reducing PEP. However, the mean cannulation and total procedural times were longer in the NKF group than in the CCM group. DISCUSSION NKF is an effective and safe procedure to gain primary biliary access in patients at high risk for developing PEP. ClinicalTrials.gov, NCT02916199.

In a recent randomized controlled trial, a double bare metal stent (DBS) showed better stent patency than single-layer metal stents. However, clear evidence comparing the efficacy of uncovered (UCDBS) and partially covered (PCDBS) DBSs for distal malignant biliary obstruction (MBO) is lacking. Therefore, we compared the clinical outcomes including stent patency of UCDBSs versus PCDBSs.A multicenter, randomized study was performed in patients with distal MBO. The primary endpoint was stent patency. Secondary endpoints were the proportion of patients with patent stents at 6 months, risk factors for stent dysfunction, overall survival, technical and clinical success rates of stent placement, and other adverse events (AEs).Among 258 included patients, 130 were randomly assigned to the PCDBS group and 128 to the UCDBS group. The mean duration of stent patency of the PCDBS (421.2 days; 95% confidence interval [CI], 346.7-495.7) was longer than that of the UCDBS (377.4 days; 95% CI, 299.7-455.0), although total stent dysfunction and stent dysfunction within 6 months were not different between groups. Multivariate analysis indicated that chemotherapy after stent placement was a significant factor for overall survival (hazard ratio, .570; 95% CI, .408-.796) and had a marginal impact on stent patency (hazard ratio, 1.569; 95% CI, .923-2.667). There were no remarkable differences in AEs, including pancreatitis, cholecystitis, and stent migration, between the 2 groups.The use of PCDBSs compared with UCDBSs in patients with distal MBO has unclear benefits regarding stent patency and overall survival, although PCDBSs have a lower rate of tumor ingrowth. (Clinical trial registration number: NCT02937246.).

Direct endoscopic necrosectomy (DEN) using a lumen-apposing metal stent (LAMS) is a standard therapy for the management of symptomatic walled-off necrosis (WON). Here, we demonstrated the efficacy of the routine placement of long plastic stents after a DEN session to treat laterally extended WON. Patients (n = 6) with symptomatic laterally extended WON who underwent DEN after long plastic stent placement were included. The primary endpoint was clinical efficacy of the procedure. The technical and clinical success rates were 100% without major adverse events. The WON extended to the pelvic cavity or pericolic area, and the WON size was between 18.6 and 35.8 cm in length. The median number of DEN sessions was 10 (range 6–16), and two or three long plastic stents were placed after every DEN session. Only one patient suffered from pneumoperitoneum during DEN, which spontaneously resolved within 20 min. Placement of a long plastic stent after DEN using LAMS is a minimally invasive and effective treatment for symptomatic laterally extended WON. Further studies are needed to define the indications and most suitable patients.

Sphincterotomes are essential for endoscopic sphincterotomy (EST) and can also be used for cannulation in ERCP. A domestic new pull-type sphincterotome (Optimos™, Taewoong, Goyang, Korea) provides acceptable technical feasibility and safety, but there are no comparison results. Thus, this study compared the clinical performance and safety of Optimos™ sphincterotome to a conventional sphincterotome (CleverCut3™, Olympus, Tokyo, Japan) in patients who underwent ERCP.From April 2021 to July 2021, a randomized prospective comparative study was conducted on 104 consecutive patients who underwent ERCP in three medical centers. The primary endpoint was the clinical performance and safety of sphincterotomes during ERCP.One hundred and four patients were assigned randomly to the Optimos™ group (n=51) or CleverCut3™ group (n=53). All demographic characteristics did not differ between the groups except the BMI. The technical success rate for cannulation, performance of EST, and total procedure time were similar in the two groups. The adverse events did not differ, even though two cases of post-ERCP pancreatitis occurred in CleverCut3™. On the other hand, in questionnaire analysis, CleverCut™ showed a better user's convenience (median [interquartile range] 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.013) and manipulability (median [interquartile range], 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.039) than Optimos™, even though the other profiles did not reveal any differences.New domestic pull-type sphincterotome can offer comparable clinical performance and safety profiles to conventional sphincterotome, but it needs refinements to increase the user's convenience and manipulability. Further improvement and innovation will be required to advance domestic medical devices.

Background and Aims Recently, a newly designed lumen-apposing metal stent (LAMS) with a conventional delivery system was developed. The purpose of this study was to evaluate the effectiveness and safety of a newly designed LAMS for EUS-guided drainage to treat symptomatic pancreatic pseudocysts. Methods This prospective multicenter cohort study included 34 patients with symptomatic pancreatic pseudocysts from 2016 to 2017. The patients underwent EUS-guided drainage with the newly designed LAMS (Niti-S SPAXUS; Taewoong Medical Co, Ltd, Ilsan, South Korea). Effectiveness outcome measurements included technical success rate, clinical success rate, successful stent removal rate, and procedural time. Safety outcome measurements included procedure and/or stent-related adverse events (AEs) and overall AEs. Patients were prospectively followed, and consecutive data were collected at discharge, at stent removal, and 20 days after stent removal. Results Thirty-four patients (mean age 51.7 ± 13.3 years, 26 men) were enrolled. The mean pseudocyst size was 9.23 ± 3.54 cm. The technical success rate was 97.1% (33/34). The clinical success rate was 94.1% (32/34). All stents were successfully removed. The mean procedural time from needle puncture to stent deployment was 10.3 ± 5.7 minutes. Four patients (11.8%) experienced procedure and/or stent-related AEs, including stent maldeployment (n = 1) and pseudocyst infection (n = 3). All patients completely recovered from the AEs. Bleeding caused by the stent or buried LAMS syndrome was not observed. No unplanned endoscopic procedures were required. Conclusions This study showed that EUS-guided drainage using the newly designed LAMS is technically feasible and effective for the treatment of symptomatic pancreatic pseudocysts. (Clinical trial registration number: NCT02730663.)

Background/Aims: Metformin has been found to have antineoplastic activity in some cancer cells. This study was performed to determine whether metformin inhibits the proliferation of bile duct cancer cells by inducing apoptosis and its effects on the expression of gene-related proteins involved in cancer growth. Methods: Human extrahepatic bile duct cancer cells (SNU-245 and SNU-1196) were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the effect of metformin on the cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and a caspase-3 activity assay. Expression levels of various proteins, with or without specific small interfering ribonucleic acid-induced gene disruption, were measured by Western blot analysis. The migratory activity of the cancer cells was evaluated by wound healing assay. Results: Metformin suppressed cell proliferation in bile duct cancer cells by inducing apoptosis. Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPKThr172). Hyperglycemia impaired metformin-induced AMPKThr172 activation and enhanced phosphorylation of AMPK at serine-485 (AMPKSer485). Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia. Conclusions: Metformin has antineoplastic effects in bile duct cancer, and hyperglycemic environment interrupts the effect of metformin. In addition, AMPK and IGF-1R play a key role in the proliferation of bile duct cancer cells.

Background and aim Magnetic resonance cholangiopancreatography (MRCP) can accurately diagnose common bile duct (CBD) stones but is laborious to interpret. We developed an artificial neural network (ANN) capable of automatically assisting physicians with the diagnosis of CBD stones. This study aimed to evaluate the ANN's diagnostic performance for detecting CBD stones in thick-slab MRCP images and identify clinical factors predictive of accurate diagnosis. Methods The presence of CBD stones was confirmed via direct visualization through endoscopic retrograde cholangiopancreatography (ERCP). The absence of CBD stones was confirmed by either a negative endoscopic ultrasound accompanied by clinical improvements or negative findings on ERCP. Our base networks were constructed using state-of-the-art EfficientNet-B5 neural network models, which are widely used for image classification. Results In total, 3156 images were collected from 789 patients. Of these, 2628 images from 657 patients were used for training. An additional 1924 images from 481 patients were prospectively collected for validation. Across the entire prospective validation cohort, the ANN achieved a sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of 93.03%, 97.05%, 97.01%, 93.12%, and 95.01%, respectively. Similarly, a radiologist achieved a sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy 91.16%, 93.25%, 93.22%, 90.20%, and 91.68%, respectively. In multivariate analysis, only bile duct diameter > 10 mm (odds ratio = 2.45, 95% confidence interval [1.08-6.07], P = 0.040) was related to ANN diagnostic accuracy. Conclusion Our ANN algorithm automatically and quickly diagnoses CBD stones in thick-slab MRCP images, therein aiding physicians with optimizing clinical practice, such as whether to perform ERCP.

Fatty pancreas is a potential risk factor for acute pancreatitis; however, whether it is also a risk factor for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been evaluated. We aimed to determine the impact of fatty pancreas on the development of PEP.We analyzed the data of patients who underwent abdominal computed tomography (CT) scan and sequential therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Fatty change in the pancreas was evaluated based on pancreatic attenuation of unenhanced image on CT scan. The risk of fatty pancreas for the development of PEP was evaluated using a logistic regression model.Of a total of 858 patients included in the study, 354 (41.3%) had fatty pancreas, while 504 (58.7%) did not have fatty pancreas. PEP developed in 28 patients (7.9%) in the fatty pancreas group and in 13 patients (2.6%) in the no fatty pancreas group. Fatty pancreas was significantly associated with the development of PEP (odds ratio [OR] [95% confidence interval [CI]] 2.38 [1.16-4.87]). A history of acute pancreatitis, female sex, difficult cannulation, and endoscopic papillary balloon dilation were also risk factors for the development of PEP. The risk for moderate-to-severe PEP development tended to be higher in the fatty pancreas group than in the no fatty pancreas group (OR [95% CI] 5.61 [0.63-49.62]).Fatty pancreas is a significant risk factor for the development of PEP. Clinicians need to be aware of the risk of fatty pancreas for the development of PEP prior to performing ERCP.

Endoscopic ultrasound (EUS)-guided tissue acquisition of pancreatic solid tumor requires a strict recommendation for its proper use in clinical practice because of its technical difficulty and invasiveness. The Korean Society of Gastrointestinal Endoscopy (KSGE) appointed a task force to draft clinical practice guidelines for EUS-guided tissue acquisition of pancreatic solid tumor. The strength of recommendation and the level of evidence for each statement were graded according to the Minds Handbook for Clinical Practice Guideline Development 2014. The committee, comprising a development panel of 16 endosonographers and an expert on guideline development methodology, developed 12 evidence-based recommendations in eight categories intended to help physicians make evidence-based clinical judgments with regard to the diagnosis of pancreatic solid tumor. This clinical practice guideline discusses EUS-guided sampling in pancreatic solid tumor and makes recommendations on circumstances that warrant its use, technical issues related to maximizing the diagnostic yield (e.g., needle type, needle diameter, adequate number of needle passes, sample obtaining techniques, and methods of specimen processing), adverse events of EUS-guided tissue acquisition, and learning-related issues. This guideline was reviewed by external experts and suggests best practices recommended based on the evidence available at the time of preparation. This guideline may not be applicable for all clinical situations and should be interpreted in light of specific situations and the availability of resources. It will be revised as necessary to cover progress and changes in technology and evidence from clinical practice. (Gut Liver 2021;15:354-374)

BACKGROUND AND AIM Acute variceal bleeding (AVB) is a fatal adverse event of cirrhosis, and endoscopic band ligation (EBL) is the standard treatment for AVB. We developed a novel bedside risk-scoring model to predict the 6-week mortality in cirrhotic patients undergoing EBL for AVB. METHODS Cox regression analysis was used to assess the relationship of clinical, biological, and endoscopic variables with the 6-week mortality risk after EBL in a derivation cohort (n = 1373). The primary outcome was the predictive accuracy of the new model for the 6-week mortality in the validation cohort. Moreover, we tested the adequacy of the mortality risk-based stratification and the discriminative performance of our new model in comparison with the Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease scores in the validation cohort (n = 200). RESULTS On multivariate Cox regression analysis, five objective variables (use of beta-blockers, hepatocellular carcinoma, CTP class C, hypovolemic shock at initial presentation, and history of hepatic encephalopathy) were scored to generate a 12-point risk-prediction model. The model stratified the 6-week mortality risk in patients as low (3.5%), intermediate (21.1%), and high (53.4%) (P

Although many studies have investigated the efficacy of stent placement for patients with malignant extrahepatic biliary obstruction, the clinical outcomes and adverse events of biliary stenting have not been comprehensively evaluated. We searched all relevant randomized-controlled trials that evaluated the comparative efficacy of biliary stents, including the plastic stents, uncovered self-expandable metal stents (SEMSs), and covered SEMSs in patients with malignant extrahepatic biliary obstructions. Twenty-one studies with 2326 patients were included. Both uncovered and covered SEMSs had a lower risk of recurrent biliary obstruction (RBO) compared to plastic stents (risk ratio (RR) (95% confidence interval [CI]): uncovered vs. plastic, 0.46 (0.35–0.62), covered vs. plastic, 0.46 (0.34–0.62)). A comparison of the groups using SEMSs revealed that tumor ingrowth was common in the uncovered SEMS group, while stent migration, tumor overgrowth, and occlusion by sludge were common in the covered SEMS group, however, the overall risk of RBO did not differ between these groups (RR (95% CI): uncovered vs. covered: 1.02 (0.80–1.30)). Although the main causes of RBO vary across stents, RBO risk was similar between uncovered and covered SEMS groups. Both SEMSs have superior efficacy in terms of RBO compared to plastic stents.