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Although the biliary tract is a small organ, it is diverse in location (intrahepatic bile ducts, extrahepatic bile ducts, gallbladder, and ampulla) and disease (including benign and malignant), thus a multidisciplinary approach involving endoscopists, surgeons, oncologists, radiologists, and infectious disease specialists is often required to treat biliary tract disease [...]

BackgroundIn patients with unresectable hilar malignant biliary obstruction (MBO), bilateral metal stent placement is recommended. However, treatment selection between partially stent-in-stent (SIS) and side-by-side (SBS) methods is still controversial.StudyClinical outcomes of bilateral metal stent placement by SBS and SIS methods for hilar MBO were retrospectively studied in four Japanese centers. While large-cell-type uncovered metal stents were placed above the papilla in SIS, braided-type uncovered metal stents were placed across the papilla in SBS.ResultsA total of 64 patients with hilar MBO (40 SIS and 24 SBS) were included in the analysis. Technical success rate was 100% in SIS and 96% in SBS. Functional success rate was 93% in SIS and 96% in SBS. Early adverse event rates were higher in SBS (46%) than in SIS (23%), though not statistically significant (P = 0.09). Post-procedure pancreatitis was exclusively observed in SBS group (29%). Recurrent biliary obstruction rates were 48% and 43%, and the median time to recurrent biliary obstruction was 169 and 205 days in SIS and SBS, respectively.ConclusionsOther than a trend to higher adverse event rates including post-procedure pancreatitis in SBS, clinical outcomes of SIS and SBS methods were comparable in patients with unresectable hilar MBO.

Pancreatic fluid collections (PFCs) commonly develop as complications of acute pancreatitis and ductal disruption due to chronic pancreatitis. In the revised Atlanta classification, PFCs were classified based on the presence of necrosis and duration following the onset of acute pancreatitis. Interventions are required in cases of symptomatic pancreatic pseudocysts or walled-off necrosis (WON). In the management of these PFCs, endoscopic ultrasound-guided transluminal drainage and subsequent direct endoscopic necrosectomy for WON are increasingly utilized as less invasive treatment modalities compared to surgical debridement. To date, researchers have focused predominantly on the technical aspects of endoscopic therapy for symptomatic PFCs. Given the poor physical condition of patients receiving endoscopic treatment for PFCs, systemic support may have a substantial impact on the short- and long-term outcomes of these patients. A multidisciplinary approach is required to improve the clinical outcomes of patients with infected PFCs and their associated comorbidities. However, non-interventional support during the periprocedural period of endoscopic treatment of PFCs has not been fully discussed, and there have been considerable variations in the selection of treatment options between endoscopists and centers. To address these unmet needs in the clinical management of PFCs and promote future research to improve the clinical outcomes, we conducted a review of the literature within a multicenter consortium of expert endoscopists with specific expertise in the endoscopic treatment of PFCs. In this review, we summarize the current evidence on non-interventional supportive care (e.g., continuous lavage, medications, nutritional support, and antimicrobials) and propose potential topics for future research.

BackgroundTo further clarify the clinico-epidemiological features of autoimmune pancreatitis (AIP) in Japan, we conducted the fourth nationwide epidemiological survey.MethodsThis study consisted of two stage surveys; the number of AIP patients was estimated by the first survey and their clinical features were assessed by the second survey. We surveyed the AIP patients who had visited hospitals in 2016.ResultsThe estimated number of AIP patients in 2016 was 13,436, with an overall prevalence rate of 10.1 per 100,000 persons. The estimated number of newly diagnosed patients was 3984, with an annual incidence rate of 3.1 per 100,000 persons. Compared to the 2011 survey, both numbers more than doubled. We obtained detailed clinical information of 1474 AIP patients. The male-to-female sex ratio was 2.94, the mean age was 68.1, and mean age at diagnosis was 64.8. At diagnosis, 63% patients were symptomatic and nearly half of them presented jaundice. Pancreatic cysts were found in 9% of the patients and calcifications in 6%. Histopathological examination was performed in 64%, mainly by endoscopic ultrasonography-guided fine needle aspiration. Extra-pancreatic lesions were detected in 60% of the patients. Eighty-four % patients received the initial steroid therapy, and 85% received maintenance steroid therapy. Kaplan–Meier analysis revealed that the relapsed survival was 14% at 3 years, 25% at 5 years, 40% at 10 years, and 50% at 15 years. Mortality was favorable, but pancreatic cancer accounted for death in one quarter of fatal cases.ConclusionWe clarified the current status of AIP in Japan.

BackgroundLumen-apposing metal stents (LAMSs) are increasingly used for the endoscopic management of pancreatic fluid collections (PFCs), including walled-off necrosis (WON) and pancreatic pseudocysts (PCs).ObjectiveTo evaluate the nationwide impact of implementing an LAMS (approved in Japan in 2018) on clinical outcomes in real-world settings.DesignUsing a nationwide inpatient database, we identified 5885 patients who underwent endoscopic ultrasound (EUS)-guided treatment for PFCs at 550 hospitals between 2010 and 2023. We examined the association between treatment period (pre-LAMS vs post-LAMS implementation) and clinical outcomes. Multivariable logistic and linear regression analyses were performed to estimate ORs and coefficients, respectively. Findings were validated using a multi-institutional clinical cohort (n=618) from specialty hospitals with more detailed clinical parameters with data collection during the same period.ResultsIn the pre-LAMS period, 3787 cases were treated exclusively with plastic stents. After 2018, LAMS use stabilised at around 50% among 2098 cases treated between 2019 and 2023. Compared with the pre-LAMS period, patients treated during the post-LAMS period had a higher risk of bleeding with LAMS (adjusted OR, 1.81; 95% CI: 1.55 to 2.13), but not with plastic stents (adjusted OR, 0.96; 95% CI: 0.74 to 1.26). Rates of rescue surgery, in-hospital mortality and length of stay did not differ significantly (p>0.12). The post-LAMS period was associated with increased total costs (adjusted coefficient, US$2813; 95% CI: 1503 to 4122). In analyses stratified by PFC types (WON vs PC), the association of the post-LAMS period with bleeding risk appeared to be stronger for PCs than WON (pinteraction=0.015) and WON patients had a shorter length of stay and lower total costs in the post-LAMS period (pinteraction<0.001). In the validation cohort, the elevated bleeding risk with LAMS was confirmed (adjusted OR, 1.59; 95% CI: 0.86 to 2.95, vs pre-LAMS period), though not statistically significant.ConclusionsThe implementation of LAMS was not associated with improved key clinical outcomes but was linked to a higher risk of bleeding and increased healthcare costs. These findings do not support the routine use of LAMS for EUS-guided treatment of all PFCs in standard clinical practice but may restrict it to WON cases with clear indications.

Background Procalcitonin is being increasingly used to diagnose and grade acute systemic bacterial infection at an early stage of disease onset. The aim of this prospective study was to evaluate the usefulness of procalcitonin for severity grading of acute cholangitis on patient admission. Methods Patients with acute cholangitis were prospectively enrolled. The severity of acute cholangitis was graded on the basis of the 2013 Tokyo guidelines (Japanese Society of Hepato-Biliary-Pancreatic Surgery, 2013). We compared the ability of procalcitonin level on admission to predict moderate/severe (vs mild) or severe (vs mild/moderate) acute cholangitis with the abilities of white blood cell (WBC) count and C-reactive protein (CRP) level. Results Two hundred thirteen patients were analyzed, and the severity of acute cholangitis was graded as mild, moderate, and severe in 108, 76, and 29 patients respectively. Procalcitonin level, WBC count, and CRP level all increased significantly according to the severity. In the receiver operating characteristic analyses, the area under the curve for procalcitonin for severe acute cholangitis was 0.90 [95% confidence interval (CI) 0.85–0.96] and was significantly greater than that for WBC (0.62; 95% CI 0.48–0.76) and that for CRP (0.70; 95% CI 0.60–0.80). The optimal cutoff value for procalcitonin for prediction of severe acute cholangitis was 2.2 ng/mL (sensitivity 0.97; specificity 0.73; accuracy 0.77). The areas under the curve for procalcitonin, WBC, and CRP for moderate/severe acute cholangitis were not significantly different. Conclusions Procalcitonin predicted severe acute cholangitis better than conventional biomarkers. Severe cases for which urgent biliary drainage is indicated might be identified on admission on the basis of the cutoff values for procalcitonin suggested in this study.

Cholangiocarcinoma is a life‐threatening disease with a poor prognosis. Although genome analysis unraveled some genetic mutation profiles in cholangiocarcinoma, it remains unknown whether such genetic abnormalities relate to the effects of anticancer drugs. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are exclusively found in almost 20% of intrahepatic cholangiocarcinoma (ICC). Recently, the anticancer effects of BET inhibitors including JQ1 have been shown in various tumors. In the present study, we report that the antigrowth effect of JQ1 differs among ICC cells and IDH1 mutation sensitizes ICC cells to JQ1. RBE cells harboring IDH1 mutation was more sensitive to JQ1 than HuCCT1 or HuH28 cells with wild‐type IDH1. JQ1 induced apoptosis only in RBE cells through the upregulation of proapoptotic genes BAX and BIM. We found that the antigrowth effect was not attributed to downregulation of the MYC gene as a well‐known target of JQ1 in various cancer cells. Notably, the forced expression of mutant IDH1 successfully sensitized HuCCT1 cells to JQ1. In addition, AGI‐5198, a selective inhibitor of mutant IDH1 partially reversed the decrease in viability after JQ1 treatment and also suppressed the JQ1‐induced apoptosis in RBE cells. These data suggest that IDH1 mutation contributed to the growth inhibitory effect of JQ1 in RBE cells. Furthermore, given that the effect of mutant IDH1 was not recapitulated in glioblastoma cells, the enhancement of JQ1 sensitivity by IDH1 mutation seems to be specific for ICC cells. Our findings propose a new stratified therapeutic strategy based on IDH1 mutation in ICC. Mutation of isocitrate dehydrogenase 1 (IDH1) enhanced the sensitivity of JQ1 in intrahepatic cholangiocarcinoma (ICC) cells through the induction of apoptosis. Our findings propose a new stratified therapeutic strategy based on IDH1 mutation in ICC.

BackgroundPostoperative pancreatic fluid collections (POPFCs) are common adverse events (AEs) after pancreatic surgery and may need interventions. Endoscopic ultrasound (EUS)-guided drainage for POPFCs is increasingly reported, but its appropriate timing has not been fully elucidated. The aim of this meta-analysis was to evaluate treatment outcomes of POPFCs according to the timing of EUS-guided drainage.MethodsUsing PubMed, Embase, Web of Science, and the Cochrane database, we identified clinical studies published until December 2022 with data comparing outcomes of early and delayed EUS-guided drainage for POPFCs. We pooled data on AEs, mortality, and technical and clinical success rates, using the random-effects model.ResultsFrom 1415 papers identified in the initial literature search, we identified 6 retrospective studies, including 128 and 107 patients undergoing early and delayed EUS-guided drainage for POPFCs. The threshold of early and delayed drainage ranged from 14 to 30 days. Distal pancreatectomy was the major cause of POPFCs, ranging from 44 to 100%. The pooled odds ratio (OR) for AEs was 0.81 (95% confidence interval [CI] 0.40–1.64, P = 0.55) comparing early to delayed drainage. There was no procedure-related mortality. Technical success was achieved in all cases and a pooled OR of clinical success was 0.60 (95% CI 0.20–1.83, P = 0.37).ConclusionPOPFCs can be managed by early EUS-guided drainage without an increase in AEs.

Currently, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is widely performed worldwide for various benign and malignant biliary diseases in cases of difficult or unsuccessful endoscopic transpapillary cholangiopancreatography (ERCP). Furthermore, its applicability as primary drainage has also been reported. Although recent advances in EUS systems and equipment have made EUS-HGS easier and safer, the risk of serious adverse events such as bile leak and stent migration still exists. Physicians and assistants need not only sufficient skills and experience in ERCP-related procedures and basic EUS-related procedures such as fine needle aspiration and pancreatic fluid collection drainage, but also knowledge and techniques specific to EUS-HGS. This technical review mainly focuses on EUS-HGS with self-expandable metal stents for unresectable malignant biliary obstruction and presents the latest and detailed tips for safe and successful performance of the technique.

Background Pancreatitis is one of complications after self-expandable metal stent (SEMS) placement. The purpose of this study was to evaluate risk factors for pancreatitis after endoscopic SEMS placement for malignant biliary obstruction (MBO). Methods We retrospectively reviewed 370 consecutive patients who underwent initial transpapillary SEMS placement for biliary decompression. The characteristics of inserted SEMSs were classified according to axial and radial force. Results Pancreatitis following SEMS insertion was observed in 22 patients (6%). All of them were mild according to consensus criteria. Univariate analysis indicated that injections of contrast into the pancreatic duct (frequency of pancreatitis, 10.3%), the placement of an SEMS with high axial force (8.3%), and nonpancreatic cancer (16.1%) significantly contributed to the development of pancreatitis, whereas female gender, a younger age, a covered SEMS, and a SEMS with high radial force or without a biliary sphincterotomy did not. In a multivariate risk model, SEMSs with high axial force (odds ratio [OR], 3.69; p  = 0.022) and nonpancreatic cancer (OR, 5.52; p  < 0.001) were significant risk factors for pancreatitis. Conclusions SEMSs with high axial force and an etiology of MBO other than pancreatic cancer were strongly associated with a high incidence of pancreatitis following transpapillary SEMS placement in patients with distal MBO.