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Introduction: The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with an increased risk of gallbladder and bile duct disease among patients with type 2 diabetes., Methods: We conducted a population-based cohort study using an active comparator, new-user design. We used data from the United Kingdom Clinical Practice Research Datalink to identify patients newly treated with either a DPP-4 inhibitor or sodium-glucose cotransporter-2 (SGLT-2) inhibitor between January 2013 and December 2020. We fitted Cox proportional hazards models with propensity score fine stratification weighting to estimate the hazard ratio (HR) and its 95% confidence interval (CI) for incident gallbladder and bile duct disease associated with DPP-4 inhibitors compared to SGLT-2 inhibitors., Results: DPP-4 inhibitors were associated with a 46% increased risk of gallbladder and bile duct disease (4.3 vs. 3.0 events per 1000 person-years, HR 1.46, 95% CI 1.17-1.83). At 6 months and 1 year, 745 and 948 patients, respectively, would need to be treated with DPP-4 inhibitors for one patient to experience a gallbladder or bile duct disease., Conclusions: In this population-based cohort study, the use of DPP-4 inhibitors, when compared with SGLT-2 inhibitors, was associated with a moderately increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. This outcome was still quite rare with a high number needed to harm at 6 months and 1 year., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Vanishing bile duct syndrome (VBDS) is a rare, but potentially fatal adverse reaction triggered by certain medications. Few real-world studies have shown association between antibiotics and VBDS. We sought to quantify the risk and evaluate the clinical features of VBDS associated with antibiotics., Methods: Data from 2004 to 2022 on VBDS events induced by antibiotics were retrieved from the FDA Adverse Event Reporting System (FAERS) database and disproportionality analyses were conducted. Furthermore, case reports from 2000 to 31 December 2022 on antibiotics-induced VBDS were retrieved for retrospective analysis., Results: We collected 132 VBDS reports from the FAERS database. Fluoroquinolones had the greatest proportion and highest positive signal values of VBDS. The RORs (95% CIs) for antibiotics were fluoroquinolones 23.68 (18.12-30.95), macrolides 19.37 (13.58-27.62), carbapenems 17.39 (7.77-38.96), beta-lactam 13.28 (9.69-18.20), trimethoprim/sulfamethoxazole 9.05 (5.57-14.7), and tetracycline 4.02 (1.50-10.77). Twenty-three cases from 22 studies showed evidence of VBDS, beta-lactam (52.2%) was the most frequently reported agent. The median age was 45 years, the typical initial symptoms included rash (30.4%), fatigue/asthenia (26.1%), dark urine (21.7%) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) (21.7%). The median time to onset of VBDS was 2 weeks. All cases had abnormal liver function test, and the median level of total bilirubin was 23.6 mg/dl (range 3.2-80 mg/dl). Cessation of culprit drugs and treatment with ursodeoxycholic acid (83.3%) were not associated with improved outcomes (57.1%)., Conclusion: This study identified thirteen antibacterial agents with significant reporting associations with VBDS. Fluoroquinolones may be a neglected agent of inducing VBDS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Liver and biliary disease complicates pregnancy in varying degrees of severity to the mother and fetus, and anesthesiologists may be asked to assist in caring for these patients before, during, and after birth of the fetus. Therefore, it is important to be familiar with how different liver diseases impact the pregnancy state. In addition, knowing symptoms, signs, and laboratory markers in the context of a pregnant patient will lead to faster diagnosis and treatment of such patients. This review article discusses changes in physiology of parturients, patients with liver disease, and parturients with liver disease. Next, general treatment of parturients with acute and chronic liver dysfunction is presented. The article progresses to specific liver diseases with treatments as they relate to pregnancy. And finally, important aspects to consider when anesthetizing parturients with liver disease are discussed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background: Bile duct injury and conversion-to-open-surgery rates remain unacceptably high during laparoscopic and robotic cholecystectomy. In a recently published randomized clinical trial, using near-infrared fluorescent cholangiography with indocyanine green intraoperatively markedly enhanced biliary-structure visualization. Our systematic literature review compares bile duct injury and conversion-to-open-surgery rates in patients undergoing laparoscopic or robotic cholecystectomy with versus without near-infrared fluorescent cholangiography., Methods: A thorough PubMed search was conducted to identify randomized clinical trials and nonrandomized clinical trials with ≥100 patients. Because all near-infrared fluorescent cholangiography studies were published since 2013, only studies without near-infrared fluorescent cholangiography published since 2013 were included for comparison. Incidence estimates, weighted and unweighted for study size, were adjusted for acute versus chronic cholecystitis, and for robotic versus laparoscopic cholecystectomy and are reported as events/10,000 patients. All studies were assessed for bias risk and high-risk studies excluded., Results: In total, 4,990 abstracts were reviewed, identifying 5 near-infrared fluorescent cholangiography studies (3 laparoscopic cholecystectomy/2 robotic cholecystectomy; n = 1,603) and 11 not near-infrared fluorescent cholangiography studies (5 laparoscopic cholecystectomy/4 robotic cholecystectomy/2 both; n = 5,070) for analysis. Overall weighted rates for bile duct injury and conversion were 6 and 16/10,000 in near-infrared fluorescent cholangiography patients versus 25 and 271/10,000 in patients without near-infrared fluorescent cholangiography. Among patients undergoing laparoscopic cholecystectomy, bile duct injuries, and conversion rates among near-infrared fluorescent cholangiography versus patients without near-infrared fluorescent cholangiography were 0 and 23/10,000 versus 32 and 255/10,000, respectively. Bile duct injury rates were low with robotic cholecystectomy with and without near-infrared fluorescent cholangiography (12 and 8/10,000), but there was a marked reduction in conversions with near-infrared fluorescent cholangiography (12 vs 322/10,000)., Conclusion: Although large comparative trials remain necessary, preliminary analysis suggests that using near-infrared fluorescent cholangiography with indocyanine green intraoperatively sizably decreases bile duct injury and conversion-to-open-surgery rates relative to cholecystectomy under white light alone., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The timing of cholecystectomy for acute cholecystitis has been debated with most studies favoring early cholecystectomy (< 72 h of onset). However, most reported studies are from single institution studies with only a few population-based studies. The purpose of this study is to compare clinical outcomes of patients undergoing cholecystectomy within 72 h of emergency department (ED) presentation to patients undergoing cholecystectomy following 72 h in a large statewide database., Methods: The New York SPARCS administrative database was used to identify all adult patients presenting to the ED with a diagnosis of acute cholecystitis from 2005 to 2016. Patients aged < 18, missing data, or other biliary diagnoses were excluded from the analysis. Early cholecystectomy was defined as within 72 h of presentation to the emergency department. Early vs late groups were compared in terms of overall complications, bile duct injury (BDI), hospital length of stay (LOS), 30-days ED visits and readmissions. The linear trends of yearly early/late cholecystectomies were examined using a log-linear Poisson regression models. Multivariable logistic regression model was used to compare complications, BDI, and 30-day readmission/ED visits after controlling for confounding factors. Multivariable generalized linear regression for a negative binomial distributed count data was used to compare LOS., Results: Following the application of the inclusion/exclusion criteria, there were 109,862 patients who presented to an ED with the diagnosis of acute cholecystitis. The majority of patients underwent early cholecystectomy (n = 93,761, 85.3%), whereas only 16,101 patients underwent late cholecystectomy (14.7%). There was an increasing trend of early cholecystectomy from 2005 (81.1%) to 2016 (87.8%). On multivariable regression, patients with early cholecystectomy were less likely to have complications (OR 0.542, 95% CI 0.518-0.566), had shorter LOS (ratio 0.461, 95% CI 0.458-0.465), were less likely to have 30-day readmission (OR 0.871, 95% CI 0.816-0.928), 30-day ED visits (OR 0.909, 95% CI 0.862-0.959), and bile duct injury (OR 0.654, 95% CI 0.444-0.962) compared to late cholecystectomy patients., Conclusion: Early cholecystectomy (< 72 h) is associated with fewer complications, specifically BDI, shorter LOS, and fewer 30-day readmissions and ED visits. For patients presenting to the ED for acute cholecystitis, early cholecystectomy should be preferred.

Background and Aim: Few studies have reported on a national, population-based endoscopic retrograde cholangiopancreatography (ERCP) database. Hence, in 2015, we established a multicenter ERCP database registry, the Japan Endoscopic Database (JED) Project in preparation for a nationwide endoscopic database. The objective the present study was to evaluate this registry before the establishment of a nationwide endoscopic database., Methods: From 1 January 2015 to 31 March 2017, we collected and analyzed the ERCP data of all patients who underwent ERCP in four participating centers in the JED Project based on the JED protocol., Results: Four centers carried out 4104 ERCP on 2173 patients. Data entry of ERCP information (age, 100%; gender, 100%; American Society of Anesthesiologists Physical Status Classification System, 74.5%; scope, 92.7%; time to ERCP, 100%; antithrombotic drug information, 55.0%; primary selective common bile duct [CBD] cannulation methods, 73.0%; number of attempts at primary selective CBD cannulation, 67.6%; overall selective CBD cannulation methods, 68.9%; ERCP procedure time, 66.3%; fluoroscopy time, 65.1%; adverse events, 74.9%; serum amylase levels 1 day post-ERCP, 36.5%) was accurately extracted from the four centers. Success rate of CBD cannulation by level of ERCP difficulty was 98.5%, 99.0%, and 96.4% in grades 1, 2, and 3, respectively. Complication rate by overall selective CBD cannulation method was 5.6%, 7.6%, and 10.5% in the contrast-assisted technique, guidewire-assisted technique, and cross-over method, respectively., Conclusion: Data from this evaluation of the JED Project, a multicenter ERCP database registry, suggest the feasibility of establishing a nationwide ERCP database and its challenges., (© 2019 Japan Gastroenterological Endoscopy Society.)

Background: There is a paucity of data from the developing world regarding laparoscopic cholecystectomy (LC) bile duct injuries (BDIs), despite the fact that most of the world's population live in a developing country. We assessed how referral patterns, management and outcomes after LC-BDI repair have evolved over time in patients treated at a tertiary referral center in a low and middle-income country (LMIC)., Methods: Patients with LC-BDIs requiring hepaticojejunostomy were identified from a prospective database. Clinical characteristics, geographic distance from referral hospital, timing of referral and repair, and post-operative outcomes were compared in two cohorts treated during 1991-2004 and 2005-2017., Results: Of 125 patients, 32 underwent repair in the early period, 93 in the latter. There was no difference in demographic or clinical characteristics, but a 45.6% increase in geographically distant referrals in the 2005-2017 period. Time from diagnosis to referral and referral to repair increased significantly (p = 0.031, p < 0.001), necessitating more intermediate repairs. Despite this, the number of severe complications decreased (p = 0.022) while long-term outcomes remained unchanged., Conclusion: In this study from an LMIC, geographic and logistic constraints necessitated deviation from accepted algorithms devised for well-resourced countries. When appropriately adapted, results comparable to those reported from developed countries are achievable., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The worldwide organ shortage continues to be the main limitation of liver transplantation. To bridge the gap between the demand and supply of liver grafts, it becomes necessary to use extended criteria donor livers for transplantation. Hypothermic machine perfusion (HMP) is designed to improve the quality of preserved organs before implantation. In clinical liver transplantation, HMP is still in its infancy., Methods: A systematic search of the PubMed, EMBASE, Springer, and Cochrane Library databases was performed to identify studies comparing the outcomes in patients with HMP versus static cold storage (SCS) of liver grafts. The parameters analyzed included the incidences of primary nonfunction (PNF), early allograft dysfunction (EAD), vascular complications, biliary complications, length of hospital stay, and 1-year graft survival., Results: A total of 6 studies qualified for the review, involving 144 and 178 liver grafts with HMP or SCS preservation, respectively. The incidences of EAD and biliary complications were significantly reduced with an odds ratio (OR) of 0.36 (95% confidence interval [CI] 0.17-0.77, P = .008) and 0.47 (95% CI 0.28-0.76, P = .003), respectively, and 1-year graft survival was significantly increased with an OR of 2.19 (95% CI 1.14-4.20, P = .02) in HMP preservation compared to SCS. However, there was no difference in the incidence of PNF (OR 0.30, 95% CI 0.06-1.47, P = .14), vascular complications (OR 0.69, 95% CI 0.29-1.66, P = .41), and the length of hospital stay (mean difference -0.30, 95% CI -4.10 to 3.50, P = .88) between HMP and SCS preservation., Conclusions: HMP was associated with a reduced incidence of EAD and biliary complications, as well as an increased 1-year graft survival, but it was not associated with the incidence of PNF, vascular complications, and the length of hospital stay.

Background: The incidence and several risk factors of biliary complication (BC) following pediatric liver transplantation (LT) are widely known, but data on long-term outcomes and management is limited. This retrospective study aimed to investigate the incidence, associated risk factors, management, and outcomes of early and late BC in pediatric LT., Methods: This study enrolled 134 pediatric patients (< 18 years old) who underwent LT at a tertiary care center in Taiwan between January 2001 and December 2015. Diagnosis of BC was based on clinical, biochemical, and radiologic examinations. Clinical data and chart records were reviewed and compared between the groups., Results: Among the 134 children, 21 children (15.7%) had BC after LT. Nine children had early complications, including leakage plus stricture (n = 2), stricture only (n = 2), and leakage only (n = 5). Twelve children had late BC; all of whom had anastomotic stricture. Of the 21 patients with BC, 11 patients (52.4%) were treated without surgery. The median time of first treatment for BC was 6.5 months (range, 11 days to 6.2 years). Five of the 9 patients with early complications and two of the 12 patients with late complications died of biliary tract infection. The major risk factors of BC in pediatric LT were (1) recipient age > 2 years, (2) Kasai portoenterostomy revision, and (3) hepatic artery thrombosis., Conclusions: Several risk factors of BC in pediatric LT were identified. Children with early BC appeared to have relatively unfavorable outcomes. However, late BC treated by either radiological or surgical methods appeared to have a relatively good long-term prognosis.

Biliary complication (BC) is still regarded as the Achilles' heel of a living donor liver transplantation (LDLT). This study aims to evaluate the longterm outcomes of the duct-to-duct (DD) biliary reconstruction using 7-0 suture and to identify the risk factors of BCs after LDLTs. Data of 140 LDLTs between 2006 and 2015 were analyzed. All biliary reconstructions were performed as DD anastomoses using 7-0 suture: 102 for the right lobe, 20 for the left lobe, and 18 for right posterior sector grafts. BC was defined as a bile leakage (BL) or a biliary stricture (BS), and the median follow-up time after LDLT was 65 months. A total of 19 recipients (13.5%) developed BCs (8 BLs and 16 BSs) after LDLT. The survival rates between recipients with and without BCs were 83% and 86.7%, respectively (P = 0.88). In univariate analyses, the risk factors for BC were small diameter of the graft's bile duct, long warm ischemic time, small graft-to-recipient weight ratio, and no use of external biliary stent (EBS). The graft's bile duct diameter ≤ 3 mm and no use of EBS were determined as independent risk factors (hazard ratios of 9.74 and 7.68, respectively) in multivariate analyses. The 116 recipients with EBS had no BL, 11 had BSs (9%), while 24 without EBS had 8 BLs (33%) and 5 BSs (21%). After a propensity score match between the recipients with and without EBS, the EBS group (24) developed only 1 BS (4%). In conclusion, DD anastomosis using 7-0 suture combined with EBS could provide favorable longterm outcomes after LDLT, which should thus be considered the surgical technique of choice for LDLTs., (© 2018 by the American Association for the Study of Liver Diseases.)

Diseases of the liver and biliary tree have been described with significant frequency among patients with human immunodeficiency virus (HIV), and its advanced state, acquired immunodeficiency syndrome (AIDS). Through a variety of mechanisms, HIV/AIDS has been shown to affect the hepatic parenchyma and biliary tree, leading to liver inflammation and biliary strictures. One of the potential hepatobiliary complications of this viral infection is AIDS cholangiopathy, a syndrome of biliary obstruction and liver damage due to infection-related strictures of the biliary tract. AIDS cholangiopathy is highly associated with opportunistic infections and advanced immunosuppression in AIDS patients, and due to the increased availability of highly active antiretroviral therapy, is now primarily seen in instances of poor access to anti-retroviral therapy and medication non-compliance. While current published literature describes well the clinical, biochemical, and endoscopic management of AIDS-related cholangiopathy, information on its epidemiology, natural history, and pathology are not as well defined. The objective of this review is to summarize the available literature on AIDS cholangiopathy, emphasizing its epidemiology, course of disease, and determinants, while also revealing an updated approach for its evaluation and management., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.

Background: Tuberculosis (TB) remains one of the major infectious diseases worldwide. Adverse reactions are common during TB treatment. Few reports, however, are available on treatment-related acute biliary events (ABEs), such as cholelithiasis, biliary obstruction, acute cholecystitis, and cholangitis., Methods: We first report four pulmonary TB patients who developed ABEs during anti-TB treatment. Abdominal sonography revealed multiple gall stones with dilated intrahepatic ducts in three patients and cholecystitis in one patient. To investigate the incidence of and risk factors for ABEs during anti-TB treatment, we subsequently conducted a nationwide cohort study using the National Health Insurance Research Database of Taiwan., Results: A total of 159,566 pulmonary TB patients were identified from the database between 1996 and 2010, and among them, 195 (0.12%) developed ABEs within 180 days after beginning anti-TB treatment. Logistic regression analysis revealed that the risk factors associated with ABEs are older age (relative risk [RR]: 1.32 [1.21-1.44] per 10-year increment) and diabetes mellitus (RR: 1.59 [1.19-2.13])., Conclusions: Although infrequently encountered, ABEs should be considered among patients with TB who experience abdominal discomfort with hyperbilirubinemia, especially patients who have older age or diabetes.

Living donor liver transplantation (LDLT) is a technically demanding endeavor, requiring command of the complex anatomy of partial liver grafts. We examined the influence of anatomic variation and reconstruction techniques on surgical outcomes and graft survival in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Data from 272 adult LDLT recipients (2011-2015) included details on anatomic characteristics and types of intraoperative biliary reconstruction. Associations were tested between reconstruction technique and complications, which included first biliary complication (BC; leak, stricture, or biloma) and first vascular complication (VC; hepatic artery thrombosis [HAT] or portal vein thrombosis [PVT]). Time to patient death, graft failure, and complications were estimated using Kaplan-Meier curves and tested with log-rank tests. Median posttransplant follow-up was 1.2 years. Associations were found between the type of biliary reconstruction and the incidence of VC (P = 0.03) and BC (P = 0.05). Recipients with Roux-en-Y hepaticojejunostomy had the highest probability of VC. Recipients with biliary reconstruction involving the use of high biliary radicals on the recipient duct had the highest likelihood of developing BC (56% by 1 year) compared with duct-to-duct (42% by 1 year). In conclusion, the varied surgical approaches in the A2ALL centers offer a novel opportunity to compare disparate LDLT approaches. The choice to use higher biliary radicals on the recipient duct for reconstruction was associated with more BC, possibly secondary to devascularization and ischemia. The use of Roux-en-Y biliary reconstruction was associated with VCs (HAT and PVT). These results can be used to guide biliary reconstruction decisions in the setting of anatomic variants and inform further improvements in LDLT reconstructions. Ultimately, this information may contribute to a lower incidence of technical complications after LDLT. Liver Transplantation 23 1519-1530 2017 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

Background: There is still a debate regarding the optimal management of bile duct injury following cholecystectomy. Our aim was to ascertain if delayed referral influenced clinical outcomes for patients with BDI treated in our institution., Materials and Methods: We interrogated a prospectively maintained database, including all patients with BDI (Bismuth and Strasberg classifications) post LC managed in our unit from 2000-2014. Referrals were arbitrarily defined as early (<96 h from the injury) and delayed (>96 h)., Results: 68 patients with BDI were managed. Patient demographics, referral time, level of injury and morbidity data was collected. 50 patients (77%) required a surgical bile duct reconstruction. The Early referral Group included 33 patients (52.4%) and Delayed referral group 30 (47.6%). The patients referred late had a significantly high incidence of right hepatic artery injury (23% vs. 3%) and the overall number of complications (0.0001). The average number of surgical interventions (2.5 vs 1.8, p < 0.05) and invasive procedures (4 vs. 2.5, p < 0.05) per patient was high in the late referral group. There was significant difference in the interval between BDI-to-reconstruction (median 3 vs. median 88 days, p < 0.05) and referral-to-hospital discharge (median 9 vs. median days 59, p < 0.05). On multivariate analysis only delayed referral (OR 7.58, 95% CI 2.1-26.6) and Strasberg-E injuries (OR 4.86, 95% CI 1.1-20.9) were significant., Conclusion: A late referral was associated with a higher incidence of post-treatment complications, greater need for invasive procedures and a longer recovery period. These observations support the need for early patient transfer to a tertiary institution following BDI., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: Although patient and graft survival rate has increased in recent years, biliary complications after liver transplantation are associated with significant morbidity and mortality., Methods and Materials: We reviewed the database of 1930 patients who underwent deceased donor liver transplantation between 2000 and 2013. The patients had abnormal results in liver tests, as well as fever and jaundice. Abdominal sonography was performed, and if complication was identified, the patient underwent an interventional procedure by endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography. If the complication was not resolved by the mentioned procedures, exploration of common bile duct and Roux-en-Y choledochojejunostomy or revision of Roux-en-Y choledochojejunostomy was done., Results: Our study group comprised 105 patients including 66 (63%) men and 39 (37.1%) women with a mean age of 36.7 ± 12.5 years (range: 15-66 years). Among 1930 patients, 105 (5.4%) cases presented with biliary complication after liver transplantation, of which 97 (5%) and 8 (0.4%) cases presented with biliary stricture and bile leak/biloma, respectively., Conclusion: In our study, most patients with biliary complications after liver transplantation responded to interventional procedures, with 37.1% requiring surgical exploration.

Aim: To present clinical characteristics, diagnosis and treatment strategies in elderly patients with biliary diseases., Methods: A total of 289 elderly patients with biliary diseases were enrolled in this study. The clinical data relating to these patients were collected in our hospital from June 2013 to May 2016. Patient age, disease type, coexisting diseases, laboratory examinations, surgical methods, postoperative complications and therapeutic outcomes were analyzed., Results: The average age of the 289 patients with biliary diseases was 73.9 ± 8.5 years (range, 60-102 years). One hundred and thirty-one patients (45.3%) had one of 10 different biliary diseases, such as gallbladder stones, common bile duct stones, and cholangiocarcinoma. The remaining patients (54.7%) had two types of biliary diseases. One hundred and seventy-nine patients underwent 9 different surgical treatments, including pancreaticoduodenectomy, radical resection of hilar cholangiocarcinoma and laparoscopic cholecystectomy. Ten postoperative complications occurred with an incidence of 39.3% (68/173), and hypopotassemia showed the highest incidence (33.8%, 23/68). One hundred and sixteen patients underwent non-surgical treatments, including anti-infection, symptomatic and supportive treatments. The cure rate was 97.1% (168/173) in the surgical group and 87.1% (101/116) in the non-surgical group. The difference between these two groups was statistically significant ( χ 2 = 17.227, P < 0.05)., Conclusion: Active treatment of coexisting diseases, management of indications and surgical opportunities, appropriate selection of surgical procedures, improvements in perioperative therapy, and timely management of postoperative complications are key factors in enhancing therapeutic efficacy in elderly patients with biliary diseases., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.

Background: Since the introduction of laparoscopic cholecystectomy (LC), there has been continued evolution in technique, instrumentation and postoperative management. With increased experience, LC has migrated to the outpatient setting. We asked whether increased availability and experience has impacted incidence of and indications for LC., Methods: The New York (NY) State Planning and Research Cooperative System longitudinal administrative database was utilized to identify patients who underwent cholecystectomy between 1995 and 2013. ICD-9 and CPT procedure codes were extracted corresponding to laparoscopic and open cholecystectomy and the associated primary diagnostic codes. Data were analyzed as relative change in incidence (normalized to 1000 LC patients) for respective diagnoses., Results: From 1995 to 2013, 711,406 cholecystectomies were performed in NY State: 637,308 (89.58 %) laparoscopic. The overall frequency of cholecystectomy did not increase (1.23 % increase with a commensurate population increase of 6.32 %). Indications for LC during this time were: 72.81 % for calculous cholecystitis (n = 464,032), 4.88 % for biliary colic (n = 31,124), 8.98 % for acalculous cholecystitis (n = 57,205), 3.01 % for gallstone pancreatitis (n = 19,193), and 1.59 % for biliary dyskinesia (n = 10,110). The incidence of calculous cholecystitis declined (-20.09 %, p < 0.0001) between 1995 and 2013; meanwhile, other diagnoses increased in incidence: biliary colic (+54.96 %, p = 0.0013), acalculous cholecystitis (+94.24 %, p < 0.0001), gallstone pancreatitis (+107.48 %, p < 0.0001), and biliary dyskinesia (+331.74 %, p < 0.0001). Outpatient LC incidence catapulted to 48.59 % in 2013, from 0.15 % in 1995, increasing >320-fold. Analysis of LC through 2014 revealed increasing rates of digestive, infectious, respiratory, and renal complications, with overall cholecystectomy complication rates of 9.29 %., Conclusion: A shifting distribution of operative indications and increasing rates of complications should prompt careful consideration prior to surgery for benign biliary disease. For what is a common procedure, LC carries substantial risk of complications, thus requiring the patient to be an active participant and to share in the decision-making process.

Bile duct loss during the course of drug-induced liver injury is uncommon, but can be an indication of vanishing bile duct syndrome (VBDS). In this work, we assess the frequency, causes, clinical features, and outcomes of cases of drug-induced liver injury with histologically proven bile duct loss. All cases of drug-induced liver injury enrolled into a prospective database over a 10-year period that had undergone liver biopsies (n = 363) were scored for the presence of bile duct loss and assessed for clinical and laboratory features, causes, and outcomes. Twenty-six of the 363 patients (7%) with drug-, herbal-, or dietary-supplement-associated liver injury had bile duct loss on liver biopsy, which was moderate to severe (<50% of portal areas with bile ducts) in 14 and mild (50%-75%) in 12. The presenting clinical features of the 26 cases varied, but the most common clinical pattern was a severe cholestatic hepatitis. The implicated agents included amoxicillin/clavulanate (n = 3), temozolomide (n = 3), various herbal products (n = 3), azithromycin (n = 2), and 15 other medications or dietary supplements. Compared to those without, those with bile duct loss were more likely to develop chronic liver injury (94% vs. 47%), which was usually cholestatic and sometimes severe. Five patients died and 2 others underwent liver transplantation for progressive cholestasis despite treatment with corticosteroids and ursodiol. The most predictive factor of poor outcome was the degree of bile duct loss on liver biopsy., Conclusion: Bile duct loss during acute cholestatic hepatitis is an ominous early indicator of possible VBDS, for which at present there are no known means of prevention or therapy. (Hepatology 2017;65:1267-1277)., (© 2016 by the American Association for the Study of Liver Diseases.)

INTRODUCTION Biliary-enteric anastomoses are performed for a range of indications and may result in early and late complications. The aim of this study was to assess the risk factors and management of anastomotic leak and stricture following biliary-enteric anastomosis. METHODS A retrospective analysis of the medical records of patients who underwent biliary-enteric anastomoses in a tertiary referral centre between 2000 and 2010 was performed. RESULTS Four hundred and sixty-two biliary-enteric anastomoses were performed. Of these, 347 (75%) were performed for malignant disease. Roux-en-Y hepaticojejunostomy or choledocho-jejunostomy were performed in 440 (95%) patients. Perioperative 30-day mortality was 6.5% (n=30). Seventeen patients had early bile leaks (3.7%) and 17 had late strictures (3.7%) at a median of 12 months. On univariable logistic regression analysis, younger age was a significant risk factor for biliary anastomotic leak. However, on multivariable analysis only biliary reconstruction following biliary injury (odds ratio [OR]=6.84; p=0.002) and anastomosis above the biliary confluence (OR=4.62; p=0.03) were significant. Younger age and biliary reconstruction following injury appeared to be significant risk factors for biliary strictures but multivariable analysis showed that only younger age was significant. CONCLUSIONS Biliary-enteric anastomoses have a low incidence of early and late complications. Biliary reconstruction following injury and a high anastomosis (above the confluence) are significant risk factors for anastomotic leak. Younger patients are significantly more likely to develop an anastomotic stricture over the longer term.

Up-front cholecystectomy is the recommended therapy for acute cholecystitis (AC). However, the scientific basis for the definition of the optimal timing for surgery is scarce. The aim of this study was to analyze how the timing of surgery, after the admission to hospital for AC, affects the intra- and postoperative outcomes. Within the national Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks), all patients undergoing cholecystectomy for acute cholecystitis between January 2006 and December 2014 were identified. Data regarding patient characteristics, intra- and postoperative adverse events (AEs), bile duct injuries, and 30- and 90-day mortality risk were captured, and the correlation between the surgical timing and these parameters was analyzed. In total, data on 87,108 cholecystectomies were analyzed of which 15,760 (18.1 %) were performed due to AC. Bile duct injury, 30- and 90-day mortality risk, and intra- and postoperative AEs were significantly higher if the time from admission to surgery exceeded 4 days. The time course between surgery and complication risks seemed to be optimal if surgery was done within 2 days after hospital admission. Although AC patients operated on the day of hospital admission had a slightly increased AE rate as well as 30- and 90-day mortality rates than those operated during the interval of 1-2 days after admission, the bile duct injury and conversion rates were, in fact, significantly lower. The optimal timing of cholecystectomy for patients with AC seems to be within 2 days after admission. However, the somewhat higher frequency of AE on admission day may emphasize the importance of optimizing the patient before surgery as well as ensuring that adequate surgical resources are available., Competing Interests: Compliance with Ethical StandardsConflict of InterestThe authors declare that they have no conflict of interest.Author contributionsMB, JÖ, GS, and LE conceived of the study and design the study. MB and LE performed the data acquisition. MB, JÖ, GS, MH, LL, and LE performed the quality control of data and algorithms. MB, JÖ, MH, and LE performed the data analysis and interpretation, GS and LE performed the statistical analysis. MB, JÖ, GS, LL, MH, and LE prepared, edited, and reviewed the manuscript. All authors have approved of the final draft submitted.

Importance: The use of dipeptidyl-peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) analogues-a group of drugs used in the management of type 2 diabetes mellitus-may be associated with an increased risk of bile duct and gallbladder disease. To date, no observational study has assessed this possible association., Objective: To determine whether the use of DPP-4 inhibitors and GLP-1 analogues is associated with an increased risk of incident bile duct and gallbladder disease in patients with type 2 diabetes., Design, Setting, and Participants: A population-based cohort study linked the United Kingdom Clinical Practice Research Datalink with the Hospital Episodes Statistics database, yielding a cohort of 71 369 patients, 18 years or older, initiating an antidiabetic drug (including oral and injectable agents) between January 1, 2007, and March 31, 2014., Exposures: Current use of DPP-4 inhibitors and GLP-1 analogues (alone or in combination therapy) compared with current use of at least 2 oral antidiabetic drugs., Main Outcomes and Measures: Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs of incident bile duct or gallbladder events (cholelithiasis, cholecystitis, cholangitis) causing hospitalization, comparing current use of DPP-4 inhibitors and GLP-1 analogues with current use of at least 2 oral antidiabetic drugs., Results: During 227 994 person-years of follow-up, 853 of the 71 369 patients were hospitalized for bile duct and gallbladder disease (incidence rate per 1000 person-years, 3.7; 95% CI, 3.5-4.0). Current use of DPP-4 inhibitors was not associated with an increased risk of bile duct and gallbladder disease compared with current use of at least 2 oral antidiabetic drugs (3.6 vs 3.3 per 1000 person-years; adjusted HR, 0.99; 95% CI, 0.75-1.32). In contrast, the use of GLP-1 analogues was associated with an increased risk of bile duct and gallbladder disease compared with current use of at least 2 oral antidiabetic drugs (6.1 vs 3.3 per 1000 person-years; adjusted HR, 1.79; 95% CI, 1.21-2.67). In a secondary analysis, GLP-1 analogues were also associated with an increased risk of cholecystectomy (adjusted HR, 2.08; 95% CI, 1.08-4.02)., Conclusions and Relevance: The use of GLP-1 analogues was associated with an increased risk of bile duct and gallbladder disease. Physicians should be aware of this potential adverse event when prescribing these drugs.

Bile duct is usually sterile, and the isolating of microorganisms (bacteriobilia) has been related to some factors, such as age, biliary drainage before pancreatic surgery or bile duct stones. Gramnegative strains remain the most frequent pathogens, especially Escherichia coli. Among grampositives Enterococcus spp should be mentioned. Currently, there is controversy about whether the presence of bacteriobilia has an impact on unfavorable outcome of biliary disease or surgical procedures or mortality rates, with complications such as surgical site infections or bacteremia. In high-risk patients, such as immunosuppressed or those underwent pancreaticoduodenectomy, bile duct cultures performed routinely, even if there are not clinical data of infection, could be necessary in order to start antibiotic treatment or to reduce its spectrum.

Introduction: Predicting the clinical course of primary sclerosing cholangitis (PSC) is difficult. There are currently a paucity of studies evaluating serum chemistries as predictors of conventional clinical endpoints. The purpose of this study was to prognosticate key clinical endpoints in patients with PSC who had elevated serum liver chemistries at the time of their initial presentation., Methods: We performed a retrospective cohort study of PSC patients at our institution. The aim of our study was to determine the association between elevated liver chemistries at initial presentation-bilirubin, alanine transaminase, aspartate transaminase, or alkaline phosphatase-with a primary outcome of either cholangiocarcinoma, liver transplantation, death, or composite of the 3. The secondary endpoints examined were development of severe biliary ductal disease and need for biliary stent placement., Results: Eighty-one PSC patients (61 males and 20 females) were included in this study. By univariate analysis, there was a significant association between initial bilirubin elevation >2x the upper limit of normal (ULN) and death (P<0.009). Multivariate regression analysis revealed that an elevated initial serum total bilirubin >2xULN (P<0.017) significantly predicted the composite endpoint. By univariate analysis of pre-endoscopic retrograde cholangiopancreatography labs, serum bilirubin level elevation >2xULN showed an association with severity of biliary ductal disease (P<0.0001). A logistic regression of outcome variables also proved that >2xULN serum bilirubin levels predicted the ductal disease severity (P<0.0001)., Conclusions: An initial elevation of serum total bilirubin >2xULN in PSC patients correlates positively with the development of cholangiocarcinoma, subsequent liver transplantation, and death. Elevated bilirubin also correlates positively with the severity of cholangiographic findings.

Background: The primary focus of the study was to analyze the risk factors for bile leakage after hepatectomy for benign or malignant tumors., Methods: A total of 411 patients who had undergone hepatectomy between December 2006 and December 2011 were retrospectively analyzed. The severity of bile leakage was graded according to the ISGLS classification. Twenty-eight pre- and postoperative parameters were analyzed., Results: The overall bile leakage incidence was 10.2% (42/411). The severity of the leakage was classified according to the ISGLS classification. Bile leakage was detected early in case of abdominal drainage (11.4% vs 1.9%, P=0.034). It prolonged the time of hospitalization (16 vs 9 days, P=0.001). In all patients, wedge resection was associated with a higher incidence of bile leakage in contrast to anatomical resections (25.6% vs 4.1%, P<0.0001) regardless of the underlying liver disease. Furthermore, total vascular exclusion increased risk of bile leakage (P=0.008)., Conclusions: Bile leakage as a major issue after hepatic resection is related to the postoperative morbidity and the hospitalization time. It is associated with non-anatomical resection and a total vascular exclusion.

Background: The biliary anastomosis remains to be the Achilles' heel of liver transplantation. The incidence of biliary complications (e.g., stenosis and leakage) is immanent and the optimal type of reconstruction is unclear. The aim of this study was to compare 2 different bile duct suture techniques regarding their benefits in the prevention of biliary complications., Material and Methods: From 1992 to 2012, the transplanted patients (n=394) of our center were analyzed retrospectively in terms of suture techniques and consecutive biliary complications. Secondary, possible risk factors (cold ischemic time, donor age, and preoperative liver function) were examined. An end-to-end choledocho-choledochostomy without T-tube was performed during orthotopic liver transplantation whenever possible. In group 1 (n=123) the biliary reconstruction was performed completely by continuous-suture technique. In group 2 (n=164) continuous-suture technique was also performed in posterior wall of the bile duct, but the anterior wall was closed by interrupted-suture technique., Results: The overall biliary complication rate was 19.6%. There were no significant differences in biliary complications between the groups. Analysis of risk factors showed no influence on the complication rate., Conclusions: The argument for the interrupted-suture technique is a better overview and a lower risk to grab the posterior wall during the anastomotic realization. The threads of the anterior wall can be presented individually and then be knotted.

Purpose: Cholecystectomy in patients with an intact gallbladder after endoscopic removal of stones from the common bile duct (CBD) remains controversial. We conducted a case-control study to determine the risk of recurrent CBD stones and the benefit of cholecystectomy for prevention of recurrence after endoscopic removal of stones from the CBD in Korean patients., Materials and Methods: A total of 317 patients who underwent endoscopic CBD stone extraction between 2006 and 2012 were included. Possible risk factors for the recurrence of CBD stones including previous cholecystectomy history, bile duct diameter, stone size, number of stones, stone composition, and the presence of a periampullary diverticulum were analyzed., Results: The mean duration of follow-up after CBD stone extraction was 25.4±22.0 months. A CBD diameter of 15 mm or larger [odds ratio (OR), 1.930; 95% confidence interval (CI), 1.098 to 3.391; p=0.022] and the presence of a periampullary diverticulum (OR, 1.859; 95% CI, 1.014 to 3.408; p=0.045) were independent predictive factors for CBD stone recurrence. Seventeen patients (26.6%) in the recurrence group underwent elective cholecystectomy soon after endoscopic extraction of CBD stones, compared to 88 (34.8%) in the non-recurrence group; the difference was not statistically significant (p=0.212)., Conclusion: A CBD diameter of 15 mm or larger and the presence of a periampullary diverticulum were found to be potential predictive factors for recurrence after endoscopic extraction of CBD stones. Elective cholecystectomy after clearance of CBD stones did not reduce the incidence of recurrent CBD stones in Korean patients.

Purpose: To investigate the incidence, complications, and risk factors of the migration of internal pancreaticojejunostomy (PJ) stents into the bile ducts in patients undergoing pancreatoduodenectomy., Methods: Postoperative computed tomography (CT) and clinical data of 802 patients with CT-detectable internal PJ stents were reviewed to assess the occurrence of stent migration into the bile ducts and stent-induced complications with their clinical significance. Risk factors for stent migration and stent-induced complications were determined., Results: Stent migration into the bile ducts occurred in 135 patients (16.8 %); 40 of these (29.6 %) showed stent-induced complications including bile duct stricture, stone, and liver abscess. Clinically significant complications were identified in only eight patients. Neither the stent length nor diameter was associated with stent migration. A small stent diameter, peripheral location of the stent, absence of stent remigration from the bile ducts to the intestine, and longer stent retention time in the bile ducts were risk factors of stent-induced complications., Conclusions: The incidence of internal PJ stent migration into the bile ducts was 16.8 %. Migrated stents frequently caused complications, although they were mostly subclinical. Stent-induced complications were associated with stent diameter and location, stent remigration to the intestine, and stent retention time in the bile ducts.

This meta-analysis aimed to compare outcomes following bile duct reconstruction in patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation depending on whether duct-to-duct or Roux-en-Y anastomosis was utilized. An electronic search was performed of the MEDLINE, EMBASE, PubMed databases using both subject headings (MeSH) and truncated word searches. Pooled risk ratios and mean difference were calculated using the fixed-effects and random-effects models for meta-analysis. Ten studies including 910 patients met the inclusion criteria. There was no difference in the overall incidence of biliary strictures between the two groups [odds ratio (OR) 1.06 (0.68, 1.66); (P = 0.80)]. The anastomotic stricture rate was similar, [OR 1.18 (0.56, 2.50); (P = 0.67)]. Ascending cholangitis was higher in the Roux-en-Y group [OR 2.91 (1.17, 7.23); (P = 0.02)]. Anastomotic bile leak rates, graft survival, PSC recurrence and number of patients diagnosed with cholangiocarcinoma following transplantation were comparable between both groups. Duct-to-duct and Roux-en-Y reconstruction had comparable outcomes. Both techniques are associated with similar incidence of biliary stricture. The bilioenteric reconstruction was associated with a higher risk of cholangitis. The incidence of de novo cholangiocarcinoma was similar in both groups. Duct-to-duct reconstruction should be considered when feasible in patients with PSC., (© 2015 Steunstichting ESOT.)

Background: With the popularity of endoscopic sphincterotomy (EST), long-term complications of EST are receiving increasingly more attention, but the mechanisms have not been sufficiently elucidated., Aim: This study aimed to investigate the relationship between long-term complications of EST and sphincter of Oddi (SO) function and other associated risk factors., Patients and Methods: A total of 139 patients with choledocholithiasis who had undergone EST were consecutively enrolled, and divided into two groups: patients with long-term complications (LC group) and patients without complications (control group). Before and 2 years after EST, sphincter of Oddi manometry and bacterial culture were performed to evaluate the functional change in SO and infection of the biliary duct., Results: With an average follow-up duration of 45.8 months, 25 (18.0%) patients developed long-term complications (LC group). Compared with before EST, contraction amplitude and frequency of SO in both groups were markedly reduced after EST, but the changes were not significantly different between the two groups (P>0.05). The rates of bacterial infection in the biliary tract increased significantly in the LC group compared with the control group after EST: 57.1% (12/21) versus 32.7% (35/107), respectively (P=0.034), although these were similar before EST in both the groups. Logistic regression analysis showed that cholecystolithiasis, common bile duct diameter 15 mm or more, and maximum stone diameter 15 mm or more were major risk factors for long-term complications., Conclusion: Weakened SO function is not a decisive factor for long-term complications of EST, which were mainly influenced by biliary tract infection and high risk factors of the biliary tract.

The aim of this study was to review the clinical, radiographic, and pathologic features of cases of benign segmental cholangiectasia in non-Asian US patients with clinical concern for cholangiocarcinoma and compare these features with cases of recurrent pyogenic cholangitis (RPC) in Asian patients. A total of 10 non-Asian US patients with benign segmental cholangiectasia were included in this study. Nine of them underwent partial hepatic resection due to cholangiographic findings of segmental cholangiectasia with mural thickening and/or proximal biliary stricture. One was found to have markedly dilated and thickened intrahepatic bile ducts at the time of autopsy. Clinical and radiographic findings were reviewed. Elastin stains and immunostains for immunoglobulin G4, cluster of differentiation (CD1a), and Langerin were performed. Six comparison cases of RPC in Asian US patients were also examined. Histologic examination of resection specimens revealed markedly dilated large intrahepatic bile ducts with variable degrees of mural fibrosis, periductal gland hyperplasia, inflammation, and liver parenchymal atrophy. These changes were not associated with a ductular reaction. There was no evidence of biliary dysplasia or biliary cirrhosis in any cases. No gross or microscopic feature definitively separated the Asian from non-Asian patients. The etiology of this disorder in non-Asian US patients is unclear. It does not appear to represent a localized variant of Caroli disease or primary sclerosing cholangitis. The high degree of similarity shared by these cases and classic RPC suggests a common pathogenic mechanism, although the pathologic features tend to be less well developed in the cases from the non-Asian US patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first-year posttransplant from IC. Our program has almost exclusively utilized either anti-thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Quality of life after bile duct injury is a relevant health issue besides physician-oriented outcomes. A prospective study was performed to explore short- and long-term outcomes after surgical repair., Method: We studied a cohort of patients with Strasberg E injuries who underwent Roux-en-Y jejunal anastomosis from 1990 to 2008. The Short Form Health Survey (SF-36) was selected as the appropriate quality of life assessment instrument. Two groups were comprised: Group I included patients with 10-year follow-up after surgery. Group II included patients operated during 2008 with preoperative 1- and 5-year questionnaires., Results: Group I patients (N = 41) were operated from 1990 to 2003 and Group II (N = 44) during 2008. There is a significant improvement in quality of life after the first year of repair in all domains. Readmissions (48 vs 25 %; p < 0.01), colangitis (46 vs 14 %; p < 0.001), and hepatojejunal redo (26 vs. 4 %; p < 0.0001) were less frequent in Group II. No differences in quality of life summary scores were found between Group I and II., Conclusions: Quality of life improves significantly after the first year of surgical repair, reaching a plateau at 5 years. No correlation exists with physician-centered outcomes.

Ischemic-type biliary lesions (ITBLs) are now a discussed cause of morbidity and mortality in liver transplant recipients, even if not definitively characterized. We reviewed 13 years of donor and recipient data between April 2001 and April 2013. We evaluated the incidence of ITBL occurrence, exploring the possible predisposing factors, focusing on the relationship between severe macrovesicular steatosis of the graft and incidence of ITBL. A total of 445 grafts were harvested: 416 of them were transplanted at our institution, the remaining 29 were discarded by our donor team as showing more than 40% macrovesicular steatosis. Mild-moderate (20% to 40%) macrovesicular steatosis (P<.001) and cold ischemia time (P=.048) significantly increased the risk of ITBLs, also resulting in independent risk factors at multivariate analysis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Androgen-deprivation therapy (ADT) by either a gonadotropin-releasing hormone (GnRH) agonist or bilateral orchiectomy improves disease-related outcomes of men with prostate cancer but has a variety of adverse metabolic effects including obesity, increased abdominal girth, increased triglycerides, and insulin resistance. Each is a risk factor for gallstone disease. Additionally, GnRH agonist treatment was recently shown in metabolomic analyses to increase plasma levels of some bile acids., Objective: To assess the relationship between ADT and the incidence of biliary disease in men with prostate cancer., Design, Setting, and Participants: We studied 183 842 men >65 yr of age living in Surveillance, Epidemiology, and End Results regions who were diagnosed with prostate cancer from 1992 to 2007 and followed through 2009., Outcome Measurements and Statistical Analysis: We calculated incidence rates for biliary disease during treatment with GnRH agonists, orchiectomy, or no therapy. We used Cox proportional hazard models to assess the association of ADT with biliary disease., Results and Limitations: Among 183 842 men with locoregional prostate cancer, 48.4% received GnRH agonist treatment and 2.2% underwent bilateral orchiectomy during follow-up. GnRH agonist treatment was associated with a significantly higher incidence of biliary disease compared with no treatment (15.7 vs 13.4 cases per 1000 person-years; p<0.001). In adjusted analyses, GnRH agonist use was associated with the risk of biliary disease (adjusted hazard ratio: 1.10; 95% confidence interval, 1.05-1.15; p<0.001). Orchiectomy was not significantly associated with biliary disease., Conclusions: GnRH agonist treatment may be associated with a greater risk of incident biliary disease., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the operative outcomes of early and delayed cholecystectomy for acute cholecystitis., Background: Randomized trials comparing early to delayed cholecystectomy for acute cholecystitis have limited contemporary external validity. Furthermore, no study to date has been large enough to assess the impact of timing of cholecystectomy on the frequency of serious rare complications including bile duct injury and death., Methods: This is a population-based retrospective cohort study of patients emergently admitted to hospital with acute cholecystitis and managed with cholecystectomy over the period of April 1, 2004, to March 31, 2011. We used administrative records for the province of Ontario, Canada. Patients were divided into 2 exposure groups: those who underwent cholecystectomy within 7 days of emergency department presentation on index admission (early cholecystectomy) and those whose cholecystectomy was delayed. The primary outcome was major bile duct injury requiring operative repair within 6 months of cholecystectomy. Secondary outcomes included major bile duct injury or death, 30-day postcholecystectomy mortality, completion of cholecystectomy with an open approach, conversion among laparoscopic cases, and total hospital length of stay. Propensity score methods were used to address confounding by indication., Results: From 22,202 patients, a well-balanced matched cohort of 14,220 patients was defined. Early cholecystectomy was associated with a lower risk of major bile duct injury [0.28% vs 0.53%, relative risk (RR)=0.53, 95% confidence interval [CI]: 0.31-0.90], of major bile duct injury or death (1.36% vs 1.88%, RR=0.72, 95% CI: 0.56-0.94), and, albeit non-significant, of 30-day mortality (0.46% vs 0.64%, RR=0.73, 95% CI: 0.47-1.15). Total hospital length of stay was shorter with early cholecystectomy (mean difference 1.9 days, 95% CI: 1.7-2.1). No significant differences were observed in terms, open cholecystectomy (15% vs 14%, RR=1.07, 95% CI: 0.99-1.16) or in conversion among laparoscopic cases (11% vs 10%, RR=1.02, 95% CI: 0.93-1.13)., Conclusions: These results support the benefit of early overdelayed cholecystectomy for patients with acute cholecystitis.

Background: After hepatectomy, bile leaks remain a major cause of morbidity, cost, and disability. This study was designed to determine if a novel intraoperative air leak test (ALT) would reduce the incidence of post-hepatectomy biliary complications., Study Design: Rates of postoperative biliary complications were compared among 103 patients who underwent ALT and 120 matched patients operated on before ALT was used. All study patients underwent major hepatectomy without bile duct resection at 3 high-volume hepatobiliary centers between 2008 and 2012. The ALT was performed by placement of a transcystic cholangiogram catheter to inject air into the biliary tree, the upper abdomen was filled with saline, and the distal common bile duct was manually occluded. Uncontrolled bile ducts were identified by localization of air bubbles at the transection surface and were directly repaired., Results: The 2 groups were similar in diagnosis, chemotherapy use, tumor number and size, resection extent, surgery duration, and blood loss (all, p > 0.05). Single or multiple uncontrolled bile ducts were intraoperatively detected and repaired in 62.1% of ALT vs 8.3% of non-ALT patients (p < 0.001). This resulted in a lower rate of postoperative bile leaks in ALT (1.9%) vs non-ALT patients (10.8%; p = 0.008). Independent risk factors for postoperative bile leaks included extended hepatectomy (p = 0.031), caudate resection (p = 0.02), and not performing ALT (p = 0.002) (odds ratio = 3.8; 95% CI, 1.3-11.8; odds ratio = 4.0; 95% CI, 1.1-14.3; and odds ratio = 11.8; 95% CI, 2.4-58.8, respectively)., Conclusions: The ALT is an easily reproducible test that is highly effective for intraoperative detection and repair of open bile ducts, reducing the rate of postoperative bile leaks., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnancy. We aimed to estimate the risk of developing hepatobiliary disease in women with ICP and the odds of developing ICP in women with prevalent hepatobiliary disease. We analyzed data of women with births between 1973 and 2009 and registered in the Swedish Medical Birth Register. By linkage with the Swedish Patient Register, we identified 11,388 women with ICP who were matched to 113,893 women without this diagnosis. Diagnoses of preexisting or later hepatobiliary disease were obtained from the Patient Register. Main outcome measures were hazard ratios (HRs) for later hepatobiliary disease in women with ICP and odds ratios (ORs) for developing ICP in preexisting hepatobiliary disease. Risk estimates were calculated through Cox and logistic regression analyses. Women with ICP were more often diagnosed with later hepatobiliary disease (HR 2.62; 95% confidence interval [CI] 2.47-2.77; increment at 1% per year), hepatitis C or chronic hepatitis (HR 4.16; 3.14-5.51 and 5.96; 3.43-10.33, respectively), fibrosis/cirrhosis (HR 5.11; 3.29-7.96), gallstone disease or cholangitis (HR 2.72; 2.55-2.91, and 4.22; 3.13-5.69, respectively) as compared to women without ICP (P < 0.001 for all HRs). Later ICP was more common in women with prepregnancy hepatitis C (OR 5.76; 1.30-25.44; P = 0.021), chronic hepatitis (OR 8.66; 1.05-71.48; P = 0.045), and gallstone disease (OR 3.29; 2.02-5.36; P < 0.0001)., Conclusion: Women with ICP have substantially increased risk for later hepatobiliary disease. Beyond gallstone-related morbidity we found a strong positive association between ICP and hepatitis C both before and after ICP diagnosis. Thus, we advocate testing for hepatitis C in women with ICP, in particular, since this potentially life-threatening infection can be treated successfully in the majority of patients., (Copyright © 2013 by the American Association for the Study of Liver Diseases.)

Objective: Multiple biliary hamartomas (MBHs) are rare benign malformations of the intrahepatic bile ducts. There are only a handful of clinical studies based on large populations on the incidence of MBHs., Materials and Methods: A series of 1697 consecutive liver needle biopsies was examined for the occurrence of MBHs., Results: A total of six patients (0.35%, four men and two women, a 2 : 1 ratio) were confirmed by histology to have MBHs. Of the total of 1697 patients, 59 (3.5%) patients were younger than 18 years of age, 828 patients (48.8%) were between 18 and 38 years of age, and 810 patients (47.7%) were older than 38 years of age. Of the six MBHs patients, one was 17 years of age and the other five patients were older than 39 years of age. The median (range) age of the patients was 42 (17-63) years. Although nearly half (48.8%) of the biopsied patients were between 18 and 38 years of age, no MBH was found in this group. All MBHs patients were diagnosed with fibrosis/cirrhosis by initial ultrasound scanning; however, only two patients were confirmed to have cirrhosis by histological examination. Of those two patients with cirrhosis, one had concomitant congenital hepatic fibrosis and the other had concomitant cirrhotic hepatitis B. The latter patient developed hepatocellular carcinoma 1 year after biopsy. No kidney cysts were found in any of the six MBHs patients. MRI scanning was performed in four patients and the results were consistent with the histological diagnosis., Conclusion: MBHs are not common in patients who undergo liver biopsy and, in this study, the occurrence was higher in the older age group.

Introduction: Pancreaticobiliary maljunction (PBM) is a congenital anomaly, which can be defined as a union of the pancreatic and biliary ducts located outside off the duodenal wall. We herein investigate clinical features of PBM including as the 2nd report of a Japanese nationwide survey., Patients and Methods: During a period of 18 years (from 1990 to 2007), 2,561 patients with PBM were registered at 141 medical institutions in Japan. Among them, eligible patients (n = 2,529) were divided into two groups: adult (n = 1,511) and pediatric patients (n = 1,018). Comparisons of clinical features including associated biliary cancers were performed according to the biliary dilatation (BD), age factor, and time era., Results: Only one case in pediatric patients with BD combined with a bile duct cancer (0.1 %). In adult patients, the bile duct cancer and the gallbladder cancer was seen in 6.9 and 13.4 % patients with BD and in 3.1 and 37.4 % patients without BD, respectively. In adult patients with BD, the occurrence rates of biliary cancers were increased in latter period (00'-07') compared with former period (90'-99'). The ratio of biliary cancer localization was changed between former and latter period, and the bile duct cancer was increased in latter period (from 5.5 to 9.3 %)., Conclusions: The largest series of PBM were evaluated to clarify the clinical features including the associated biliary cancer in this Japan-nationwide survey. This report could be widely used in the future as a reference data for diagnosis and treatment of PBM.

Background: Natural catastrophes increase infectious disease morbidity rates. On March 11, 2011, a 9.0-magnitude earthquake and associated Pacific coast tsunami struck East Japan. The aim of this study was to investigate the characteristics of patients with infectious diseases who needed hospitalization after this disaster., Methods: We searched the medical records of 1,577 patients admitted to Tohoku University Hospital in the Sendai area within 1 month (March 11, 2011-April 11, 2011) after the disaster. We examined (1) changes in the rates of hospitalizations for infectious diseases over time and (2) the variety of infectious diseases., Results: The number of hospitalized patients with infectious diseases increased after the fi rst week to double that during the same period in 2010. Pneumonia comprised 43% of cases, and 12% consisted of skin and subcutaneous tissue infection, including tetanus. Pneumonia was prevalent in elderly patients (median age, 78 years) with low levels of serum albumin and comorbid conditions, including brain and nervous system disorders. Sputum cultures contained Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae , known pathogens of community-acquired pneumonia in Japan. In addition, 20.5% of patients had positive results for urinary pneumococcal antigen., Conclusions: Among hospitalized patients, infectious diseases were significantly increased after the disaster compared with the same period in 2010, with pneumonia being prominent. The analyses suggest that taking appropriate measures for infectious diseases, including pneumonia, may be useful for disaster preparedness and medical response in the future.

Aim: To determine the outcome of patients with biliary fistula (BF) after treatment for hydatid disease of the liver., Methods: Between January 2000 and December 2010, out of 301 patients with a diagnosis of hydatid cyst of the liver, 282 patients who underwent treatment [either surgery or puncture, aspiration, injection and reaspiration (PAIR) procedure] were analysed. Patients were grouped according to the presence or absence of postoperative biliary fistula (PBF) (PBF vs no-PBF groups, respectively). Preoperative clinical, radiological and laboratory characteristics, operative characteristics including type of surgery, peroperative detection of BF, postoperative drain output, morbidity, mortality and length of hospital stays of patients were compared amongst groups. Multivariate analysis was performed to detect factors predictive of PBF. Receiver operative characteristics (ROC) curve analysis were used to determine ideal cutoff values for those variables found to be significant. A comparison was also made between patients whose fistula closed spontaneously (CS) and those with intervention in order to find predictive factors associated with spontaneous closure., Results: Among 282 patients [median (range) age, 23 (16-78) years; 77.0% male]; 210 (74.5%) were treated with conservative surgery, 33 (11.7%) radical surgery and 39 (13.8%) underwent percutaneous drainage with PAIR procedure A PBF developed in 46 (16.3%) patients, all within 5 d after operation. The maximum cyst diameter and preoperative alkaline phosphatase levels (U/L) were significantly higher in the PBF group than in the no-PBF group [10.5 ± 3.7 U/L vs 8.4 ± 3.5 U/L (P < 0.001) and 40.0 ± 235.1 U/L vs 190.0 ± 167.3 U/L (P = 0.02), respectively]. Hospitalization time was also significantly longer in the PBF group than in the no-PBF group [37.4 ± 18.0 d vs 22.4 ± 17.9 d (P < 0.001)]. A preoperative high alanine aminotransferase level (> 40 U/L) and a peroperative attempt for fistula closure were significant predictors of PBF development (P = 0.02, 95%CI: -0.03-0.5 and P = 0.001, 95%CI: 0.1-0.4), respectively. Comparison of patients whose PBF CS or with biliary intervention (BI) revealed that the mean diameter of the cyst was not significantly different between CS and BI groups however maximum drain output was significantly higher in the BI group (81.6 ± 118.1 cm vs 423.9 ± 298.4 cm, P < 0.001). Time for fistula closure was significantly higher in the BI group (10.1 ± 3.7 d vs 30.7 ± 15.1 d, P < 0.001). The ROC curve analysis revealed cut-off values of a maximum bilious drainage < 102 mL and a waiting period of 5.5 postoperative days for spontaneous closure with the sensitivity and specificity values of (83.3%-91.1%, AUC: 0.90) and (97%-91%, AUC: 0.95), respectively. The multivariate analysis demonstrated a PBF drainage volume < 102 mL to be the only statistically significant predictor of spontaneous closure (P < 0.001, 95%CI: 0.5-1.0)., Conclusion: Patients with PBF after hydatid surgery often have complicated postoperative course with serious morbidity. Patients who develop PBF with an output < 102 mL might be managed expectantly.

To study the prevalence and risk factors of digestive diseases in children performed continuous screening questionnaire 786 children from 1.5 to 7 years. Were Revealed that 47.1 +/- 3.5% of children have symptoms of diseases of the gastrointestinal tract and biliary system. This symptoms occur in children aged 4 to 7 years in 2.3 times more frequently than in children from 1.5 to 3 years. In-depth study was revealed that the frequency of biliary dyskinesia (BD) was 33 +/- 3.3%, chronic gastritis (CG) and gastroduodenitis (CGD)--6.2 +/- 1.8%, chronic cholecystitis--4.2 +/- 1.4%, functional disorders of the stomach (FSD)--2.8 +/- 1.2%, and peptic duodenal ulcer (DU)--0.3 + 0.4%. In the structure of digestive diseases in children from 1.5 to 7 years on the 1st place are BD--70% on the 2nd--CG and CGD--14.7% on the 3rd chronic cholecystitis--8.9%, on the 4th FSD-5.9% and 5th place DU-0.5%. For dispensary observation in the children's clinic with digestive diseases consist of only 7.9 +/- 1.9% of children, which is 5.9 times lower than according to the active diagnostics data. The leading medical and social risk factors and their complex influence on the formation of digestive disorders in infants and preschool children.

Introduction: Living donor liver transplantation (LDLT) is an effective treatment for patients with terminal chronic liver disease, despite the high incidence of biliary complications. The objective is to evaluate the results and long-term impact of biliary complications after THDV., Patients and Methods: From 2000 to 2010, 70 right lobe LDLT were performed. Biliary complications (leakage and stenosis) of the 70 LDLT recipients were collected prospectively and analyzed retrospectively., Results: A total of 39 patients (55.7%) had some type of biliary complication. Twenty nine presented a leak, and of these, 14 subsequently developed a stricture. In addition, 10 patients had a stenosis without prior leakage. The median time to onset of stenosis was almost a year. Patients with previous biliary leakage were more likely to develop stenosis (58% vs. 29.5% at 5 years, P=.05). With a median follow up of 80 months, 70.8% of patients were successfully treated by interventional radiology. After excluding early mortality, there were no differences in survival according to biliary complications. A decrease of biliary complications was observed in the last 35 patients compared with the first 35., Conclusions: LDLT is associated with a high incidence of biliary complications. However, long-term outcome of patients is not affected. After a median follow-up time of nearly seven years, no differences were found in survival according to the presence of biliary complications., (Copyright © 2012 AEC. Published by Elsevier España, S.L. All rights reserved.)

Background: Advances in technique, technology, and perioperative care have allowed for the more frequent performance of complex and extended hepatic resections. The purpose of this study was to determine if this increasing complexity has been accompanied by a rise in liver-related complications., Methods: A large prospective single-institution database of patients who underwent hepatic resection was used to identify the incidence of liver-related complications. Liver resections were divided into an early era and a late era with equal number of patients (surgery performed before or after 18 May 2006). Patient characteristics and perioperative factors were compared between the two groups., Results: Between 1997 and 2011, 2,628 hepatic resections were performed, with a 90-day morbidity and mortality rate of 37 and 2 %, respectively. We identified higher rates of repeat hepatectomy (12.2 vs 6.1 %; p < 0.001), two-stage resection (4.0 vs 1 %; p < 0.001), extended right hepatectomy (17.6 vs 14.6 %; p = 0.04), and preoperative portal vein embolization (9.1 vs 5.9 %; p < 0.001) in the late era. The incidence of perihepatic abscess (3.7 vs 2.1 %; p = 0.02) and hemorrhage (0.9 vs 0.3 %; p = 0.045) decreased in the late era and the incidence of hepatic insufficiency (3.1 vs 2.6 %; p = 0.41) remained stable. In contrast, the rate of bile leak increased (5.9 vs 3.7 %; p = 0.011). Independent predictors of bile leak included bile duct resection, extended hepatectomy, repeat hepatectomy, en bloc diaphragmatic resection, and intraoperative transfusion., Conclusions: The complexity of liver surgery has increased over time, with a concomitant increase in bile leak rate. Given the strong association between bile leak and other poor outcomes, the development of novel technical strategies to reduce bile leaks is indicated.

Background/purpose: Hepaticojejunostomy is a well-accepted method, whereas duct-to-duct anastomosis is gaining popularity for bile duct reconstruction in pediatric living donor liver transplantation (LDLT). Biliary complications, especially biliary anastomotic stricture (BAS), are not clearly defined. The aim of the present study is to determine the rate of BAS and its associated risk factors., Methods: The study included 78 pediatric patients (<18 years old) who underwent LDLT during the period from end of September 1993 to end of November 2010. The diagnosis of BAS was based on clinical, biochemical, histologic, and radiologic results., Results: All patients received left-side grafts. Thirteen patients (16.7%) developed BAS after LDLT. Among them, 3 patients (23.1%) had duct-to-duct anastomosis during LDLT. The median follow-up period for the BAS group and the non-BAS group was 57.8 and 79.5 months, respectively (P = .683). Ten of the patients with BAS required percutaneous transhepatic biliary drainage with or without dilatation for treating the stricture. Multivariable analysis showed that hepatic artery thrombosis and duct-to-duct anastomosis were 2 risk factors associated with BAS., Conclusion: In pediatric LDLT, hepaticojejunostomy is the preferred method for bile duct reconstruction, but more large-scale research needs to be done to reconfirm this result., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Context: Few studies have examined morbidity and mortality associated with hepatobiliary disease in diabetes. Most have used administrative databases and/or have had limited/incomplete data including recognized risk factors for hepatobiliary disease., Objective: The objective of the study was to explore the relationship between type 2 diabetes and hepatobiliary disease in well-characterized patients with detailed risk factor data including viral hepatitis status and hemochromatosis genotype., Design: This was a community-based longitudinal observational study., Setting: The study was conducted in an urban Australian community., Patients: The study included 1294 patients of mean ± SD aged 64.1 ± 11.3 yr and 5156 age-, gender-, and ZIP code-matched nondiabetic controls., Main Outcome Measures: Prevalent and incident hepatobiliary disease and hepatobiliary disease-related death were measured. Competing risks proportional hazard models provided independent associates of these end points., Results: During 13,705 patient-years (mean 11.5 yr), 144 patients had an initial hepatobiliary disease-related hospitalization/cancer registration vs. 403 controls during 63,937 person-years of follow-up, an incidence rate ratio of 1.66 (95% confidence interval 1.37-2.02). Incident hepatobiliary disease was associated with a lower glycosylated hemoglobin and higher urinary albumin to creatinine ratio. Nearly half of the patients (49.9%) died during follow-up [crude mortality ratio vs. nondiabetic controls 1.97 (1.16-3.32)], and 21 (3.3%) from hepatobiliary disease including two cases of cirrhosis attributable to nonalcoholic steatohepatitis. Hepatobiliary disease-related death was independently predicted by prior hepatobiliary disease, hepatitis C seropositivity, retinopathy, and peripheral neuropathy; higher educational level and higher fasting serum glucose were protective., Conclusions: Hepatobiliary disease and associated mortality are increased in type 2 diabetes. Multiple factors including fatty infiltration, microangiopathy, and direct glucotoxicity are likely to contribute, but hospitalization and death due to cirrhosis from nonalcoholic steatohepatitis appear uncommon.

Backgrounds and Aims: Accurate assessment of graft bile duct is important to plan surgical procedure. Magnetic resonance cholangiopancreatography (MRCP) has become an important diagnostic procedure in evaluation of pancreaticobiliary ductal abnormalities and has been reported as highly accurate. We aim to estimate the efficacy of preoperative MRCP on depicting biliary anatomy in living donor liver transplantation (LDLT), and to determine whether inaccurate preoperative imaging assessment would increase the biliary complications after LDLT., Methods: The data of 118 cases LDLT were recorded. Information from preoperative MRCP was assessed using intraoperative cholangiography (IOC) as the gold standard. The possible risk factors of recipient biliary complications were analyzed., Results: Of 118 donors, 84 had normal anatomy (type A) and 34 had anatomic variants (19 cases of type B, 9 cases of type C, 1 case of type E, 2 cases of type F and 3 cases of type I) confirmed by IOC. MRCP correctly predicted all 84 normal cases and 17 of 34 variant cases, and showed an accuracy of 85.6% (101/118). The incidence of biliary complications was comparable between cases with accurate and inaccurate classification of biliary tree from MRCP, and between cases with normal and variant anatomy of bile duct. While cases with graft duct opening ≤5mm showed a significant higher incidence of total biliary complications (21.1% vs. 6.6%, P=0.028) and biliary stricture (10.5% vs. 1.6%, P=0.041) compared with cases with large duct opening >5mm., Conclusion: MRCP could correctly predict normal but not variant biliary anatomy. Inaccurate assessment of biliary anatomy from MRCP not increases the rate of biliary complications, while small-sized graft duct may cause an increase in biliary complications particularly biliary stricture after LDLT., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)