Hepatolithiasis: Epidemiology, presentation, classification and management of a complex disease.

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts, above the hilar confluence of the hepatic ducts. The disease is more prevalent in Asia, mainly owing to socioeconomic and dietary factors, as well as the prevalence of biliary parasites. In the last century, owing to migration, its global incidence has increased. The main pathophysiological mechanisms involve cholangitis, bile infection and biliary strictures, creating a self-sustaining cycle that perpetuates the disease, frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of "recurrent pyogenic cholangitis". Furthermore, long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma. Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment. The management of symptomatic patients and those with complications can be complex, and relies upon a multidisciplinary team of hepatologists, endoscopists, interventional radiologists and hepatobiliary surgeons, with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications. This comprehensive review provides insight on various aspects of hepatolithiasis, with a focus on epidemiology, new evidence on pathophysiology, most important clinical aspects, different classification systems and contemporary management.

Impact of Preoperative Cholangitis on Short-term Outcomes Among Patients Undergoing Liver Resection.

BACKGROUND: The impact of preoperative cholangitis (PC) on perioperative outcomes among patients undergoing liver resection remains poorly defined. We sought to characterize the prevalence of PC among patients undergoing hepatectomy and define the impact of PC on postoperative outcomes. METHODS: Patients who underwent liver resection between 2013 and 2015 were identified using the Center for Medicare Services (CMS) 100% Limited Data Set (LDS) Standard Analytic Files (SAFs). Short-term outcomes after liver resection, stratified by the presence of PC, were examined. Subgroup analyses were performed to evaluate the relationship between the timing of liver resection relative to PC. RESULTS: Among 7392 patients undergoing liver resection, 251 patients (3.4%) experienced PC. Patients with PC were more likely to be male (59.0% vs. 50.6%) and to have a benign diagnosis (34.3% vs. 19.8%) compared with patients without PC (both p<0.05). On multivariable analysis, PC was associated with increased odds of experiencing a complication (OR 1.54, 95%CI 1.17-2.03), extended LOS (OR 2.60, 95%CI 1.99-3.39), 90-day mortality (OR 2.31, 95%CI 1.64-3.26), and higher Medicare expenditures (OR 3.32, 95%CI 2.55-4.32). Among patients with PC, requirement of both endoscopic and percutaneous biliary drainage (OR 5.16, 95%CI 1.36-9.61), as well as liver resection < 2 weeks after PC (OR 2.92, 95%CI 1.13-7.57) were associated with higher odds of 90-day mortality. CONCLUSION: Approximately 1 in 30 Medicare beneficiaries undergoing liver resection had a history of PC. PC was associated with an increased risk of adverse short-term outcomes and higher healthcare expenditures among patients undergoing hepatectomy.

Postbiliary drainage rates of cholangitis are impacted by procedural technique for patients with supra-ampullary cholangiocarcinoma: A SEER-Medicare analysis.

BACKGROUND: The optimal approach to biliary drainage for patients with supra-ampullary cholangiocarcinoma remains undetermined. Violation of sphincter of Oddi results in bacterial colonization of bile ducts and may increase postdrainage infectious complications. We sought to determine if rates of cholangitis are affected by the type of drainage procedure. METHODS: We examined the Surveillance, Epidemiology, and End Results-Medicare linked database from 1991 to 2013 for cholangiocarcinoma. Biliary drainage procedures were categorized as sphincter of Oddi violating (SOV) or sphincter of Oddi preserving (SOP). Patients were stratified by resection. RESULTS: A total of 1914 patients were included in the final analysis. A total of 1264 patients did not undergo a postdrainage resection (SOP 83, SOV 1181) while 650 did undergo a postdrainage resection (SOP 26, SOV 624). For those patients not undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was 19% compared with 34% in the SOV cohort (P = 0.007). For those patients undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was less than 42.3% compared with 30% in the SOV cohort (P = 0.66). CONCLUSION: For patients with supra-ampullary cholangiocarcinoma that did not undergo resection, biliary drainage procedures that violated the sphincter of Oddi were associated with increased rates of cholangitis.

Hospitalization Burden of Biliary Strictures and Cholangitis After Pancreaticoduodenectomy.

BACKGROUND: Postsurgical biliary disease in Roux-en-y and cholecystectomies has been investigated, but less literature exists regarding biliary complications after Whipple procedure (pancreaticoduodenectomy [PD]). Moreover, the hospital burden incurred after this complication has not been previously examined. The aim of this study is to assess the trends in hospitalization for biliary strictures and cholangitis after PD. MATERIALS AND METHODS: The National Inpatient Sample identified all cases with a PD and a primary diagnosis of biliary complication in 2014. Cases were identified using the International Classification of Diseases, Clinical Modification codes. Primary outcomes were association of biliary complications with mortality, cost of admission, and length of stay. RESULTS: A total of 10,145 patients in 2014 were documented with a previous PD. Mortality was 50-fold greater without biliary complications (2.7% versus 0.05%), but a 95% increased length of stay (25.8 d versus 13.2 d, P = 0.014) and 70% increased cost of admission ($293,894 versus $165,862, P = 0.092) occurred with biliary complications. Regression analysis revealed increased length of stay in all cohorts (adjusted odds ratio: 14.3, P = 0.007) and increased cost of admission with cholangitis (adjusted odds: 458283, P = 0.00). Finally, there was increased biliary strictures, cost of hospitalization, and length of stay from 2011 to 2014. CONCLUSIONS: Biliary disease due to the PD appears to longitudinally increase length of stay and cost of hospitalization. Compared with gastrointestinal bleed and delayed gastric emptying, biliary strictures and cholangitis are still very high acuity, requiring more extensive medical resources. Minimally invasive surgeries and robotics could play a vital role in minimizing biliary complications and the ensuing hospitalization burden.

Factors and Outcomes Associated with MRCP Use prior to ERCP in Patients at High Risk for Choledocholithiasis.

Background. Consensus guidelines recommend that patients at high risk for choledocholithiasis undergo endoscopic retrograde cholangiopancreatography (ERCP) without additional imaging. This study evaluates factors and outcomes associated with performing magnetic resonance cholangiopancreatography (MRCP) prior to ERCP among patients at high risk for choledocholithiasis. Methods. An institutional administrative database was searched using diagnosis codes for choledocholithiasis, cholangitis, and acute pancreatitis and procedure codes for MRCP and ERCP. Patients categorized as high risk for choledocholithiasis were evaluated. Results. 224 patients classified as high risk, of whom 176 (79%) underwent ERCP only, while 48 (21%) underwent MRCP prior to ERCP. Patients undergoing MRCP experienced longer time to ERCP (72 hours versus 35 hours, p < 0.0001), longer length of stay (8 days versus 6 days, p = 0.02), higher hospital charges ($23,488 versus $19,260, p = 0.08), and higher radiology charges ($3,385 versus $1,711, p < 0.0001). The presence of common bile duct stone(s) on ultrasound was the only independent factor associated with less use of MRCP (OR 0.09, p < 0.0001). Conclusions. MRCP use prior to ERCP in patients at high risk for choledocholithiasis is common and associated with greater length of hospital stay, higher radiology charges, and a trend towards higher hospital charges.

Microbiological Assessment of Bile and Corresponding Antibiotic Treatment: A Strobe-Compliant Observational Study of 1401 Endoscopic Retrograde Cholangiographies.

The aim of this study was to determine the antibiotic susceptibility profiles of bacteria in bile samples and to analyze the clinical relevance of the findings as only limited information about risk factors for elevated frequence of bacterial and fungal strains in routinely collected bile samples has been described so far.A prospective cohort study at a tertiary care center was conducted. Seven hundred forty-four patients underwent 1401 endoscopic retrograde cholangiographies (ERCs) as indicated by liver transplantation (427/1401), primary sclerosing cholangitis (222/1401), choledocholithiasis only (153/1401), obstruction due to malignancy (366/1401), or other conditions (233/1401). Bile samples for microbiological analysis were obtained in all patients.The 71.6% (823/1150) samples had a positive microbiological finding, and 57% (840/1491) of the bacterial isolates were gram-positive. The main species were Enterococcus spp (33%; 494/1491) and Escherichia coli (12%; 179/1491). Of the samples, 53.8% had enteric bacteria and 24.7% had Candida spp; both were associated with clinical and laboratory signs of cholangitis (C-reactive proteins 35.0 ±â€Š50.1 vs 44.8 ±â€Š57.6; 34.5 ±â€Š51.2 vs 52.9 ±â€Š59.7; P < 0.001), age, previous endoscopic intervention, and immunosuppression. Multi-resistant (MR) strains were found in 11.3% of all samples and were associated with clinical and laboratory signs of cholangitis, previous intervention, and immunocompromised status. In subgroup analysis, strain-specific antibiotic therapy based on bile sampling was achieved in 56.3% (89/158) of the patients. In cases with a positive bile culture and available blood culture, blood cultures were positive in 29% of cases (36/124), and 94% (34/36) of blood cultures had microbial species identical to the bile cultures.Bactobilia and fungobilia can usually be detected by routine microbiological sampling, allowing optimized, strain-specific antibiotic treatment. Previous endoscopic intervention, clinical and laboratory signs of cholangitis, and age are independent risk factors. MR bacteria and fungi are an evolving problem in cholangitis, especially in immunocompromised patients.

Assessment of efficacy and safety of EUS-guided biliary drainage: a systematic review.

BACKGROUND AND AIMS: EUS-guided biliary drainage (EUS-BD) has emerged as an alternative procedure after failed ERCP. However, limited data on the efficacy and safety of EUS-BD are available. Therefore, a systematic review was conducted to evaluate the efficacy and safety of EUS-BD and to evaluate transduodenal (TD) and transgastric (TG) approaches. METHODS: PubMed and EMBASE were searched to identify relevant studies published in the English language for inclusion in this systematic review and meta-analysis. Data from eligible studies were combined to calculate the cumulative technical success rate (TSR), functional success rate (FSR), and adverse-event rate of EUS-BD and the pooled odds ratio of TSR, FSR, and adverse-event rate of the TD approach when compared with the TG approach. RESULTS: Forty-two studies with 1192 patients were included in this study, and the cumulative TSR, FSR, and adverse-event rate were 94.71%, 91.66%, and 23.32%, respectively. The common adverse events associated with EUS-BD were bleeding (4.03%), bile leakage (4.03%), pneumoperitoneum (3.02%), stent migration (2.68%), cholangitis (2.43%), abdominal pain (1.51%), and peritonitis (1.26%). Ten studies were included in the meta-analysis for comparative evaluation of TD and TG approaches for EUS-BD. Compared with the TG approach, the pooled odds ratio of the TSR, FSR, and adverse-event rate of the TD approach were 1.36 (95% CI, .66-2.81; P > .05), .84 (95% CI, .50-1.42; P > .05), and .61 (95% CI, .36-1.03; P > .05), respectively, which indicated no significant difference in the TSR, FSR, and adverse-event rate between the 2 groups. CONCLUSIONS: Although it is associated with significant morbidity, EUS-BD is an effective alternative procedure for relieving biliary obstruction. There was no significant difference between the TD and TG approaches for EUS-BD.

Cholangitis in children with biliary atresia: health-care resource utilisation.

AIM: Cholangitis is a well-known complication that contributes to morbidity, mortality, as well as health-care utilisation in children with biliary atresia who have undergone the Kasai portoenterostomy. The aim of the study was to determine the common causative organisms for cholangitis and characterise its burden, health-care resource and service utilisation and cost. METHODS: This was a retrospective chart review of children who underwent Kasai portoenterostomy in our institution from 1988 to 2011. The causative organisms were identified based on culture reports. The burden of the disease was estimated based on the number of patients experiencing one or more episodes of cholangitis. Health-care resource and service utilisation were based on different categories, and cost was computed based on the charges at the institution. RESULTS: Twenty-seven (64.3%) out of 42 children included in the analysis experienced at least one episode of cholangitis. There were a total of 97 episodes of cholangitis, with an average of 3.6 (1-15) episodes per patient. The average length of stay per episode of cholangitis was 14.8 (2-64) days. Common organisms isolated during blood cultures were Klebsiella pneumoniae, Enterococcus, Escherichia coli and Pseudomonas aeruginosa. The estimated cost per in-patient admission of 15 days (rounded off) for a single episode of cholangitis was $SG 8986.61 ($US 7369.02). CONCLUSION: The knowledge about the incidence and cost of cholangitis will allow physicians to counsel parents of children newly diagnosed with biliary atresia and to better prepare them both emotionally and financially for what to expect.

Prediction of drainage effectiveness during endoscopic stenting of malignant hilar strictures: the role of liver volume assessment.

BACKGROUND: The optimal endoscopic approach to the drainage of malignant hilar strictures remains controversial, especially with regard to the extent of desirable drainage and unilateral or bilateral stenting. OBJECTIVE: To identify useful criteria for predicting successful endoscopic drainage. DESIGN AND SETTING: Retrospective 2-center study in the greater Paris area in France. PATIENTS: A total of 107 patients who had undergone endoscopic stenting for hilar tumors Bismuth type II, III, or IV and a set of contemporaneous cross-sectional imaging data available. INTERVENTIONS: The relative volumetry of the 3 main hepatic sectors (left, right anterior, and right posterior) was assessed on CT scans. The liver volume drained was estimated and classified into 1 of 3 classes: less than 30%, 30% to 50%, and more than 50% of the total liver volume. MAIN OUTCOME MEASUREMENTS: The primary outcome was effective drainage, defined as a decrease in the bilirubin level of more than 50% at 30 days after drainage. Secondary outcomes were early cholangitis rate and survival. RESULTS: The main factor associated with drainage effectiveness was a liver volume drained of more than 50% (odds ratio 4.5, P = .001), especially in Bismuth III strictures. Intubating an atrophic sector (<30%) was useless and increased the risk of cholangitis (odds ratio 3.04, P = .01). A drainage > 50% was associated with a longer median survival (119 vs 59 days, P = .005). LIMITATIONS: Heterogeneous population and volume assessment methodology to improve in further prospective studies. CONCLUSION: Draining more than 50% of the liver volume, which frequently requires bilateral stent placement, seems to be an important predictor of drainage effectiveness in malignant, especially Bismuth III, hilar strictures. A pre-ERCP assessment of hepatic volume distribution on cross-sectional imaging may optimize endoscopic procedures.

Prospective assessment of the role of antibiotic prophylaxis in ERCP.

BACKGROUND/AIMS: Despite the existence of published recommendations, various studies of antibiotic prophylaxis have reached conflicting conclusions, and controversy exists regarding the role of antibiotic prophylaxis in ERCP. The aim of this study was to analyze the efficacy of the intramuscular administration of clindamicine and gentamicine before ERCP. METHODOLOGY: Sixty-one consecutive patients referred for ERCP were prospectively randomized to receive either clindamicine 600mg and gentamicine 80mg, both intramuscularly one hour before the ERCP (group I; 31 patients) or not (group II; 30 patients). Two blood samples were obtained from every patient (just before endoscopy and within 5 minutes of withdrawal of the endoscope) and were incubated for 7 days and examined daily for growth of bacteria. Patients were closely monitored for 7 days after endoscopy to detect the development of infectious complications. RESULTS: Only 7 cultures from 7 patients were positive. Four were obtained post-ERCP (two patients in group I and two in group II) and the remaining three before endoscopy. The post-ERCP isolated bacteria were: Streptococcus mitis, Peptoestreptococcus anaerobious, Moraxella spp and Escherichia coli. Two patients, one from each group, developed post-ERCP cholangitis that were solved with medical treatment. CONCLUSIONS: Our findings indicate that ERCP induce bacteremia in a small group of patients and suggest that prophylactic administration of clindamicine plus gentamicine does not reduce the incidence of bacteremia and cholangitis, and do not support the routine use of prophylactic antibiotics prior to ERCP.

The incidence and management of biliary complications following liver transplantation in children.

Biliary complications following liver transplantation are a cause of significant morbidity and mortality. During the period 1988-1993 ten cases of biliary complications occurred after 98 transplantations in 78 children. The complications were four bile leaks, three intrahepatic biliary strictures (one with recurrent cholangitis), two anastomotic biliary strictures (one with recurrent cholangitis) and one recurrent cholangitis. All leaks occurred within 6 weeks of transplantation whereas all strictures and cholangitic episodes occurred after 3 months. Two biliary complications (20%) - one intrahepatic and one anastomotic stricture - developed secondary to hepatic artery thrombosis. The incidence of biliary complications was 13.2% with whole liver grafts as compared to 6.7% with partial liver grafts and it was 4.3% with duct-to-duct anastomosis as compared to 12.0% with Roux-en-Y hepatico-jejunostomy. Seven children required intervention for management of biliary complications and three were managed conservatively. There were no deaths related to the biliary complications.

Atención médica en colangitis aguda / Medical care in acute cholangitis

Es un estudio descriptivo de 57 pacientes con diagnósticode colangitis aguda, operados en el Hospital Salvador entre enero de 1987 y junio de 1989. Se establecen un grupo de colangitis y otro de colangitis complicada,estudiándose las variables de atención médica y los factores asociados a una mayor morbimortalidad y su costo económico. Este se midió según días-camas ocupados, uso de ecografía y de antibióticos en el pre y postoperatorio. Se encontró que la colangitis es más grave por demora en el diagnóstico. Ello lleva a operaciones más largas y más complejas, aumento de días-cama y uso de antibióticos de alto costo por más tiempo, además de mayor morbilidad y mortalidad postoperatorias. Llamó la atención el menor empleo de ecografía en las colangitis complicadas. Se concluye que los factores estudiados repercuten, además del sufrimiento de los pacientes y sus familiares, en un mayor costo de la atención médica. Este costo va, según los valores establecidos por el Servicio, desde $29.355 (103 dólares) con colangitis simple hasta $50.717 (179 dólares) en colangitis complicada, por paciente y sin considerar el gasto en ecografía, exámenes de laboratorio y operación. Estos valores se duplicarían aproximadamente si se incluye el acto quirúrgico. La ecografía tiene poco impacto dado el bajo valor establecido