Biliotórax: una entidad rara para un diagnóstico frecuente. Un reporte de caso / Bilothorax: a Rare Entity for a Frequent Diagnosis. A Case Report

Introducción: El biliotórax es una condición infrecuente definida por la presencia de bilis en el espacio pleural. Actualmente, hay alrededor de 70 casos descritos en la litera-tura. Sigue siendo relativamente desconocido, por lo tanto, poco sospechado. Esta entidad suele ser el resultado de una lesión iatrogénica, a menudo secundaria a cirugías o traumatismos del tracto biliar, que conduce a la formación de una fístula pleurobiliar.

Introduction: Bilothorax is a rare condition defined by the presence of bile in the pleural space. Currently, there are around 70 cases described in the literature. It remains relatively unknown and, therefore, little suspected. This entity is usually the result of an iatrogenic injury, often secondary to surgery or trauma to the biliary tract, leading to the formation of a pleurobiliary fistula

Íleo biliar: reporte de casos / GALLSTONE ILEUS: CASES REPORT

El íleo biliar se define como una obstrucción intestinal mecánica secundaria a la presencia de un cálculo biliar. Menos del 1% de los casos de obstrucción intestinal se derivan de esta etiología. La causa más frecuente es la impactación del cálculo en el íleon, tras su paso por una fístula bilioentérica. Es una complicación rara y potencialmente grave de la colelitiasis. Esta patología se presenta más en adultos mayores, la edad promedio en la que se presenta es entre los 60 y 84 años, afectando principalmente al sexo femenino, atribuido a la mayor frecuencia de patología biliar en dicho sexo. Presenta una alta morbimortalidad, principalmente por la dificultad y la demora diagnóstica.

Gallstone ileus is defined as a mechanical intestinal obstruction secondary to the presence of a gallstone. Less than 1% of cases of intestinal obstruction are derived from this etiology. Te most frequent cause is the impaction of the stone in the ileum, after passing through a bilioenteric fistula. It is a rare and potentially serious complication of cholelithiasis. Tis pathology occurs more in the elderly, the average age at which it occurs is between 60 and 84 years, mainly affecting the female sex, attributed to the higher frequency of biliary pathology in said sex. It presents a high morbidity and mortality, mainly due to the difficulty and the diagnostic delay

Estudio complementario de la patología biliar complicada y el manejo de la litiasis coledociana en dos tiempos / Complementary evaluation of complicated gallstone disease and two-stage management of choledochal lithiasis

RESUMEN Antecedentes: la litiasis biliar tiene una prevalencia actual en Occidente del 10-20%. El 7-16% de los pacientes presentan también coledocolitiasis. El diagnóstico preoperatorio de coledocolitiasis es difícil de establecer. Objetivo: establecer nuestra experiencia en el estudio de la patología biliar complicada y el manejo de la coledocolitiasis en dos tiempos, como terapéutica de elección. Material y métodos: estudio prospectivo, observacional. Pacientes con patología biliar sometidos a procedimientos en el Servicio de Cirugía General del Hospital Vidal, desde el 30/06/2019 al 30/12/2019. Resultados: la ecografía hepato-bilio-pancreática (HPB) es específica, con exactitud del 80,9% y sensibilidad del 50%. La colangio resonancia magnética (CRNM) es 100% específica, tiene exactitud del 84,6% y sensibilidad de 67%. La colangio pancreatografía retrógrada endoscópica (ERCP -por sus siglas en inglés-), durante la primera colangiografía mostró en el 100% litiasis coledociana, pero, luego del tratamiento, la colangiografía de "control" muestra 0% de sensibilidad, 100% especificidad, con exactitud del 15,4%. En los hallazgos intraoperatorios, el cístico dilatado en asociación con alteraciones humorales ha demostrado una sensibilidad del 100%, especificidad del 90% y tasa de exactitud de 93,6%. Conclusión: la colangiografía intraoperatoria (CIO) es el procedimiento de referencia ("gold standard") en el abordaje de la patología biliar complicada, siendo su uso sistemático. La asociación entre alteraciones de parámetros humorales y el cístico dilatado resulta un parámetro con alto valor predictivo para la presencia de litiasis coledociana.

ABSTRACT Background: Nowadays, the prevalence of gallstones ranges between 10 and 20% in Western world, and 7-16% of the patients also present choledocholithiasis. The preoperative diagnosis of choledocholithiasis is difficult. Objective: To establish our experience in the evaluation of complicated gallstone disease and two-stage management of choledochal lithiasis as standard or care. Material and methods: This prospective and observational study included patients hospitalized with gallstone disease undergoing procedures in the Department of General Surgery of Hospital Vidal from June 30, 2019, to December 30, 2019. Results: Ultrasound of the liver, biliary tract and pancreas was specific, with accuracy of 80.9% and sensitivity of 50%. Magnetic resonance cholangiopancreatography (MRCP) had a sensitivity of 100%, accuracy of 84.6% and sensitivity of 67%. As for endoscopic retrograde cholangiopancreatography (ERCP), the diagnosis of choledocholithiasis was made in 100% of the cases during the first cholangiography while "control" cholangiography had a sensitivity of 0%, specificity of 100% and accuracy of 15.4%. The presence of a dilated cystic duct intraoperatively in association with abnormal biochemical parameters had a sensitivity of 100%, specificity of 90%, and accuracy of 93.6%. Conclusion: Intraoperative cholangiography (IOC) is the gold standard procedure for the management of complicated gallstone disease. The association of biochemical parameters and a dilated cystic duct has high predictive value for choledochal lithiasis.

Agenesia de la vesícula biliar / Agenesia of the gallbladder

La agenesia de la vesícula biliar (AVB) es una entidad congénita rara. La mayoría de los pacientes, permanecen asintomáticos, mientras que los que presentan síntomas informan síntomas que imitan el cólico biliar. La evaluación inicial para la sospecha de patología de la vesícula biliar, como la ecografía del cuadrante superior derecho, Puede ser engañosa o no concluyente. En consecuencia, algunos pacientes son finalmente diagnosticados intra-operatoriamente. Por lo tanto, deben mantener la AVB como un diagnóstico diferencial y deben realizarse como la colangiopancreatografía por resonancia magnética (CPRMN) cuando otras pruebas no sean concluyentes. Presentamos una mujer de 39 años que presento síntomas crónicos compatibles con cólico biliar y una ecografía equívoca informada como escleroatrófica con colelitiasis. Se le realizó laparoscopia durante la cual se constató la ausencia de vesícula biliar. La CPRM posoperatoria confirmó el diagnóstico de AG.

Gallbladder agenesis (GA) is a rare congenital entity. Most patients remain asymptomatic, while those with symptoms report symptoms that mimic bile colic. Initial evaluation for suspected gallbladder pathology, such as ultrasound of the right upper quadrant, May be misleading or inconclusive. As a result, some patients are eventually diagnosed intra-operatively. Therefore, GA should be maintained as a differential diagnosis and should be performed as magnetic resonance cholangiopancreatography (MRI) when other tests are inconclusive. We present a 39-year-old woman who has chronic symptoms compatible with biliary colic and an equivocal ultrasound reported as scleroatrofic with cholelithiasis. Laparoscopy was performed during which the absence of gallbladder was found. Postoperative CPRM confirmed the diagnosis of GA.

Does age influence in endoscopic therapeutic success on the biliary tract? / A idade influencia no sucesso terapêutico endoscópico sobre a via biliar?

ABSTRACT Background: Retrograde endoscopic cholangiopancreatography (ERCP) effectively treats biliary and pancreatic disorders. Its indications are limited and precise, since its misuse delays adequate treatment, increases costs and to patient´s adverse events. Aim: To compare clinical, radiological and exploratory characteristics in relation to therapeutic success in patients undergoing ERCP in relation to age. Method: 421 patients who underwent the method were retrospectively studied; those who were not able to access the duodenal papilla were excluded. The patients were divided into two age groups: <60 years (group 1) and >60 years (group 2), and the variables of gender, examination indications, radiological findings, therapeutic success, diagnosis and the occurrence of immediate adverse events were analyzed. Results: 177 patients were allocated to group 1 and 235 to group 2. The main indication found in both groups was choledocholithiasis. In group 2, the number of cases of acute cholangitis (p=0.001), biliary stenosis (p=0.002) and papilla cancer (p=0.046) was higher. In this group, urgent indication for ERCP was higher (p=0.042), as well as the diagnosis of biliary tract dilatation (p<0.001). The placement of prostheses was the most common procedure performed in both groups, but the greatest number of patients in absolute quantity occurred in group 2. In group 1, the success in catheterization and the chance of achieving clearing of the biliary tract was significantly higher in compared to group 2 (p=0.016, OR=2.1). Conclusion: The success of catheterization and complete clearance of the bile duct was significantly higher in the group of young patients.

RESUMO Racional: A colangiopancreatografia endoscópica retrógrada (CPRE) trata eficazmente afecções biliares e pancreáticas. Suas indicações são limitadas e precisas, uma vez que seu uso indevido atrasa o tratamento adequado, aumenta os custos e submete pacientes a eventos adversos. Objetivo: Comparar as características clínicas, radiológicas e exploratórias em relação ao sucesso terapêutico em pacientes submetidos à CPRE com relação à idade. Método: Foram estudados retrospectivamente 421 pacientes submetidos ao método sendo excluídos aqueles onde não foi possível ao acesso a papila duodenal. Os pacientes foram divididos em dois grupos etários: <60 anos (grupo 1) e >60 anos (grupo 2) e analisadas as variáveis gênero, indicações do exame, achados radiológicos, sucesso terapêutico, diagnóstico e a ocorrência de eventos adversos imediatos. Resultados: 177 pacientes foram alocados no grupo 1 e 235 no grupo 2. A principal indicação encontrada em ambos os grupos foi coledocolitíase. No grupo 2, o número de casos de colangite aguda (p=0,001), estenose biliar (p=0,002) e neoplasia de papila (p=0,046) foi superior. Nesse grupo a indicação da CPRE em caráter de urgência foi superior (p=0,042), bem como o diagnóstico de dilatação da via biliar (p<0,001). A colocação de próteses foi o procedimento mais comumente realizado nos dois grupos, mas o maior número de doentes em quantidade absoluta ocorreu no grupo 2. No grupo 1, o sucesso na cateterização e a chance de conseguir o clareamento da via biliar foi significativamente superior em relação ao grupo 2 (p=0,016, OR=2,1). Conclusão: O sucesso da cateterização e o clareamento completo da via biliar foi significativamente superior no grupo de pacientes jovens.

Research Progress of Antibacterial Biliary Stent / 中国医疗器械杂志

Biliary stent has been widely used in the treatment of biliary stricture and obstruction, it can relieve the pain of patients effectively, but bacterial infection and stent obstruction are still troublesome after surgery. We introduce the mechanism of infection and stent blockage caused by bacterial invasion after biliary stent implantation, and expound the formation mechanism of bacterial biofilm and bile sludge in this review. Antibacterial biliary stent is an effective way to inhibit biliary tract infection, the literatures on antibacterial modification of biliary stent with different antibacterial methods in domestic and abroad are reviewed, and the research prospect of antibacterial biliary stent is summarized and prospected.

Guidelines for diagnosis and treatment of acute biliary tract infections(2021) / 中华外科杂志

To further improve the standard of diagnosis and treatment of acute biliary tract infections in China, the Branch of Biliary Surgery, Society of Surgery, Chinese Medical Association has revised the guidelines for the diagnosis and treatment of acute biliary tract infections (2011).The guidelines describe the risk factors of acute biliary tract infections, propose diagnostic methods and severity classification criteria, and define the treatment of acute biliary tract infections and the standardized application of antibiotics. The treatment of acute biliary tract infection should be combined with surgical care, antimicrobial therapy and systemic management, and should be completed under the guidance of experienced surgical specialist. Reasonable selection of diagnosis and treatment measures, accurate understanding of surgical procedures and standardized use of antibiotics can achieve maximum treatment result for acute biliary tract infection.

Cirugia biliar en época de pandemia Experiencia del Hospital de Clínicas "Pte. Nicolás Avellaneda" - (Tucumán-Argentina). / BILIARY SURGERY IN A TIME OF PANDEMIC AT THE CLINICAL HOSPITAL "Pte. NICOLAS AVELLANEDA" TUCUMAN, ARGENTINA

Antecedentes: La rápida diseminación mundial de la enfermedad COVID-19 llevó a declarar la Emergencia Sanitaria, en Argentina se decretó el Aislamiento Social Preventivo y Obligatorio el 20 de Marzo, siguiendo con estos lineamientos Tucumán tuvo que adaptarse reestructurando su Sistema Provincial de Salud, quedando el Hospital de Clínicas Pte. Nicolás Avellaneda, como único hospital polivalente para patologías prevalentes. Objetivo: Mostrar el manejo quirúrgico integral mininvasivo de la patología biliar (laparoscópico, endoscópico, percutáneo y combinado), con plena vigencia de la CMA en este momento de Pandemia, durante el periodo del 20 de Marzo al 29 de Mayo del 2020. Material y métodos: Estudio descriptivo, prospectivo de corte transversal, de la patología quirúrgica biliar a quienes se le realizó Cribado Epidemiológico, exámenes preoperatorios, de ser necesaria una Tomografía Computada de Tórax; con Consentimiento Informado. Resultados: En el periodo estudiado, en el contexto de la pandemia se realizaron 51 intervenciones de la vía biliar; las vías de abordaje de elección fueron de cuatros tipos, según el orden de frecuencia: laparoscópico 65%, combinado 25%, endoscópico 8% y percutáneo 2%, con la modalidad de CMA (Cirugía Mayor Ambulatoria) se realizó 20% y 80% con internación hospitalaria, de los cuales tuvieron un promedio de un día y medio de estadía postoperatorio. Conclusión: La aparición de la Pandemia nos dió la oportunidad de incorporar nuevas técnicas mininvasivas y fortalecer la CMA. Para poder realizar esta labor, es necesario priorizar la seguridad en el entorno de trabajo y la atención de los pacientes.

Health Emergency, in Argentina Preventive and Mandatory Social Isolation was decreed on March 20, following these guidelines Tucumán had to restructure its Provincial Health System, leaving the Hospital Clinicas Pte. Nicolás Avellaneda, as the only multipurpose hospital for prevalent pathologies. Objective: To show the comprehensive minimally invasive surgical management of biliary pathology (laparoscopic, endoscopic, percutaneous, and combined), with full effect of the CMA at this time of the Pandemic, during the period from March 20 to May 29, 2020. Material and Methods: Descriptive, prospective, cross-sectional study of biliary surgical pathology for those who underwent Epidemiological Screening, preoperative examinations, if necessary, a Computed Tomography of the Thorax; with Informed Consent. Results: In the period studied, 51 bile duct problems were performed in the context of the pandemic; the approach routes of choice were of four types, according to the order of frequency: laparoscopic 65%, combined 25%, endoscopic 8% and percutaneous 2%, with the flexibility of CMA (Major Ambulatory Surgery) performed 20% and 80% with hospitalization, of which they had an average of one and a half days of postoperative stay. Conclusion: The appearance of the Pandemic gave us the opportunity to incorporate new minimally invasive techniques and strengthen the CMA. In order to carry out this work, it is necessary to prioritize safety in the work environment and patient care

Posttraumatic biloma formation: diagnosis and management

One of the rarest complications of the hepatic trauma is a biloma, defined as an abnormal bile collection outside the biliary tree, with intra or extrahepatic localization. Patients with biloma do not present with specific clinical features, which demands a challenging radiological diagnosis. In this report, we present a case of biloma due to blunt hepatic trauma, in which the patient experienced a changing symptomatic spectrum after surgery and had an interesting radiological investigation. The clinical course, imaging features, and management of this case are discussed. (AU)

Comparative evaluation of magnetic resonance cholangiopancreatography and perioperative cholangiography in patients with suspect choledocholithiasis / Avaliação comparativa da colangiopancreatografia por ressonância magnética e da colangiografia peroperatória na suspeita de coledocolitíase

ABSTRACT Background: Cholelithiasis is a highly prevalent condition, and choledocholitiasis is a high morbidity complication and requires accurate methods for its diagnosis. Aim: To evaluate the population of patients with suspected choledocholitiasis and check the statistical value of magnetic resonance cholangiopancreatography, ultrasonography, the laboratory and the clinic of these patients comparing them to the results obtained by perioperative cholangiography. Methods: This is a retrospective cohort study, which were evaluated 76 patients with cholelithiasis and suspected choledocholithiasis. Results: It was observed that the presence of dilatation of the biliary tract or choledocholithiasis in the ultrasonography was four and eight times increased risk of perioperative cholangiography for positive choledocholithiasis, respectively. For each unit increased in serum alkaline phosphatase was 0.3% increased the risk of perioperative cholangiography for positive choledocholithiasis. In the presence of dilatation of the bile ducts in the ultrasonography was four times greater risk of positive magnetic resonance cholangiopancreatography for choledocholithiasis. In the presence of pancreatitis these patients had five times higher risk of positive magnetic resonance cholangiopancreatography for choledocholithiasis. On the positive magnetic resonance cholangiopancreatography presence to choledocholithiasis was 104 times greater of positive perioperative cholangiography for choledocholithiasis. Conclusions: The magnetic resonance cholangiopancreatography is a method with good accuracy for propedeutic follow-up for the diagnosis of choledocholithiasis, consistent with the results obtained from the perioperative cholangiography; however, it is less invasive, with less risk to the patient and promote decreased surgical time when compared with perioperative cholangiography.

RESUMO Racional: A colelitíase é afecção de alta prevalência, sendo a coledocolitíase complicação de elevada morbidade e que necessita de métodos acurados para seu diagnóstico. Objetivo: Avaliar o perfil populacional de pacientes com suspeita de coledocolitíase e verificar o valor estatístico da colangiopancreatografia por ressonância magnética, da ultrassonografia, dos exames laboratoriais e da clínica desses pacientes e compará-los aos resultados obtidos pela colangiografia peroperatória. Métodos: Trata-se de estudo longitudinal, de coorte, retrospectivo, no qual foram avaliados 76 pacientes com diagnóstico de colelitíase e suspeita de coledocolitíase. Resultados: Observou-se que na presença de dilatação das vias biliares ou coledocolitíase na ultrassonografia havia risco quatro e oito vezes maior, respectivamente, de colangiografia peroperatória positiva para coledocolitíase. Para cada unidade de aumento na fosfatase alcalina sérica houve aumento em 0,3% no risco de colangiografia peroperatória positiva para coledocolitíase. Na presença de dilatação das vias biliares na ultrassonografia ou clínica de pancreatite havia risco quatro e cinco vezes maior, respectivamente, de colangiopancreatografia por ressonância magnética positiva para coledocolitíase. Na presença de colangiopancreatografia por ressonância magnética positiva para coledocolitíase o risco foi 104 vezes maior de colangiografia peroperatória positiva para coledocolitíase. Conclusão: A colangiopancreatografia por ressonância magnética para seguimento propedêutico tem boa acurácia para o diagnóstico de coledocolitíase, e concordante com os resultados obtidos na colangiografia peroperatória. O método é menos invasivo, com menores riscos ao paciente e com diminuição do tempo cirúrgico dispendido para realização da colangiografia peroperatória.

Review of the 2017 European Society of Gastrointestinal Endoscopy Guidelines for Endoscopic Ultrasound - Guided Sampling in Pancreaticobiliary Lesions / 대한소화기학회지

EUS currently plays an important role in the diagnosis and treatment of digestive diseases. In addition, EUS-guided sampling has been applied to pancreaticobiliary lesions for the accurate diagnosis of pancreaticobiliary lesions. Many new instruments and studies for EUS-guided sampling are being developed and attempted. This review introduces and summarizes the key recommendations made in the recent guideline for EUS-guided sampling developed by the European Society of Gastrointestinal Endoscopy.

A consensus statement on the standardized application of antibacterial agents in biliary tract surgery (2019) / 中华外科杂志

The standardized application of antibacterial agents in the treatment of biliary tract diseases is of great significance.On the basis of international and domestic guidelines and consensuses, combining with the actual situation of Chinese biliary tract infection, Study Group of biliary Tract Surgery in Chinese Society of Surgery of Chinese Medical Association and Enhanced Recovery After Surgery Committee of Chinese Research Hospital Association and Editorial Board of Chinese Journal of Surgery organized experts to make recommendations which adopted a problem-oriented approach on the severity grade of biliary tract infection, the protocol of specimen examination, the use of antibiotics, the indication of drug withdrawal, the agents application strategy of drug-resistant bacteria infection and special situation to guide surgeons getting the accurate judgement of the severity of biliary tract infection and the formulation of standard protocols for the use of antibacterial agents on the premise of following the bacteriological and drug resistance monitoring information.

Characterization of Intraductal Papillary Neoplasm of the Bile Duct with Respect to the Histopathologic Similarities to Pancreatic Intraductal Papillary Mucinous Neoplasm

Intraductal papillary neoplasms of the bile duct (IPNBs) are known to show various pathologic features and biological behaviors. Recently, two categories of IPNBs have been proposed based on their histologic similarities to pancreatic intraductal papillary mucinous neoplasms (IPMNs): type 1 IPNBs, which share many features with IPMNs; and type 2 IPNBs, which are variably different from IPMNs. The four IPNB subtypes were re-evaluated with respect to these two categories. Intestinal IPNBs showing a predominantly villous growth may correspond to type 1, while those showing papillay-tubular or papillay-villous growth correspond to type 2. Regarding gastric IPNB, those with regular foveolar structures with varying numbers of pyloric glands may correspond to type 1, while those with papillary-foveolar structures with gastric immunophenotypes and complicated structures may correspond to type 2. Pancreatobiliary IPNBs that show fine ramifying branching may be categorized as type 1, while others containing many complicated structures may be categorized as type 2. Oncocytic type, which displays solid growth or irregular papillary structures, may correspond to type 2, while papillary configurations with pseudostratified oncocytic lining cells correspond to type 1. Generally, type 1 IPNBs of any subtype develop in the intrahepatic bile ducts, while type 2 IPNBs develop in the extrahepatic bile duct. These findings suggest that IPNBs arising in the intrahepatic ducts are biliary counterparts of IPMNs, while those arising in the extrahepatic ducts display differences from prototypical IPMNs. The recognition of these two categories of IPNBs with reference to IPMNs and their anatomical location along the biliary tree may deepen our understanding of IPNBs.

Bile Acid Transporters Are Expressed and Heterogeneously Distributed in Rat Bile Ducts

BACKGROUND/AIMS: Cholangiocytes are capable of reabsorbing bile salts from bile, but the pathophysiological significance of this process is unclear. To this end, we detected the expression and distribution of bile acid transport proteins in cholangiocytes from normal rat liver and analyzed the possible pathophysiological significance. METHODS: Bile duct tissues of Sprague-Dawley rats were isolated by enzymatic digestion and mechanical isolation, and then divided into large and small bile duct tissues. Immunohistochemistry, real-time polymerase chain reaction and Western blotting were used to determine the expression of the apical sodium-dependent bile acid transporter (ASBT), ileal bile acid binding protein (IBABP), and basolateral organic solute transporter α (Ostα) in the biliary tract system of rats. Differences in the expression and distribution of these proteins were analyzed. RESULTS: In cholangiocytes, ASBT and IBABP were mainly expressed in cholangiocytes of the large bile ducts, in which the expression of both was significantly higher than that in the small ducts (p0.05). CONCLUSIONS: Bile acid transporters are expressed and heterogeneously distributed in rat bile ducts, indicating that bile acid reabsorption by cholangiocytes might mainly occur in the large bile ducts. These findings may help explore the physiology of bile ducts and the pathogenesis of various cholangiopathies.

Safety Evaluation of Paclitaxel-Eluting Biliary Metal Stent with Sodium Caprate in Porcine Biliary Tract

BACKGROUND/AIMS: Metallic stents designed to relieve malignant biliary obstruction are susceptible to occlusive tumor ingrowth or overgrowth. In a previous report, we described metallic stents covered with paclitaxel-incorporated membrane (MSCPM-I, II) to prevent occlusion from tumor ingrowth via antitumor effect. This new generation paclitaxel-eluting biliary stent is further endowed with sodium caprate (MSCPM-III) for enhanced drug delivery. The purpose of this study is to examine the safety of its drug delivery system in the porcine biliary tract. METHODS: MSCPM-III (10% [wt/vol] paclitaxel) and covered metal stents (CMSs) were endoscopically inserted in porcine bile ducts in vivo. Histologic biliary changes, levels of paclitaxel released, and various serum analytes (albumin, alkaline phosphate, aspartate transaminase, alanine transaminase, total protein, total bilirubin, and direct bilirubin) were assessed. RESULTS: Based on the intensity of reactive inflammation and fibrosis, changes in porcine biliary epithelium secondary to implanted MSCPM-III were deemed acceptable (i.e., safe). Histologic features in the MSCPM-III and CMS groups did not differ significantly. In a related serum analysis, paclitaxel release from MSCPM-III stents was below the limit of detection for 28 days. Biochemical analyses were also similar for the two groups, and no evidence of hepatic or renal toxicity was found in animals receiving MSCPM-III stents. CONCLUSIONS: In a prototypic porcine trial, this newly devised metal biliary stent incorporating both paclitaxel and sodium caprate appears to be safe in the porcine bile duct.

Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied. MATERIALS AND METHODS: We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC. RESULTS: Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression. CONCLUSION: Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.

Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain. MATERIALS AND METHODS: Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS). RESULTS: Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320). CONCLUSION: sGemCis maintenance is not associated with an improved survival outcome.

Therapeutic Targeting of the DNA Damage Response Using an ATR Inhibitor in Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor. MATERIALS AND METHODS: A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings. RESULTS: Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug. CONCLUSION: In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.

Ultrasound-guided transhepatic computed tomography cholecystography in beagle dogs

This study was performed to evaluate the feasibility of ultrasound-guided computed tomography (CT) cholecystography and to establish an optimal protocol. In 8 healthy beagles, CT cholecystography was conducted using four contrast formulas; two dilution ratios (1:1 vs. 1:3) and two total volumes (8 mL vs. 16 mL) of 300 mgI/kg iohexol after ultrasound-guided percutaneous contrast injection into the gallbladder. CT images were obtained at 3, 10, and 30 min after injection and assessed qualitatively and quantitatively. For all contrast formulas, CT cholecystography showed the gallbladder and the intra- and extrahepatic bile ducts. The volume of the gallbladder and size of bile duct were significantly larger when using a volume of 16 mL iohexol than an 8 mL volume regardless of the dilution ratio. The distinction between the common bile duct and duodenum, the filling of the gallbladder, and the patency of bile duct were effectively assessed using a 16 mL volume of contrast agent with either dilution ratio. Beam-hardening artifacts deteriorated CT image quality for visualizing the biliary system when using the dilution ratio of 1:1. Patency of the bile tract could be easily evaluated using a curvilinear planar reconstruction. There was no significant difference in CT scan time among the different conditions. Minor leakage of contrast agent temporarily occurred after contrast injection in 30% of 32 sets of CT cholecystography. Ultrasound-guided percutaneous cholecystography can visualize both gallbladder and biliary tract with minimal artifacts using a contrast agent volume of 16 mL with a 1:3 dilution ratio.