Íleo biliar complicado con infección con SARS-CoV-2. Reporte de caso / Gallstone ileus: a challenge in the management of bile duct pathology. Case Report

Introducción: El Íleo biliar (IB) es una obstrucción intestinal mecánica muy poco frecuente, del 1 al 4 % de todas las obstrucciones intestinales, y es más común en pacientes de edad avanzada. Se produce a través de una fístula bilioentérica en el intestino delgado, sobre todo en el íleon distal. Luego de tener un enfoque diagnóstico mediante imagenología, en su gran mayoría, se opta por el tratamiento quirúrgico para eliminar el o los cálculos impactados. El éxito de esta intervención depende en gran medida del tamaño del cálculo biliar, de la ubicación de la obstrucción intestinal y comorbilidades preexistentes. Caso clínico: Mujer de 78 años con cuadro clínico de obstrucción intestinal, emesis de contenido fecaloide y sintomática respiratoria; se evidenció una masa concéntrica a nivel de íleon distal y proceso neumónico concomitante por tomografía toracoabdominal. Se realizó laparotomía exploratoria con enterolitotomía, extracción de cálculo y anastomosis íleo-ileal y fue trasladada a la UCI en donde presentó falla ventilatoria y requerimiento de ventilación mecánica; se confirmó infección viral por SARS-CoV-2 mediante RT - PCR. Discusión: El IB es una obstrucción intestinal que ocurre con mayor frecuencia en pacientes de edad avanzada. Se habla de la fisiopatología y mecanismo de producción de la fístula entérica y se presentan opciones diagnósticas, terapéuticas y quirúrgicas para dirigir el manejo clínico más apropiado. Conclusión: El IB es difícil de diagnosticar. Debido a su baja incidencia, no existe un consenso que paute el manejo a seguir en los pacientes con diagnóstico de IB. Aunque el tratamiento estándar es la intervención quirúrgica, hay diversas opiniones en cuanto al tipo de cirugía a realizar.

Introduction: Biliary ileus (BI) is a very rare mechanical intestinal obstruction, responsible for 1-4% of all intestinal obstructions and more frequent in elderly patients. It occurs through a bilioenteric fistula in the small bowel, mainly in the distal ileum. After a diagnostic imaging approach, the vast majority opt for surgical treatment to remove the impacted stone or stones. The success of this intervention depends largely on the size of the stone, the location of the bowel obstruction and pre-existing comorbidities. Case report: 78-year-old woman with clinical symptoms of intestinal obstruction, fecaloid emesis, respiratory symptoms, concentric mass at the level of the distal ileum and concomitant pneumonic process in the thoraco-abdominal CT scan. Exploratory laparotomy was performed, with total lithotomy, extraction of the calculus and ileo-ileal anastomosis, and she was transferred to the ICU, where she presented ventilatory failure and required mechanical ventilation. SARS-CoV-2 infection was confirmed with RT-PCR. Discussion: IB is an intestinal obstruction that occurs more frequently in elderly patients. The pathophysiology and the mechanism of production of enteric fistula are discussed and diagnostic, therapeutic and surgical options are presented to guide the most appropriate clinical management. Conclusion: Enteric fistula is difficult to diagnose. Due to its low incidence, there is no consensus on the management of patients diagnosed with IB. Although the standard treatment is surgical intervention, there are divergent opinions as to the type of surgery to be performed.

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: Case 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.

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.

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.

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.

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

Incidence and Overall Survival of Biliary Tract Cancers in South Korea from 2006 to 2015: Using the National Health Information Database

BACKGROUND/AIMS: There have been no nationwide studies to investigate the trends in incidence and 5-year survival rates of intra- and extrahepatic bile duct cancers and gall-bladder cancer. Therefore, our study aimed to describe the incidence and 5-year survival rates of biliary tract cancers by subsites in South Korea. METHODS: A total of 86,134 patients with biliary tract cancers were selected from the National Health Information Database. Age-standardized incidence rates and annual percentage changes were calculated. Life-table methods and log-rank tests were used to determine the differences in survival rates. Cox-proportional hazard models were used to estimate the hazard ratio of the patients with biliary tract cancers. RESULTS: The incidence rate of intra-hepatic bile duct cancer decreased by 1.3% annually from 8.8 per 100,000 in 2006 to 7.8 per 100,000 in 2015. Extrahepatic bile duct cancer also showed a decreasing trend by 2.2% per year from 8.7 per 100,000 in 2006 to 6.7 per 100,000 in 2015. Gallbladder cancer showed the greatest decline, with an annual percentage change of 2.8% from 6.3 per 100,000 to 5.2 per 100,000 during the same period. The 5-year survival rates were 30.0% in gallbladder cancer, 27.8% in extrahepatic bile duct cancer, and 15.9% in intra-hepatic bile duct cancer. CONCLUSIONS: The overall incidence rates of intrahepatic and extrahepatic bile duct cancer and gallbladder cancer decreased from 2006 to 2015. Among biliary tract cancers, intrahepatic bile duct cancers exhibited the highest incidence rate and the worst survival rate.

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.

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.

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.

Review of the 2017 European Society of Gastrointestinal Endoscopy Guidelines for Endoscopic Ultrasound / 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.

Gallbladder Paraganglioma Associated with SDHD Mutation: a Potential Pitfall on ¹⁸F-FDOPA PET Imaging / 대한핵의학회잡지

A 36-year-old male patient initially presented with hypertension, tinnitus, bilateral carotid masses, a right jugular foramen, and a periaortic arch mass with an elevated plasma dopamine level but an otherwise normal biochemical profile. On surveillance MRI 4 years after initial presentation, he was found to have a 2.2-cm T2 hyperintense lesion with arterial enhancement adjacent to the gallbladder, which demonstrated avidity on ⁶⁸Ga-DOTATATE PET/CTand retrospectively on ¹⁸F-FDOPA PET/CT but was nonavid on ¹⁸F-FDG PET/CT. Biochemical work-up including plasma catecholamines, metanephrines, and chromogranin A levels were found to be within normal limits. This lesion was surgically resected and was confirmed to be a paraganglioma (PGL) originating from the gallbladder wall on histopathology. Pheochromocytoma (PHEO) and PGL are rare tumors of the autonomic nervous system. Succinate dehydrogenase subunit D (SDHD) pathogenic variants of the succinate dehydrogenase complex are usually involved in parasympathetic, extra-adrenal, multifocal head, and neck PGLs. We report an unusual location of PGL in the gallbladder associated with SDHD mutation which could present as a potential pitfall on ¹⁸F-FDOPA PET/CT as its normal excretion occurs through biliary system and gallbladder. This case highlights the superiority of ⁶⁸Ga-DOTATATE in comparison to ¹⁸F-FDOPA and ¹⁸F-FDG in the detection of SDHD-related parasympathetic PGL.ClinicalTrials.gov Identifier: NCT00004847.

Sex and Gender Medicine in Pancreatobiliary Diseases / 대한췌담도학회지

Sex and gender medicine investigates the impact of sex and gender differences on normal conditions, pathogenesis, and clinical features of diseases. By considering sex and gender differences during diagnosis, treatment and prevention, a person can receive the best individualized treatment based on scientific evidence. In this review, sex and gender differences in the field of pancreatobiliary diseases are described regarding gallstones, acute cholecystitis, acute and chronic pancreatitis, and cancers of the pancreas and biliary tract. In addition, recent policy on clinical and preclinical research which states that sex and gender analysis should be included during planning, conducting, and interpretation of the researches and websites containing resources about sex and gender medicine are introduced. This review highlights the importance of considering sex and gender aspect in research, clinics, and medical education.

Papillary Cannulation Facilitated by Submucosal Saline Injection into an Intradiverticular Papilla

Endoscopic retrograde cholangiopancreatography (ERCP) of the intradiverticular papilla with its invisible orifice remains challenging. Several techniques have been introduced to evert the papillary opening to facilitate cannulation. A 79-year-old woman with bile duct stones underwent ERCP, which revealed that the papilla was located inside a large diverticulum and tended to rotate inward with a trial of papillary cannulation. Submucosal papillary injection of 3 cc of normal saline was performed at 3 and 9 o’clock. Eversion and fixation of a papilla in the diverticulum with this technique allowed selective cannulation of the biliary tree. Stones were retrieved after endoscopic papillary balloon dilation without complications. She had an uneventful post-procedural course. Our findings suggest that submucosal saline injection technique is safe and effective for selective cannulation and can be recommended when cannulation is very difficult because of an intradiverticular papilla.

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.

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.