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

Les péritonites biliaires: aspects diagnostiques et thérapeutiques / Biliary peritonitis: diagnostic and therapeutic aspects

Buts : Le but était de décrire les aspects diagnostiques et thérapeutiques des péritonites biliaires. Patients et méthodes : Il s'est agi d'une étude transversale descriptive à collecte rétrospective sur une période de 10 ans incluant les patients opérés pour péritonite biliaire. Résultats : Nous avons colligé 10 cas de péritonite biliaire d'un 'âge moyen de 38 ans avec un sex-ratio de 2,3. Deux patients présentaient une contusion abdominale par suite d'un accident de la circulation routière. Une douleur abdominale maximale à l'hypochondre droit était présente chez trois patients, des signes d'irritation péritonéale chez tous les patients, un sérodiagnostic de Widal et Félix positif chez huit patients. À la laparotomie médiane la vésicule biliaire était perforée chez trois patients, gangrénée chez cinq, phlegmoneuse chez un, scléro-atrophique chez un. La cholécystectomie a été réalisée chez tous les patients. La péritonite biliaire était d'origine traumatique chez deux patients, et typhique chez huit. En post opératoire on notait quatre cas de sepsis, et trois cas de suppuration pariétale. Trois patients sont décédés. Conclusion : les péritonites biliaires découvertes lors de laparotomies pour péritonite, étaient secondaires à des cholécystites typhiques, et avaient une forte morbi-mortalité.

Aims: The aim was to describe the diagnostic and therapeutic aspects of biliary peritonitis. PATIENTS AND METHODS: This was a descriptive cross-sectional study with retrospective collection over a period of 10 years including patients operated on for biliary peritonitis. Results: We collected 10 cases of biliary peritonitis with an average age of 38 years with a sex ratio of 2.3. Two patients presented with an abdominal contusion following a road traffic accident. Maximum abdominal pain in the right hypochondrium was present in three patients, signs of peritoneal irritation in all patients, positive Widal and Felix serodiagnosis in eight patients. At midline laparotomy, the gallbladder was perforated in three patients, gangrenous in five, phlegmonous in one, sclero-atrophic in one. Cholecystectomy was performed in all patients. Biliary peritonitis was of traumatic origin in two patients, and typhoid in eight. Postoperatively, there were four cases of sepsis and three cases of parietal suppuration. Three patients died. Conclusion: Biliary peritonitis discovered during laparotomies for peritonitis, was secondary to typhoid cholecystitis, and had a high morbidity and mortality.

Papel del ácido ursodesoxicólico en 40 años de tratamiento para la colangitis biliar primaria / Role of ursodeoxycholic acid in 40 years of treatment for primary biliary cholangitis

La colangitis biliar primaria es una enfermedad hepática autoinmune que conduce a la destrucción progresiva de los conductos biliares intrahepáticos, lo que aumenta el riesgo de desarrollar cirrosis e hipertensión portal. Actualmente, el ácido ursodesoxicólico es el medicamento de primera línea para el tratamiento de esta entidad. Este medicamento desplaza los ácidos biliares hidrofóbicos y aumenta las concentraciones de ácidos biliares hidrofílicos en la bilis, lo cual favorece la integridad de los conductos biliares, adicionalmente, tiene efectos antiinflamatorios y propiedades inmunomo-duladoras y antiapoptóticas. En los últimos 40 años, numerosos ensayos clínicos han respaldado la eficacia clínica del ácido ursodesoxicólico y su seguridad cuando se utiliza en pacientes con colan-gitis biliar primaria. Se realiza una revisión del ácido ursodesoxicólico en el contexto de colangitis biliar primaria, se describe su historia, mecanismos de acción, efectos secundarios y dosificación. Finalmente, se menciona su uso en situaciones especiales como son el embarazo y la lactancia

Primary biliary cholangitis is an autoimmune liver disease that leads to progressive destruction of intrahepatic bile ducts, increasing the risk of developing cirrhosis and portal hypertension. Currently, ursodeoxycholic acid is the first-line drug for the treatment of this condition. This drug displaces hy-drophobic bile acids and increases concentrations of hydrophilic bile acids in the bile, which favors the integrity of the bile ducts, additionally, it has anti-inflammatory effects and immunoprotective and antiapoptotic properties. Over the past 40 years numerous clinical trials have supported the clinical efficacy of ursodeoxycholic acid and its safety when used in patients with primary biliary cholangitis. A review of ursodeoxycholic acid in the context of primary biliary cholangitis is carried out, and its history, mechanisms of action, side effects and dosage are described. Finally, its use in special situations such as pregnancy and lactation are discussed.

Expert consensus on the diagnosis and treatment of intrahepatic cholestasis (2021 edition) / 中华肝脏病杂志

Intrahepatic cholestasis is a clinical syndrome due to the defect of bile acid synthesis, abnormal bile excretion, and mechanical or functional disturbance of intrahepatic bile flows caused by hepatic parenchymal cell and/or intrahepatic bile duct diseases. It commonly occurs as cholestatic liver diseases, intrahepatic cholestasis of pregnancy, and genetic/metabolic-related cholestatic diseases. In recent years, new information and progress in diagnosis and treatment of intrahepatic cholestatic diseases have been achieved. In order to provide updated clinical reference and guidance for clinicians, we organized experts to compile the Expert Consensus on the Diagnosis and Treatment of Intrahepatic Cholestasis (2021), on the basis of the 2015 edition.

Bear bile powder attenuates senecionine-induced hepatic sinusoidal obstruction syndrome in mice / 中国天然药物

Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.

Hiperbilirrubinemia: visión del patólogo / Hyperbilirubinemia: pathologist's view

Los niveles de bilirrubina sérica normal en el adulto varían entre 0,3 mg/dL y 1,2 mg/dL, y su valor está determinado por la tasa de captación hepática, conjugación y excreción. La ictericia se hace evidente cuando los niveles de bilirrubina sérica se elevan por encima de 2,5 mg/dL a 3 mg/dL, siendo un indicador de enfermedad subyacente. La bilis es producida por los hepatocitos y fluye desde los canalículos, canales de Hering, conductos biliares intrahepáticos, conductos hepáticos derechos e izquierdos hasta llegar al duodeno. A nivel histopatológico, cualquier entidad que lleve a la acumulación intrahepática de bilis por disfunción hepatocelular u obstrucción biliar genera colestasis, que se observa en la biopsia hepática como la acumulación de tapones de color marrón verdoso de pigmento biliar en los hepatocitos, y secundariamente se observan los canalículos dilatados. Las causas de colestasis intrahepática son diversas e incluyen enfermedades como colangitis biliar primaria, colangitis esclerosante primaria, hepatitis autoinmune, hepatitis virales y toxicidad medicamentosa. Esta revisión tiene como objetivo analizar algunos tipos de hiperbilirrubinemia, resaltando sus características histopatológicas.

Normal serum bilirubin levels in adults range from 0.3 mg/dL to 1.2 mg/dL, and its value is determined by the rate of hepatic uptake, conjugation, and excretion. Jaundice becomes apparent when serum bilirubin levels rise above 2.5 mg/dL to 3.5 mg/dL and is an indicator of underlying disease. Bile is produced by hepatocytes and flows from the canaliculi, Hering's canals, intrahepatic bile ducts, and right and left hepatic ducts to the duodenum. Pathologically, any condition that leadsto intrahepatic accumulation of bile due to hepatocellular dysfunction or biliary obstruction, generates cholestasis, which is observed in liver biopsy as the accumulation of greenish-brown deposits of bile pigment in hepatocytes, with dilated canaliculi. The causes of intrahepatic cholestasis are diverse and include diseases such as primary biliary cholangitis and primary sclerosing cholangitis, autoimmune hepatitis, viral hepatitis, and drug toxicity. This review aims to analyze some types of hyperbilirubinemia, highlighting their histopathological characteristics.

Esfincterotomia isolada versus esfincterotomia associada a passagem de prótese biliar no tratamento de fístulas biliares: 10 anos de experiência de um hospital quaternário / Sphincterotomy alone versus sphincterotomy and biliary stent placement in the treatment of bile leaks: 10 year experience at a quaternary hospital

ABSTRACT BACKGROUND: Hepatobiliary surgery and hepatic trauma are frequent causes of bile leaks and this feared complication can be safely managed by endoscopic retrograde cholangiopancreatography (ERCP). The approach consists of sphincterotomy alone, biliary stenting or a combination of the two but the optimal form remains unclear. OBJECTIVE: The aim of this study is to compare sphincterotomy alone versus sphincterotomy plus biliary stent placement in the treatment of post-surgical and traumatic bile leaks. METHODS: We retrospectively analyzed 31 patients with the final ERCP diagnosis of "bile leak". Data collected included patient demographics, etiology of the leak and the procedure details. The treatment techniques were divided into two groups: sphincterotomy alone vs. sphincterotomy plus biliary stenting. We evaluated the volume of the abdominal surgical drain before and after each procedure and the number of days needed until cessation of drainage post ERCP. RESULTS: A total of 31 patients (18 men and 3 women; mean age, 51 years) with bile leaks were evaluated. Laparoscopic cholecystectomy was the etiology of the leak in 14 (45%) cases, followed by conventional cholecystectomy in 9 (29%) patients, hepatic trauma in 5 (16%) patients, and hepatectomy secondary to neoplasia in 3 (9.7%) patients. The most frequent location of the leaks was the cystic duct stump with 12 (38.6%) cases, followed by hepatic common duct in 10 (32%) cases, common bile duct in 7 (22%) cases and the liver bed in 2 (6.5%) cases. 71% of the patients were treated with sphincterotomy plus biliary stenting, and 29% with sphincterotomy alone. There was significant difference between the volume drained before and after both procedures (P<0.05). However, when comparing sphincterotomy alone and sphincterotomy plus biliary stenting, regarding the volume drained and the days needed to cessation of drainage, there was no statistical difference in both cases (P>0.005). CONCLUSION: ERCP remains the first line treatment for bile leaks with no difference between sphincterotomy alone vs sphincterotomy plus stent placement.

RESUMO CONTEXTO: Cirurgia hepatobiliar e trauma hepático são causas frequentes de fístulas biliares, e esta temida complicação pode ser manejada de forma segura através da colangiopancreatografia retrógrada endoscópica (CPRE). O procedimento consiste em esfincterotomia isolada, passagem de prótese biliar ou combinação das duas técnicas, porém a forma ideal permanece incerta. OBJETIVO: O objetivo desse estudo é comparar a realização de esfincterotomia isolada versus locação de prótese biliar no tratamento de fístulas pós-cirúrgicas e traumáticas. MÉTODOS: Foram analisados de forma retrospectiva 31 CPREs com diagnóstico final de "fístula biliar". A informação colhida incluía dados demográficos dos pacientes, etiologia das fístulas e detalhes dos procedimentos. As técnicas de tratamentos foram divididas em dois grupos: esfincterotomia isolada vs esfincterotomia associada a locação de prótese biliar. Foram analisados os volumes dos drenos abdominais cirúrgicos antes e depois de cada procedimento e o número de dias necessários para que ocorresse cessação da drenagem pelo dreno abdominal cirúrgico após a CPRE. RESULTADOS: Um total de 31 pacientes (18 homens e 3 mulheres; idade média de 51 anos) com fístulas biliares foram avaliados. Colecistectomia laparoscópica foi a etiologia da fístula em 14 (45%) casos, seguida de colecistectomia convenvional em 9 (29%) pacientes, trauma hepático em 5 (16%) pacientes, e hepatectomia secundária a neoplasia em 3 (9,7%) pacientes. As localizações mais frequentes das fístulas foram: coto do ducto císticos com 12 (38,6%) casos, seguido de ducto hepático comum em 10 (32%) casos, ducto colédoco em 7 (22%) cases e leito hepático em 2 (6,5%) casos. 71% dos pacientes foram tratados com esfincterotomia associada a passagem de prótese biliar e 29% com esfincterotomia isolada. Houve diferença estatística em relação ao volume drenado antes e depois de ambos os procedimentos (P<0,05). Entretanto, quando comparada esfincterotomia isolada e esfincterotomia associada a passagem de prótese biliar, em relação ao volume drenado e ao número de dias necessários para cessação da drenagem, não houve diferença estatística em ambos os casos (P>0,005). CONCLUSÃO: A CPRE permanece como tratamento de primeira linha no tratamento de fístulas biliares, sem diferença entra a esfincterotomia isolada versus esfincterotomia associada a passagem de prótese biliar.

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.

Current quality standards of cattle bile and sheep bile quality standards and discussion on related problems / 中国中药杂志

To analyze quality standards of cattle bile and sheep bile, and to discuss the related problems in the standards. The results showed that physical forms of the related medicinal materials of cattle bile and sheep bile were chaotic, and the technical methods adopted in the quality standards were generally backward. In addition, there were still problems that some medicinal material standards lacked necessary test items, which were especially obvious in the relevant medicinal material standards of sheep bile and brought difficulties to quality evaluation and control. We suggest that physical forms of cattle bile and sheep bile in quality standards should be determined, and inspection items should be completed. Based on mainstream analytical technology, some technical methods of these standards should be improved.

Bile acid derivatives-focused chemical profiling in snake bile / 中国中药杂志

As a precious traditional Chinese medicine(TCM), snake bile has been widely used in numerous Chinese medicine prescriptions. Bile acid(BA) derivatives have been demonstrated as the primary chemical family in snake bile. In-depth chemical characterization of BAs is of great importance towards the establishment of quality standards and clarification of the effective material basis for snake bile. This study firstly employed ~1H-NMR to preliminarily analyze the chemical profiles of snake bile, an automated fraction collector was subsequently implemented to obtain the fractions-of-interest. The fraction was then concentrated and re-analyzed by LC-MS. Based on ~1H-NMR, BAs were found to be the main components of snake bile, and six BAs including CDCA, CA, TCDCA, TCA, TDCA and GCA were tentatively identified from the representative spectrum with the assistance of literature and reference compounds. Whereas the content of TCA in snake bile was too great, resulting in a great obstacle for the detection of trace components, the automated fraction collector was subsequently implemented to obtain the fractions-of-interest for LC-MS analysis. According to matching MS/MS information and retention time with reference compounds as well as database retrieval, a total of 57 BAs were detected and annotated. Because of the combination of ~1H-NMR and LC-MS platforms, the findings are beneficial for the in-depth characterization of BAs in snake bile, which provides references for the establishment of quality control and evaluation methods of snake bile.

Key to Indigo Naturalis' oral effectiveness: in vivo and in vitro verification of bile action / 中国中药杂志

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that " Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.

Cáncer de vesícula biliar ¿la contaminación por bilis afecta el pronóstico? / Gallbladder Cancer: does bile contamination affect the prognosis?

Resumen Introducción: En algunas áreas el cáncer de la vesícula biliar se detecta en hasta el 3,5% de los pacientes intervenidos por colelitiasis. Con el objetivo de evaluar el rol de la ruptura de la vesícula y la consiguiente contaminación por bilis, se evaluó una serie de pacientes portadores de cáncer de vesícula diagnosticado posterior a la colecistectomía. Materiales y Método: El estudio se efectuó en 109 pacientes en quienes se diagnosticó un cáncer de vesícula posterior a la colecistectomía. El grupo a estudiar se dividió de acuerdo a la ocurrencia o no de contaminación por bilis al momento de la colecistectomía, como también de acuerdo a la magnitud de ésta. Resultados: De los pacientes estudiados, en 32 se documentó la ocurrencia de contaminación por bilis al momento de la colecistectomía. De estos, en 13 la contaminación fue considerada mayor. El tiempo promedio de seguimiento fue de 33 meses, 35 pacientes (32,1%) fallecieron durante el seguimiento. La sobrevida media de la totalidad de la serie que tuvo contaminación por bilis no se diferenció de los pacientes sin contaminación. Sin embargo, el grupo que tuvo una contaminación catalogada como mayor, presentó una sobrevida estadísticamente inferior al resto de los pacientes. Finalmente, se realizó un análisis mediante el modelo de regresión de COX que incluyó edad, género, nivel de invasión y tipo de contaminación, resultando la existencia de contaminación mayor por bilis un factor independientemente asociado al pronóstico. Conclusión: La presencia de ruptura vesicular y contaminación mayor por bilis debiera considerarse un factor pronóstico.

Background: Incidental gallbladder cancer is observed in up to 3.5% of patients undergoing laparoscopic cholecystectomy. To study the role of wall perforation on the prognosis, we evaluated a series of patients in whom perforation occurred during the cholecystectomy. Materials and Method: 109 patients who underwent a laparoscopic cholecystectomy in whom final diagnosis was gallbladder cancer were the focus of the study. We divided the patients according the occurrence of spillage. Furthermore, patients with spillage were divided into two categories according the spillage magnitude. Results: Of the patients, spillage was documented in 32 (29.3%). In 13 patients spillage was considered major. The median follow-up of patients was 36 months, while 35 (32.1%) patients died during the follow-up. Five-year survival of all patients with spillage was not statistically different from the group without spillage. However, the group with major spillage had a statistically worse survival than the rest. A Cox regression analysis including age, gender, level of invasion and spillage category showed that major spillage was independently associated with a worse prognosis.

La vesícula biliar como reservorio y protectora del tracto digestivo / The gallbladder as reservoir and protector of the digestive tract

Introducción: Estudios anatomofisiológicos y biomoleculares de la vesícula biliar han permitido redefinir su función no solo como reservorio de la secreción biliar, sino como protectora intestinal, concepto que se fundamenta en su capacidad de control de la bioactividad y la toxicología de los ácidos biliares, el metabolismo del colesterol, los fosfolípidos y otros componentes de la secreción hepatobiliar. Objetivo: Describir las actualidades de la funcionabilidad de la vesícula biliar como reservorio y protectora del tracto digestivo dirigido a que cirujanos generales, gastroenterólogos, clínicos y fisiólogos amplíen sus conocimientos sobre la función de la vesícula biliar. Métodos: Se realiza una revisión crítica de las funciones de la vesícula biliar que favorecen mantener la integridad de la pared intestinal. Conclusión: La descripción actualizada de la funcionabilidad de la vesícula biliar ofrece un resultado relevante dentro del marco conceptual en relación a su función protectora que se traduce en el mantenimiento de la integridad del epitelio y la microbiota intestinal(AU)

Introduction: Anatomic-physiological and biomolecular studies of the gallbladder have made it possible to redefine its function not only as a reservoir for bile secretion, but also as intestinal protector. This concept is supported by its capacity to control the bioactivity and toxicology of bile acids, cholesterol metabolism, phospholipids and other components of hepatobiliary secretion. Objective: Present an update on the role of the gallbladder as reservoir and protector of the digestive tract intended for general surgeons, gastroenterologists, clinicians and physiologists to broaden their knowledge about the functions of the gallbladder. Methods: A critical review was conducted of the functions of the gallbladder which facilitate maintenance of the integrity of the intestinal wall. Conclusion: The updated description of the functions of the gallbladder is a relevant contribution to the conceptual framework of its protective function, which ensures the maintenance of the integrity of the epithelium and the intestinal microbiota(AU)

The diversity of ursodeoxycholic acid precursors from bile waste of commercially available fishes, poultry and livestock in Indonesia

Ursodeoxycholic acid (UDCA), a secondary bile acid (BA), has been used as a drug to treat various liver diseases. UDCA is synthesised from cholic or chenodeoxycholic acid (CA/CDCA), two primary BAs frequently used as the starting materials. Nowadays, swine, cattle, and poultry bile are the main sources of those BAs. However, other commercial animals could be promising sources as well. We identified two livestock, two poultries, and eight fishes that are commercially cultivated in Indonesia. Four free BAs including CA, CDCA, deoxycholic acid (DCA), and lithocholic acid (LA) were identified for their occurrences using thin-layer chromatography and high-performance liquid chromatography. CA was detected in cow, duck, red tilapia, gourami, the common carp, and grouper, whereas CDCA was only detected in two poultries and the common carp. The occurrence of DCA was common and abundant in most tested animals. In contrast, the presence of LA was found to be very low in all samples. The biliary bile of tilapia has been found to contain a high abundance of free CA (43% of the total bile). A simple extraction was able to purify CA from biliary bile of tilapia. This is a new promising and competitive source of CA.

Identification of metabolites of Zhali Nusi Prescription in rat plasma, bile, urine and feces after oral administration / 中国中药杂志

This study was designed to determine the metabolites of Zhali Nusi Prescription(ZLNSP) in rats. The ultra-high performance liquid chromatography-LTQ Orbitrap mass spectrometric(UHPLC-LTQ-Orbitrap-MS) and mass defect filter techniques were applied to analyze the metabolites of ZLNSP in rat plasma, bile, urine and feces. The biological samples were analyzed by ACQUITY UPLC BEH T_3 column(2.1 mm×100 mm,1.7 μm), with 0.1% formic acid water(A)-acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). An analytical method for biological samples of rats was established, and 8 prototype components and 36 metabolites were identified. The results showed that the metabolic pathways of the main components of ZLNSP in rats included methylation, glucuronidation, sulfation and so on. It provi-ded information for the therapeutic effect of ZLNSP in vivo.

Investigation of chemical profile of bile acids and determination of them in cultured Bovis Calculus with UPLC-QDA / 中国中药杂志

In this study, 10 batches of samples of cultured Bovis Calculus(cow-bezoar) were determined for the investigation of chemical profile of bile acids with the UPLC-QDA method established. The results showed that nine common bile acids, cholic acid(CA), deoxycholic acid(DCA), chenodeoxycholic acid(CDCA), taurocholic acid(TCA), taurodeoxycholic acid(TDCA), taurochenodeoxycholic acid(TCDCA), glycocholic acid(GCA), glycodeoxycholic acid(GDCA) and glycochenodeoxycholic acid(GCDCA), were founded in samples and 7 bile acids were quantified except GDCA and GCDCA. In these samples, unconjugated bile acids, the major type of bile acids, accounted for more than 97% of all types of bile acids. As for unconjugated bile acids, CA was the most major bile acid in cultured cow-bezoar and it was about twice as much as DCA. The relative low-cost method established in the current study is accurate, rapid and sensitive, which is suitable for the studies of other drugs from animal bile.

Bile acid detection by biosensors-a review / 生物工程学报

Bile acids facilitate the absorption of lipids, and affect the development of various diseases by regulating intestinal flora structure and modulating immunity and metabolism. It is therefore important to quantitatively detect bile acids. Current analytical methods are still immature due to constituent complexity, structural heterogeneity and bioactive variability of bile acids. Detection of individual bile acids is of significance for pharmacological research, clinical diagnosis and disease prevention. Advances have been made in bile acid analysis from multiple sources including serum, bile, urine and feces, although several limitations still exist for bile acid quantification. Here we review research progress in conventional bile acid assays, including spectrophotometry, thin-layer chromatography, liquid/gas chromatography and liquid/gas chromatography-mass spectrometry. Moreover, we emphasize the development of bile acid biosensors that may have promising prospects.

Successful Treatment with Rituximab and Immunoadsorption for an Auto-Antibody Induced Bile Salt Export Pump Deficiency in a Liver Transplanted Patient / 대한소아소화기영양학회지

We present an 8 years old girl who was diagnosed at 6 months of age of Progressive Familial Intrahepatic Cholestasis type 2. Although liver transplantation (LT) was classically considered curative for these patients, cholestasis recurrence with normal gamma-glutamyl transpeptidase (GGT), mediated by anti-bile salt export pump (BSEP) antibodies after LT (auto-antibody Induced BSEP Deficiency, AIBD) has been recently reported. Our patient underwent LT at 14 months. During her evolution, patient presented three episodes of acute rejection. Seven years after the LT, the patient presented pruritus with cholestasis and elevation of liver enzymes with persistent normal GGT. Liver biopsy showed intrahepatic cholestasis and giant-cell transformation with very low BSEP activity. Auto-antibodies against BSEP were detected therefore an AIBD was diagnosed. She was treated with Rituximab and immunoadsorption with resolution of the AIBD. As a complication of the treatment she developed a pneumocystis infection successfully treated with corticoids, cotrimoxazol and anidulafungin.

Bear Bile Powder Inhibits Growth of Hepatocellular Carcinoma via Suppressing STAT3 Signaling Pathway in Mice / 中国结合医学杂志

OBJECTIVE@#To evaluate the inhibitory effect of bear bile powder (BBP) on hepatocellular carcinoma (HCC) growth in vivo and investigate the underlying mechanisms.@*METHODS@#A HCC xenograft mouse model was developed by producing with huh7 cells. After 5 days following xenograft implantation, ten HCC xenograft mice were given intra-gastric administration with 10 mg/(kg•d) dose of BBP or saline for 3 weeks. Tumor growth in HCC xenograft mice was evaluated by measuring the tumor weight and volume. Cell apoptosis, proliferation or tumor angiogenesis were examined via immunohistochemical (IHC) staining for transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), proliferating cell nuclear antigen (PCNA) or cluster of differentiation 31 (CD31), respectively. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) were determined by Western blot. The mRNA and protein expressions of Bcl-2, Bax, Cyclin D1 and Cyclin-dependent kinase 4 (CDK4) in HCC tumor tissues were respectively determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The protein expression of vascular endothelial growth factor A (VEGF-A) in tumor tissues was examined by IHC staining.@*RESULTS@#BBP treatment led to a significant decrease on tumor volume and tumor weight in HCC mice (P<0.05) and had no effect on the change of body weight. In addition, BBP profoundly promoted cell apoptosis, inhibited cell proliferation and intratumoral microvessel density in HCC tumor tissues (P<0.05). Moreover, BBP treatment remarkably suppressed the STAT3 phosphorylation and modulated the expression of critical target genes including Bcl-2, Bax, Cyclin D1, CDK4 and VEGF-A in HCC mice.@*CONCLUSION@#BBP exerts its anti-cancer activities via suppressing STAT3 signaling pathway and affecting multiple intracellular targets.

Comparison study for surgical outcomes of right versus left side hemihepatectomy to treat hilar cholangiocellular carcinoma

PURPOSE: Major liver resection and radical lymph node dissection has been accepted as a definite treatment of choice for hilar cholangiocarcinoma (HC). However, the perioperative and survival outcomes of right hemihepatectomy (RH) and left hemihepatectomy (LH) still remain controversial. Thus, this study aimed to compare the surgical and oncological outcomes of RH and LH in HC patients.METHODS: From January 2000 to January 2018, a total of 326 patients underwent surgical resection for HC at Yonsei University College of Medicine in Seoul, Korea. Among the 326 patients, we excluded 130 patients and selected 196 patients, who underwent hemihepatectomy with caudate lobectomy. Among these 196 patients, 114 patients underwent RH, and 82 patients underwent LH. We compared the clinicopathological features as well as the surgical and oncologic outcomes of the RH and LH groups.RESULTS: There were no significant differences in disease-free survival (P = 0.473) or overall survival (P = 0.946) in the RH and LH groups. The LH group had fewer complications compared with the RH group, including postoperative ascites (RH: 15 [13.2%] vs. LH: 3 [3.7%], P = 0.023); however, the LH group had more bile leakage complications (RH: 5 [4.4%] vs. LH: 12 [14.6%], P = 0.012). The average time lag from portal vein embolization to operation was 25.80 ± 12.06 days (n = 45). There was no difference in postoperative liver failure (P = 0.402), although there were significantly more frequent ascites after RH (P = 0.023).CONCLUSION: LH might be a good alternative option for the surgical treatment of HC given appropriate tumor location and biliary anatomy indications.