RESUMO
BACKGROUND: Visceral hemangiomatosis is a benign tumor (rarer than hemangioma) that has not been reported to occur in the pancreas, duodenum, or choledoch. It can be easily confused with other pancreatic tumors or choledocholithiasis. Herein, we describe a case of a child with pancreaticoduodenal and choledochal hemangiomatosis and the key characteristics for the accurate diagnosis of pancreatic tumors based on previous reports and our findings. CASE PRESENTATION: We report a case of a 2-year and 9-month-old child who presented with repeated and fluctuating jaundice for 3 months with a history of endoscopic stone removal in a local hospital, following the diagnosis of choledocholithiasis. An abdominal computed tomography revealed a previously undiagnosed pancreatic head tumor and celio-mesenteric trunk (a rare vascular variation). This was misdiagnosed as a pancreatic neuroendocrine tumor. Since the patient's parents refused FNA biopsy and insisted on surgery, pancreaticoduodenectomy was performed; however, postoperatively, the child was correctly diagnosed with pancreaticoduodenal and choledochal hemangiomatosis. Although the patient was in good condition and had gained 4 kg in weight 3 months postoperatively, pancreaticoduodenectomy could have been avoided if an accurate diagnosis had been established before or during the operation. CONCLUSION: Our report highlights the difficulty in diagnosing visceral hemangiomatosis. Radiologists, endoscopists, and surgeons should consider this possibility in cases of repeated and fluctuating jaundice that cannot be explained by choledocholithiasis alone.
Assuntos
Coledocolitíase , Hemangioma , Neoplasias Pancreáticas , Criança , Coledocolitíase/patologia , Hemangioma/patologia , Humanos , Lactente , Pâncreas/irrigação sanguínea , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Doenças Raras/patologiaRESUMO
Choledocholithiasis is a chronic common disease. The incidence of cholelithiasis is 5%-15%, of which 5%-30% are combined with Choledocholithiasis. Although endoscopic cholangiopancreatography (ERCP) + endoscopic sphincterotomy (EST) is the most common treatment procedure, which clearance rate is up to 95%, the incidence of recurrent choledocholithiasis was 4%-25%. The risk factors of recurrence after choledocholithiasis clearance are the focuses of current researches, which are caused by multiple factors. We first systematically summarize the risk factors of common bile duct stones (CBDS) recurrence into five aspects: first-episode stone related factors, congenital factors, biological factors, behavioral intervention factors, and the numbers of stone recurrence.
Assuntos
Coledocolitíase/epidemiologia , Colangiopancreatografia Retrógrada Endoscópica , Coledocolitíase/diagnóstico , Coledocolitíase/patologia , Coledocolitíase/cirurgia , Ducto Colédoco/patologia , Ducto Colédoco/cirurgia , Humanos , Incidência , Recidiva , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Esfinterotomia Endoscópica , Resultado do TratamentoRESUMO
OBJECTIVE: Choledocholithiasis (CDL), a potential risk for cholangiocarcinoma (CCA) development, is often a consequence of bacterial infection. Thus, the microbial population that contributes to CDL might also be involved in CCA development. We compared the microbiome in bile fluid of CDL patients and CCA patients. METHODS: Bile samples were collected from CDL (n = 30) and CCA (n =30) patients. Microbial profiling was performed individually by the sequencing of V3-V4 regions of the 16S rRNA gene. RESULTS: Enterobacter, Pseudomonas, and Stenotrophomonas species were much more abundant in bile samples from CCA compared to CDL (p.
Assuntos
Bactérias/classificação , Bactérias/genética , Neoplasias dos Ductos Biliares/microbiologia , Colangiocarcinoma/microbiologia , Coledocolitíase/microbiologia , Microbiota , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Coledocolitíase/genética , Coledocolitíase/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND AND AIMS: Circular RNAs (circRNAs) and extracellular vesicles (EVs) are involved in various malignancies. We aimed to clarify the functions and mechanisms of dysregulated circRNAs in the cells and EVs of cholangiocarcinoma (CCA). APPROACH AND RESULTS: CircRNA microarray was used to identify circRNA expression profiles in CCA tissues and bile-derived EVs (BEVs). CCA-associated circRNA 1 (circ-CCAC1) expression was measured by quantitative real-time PCR. The clinical importance of circ-CCAC1 was analyzed by receiver operating characteristic curves, Fisher's exact test, Kaplan-Meier plots, and Cox regression model. The functions of circ-CCAC1 and exosomal circ-CCAC1 were explored in CCA cells and human umbilical vein endothelial cells (HUVECs), respectively. Different animal models were used to verify the in vitro results. RNA sequencing, bioinformatics, RNA immunoprecipitation, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and luciferase reporter assays were used to determine the regulatory networks of circ-CCAC1 in CCA cells and HUVECs. Circ-CCAC1 levels were increased in cancerous bile-resident EVs and tissues. The diagnostic and prognostic values of circ-CCAC1 were identified in patients with CCA. For CCA cells, circ-CCAC1 increased cell progression by sponging miR-514a-5p to up-regulate Yin Yang 1 (YY1). Meanwhile, YY1 directly bound to the promoter of calcium modulating ligand to activate its transcription. Moreover, circ-CCAC1 from CCA-derived EVs was transferred to endothelial monolayer cells, disrupting endothelial barrier integrity and inducing angiogenesis. Mechanistically, circ-CCAC1 increased cell leakiness by sequestering enhancer of zeste homolog 2 in the cytoplasm, thus elevating SH3 domain-containing GRB2-like protein 2 expression to reduce the levels of intercellular junction proteins. In vivo studies further showed that increased circ-CCAC1 levels in circulating EVs and cells accelerated both CCA tumorigenesis and metastasis. CONCLUSIONS: Circ-CCAC1 plays a vital role in CCA tumorigenesis and metastasis and may be an important biomarker/therapeutic target for CCA.
Assuntos
Neoplasias dos Ductos Biliares/sangue , Carcinogênese/metabolismo , Colangiocarcinoma/sangue , Endotélio Vascular/metabolismo , Neovascularização Patológica/metabolismo , RNA Circular/sangue , RNA Circular/genética , Animais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Coledocolitíase/sangue , Coledocolitíase/genética , Coledocolitíase/patologia , Vesículas Extracelulares/metabolismo , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , Camundongos Nus , Reação em Cadeia da Polimerase em Tempo Real , Transfecção , Carga Tumoral/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Laparoscopic cholecystectomy (LC) is the criterion standard for treating patients with symptomatic gallstone disease; however, the optimal technique for extracting common bile duct stones remains unclear. Recent studies have noted improved outcomes with single-stage techniques, such as intraoperative endoscopic retrograde cholangiopancreatography (iERCP) and laparoscopic common bile duct exploration (LCBDE); however only few studies have directly compared those two single-stage techniques. OBJECTIVES: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, we retrospectively analyzed the postoperative outcomes of all patients who underwent single-stage LC for choledocholithiasis from 2005 to 2017. Using Current Procedural Terminology (CPT) codes, as well as International Classification of Diseases, Ninth Revision (ICD-9) and 10th Revision (ICD-10) codes, we stratified patients into two cohorts: those who underwent iERCP and LCBDE. Applying univariate techniques, we evaluated baseline characteristics and postoperative outcomes for both cohorts. Our primary outcomes of interest were 30-day morbidity and 30-day mortality; our secondary outcomes included rates of reoperation, readmission, operative time, and hospital length of stay. RESULTS: Of the 1814 single-stage LC patients during our 13-year study period, 1185 (65.3%) underwent LCBDE; 629 (34.6%) underwent iERCP. Our univariate analysis showed that the two cohorts were homogeneous in terms of baseline characteristics, including demographics, preoperative comorbidities, laboratory values, and American Society of Anesthesiologists (ASA) scores. 30-day postoperative morbidity (including infectious and noninfectious complications) and overall mortality between groups were low and comparable. The mean operative time was slightly longer with LCBDE (125.1 ± 62.0 min) than iERCP (113.5 ± 65.2 min; P < 0.001), however the mean hospital length of stay, readmission rate, and reoperation rate were similar. CONCLUSION: We found that both iERCP and LCBDE resulted in low, comparable rates of morbidity and mortality. Centers with readily available endoscopic expertise might favor iERCP for its ease of access and shorter operative time. However, LCBDE remains an appropriate technique for patients with choledocholithiasis, especially when immediate endoscopic intervention is unavailable.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomia Laparoscópica/métodos , Coledocolitíase/cirurgia , Ducto Colédoco/cirurgia , Coledocolitíase/mortalidade , Coledocolitíase/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Many patients with intrahepatic cholelithiasis need surgical treatment during their life. For patients with hepatolithiasis, conventional therapy methods suggest partial hepatectomy or hepatic transplantation, while both kinds of surgery carry a considerable risk and trauma. Under such conditions, percutaneous transhepatic cholangioscopic lithotripsy provides an alternative method for hepatolithiasis treatment. Conventional rigid choledochoscope applied in percutaneous transhepatic cholangioscopic lithotripsy often lack sufficient flexibility for complete intrahepatic bile duct inspection. In this article, we report a case of one patient with complex hepatolithiasis and choledocholithiasis who received percutaneous transhepatic cholangioscopic lithotripsy using the newly-developed soft fiber-optic choledochoscope. This treatment represents a safe and effective outcome. We came to the conclusion that soft fiber-optic choledochoscope guided percutaneous transhepatic cholangioscopic lithotripsy seems a promising treatment option for selected patients with hepatolithiasis, especially for those who cannot accept conventional methods.
Assuntos
Coledocolitíase , Litotripsia , Hepatopatias , Idoso , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/patologia , Coledocolitíase/cirurgia , Humanos , Laparoscopia/instrumentação , Litotripsia/instrumentação , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Hepatopatias/cirurgia , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: The removal of large bile duct stones (> 15 mm) by conventional endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilation (EPBD) can be challenging, requiring mechanical lithotripsy (ML) in addition to EST or EPBD. The primary complication of ML is basket and stone impaction, which can lead to complications such as pancreatitis and cholangitis. The present study aims to investigate the efficacy of limited EST plus endoscopic papillary large balloon dilation (EST-EPLBD) for large bile duct stone extraction with an extent of cutting < 1/2 the length of the papillary mound. METHODS: We enrolled 185 patients with ≥15 mm bile duct stones who received EST, EPLBD and limited EST-EPLBD treatment from January 1, 2010 to February 28, 2018, at Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan). All patients were categorized into three groups: EST group (n = 31), EPLBD group (n = 96), and limited EST-EPLBD group (n = 58). The primary outcome variables were the success rate of complete stone removal and complications. RESULTS: The limited EST-EPLBD group exhibited a higher success rate of the first-session treatment compared with the EST and EPLBD groups (98.3% vs. 83.9% vs. 86.5%; P = 0.032) but required a longer procedure time (32 (12-61) min vs. 23.5 (17-68) min vs. 25.0 (14-60) min; P = 0.001). The need for ML during the procedure was 4 (12.9%) in the EST group, 10 (10.4%) in the EPLBD group and 2 (3.4%) in the limited EST-EPLBD group. Post-procedure bleeding in the EST group was more common than that in the limited EST-EPLBD group (9.7% vs. 0%; P = 0.038). Furthermore, dilated bile duct was the only risk factor for bile duct stone recurrence in the limited EST-EPLBD group. CONCLUSIONS: Limited EST-EPLBD exhibits a higher success rate but requires marginally longer procedure time for the first-session treatment. Furthermore, dilated bile duct is the only risk factor for bile duct stone recurrence in patients undergoing limited EST-EPLBD.
Assuntos
Ampola Hepatopancreática/cirurgia , Coledocolitíase/cirurgia , Dilatação/métodos , Enteroscopia de Balão Único/métodos , Esfinterotomia Endoscópica/métodos , Adulto , Cateterismo , Coledocolitíase/patologia , Dilatação/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Enteroscopia de Balão Único/instrumentação , Resultado do TratamentoRESUMO
INTRODUCTION: In Roux-en-Y reconstructions, choledocholithiasis could represent a really challenging condition to treat which can be treated by a surgical-assisted ERCP. Only six cases of transjejunal laparoscopic-assisted ERCP (LAERCP) can be found in literature to date and no large series are present. METHODS: A young woman who had undergone a laparoscopic Roux-en-Y gastric bypass 2 years earlier came complaining recurrent abdominal pain. Radiologic exams found stones in the common bile duct and no signs of internal hernia. We therefore decided to perform a transjejunal LAERCP finding a concomitant internal hernia in the Petersen's space which was repaired at the same time. RESULTS: The post-operative course was uneventful. CONCLUSION: Transjejunal LAERCP is a feasible technique to deal with choledocholithiasis, and it allows at the same time to identify and treat concomitant conditions like internal hernias.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Coledocolitíase/etiologia , Coledocolitíase/cirurgia , Derivação Gástrica/efeitos adversos , Jejuno/cirurgia , Complicações Pós-Operatórias/cirurgia , Adulto , Coledocolitíase/patologia , Feminino , Derivação Gástrica/métodos , Hérnia Abdominal/etiologia , Hérnia Abdominal/patologia , Hérnia Abdominal/cirurgia , Humanos , Jejuno/patologia , Laparoscopia/métodos , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/patologia , Adulto JovemRESUMO
Follicular cholecystitis (FC) is a relatively rare entity with uncertain causal associations. In this study, we aimed to explore different clinicopathologic associations of FC, and to better characterize the entity. A retrospective review of archival hematoxylin and eosin slides and pertinent clinical information was undertaken for all cholecystectomy cases with a rendered diagnosis of "follicular cholecystitis," from 1991 to 2017. Concurrent conventional chronic cholecystitis (CC) and lymphocytic cholecystitis (LC) were documented. Forty-three consecutive patients were confirmed to have FC. The majority of the patients (88.4%) had at least one other histologic association in the gallbladder (LC, CC, or both). Remarkably, functional distal biliary obstruction (from choledocholithiasis, sclerosing cholangitis, distal biliary strictures, or malignancies of the pancreatic head or ampulla) was found in 76.7% of the patients, irrespective of the presence of other concurrent histologic findings. FC associated with CC was relatively more common in females (61%) and strongly associated with cholelithiasis (70%). However, those without CC were predominantly males (70%) and had a significant association with LC (75%). All four cases of FC without any other histologic associations who had clinical information available showed some form of distal biliary obstruction. FC cases without concurrent LC were often associated with CC (74%). FC is strongly associated with extrahepatic biliary obstruction distal to the gallbladder. Therefore, this finding at routine cholecystectomy may warrant further evaluation to rule out a cause for distal biliary tract obstruction. Additionally, it is commonly associated with other concomitant histologic abnormalities in the gallbladder such as CC and/or LC.
Assuntos
Colecistite/patologia , Adulto , Idoso , Colecistectomia , Colecistite/cirurgia , Coledocolitíase/patologia , Colelitíase/patologia , Doença Crônica , Feminino , Vesícula Biliar/patologia , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Recidiva , Estudos RetrospectivosRESUMO
BACKGROUND/PURPOSE: The incidence of choledocholithiasis is increasing. The diagnosis of common bile duct (CBD) obstruction is based on abnormal CBD size. Establishing norms for CBD size in children would improve diagnostic accuracy. We analyzed ultrasounds (US) to determine normal pediatric CBD size based on age and then validated this against patients with choledocholithiasis. METHODS: A retrospective review was conducted for children less than 21 years of age with US defined CBD size. Patients were stratified into age groups by ANOVA statistical analysis. Secondary analysis included patients with confirmed choledocholithiasis in comparison to the normal cohort. RESULTS: A total of 778 patients had US without pathology. Group 1 (<1 year) had a mean CBD of 1.24±0.54 mm, group 2 (1-10 years) 1.97±0.71 mm, and group 3 (>10 years) 2.98±1.17 mm, p<0.05. Fourteen additional patients were found to have choledocholithiasis with a mean CBD size of 8.1 mm. All patients with choledocholithiasis had CBD sizes outside of our normal range, but only 50% of patients had enlarged CBD size based on adult normal range of values. CONCLUSION: Normal CBD size in children is less than a normal adult patient. More accurate normal values will aid in determining if a child needs further evaluation for possible obstruction of the CBD. TYPE OF STUDY: diagnostic Level of evidence: III.
Assuntos
Ducto Colédoco , Ultrassonografia , Adolescente , Criança , Pré-Escolar , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/patologia , Ducto Colédoco/anatomia & histologia , Ducto Colédoco/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Estudos RetrospectivosRESUMO
PURPOSE: To compare anthropometric data (body mass index [BMI]) in patients without lithiasis to patients with symptomatic simple cholelithiasis or choledocholithiasis. METHODS: We retrospectively reviewed data from 147 patients undergoing laparoscopic cholecystectomy between 2001-2015. Complete growth data from 98 patients was compared with anthropometric data from the population of the Czech Republic and a control group (BMI of 100 consecutive patients without biliary stones in abdominal ultrasound who were admitted to a surgical department for suspected appendicitis). RESULTS: The BMI of 75 children with simple cholelithiasis and 23 with choledocholithiasis was compared to the standard Czech pediatric population and to the control group. The median age (simple cholelithiasis and choledocholithiasis) was 16 years, and 35 patients (24%) had a family history of gallstones. Types of lithiasis included multiple (n = 120), solitary (n = 11), and sludge (n = 10). Five cases had polyps and one had gallbladder dysplasia. Patients with simple cholelithiasis had significantly higher BMI compared to the control group without cholelithiasis (p<0.0001) and the standard Czech population (p = 0.03). Patients with choledocholithiasis had a mean BMI significantly higher than that of the general population (p = 0.001) and the control group (p = 0.0001). Patients with choledocholithiasis had significantly higher BMI than those with simple cholelithiasis (p = 0.03). CONCLUSION: Patients with cholelithiasis had significantly higher BMI than the general population, and patients with choledocholithiasis had significantly higher BMI than patients with simple lithiasis. Elevated BMI is a risk factor for developing choledocholithiasis. ERCP and early laparoscopic cholecystectomy in patients with choledocholithiasis offer equivalent outcomes in patients with simple cholelithiasis.
Assuntos
Coledocolitíase/etiologia , Colelitíase/etiologia , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Colangiopancreatografia Retrógrada Endoscópica , Colecistectomia Laparoscópica , Coledocolitíase/patologia , Coledocolitíase/cirurgia , Colelitíase/patologia , Colelitíase/cirurgia , República Tcheca , Feminino , Humanos , Lactente , Masculino , Obesidade/complicações , Obesidade/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Choledocholithiasis is one of the more common benign disorders of the biliary tract with multiple features of presentation and several alternatives for its diagnosis and treatment. Our aim was to perform a based-evidence revision to propose a diagnostic and therapeutic algorithm. The raised values of gamma glutamiltranspeptidase, alkaline phosphatase and total bilirubin, are well predictors for a choledocholithiasis. The image evidence for a pre-operative detection with higher sensibility, specificity and better cost-effectiveness is the cholangioresonance. For its intraoperative detection, the cholangiography is the method most frequently used, though cholangioscopy is likewise useful. In the case of a post-operative suspicious, the cholangiography through the T tube is the gold standard. With regard to the treatment of the choledocholithiasis, the different stages are analyzed. depending if the detection was performed pre, intra or postoperatively. As a conclusion, the approach of the choledocholithiasis in one step seems to be better that to perform it in two steps, being the laparoscopic exploration for bile ducts stones more safety than the use of the intraoperative ERCP (endoscopic retrograde cholangiopancreatography) .The postoperative ERCP is not recommended excepting in very selected cases, and the biliodigestive derivations should be reserved only for the primary lithiasis of the common bile duc
Assuntos
Humanos , Ductos Biliares/cirurgia , Colangiografia , Cálculos da Bexiga Urinária/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Coledocolitíase/patologia , Síndrome de Mirizzi/terapiaRESUMO
BACKGROUND: The aim of this study was to evaluate the benefits of cholecystectomy on mitigating recurrent biliary complications following endoscopic treatment of common bile duct stone. METHODS: We used the data from the Taiwan National Health Insurance Research Database to conduct a population-based cohort study. Among 925 patients who received endoscopic treatment for choledocholithiasis at the first admission from 2005 to 2012, 422 received subsequent cholecystectomy and 503 had gallbladder (GB) left in situ. After propensity score matching with 1:1 ratio, the cumulative incidence of recurrent biliary complication and overall survival was analyzed with Cox's proportional hazards model. The primary endpoint of this study is recurrent biliary complications, which require intervention. RESULTS: After matching, 378 pairs of patients were identified with a median follow-up time of 53 (1-108) months. The recurrent rate of biliary complications was 8.20% in the cholecystectomy group and 24.87% in the GB in situ group (p < 0.001). In the multivariate Cox regression analysis, the only independent risk factor for recurrent biliary complications was GB left in situ (hazard ratio [HR] 3.55, 95% CI 2.36-5.33). CONCLUSIONS: Cholecystectomy after endoscopic treatment of common bile duct stone reduced the prevalence of recurrent biliary complications.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Colecistectomia , Coledocolitíase/cirurgia , Idoso , Idoso de 80 Anos ou mais , Coledocolitíase/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoAssuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Coledocolitíase/diagnóstico por imagem , Cálculos Biliares/cirurgia , Obstrução Intestinal/etiologia , Idoso de 80 Anos ou mais , Coledocolitíase/patologia , Cálculos Biliares/complicações , Humanos , Íleus/etiologia , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/cirurgia , Laparotomia/métodos , Masculino , Complicações Pós-Operatórias , Resultado do TratamentoRESUMO
Cholestatic liver injury results from impaired bile flow or metabolism and promotes hepatic inflammation and fibrogenesis. Toxic bile acids that accumulate in cholestasis induce apoptosis and contribute to early cholestatic liver injury, which is amplified by accompanying inflammation. The aim of the current study was to evaluate the role of the antiapoptotic caspase 8-homolog cellular FLICE-inhibitory (cFLIP) protein during acute cholestatic liver injury. Transgenic mice exhibiting hepatocyte-specific deletion of cFLIP (cFLIP-/-) were used for in vivo and in vitro analysis of cholestatic liver injury using bile duct ligation (BDL) and the addition of bile acids ex vivo. Loss of cFLIP in hepatocytes promoted acute cholestatic liver injury early after BDL, which was characterized by a rapid release of proinflammatory and chemotactic cytokines (TNF, IL-6, IL-1ß, CCL2, CXCL1, and CXCL2), an increased presence of CD68+ macrophages and an influx of neutrophils in the liver, and resulting apoptotic and necrotic hepatocyte cell death. Mechanistically, liver injury in cFLIP-/- mice was aggravated by reactive oxygen species, and sustained activation of the JNK signaling pathway. In parallel, cytoprotective NF-κB p65, A20, and the MAPK p38 were inhibited. Increased injury in cFLIP-/- mice was accompanied by activation of hepatic stellate cells and profibrogenic regulators. The antagonistic caspase 8-homolog cFLIP is a critical regulator of acute, cholestatic liver injury. NEW & NOTEWORTHY The current paper explores the role of a classical modulator of hepatocellular apoptosis in early, cholestatic liver injury. These include activation of NF-κB and MAPK signaling, production of inflammatory cytokines, and recruitment of neutrophils in response to cholestasis. Because these signaling pathways are currently exploited in clinical trials for the treatment of nonalcoholic steatohepatitis and cirrhosis, the current data will help in the development of novel pharmacological options in these indications.
Assuntos
Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/deficiência , Coledocolitíase/metabolismo , Ducto Colédoco/cirurgia , Células Estreladas do Fígado/metabolismo , Hepatite/metabolismo , Hepatócitos/metabolismo , Cirrose Hepática/metabolismo , Fígado/metabolismo , Animais , Apoptose , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/toxicidade , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Células Cultivadas , Coledocolitíase/etiologia , Coledocolitíase/genética , Coledocolitíase/patologia , Citocinas/metabolismo , Predisposição Genética para Doença , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/patologia , Hepatite/etiologia , Hepatite/genética , Hepatite/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Mediadores da Inflamação/metabolismo , Ligadura , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Camundongos Knockout , Necrose , Infiltração de Neutrófilos , Estresse Oxidativo , Fenótipo , Transdução de Sinais , Fatores de Tempo , Fator de Transcrição RelA/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin. Previous bile proteomic analyses in patients with PSC have revealed changes in disease activity specific to malignant transformation. In this study, we established a reference bile duct-derived bile proteome for PSC that can be used to evaluate biliary pathophysiology. Samples were collected from patients with PSC or with choledocholithiasis (control) (n=6 each). Furthermore, patients with PSC-associated cholangiocarcinoma (CC) and with CC without concomitant PSC were analyzed. None of the patients showed signs of inflammation or infection based on clinical and laboratory examinations. Proteins overexpressed in patients with PSC relative to control patients were detected by two-dimensional difference gel electrophoresis and identified by liquid chromatography-tandem mass spectrometry. Functional proteomic analysis was performed using STRING software. A total of 101 proteins were overexpressed in the bile fluid of patients with PSC but not in those of controls; the majority of these were predicted to be intracellular and related to the ribosomal and proteasomal pathways. On the other hand, 91 proteins were found only in the bile fluid of controls; most were derived from the extracellular space and were linked to cell adhesion, the complement system, and the coagulation cascade. In addition, proteins associated with inflammation and the innate immune response-e.g., cluster of differentiation 14, annexin-2, and components of the complement system-were upregulated in PSC. The most prominent pathways in PSC/CC-patients were inflammation associated cytokine and chemokine pathways, whereas in CC-patients the Wnt signaling pathway was upregulated. In PSC/CC-patients DIGE-analysis revealed biliary CD14 and Annexin-4 expression, among others, as the most prominent protein that discriminates between both cohorts. Thus, the bile-duct bile proteome of patients with PSC shows disease-specific changes associated with inflammation and the innate immune response even in the absence of obvious clinical signs of cholangitis, malignancy, or inflammation. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.
Assuntos
Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares/metabolismo , Bile/química , Colangiocarcinoma/metabolismo , Colangite Esclerosante/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Bile/imunologia , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares/patologia , Estudos de Casos e Controles , Colangiocarcinoma/imunologia , Colangiocarcinoma/patologia , Colangite Esclerosante/imunologia , Colangite Esclerosante/patologia , Coledocolitíase/metabolismo , Coledocolitíase/patologia , Estudos de Coortes , Citocinas/análise , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata , Receptores de Lipopolissacarídeos , Masculino , Pessoa de Meia-Idade , Proteômica , Regulação para Cima , Via de Sinalização Wnt/imunologiaAssuntos
Colangite/complicações , Colangite/diagnóstico , Coledocolitíase/diagnóstico , Coledocolitíase/patologia , Colangiografia , Colangiopancreatografia por Ressonância Magnética , Colangite/cirurgia , Coledocolitíase/cirurgia , Feminino , Hepatectomia , Humanos , Pessoa de Meia-Idade , Radiografia Abdominal , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Aging has been associated with increasing common bile duct (CBD) diameter and reported as independently predictive of the likelihood of choledocolithiasis. These associations are controversial with uncertain diagnostic utility in patients presenting with symptomatic disease. The current study examined the relationship between age, CBD size, and the diagnostic probability of choledocolithiasis. METHODS: Symptomatic patients undergoing evaluation for suspected choledocolithiasis from January 2008 to February 2011 were reviewed. In the cohort without choledocolithiasis, the relationship between aging and CBD size was examined as a continuous variable and by comparing mean CBD size across stratified age groups. Multivariate analysis examined the relationship between increasing age and diagnostic probability of choledocolithiasis in all patients. RESULTS: Choledocolithasis was diagnosed by MR cholangiopancreatography (MRCP) or endoscopic retrograde (ERCP) in 496 of 1,000 patients reviewed. Mean CBD was 6.0 mm (±2.8 mm) in the 504 of 1,000 patients without choledocolithiasis on ERCP/MRCP. Increasing age had no correlation with CBD size as a continuous variable (r2 = 0.011, p = 0.811). No difference occurred across age groups (Kruskal-Wallis, p = 0.157). Age had no association with diagnostic likelihood of choledocolithiasis (AOR [95% CI] 0.99 [0.98-1.01], adjusted-p = 0.335). CONCLUSION: In a large population undergoing investigation for biliary disease, increasing age was neither associated with increasing CBD diameter nor predictive of the likelihood of choledocolithiasis.
Assuntos
Envelhecimento/patologia , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/patologia , Ducto Colédoco/patologia , Adulto , Fatores Etários , Idoso , Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Estudos RetrospectivosRESUMO
An 18-year-old man presented with spontaneous severe epigastric pain, progressing and radiating to back since 3 days. It was associated with epigastric tenderness, bilious vomiting and jaundice. He had been intermittently experiencing these symptoms for the last 1 year. No known comorbid. Ultrasound showed a poorly visualised heterogeneous focus at porta hepatis; considering poor visualisation, this might represent an enlarged calcified lymph node or cystic duct calculus causing extrinsic compression or a large sludge ball within the common bile duct (CBD), leading to dilatation of common hepatic duct and intrahepatic biliary system. Subsequent magnetic resonance cholangiopancreatography revealed a focal saccular dilatation of middle part of CBD, a type I-B choledochal cyst, large heterogeneous focus seen within it representing choledochocystolithiasis. Later, CT was performed for further characterisation of surrounding anatomy and pathology, which confused the appearance of choledochocystolithiasis for Mirizzi syndrome. Later, surgery and histopathology confirmed type I-B choledochocystolithiasis and chronic cholecystitis.
Assuntos
Ductos Biliares Intra-Hepáticos/patologia , Colecistite/diagnóstico , Cisto do Colédoco/diagnóstico , Coledocolitíase/diagnóstico , Ducto Colédoco/patologia , Síndrome de Mirizzi/diagnóstico , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Adolescente , Colangiografia/métodos , Colecistite/etiologia , Cisto do Colédoco/complicações , Cisto do Colédoco/patologia , Coledocolitíase/complicações , Coledocolitíase/patologia , Colelitíase/complicações , Colelitíase/diagnóstico , Colelitíase/patologia , Dilatação Patológica/etiologia , Humanos , Masculino , Ultrassonografia/métodosRESUMO
BACKGROUND: Patients with gallstone disease can present with elevated liver function tests (LFTs). It is often challenging to differentiate those with a common bile duct (CBD) stone from those without a CBD stone on the basis of the LFTs levels. In this study, we aim to evaluate the predictors of a CBD stones among patients presenting with symptomatic gallbladder disease and elevated LFTs. PATIENTS AND METHODS: We retrospectively examined all patients who had undergone a cholecystectomy between January 2010 and December 2015. Patients with symptomatic cholelithiasis and increased LFTs were included. Patient characteristics, imaging findings, lab findings, endoscopic interventions, and operative report were recorded and evaluated. The diagnosis of CBD stones was made on the basis of ERCP and IOC findings. RESULTS: We included 354 patients in the final analysis. Of these, 113 (32%) had confirmed choledocholithiasis. The prevalence of CBD stones among biliary colic, acute cholecystitis, and pancreatitis patients was 47, 25, and 26%, respectively. γ-Glutamyl transferase and direct bilirubin had the highest sensitivities for CBD stones among these patients (83 vs. 79%). In the setting of biliary colic, total bilirubin was highly predictive of CBD stones with a positive predictive value of 85%. In the setting of acute cholecystitis, elevated LFTs were even less significant in predicting stones, with a positive predictive value of less than 40% for most. CONCLUSION: Although γ-glutamyl transferase and bilirubin levels showed a relatively higher sensitivity for CBDS compared with the other LFTs, these were not reliable enough because of high false-positive as well as false-negative values, especially in patients presenting with acute cholecystitis.