BACKGROUND: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients.
METHODS: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients.
RESULTS: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05).
CONCLUSIONS: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.

暂无摘要。

OBJECTIVE: Extrahepatic bile duct cancer (EBDC) is a compound malignant tumor mainly consisting of extrahepatic cholangiocarcinoma and gallbladder carcinoma. Most EBDC patients are diagnosed at an advanced stage characterized by distant metastases, and the liver is one of the common sites of metastasis. Hence, the purpose of this study is to investigate the clinicopathological features, identify prognostic risk factors, and assess the long-term prognosis of extrahepatic bile duct cancer liver metastasis (EBDCLM).
METHODS: We identified 1922 eligible EBDCLM patients from the SEER database.Cox regression models were used to predict independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS),and Kaplan-Meier survival curves were drawn. A nomogram was constructed based on the results of multivariate Cox analysis, and the predictive effect of the nomogram was evaluated.
RESULTS: Age, surgery, chemotherapy, brain metastasis, and lung metastasis were common independent prognostic factors for OS and CSS, and radiotherapy and bone metastasis were independent prognostic factors for CSS. The Kaplan-Meier survival curves showed a significant increase in survival for patients aged less than or equal to 70 years, undergoing surgery and chemotherapy, and without lung metastases. The results showed that the nomogram constructed by us had good predictability and ha d strong clinical application value.
CONCLUSIONS: Our study identified age, surgery, chemotherapy, brain metastasis, and lung metastasis as independent prognostic factors for EBDCLM patients. The nomogram can accurately predict the survival probability, which is helpful for clinicians to assess the prognosis of patients with advanced EBDC and provide personalized clinical decisions.

Extrahepatic biliary tract obstruction (EHBO) is uncommonly encountered in cats. Surgical treatment aims to decompress the biliary tract and insure bile duct patency. In veterinary medicine, cholecystotomy is not widely used in practice. The objective was to describe the use of cholecystotomy, retrograde hydropulsion of choleliths, and choledochal stenting to remove choleliths from the extrahepatic biliary tract back in the gallbladder. Three adult domestic shorthair cats were presented with anorexia, lethargy, and vomiting. Serum biochemistry revealed hyperbilirubinemia and increased hepatic enzymes. Abdominal ultrasonography showed evidence of EHBO requiring surgical intervention. Choleliths were localized in the proximal and middle portions of the common bile duct (CBD) in the first case, in the distal portion of the CBD and within the major duodenal papilla in the second case, and in the middle and distal portions of the CBD in the third case. Cholecystotomy was followed by retrograde hydropulsion of the choleliths into the gallbladder, after which choledochal stenting was performed. Complications were defined as major when requiring additional medical or surgical treatment, or minor when not. Three major complications were reported. In 2 cases, severe anemia requiring blood transfusion occurred 24 h postoperatively; in 1 case, EHBO recurrence was encountered 41 d postoperatively. All cats were discharged within 4 d following surgery. Two cats were still alive at 12 and 14 mo after surgery, respectively. In the last case, owners refused revision surgery and the cat was euthanized. Key clinical message: Cholecystotomy combined with retrograde hydropulsion of choleliths permitted removal of choleliths and decompression of the biliary tract in 3 cats. Major complications included severe anemia and EHBO recurrence.
Cholécystotomie combinée, hydropulsion rétrograde et pose de stent cholédocien pour traiter l’obstruction des voies biliaires extra-hépatiques chez 3 chats. Les obstructions biliaires extra-hépatiques (OBEH) sont peu fréquentes chez le chat. Le traitement chirurgical vise à lever l’obstruction et s’assurer de la perméabilité des voies biliaires. En médecine vétérinaire, la cholécystotomie est une technique peu pratiquée. L’objectif de ce rapport de cas était de décrire l’utilisation de la cholécystotomie, de l’hydropulsion rétrograde des cholélithes et d’une prothèse endoluminale cholédoquale (PEC) pour repousser les cholélithes présents dans les voies biliaires extrahépatiques dans la vésicule biliaire (VB).Trois chats européens adultes ont été présentés pour anorexie, léthargie et vomissements. La biochimie sérique a révélé une hyperbilirubinémie et une augmentation des enzymes hépatiques. L’échographie abdominale a mis en évidence une OBEH nécessitant une intervention chirurgicale. Les cholélithes étaient situés dans la portion proximale et moyenne du canal cholédoque pour le premier cas; dans la portion distale et la papille duodénale majeure dans le second cas; dans la portion moyenne et distale pour le troisième cas. Une cholécystotomie a été suivie d’une rétro-hydropulsion des cholélithes dans la VB, puis une PEC a été placée. Les complications ont été définies comme majeures lorsqu’elles nécessitaient un traitement médical ou chirurgical supplémentaire, ou mineures lorsqu’elles n’en nécessitaient pas.Trois complications majeures ont été rapportées : chez 2 cas, une anémie sévère a été observée 24 h après l’intervention, nécessitant une transfusion sanguine; chez un cas, une récidive d’obstruction biliaire a eu lieu à 41 jours postopératoire. Tous les patients sont sortis de l’hôpital dans les 4 jours suivant l’opération. Deux cas étaient encore en vie 12 et 14 mois après l’intervention. Pour le dernier cas, la seconde chirurgie a été refusée par les propriétaires et le chat a été euthanasié.Message clinique clé :La cholécystotomie combinée à l’hydropulsion rétrograde des cholélithes a permis le retrait de cholélithes obstructives (dont certaines distales) et la décompression du tractus biliaire chez 3 chats. Les complications majeures incluaient une anémie sévère et une récidive d’obstruction biliaire.(Traduit par les auteurs).

A 76-year-old woman with a suspected double extrahepatic bile duct was referred to our hospital. MRCP revealed that the left hepatic and posterior ducts combined to form the ventral bile duct and that the anterior duct formed the dorsal bile duct. ERCP demonstrated that the ventral bile duct was linked with the Wirsung duct. Amylase levels in the bile were unusually high. Based on these findings, we diagnosed a double extrahepatic bile duct with pancreaticobiliary maljunction and choledocholithiasis. Duplicate bile duct resection and bile duct jejunal anastomosis were performed considering the risk of biliary cancer due to pancreaticobiliary maljunction. The resected bile duct epithelium demonstrated no atypia or hyperplastic changes.

A potbelly pig was evaluated for anorexia and icterus. Clinicopathologic abnormalities suggested an active inflammatory hepatobiliary process. Ultrasound and CT of the abdomen revealed an extrahepatic biliary obstruction of the common bile duct (CBD). Surgical exploration and choledochotomy revealed a markedly dilated CBD containing a large volume of intraluminal inspissated biliary material. This case report describes the imaging findings of an extrahepatic biliary obstruction secondary to abscessation within the CBD in a pig.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) parameters are prognostic factors in multiple malignancies. However, the prognostic value in bile duct carcinoma is unclear. We evaluated the impact of metabolic parameters of 18F-FDG-PET/CT in resectable extrahepatic bile duct carcinoma.
METHODS: We retrospectively reviewed the records of 100 patients with extrahepatic bile duct carcinoma who had undergone 18F-FDG-PET/CT and subsequent surgical resection between January 2017 and January 2023. We calculated maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and investigated their prognostic significance.
RESULTS: The optimal cutoff values of SUVmax, MTV, and TLG for predicting overall survival (OS) after surgery were 3.88, 3.55 and 7.55, respectively. In multivariate analysis, each metabolic parameter influenced both OS and recurrence-free survival (RFS). TLG showed the lowest Akaike information criteria statistic value, indicating that it had the best ability to predict OS and RFS. High TLG was significantly associated with the number of lymph node metastases and poorly differentiated type. Patients with high TLG showed poorer RFS and OS, which were significantly worse than in those with low TLG.
CONCLUSIONS: Tumor TLG predicted tumor malignancy potential and could be a useful prognostic predictor for extrahepatic bile duct carcinoma.

OBJECTIVE: Syndromic biliary atresia is a cholangiopathy characterized by fibro-obliterative changes in the extrahepatic bile duct (EHBD) and congenital malformations including laterality defects. The etiology remains elusive and faithful animal models are lacking. Genetic syndromes provide important clues regarding the pathogenic mechanisms underlying the disease. We investigated the role of the gene Pkd1l1 in the pathophysiology of syndromic biliary atresia.
METHODS: Constitutive and conditional Pkd1l1 knockout mice were generated to explore genetic pathology as a cause of syndromic biliary atresia. We investigated congenital malformations, EHBD and liver pathology, EHBD gene expression, and biliary epithelial cell turnover. Biliary drainage was functionally assessed with cholangiography. Histology and serum chemistries were assessed after DDC (3,5-diethoxycarbony l-1,4-dihydrocollidine) diet treatment and inhibition of the ciliary signaling effector GLI1.
RESULTS: Pkd1l1-deficient mice exhibited congenital anomalies including malrotation and heterotaxy. Pkd1l1-deficient EHBDs were hypertrophic and fibrotic. Pkd1l1-deficient EHBDs were patent but displayed delayed biliary drainage. Pkd1l1-deficient livers exhibited ductular reaction and periportal fibrosis. After DDC treatment, Pkd1l1-deficient mice exhibited EHBD obstruction and advanced liver fibrosis. Pkd1l1-deficient mice had increased expression of fibrosis and extracellular matrix remodeling genes (Tgfα, Cdkn1a, Hb-egf, Fgfr3, Pdgfc, Mmp12, and Mmp15) and decreased expression of genes mediating ciliary signaling (Gli1, Gli2, Ptch1, and Ptch2). Primary cilia were reduced on biliary epithelial cells and altered expression of ciliogenesis genes occurred in Pkd1l1-deficient mice. Small molecule inhibition of the ciliary signaling effector GLI1 with Gant61 recapitulated Pkd1l1-deficiency.
CONCLUSIONS: Pkd1l1 loss causes both laterality defects and fibro-proliferative EHBD transformation through disrupted ciliary signaling, phenocopying syndromic biliary atresia. Pkd1l1-deficient mice function as an authentic genetic model for study of the pathogenesis of biliary atresia.
UNASSIGNED: The syndromic form of biliary atresia is characterized by fibro-obliteration of extrahepatic bile ducts and is often accompanied by laterality defects. The etiology is unknown, but Pkd1l1 was identified as a potential genetic candidate for syndromic biliary atresia. We found that loss of the ciliary gene Pkd1l1 contributes to hepatobiliary pathology in biliary atresia, exhibited by bile duct hypertrophy, reduced biliary drainage, and liver fibrosis in Pkd1l1-deficient mice. Pkd1l1-deficient mice serve as a genetic model of biliary atresia and reveal ciliopathy as an etiology of biliary atresia. This model will help scientists uncover new therapeutic approaches for patients with biliary atresia, while pediatric hepatologists should validate the diagnostic utility of PKD1L1 variants.

BACKGROUND: There is a paucity of evidence supporting the use of adjuvant radiation therapy in resected biliary cancer. Supporting evidence for use comes mainly from the small SWOG S0809 trial, which demonstrated an overall median survival of 35 months. We aimed to use a large national database to evaluate the use of adjuvant chemoradiation in resected extrahepatic bile duct and gallbladder cancer.
METHODS: Using the National Cancer Database, we selected patients from 2004 to 2017 with pT2-4, pN0-1, M0 extrahepatic bile duct or gallbladder adenocarcinoma with either R0 or R1 resection margins, and examined factors associated with overall survival (OS). We examined OS in a cohort of patients mimicking the SWOG S0809 protocol as a large validation cohort. Lastly, we compared patients who received chemotherapy only with patients who received adjuvant chemotherapy and radiation using entropy balancing propensity score matching.
RESULTS: Overall, 4997 patients with gallbladder or extrahepatic bile duct adenocarcinoma with available survival information meeting the SWOG S0809 criteria were selected, 469 of whom received both adjuvant chemotherapy and radiotherapy. Median OS in patients undergoing chemoradiation was 36.9 months, and was not different between primary sites (p = 0.841). In a propensity score matched cohort, receipt of adjuvant chemoradiation had a survival benefit compared with adjuvant chemotherapy only (hazard ratio 0.86, 95% confidence interval 0.77-0.95; p = 0.004).
CONCLUSIONS: Using a large national database, we support the findings of SWOG S0809 with a similar median OS in patients receiving chemoradiation. These data further support the consideration of adjuvant multimodal therapy in resected biliary cancers.

OBJECTIVE: The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aimed to evaluate the role of PTEN in the pathogenesis of eCCA and identify novel therapeutic targets for this disease.
METHODS: The Pten gene was genetically deleted using the Cre-loxp system in biliary epithelial cells. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry, reverse-transcription PCR, cell culture, and RNA sequencing. Some features were compared to those in human eCCA samples. Further mechanistic studies utilized the conditional knockout of Trp53 and Aurora kinase A (Aurka) genes. We also tested the effectiveness of an Aurka inhibitor.
RESULTS: We observed that genetic deletion of the Pten gene in the extrahepatic biliary epithelium and peri-ductal glands initiated sclerosing cholangitis-like lesions in mice, resulting in enlarged and distorted extrahepatic bile ducts in mice as early as 1 month after birth. Histologically, these lesions exhibited increased epithelial proliferation, inflammatory cell infiltration, and fibrosis. With aging, the lesions progressed from low-grade dysplasia to invasive carcinoma. Trp53 inactivation further accelerated disease progression, potentially by downregulating senescence. Further mechanistic studies showed that both human and mouse eCCA showed high expression of AURKA. Notably, the genetic deletion of Aurka completely eliminated Pten deficiency-induced extrahepatic bile duct lesions. Furthermore, pharmacological inhibition of Aurka alleviated disease progression.
CONCLUSIONS: Pten deficiency in extrahepatic cholangiocytes and peribiliary glands led to a cholangitis-to-cholangiocarcinoma continuum that was dependent on Aurka. These findings offer new insights into preventive and therapeutic interventions for extrahepatic CCA.
UNASSIGNED: The aberrant PTEN-PI3K-AKT signaling pathway is commonly observed in human extrahepatic cholangiocarcinoma (eCCA), a disease with a poor prognosis. In our study, we developed a mouse model mimicking cholangitis to eCCA progression by conditionally deleting the Pten gene via Pdx1-Cre in epithelial cells and peribiliary glands of the extrahepatic biliary duct. The conditional Pten deletion in these cells led to cholangitis, which gradually advanced to dysplasia, ultimately resulting in eCCA. The loss of Pten heightened Akt signaling, cell proliferation, inflammation, fibrosis, DNA damage, epigenetic signaling, epithelial-mesenchymal transition, cell dysplasia, and cellular senescence. Genetic deletion or pharmacological inhibition of Aurka successfully halted disease progression. This model will be valuable for testing novel therapies and unraveling the mechanisms of eCCA tumorigenesis.