Combined cholecystotomy, retrograde hydropulsion, and choledochal stenting to treat extrahepatic biliary tract obstruction in 3 cats.

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).

[Double extrahepatic bile duct with pancreaticobiliary maljunction:a case report].

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.

PTEN deficiency induces an extrahepatic cholangitis-cholangiocarcinoma continuum via aurora kinase A in mice.

BACKGROUND & AIMS: 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. IMPACT AND IMPLICATIONS: 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.

Total lesion glycolysis by 18F-fluorodeoxyglucose positron emission tomography predicts tumor aggressiveness in patients with extrahepatic bile duct carcinoma.

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.

Pkd1l1-deficiency drives biliary atresia through ciliary dysfunction in biliary epithelial cells.

BACKGROUND & AIMS: 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. IMPACT AND IMPLICATIONS: 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.

Computed tomographic diagnosis of a common bile duct abscess and secondary extrahepatic biliary duct obstruction in a potbelly pig.

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.

Biliary atresia: the development, pathological features, and classification of the bile duct.

Biliary atresia is an occlusive biliary disease involving intrahepatic and extrahepatic bile ducts. Its etiology and pathogenesis are unclear. There are many manifestations of bile duct involvement in biliary atresia, but little is known about its occurrence and development. In addition, different classification methods have been proposed in different periods of biliary atresia, each with its advantages and disadvantages. The combined application of biliary atresia classification will help to improve the survival rate of patients with native liver. Therefore, this article reviews the development, pathological features, and classification of intrahepatic and extrahepatic bile ducts in biliary atresia, to provide a reference for the study of the pathogenesis and the choice of treatment methods.

A case of spindle and giant cell-type undifferentiated carcinoma of the extrahepatic bile duct.

Spindle and giant cell type undifferentiated carcinoma of the extrahepatic bile duct is an uncommon malignancy. We report a case involving the common bile duct in a 72-year-old male with jaundice who was admitted to our hospital. Diagnostic imaging, including abdominal computed tomography and magnetic resonance imaging, revealed a mass in the distal common bile duct, accompanied by dilatation of both intra- and extrahepatic bile ducts and regional lymph node enlargement. Endoscopic retrograde cholangiography demonstrated stenosis in the distal common bile duct, with a biopsy confirming adenocarcinoma. The patient underwent endoscopic retrograde biliary drainage followed by a subtotal stomach-preserving pancreaticoduodenectomy with regional lymphadenectomy. Microscopic examination revealed that the tumor predominantly comprised spindle and giant atypical cells within the stroma. Immunohistochemical analysis showed the tumor cells expressing cytokeratins and mesenchymal markers, confirming the diagnosis of spindle and giant cell type undifferentiated carcinoma of the common bile duct. Ki-67 labeling index was observed to be above 80%. Postoperatively, intra-abdominal lymph node recurrence was noted at two months, and multiple liver metastases were identified at three months. The patient died seven months post-surgery. The literature pertaining to this rare disease is reviewed and discussed.

Osteosarcopenia is a significant predictor of recurrence and the prognosis after resection for extrahepatic bile duct cancer.

PURPOSE: This study examined the impact of osteosarcopenia on recurrence and the prognosis after resection for extrahepatic biliary tract cancer (EBTC). METHODS: We retrospectively analyzed 138 patients after resection for perihilar cholangiocarcinoma (11), distal cholangiocarcinoma (54), gallbladder carcinoma (30), or ampullary carcinoma (43). Osteosarcopenia is defined as the concomitant occurrence of osteopenia and sarcopenia. We investigated the relationship between osteosarcopenia and the overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses. RESULTS: Osteosarcopenia was identified in 38 patients (27.5%) before propensity score (PS) matching. In the multivariate analysis, the independent recurrence factors were the prognostic nutrition index (p = 0.015), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.004), perineural invasion (p = 0.002), and non-curability (p = 0.008), whereas the independent prognostic factors were prognostic nutrition index (p = 0.030), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.007), lymphatic invasion (p = 0.018), and non-curability (p = 0.004). After PS matching, there was no significant difference in the variables between the patients with and without osteosarcopenia (n = 34 each). The 5-year DFS and OS after PS matching in patients with osteosarcopenia were significantly worse than in patients without osteosarcopenia (17.6% vs. 38.8%, p = 0.013 and 20.6% vs. 57.4%, p = 0.0005, respectively). CONCLUSIONS: Preoperative osteosarcopenia could predict the DFS and OS of patients after resection for EBTC.

Laparoscopic Resection of the Middle Bile Duct for Cholangiocarcinoma (with Video).

BACKGROUND: Surgical resection remains the sole approach to achieving long-term survival in cholangiocarcinoma cases. The universally recognised standard procedures for such cases include pancreaticoduodenectomy (PD) or hemihepatectomy accompanied by bile duct reconstruction. Nevertheless, some patients may still attain curative intent through bile duct segmental resection (BDR). However, these procedures are still in the experimental stage and should only be recommended for carefully chosen patients. METHODS: A 57-year-old male patient was admitted to our department after two weeks of escalating jaundice and abdominal discomfort. Upon admission, his total bilirubin was recorded at 102 µmol/L, and his direct bilirubin was 87 µmol/L. His carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) levels were normal. Enhanced computed tomography (CT) and magnetic resonance imaging (MRI) scans revealed a thickened and enhanced biliary tree extending from the cystic duct junction to the common hepatic duct no vascular invasion indicated by three-dimensional reconstruction. RESULTS: The patient underwent laparoscopic resection of the extrahepatic bile duct, accompanied by radical lymphadenectomy with skeletonisation and biliary reconstruction, was successfully conducted within 320 min, with a minimal blood loss of only 50 ml. The histological grading of the procedure was T2bN0M0 (stage II). The patient was discharged on the sixth postoperative day without complications. Following this, he underwent a regimen of single-agent capecitabine chemotherapy. After an 18-month follow-up period, no recurrence was observed. CONCLUSIONS: Our experience suggests that in selected patients diagnosed with middle bile duct cholangiocarcinoma, laparoscopic resection could potentially reach the standard of lymphadenectomy through skeletonisation.

Comparative dosimetric study of spot-scanning proton therapy versus volumetric-modulated radiation therapy for extrahepatic bile duct cancer.

This study aimed to compare the dose distributions and clarify the dosimetric characteristics of spot-scanning proton therapy (SSPT) and photon volumetric modulated arc therapy (VMAT) for extrahepatic bile duct cancer (EBDC). This retrospective study included 10 patients with EBDC treated with real-time image-gated SSPT. Using the simultaneous integrated boost technique, the 2 prescription dose levels for planning target volumes were 72.6 and 44 Gy, delivered in 22 fractions. Plan quality comparisons were conducted by analyzing various parameters, including homogeneity, conformity, dose to organs at risk, and normal tissue complication probability (NTCP) for radiation-induced liver damage (RILD). The target dose distributions using SSPT were almost equivalent to those achieved using photon VMAT. There was a significant reduction in all liver dose parameters, the NTCP value for RILD, and kidney dose (mean, V12 Gy, and V18 Gy) in SSPT than in photon VMAT. No significant differences were observed in the intestinal doses in the high-dose area. Thus, compared with photon VMAT, SSPT for EBDC significantly reduced radiation doses to the liver and kidneys and has shown potential clinical benefits of reduced radiation-induced toxicity.

A case of congenital biliary dilatation without pancreaticobiliary maljunction, so-called Type Ib according to Todani's classification.

Congenital biliary dilatation (CBD) is a congenital malformation of focal dilatation of the extrahepatic bile ducts, including the common bile duct, and is often associated with pancreaticobiliary maljunction (PBM). In this article, we report a CBD case that presented with focal dilation of the common bile duct without PBM (Todani's classification type Ib). The patient was a 32-year-old man who visited a doctor with a chief complaint of abdominal distension. Computed tomography revealed cystic dilatation of the common bile duct, and the patient was referred to our institution. Magnetic resonance cholangiopancreatography showed cystic dilatation of the common bile duct with a maximum diameter of 7 cm; however, evaluating the presence of PBM was challenging. Endoscopic ultrasonography showed small gallstones and debris in the dilated common bile duct and no thickening of the gallbladder wall. Endoscopic retrograde cholangiopancreatography revealed no PBM or markedly elevated bile amylase levels. Based on these findings, the patient was diagnosed with Todani Type Ib CBD. Since this patient did not have pancreatobiliary reflux, it was unclear whether the risk of developing biliary tract cancer was high, and since the treatment was highly invasive, the decision was to follow up without surgical treatment.

Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814).

PURPOSE: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. MATERIALS AND METHODS: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. RESULTS: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. CONCLUSION: Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

The contribution of new methods in cytology for increasing sensitivity in the diagnosis of extrahepatic bile duct lesions.

The aim of this review is to provide a comprehensive analysis of the existing literature pertaining to cytology of extrahepatic bile ducts. A search using the keywords "biliary brush cytology" was conducted in the PubMed database, with a focus on recent articles. The inclusion criteria primarily encompassed publications addressing problematic biliary stenosis. Emphasis was placed on identifying articles that explored innovative or less-utilized examination techniques aimed at enhancing the sensitivity of cytological examination. This review presents a comprehensive overview of the various types of materials used in sampling and the corresponding sampling methods. Additionally, it explores cytological and cytogenetic techniques, such as fluorescence in situ hybridization (FISH) and genetic methods (miRNA, NGS, cfDNA). These techniques possess the potential to improve the accuracy of diagnosing bile duct tumors, although their sensitivity varies. Furthermore, their utilization can facilitate early therapy, which plays a crucial role in patient prognosis. Each examination is always dependent on the quality and quantity of material delivered. A higher sensitivity of these examinations can be achieved by combining biliary cytology and other complementary methods.

Heterogeneous murine peribiliary glands orchestrate compartmentalized epithelial renewal.

The extrahepatic branches of the biliary tree have glands that connect to the surface epithelium through narrow pits. The duct epithelia undergo homeostatic renewal, yet the identity and multiplicity of cells that maintain this tissue is unknown. Using marker-free and targeted clonal fate mapping in mice, we provide evidence that the extrahepatic bile duct is compartmentalized. Pit cholangiocytes of extramural glands renewed the surface epithelium, whereas basally oriented cholangiocytes maintained the gland itself. In contrast, basally positioned cholangiocytes replenished the surface epithelium in mural glands. Single-cell sequencing identified genes enriched in the base and surface epithelial populations, with trajectory analysis showing graded gene expression between these compartments. Epithelia were plastic, changing cellular identity upon fasting and refeeding. Gain of canonical Wnt signaling caused basal cell expansion, gastric chief cell marker expression, and a decrease in surface epithelial markers. Our results identify the cellular hierarchy governing extrahepatic biliary epithelial renewal.

Difficulty of adjuvant chemotherapy administration in patients with biliary tract cancer.

PURPOSE: This study aimed to elucidate the difficulty of adjuvant chemotherapy administration in patients with biliary tract carcinoma (BTC). METHODS: Clinical data of patients with BTC who underwent curative-intent surgery were retrospectively analyzed. The eligible patients were stratified into two groups according to the presence or absence of adjuvant chemotherapy administration (adjuvant and non-adjuvant groups), and the clinicopathological features were compared between the two groups. The ratios of adjuvant chemotherapy administration were investigated in each surgical procedure. Independent factors associated with no administration of adjuvant chemotherapy were analyzed using multivariate analyses. RESULTS: Among 168 eligible patients, 141 (83.9%) received adjuvant chemotherapy (adjuvant group), while 27 (16.1%) did not (non-adjuvant group). The most common surgical procedure was pancreaticoduodenectomy in the adjuvant group, and it was hepatectomy with extrahepatic bile duct resection (BDR) in the non-adjuvant group, respectively. The rate of no adjuvant chemotherapy was significantly higher in patients who underwent hepatectomy with BDR than in those who underwent other surgeries (p < 0.001). The most common cause of no adjuvant chemotherapy was bile leak in 12 patients, which occurred after hepatectomy with BDR in ten patients. Multivariate analyses revealed that hepatectomy with BDR and preoperative anemia were independently associated with no adjuvant chemotherapy (p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Hepatectomy with BDR and subsequent refractory bile leak can be the obstacle to adjuvant chemotherapy administration in patients with BTC.

Clinical significance of extrahepatic bile duct resection for T2 gallbladder cancer using data from the Japanese Biliary Tract Cancer Registry between 2014 and 2018.

PURPOSE: The present study aimed to determine whether concomitant extrahepatic bile duct resection (EHBDR) improves the prognosis of patients with T2 gallbladder cancer (GBC). METHODS: Between 2014 and 2018, 4947 patients with GBC were registered in the National Biliary Tract Cancer Registry in Japan. This included 3804 patients (76.9%) who underwent curative-intent surgical resection; 1609 of these patients had pT2 GBC with no distant metastasis. Of the 1609 patients with GBC, 520 underwent EHBDR and 1089 did not. We compared the patients' backgrounds and disease-specific survival rates between the groups. RESULTS: The frequency of lymph node metastasis was significantly higher in the EHBDR group than in the non-EHBDR group (38.2% vs. 20.7%, p < .001). In the entire cohort, however, there was no significant difference in disease-specific survival between the two groups (76% vs. 79%, p = .410). The EHBDR group had a significantly higher incidence of postoperative complications (Clavien-Dindo classification grade = 3) (32.4% vs. 11.7%, p < .001). When we focused on the survival of only T2N1 patients who underwent gallbladder bed resection, the prognosis was significantly improved for the EHBDR group (5-year survival rate: 64% vs. 54%, p = .017). The non-EHBDR group was subcategorized into two groups: D2 dissection and D1 dissection or sampling, and survival curves were compared between these subgroups. Although the EHBDR group tended to have a favorable prognosis compared to the D2 group, this difference was not significant (p = .167). However, the EHBDR group had a significantly greater prognosis than the D1 dissection or sampling group (5 year-survival rate: 64 vs. 49%, p = .027). CONCLUSIONS: The EHBDR may improve the prognosis of patients with T2 gall bladder cancer with lymph node metastases; however, its indication should be carefully determined because of the increased risk of postoperative complications.