Search Results (42)

Background/Objectives: Primary biliary neuroendocrine tumors (PBilNETs) are exceptionally rare biliary tract neoplasms that are frequently misdiagnosed preoperatively as cholangiocarcinoma because of overlapping clinical and radiological findings. This systematic review aimed to summarize overall evidence regarding presentation, diagnostic evaluation, surgical management, and outcomes of PBilNETs. Methods: A systematic search of PubMed, Scopus, and Embase databases was performed according to PRISMA guidelines for studies published between January 2000 and December 2025. Studies including adult patients with histologically confirmed and surgically treated PBilNETs were eligible. Data regarding demographics, symptoms, imaging findings, surgical treatment, histopathology, immunohistochemistry, and outcomes were extracted and analyzed. Results: Fifty-eight studies involving 79 patients met the inclusion criteria. Median age at diagnosis was 49 years, with female predominance. Obstructive jaundice, abdominal pain, and pruritus were the most common presenting symptoms. Most tumors originated from the hilar or extrahepatic bile ducts. Preoperative diagnosis was challenging, as most lesions were initially considered cholangiocarcinomas. Surgical resection was the main therapeutic approach and included bile duct excision with biliary reconstruction, pancreaticoduodenectomy, or hepatic resection according to tumor location. Histopathological analysis demonstrated predominantly well- or moderately differentiated neuroendocrine neoplasms with frequent chromogranin A and synaptophysin positivity. Favorable long-term outcomes were reported, with high postoperative survival and limited recurrence during follow-up. Conclusions: PBilNETs remain diagnostically challenging because of their rarity and nonspecific presentation; however, they appear to exhibit a less aggressive biological behavior than conventional biliary adenocarcinomas. Surgical resection remains the cornerstone of treatment, while further multicenter studies are required to optimize diagnostic and therapeutic strategies. The findings also support an individualized multidisciplinary approach integrating clinical presentation, advanced imaging, histopathological grading, and immunohistochemical profiling to optimize personalized management of these rare tumors. Full article

Background: Optimal biliary drainage in unresectable malignant hilar obstruction remains challenging, particularly in Bismuth type III disease due to complex biliary anatomy. Emerging evidence suggests that the adequacy of biliary decompression may be more important than the drainage modality itself in determining clinical outcomes. Aim: To compare the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) in unresectable Bismuth type III malignant hilar obstruction, with particular emphasis on drainage adequacy. Methods: This retrospective two-center study included 199 patients with unresectable Bismuth type III malignant hilar obstruction (ERCP: n = 102; PTBD: n = 97). Drainage adequacy was defined as decompression of at least 50% of the non-atrophic liver using a segment-based anatomical approach. Bilirubin response was evaluated at predefined time points (days 7, 14, and 28). The primary outcome was biochemical response, while secondary outcomes included reintervention, complications, hospital stay, receipt of systemic therapy, and mortality. Results: Baseline characteristics were comparable between groups (mean age 66.8 ± 11.2 vs. 68.4 ± 10.7 years, p = 0.412; male sex 58.3% vs. 61.5%, p = 0.721). PTBD achieved significantly higher rates of adequate drainage than ERCP (p = 0.006). Although biochemical response rates were numerically higher in the PTBD group, multivariable analysis identified drainage adequacy—rather than drainage modality—as the strongest independent predictor of treatment success. Reintervention rates were significantly higher and time to reintervention significantly shorter in the ERCP group (p < 0.001). Cholangitis and post-procedural pain scores were more frequent following PTBD, whereas post-ERCP pancreatitis occurred exclusively after ERCP. No significant differences were observed in 30-day or 1-year mortality between groups. Conclusions: In unresectable Bismuth type III malignant hilar obstruction, drainage adequacy appears to be the principal determinant of clinical success. Although PTBD more frequently achieves adequate biliary decompression, outcomes seem to depend primarily on the effectiveness of drainage rather than the drainage modality itself. Full article

Miniprobe endoscopic ultrasonography (mEUS) combines high-resolution imaging of the gastrointestinal (GI) wall and bile ducts with ease of applicability during routine endoscopy. This narrative review aims to provide an overview of known and emerging fields of application for mEUS in gastrointestinal endoscopy. After its initial development in pancreatobiliary scenarios in the early 1990s, mEUS has been recently reconsidered a third-space endoscopic technique that is progressively developing and spreading for the treatment of early gastrointestinal neoplastic lesions. The high spatial resolution of mEUS provides an accurate assessment of the degree of submucosal invasion in early esophageal, gastric, and colorectal neoplasia, while the small caliber of catheters allows for mEUS employment in settings where standard echoendoscopes are impractical (e.g., severe stenoses or proximal colonic lesions). Beyond cancer staging, mEUS offers point-of-care characterization of subepithelial lesions by defining the layer of origin and echo-pattern, eventually defining endoscopic resectability, but definitive diagnosis remains histological. In pancreatobiliary diseases, miniprobe intraductal ultrasonography (IDUS) shows its strongest application for indeterminate biliary strictures when endoscopic retrograde cholangiopancreatography (ERCP)-based sampling strategies and brushing cytology show inconclusive diagnoses, and in choledocholithiasis, particularly for the detection of small stones/sludge and confirmation of duct clearance. IDUS is also valuable for the staging of ampullary tumors, for longitudinal extension mapping in hilar cholangiocarcinoma and for selected portal biliopathy scenarios. Overall, mEUS and IDUS are high-resolution adjuncts that can meaningfully refine local decision-making in the treatment of superficial epithelial/subepithelial tumors or lesions involving the bile ducts. Limitations include shallow penetration, lack of tissue acquisition capability, a relative increase in post-ERCP pancreatitis risk for intraductal use, and substantial cost with limited availability in lower-volume centers. Full article

In the hepatobiliary system, the majority of neoplasms grow within the hepatic parenchyma; however, some arise, grow, and/or spread within the lumen of the intrahepatic large bile ducts and the perihilar/distal bile ducts (collectively referred to as large bile ducts), representing specialized ductal organs associated with unique peribiliary glands and being distinct from the intrahepatic small bile ducts and bile ductules embedded within the hepatic parenchyma. Precursors of cholangiocarcinoma (CCA) arising within the lumen of large bile ducts have recently been proposed. Neoplasms growing and spreading within the lumen of large bile ducts have been categorized into four groups and are discussed here in light of updated pathological findings. (i) Precursor(s) of CCA arising in the large bile ducts (large-duct-type intrahepatic CCA and perihilar/distal CCA): These precursors include high-grade biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), and intraductal oncocytic papillary neoplasm (IOPN). High-grade BilIN presents as a flat, microscopic lesion with dysplastic cytoarchitectural alterations and grows along the luminal surface of large bile ducts, whereas the latter two present as grossly visible polypoid or tumorous lesions composed of papillary, villous, or tubular proliferation of neoplastic epithelium with delicate fibrovascular cores. These lesions may eventually progress to invasive CCA. Intraductal tubulopapillary neoplasm of the bile duct (ITPN), previously categorized as another precursor of CCA arising in large bile ducts, appears to represent a heterogeneous group of neoplasms with respect to progression and presumed cell of origin. Some ITPNs are frequently associated with nodular invasive carcinoma resembling small-duct-type intrahepatic CCA (SD-iCCA) and share genetic alterations with SD-iCCA; such cases may arise in association with small bile ducts or bile ductules. In contrast, other ITPNs exhibit cystic changes with tubulopapillary features and may arise in association with peribiliary glands or cysts. (ii) Secondary growth and spread of biliary neoplasms: This category comprises several patterns. First, intraepithelial neoplastic spread directly and continuously from the primary neoplastic lesion is observed in almost all cases of high-grade BilIN, IPNB, and IOPN; it spreads laterally along the luminal surface of the proximal and distal bile ducts and extends vertically into the adjacent peribiliary glands. Intraluminal cast-like spread in the bile ducts adjacent to the primary neoplastic lesion also occurs in some precursor lesions, particularly in ITPN. Implantation of a biliary neoplasm from one part of the biliary tract to another results in discontinuous, multifocal biliary neoplasms, particularly in IPNB, and occurs mainly in the distal bile ducts relative to the main tumor. Multicentric tumorigenesis may contribute to the multifocal development of precursors and CCA in the bile ducts. The accumulation of additional genetic alterations, beyond the common mutations detected in primary tumors, may contribute to metachronous recurrence of CCA after curative resection of the primary biliary tumor. Cancerization of the duct (COD) by CCA may also contribute to secondary growth and spread within the bile duct lumen. Specifically, flat-type cancerization of pre-existing non-neoplastic bile ducts, resembling high-grade BilIN, occurs in approximately one-third of hilar CCA cases. Intraductal polypoid, cast-like cancerization within the lumen of adjacent bile ducts, resembling polypoid precursors of CCA, can also occur in approximately one-tenth of SD-iCCA. (iii) Prominent intraductal polypoid growth of invasive CCA: Invasive CCA rarely presents with predominant intraductal polypoid carcinoma that is continuous with periductal infiltrating CCA; this pattern can be referred to as polypoid invasive CCA. (iv) Nonbiliary neoplasms presenting bile duct tumor thrombus (BDTT): BDTT associated with hepatocellular carcinoma and with extrahepatic malignancies extending into the bile duct lumen can mimic the intraluminal growth and spread patterns of the above-mentioned biliary neoplasms. In conclusion, intraluminally growing biliary neoplasms in the large bile ducts comprise a heterogeneous group that can be reasonably classified into four categories. This categorization may facilitate understanding of these intrabiliary growing neoplasms. Full article

Liver transplantation (LT) is the definitive treatment for patients with end-stage liver disease. Since its inception in the 1960s, transplant medicine has undergone substantial advances in surgical technique, immunosuppression, organ preservation, and organ allocation policies. According to the 2023 WHO census, approximately 47,180 LT procedures occur worldwide each year, with living donors contributing to up to 23% of cases. Additional milestones include the expansion of transplant eligibility to patients with hilar cholangiocarcinoma and advanced colorectal liver metastasis, the incorporation of viscoelastic testing into perioperative blood management algorithms, and the increasing use of mechanical circulatory support for pre-transplant optimization. In parallel, medical training has evolved to meet the complexities associated with these high-risk procedures. Structured fellowship programs now provide focused expertise, and guide investigations to resolve complex clinical dilemmas. Experience accumulated over decades has improved clinicians’ ability to manage the expanding spectrum of comorbidities seen in contemporary transplant candidates. Key perioperative challenges include accurate assessment of fluid status, optimization of intravascular volume, management of vasoplegia, intraoperative renal replacement therapy, treatment of right-ventricular failure, and the mitigation of severe lactic acidosis. As transplant recipients increasingly present at older ages and with multiple comorbidities, perioperative management has become more demanding. One emerging strategy for select high-risk patients involves performing concurrent surgical procedures within a single operative session. This narrative review focuses on the intraoperative management of five variables that proved challenging during the first case of concurrent liver transplantation and off-pump coronary artery bypass surgery in our institution. Full article

Malignant biliary obstruction is commonly treated with biliary stenting either endoscopically or percutaneously; however, tumor ingrowth might occlude the stent, often leading to recurrent jaundice and repeat interventions. Endobiliary microwave ablation (MWA) is an emerging adjunct intended to devitalize intraductal tumors and potentially prolong stent patency. This review assesses the state of the art of endobiliary ablation for malignant biliary obstruction, focusing on the technique and safety of percutaneous procedures, as well as patient outcomes. It also discusses the use of flexible endobiliary MWA for hilar cholangiocarcinoma. The review covers ablation methods such as radiofrequency and MWA, which can be performed endoscopically or percutaneously. Research indicates that endobiliary thermal ablation is technically feasible and can be safely combined with stenting. Some studies suggest it may prolong stent patency and decrease the necessity for repeat procedures compared with stenting alone. Percutaneous techniques may be particularly helpful in complex hilar cases, allowing accurate energy delivery, protection of secondary bile ducts, and tailored stent placement. New microwave systems can heat tissue more deeply and evenly than radiofrequency ablation, which may improve local tumor control. Endobiliary thermal ablation appears to be a useful supplement to stenting, especially for patients with unresectable hilar cholangiocarcinoma. Flexible percutaneous MWA probes could make this treatment more widely available. Still, more high-quality studies are needed to find optimal ablation settings, identify which patients benefit most, and compare this method with standard stenting. Full article

Background: Hilar cholangiocarcinoma (HC) is a highly aggressive malignancy with a poor prognosis, highlighting the urgent need to elucidate its molecular drivers. This study aimed to systematically identify and functionally validate key genes and pathways driving HC pathogenesis. Methods: RNA sequencing (RNA-seq) was performed on paired primary HC tumors and matched adjacent non-tumorous tissues to identify differentially expressed genes (DEGs). Subsequent bioinformatic analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein–protein interaction (PPI) network construction, were conducted to characterize the functional landscape and identify hub genes. Transwell assays and orthotopic metastatic models were used to investigate the functions of Contactin-1 (CNTN1) in HC invasion in vitro and metastasis in vivo. Results: RNA-seq analysis identified 35 DEGs in HC, mainly involved in cell adhesion, cytoskeletal regulation, and axon development. PPI network analysis identified six hub genes, including CNTN1, NCAM1, PLP1, GPM6B, SLC1A3, and PMP2. Furthermore, we demonstrated that CNTN1, a neuronal membrane glycoprotein, was markedly up-regulated in HC at both mRNA and protein levels, and its elevated expression correlated with poor prognosis. Gain- and loss-of-function studies demonstrated that CNTN1 promotes HC cell invasion in vitro and metastasis in vivo. Mechanistically, CNTN1 exerts its pro-invasive effects by activating the PI3K-AKT signaling pathway and inducing epithelial–mesenchymal transition (EMT). Conclusions: Our integrated analysis identifies CNTN1 as a critical oncogenic driver in HC, promoting metastasis through PI3K-AKT-mediated EMT. These findings nominate CNTN1 as a potential prognostic biomarker and therapeutic target in HC. Full article

Malignant biliary obstruction (MBO) represents a critical clinical challenge characterized by bile duct compromise leading to severe complications, including intractable jaundice, recurrent cholangitis, biliary cirrhosis, and hepatic failure. Classification into distal MBO (DMBO) and hilar MBO (HMBO) guides therapeutic decision-making, with the former predominantly caused by pancreatic head adenocarcinoma and extrahepatic cholangiocarcinoma, while perihilar cholangiocarcinoma represents the principal etiology of the latter. The high morbidity and mortality associated with MBO necessitate prompt, expert intervention. While endoscopic retrograde cholangiopancreatography (ERCP) with transpapillary biliary drainage (TBD) has traditionally served as the cornerstone of management for unresectable tumors, endoscopic ultrasound (EUS)-guided biliary drainage has emerged as a compelling alternative, particularly when conventional ERCP proves technically unsuccessful or anatomically unfeasible. This review comprehensively examines current endoscopic strategies for MBO, emphasizing the complementary roles of ERCP and EUS-based techniques. Optimal outcomes require intervention by experienced endoscopists at high-volume tertiary centers, with individualized treatment selection based on anatomical considerations, tumor characteristics, patient factors, and local expertise. Full article

Background: Surgical resection (SR) and liver transplantation (LT) are the main curative options for non-hepatocellular carcinoma (non-HCC) liver malignancies, including colorectal liver metastases (CRLMs), intrahepatic cholangiocarcinoma (iCCA), hilar cholangiocarcinoma (hCCA), and neuroendocrine tumor liver metastases (NETLMs). Resection aims for negative margins and adequate hepatic reserve, while LT offers treatment for unresectable disease but is limited by donor scarcity, immunosuppression, and ethical constraints. Methods: A targeted literature search (2005–2025) was conducted using PubMed and Google Scholar with predefined MeSH terms combining “liver resection,” “hepatectomy,” and “liver transplantation” across non-HCC malignancies. Relevant studies, reviews, and guidelines were included. Results: For CRLMs, SR remains standard with 5-year overall survival (OS) up to 58%, while LT offers 60–83% in highly selected unresectable cases. In iCCA, resection achieves median survival around 40 months, and LT yields OS up to 69% in very early or neoadjuvant-controlled disease. For hCCA, the Mayo protocol combining neoadjuvant therapy with LT provides 5-year OS of 65–80%. In NETLMs, LT achieves 63–97% OS under strict criteria. Conclusions: SR remains first-line for resectable non-HCC malignancies, while LT provides superior outcomes in unresectable yet biologically favorable disease, emphasizing careful selection and organ allocation. Full article

Malignant hilar biliary obstruction (MHBO) is a complex clinical condition commonly observed in individuals with advanced cholangiocarcinoma and other hepatobiliary malignancies. Endoscopic stenting remains the primary palliative intervention for unresectable cases; however, the optimal strategy has not been clearly defined owing to the anatomical intricacies of the hilar region and the heterogeneity of disease presentation. This narrative review summarizes current evidence and ongoing debates on functional liver volume-based drainage, unilateral versus bilateral stenting, stent type selection, and above-the-papilla approaches. In addition, we highlight recent progress in endoscopic ultrasound-guided biliary drainage as a promising alternative or complementary approach when conventional transpapillary drainage proves inadequate. With recent advances in systemic therapies, including immunotherapy, patient survival has improved, underscoring the need for durable, reintervention-friendly stent strategies. Although uncovered metal stents have long been regarded as the standard for unresectable cases, their limitations in reintervention have prompted renewed consideration of both stent type and drainage technique. Robust prospective studies remain essential to establish standardized, evidence-based guidelines that optimize patient benefit and improve long-term outcomes in unresectable MHBO. Full article

Background: Perihilar cholangiocarcinoma (pCCA), especially the periductal-infiltrating subtype, is notoriously difficult to diagnose due to subtle imaging findings and the absence of a mass. Case Presentation: We describe a 56-year-old man with morbid obesity and deep vein thrombosis (DVT), admitted for severe cholestatic jaundice. Initial ultrasound and two ERCPs were inconclusive, with only mild hilar duct dilation on CT. MRI was not possible due to the severe weight of the patient. Only at the 3rd ERCP with digital cholangioscopy were irregular mucosa and tumor infiltration observed, and a biopsy confirmed moderately to poorly differentiated adenocarcinoma. The patient deteriorated rapidly after discharge, returning in septic shock. Despite laparoscopy excluding cholecystitis and cirrhosis, he died from multiorgan failure. Autopsy revealed diffuse hilar tumor infiltration, nodal metastases, and fatal pulmonary tumor embolism (Bismuth IV). Conclusions: This case highlights the necessity of early escalation to cholangioscopy in unresolved cholestasis, the importance of recognizing paraneoplastic thrombosis, and the value of autopsy in clarifying cause of death. Full article

Perihilar cholangiocarcinoma (pCCA) is the most common subtype of a rare malignancy arising from the biliary tract. Its challenging diagnosis results in delayed treatment, most often when the disease is locally advanced or widespread. Management includes surgery followed by systemic chemotherapy; however, a negative resection margin (R0) is the mainstay for achieving an adequate survival benefit, in the absence of metastatic disease. While minimally invasive surgery (MIS) initially is adopted across every surgical field, laparoscopy’s inherent limitations hinder its implementation for the treatment of pCCA and results in skepticism even for the robotic approach. However, since its initial feasibility phase fifteen years ago, comparable results to open surgery have been reported regarding its safety and oncologic outcomes, in highly selected patients. Moreover, the robotic approach seems to be associated with favorable outcomes regarding post-operative complications, length of hospital stay, and estimated blood loss. International guidelines for the diagnosis and management of pCCA, centralization, definition of a learning curve for MIS, and more comparative studies assessing long term outcomes and randomization are key elements to ensure patient’s safety and technical efficiency. The aim of our review is to provide an updated perspective of the existing literature in the utilization of MIS for patients with pCCA. Full article

Introduction: Distinguishing benign from malignant biliary strictures remains challenging despite diagnostic advancements. Follicular cholangitis, a rare benign condition, presents with symptoms and imaging similar to malignancies like cholangiocarcinoma, often complicating diagnosis, particularly when tumor markers are elevated and imaging suggests metastasis. Case presentation: A 57-year-old woman with hypertension and diabetes was admitted with jaundice. Elevated bilirubin and liver enzymes alongside high carbohydrate antigen 19-9 (CA19-9) levels but normal carcinoembryonic antigen (CEA) were noted. Imaging showed thickening from the hilar duct to the proximal common bile duct, accompanied by suspected lymph node metastases. Comprehensive ERCP-guided biopsies found no malignancy. Surgical resection led to a diagnosis of follicular cholangitis. Conclusions: Follicular cholangitis’ long-term prognosis is elusive due to its rarity, and preoperative diagnosis is challenging. Increased awareness may improve diagnostic and treatment approaches, as this case adds to the disease’s understanding. Full article

Background: Mass-forming intrahepatic cholangiocarcinoma (mICC) is the most frequent type of ICC. In contrast-enhanced computed tomography, mICC is visualized as a hypodense lesion with distal dilatation of intrahepatic bile ducts. The presented case illustrates the unusual manifestation of mICC in a 71-year-old male patient, where despite the extensive tumor mass and the hilar infiltration, the dilatation of intrahepatic bile ducts and cholestasis were not noted. Methods: A literature review on PubMed was performed. Primarily, 547 records were identified, and the titles and abstracts were systematically searched. Regarding the inclusion and exclusion criteria, 31 papers describing the non-cancerous liver lesions mimicking ICC were included in the further analysis. Results: In 41.9% of the analyzed non-cancerous lesions, the obstruction of the bile ducts was not noted, similar to our patient. A significant cholestasis has been found in 30.03% of analyzed patients. The invasion of the liver hilum was noted in one-third of the patients. Conclusions: Atypical radiological features in lesions suspected of ICC, such as the absence of intrahepatic bile-duct dilation, are common in benign lesions. In the case of radiologically atypical lesions suspected of ICC, the diagnostic imaging needs to be correlated with clinical data, and the diagnosis should be confirmed with a pathological examination. Full article

Background/Purpose: Differential diagnosis of isolated immunoglobin (Ig)G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma is challenging. We aimed to clarify the role of endoscopic retrograde cholangiography (ERCP)-related procedures in the differential diagnosis of isolated IgG4-SC and perihilar cholangiocarcinoma (PHCC). Methods: Seven patients with hilar-type isolated IgG4-SC diagnosed at Hiroshima University Hospital and sixty-five patients with surgically resected invasive PHCC were enrolled, and the diagnostic yields of intraductal ultrasonography (IDUS), peroral cholangioscopy (POCS), and pathological examinations were determined. Results: In six of seven (86%) patients with isolated IgG4-SC, the stricture was in the perihilar bile duct. IDUS showed that symmetrical wall thickening (40% vs. 5%, p = 0.04), homogeneous internal echo (80% vs. 5%, p < 0.001), and smooth outer margins (80% vs. 6%, p < 0.001) were more frequent in isolated IgG4-SC than in PHCC. POCS showed a smooth mucosal surface more frequent in isolated IgG4-SC (75% vs. 7%, p = 0.006). Only one patient had two pathological findings characteristic of IgG4-SC. The sensitivity for diagnosing PHCC was 81% using two or more combined sampling methods. Conclusions: Pathological examinations have limitations in the differential diagnosis of isolated-IgG4-SC and PHCC, and a diagnostic strategy that combines multiple ERCP-related procedures, including IDUS and POCS, is recommended. Full article