Resection of perihilar cholangiocarcinoma (pCCA) is associated with significant perioperative morbidity and mortality. We sought to evaluate surgical outcomes following resection of pCCA over time.

Patients who underwent curative-intent resection with hepatectomy for pCCA at a single institution were divided into two cohorts based on date of resection: past cohort (1996-2013), and recent cohort (2014-2023).

The study included 100 patients: 55 (55%) in the past (1996-2013) and 45 (45%) in the recent (2014-2023) cohorts. There were no differences between cohorts in age, sex, or Bismuth-Corlette classification between the two cohorts. Preoperative cholangitis was less common in the recent cohort (31% vs. 53%, p = 0.03). The proportions of right and left hepatectomies were similar in both cohorts. However, for patients with Bismuth-Corlette types I, II, and IV tumors (n = 35), left hepatectomy was more frequently performed in the recent cohort (61% vs. 13%, p = 0.005). There were trends toward lower rates of major complications (38% vs. 55%, p = 0.095) in the recent cohort. There was significantly less perioperative mortality (2% vs. 15%, p = 0.039) and no postoperative hepatic insufficiency in the recent cohort (0% vs. 20%, p = 0.001). Median recurrence-free survival was similar in the past and recent cohorts (29 vs. 37 months, respectively; p = 0.560), but median overall survival was improved in the recent cohort (33 months vs. not reached, p = 0.009).

Perioperative management to reduce preoperative cholangitis and liver insufficiency, advances in surgical technique, and consideration of left-sided hepatic resection have resulted in significantly improved outcomes in patients undergoing hepatectomy for pCCA.

Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus.

This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM).

A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM).

The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.

The prognostic factors for overall survival (OS) in perihilar cholangiocarcinoma (pCCA) included resection margin (RM) and lymph node metastases (LNM). Nevertheless, the advantage associated with a negative RM in patients with LNM remains unresolved.

The study retrospectively analyzed patients with pCCA underwent curative-intent resection between October 2013 and December 2018. The evaluation of the OS was conducted based on the presence of LNM and the status of RM.

Of the 167 resected pCCA patients, 87 (52.1 ​%) were LNM negative, and 80 (47.9 ​%) were LNM positive. Of the 87 LNM-negative patients, 68 (78.2 ​%) were R0 resections, and 19 (21.8 ​%) were R1 resections. In LNM-negative patients, the OS was longer in the R0 resection than the R1 resection group (median survival time (MST) of 32.1 vs 15.7 months, respectively; p ​< ​0.001). Of the 80 LNM-positive patients, 35 were R0 resections and 45 were R1 resections. Among patients with LNM positivity, the OS rates were similar between the groups who underwent R1 resection and R0 resection (MST of 8.4 vs 8.0 months, respectively; p ​= ​0.109).

In patients with pCCA, the RM status was the most important prognostic factor for LNM-negative patients. However, there was no impact in LNM-positive patients.

Perihilar cholangiocarcinoma (PHC) is a challenging malignancy with a poor prognosis, and the role of robotic surgery in its management remains debated. This systematic review aims to assess the feasibility of robotic surgery for PHC.

A systematic literature search was conducted following PRISMA guidelines in Medline, Cochrane Library, and Web of Science for English-language studies on robotic surgery for PHC between 2000 and 2024.

Of the initial 405 manuscripts identified, five studies comprising 110 patients met the inclusion criteria. Pooled analysis showed that operative time ranged from 276 (170-500) to 840 (770-890) minutes, with intraoperative blood loss between 125 (50-425) and 700 (600-800) ml. The rates of overall and major morbidity were 50.0% and 13.6%, respectively. The 30-day and 90-day postoperative mortality rates were 1.8% and 1.9%, respectively. R0 resections were achieved in 78.2% of patients, with a median lymph node retrieval of 7 (8 ± 6.6) to 11 (6-31). Follow-up duration ranged from 7.5 (8.3 ± 2.3) to 15 (19 ± 16) months, recurrence was observed in 14.3% (6/42) of patients.

Robotic surgery for PHC demonstrates promising perioperative outcomes; however, further studies are needed to assess its long-term oncological efficacy compared with traditional approaches.

Future liver remnant hypertrophy is the primary endpoint of portal vein embolization before major hepatectomy. However, even when adequate future liver remnant is achieved, postoperative hepatic insufficiency is not universally averted. We aimed to identify preoperative risk factors of postoperative hepatic insufficiency despite the use of portal vein embolization.

Patients who underwent portal vein embolization followed by major hepatectomy at 6 academic medical centers were retrospectively reviewed. Postoperative hepatic insufficiency was defined as postoperative peak bilirubin >7 mg/dL. Preoperative variables associated with postoperative hepatic insufficiency were analyzed.

From 2008 to 2019, 164 patients underwent portal vein embolization followed by major hepatectomy. Twenty (12%) patients developed postoperative hepatic insufficiency. On univariate analysis, postoperative hepatic insufficiency was associated with older age, performance status, preoperative biliary drainage, smaller pre- and post-portal vein embolization future liver remnant volumes, diagnosis of cholangiocarcinoma/gallbladder cancer, and preoperative cholangitis. There was significant future liver remnant hypertrophy noted even in the setting of postoperative hepatic insufficiency (from 27% to 39%); however, degree of hypertrophy >5% (100% vs 93%, P = .6) and kinetic growth rate >2%/week (95% vs 82%, P = .3) did not differ between the postoperative hepatic insufficiency and non-postoperative hepatic insufficiency groups. On multivariate analysis, the diagnosis of cholangiocarcinoma/gallbladder cancer and preoperative cholangitis (postoperative hepatic insufficiency incidence 34% and 62%, respectively), but not future liver remnant volumetrics, were independently associated with postoperative hepatic insufficiency. Postoperative hepatic insufficiency raised post-hepatectomy 90-day mortality from 3.5% to 45% and hospitalization from 7 days to 16 days (both P < .001).

Postoperative hepatic insufficiency still occurs in 12% of patients after major hepatectomy despite preoperative portal vein embolization. In addition to traditional volumetric information, surgeons should be aware of preoperative cholangitis and cholangiocarcinoma/gallbladder cancer as powerful predictors of this fatal complication.

Cholangiocarcinoma is characterized by its high malignancy, frequent recurrence and insensitivity to conventional radiotherapy and chemotherapy. This resistance may be associated with the presence of cells in the G0/G1 arrest phase within the cancer. Cancer cells in the G0/G1 phase are resistant to therapies targeting actively dividing cells, allowing them to evade conventional adjuvant treatments and survive. When conditions become favorable, these quiescent cells can re-enter the cell cycle, proliferate and potentially contribute to cancer recurrence. However, the biomarkers for identifying cells in the G0/G1 arrest phase within cholangiocarcinoma and the molecular mechanisms inducing G0/G1 arrest remain unclear. In our study, we first identified APOC1 as a characteristic gene for G0/G1 phase arrest in cholangiocarcinoma through bulk RNA sequencing (bulkRNA-seq). We then used single-cell RNA sequencing(scRNA-seq) for cell cycle inference and localized the expression peaks of APOC1 to verify its active cell cycle phase. Our experiments demonstrated that APOC1 can induce G0/G1 phase arrest in cholangiocarcinoma cells by inhibiting the Wnt/β-catenin signaling pathway, thereby suppressing cell proliferation, migration and invasion. This suggests that APOC1 may serve as a key regulatory factor and an important biomarker for cells in the G0/G1 phase of cholangiocarcinoma.

Stent placement for biliary drainage in patients with malignant hilar biliary obstruction (MHBO) has been a topic of long-standing debate, and the best approach remains controversial. Therefore, we aimed to evaluate the efficacy, safety, and removability of multi-hole fully covered self-expandable metal stents (MH-FCSEMSs) in a preclinical experiment using swine hilar bile duct obstruction (HBDO) models and to assess the feasibility and safety of stent placement in patients with MHBO.

Three minipigs underwent endoscopic retrograde cholangiopancreatography (ERCP)-guided endobiliary-radio frequency ablation (EB-RFA) to establish Bismuth type II hilar bile duct stenosis models. Four weeks after EB-RFA, 10-mm diameter and 4-cm length MH-FCSEMSs were endoscopically inserted into the left intrahepatic bile duct of the models. Stent patency and migration, as well as adverse events including cholangitis and endoscopic stent removability, were assessed three months after stent placement. Additionally, clinical applications of MH-FCSEMS were performed in two patients with MHBO to determine feasibility, safety, and stent patency.

MH-FCSEMSs were successfully inserted into the left main intrahepatic bile duct and common hepatic duct of the models under ERCP in all three animals without any technical difficulties. Cholangiograms performed 12 weeks after MH-FCSEMS placement showed no stent migration, and all were successfully removed from the animal models. The functional success rate, defined as a decrease in serum total bilirubin level of more than 50% at 12 weeks after stent placement, was 100%. Moreover, MH-FCSEMSs were successfully inserted in two patients with hilar cholangiocarcinoma. The procedures were technically feasible, and no major periprocedural complications were noted.

The preliminary long-term results of both preclinical and clinical pilot studies suggest that endoscopic biliary drainage using MH-FCSEMS may be a safe and effective treatment option for stenting and stent revision in the management of HBDO. Further studies comparing clinical outcomes to those of MH-FCSEMS without multi-hole in malignant hilar biliary obstruction will be needed to verify the clinical benefits.

Despite complete resection, the recurrence rate of biliary tract cancer (BTC) remains high, leading to poor prognosis. Postoperative adjuvant chemotherapy (ACT) following radical resection may substantially reduce the recurrence risk by eradicating micrometastatic lesions. However, the benefits of postoperative ACT and the optimal ACT strategy are still unclear for BTC. The objectives of this study are to evaluate the prognostic value of ACT and compare the effectiveness of different ACTs among BTC patients after curative resection.

A comprehensive literature search was conducted across PubMed, Cochrane Library, Web of Science, and EMBASE databases to identify randomized controlled trials (RCTs) comparing the benefits of ACT versus no intervention or other ACTs in BTC patients after curative resection. A random-effects network meta-analysis was performed to compare overall survival (OS) and relapse-free survival (RFS). The quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation framework.

Eight RCTs comprising 1803 patients were included in the meta-analysis. ACT was associated with significant improvements in 5-year all-cause mortality [four RCTs, hazard rate (HR) 0.93; 95% confidence interval (CI), 0.87-1.00, marginally significant; low-certainty evidence], RFS (five RCTs, HR 0.87; 95% CI, 0.78-0.98; moderate-certainty evidence), and OS (7 studies, HR 0.85; 95% CI, 0.75-0.96; low-certainty evidence) compared with observation. ACT had significantly better survival benefits on patients with negative margins (R0), lymph node-positive (N+), and tumor node metastasis classification (TNM) stage I/II ( P < 0.05). Further network meta-analysis demonstrated that fluorouracil-based ACT was significantly inferior to gemcitabine-based ACT (HR 1.20; 95% CI, 1.10-1.25) in improving RFS. However, both were superior to observation ( P < 0.05). No statistical difference in OS was observed between gemcitabine-based and fluorouracil-based chemotherapy (HR 1.00; 95% CI, 0.86-1.20). In subgroup analysis, fluorouracil-based ACT but not gemcitabine-based ACT achieved significantly better OS benefits on patients with N+ (HR 0.67; 95% CI, 0.52-0.86) and R0 (HR 0.69; 95% CI, 0.54-0.88).

Compared with observation, ACT should be routinely recommended to improve survival outcomes in BTC patients after curative resection, especially for those with R0, N+, and TNM stage I/II. Gemcitabine-based ACT performed better than other chemotherapies in improving RFS. This network meta-analysis provides precise information for determining the best adjuvant treatment for resected BTC. Further thorough and high-quality RCTs are needed.

The extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC) remains unclear. This research aimed to explore the pattern and extent of intrahepatic infiltration of PHCC to guide surgical treatment and pathological research.

This study included 62 patients diagnosed with PHCC who underwent major hepatectomy. A whole-mount digital liver pathology system (WDLPS) for hepatectomy specimens greater than 10×10 cm was used to panoramically assess the intrahepatic infiltration extent of PHCC.

The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important parts of intrahepatic infiltration for PHCC explored by WDLPS. The study confirmed that 75.8% of PHCCs had RLI and the infiltration distance in all patients were within 15 000 µm, 62.9% of PHCCs had DIHI greater than 1 cm away from the main tumor in the liver parenchyma. The recurrence-free survival rates and overall survival rates of patients with DIHI were poorer than the patients without DIHI ( P <0.0001, P =0.0038). Arterial invasion on the resected side could be an excellent predictor. A total of 105 liver lobes were resected from 62 PHCC patients. The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC were 79%, 100%, 100%, and 69%, respectively.

The presence of DIHI in most PHCCs was a significant factor for the poor survival. Based on the extent of intrahepatic infiltration, minor hepatectomy was not suitable as the curative surgery for PHCC. Major hepatectomy and liver transplantation were the ideal radical treatment.

The aim is to assess and contrast the effectiveness and safety of employing robotic surgery versus traditional open surgery in managing cases of hilar cholangiocarcinoma.

Computer searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Database to identify case-control studies comparing robotic surgery with traditional open surgery in the treatment of hilar cholangiocarcinoma from inception until July 2023. References from retrieved articles were reviewed to broaden the search. This review was prospectively registered in the PROSPERO database (PROSPERO ID: CRD42024527511) and reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. The primary outcome measures included operation time, intraoperative blood transfusion rate, R0 resection rate, lymph node metastasis rate, incidence of postoperative complications, and postoperative hospital stay. Data analysis was performed using RevMan 5.4 software, calculating combined odds ratios (OR), mean differences (MD), and 95% CI.

A total of 4 studies encompassing 267 patients diagnosed with hilar cholangiocarcinoma (177 males and 90 females, mean age of (58.8±5.7) years) were included in this analysis. Among these, 165 patients underwent open surgery, while 102 patients underwent robotic surgery. The results of the meta-analysis demonstrated comparable outcomes between the two groups. Specifically, the operation time between the robotic surgery and open surgery cohorts did not significantly differ (MD=-103.96, 95% CI: -216.90 to 8.98, P = 0.070 ). Additionally, the intraoperative blood transfusion rate (OR=1.32, 95% CI: 0.43-4.07, P =0.630), R0 resection rate (OR=1.41, 95% CI: 0.71-2.81, P=0.330 ), and lymph node metastasis rate (OR=1.62, 95% CI: 0.46-5.63, P=0.450 ) showed no significant differences between the groups. Similarly, there were no statistically significant disparities observed in the incidence of postoperative complications (OR=0.60, 95% CI: 0.28-1.31, P=0.200 ) and postoperative hospital stay (MD=2.17, 95% CI: -11.56 to 15.90, P=0.760 ).

In the treatment of hilar cholangiocarcinoma, robotic surgery demonstrates comparable safety and feasibility to traditional open surgery. However, due to the limited quantity and quality of the included studies, these conclusions warrant validation through additional high-quality investigations.

In patients with hilar cholangiocarcinoma (HCCA), radical resection can be achieved by resection and reconstruction of the vasculature. However, whether vascular reconstruction (VR) improves long-term and short-term prognosis has not been demonstrated comprehensively.

This was a retrospective multicenter study of patients who received surgery for HCCA with or without VR. Variables associated with overall survival (OS) and recurrence-free survival (RFS) were identified based on Cox regression. Kaplan-Meier curves were used to explore the impact of VR. Restricted mean survival time (RMST) was used for comparisons of short-term survival between the groups. Patients' intraoperative and postoperative characteristics were compared.

Totally 447 patients were enrolled. We divided these patients into 3 groups: VR with radical resections (n = 84); non-VR radical resections (n = 309) and non-radical resection (we pooled VR-nonradical and non-VR nonradical together, n = 54). Cox regression revealed that carbohydrate antigen 242 (CA242), vascular invasion, lymph node metastasis and poor differentiation were independent risk factors for OS and RFS. There was no significant difference of RMST between the VR and non-VR radical groups within 12 months after surgery (10.18 vs. 10.76 mon, P = 0.179), although the 5-year OS (P < 0.001) and RFS (P < 0.001) were worse in the VR radical group. The incidences of most complications were not significantly different, but those of bile leakage (P < 0.001) and postoperative infection (P = 0.009) were higher in the VR radical group than in the non-VR radical group. Additionally, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) up to 7 days after surgery tended to decrease in all groups. There was no significant difference in the incidence of postoperative liver failure between the VR and non-VR radical groups.

Radical resection can be achieved with VR to improve the survival rate without worsening short-term survival compared with resection with non-VR. After adequate assessment of the patient's general condition, VR can be considered in the resection.

Resection margin status is the important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the effect of positive RM on survival.

Patients with pCCA underwent curative resection between 2013 and 2018 were retrospectively reviewed. Resection margin status was divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+).

Of the 167 pCCA patients, 62 (37.1%) had R1 margin. Among 62 R1 patients; 17 (27.4%) had positive DM alone, 20 (32.3%) had positive RM alone and 25 (40.3%) had both positive DM and RM. The R1 patients had a significantly greater number of lymph node metastasis (LNM) and advanced tumor staging than R0 patients, however there was no difference between the RM + and DM + patients. The median survival time of patients with RM + was significantly poorer than R0 patients (13.8 vs. 24.5 months; p < 0.001, respectively) and similar to the DM + patients (9.1 months, p = 0.556). However, in patients with LNM, those who underwent R0 resection had no statistically significant difference in survival outcomes compared to those with R1 resection.

Positive resection margin remains the important prognostic factor, and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM.

Relief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy - including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented.

We performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients.

56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) < 2 mg/dl: 66.1% vs. 27.8%, p = < 0.001, > 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia.

Biliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients.

Perihilar cholangiocarcinoma (pCCA) is a highly lethal hepatobiliary cancer. Radical resection offers the best chance for extended survival, but the efficacy of left-sided hepatectomy (LH) versus right-sided hepatectomy (RH) remains controversial.

A systematic review and meta-analysis of non-randomized cohort studies comparing LH and RH in patients with resectable pCCA was conducted. Subanalyses were performed based on year of publication, region, number of cases and Bismuth classification (BC) ≥ III.

Nineteen studies involving 3838 patients were included, with 1779 (46 %) undergoing LH and 2059 (54 %) undergoing RH. LH was associated with increased overall survival (OS) in subgroup analysis of studies reporting hazard ratios (HR) (logHR 0.59; p = 0.04). LH showed higher rates of arterial resection (14 % vs. 1 %), transfusion (51 % vs. 41 %), operation time (MD 31.44 min), and bile leakage (21 % vs. 18 %), but lower rates of post-hepatectomy liver failure (9 % vs. 21 %) and 90-day mortality (8 % vs 16 %). Three-year disease-free survival rates increased in Western centers but decreased in Eastern centers.

LH is linked to higher OS in this analysis but is a more demanding technique. Resection side decision should consider several factors, including future liver remnant, tumor location, vascular involvement, and surgical expertise.

Cholangiocarcinomas (CCAs), a heterogeneous group of challenging malignant tumours which originate from the biliary epithelium, are associated with an alarming increasing incidence during recent decades that varies between different regions of the globe. Thus, awareness represents the key operating factor. Our purpose was to overview the field of CCAs following a double perspective: the constellation of the risk factors, and the presence of the paraneoplastic syndromes, emphasizing the endocrine features amid the entire multidisciplinary panel. This is a narrative review. A PubMed-based search of English-language original articles offered the basis of this comprehensive approach. Multiple risk factors underlying different levels of statistical evidence have been listed such as chronic biliary diseases and liver conditions, inflammatory bowel disease, parasitic infections (e.g., Opisthorchis viverrini, Clonorchis sinensis), lifestyle influence (e.g., alcohol, smoking), environmental exposure (e.g., thorotrast, asbestos), and certain genetic and epigenetic interplays. With regard to the endocrine panel, a heterogeneous spectrum should be taken into consideration: non-alcoholic fatty liver disease, obesity, type 2 diabetes mellitus, and potential connections with vitamin D status, glucagon-like peptide 1 receptor, or the galanin system, respectively, with exposure to sex hormone therapy. Amid the numerous dermatologic, hematologic, renal, and neurologic paraneoplastic manifestations in CCAs, the endocrine panel is less described. Humoral hypercalcaemia of malignancy stands as the most frequent humoral paraneoplastic syndrome in CCAs, despite being exceptional when compared to other paraneoplastic (non-endocrine) manifestations and to its reported frequency in other (non-CCAs) cancers (it accompanies 20-30% of all cancers). It represents a poor prognosis marker in CCA; it may be episodic once the tumour relapses. In addition to the therapy that targets the originating malignancy, hypercalcaemia requires the administration of bisphosphonates (e.g., intravenous zoledronic acid) or denosumab. Early detection firstly helps the general wellbeing of a patient due to a prompt medical control of high serum calcium and it also provides a fine biomarker of disease status in selected cases that harbour the capacity of PTHrP secretion. The exact molecular biology and genetic configuration of CCAs that display such endocrine traits is still an open matter, but humoral hypercalcaemia adds to the overall disease burden.

The aim of this study was to describe our preliminary experience in the procedure of laparoscopic radical resection of hilar cholangiocarcinoma and to evaluate its feasibility, safety, and clinical efficacy.

A retrospective analysis was conducted on 44 patients with hilar cholangiocarcinoma who underwent laparoscopic surgery at our hospital from August 2019 to September 2023. Clinical data were collected from these patients, including 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb.

Laparoscopic radical resection of hilar cholangiocarcinoma was successfully performed in 38 patients (86.3%). Among the remaining patients, 3 required vascular reconstruction to complete radical surgery and were converted to laparotomies, while 3 others underwent T-tube drainage only due to unresectable metastases. The median operation time was 285 min (range, 190-450), and the median estimated blood loss was 360 mL (range, 260-1200). The postoperative hospital stay duration was 14.3 ± 3.6 days. No perioperative mortality was observed. Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) of Grade I, 3 cases (6.8%) of Grade II, 1 case (2.2%) of Grade IIIa, and no Grade IIIb or IV complications. The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3-43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years.

Total laparoscopic radical resection of hilar cholangiocarcinoma can be performed safely, feasibly, and effectively by experienced surgeons after an accurate preoperative evaluation.

Portal vein embolization (PVE) is recommended as a preoperative procedure for patients with biliary tract cancer scheduled to undergo hepatic resection of more than 50%-60% of the liver. However, details and/or information regarding the follow-up of unresectable cases are often lacking, and the clinical course of unresectable cases is not well analyzed and reported. This study aimed to clarify the clinical prognosis of patients with unresectable biliary tract cancer after PVE. We retrospectively analyzed the clinical backgrounds of patients with biliary tract cancer who underwent PVE without subsequent resection between January 2011 and October 2022. Of the 21 patients with biliary tract cancer who underwent PVE during the study period, eight (38%) cases were unsuitable for resection after PVE for the following reasons: intraoperatively detected dissemination (n=2), para-aortic lymph node metastasis (n=1), liver metastasis (n=1), decreased liver function (n=2), development of liver metastasis while waiting (n=1), and insufficient residual liver volume (n=1). All patients received subsequent chemotherapy, including gemcitabine plus S-1 therapy in three cases, gemcitabine plus cisplatin plus S-1 in three cases, and gemcitabine plus cisplatin or S-1+cisplatin in one case each. As there is currently no curative treatment for biliary tract cancer other than surgery, multidisciplinary management and treatment of patient factors, including tumor factors and liver function, are essential to reducing the number of unresectable cases after PVE.

Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA).

We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated.

A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%.

For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.

Although robotic radical resection for hilar cholangiocarcinoma (HCCA) has been reported in some large hepatobiliary centers, biliary-enteric reconstruction (BER) remains a critical step that hampers the operation's success. This study aimed to evaluate the feasibility and quality of BER in robotic radical resection of HCCA and propose technical recommendations. A retrospective study was conducted on patients with HCCA who underwent minimally invasive radical resection at Zhejiang Provincial People's Hospital between January 2016 and July 2023. A 1:2 propensity score matching (PSM), widely used to reduce selection bias, was performed to evaluate the outcomes, especially BER-related data, between the robotic and laparoscopic surgery. Forty-six patients with HCCA were enrolled; ten underwent robotic-assisted resection, while the others underwent laparoscopic surgery. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robot-assisted and laparoscopic groups, respectively. The baseline characteristics of both groups were generally well-balanced. The average liver resection time was longer in the robotic group than in the laparoscopic group (139.5 ± 38.8 vs 108.1 ± 35.8 min, P = 0.036). However, the former had less intraoperative blood loss [200 (50-500) vs 310 (100-850) ml], despite no statistical difference (P = 0.109). The number of residual bile ducts was 2.6 ± 1.3 and 2.7 ± 1.2 (P = 0.795), and anastomoses were both 1.6 ± 0.7 in the two groups (P = 0.965). The time of BER was 38.4 ± 13.6 and 59.1 ± 25.5 min (P = 0.024), accounting for 9.9 ± 2.8% and 15.4 ± 4.8% of the total operation time (P = 0.001). Although postoperative bile leakage incidence in laparoscopic group (40%) was higher than that in robotic group (10%), there was no significant difference between the two groups (P = 0.204); 6.7 ± 4.4 and 12.1 ± 11.7 days were observed for tube drawing (P = 0.019); anastomosis stenosis and calculus rate was 10% and 30% (P = 0.372), 0% and 15% (P = 0.532), respectively. Neither group had hemorrhage- or bile leakage-related deaths. Robotic radical resection for HCCA may offer perioperative outcomes comparable to conventional laparoscopic procedures and tends to be advantageous in terms of anastomosis time and quality. We are optimistic about its wide application in the future with the improvement of surgical techniques and experience.

Biliary tract cancers comprise a heterogeneous collection of malignancies usually described as cholangiocarcinoma of the intra- or extrahepatic bile duct, including perihilar cholangiocarcinoma and gallbladder cancer.

A review of pertinent parts of the ESSO core curriculum for the UEMS diploma targets (Fellowships exam, EBSQ), based on updated and available guidelines for diagnosis, surgical treatment and oncological management of cholangiocarcinoma.

Following the outline from the ESSO core curriculum we present the epidemiology and risk factors for cholangiocarcinoma, as well as the rationale for the current diagnosis, staging, (neo-)adjuvant treatment, surgical management, and short- and long-term outcomes. The available guidelines and consensus reports (i.e. NCCN, BGS and ESMO guidelines) are referred to. Recognition of biliary tract cancers as separate entities of the intrahepatic biliary ducts, the perihilar and distal bile duct as well as the gallbladder is important for proper management, as they each provide distinct clinical, molecular and treatment profiles to consider.

Core competencies in knowledge to the diagnosis, management and outcomes of biliary tract cancers are presented.

Although post-hepatectomy liver failure (PHLF) can accurately predict short-term mortality of liver resection for perihilar cholangiocarcinoma (pCCA), its significance in predicting long-term overall survival (OS) is still uncertain.

Retrospective analysis was performed on patients with pCCA who underwent liver resection between October 2013 and December 2018. The patients were divided into 3 groups; No PHF, PHLF (all grade) and grade B/C PHLF according to The International Study Group of Liver Surgery (ISGLS) criteria.

A total of 177 patients were enrolled, 65 (36.7%) had PHLF; 25 (14.1%) had grade A, and 40 (22.6%) had grade B/C. Prior to surgery, patients with PHLF showed significantly greater bilirubin levels and CA 19-9 level than those without (11.5 vs 6.7 mg/dL, p = 0.002 and 232.4 vs 85.9 U/mL, p = 0.005, respectively). Additionally, pre-operative future liver remnant volume in PHLF group was lower than no PHLF group significantly (39.6% vs 43.5%, p = 0.006). Major complication and 90-day mortality were higher in PHLF group than no PHLF group (69.2% vs 20.5%, p < 0.001 and 29.2% vs 3.6%, p < 0.001, respectively). The OS in both grade A PHLF and grade B/C PHLF was significantly worse compared to no PHLF, with median survival times of 8.4, 3.3, and 19.2 months, respectively (p < 0.001 and p < 0.001, respectively). Multivariable analysis revealed that PHLF was independently prognostic factor for long-term survival.

To achieve negative resection margin, the surgical resection in pCCA was aggressive, however this increased the risk of PHLF, which also affects the OS. Consequently, it is necessary for establishing a balance between aggressive surgery and PHLF.

The optimal surgical approach for Bismuth II hilar cholangiocarcinoma (HCCA) remains controversial. This study compared perioperative and oncological outcomes between minor and major hepatectomy.

One hundred and seventeen patients with Bismuth II HCCA who underwent hepatectomy and cholangiojejunostomy between January 2018 and December 2022 were retrospectively investigated. Propensity score matching created a cohort of 62 patients who underwent minor (n = 31) or major (n = 31) hepatectomy. Perioperative outcomes, complications, quality of life, and survival outcomes were compared between the groups. Continuous data are expressed as the mean ± standard deviation, categorical variables are presented as n (%).

Minor hepatectomy had a significantly shorter operation time (245.42 ± 54.31 vs. 282.16 ± 66.65 min; P = 0.023), less intraoperative blood loss (194.19 ± 149.17 vs. 315.81 ± 256.80 mL; P = 0.022), a lower transfusion rate (4 vs. 11 patients; P = 0.038), more rapid bowel recovery (17.77 ± 10.00 vs. 24.94 ± 9.82 h; P = 0.005), and a lower incidence of liver failure (1 vs. 6 patients; P = 0.045). There were no significant between-group differences in wound infection, bile leak, bleeding, pulmonary infection, intra-abdominal fluid collection, and complication rates. Postoperative laboratory values, length of hospital stay, quality of life scores, 3-year overall survival (25.8 % vs. 22.6 %; P = 0.648), and 3-year disease-free survival (12.9 % vs. 16.1 %; P = 0.989) were comparable between the groups.

In this propensity score-matched analysis, overall survival and disease-free survival were comparable between minor and major hepatectomy in selected patients with Bismuth II HCCA. Minor hepatectomy was associated with a shorter operation time, less intraoperative blood loss, less need for transfusion, more rapid bowel recovery, and a lower incidence of liver failure. Besides, this findings need confirmation in a large-scale, multicenter, prospective randomized controlled trial with longer-term follow-up.

Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021.

Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop.

In November 2021, the finalized draft was presented for public scrutiny during a formal hearing.

The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed.

A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA).

The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin-globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child-pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients.

The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC.

Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53-79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.

To compare the clinical efficacy and safety of robot-assisted resection and open surgery for cholangiocarcinoma (CCA). We conducted a comprehensive search of PubMed, the Cochrane Library, and Embase databases for studies comparing treatment for CCA, covering the period from database inception to January 30, 2024. Two researchers will independently screen literature and extract data, followed by meta-analysis using Review Manager 5.3 software. A total of 5 articles with 513 patients were finally included. Among them, 231 in the robotic group, and 282 in the open group. The Meta-analysis revealed that the robotic group had a significant advantage in terms of intraoperative blood loss (MD =  - 101.44, 95% CI - 135.73 to - 67.15, P < 0.05), lymph node harvest(MD = 1.03, 95% CI 0.30- 1.76, P < 0.05) and length of hospital stay(MD =  - 1.92, 95% CI - 2.87 to- 0.97, P < 0.05). However, there were no statistically significant differences between the two groups in terms of transfusion rate (OR = 0.62, 95% CI 0.31-1.23, P > 0.05), R0 resection (OR = 1.49, 95% CI 0.89- 2.50, P > 0.05), 30-day mortality (OR = 1.68, 95% CI 0.43-6.65, P > 0.05) and complications (OR = 0.76, 95% CI 0.30- 1.95, P > 0.05). Robotic-assisted radical resection for CCA is feasible and safe, and its long-term efficacy and oncological outcomes need to be confirmed by further studies.

Congenital biliary dilatation (CBD) necessitates the timely removal of dilated bile ducts. Accurate differentiation between CBD and secondary biliary dilatation (SBD) is crucial for treatment decisions, and identification of CBD with intrahepatic involvement is vital for surgical planning and supportive care. This study aimed to develop quantitative models based on bile duct morphology to distinguish CBD from SBD and further identify CBD with intrahepatic involvement.

The retrospective study included 131 CBD and 209 SBD patients between December 2014 and December 2021 for model development, internal validation, and testing. A separate cohort of 15 CBD and 34 SBD patients between January 2022 and December 2022 was recruited for temporally-independent validation. Quantitative shape-based (Shape) and diameter-based (Diam) morphological characteristics of bile ducts were extracted to build a CBD diagnosis model to distinguish CBD from SBD and an intrahepatic involvement identification model to classify CBD with/without intrahepatic involvement. The diagnostic performance of the models was compared with that of experienced hepatobiliary surgeons.

The CBD diagnosis model using clinical, Shape, and Diam characteristics showed good performance with an AUROC of 0.942 (95% CI: 0.890-0.994), AUPRC of 0.917 (0.855-0.979), accuracy of 0.891, sensitivity of 0.950, and F1-score of 0.864. The model outperformed two experienced surgeons in accuracy, sensitivity, and F1-score. The intrahepatic involvement identification model using clinical, Shape, and Diam characteristics yielded outstanding performance with an AUROC of 0.944 (0.879-1.000), AUPRC of 0.982 (0.947-1.000), accuracy of 0.932, sensitivity of 0.971, and F1-score of 0.957. The models demonstrated generalizable performance on the temporally-independent validation cohort.

This study developed two robust quantitative models for distinguishing CBD from SBD and identifying CBD with intrahepatic involvement, respectively, based on morphological characteristics of the bile ducts, showing great potential in risk stratification and surgical planning of CBD.

Distinguishing malignant from benign causes of obstruction at the liver hilum can pose a diagnostic dilemma. This study aimed to determine factors that predict benign causes of hilar obstruction and long-term outcomes after resection.

Consecutive patients who underwent surgery for hilar obstruction at a single institution between 1997 and 2022 were retrospectively analyzed. Median follow-up was 26 months (range 0-281 months).

Among 182 patients who underwent surgery for hilar obstruction, 25 (14%) patients were found to have benign disease. Median CA19-9 level after normalization of serum bilirubin was 80 U/mL (range 1-5779) and 21 U/mL (range 1-681) among patients with malignant and benign strictures, respectively (p = 0.001). Cross-sectional imaging features associated with malignancy were lobar atrophy, soft tissue mass/infiltration, and vascular involvement (all p < 0.05). Factors not correlated with malignancy were jaundice upon presentation, peak serum bilirubin, sex, and race. Preoperative bile duct brushing or biopsy had sensitivity and specificity rates of 82% and 55%, respectively. Among patients who underwent resection with curative intent, grade 3-4 complications occurred in 55% and 29% of patients with malignant and benign strictures, respectively (p = 0.028). Postoperative long-term complications of chronic portal hypertension and recurrent cholangitis occurred in ≥ 10% of patients with both benign and malignant disease (p = non-significant).

Strictures at the liver hilum continue to present diagnostic and management challenges. Postoperative complications and long-term sequelae of portal hypertension and recurrent cholangitis develop in a significant number of patients after resection of both benign and malignant strictures.

For patients with hilar cholangiocarcinoma (HC) undergoing hemi-hepatectomy, there are controversies regarding the requirement of, indications for, and timing of preoperative biliary drainage (PBD). Dynamic three-dimensional volume reconstruction could effectively evaluate the regeneration of liver after surgery, which may provide assistance for exploring indications for PBD and optimal preoperative bilirubin value. The purpose of this study was to explore the indications for PBD and the optimal preoperative bilirubin value to improve prognosis for HC patients undergoing hemi-hepatectomy.

We retrospectively analyzed the data of HC patients who underwent hemi-hepatectomy in the First Affiliated Hospital of China Medical University from 2012 to 2023. The liver regeneration rate was calculated using three-dimensional volume reconstruction. We analyzed the factors affecting the liver regeneration rate and occurrence of postoperative liver insufficiency.

This study involved 83 patients with HC, which were divided into PBD group (n=36) and non-PBD group (n=47). The preoperative bilirubin level may be an independent risk factor affecting the liver regeneration rate (P=0.014) and postoperative liver insufficiency (P=0.016, odds ratio=1.016, β=0.016, 95% CI=1.003-1.029). For patients whose initial bilirubin level was >200 μmol/L (n=45), PBD resulted in better liver regeneration in the early stage (P=0.006) and reduced the incidence of postoperative liver insufficiency [P=0.012, odds ratio=0.144, 95% confidence interval (CI)=0.031-0.657]. The cut-off value of bilirubin was 103.15 μmol/L based on the liver regeneration rate. Patients with a preoperative bilirubin level of ≤103.15 μmol/L shown a better liver regeneration (P<0.01) and lower incidence of postoperative hepatic insufficiency (P=0.011, odds ratio=0.067, 95% CI=0.008-0.537).

For HC patients undergoing hemi-hepatectomy whose initial bilirubin level is >200 μmol/L, PBD may result in better liver regeneration and reduce the incidence of postoperative liver insufficiency. Preoperative bilirubin levels ≤103.15 μmol/L maybe recommended for leading to a better liver regeneration and lower incidence of postoperative hepatic insufficiency.

Adequate preoperative biliary drainage (PBD) is recommended in most patients with resectable perihilar cholangiocarcinoma (pCCA). Most expert centers use endoscopic plastic stents rather than self-expandable metal stents (SEMSs). In the palliative setting, however, use of SEMSs has shown longer patency and superior survival. The aim of this retrospective study was to compare stent dysfunction of SEMSs versus plastic stents for PBD in resectable pCCA patients.

In this multicenter international retrospective cohort study, patients with potentially resectable pCCAs who underwent initial endoscopic PBD from 2010 to 2020 were included. Stent failure was a composite end point of cholangitis or reintervention due to adverse events or insufficient PBD. Other adverse events, surgical outcomes, and survival were recorded. Propensity score matching (PSM) was performed on several baseline characteristics.

A total of 474 patients had successful stent placement, of whom 61 received SEMSs and 413 plastic stents. PSM (1:1) resulted in 2 groups of 59 patients each. Stent failure occurred significantly less in the SEMSs group (31% vs 64%; P < .001). Besides less cholangitis after SEMSs placement (15% vs 31%; P = .012), other PBD-related adverse events did not differ. The number of patients undergoing surgical resection was not significantly different (46% vs 49%; P = .71). Complete intraoperative SEMSs removal was successful and without adverse events in all patients.

Stent failure was lower in patients with SEMSs as PBD compared with plastic stents in patients with resectable pCCA. Removal during surgery was quite feasible. Surgical outcomes were similar.

Surgery for perihilar cholangiocarcinoma (pCCA) is associated with high rates of postoperative morbidity and mortality. Extended liver resection (EXT) increases R0 resection rate and survival; however, patients with high perioperative risk are not suitable for extended resection. This study aimed to compare overall survival and surgical morbidity in patients with extended liver resection and parenchyma-preserving hepatectomy (PPH).

Between January 2010 and November 2020, 113 consecutive patients with pCCA underwent surgery at our institution. Eighty-two patients were resected in curative intent. Sixty-four patients received extended liver resection, and 18 patients PPH. Outcomes of resections were evaluated.

There was no significant difference in overall survival in patients with PPH compared to extended liver resection (log-rank p = 0.286). Patients with PPH experienced lower rates of postoperative morbidity and mortality. There was no case of in-house mortality in PPH-resected patients compared to 10 cases (16%) in patients that received EXT (p = 0.073).

PPH shows similar overall survival with lower rates of postoperative morbidity and mortality. Our findings support the role of a PPH, in selected patients with pCCA, that are not suitable for extended resection due to increased perioperative risk.

Hepatobiliary cancer (HBC) includes hepatocellular carcinoma and biliary tract carcinoma (cholangiocarcinoma and gallbladder carcinoma), and its morbidity and mortality are significantly correlated with disease stage. Surgery is the cornerstone of curative therapy for early stage of HBC. However, a large proportion of patients with HBC are diagnosed with advanced stage and can only receive systemic treatment. According to the results of clinical trials, the first-line and second-line treatment programs are constantly updated with the improvement of therapeutic effectiveness. In order to improve the therapeutic effect, reduce the occurrence of drug resistance, and reduce the adverse reactions of patients, the treatment of HBC has gradually developed from single-agent therapy to combination. The traditional therapeutic philosophy proposed that patients with advanced HBC are only amenable to systematic therapies. With some encouraging clinical trial results, the treatment concept has been revolutionized, and patients with advanced HBC who receive novel systemic combination therapies with multi-modality treatment (including surgery, transplant, TACE, HAIC, RT) have significantly improved survival time. This review summarizes the treatment options and the latest clinical advances of HBC in each stage and discusses future direction, in order to inform the development of more effective treatments for HBC.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.