Intrahepatic and peri-hilar cholangiocarcinoma are life threatening disease with poor outcomes despite optimal treatment currently available (5-year overall survival following resection 20-35%, and <10% cured at 10-years post resection). The insidious onset makes diagnosis difficult, the majority do not have a resection option and the high recurrence rate post-resection suggests that occult metastatic disease is frequently present. Advances in perioperative management, such as ipsilateral portal vein (and hepatic vein) embolisation methods to increase the future liver remnant volume, genomic profiling, and (neo)adjuvant therapies demonstrate great potential in improving outcomes. However multiple areas of controversy exist. Surgical resection rate and outcomes vary between centres with no global consensus on how 'resectable' disease is defined - molecular profiling and genomic analysis could potentially identify patients unlikely to benefit from resection or likely to benefit from targeted therapies. FDG-PET scanning has also improved the ability to detect metastatic disease preoperatively and avoid futile resection. However tumours frequently invade major vasculo-biliary structures, with resection and reconstruction associated with significant morbidity and mortality even in specialist centres. Liver transplantation has been investigated for very selected patients for the last decade and yet the selection algorithm, surgical approach and both value of both neoadjuvant and adjuvant therapies remain to be clarified. In this review, we discuss the contemporary management of intrahepatic and peri-hilar cholangiocarcinoma.

We sought to characterize the benefit of lymphadenectomy among patients undergoing curative-intent surgery for perihilar cholangiocarcinoma (pCCA) utilizing the therapeutic index.

Data on patients who underwent curative-intent resection for pCCA were obtained from 8 high-volume international hepatobiliary centers. Multivariable Cox regression analysis was used to assess clinicopathological factors associated with overall survival (OS). The therapeutic index was determined to assess the therapeutic benefit of lymphadenectomy.

Among 341 patients, median number of lymph nodes (LNs) evaluated was 7 (IQR: 4-11). A total of 127 (37.2 %) patients underwent lymphadenectomy of station 12 only, while 146 (42.8 %) patients had LNs from stations 12 plus 8 ± 13 harvested. On multivariable analysis, lymphadenectomy of stations 12 plus 8 ± 13 was associated with improved OS (referent, station 12 only: HR 0.51, 95%CI 0.32-0.80). The therapeutic index was highest among patients who underwent LN evaluation of stations 12 plus 8 ± 13 (33.1) and had ≥6 LNs harvested (26.3).

At the time of surgery of pCCA, lymphadenectomy should include station 12, as well as stations 8 and 13, with the goal to evaluate ≥6 LNs to ensure optimal staging and maximize the therapeutic benefit for patients.

This study aims to clarify the benefit of adjuvant chemotherapy (AC) in resectable cholangiocarcinoma (CCA) and develop a predictive risk score for treatment selection.

Patients with resected CCA undergoing curative surgery, with or without AC, were identified from three centers in Thailand. Patients with R2 resection and 30 days postoperative death were excluded. Using the largest center as the discovery cohort, we generated propensity score matching (PSM). A predictive model for overall survival (OS) was identified, and a predictive risk score was developed from the PSM discovery cohort, classifying patients into high- and low-risk groups. The proposed risk score was validated in the other two centers.

In the discovery cohort, 493 patients were identified. After PSM, 328 patients were categorized into surgery (n = 164) and surgery + AC (n = 164) groups. The baseline characteristics in the PSM discovery cohort were well-balanced. In the validation cohort (n = 83), patients with positive lymph node 1 received AC more frequently than those under observation (47% v 18%; P = .02). A MINT pathologic risk score was developed from multivariate analysis for OS. The score includes margin, perineural invasion, pathologic nodal status, and pathologic tumor size. In the PSM discovery cohort, for the low-risk score group, the surgery group had significantly longer OS compared with the surgery + AC group (49.4 v 31.5 months; hazard ratio [HR], 1.78 [95% CI, 1.11 to 2.86]; P = .016). Conversely, for the high-risk score group, the surgery + AC group had better OS than the surgery group (18.8 v 8 months; HR, 0.60 [95% CI, 0.46 to 0.79]; P < .001). The results were comparable in the validation cohort.

Patients with resected CCA with a high-risk MINT pathologic risk score were likely to benefit from AC, whereas those with a low-risk score were not. Further validation in a larger prospective cohort is warranted.

Gallbladder cancer is associated with late diagnosis and poor prognosis. Current study aims to develop a prognostic nomogram for predicting survival of gallbladder cancer patients after surgery.

Two large cohorts were included in this analysis. One consisted of 1753 gallbladder cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database, and the other consisted of 239 patients from Shanghai Renji hospital. Significant prognostic factors were identified and integrated to develop the nomogram. Then the model was subjected to bootstrap internal validation and external validation.

Univariate and multivariate analysis indicated that age, tumor histology, T-stage, N-stage and M-stage were significant prognostic factors, which were all included to build the nomogram. The model showed good discrimination, with a concordance index (C-index) of 0.724 (95% CI, 0.708-0.740), and good calibration. Application of the nomogram in the validation cohort still presented good discrimination (C-index, 0.715 [95% CI 0.672-0.758]) and good calibration. In the primary cohort, the C-index of the nomogram was 0.724, which was significantly higher than the Nevin staging system (C-index = 0.671; P < 0.001) and the 8th TNM staging system (C-index = 0.682; P < 0.001). In the validation cohort, the C-index of the nomogram was 0.715, which was also higher than the Nevin staging system (C-index = 0.692; P < 0.05) and the 8th TNM staging system (C-index = 0.688; P = 0.06).

The proposed nomogram resulted in more-accurate prognostic prediction for patients with gallbladder cancer after surgery.

Standard portal vein resection (PVR) has been proposed to improve oncological outcomes in patients with perihilar cholangiocarcinoma (PHC), however it potentially introduces an increased risk of morbidity. The policy in Amsterdam UMC(AMC) is to resect the portal vein bifurcation selectively when involved, while in Charité-Universitätsmedizin Berlin, standard PVR is performed with right trisectionectomy. The objective of this study was to analyze postoperative outcomes and survival after standard or selective PVR for PHC.

A retrospective study was performed including PHC-patients undergoing right-sided resection in Amsterdam (2000-2018) and Berlin (2005-2015). Primary outcomes were 90-day mortality, severe morbidity (Clavien-Dindo≥3), and overall survival (OS). A propensity score comparison (1:1 ratio) was performed corrected for age/sex/ASA/jaundice/tumor diameter/N-stage/Bismuth-Corlette type-IV.

A total of 251 patients who underwent right-sided resection for PHC were evaluated: 87 in the selective (Amsterdam) and 164 in the standard PVR-group (Berlin). Major differences in baseline characteristics were observed, with higher ASA and AJCC-stage in the standard PVR-group (Berlin). Severe morbidity and 90-day mortality were comparable before matching (selective/Amsterdam:68% and 19%, standard/Berlin:61% and 17%,p = 0.284 and p = 0.746, respectively). After propensity score matching, both short term outcomes and OS were comparable (selective/Amsterdam (n = 45) 33 months (95%CI:20-45), standard/Berlin (n = 45) 31 months (95%CI:24-38,p = 0.747)).

In this combined cohort, standard PVR was not associated with increased severe morbidity or mortality. After propensity score matching, survival was comparable after selective (Amsterdam) and standard PVR (Berlin).

Despite being the second most frequent primary liver tumor in humans, early diagnosis and treatment of cholangiocarcinoma (CCA) are still unsatisfactory. In fact, survival after 5 years is expected in less than one fourth of patients diagnosed with this disease. Rare incidence, late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical setting. Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms. Location within the biliary tree has helped to distinguish between intrahepatic, perihilar and distal CCA types. Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy. Novel findings are expected to significantly improve the management of this malignancy in the near future. In this changing scenario our review focuses on the current and future strategies for CCA treatment. Both systemic and surgical treatments are discussed in detail. The results of the main studies in this field are reported, together with the ongoing trials. The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome.

Biliary malignancies, although rare, can be some of the most challenging to manage surgically. Intrahepatic cholangiocarcinomas are resectable if there is no evidence of metastatic disease. These tumors are managed with anatomic resection and portal lymphadenectomy when centrally located or multiple in a single lobe. Non-anatomic resection can be performed for solitary peripheral tumors with minimally invasive techniques. It is not our practice to routinely employ neoadjuvant chemotherapy prior to resection of these tumors. Hepatic arterial infusion chemotherapy is utilized at our institution in highly selected patients in the context of an ongoing clinical trial for unresectable tumors. Hilar cholangiocarcinomas, when resectable (i.e., ipsilateral arterial involvement or lack of vascular involvement), are managed with right or left (extended) hepatectomy, caudate resection, and portal lymphadenectomy. Distal cholangiocarcinomas are managed with pancreaticoduodenectomy. Neoadjuvant chemotherapy is not routinely used in our treatment algorithm of extrahepatic cholangiocarcinomas. Nodal involvement and positive margin (R1) resection necessitates adjuvant chemotherapy. Finally, gallbladder carcinoma is managed with radical cholecystectomy, anatomic segment IVb/V resection, and portal lymphadenectomy. Adjuvant chemotherapy is employed routinely amongst patients with T2 or higher tumors and those with positive lymph nodes.

Biliary tract cancers, including intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder cancer, are low-incidence malignancies in most high-income countries, but represent a major health problem in endemic areas; moreover, the incidence of intrahepatic cholangiocarcinoma is rising globally. Surgery is the cornerstone of cure; the optimal approach depends on the anatomical site of the primary tumour and the best outcomes are achieved through management by specialist multidisciplinary teams. Unfortunately, most patients present with locally advanced or metastatic disease. Most studies in advanced disease have pooled the various subtypes of biliary tract cancer by necessity to achieve adequate sample sizes; however, differences in epidemiology, clinical presentation, natural history, surgical therapy, response to treatment, and prognosis have long been recognised. Additionally, the identification of distinct patient subgroups harbouring unique molecular alterations with corresponding targeted therapies (such as isocitrate dehydrogenase-1 mutations and fibroblast growth factor receptor-2 fusions in intrahepatic cholangiocarcinoma, among others) is changing the treatment paradigm. In this Seminar we present an update of the causes, diagnosis, molecular classification, and treatment of biliary tract cancer.