Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma

Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.

Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures

Biliary tract cancers (BTCs) include a heterogenous group of aggressive malignancies with limited therapeutic options. According to their anatomical location, these hepatobiliary tumors are usually classified into intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer (GBC). Unfortunately, BTCs are often diagnosed when already metastatic, and although the advent of genomic sequencing has led to a deeper understanding of iCCA pathogenesis, very little data are currently available about the molecular landscape of eCCA. Moreover, despite novel systemic treatments emerging in BTC, the grim prognosis of eCCA patients has not changed in the past decade, and no targeted therapies have been approved so far. The aim of the current review is to provide an overview regarding molecular features and potential targeted therapies in eCCA, together with novel therapeutic approaches and future directions of translational and clinical research on this highly aggressive disease that poses many unanswered questions.

Hepatobiliary tumors in adolescents and young adults: Site, age and gender distribution.

e16651 Background: Hepatobiliary cancer is one of the common cancers within Asia with 80% of global cases occurring in the continent alone. Currently little is known about the incidence of hepatobiliary cancer in the Adolescent and Young Adults (AYA). In this population, hepatobiliary cancer may present in an insidious manner due to low suspicion and management may result in a higher likelihood of survivors with long-term treatment-related toxicities. We aim to highlight the clinicopathological features and treatment outcomes in this age-group in an Asian high-volume tertiary cancer institution. Methods: Patients diagnosed between the age of 16-39 with hepatobiliary cancers between 1st January 2015 to 31st December 2019 in a single-centre institution in Singapore were included in this study. Results: There was a total of 84 AYA patients with hepatobiliary tumours who were referred to our institution. Median age of diagnosis was 35 years old (n = 84). 32 patients (38.1%) had hepatocellular carcinoma, 22 patients (26.2%) had biliary tract tumours, 11 patients (13.1%) had neuroendocrine cancers while 19 patients (22.6%) had other tumour types (Figure 1). Male incidence was highest in all hepatobiliary AYAs (n = 56, 66.7%, p = 0.002) and hepatocellular carcinomas (n = 25, 78.1%, p = 0.001) (Table). 65 patients (77.4%) remain alive as of 31st December 2019. Conclusions: Patterns of hepatobiliary incidence differ between sexes. In the young AYA population, hepatocellular precursor cells may have sex-specific features affecting malignant potentials. More studies should be done to further elucidate the genomic and epidemiology of hepatobiliary tumours in the younger population of patients to better outcomes in this population. [Table: see text]

Survival outcomes according to the tumor mutation burden and PD-L1 expression in hepatobiliary tumors.

566 Background: Hepatobiliary (HB) tumors are aggressive tumors with emerging evidence for increasing sensitivity to immune checkpoint inhibitors (ICI). Tumor mutation burden (TMB) was found to be a quantitative biomarker associated with production of neoantigens within the tumor and predict the sensitivity to immune therapy. Herein, we explore the TMB, microsatellite instability (MSI) and PD-L1 expression as a potential biomarker of response to immune therapy in HB tumors. Methods: We retrospectively assessed all patients with hepatobiliary malignancies who have undergone next generation sequencing (NGS) between October 2009 and June 2019. We then analysed the tumor mutation burden and PD-L1 of these tumors and also identified frequency of patients with no clinically actionable mutations. Results: In our total 61 patients with HB tumors predominantly were male (62.3%) with mean age of 63 years. Thirty-four patients had hepatocellular carcinoma, 22 patients had cholangiocarcinoma and 5 patients had gallbladder carcinoma. The most common risk factors were smoking status, cirrhosis, alcohol consumption and hepatitis C virus. The mean TMB reported was 3.2 (1.16 – 7.35). MSI was identified in 13 patients and one was indeterminate. Only 17 patients had PD-L1 positive. At least, 37 patients had one clinically actionable mutation while 24 patients had no clinically actionable mutations. Mean overall survival was 16.6 months, but no statistically significant difference was found by high PD-L1 (3 vs 3.7 months, p=0.3) expression. Conclusions: Our data suggests the TMB in HB tumors is low in general irrespective of their underlying risk factors. We also noted more than half had microsatellite stable tumors and PD-L1 expression. Future larger studies are needed to evaluate TMB, MSI and PD-L1 as a potential biomarker in hepatobiliary tumors to help select patients that will benefit from immune therapy.