The 8th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2017). The Art & Science of Conquering Liver Cancer. Singapore, July 14-16, 2017: Abstracts

2017 Liver Cancer  
Primary Liver Cancer (PLC) is a most common malignancy and the second cause of cancer deaths in China. Hepatocellular carcinoma (HCC) accounts for about 90% of PLC, and high-risk population for HCC include HBV/HCV infection, alcohol abuse, non-alcoholic steatohepatitis (NASH), aflatoxin contamination, cirrhosis from any cause and HCC family history, especially in male patients over the age of 40 years. Routine immunization with HBV vaccination is an approach to decrease the prevalence of HCC.
more » ... eatment of hepatitis B and cirrhosis is closely associated to the outcome of HCC. Surveillance by screening with AFP serosurvey and ultrasound in high-risk population at a regular interval of 6 months is a main procedure for early detection of HCC. The critical challenges for management of HCC in Chinese patients include decompensated cirrhosis, vascular invasion, distant metastasis, low resectability and high recurrence rate. The clinical guideline for management of HCC in China focuses on early diagnosis, multiple modalities of treatment, and prevention of recurrence and metastasis for HCC. A new guideline for pathological diagnosis of liver cancer has recently been published. The clinical diagnosis of HCC is mainly based on imaging assessment. Primovist-enhanced MRI may provide a more valuable diagnosis of focal liver lesions. New biomarkers for clinical diagnosis and outcome prediction are being investigated. Surgery is widely utilized to treat HCC in early and intermediate stages. Recent data indicated that palliative resection for BCLC-B HCC might be more effective to improve prognosis compared to TACE. Novel interventional approaches to treating HCC have been developed in recent years. The local ablation is safe and effective in small HCC ≤3 cm in diameter. Randomized clinical trials indicated similar survival and recurrence rates between surgery and RFA. TACE is suitable for both BCLC-B and C HCC patients. Molecular targeted therapy of sorafenib revealed an encouraging outcome in inoperable and metastatic HCC patients. Intensive studies are investigated to further improve the efficacy of sorafenib combined with other treatment modalities, including surgical resection, ablation, TACE and chemotherapy. Clinical trials with new molecular targeted therapy and chemotherapy in HCC patients are also conducted in China. Portal vein tumor thrombosis (PVTT) is one of the key problems of treatment efficacy and prognosis for HCC patients. Various procedures including surgery, TACE, radiotherapy, molecular targeted therapy and combination therapy are investigated to deal with PVTT in HCC patients. The replication and activation of Hepatitis B/C viruses (HBV/HCV) are closely associated to the recurrence and progression of HCC. An expert consensus has been paid more attention to the indication and application of antiviral therapy on HBV/HCV-related HCC. In summary, multidisciplinary team (MDT) is an optimal approach to personalized treatment with combination therapy of HCC. Introduction: Beginning in 1967, the Liver Cancer Study Group of Japan (LCSGJ) started a nationwide prospective registry of patients with HCC. Patients were followed-up after diagnosis with surveys published every two years. In the 18th and most recent follow-up survey for the period 2004-2005, 20,153 patients were newly diagnosed with HCC and 30,677 previously diagnosed patients were being followed-up at 544 institutions, respectively. This follow-up survey showed that, of 17,804 measurable tumors in patients initially diagnosed in the period 2004-2005, 855 (4.80%) were ≤1 cm, 5,106 (28.68%) were 1-2 cm, 4,272 (23.99%) were 2-3 cm, 3,833 (21.53%) were 3-5 cm, and 3,738 (21.00%) were 5-10 cm in diameter, respectively. Background: To determine the effectiveness of surveillance and treatment methods longitudinally, we analyzed improvements over time in overall survival (OS) of 173,378 patients with HCC prospectively entered into the LCSGJ registry between 1978 and 2005. Methods: All patients from more than 700 institutions throughout Japan with HCC were entered into the LCSGJ registry. Patients were grouped by years of diagnosis, with OS and 5-year OS rates being calculated. We also assessed OS and 5-year OS rates in patients who underwent resection, local ablation, transarterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy (HAIC) and in those with baseline serum alpha-fetoprotein (AFP) levels ≥400 ng/ml. Results: The 5-and 10-year OS rates in the cohort of 173,378 patients were 37.9% and 16.5%, respectively. However, over time, the mean maximum tumor size decreased significantly, whereas 5-year OS rates and median survival time increased significantly. Similar findings were observed separately in patients who underwent resection, local ablation, TACE, and HAIC, as well as in patients with AFP levels ≥400 ng/ml. Conclusion: The establishment of a nationwide HCC surveillance program in Japan has contributed to longer median OS and increased OS rates in patients diagnosed with this disease. These findings suggest that the establishment of a surveillance program in other countries with patients at risk for HCC may provide significant survival benefits. Chronic infection with hepatitis B or C virus is the principal cause of hepatocellular carcinoma (HCC) (≥75% of all cases). Of the many non-viral factors relevant to HCC development, obesity and diabetes, and the subsequent development of nonalcoholic steatohepatitis (NASH), are particularly significant risk factors. The most recent report from the USA has shown convincingly that the number of NASH-associated HCC cases is increasing around 9% per annum. Other non-viral causes of HCC include iron overload syndromes, alcohol use, tobacco use, the use of oral contraceptives, and aflatoxin ingestion. Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifesta tion of metabolic syndrome and is becoming more prevalent worldwide. Patients with active inflammatory NAFLD, termed NASH, are at particular risk of HCC development, even if their livers are not cirrhotic. Although the debate on the relative contributions made by obesity and diabetes to HCC development in the presence and absence of NAFLD continues, several recent publications have addressed HCC developing in NAFLD patients. NASH-associated HCC may be of multi-centric origin, similar to HCC caused by viral hepatitis; both tumor recurrence and de novo HCC should be considered. Also, HCC is difficult to evaluate in NASH patients because histological data are required for NASH diagnosis, which can trigger selection bias. Furthermore, the characteristic features of NASH disappear in the end-stage of disease (the so-called "burned-out" NASH), rendering diagnosis impossible. The precise mechanisms triggering the development of NASH-associated HCC remain unclear. Genetic susceptibility is likely to be key in determining individual risk, and DNA studies may soon identify biomarkers detecting those at higher risk. Apart from older age and advanced fibrosis, pathophysiological factors associated with the development of NAFLD per se, including insulinresistance, oxidative stress, and inflammatory cytokine production, are likely to contribute to hepatocarcinogenesis. External factors such as hyper-nutrition and a sedentary lifestyle undoubtedly trigger pathological changes in adipose and liver tissue, but the responses vary greatly from one individual to another; it remains unclear why a minority develops progressive liver disease and HCC. Recently, sarcopenia was reported to be an independent risk factor associated with the development of NAFLD/NASH and (possibly) advanced fibrosis. A role for vitamin D in the development of NAFLD is also emerging. A multilevel preventative approach will hopefully reduce the incidence of non-viral HCC. There is an urgent need to elucidate the pathogenesis and clinical features of HCC in NASH patients. Further studies are also required to identify patients at high risk of NAFLD/NASH who require more stringent surveillance to prevent HCC, and to establish effective treatments. Introduction: Despite recent success in cancer immunotherapies, the dynamics between tumor-microenvironment and the systemic immune system remain elusive. Our immunological analysis aims to identify and characterise important immunological components in hepatocellular carcinoma (HCC) for their potential clinical implications. Methods: Our approach consisted of seamless integration of high dimensional mass cytometry by time-of-flight (CyTOF) to identify multiple immune subsets residing in the tumor, its adjacent non-tumor liver tissues and peripheral blood in patients with hepatocellular carcinoma (HCC); next-generation sequencing for deep characterization of these distinct tumor-infiltrating leukocytes and RNA expression analysis of a total of 800 cancer-immune genes in tumor versus its adjacent non-tumor microenvironment. Results: We described an immune gradient of progressively more suppressive immune subsets, which includes exhausted T cells, regulatory-T cells, and tumor-associated macrophages, from the periphery, the adjacent nontumor tissues to tumor. The higher expression of multiple exhaustion markers including PD-1, CTLA-4, Lag-3 and Tim-3 on tumour-infiltrating CD8+CD45RO+ memory T cells demonstrated the preferentially enrichment of these exhausted T cells in the tumor microenvironment. This phenomenon could also served as a immunotherapeutic target using check-point inhibitors immunotherapy in HCC. Further functional characteristics of these cells using RNA sequencing and NanoString showed that their phenotypes are profoundly related to the microenvironment where they reside. Conclusion: The current approach provides a holistic analysis of tumor immune microenvironment which mapped the immune landscape of tumor in unprecedented detail. It serves as a platform for the design of immunomonitoring and immunotherapy for cancers.
doi:10.1159/000478029 fatcat:mq43zbb47jglhhsejx5iudbrwu