Among a cohort of HCC patients with surgery and radiofrequency ablation, 89 patients were chosen adjusting age, gender, and Barcelona Clinic LiverCancer (BCLC) staging with 89 patients with initial HCC therapy AbstractText: HCC recurrence rates at the end of first and second year were 18.1 and 22.1% in patients ...
Infectious Diseases (1), Oncology (1), Immune System Diseases (1) Hepatocellular Carcinoma (3), Neoplasms (2), Liver Neoplasms (1), more mentions
BACKGROUND AND AIMS: According to the clonal model of tumor evolution, trunk alterations arise at early stages and are ubiquitous. Through the characterization of early stages of hepatocarcinogenesis, we aimed to identify trunk alterations in HCC and study their intra- and inter-tumor distribution in advanced lesions.
METHODS: 151 samples representing the multi-step process of hepatocarcinogenesis were analyzed by targeted-sequencing and SNP array. Genes altered in early lesions [31 dysplastic nodules (DNs) and 38 small HCCs (sHCC)] were defined as trunk. Their distribution was explored in: a) different regions of large tumors (43 regions, 21 tumors), and b) different nodules of the same patient [39 tumors, 17 patients]. Multinodular lesions were classified as intrahepatic metastases (IMs) or synchronous tumors based on chromosomal aberrations.
RESULTS: TERT promoter mutations (10.5%) and broad copy-number aberrations in chromosomes 1 and 8 (3-7%) were identified as trunk gatekeepers in DNs and were maintained in sHCCs. Trunk drivers identified in sHCCs included TP53 (23%) and CTNNB1 (11%) mutations, and focal amplifications or deletions in known drivers (6%). Overall, TERT, TP53 and CTNNB1 mutations were the most frequent trunk event and at least one was present in 51% of sHCCs. Around 90% of mutations in these genes were ubiquitous among different regions of large tumors. In multinodular HCCs, 35% of patients harbored IMs; 85% of mutations in TERT, TP53 and/or CTNNB1 were retained in primary and metastatic tumors.
CONCLUSIONS: Trunk events in early stages (TERT, TP53, CTNNB1 mutations) were ubiquitous across different regions of the same tumor and between primary and metastatic nodules in >85% of cases. This concept supports the knowledge that single biopsies would suffice to capture trunk mutations in HCC.
LAY SUMMARY: Trunk alterations arise at early stages of cancer and are shared among all malignant cells of the tumor. In order toidentify trunk alterations in HCC, we characterized early stages of hepatocarcinogenesis represented by dysplastic nodules and small lesions. Mutations inTERT,TP53andCTNNB1genes were the only ones found at this early stage. Analyses in more advanced lesions showed that mutations in these same genes were shared between different regions of the same tumor and between primary and metastatic tumors, suggesting their trunk role in this disease.
BACKGROUND & AIMS: Development of hepatocellular carcinoma (HCC) is associated with alterations in the transforming growth factor beta (TGFβ) signaling pathway, which regulates liver inflammation and can have tumor suppressor or promoter activities. Little is known about the roles of specific members of this pathway at specific of HCC development. We took an integrated approach to identify and validate the effects of changes in this pathway in HCC and identify therapeutic targets.
METHODS: We performed transcriptome analyses for a total of 488 HCCs that include data from The Cancer Genome Atlas. We also screened 301 HCCs reported in the Catalogue of Somatic Mutations in Cancer and 202 from Cancer Genome Atlas for mutations in genome sequences. We expressed mutant forms of spectrin beta, non-erythrocytic 1 (SPTBN1) in HepG2, SNU398, and SNU475 cells and measured phosphorylation, nuclear translocation, and transcriptional activity of SMAD family member 3 (SMAD3).
RESULTS: We found somatic mutations in at least 1 gene whose product is a member of TGFβ signaling pathway in 38% of HCC samples. SPTBN1 was mutated in the largest proportion of samples (12/202, 6%). Unsupervised clustering of transcriptome data identified a group of HCCs with activation of the TGFβ signaling pathway (increased transcription of genes in the pathway) and a group of HCCs with inactivation of TGFβ signaling (reduced expression of genes in this pathway). Patients with tumors with inactivation of TGFβ signaling had shorter survival times than patients with tumors with activation of TGFβ signaling (P=.0129). Patterns of TGFβ signaling correlated with activation of the DNA damage response and sirtuin signaling pathways. HepG2, SNU398, SNU475 cells that expressed the D1089Y mutant or with knockdown of SPTBN1 had increased sensitivity to DNA crosslinking agents and reduced survival compared to cells that expressed normal SPTBN1 (controls).
CONCLUSIONS: In genome and transcriptome analyses of HCC samples, we found mutations in genes in the TGFβ signaling pathway in almost 40% of samples. These correlated with changes in expression of genes in the pathways; upregulation of genes in this pathway would contribute to inflammation and fibrosis whereas downregulation would indicate loss of TGFβ tumor suppressor activity. Our findings indicate that therapeutic agents for HCCs can be effective, based on genetic features of the TGFβ pathway; agents that block TGFβ should be used only in patients with specific types of HCCs.
... therapeutic target to promote liver regeneration AbstractText: 96 patients undergoing liver resection for malignant livertumors were prospectively included... HT levels seem to substantially affect the outcome of patients after liver resection for livertumors... overall survival is negatively affected by both postoperative early disease recurrence and morbidity Keyword: Livercancer.
... veterans with chronic HBV infection, risk of HCC is highest among APIs, followed by whites and AAs. Cirrhosis increased HCC risk. Among patients without cirrhosis, male patients who are older than 40 years and have increased levels of alanine aminotransferase might benefit from HCC surveillance, regardless of race Keyword: ALT. Keyword: Livercancer. Keyword: hepatoma. Keyword: surveillance. Keyword: viral hepatitis.
Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, livercancer, and death. Direct-acting antivirals (DAAs), e.g. sofosbuvir, are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate hepatitis C virus (HCV) from the blood (sustained virological response.
Infectious Diseases (9), Oncology (1) Hepatitis C (7), Hepatocellular Carcinoma (2), Ascites (2), more mentions
This prospective intention-to-treat validation study evaluated the liver tunnel (LT) technique for patients having ≥1 deep centrally located livertumor, with or without middle hepatic vein (MHV) invasion.Conservative surgery has been proposed for patients with deep livertumors having complex relationships. LT is one such novel technique.Eligible patients were prospectively enrolled for LT.
Neoplasms (3), Hepatocellular Carcinoma (2), Cholangiocarcinoma (2), more mentions
AbstractText: Ischemia-reperfusion injury during hepatic resection has been shown to accelerate progression of livercancer. However, the prognostic relevance of remnant liver ischemia (RLI) after resection of colorectal liver metastases (CLMs) is unknown to date AbstractText: To assess the prognostic influence of RLI after resection of CLMs and to identify correlates of greater extent of RLI AbstractText: This study ...
... to receipt of an interferon-only regimen AbstractText: DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared to treatment with interferon AbstractText: Eradication of hepatitis C infection with direct-acting antiviral agents reduces the risk of livercancer dramatically Keyword: Livercancer. Keyword: hepatitis C treatment.
Immune System Diseases (7), Infectious Diseases (3), Oncology (2) Cirrhosis (4), Hepatitis C (3), Hepatocellular Carcinoma (2), more mentions
... overall survival (OS).The median age at NET diagnosis was 56 years, 50% of the patients were male, 46% of NET primaries were located in the pancreas, 71% of tumors were nonfunctional, 25% were World Health Organization (WHO) grade III, and 20% had at least a 25% hepatictumor burden.
Blood Disorders and Hematology (1) Neoplasms (3), Neuroendocrine Tumors (2), Leukopenia (1), more mentions
AbstractText: Primary livercancer (PLC) is the sixth most common cancer worldwide and the second most common cause of cancer death. Future predictions can inform health planners and raise awareness of the need for cancer control action. We predicted the future burden of PLC in 30 countries around 2030. Incident cases of PLC (ICD-10 C22) were obtained from 30 ...
Oncology (6), Anti-Obesity and Weight Loss (1) Neoplasms (4), Liver Neoplasms (2), Obesity (1), more mentions
Drug development in HCC has been characterized in the past by many failures. Despite good rationales and promising phase II data, many phase III trials failed. Immunotherapy represents an alternate treatment approach and has been successful in many different types of cancer. Being an inflammation induced cancer HCC represents a very interesting target for immune based approaches and indeed early results from clinical trials testing immune checkpoint inhibitors are not only promising but have already led to evaluation of such in a phase III setting. Here we summarize our current knowledge on the rationale, mechanism of action and clinical data for immune checkpoint blockade in HCC. In addition, we provide an overview about other novel immune based approaches currently under development for the treatment of HCC such as adoptive cell based and antibody-based approaches.
AbstractText: Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) and conventional staged hepatectomy (CSH) are options for patients with unresectable livertumors due to insufficient future liver remnant (FLR) AbstractText: A retrospective comparison of clinical data, liver volumetry and surgical outcomes between 10 ALPPS and 29 CSH ...
AbstractText: Hepatocellular adenoma (HCA) is a benign livertumour that may be complicated by bleeding or malignant transformation. Present guidelines advise cessation of oral contraceptives and surgical resection if the lesion is still larger than 5 cm at 6 months after diagnosis. The aim of this study was to evaluate whether this 6-month interval is sufficient to expect regression ...