Opportunities for Chemoprevention of Hepatocellular Carcinoma
10:50 - 11:10, Room 104 (104講堂)
Opportunities for chemoprevention of hepatocellular carcinoma
Hepatocellular carcinoma (HCC) occurs far most commonly in the setting of chronic underlying liver disease, a condition that is prevalent in many Asian countries. China alone accounts for more than 50% of the world’s cases of HCC. Despite efforts to identify and screen patients at risk for HCC, this cancer is most commonly diagnosed at an advanced stage. Given the limited effectiveness of therapies for advanced HCC, prevention could have a major impact on global health. And even in cases in which HCC is diagnosed early and effectively treated, subsequent development of metachronous HCC in the diseased liver is common. This provides and additional strong rationale for development of an effective agent for HCC prevention.
Epidermal growth factor (EGF) is an important mitogen for hepatocytes and overexpression leads to development of HCC in animal models. A single nucleotide polymorphism (SNP) in the 5’ untranslated region of the EGF gene allows for a guanine (G) or adenine (A) in this position of the gene. This SNP is functional, as the G-containing allele yields EGF RNA transcripts with a longer half-life than transcripts from the A-containing allele. The G allele correlates with higher EGF in the liver and increased signaling as assessed by liver phospho-EGFR measurements. And the G allele and higher EGF levels are associated with an increased risk for HCC. Models for HCC risk that incorporate the EGF SNP status better stratify risk for HCC. In preclinical models, reduction of EGFR signaling by use of small molecule EGFR inhibitors (e.g. erlotinib) results in improvement of liver function and reduction of risk for HCC. These encouraging results are being explored in a clinical trial of erlotinib in patients with liver fibrosis or cirrhosis.
Resecting Unresectable Colorectal Carcinoma Liver Metastases
15:40 - 16:05, Room 104 (104講堂)
Resecting unresectable colorectal carcinoma liver metastases
The gold standard therapy for management of patients with colorectal carcinoma liver metastases remains surgical resection. Long term survival is achieved for a subset of patients with colorectal carcinoma liver metastases even after resection of an extensive number of metastases. The data supporting use of alternative therapies -- which thermal ablation, stereotactic body radiotherapy (SBRT), and internal radiotherapy -- are not as strong as the data supporting resection. But patients are commonly deemed “unresectable” such that some or all of their liver metastases are managed by one of these alternative therapies. Common reasons for inappropriately labeling liver metastases as unresectable include tumor involvement of hepatic veins or IVC, bilateral distribution, or inadequate future liver remnant. Several important surgical techniques have been developed to enable resection of liver tumors in these circumstances. These include creation of a future liver remnant from a single Couinaud liver segment, IVC reconstruction during liver resection, hepatic vein reconstruction during liver resection, and methods to cryopreserve the future liver remnant in situ to allow the time necessary for vascular reconstructions.