Hepatocellular Carcinoma 2009 and Beyond: from the Surveillance to Molecular Targeted Therapy

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor which is becoming more prevalent worldwide. Patients at high risk of developing HCC, namely hepatitis B- and C-related liver cirrhosis patients, should be entered into surveillance programs, which should be performed using both ultrasonography and 3 tumor markers (AFP, PIVKA-II, AFP-L3). The surveillance interval needs to be shortened for patients at higher risk of HCC. Therefore, super-high-risk patients should be screened at 3- to 4-month intervals based on their risk of developing HCC. Sonazoid-enhanced US is extremely useful to characterize hepatic tumors when compared with multidetector-row computed tomography (MDCT). Moreover, Sonazoid-enhanced US with defect reperfusion imaging is a breakthrough approach in the treatment of HCC. This technique will markedly change the therapeutic strategy for liver cancer. Furthermore, diagnostic capability using the new imaging technique Gd-EOB-DTPA MRI is promising. A reduced uptake (low intensity) in the hepatobiliary phase of Gd-EOB-DTPA MRI strongly suggests HCC (including early-stage HCC) or a high-grade dysplastic nodule with high malignant potential. Empirically, intrahepatic arterial infusion chemotherapy using implanted reservoir port is known to be effective for advanced HCC with vascular invasion; however, no randomized study exists to prove its efficacy. Further controlled study is necessary to establish this treatment option as a standard of care in a treatment algorithm for HCC. In contrast, sorafenib was established as the first choice of treatment as a standard of care in advanced HCC patients with preserved liver function and vascular invasion/extrahepatic spread. Furthermore, global clinical trials are now ongoing using sorafenib as an adjuvant setting after resection, ablation or TACE. Efficacy of combined use of sorafenib with TACE or intra-arterial infusion chemotherapy is not clear. In order to clarify this issue a randomized clinical trial for intermediate and advanced HCC comparing sorafenib alone versus sorafenib combined with maintenance TACE/intra-arterial infusion chemotherapy and/or intra-arterial infusion chemotherapy is scheduled to be initiated in Japan in 2009. If positive results are obtained by these trials, its impact on treatment strategy for HCC will be drastically changed.

Therapeutic evaluation of sorafenib for hepatocellular carcinoma using contrast-enhanced ultrasonography: Preliminary result

“…A single focus point was set at the deep site of the lesion, and a bolus intravenous injection of 0.5 ml Sonazoid was administered via a left cubital venous line followed by flushing with 10 ml normal saline. In the post-vascular phase 10-15 min subsequent to the injection of Sonazoid, 0.5 ml Sonazoid was intravenously injected for the target lesion using the re-injection method (19) to compare the presence or absence of intratumoral necrosis 60-90 sec subsequent to the re-injection, in addition to the intratumoral vascular architecture on the MFI findings prior to and subsequent to the administration of sorafenib. (15).…”

Early changes in apparent diffusion coefficient as an indicator of response to sorafenib in hepatocellular carcinoma

“…Hepatocellular carcinoma (HCC) is becoming more prevalent not only in Southeast Asia and Africa but also in western countries (Kudo, 2008). Of all patients, 30% to 40% are diagnosed in the early stages and can be given potentially curative treatments, such as surgical resection, liver transplantation, and radiofrequency ablation; on the basis of early diagnosis and treatment, five-year survival rates of up to 60% to 70% can be achieved in early stage patients (Llovet et al, 2003).…”

Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma

“…For example, increased levels of anti-apoptotic proteins such as FLIP and survivin or decreased levels of proapoptotic proteins such as FADD have been described in HCC. 3,4 Although the multi-kinase inhibitor sorafenib has been approved for advanced HCC in 2007, 5 and molecular targeted agents such as imatinib, trastuzumab and gefitinib have been reported to be possible new treatments, 6 there is still an urgent need to develop an effective systemic therapy for patients with advanced HCC.…”