Salvage therapy for hepatocellular carcinoma with thalidomide

AIM:To evaluate the clinical benefit of thalidomide in patients with advanced hepatocellular carcinoma (hepatoma).METHODS:From March 2000 to July 2002, patients who had advanced hepatocellular carcinoma and failed to or were unsuited for aggressive treatment, were enrolled and took thalidomide 150 to 300mg/d. All cases were followed till April 2003. Data collection included viral hepatitis, grade of cirrhosis, total dosage of thalidomide, side effect, stage of hepatoma by Okuda and CLIP classification, and prognosis.The subjects were divided into A and B groups, depending on 5000 mg dosage of thalidomide. Survival time of all cases and in the two subgroups was evaluated.RESULTS:Ninety-nine patients with hepatoma were enrolled,81 men and 18 females with median age 58±14.1 years.Eighty-six percent had viral hepatitis and one case was alcoholism. Hepatoma was diagnosed with histology, alpha-fetoprotein (aFP) >400ng/mL, or image examination, there were 30,33 and 36 cases respectively. At the time of thalidomide therapy, more than 81% had cirrhotic status.Twenty-two patients were in group A (<5 000 rag) with median survival time about 25 days, for 77 cases in group B(≥5000mg) the median survival time was about 109 days.Six subjects had partial response. Most adverse effects were skin rush, neuropathy, somnolence, and constipation.CONCLUSION: Several patients responded to thalidomide therapy. As a single drug therapy, thalidomide might not have good therapeutic effect for all cases, but a small ratio of patients had exciting response, the resistance or tumor escape would develop after long-term use. Up to now, no defined facts could be used to predict response. The effect of thalidomide on hepatoma might be associated with the dosage. As salvage therapy, thalidomide has its value.Combination or adjuvant therapy will be the next trial.

Does surgical resection of hepatocellular carcinoma accelerate cancer dissemination?

AIM: This study was to investigate whether surgery could increase cancer dissemination and postoperative recurrence in patients with hepatocellular carcinoma (HCC) by detection of human α-fetoprotein messenger RNA (hAFP mRNA), hAFP mRNA in the peripheral blood of patients with HCC has been considered as a surrogate marker for circulating tumor cells. METHODS: Eighty-one consecutive patients who underwent curative resection for HCC entered this prospective cohort study. We examined hAFP mRNA from the peripheral blood obtained preoperatively, perioperatively, and postoperatively to correlate the prognosis after curative resections from HCC patients and from the control subjects. Detection of hAFP mRNA by reverse transcriptase and polymerase chain reaction amplification (RT-PCR) was performed with primers specifically. The relations between the clinical variables (age,sex, associated liver cirrhosis, hepatitis B virus infection,hepatitis C virus infection, serum α-fetoprotein and ChildPugh class), the histological variables (size, capsule, vascular permeation, grade of differentiation, and daughter nodules),hAFP mRNA in peripheral blood of 3 different sessions, and postoperative course (recurrence, and recurrence related death) were analysed. RESULTS: No hAFP mRNA was detected in control group subjects. Twenty-two (27%), 24 (30%) and 19 (23%) of 81 HCC patients had hAFP mRNA positivity in the preoperative,perioperative and postoperative peripheral blood. The preoperative presence did not influence the risk of HCC recurrence (55% vs 41%, P=0.280). In contrast, patients with postoperative presence had a significantly higher recurrence (90% vs31%, P<0.001; odds ratio 19.2; 95% confidence interval: 4.0-91.7). In the multivariate analysis by COX proportional hazards model, postoperative positivity had a significant influence on recurrence (P=0.067) and recurrence related mortality (P=-0.017). Whereas, the perioperative positivity of hAFP mRNA did not increase HCC recurrence (58% vs.39% , P=0.093). The correlation between perioperative hAFP mRNA positivity and recurrence related mortality had no statistical significance (P=0.836). CONCLUSION: From our study, perioperative detection of hAFP mRNA in peripheral blood of patients has no clinical relevance and significant role in the prediction of HCC recurrence. Surgical resection itself may not accelerate cancer dissemination and does not increase postoperative recurrence significantly either.