Validating a Markov model of treatment for hepatitis C virus-related hepatocellular carcinoma.

OBJECTIVE: We created and validated a Markov model to simulate the prognosis with treatment for HCV-related hepatocellular carcinoma (HCC) for assessment of cost-effectiveness for alternative treatments of HCC. METHOD: Markov state incorporated into the model consisted of the treatment as a surrogate for HCC stage and underlying liver function. Retrospective data of 793 patients from three university hospitals were used to determine Kaplan-Meier survival curves for each treatment and transition probabilities were derived from them. RESULTS: There was substantial overlap in the 95% CIs of the Markov model predicted and the Kaplan-Meier survival curves for each therapy. The predicted survival curves were also similar with those from the nationwide survey data supporting the external validity of our model. CONCLUSIONS: Our Markov model estimates for prognosis with HCC have both internal and external validity and should be considered applicable for estimating cost-effectiveness related to HCC.

Percutaneous radiofrequency ablation therapy with combined angiography and computed tomography assistance for patients with hepatocellular carcinoma.

BACKGROUND: Radiofrequency ablation (RFA) for patients with hepatocellular carcinoma (HCC) has been reported previously. This technique is superior to percutaneous microwave coagulation therapy (PMCT) for the enlargement of the necrotic area. Therefore, a few treatment sessions of RFA for patients with small HCC lesions measuring < 3 cm in greatest dimension can achieve complete necrosis. To achieve this with a one-treatment RFA session, the authors designed the technique of RFA with angiography combined with computed tomography (angio-CT) assistance. The advantages of this technique are that it is possible to detect small satellite nodules and to evaluate the real-time therapeutic effect immediately after RFA. METHODS: Ten patients with 12 HCC lesions measuring < 4 cm in greatest dimension underwent RFA with angio-CT assistance. The authors performed standard RFA for six patients (seven tumors) and RFA with balloon occlusion of the hepatic artery (balloon-occluded RFA [BoRFA]) for four patients (five tumors). Final therapeutic efficacy was evaluated with dynamic CT scans performed 2 weeks after treatment. RESULTS: On CT arteriography (CTA) obtained immediately after treatment, a hyperattenuating ring around the nonenhanced region was apparent in all patients. On CT scans obtained 2 weeks after treatment, this ring disappeared, and the greatest dimension of the nonenhanced region was slightly larger than that on the CTA obtained immediately after treatment. The authors achieved complete eradication with one treatment session of RFA in 8 of 10 patients (80%). Local recurrence occurred in one patient 10 months after treatment. The greatest dimension of the area coagulated by BoRFA was significantly larger (greatest long-axis dimension, 38.2 +/- 2.8 mm; greatest short-axis dimension, 35.0 +/- 1.7 mm; n = 5 lesions) than without it (greatest long-axis dimension, 30.0 +/- 4.1 mm; greatest short-axis dimension, 27.0 +/- 4.3 mm; n = 4 lesions; greatest long-axis dimension, P = 0.009; greatest short-axis dimension, P = 0.006). No major complications occurred in any patient. CONCLUSIONS: The authors were able to achieve success with a single treatment session in patients with small HCC using RFA with angio-CT assistance. They consider that RFA with angio-CT assistance is a safe and effective technique for the treatment of patients with small HCC.

Numerical aberrations of chromosomes 16, 17, and 18 in hepatocellular carcinoma: a FISH and FCM analysis of 20 cases.

Conventional cytogenetic studies have demonstrated frequent abnormalities of specific chromosomes in hepatocellular carcinoma, although there are few reports examining the relationship between chromosomal aberrations and clinicopathologic features. In this study, numerical aberrations of chromosomes 16, 17, and 18 were examined by fluorescence in situ hybridization using pericentromeric DNA probes in 20 cases of surgically removed hepatocellular carcinoma. DNA ploidy analysis was also performed by flow cytometry. Numerical abnormalities of chromosomes 16, 17, and 18 were found in 7 of 19 cases, 15 of 20 cases, and 12 of 20 cases, respectively. Gain and/or loss of more than one chromosome was detected in 16 of 19 cases. However, aneuploidy was seen in only 9 of 20 tumors by flow cytometry. The incidence of aneusomy 17 and 18 increased with tumor size and stage progression. Fluorescence in situ hybridization analysis demonstrated that numerical chromosomal aberrations accumulated with tumor progression in hepatocellular carcinoma.

Wild-type p53 gene-induced morphological changes and growth suppression in hepatoma cells.

The human hepatocellular carcinoma (HCC) cell line, HLF, expresses only mutant-type p53 (mt-p53), which has an amino acid substitution at the 244th residue from glycine to alanine. HLF cells were transfected with wild-type p53 (wt-p53) cDNA construct pC53-SN3, mt-p53 cDNA construct pC53-SCX [which differs by a single nucleotide, resulting in alanine instead of valine at the 143rd residue in p53 (p53-143)], or pCMV-Neo-Bam, as a control, by a liposome method. After G418 selection, three wt-p53 stable transformants (WT), four mt-p53 transformants (MT), and three control vector transformants (VT) were obtained. We analyzed the cell growth and morphological changes of these transformants under different culture conditions [fetal calf serum (FCS), 10%, 1%, and 0%]. Whereas no difference from control in the growth rate and morphology was observed under the 10% FCS conditions, serum starvation induced remarkable phenotypical changes in all three WTs, but not in the other transformant. Corresponding to these phenotypical changes, the transcriptional activity of wt-p53 was increased more than nine fold. These results indicated that serum starvation would induce wt-p53 biological function, which is tightly linked to morphological changes and growth suppression. To induce these changes, the introduction of the wt-p53 gene itself was not sufficient, and additional triggering, i.e., serum starvation, was indispensable.

Clinicopathologic features of early hepatocellular carcinoma.

BACKGROUND/AIMS: This study attempts to clarify the clinicopathologic definition of early hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: We evaluated 57 patients, with HCCs less than 3 cm in diameter, in terms of prognosis, incidence of extrahepatic metastasis, and tumor recurrence rate following treatment. RESULTS: Survival was related to both tumor number and histologic differentiation, but was not related to tumor size. Furthermore, prognosis appeared to depend on the functional reserve of the liver. The incidence of extrahepatic metastasis was related to histologic differentiation. There was no significant difference in the recurrence rates of patients with uninodular tumors in terms of tumor size. CONCLUSIONS: Our findings indicate that early HCCs measure 15 mm or less in diameter, are uninodular, and are histologically well-differentiated. Finally, the functional reserve of the liver will likely be an additional parameter that will further characterize early HCCs.

[A case of multiple liver metastasis from ileac carcinoid effectively treated with continuous intraarterial infusion of somatostatin analog].

We report a case of multiple liver metastasis from ileac carcinoid treated with continuous intraarterial infusion of somatostatin analog. A 65-year-old man who complained of chest pain was admitted to Yamaguchi University Hospital School of Medicine for further examination of cardiac angina. Liver tumors, which were detected during ECHO cardiogram examination, were diagnosed as metastasis from carcinoid by percutaneous transhepatic liver biopsy. Primary tumor was found at the ileum by colonofiberscopy. We performed ileo-cecal resection and catheterization from the gastroduodenal artery for intraarterial chemotherapy under laparotomy. After the operation, the patient was treated with continuous intraarterial infusion of somatostatin analog (100 micrograms/day, 5 days/week for 16 weeks). The tumor in segment 6 (S6) disappeared, but the tumor in S2 enlarged after the therapy. Hepatic angiography confirming the drug distribution demonstrated the occlusion of the left hepatic artery. This drug was thus distributed to the tumor in S6 but not in S2. These results suggest that somatostatin analog may have a direct anti-tumor effect. Furthermore, no side effect was observed. Thus, intraarterial infusion of somatostatin analog may be a useful therapy for liver metastasis from carcinoid.

Immunohistochemical characterization of a monoclonal antibody to hyperplastic nodules induced in rat liver by chemical carcinogens.

To investigate the specific phenotype of hyperplastic nodules (HPN) in rat liver, we produced a monoclonal antibody (HAM-6). HAM-6 was a member of the mouse IgG1 class and was specific for hyperplastic nodules, as shown by cellular radioimmunoassay and immunohistochemical studies. The antigen recognized by HAM-6 was located in the rat HPN cell membrane. HAM-6 was also slightly reactive to rat hepatocellular carcinoma, but not to normal or fetal rat liver, other normal rat organs, human hepatocellular carcinoma, or human liver cirrhosis. That is, the antigen recognized by HAM-6 appeared to be differentiated and to occur during chemical carcinogenesis. HAM-6 may be a useful marker for the investigation of premalignant states in chemical carcinogenesis.