Fumie Kurokawa

Percutaneous Radiofrequency Ablation Therapy for Patients with Hepatocellular Carcinoma during Occlusion of Hepatic Blood Flow Comparison with Standard Percutaneous Radiofrequency Ablation Therapy

The therapeutic efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is limited by the small volume of coagulation necrosis obtained at each activation of the RF system and the sometimes irregular burn shape due to the proximity of large vessels that have a cooling effect. To improve the efficacy of RFA, the authors designed RFA with balloon occlusion of the hepatic artery (balloon‐occluded RFA). In this study, we investigated the efficacy of balloon‐occluded RFA and compared the coagulation diameters obtained with balloon‐occluded RFA and standard RFA.

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

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.

Multislice dynamic MRI of hepatic tumors.

Breath-hold multislice dynamic MRI was used to diagnose 115 hepatic tumors in 55 patients. With this technique 10 slice-section images were made during a single breath-hold, achieving nearly complete liver coverage. Early enhancement images were obtained 20 s after intravenous bolus injection of gadopentetate dimeglumine. The detection rate of untreated hepatocellular carcinomas was greater with breath-hold multislice dynamic imaging (91%) than with conventional spin echo techniques (73%), because the 10 early enhancement images obtained during a single breath-hold showed the arterial dominant phase throughout the entire liver. In cases of untreated hepatocellular carcinoma 44 (86%) of the 51 lesions showed rapid enhancement on arterial dominant phase images, and 44 (86%) were demonstrated as isointensity or low intensity areas on delayed images. In cases of hepatic hemangioma, peripheral enhancement was demonstrated in 25 (89%) of the 28 lesions on arterial dominant phase images, and partial or complete hyperintense fill-in was identified in all lesions on delayed images. In patients treated with lipiodol-transcatheter arterial embolization (TAE), the breath-hold multislice dynamic imaging technique allowed evaluation of therapeutic effectiveness by revealing the hemodynamics of each nodule without the influence of lipiodol. We conclude that breath-hold multislice dynamic MRI should be used on patients with suspected hepatic tumors and in follow-up studies after lipiodol-TAE.

Hepatocellular carcinoma with nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) was originally believed to be a benign disease. However, it has been recently revealed that NASH could lead to irreversible liver disease in some patients. We report an unusual case of hepatocellular carcinoma (HCC) in a 76-year-old man with NASH. He had no history of alcohol consumption, drug use, or blood transfusion. He was negative for all serological viral markers and autoantibodies. In addition, he was obese (body mass index [BMI], 30.75 kg/m2) and had type 2 diabetes mellitus. A liver biopsy specimen showed moderate steatosis with necroinflammatory changes, ballooning degeneration, Mallory bodies, pericellular fibrosis, and evidence of nodular regeneration. He was diagnosed with NASH with cirrhosis. Simultaneously, a liver tumor, measuring 19 mm in diameter, was detected in segment 6. A tumor biopsy specimen revealed well-differentiated HCC, and imaging modalities confirmed the characteristics of HCC. To our knowledge, ten patients who had HCC with NASH were reported. In all patients with NASH and HCC, cirrhosis was present. Patients with NASH and cirrhosis may progress to HCC, and regular screening, based on tumor markers and imaging modalities, is needed to detect HCC in patients with NASH and cirrhosis.

Prognostic factors in patients with advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy

BackgroundThe prognosis of patients with advanced hepatocellular carcinoma (HCC) is poor. We aimed to clarify the prognostic factors in patients with advanced HCC receiving hepatic arterial infusion chemotherapy (HAIC).MethodsForty-four HCC patients were treated with HAIC, using low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) with/without leucovorin (or isovorin). Of these 44 patients, 15 received low-dose CDDP and 5-FU, and 29 received low-dose CDDP, 5-FU, and leucovorin or isovorin. Prognostic factors were evaluated by univariate and multivariate analyses of patient and disease characteristics.ResultsOf all patients, 5 and 12 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, 38%). The response rate (48.3%) in the low-dose CDDP and 5-FU with leucovorin/isovorin group was significantly better than that (20%) in the low-dose CDDP and 5-FU group (P = 0.002). The 1-, 2-, 3-, and 5-year cumulative survival rates of the 44 patients were 39%, 18%, 12%, and 9%, respectively. The regimen using low-dose CDDP and 5-FU with leucovorin/isovorin tended to improve survival rates (P = 0.097). Univariate and multivariate analyses showed the same variables—the Child-Pugh score (P = 0.013, P = 0.018), α-fetoprotein (AFP) level (P = 0.010, P = 0.009), and therapeutic effect after HAIC (P = 0.003, P = 0.01), respectively, to be significant prognostic factors.ConclusionsPatients who had advanced HCC with favorable hepatic reserve capacity and a lower AFP level were suitable candidates for HAIC. Moreover, the regimen using low-dose CDDP and 5-FU with leucovorin/isovorin may be suitable for advanced HCC patients, because of the improvement in the response rate and survival compared with the low-dose CDDP and 5-FU regimen without leucovorin/isovorin.

Novel arterial infusion chemotherapy using cisplatin, 5-fluorouracil, and leucovorin for patients with advanced hepatocellular carcinoma

Advanced hepatocelluar carcinoma (HCC) has a poor prognosis. In this study, the authors evaluated the efficacy of chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU), and leucovorin (LV), comparing our regimen with chemotherapy using CDDP and 5-FU. Nineteen patients with advanced HCC were treated by arterial infusion of a chemotherapeutic agent via a subcutaneously implanted injection port. In Group A (n=9), one course of chemotherapy consisted of the daily administration of CDDP (10 mg/1 h, on 5 days) and LV (12 mg/10 min, on 5 days) followed by 5-FU (250 mg/5 h, on 5 days). In Group B (n=10), except for the administration of LV, the same regimen was employed. This course was repeated each week for 4 weeks. In Group A, two patients showed a complete response (CR), and the other three showed a partial response (PR). In Group B, two patients showed PR. The response rate (CR+PR/all cases) in Group A was significantly higher than that in Group B (56 vs. 20%; P=0.022). The 1- and 2-year survival rates of Group A (66.7, 44.4%) were significantly higher than those of Group B (10, 0%) (P=0.033). These results suggest that our regimen may be useful in treating patients with advanced HCC.

Percutaneous radiofrequency ablation with cooled electrodes combined with hepatic arterial balloon occlusion in hepatocellular carcinoma

BackgroundWe have reported that percutaneous radiofrequency ablation (RFA) with balloon occlusion of the hepatic artery (balloon-occluded RFA), using an expandable electrode, increases the coagulation area. In this study, we investigated the efficacy of balloon-occluded RFA and balloon-microcatheter-occluded RFA, using a cool RF single electrode.MethodsWe studies 41 patients with 47 hepatocellular carcinoma (HCC) lesions. We treated 28 patients (32 nodules) with balloon-occluded RFA, 5 patients (6 nodules) with balloon-microcatheter-occluded RFA, and 8 patients (9 nodules) with standard RFA. Initial therapeutic efficacy was evaluated with dynamic computed tomography performed 1 week after one session of treatment.ResultsOne session of treatment was done for 20 nodules (62.5%) in the balloon-occluded RFA group and for 4 nodules (66.7%) in the balloon-microcatheter-occluded RFA group. We compared the coagulation diameter for balloon-occluded RFA (7 nodules), balloon-microcatheter-occluded RFA (6 nodules), and standard RFA (9 nodules) after one application cycle (12 min). The greatest dimension of the area coagulated by balloon-occluded RFA was significantly larger (greatest long-axis dimension, 47.6 ± 7.8 mm; greatest short-axis dimension, 33.4 ± 7.5 mm) than that coagulated by standard RFA (greatest long-axis dimension, 35.3 ± 4.7 mm; greatest short-axis dimension, 25.9 ± 3.7 mm; P = 0.002 for greatest long-axis dimension; P = 0.041 for greatest short-axis dimension). However, there was significant difference only in the greatest short-axis dimension of the area coagulated comparing balloon-microcatheter-occluded RFA and standard RFA.ConclusionsWe consider balloon-occluded RFA using a cool RF electrode to be superior to standard RFA for the treatment of HCC, especially when larger coagulation volumes are required.

Numerical Aberrations of Chromosomes 16, 17, and 18 in Hepatocellular Carcinoma (A FISH and FCM Analysis of 20 Cases)

Conventional cytogenetic studies havedemonstrated frequent abnormalities of specificchromosomes in hepatocellular carcinoma, although thereare few reports examining the relationship betweenchromosomal aberrations and clinicopathologic features. Inthis study, numerical aberrations of chromosomes 16, 17,and 18 were examined by fluorescence in situhybridization using pericentromeric DNA probes in 20 cases of surgically removed hepatocellularcarcinoma. DNA ploidy analysis was also performed byflow cytometry. Numerical abnormalities of chromosomes16, 17, and 18 were found in 7 of 19 cases, 15 of 20 cases, and 12 of 20 cases, respectively. Gainand/or loss of more than one chromosome was detected in16 of 19 cases. However, aneuploidy was seen in only 9of 20 tumors by flow cytometry. The incidence of aneusomy 17 and 18 increased with tumor sizeand stage progression. Fluorescence in situhybridization analysis demonstrated that numericalchromosomal aberrations accumulated with tumorprogression in hepatocellular carcinoma.

Arterial infusion chemotherapy using cisplatin, 5-fluorouracil, and isovorin for patients with advanced hepatocellular carcinoma, pilot study: Is a high dose of the biochemical modulator effective?

The authors report the efficacy of arterial infusion chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU), and leucovorin (LV) for patients with advanced hepatocellular carcinoma (HCC). In this study, we evaluated the efficacy of our regimen with high-dose LV, using isovorin (IV) (high dose group), comparing the previous regimen (low-dose LV; low dose group). This is a retrospective, historical, and non-controlled trial. In the high dose group (n=15), one course of chemotherapy consisted of the daily administration of CDDP (10 mg/1 h, for 5 days) and IV (12.5 mg/10 min, for 5 days) followed by 5-FU (250 mg/5 h, for 5 days). In the low dose group (n=9), changing to the administration of LV (12 mg/day), the same regimen was employed. In principle, we did this 20 times. In the high dose group, complete response (CR) was found in two patients, and partial response (PR) in six patients. Thus, the response rate was 53%. In the low dose group, CR was found in two patients, and PR in three patients. Thus, the response rate was 56%. There were no significant differences in the response rate (P=0.71), the survival rate (P=0.29) and the toxicity between the two groups. We considered the recommended dose of LV to be 12 mg/day in our regimen, although this is a preliminary study.

An antigen specific to hyperplastic liver nodules defined with monoclonal antibody: a new marker for preneoplastic cells in rat chemical hepatocarcinogenesis.

Two monoclonal antibodies (MoAbs) were prepared against the hepatocytes of hyperplastic liver nodules from rats killed in the 13th week during hepatocarcinogenesis with 2-acetylaminofluorene. The specificity of these MoAbs was confirmed by cellular radioimmunoassay. By means of immunoperoxidase staining with 2 MoAbs (HAM 6 and HAM 7), HAM 6-defined antigen was detected on the plasma membrane and/or cytoplasm of the hepatocytes in hyperplastic nodules, while HAM 7 reacted to the hepatocytes surrounding hyperplastic nodules. Therefore, HAM 6 seemed to be specific to hyperplastic nodules, but HAM 7 to be a MoAb developed accidentally to the surrounding hepatocytes by contamination of the cell suspension of hyperplastic nodules.