Ryuichi Kita

Comparison of percutaneous radiofrequency thermal ablation and surgical resection for small hepatocellular carcinoma

BackgroundThe purpose of this investigation was to compare the outcome of percutaneous radiofrequency thermal ablation therapy (PRFA) with surgical resection (SR) in the treatment of single and small hepatocellular carcinoma (HCC).MethodsWe conducted a retrospective cohort study on 231 treatment naive patients with a single HCC ≤ 3 cm who had received either curative PRFA (162 patients) or curative SR (69 patients). All patients were regularly followed up after treatment at our department with blood and radiologic tests.ResultsThe 1-, 3- and 5-year overall survival rates after PRFA and SR were 95.4%, 79.6% and 63.1%, respectively in the PRFA group and 100%, 81.4% and 74.6%, respectively in the SR group. The corresponding recurrence free survival rates at 1, 3 and 5 years after PRFA and SR were 82.0%, 38.3% and 18.0%, respectively in the PRFA group and 86.0%, 47.2% and 26.0%, respectively in the SR group. In terms of overall survival and recurrence free survival, there were no significant differences between these two groups. In comparison of PRFA group patients with liver cirrhosis (LC) (n = 127) and SR group patients with LC (n = 50) and in comparison of PRFA group patients without LC (n = 35) and SR group patients without LC (n = 19), there were also no significant differences between two groups in terms of overall survival and recurrence free survival. In the multivariate analysis of the risk factors contributing to overall survival, serum albumin level was the sole significant factor. In the multivariate analysis of the risk factors contributing to recurrence free survival, presence of LC was the sole significant factor. The rate of serious adverse events in the SR group was significantly higher than that in the PRFA group (P = 0.023). Hospitalization length in the SR group was significantly longer than in the PRFA group (P = 0.013).ConclusionsPRFA is as effective as SR in the treatment of single and small HCC, and is less invasive than SR. Therefore, PRFA could be a first choice for the treatment of single and small HCC.

Radiofrequency ablation for hepatocellular carcinoma.

Abstract Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Unfortunately, only 20% of HCC patients are amenable to curative therapy (liver transplantation or surgical resection). Locoregional therapies such as radiofrequency ablation (RFA), percutaneous ethanol injection, microwave coagulation therapy, and transcatheter arterial chemoembolisation play a key role in the management of HCC. The choice of the treatment modality depends on the size of the tumour, tumour location, anatomic considerations and the number of tumours present and liver function. RFA therapy for HCC can be performed safely using a percutaneous, laparoscopic, or an open approach, even in patients with poor functional reserve. Since the introduction of RFA, several randomised controlled trials and non-randomised studies comparing RFA and other therapies for HCC have been conducted. In addition, in the last decade there have been technical advances in RFA therapy for HCC, resulting in significant improvement in the prognosis of HCC patients treated with this modality. In this review, we primarily focus on percutaneous RFA therapy for HCC and refer to current knowledge and future perspectives for this therapy. We also discuss new emerging ablation techniques.

Bezafibrate may attenuate biliary damage associated with chronic liver diseases accompanied by high serum biliary enzyme levels.

BackgroundBezafibrate is a commonly used medicine for hyperlipidemia, and recently several reports have suggested the efficacy of bezafibrate for the treatment of primary biliary cirrhosis (PBC). To assess its efficacy for other liver diseases, we administered bezafibrate to patients with various categories of hepatobiliary impairment.MethodsBezafibrate (400 mg/day) was orally administered to 67 patients with chronic liver disease [22 with PBC, six with primary sclerosing cholangitis (PSC), 20 with chronic liver disease associated with hepatitis C virus (HCV) infection (CLD-C), seven with auto immune hepatitis (AIH), ten with alcoholic liver injury, and two with drug-induced liver injury].ResultsThe levels of biliary enzymes, such as alkaline phosphatase and γ-glutamyltranspeptidase, decreased promptly and dramatically. The abnormally high level of alanine aminotransferase also showed a gradual decrease over 6 months in five of the eight PBC patients, all three PSC patients, eight of the 17 CLD-C patients, and all seven alcoholic liver injury patients. The level of immunoglobulin M showed a gradual decrease in 17 of the 22 PBC patients.ConclusionsBezafibrate significantly reduced the level of biliary enzymes in various chronic liver diseases and may be useful for the treatment of certain liver disease subsets.

Treatment for hepatocellular carcinoma in elderly patients: a literature review.

An aging society means that the number of elderly patients with cancer is predicted to rise in the future. Hepatocellular carcinoma (HCC) usually develops in patients with hepatitis B virus infection, hepatitis C virus infection, or alcoholic liver disease. The risk of developing HCC is also known to be age-dependent and elderly patients sometimes present with HCC. The increased longevity of the population thus means that more elderly HCC patients are to be expected in the coming years. In general, many elderly patients are not receiving optimal therapy for malignancies, because it is often withheld from them because of perceived minimal survival advantage and the fear of potential toxicity. Comprehensive data with regard to treatment of elderly patients with HCC are currently limited. Furthermore, current guidelines for the management of HCC do not satisfy strategies according to age. Thus, there is urgent need for investigation of safety and clinical outcomes in elderly patients who receive therapy for HCC. In this review, we primarily refer to current knowledge of clinical characteristics and outcome in elderly patients with HCC who underwent different treatment approaches (i.e., surgical resection, liver transplantation, locoregional therapies, and molecular-targeting therapy).

Complete Response of Advanced Hepatocellular Carcinoma with Multiple Lung Metastases Treated with Sorafenib: A Case Report

Sorafenib, an oral multikinase inhibitor, has demonstrated clinical efficacy in patients with advanced hepatocellular carcinoma (HCC). However, in the SHARP trial (Sorafenib HCC Assessment Randomized Protocol trial) and the Asia-Pacific trial (conducted in the Asia-Pacific region), no cases of complete response (CR) were reported. Thereafter, only a relatively small number of CR cases were reported worldwide for sorafenib therapy. We herein report a case of CR in a patient treated with sorafenib for 4 months. The patient had advanced HCC with multiple lung metastases, and there has been no recurrence after 8 months following cessation of administration. To our knowledge, this is the first time a female treated with sorafenib alone for HCC has had a CR.

The effect of long-term supplementation with branched-chain amino acid granules in patients with hepatitis C virus-related hepatocellular carcinoma after radiofrequency thermal ablation.

Goals: To elucidate whether long-term supplementation with branched-chain amino acid (BCAA) granules improves overall survival (OS) and recurrence-free survival (RFS) after radiofrequency thermal ablation (RFA) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)⩽3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of ⩽3.5 g/dL. Background: Whether BCAA treatment after curative RFA for patients with HCV-related HCC improves OS and RFS remains unclear. Study: We compared the OS rate and the RFS rate between the BCAA group (n=115) and the control group (n=141). We also examined factors contributing to OS and RFS. Results: The 1 and 3 years OS rates after RFA were 94.0% and 70.0%, respectively, in the BCAA group, and 94.0% and 49.8%, respectively, in the control group (P=0.001). The corresponding RFS rates 1 and 3 years after RFA were 61.8% and 28.0%, respectively, in the BCAA group, and 52.0% and 12.0%, respectively, in the control group (P=0.013). In the multivariate analysis, in terms of OS, BCAA treatment, and serum albumin level of ≥3.4 g/dL, and in terms of RFS, age 70 years or older, BCAA treatment, and a serum albumin level of ≥3.4 g/dL were significant independent factors, respectively. Conclusions: BCAA treatment may improve OS and RFS after RFA in patients with HCV-related HCC⩽3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of 3.5 g/dL.

Branched-chain amino acid treatment before transcatheter arterial chemoembolization for hepatocellular carcinoma

AIM To examine the significance of branched-chain amino acid (BCAA) treatment before transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS This study included 99 patients who underwent TACE therapy for HCC at our hospital and were followed up without treatment for at least 6 mo between January 2004 and January 2010. They were divided into 2 groups: those receiving BCAA granules (n = 40) or regular diet (n = 59, control). Data obtained were retrospectively analyzed (prior to TACE, and 1 wk, 1, 3, and 6 mo after TACE) in terms of nutritional condition and clinical laboratory parameters (serum albumin level and Child-Pugh score), both of which are determinants of hepatic functional reserve. RESULTS The BCAA group comprised 27 males and 13 females with a mean age of 69.9 ± 8.8 years. The patients of the BCAA group were classified as follows: Child-Pugh A/B/C in 22/15/3 patients, and Stage II/III/IVA HCC in 12/23/5 patients, respectively. The control group comprised 32 males and 27 females with a mean age of 73.2 ± 10.1 years. In the control group, 9 patients had chronic hepatitis, Child-Pugh A/B/C in 39/10/1 patients, and StageI/II/III/IVA HCC in 1/11/35/12 patients, respectively. Overall, both serum albumin level and Child-Pugh score improved significantly in the BCAA group as compared with the control 3 and 6 mo after TACE (P < 0.05). Further analysis was performed by the following categorization: (1) child-Pugh classification; (2) liver cirrhosis subgroup with a serum albumin level > 3.5 g/dL; and (3) epirubicin dose. A similar trend indicating a significant improvement of all variables in the BCAA group was noted (P < 0.05). CONCLUSION Treatment with BCAA granules in patients who have undergone TACE for HCC is considered useful to maintain their hepatic functional reserve.

Effect of transcatheter arterial chemoembolization prior to surgical resection for hepatocellular carcinoma

The aim of the present study was to evaluate the influence of preoperative transcatheter arterial chemoembolization (TACE) on survival after surgical resection (SR) for hepatocellular carcinoma (HCC). Two hundred and thirty-five HCC patients who underwent SR with curative intent were analyzed. Overall survival (OS), recurrence-free survival (RFS) and complication rates were compared between the TACE (n=110) and control groups (n=125). Moreover, TACE subjects were classified into TACE responders (n=85) and TACE non-responders (n=25), according to the therapeutic efficacy of pretreatment TACE, and the factors contributing to OS and RFS after SR were analyzed using univariate and multivariate analyses. The 1-, 3- and 5-year OS rates were 87.4, 76.0 and 62.5%, respectively, in the TACE group and 94.9, 79.0 and 57.8%, respectively, in the control group (P=0.674). The corresponding RFS rates at 1, 3 and 5 years were 73.3, 48.9 and 33.2%, respectively, in the TACE group and 73.3, 29.4 and 16.3%, respectively, in the control group (P=0.062). No TACE-related serious adverse events (SAEs) were observed. There were no significant differences between the groups in terms of surgery-related SAEs (P=0.714), operation time (P=0.881), blood loss during surgery (P=0.334) and hospitalization period (P=0.447). Multivariate analyses identified TACE responder, TACE non-responder, total bilirubin ≥1 mg/dl, serum albumin ≥4 g/dl, pretreatment α-fetoprotein (AFP) level ≥100 ng/ml and microscopic vascular invasion as significant prognostic factors linked to OS. TACE non-responder, tumor number (multiple) and pretreatment AFP level ≥100 ng/ml were significant adverse prognostic factors linked to RFS. In conclusion, TACE is a safe procedure in patients with HCC, and the efficacy of TACE prior to surgery may be associated with clinical outcomes after SR.

Transcatheter arterial infusion chemotherapy prior to radiofrequency thermal ablation for single hepatocellular carcinoma reduces the risk of intrahepatic distant recurrence

The aim of the present study was to elucidate the effectiveness of transcatheter arterial infusion chemotherapy (TAI) of the whole liver using an epirubicin-mitomycin-lipiodol emulsion, prior to radiofrequency thermal ablation (RFA), in preventing intrahepatic distant recurrence (IDR) from single hepatocellular carcinoma (HCC). Of the 269 consecutive patients who underwent RFA in our institute for single HCC, a total of 182 patients were analyzed in the present study. The primary endpoint was comparison of the post-RFA IDR-free survival rates in patients treated using TAI with an epirubicin-mitomycin-lipiodol emulsion via the proper hepatic artery (TAI-EML) prior to RFA, and patients that received lipiodol infusion-alone prior to RFA. The secondary endpoints were local tumor progression (LTP) and overall survival (OS). Lipiodol infusion-alone prior to RFA was performed in 88 patients and TAI-EML prior to RFA in 94 patients. The mean tumor size was 2.06 cm (range, 0.9-3.2 cm) in the TAI group and 1.97 cm (range, 0.9-3.3 cm) in the lipiodol-alone group, respectively. The cumulative IDR-free survival rates at 1, 2 and 3 years were 74.0, 50.8 and 34.9%, respectively, in the lipiodol-alone group, and 90.8, 74.8 and 70.0%, respectively, in the TAI group (P<0.001). In terms of the OS, there was a significant difference between these two groups (P=0.048), although there was no significant difference in terms of the LTP (P=0.145). We concluded that TAI-EML prior to RFA appears to be useful in reducing post-RFA IDR and may contribute to improved survival rates.

Comparison of clinical characteristics and survival after surgery in patients with non-B and non-C hepatocellular carcinoma and hepatitis virus-related hepatocellular carcinoma.

Background and aims: We compared clinicopathologic data and long-term clinical outcomes among patients with non-B and non-C hepatocellular carcinoma (NBNC-HCC) who underwent curative resection (group A, n=129), those with hepatitis B virus-related HCC (group B, n=62) and those with hepatitis C virus-related HCC (group C, n=284). Methods: Clinicopathologic characteristics and cumulative overall survival (OS) and recurrence-free survival (RFS) after curative resection were compared among the three groups. Results: The proportion of patients with non-liver cirrhosis (LC) or diabetes mellitus in group A was significantly higher than that in group B or group C. The mean maximum tumor size in group A was significantly larger than that of group B or group C. Cumulative 3-year OS rates after resection were 76% in group A, 79% in group B and 72% in group C (A vs. B, P=0.638; A vs. C, P=0.090; B vs. C, P=0.091; overall significance, P=0.088). The corresponding RFS rates after resection were 38% in group A, 36% in group B and 36% in group C (A vs. B, P=0.528; A vs. C, P=0.281; B vs. C, P=0.944; overall significance, P=0.557). In subgroup analyses in patients with LC, in those without LC and in those who satisfied the Milan criteria, similar results were obtained, i.e., the difference among the three groups did not reach significance in terms of OS and RFS. Conclusion: Long-term clinical outcomes in patients NBNC-HCC after curative resection were comparable to those in patients with hepatitis virus-related HCC after curative resection.