Kiminori Uka

Pretreatment predictor of response, time to progression, and survival to intraarterial 5-fluorouracil/interferon combination therapy in patients with advanced hepatocellular carcinoma

BackgroundSeveral studies have reported survival benefits of combination therapy with intraarterial 5-fluorouracil (5-FU) and subcutaneous interferon (IFN) α for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). We investigated the pretreatment predictive factors of early response, time to progression (TTP), and survival in response to intraarterial 5-FU/IFN combination therapy.MethodsPatients with nonresectable HCC and variable PVTT grades (without PVTT to PVTT in the trunk) received intraarterial 5-FU/IFN combination therapy (n = 55).ResultsAfter two courses of the combination therapy, 1 (2%), 15 (27%), 16 (29%), 12 (22%), and 11 (20%) of 55 patients showed complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or had dropped out (DO), respectively, when their early response to treatment was assessed. Univariate analysis identified only hepatitis C virus (HCV) antibody positivity as having significantly influenced the early response (P = 0.028) and TTP (P = 0.021). Multivariate analysis identified performance status (P = 0.003) and HCV antibody positivity (P = 0.007) as significant and independent determinants of survival. PVTT grade did not influence early response, TTP, or survival. The survival rate was significantly higher in patients who achieved CR or PR than in those that assessed as SD or PD, or DO (P < 0.0001, each).ConclusionsHCV antibody positivity may be a significant pretreatment predictor of early response, TTP, and survival of patients with advanced HCC treated with 5-FU/IFN. CR or PR as the early response to the combination therapy might indicate a more favorable prognosis in patients with advanced HCC. PVTT grade did not seem to influence the efficacy of combination therapy.

FDG positron emission tomography/computed tomography for the detection of extrahepatic metastases from hepatocellular carcinoma

Aims:  To compare the efficacy of positron emission tomography (PET) computed tomography (CT), multi‐detector helical computed tomography (MDCT) and bone scintigraphy for the detection of extrahepatic metastases in patients with hepatocellular carcinoma (HCC).

Clinicopathological features of elderly patients with hepatitis C virus-related hepatocellular carcinoma

BackgroundIt is well known that the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) correlates with progression of liver fibrosis. However, there is little information on the impact of aging on hepatocarcinogenesis. The aim of this study was to elucidate the clinicopathological features of elderly patients with HCV-related HCC.MethodsThe study subjects were 693 consecutive patients newly diagnosed with HCC with anti-HCV. First, we divided them into a younger group (<70 years) and an elderly group (≥70 years) and compared clinicopathological features between the two groups. Next, we selected pure HCV-related HCC patients by excluding the patients with other probable factors for hepatocarcinogenesis (anti-HBc, interferon therapy, and alcohol) and compared the two groups again.ResultsHigher platelet count, lower male/female ratio, lower rate of habitual alcohol consumption, and better Child-Pugh class were recognized in the elderly group thant the younger group, statistically. In 133 cases of hepatic resection, fibrosis stage was lower in the elderly than the younger group. After selection of pure HCV-related HCC patients, in a stepwise multi variate analysis, male sex and platelet count <10 × 104/mm3 were significant variables associated with age <70. Regarding the latency period to HCC development, the patients who received a blood transfusion at an older age developed HCC sooner despite their lower grade of fibrosis.ConclusionsThe elderly patients developed HCC more often, despite their lower grade of fibrosis, compared with the younger patients. In addition to fibrosis, aging could be a factor affecting HCV-related hepatocarcinogenesis.

Similar effects of recombinant interferon-α-2b and natural interferon-α when combined with intra-arterial 5-fluorouracil for the treatment of advanced hepatocellular carcinoma

Aim: Intra‐arterial 5‐fluorouracil (5‐FU) plus interferon (IFN) combination therapy is effective against advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombosis. In this study, we compared the efficiency and safety of recombinant IFN‐α‐2b with natural IFN‐α as components of the combination therapy.

Efficacy of Percutaneous Cementoplasty for Bone Metastasis from Hepatocellular Carcinoma

Objective: To assess the efficacy of percutaneous cementoplasty for painful bone metastasis from hepatocellular carcinoma (HCC). Methods: Cementoplasty was performed for 22 metastatic bone tumors in 13 patients. All patients had intractable pain and were diagnosed as metastatic bone tumor from HCC. The ostyneedle was inserted in the center of the site of bone metastasis under CT guidance. VAS score, Tokuhashi score and Frankel score were used for assessment of the efficacy of cementoplasty. We also assessed the response to treatment, adverse events and prognosis. Results: Only the VAS score, but not Tokuhashi and Frankel scores, improved after cementoplasty. Cementoplasty for painful bone metastasis provided relief of severe pain but did not improve prognosis, neurological function or survival. Eleven of 13 (85%) patients showed CR or PR and the mean pain-free period was 5 months, including a 10-month pain-free period in one case. No major complications were encountered. Conclusions: Percutaneous cementoplasty can provide pain relief and improvement of quality of life, though without survival benefits, for HCC patients with painful bone metastasis.

Combination therapy of oral fluoropyrimidine anticancer drug S-1 and interferon alpha for HCC patients with extrahepatic metastases.

Purpose: There is no standard treatment for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. We assessed the efficiency and safety of the oral fluoropyrimidine anticancer drug S-1 combined with interferon alpha (IFN-α) for HCC patients with extrahepatic metastases. Methods: Twenty-nine HCC patients with extrahepatic metastases received S-1/IFN. One cycle of combination therapy represented 2 weeks followed by 2–4 weeks of rest. In each cycle, S-1 was administrated orally at 80–120 mg (depending on body surface area) every day and IFN-α intramuscularly at 5 million units thrice weekly. Results: The overall response of 29 patients was complete response (CR) in 4 (14%), partial response (PR) in 1, stable disease in 4, progressive disease in 12, and dropout in 8 patients. Objective response (CR + PR) was 17%. The time to progression and survival rate were significantly higher in patients with lung metastases (n = 19) than in those with painful bone metastases (n = 7; p = 0.0058 and 0.0015). With regard to NCI-CTC grade 3 adverse reactions, 3 (10%), 3 (10%) and 2 (7%) patients developed anorexia, leukopenia, and neutropenia, respectively. No grade 4 adverse reaction or toxicity-related death occurred. Conclusion: S-1/IFN is a potentially safe and suitable combination therapy for HCC patients with extrahepatic metastases, especially those with lung metastases.

Functional Discrepancy between Two Liver Lobes after Hemilobe Biliary Drainage in Patients with Jaundice and Bile Duct Cancer: An Appraisal Using 99mTc-GSA SPECT/CT Fusion Imaging

PURPOSE To determine the functional discrepancy between the two liver lobes using technetium 99m ((99m)Tc) diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ( GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ) single photon emission computed tomography (SPECT)/computed tomography (CT) fusion imaging following preoperative biliary drainage and portal vein embolization ( PVE portal vein embolization ) in patients with jaundice who have bile duct cancer ( BDC bile duct cancer ). MATERIALS AND METHODS This retrospective study was approved by the institutional review board, with waiver of informed consent. Preoperative (99m)Tc- GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin SPECT/CT fusion images from 32 patients with extrahepatic BDC bile duct cancer were retrospectively reviewed. Patients were classified into four groups according to the extent of biliary drainage and presence of a preoperative right PVE portal vein embolization : right lobe drainage group (right drainage), bilateral lobe drainage group (bilateral drainage), left lobe drainage group (left drainage), and left lobe drainage with right PVE portal vein embolization group (left drainage with right PVE portal vein embolization ). Percentage volume and percentage function were measured in each lobe using fusion imaging. The ratio between percentage function and percentage volume (the function-to-volume ratio) was calculated for each lobe, and the results were compared among the four groups. Statistical analysis was performed with Wilcoxon signed-rank tests and Mann-Whitney U tests. RESULTS The median values for the function-to-volume ratio in the right drainage, bilateral drainage, left drainage, and left drainage with right PVE portal vein embolization group were 1.12, 1.05, 1.02, and 0.81 in the right lobe; and 0.51, 0.88, 0.96, and 1.17 in the left lobe. Significant differences in the function-to-volume ratio were observed among the four groups (right drainage vs bilateral drainage vs left drainage vs left drainage with right PVE portal vein embolization ; with P < .002, P = .023, and P < .002 for the right lobe and P < .001, P = .023, and P < .002 for the left lobe). CONCLUSION Hepatic lobar function significantly differs between the two lobes, depending on the extent of biliary drainage and the presence of portal vein embolization.

Etiology and outcome of acute liver failure: Retrospective analysis of 50 patients treated at a single center

Background and Aim:  Acute liver failure (ALF) remains a devastating disease carrying considerable mortality. Since deceased donor liver transplantation is rarely performed in Japan, the artificial liver support system (ALS) and living donor liver transplantation (LDLT) are the main modalities used for treatment of ALF. The aim of this study was to analyze the outcome of ALF patients and to evaluate therapies for ALF according to etiology.

Prospective study of short‐term peginterferon‐α‐2a monotherapy in patients who had a virological response at 2 weeks after initiation of interferon therapy

Background and Aims:  Long‐term interferon (IFN) therapy is effective in eliminating hepatitis C virus (HCV). However, it carries the risk of adverse effects and reduced quality of life. To assess whether short‐term IFN therapy effectively eliminates HCV, we performed a prospective pilot study of pegylated (peg)IFN‐α‐2a therapy for 8 or 24 weeks.

CT/99mTc-GSA SPECT fusion images demonstrate functional differences between the liver lobes.

AIM To evaluate the functional differences between the 2 liver lobes in non-cirrhotic patients by using computed tomography/(99m)Tc-galactosyl human serum albumin (CT/(99m)Tc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODS Between December 2008 and March 2012, 264 non-cirrhotic patients underwent preoperative liver function assessment using CT/(99m)Tc-GSA SPECT fusion images. Of these, 30 patients, in whom the influence of a tumor on the liver parenchyma was estimated to be negligible, were selected. Specifically, the selected patients were required to meet either of the following criteria: (1) the presence of an extrahepatic tumor; or (2) presence of a single small intrahepatic tumor. These 30 patients were retrospectively analyzed to calculate the percentage volume (%Volume) and the percentage function (%Function) of each lobe. The ratio between the %Function and %Volume (function-to-volume ratio) of each lobe was also calculated, and the ratios were compared between the 2 lobes. Furthermore, the correlations between the function-to-volume ratio and each of 2 liver parameters [lobe volume and diameter ratio of the left portal vein to the right portal vein (LPV-to-RPV diameter ratio)] were investigated. RESULTS The median values of %Volume and %Function were 62.6% and 67.1% in the right lobe, with %Function being significantly higher than %Volume (P < 0.01). The median values of %Volume and %Function were 31.0% and 28.7% in the left lobe, with %Function being significantly lower than %Volume (P < 0.01). The function-to-volume ratios of the right lobe (1.04-1.14) were significantly higher than those of the left lobe (0.74-0.99) (P < 0.01). The function-to-volume ratio showed no significant correlation between the lobe volume in either lobe. In contrast, the function-to-volume ratio showed significant correlations with the LPV-to-RPV diameter ratio in both lobes (right lobe: negative correlation, r s = -0.37, P = 0.048; left lobe: positive correlation, r s = 0.71, P < 0.001). The function-to-volume ratio in the left lobe tended to be higher, and that in the right lobe tended to be lower, in accordance with the increase in the LPV-to-RPV diameter ratio. CONCLUSION CT/(99m)Tc-GSA SPECT fusion images demonstrated that the function of the left lobe was significantly decreased compared with that of the right lobe in non-cirrhotic livers.