Publications by authors named "Tenyu Motoyama"

31 Publications

Propofol midazolam for sedation during radiofrequency ablation in patients with hepatocellular carcinoma.

JGH Open 2021 Feb 22;5(2):273-279. Epub 2020 Dec 22.

Departmetn of Anesthesiology, Graduate School of Medicine Chiba University Chiba Japan.

Background And Aim: Standardization of the sedation protocol during radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) is needed. This randomized, single-blind, investigator-initiated trial compared clinical outcomes during and after RFA using propofol and midazolam, respectively, in patients with HCC.

Methods: Few- and small-nodule HCC patients (≤3 nodules and ≤3 cm) were randomly assigned to either propofol or midazolam. Patient satisfaction was assessed using a 100-mm visual analog scale (VAS) (1 mm = not at all satisfied, 100 mm = completely satisfied). Sedation recovery rates 1, 2, 3, and 4 h after RFA were evaluated based on Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores; full recovery was defined as a MOAA/S score of 5.

Results: Between July 2013 and September 2017, 143 patients with HCC were enrolled, and 135 patients were randomly assigned to the treatment group. Compared with midazolam, propofol exhibited similar median procedural satisfaction (propofol: 73.1 mm, midazolam: 76.9 mm, = 0.574). Recovery rates 1 and 2 h after RFA were higher in the propofol group than in the midazolam group. Meanwhile, recovery rates observed 3 and 4 h after RFA were similar in the two groups. The safety profiles during and after RFA were almost identical in the two groups.

Conclusion: Patient satisfaction was almost identical in patients receiving propofol and midazolam sedation during RFA. Propofol sedation resulted in reduced recovery time compared with midazolam sedation in patients with HCC. The safety profiles of both propofol and midazolam sedation during and after RFA were acceptable.
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http://dx.doi.org/10.1002/jgh3.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857294PMC
February 2021

A randomized placebo-controlled trial of prophylactic dexamethasone for transcatheter arterial chemoembolization.

Hepatology 2018 02 23;67(2):575-585. Epub 2017 Dec 23.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

This randomized, double-blind, placebo-controlled trial evaluated dexamethasone efficacy at preventing fever, anorexia, and nausea/vomiting, the most frequent adverse events of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Child-Pugh class A/B patients with HCC and no macrovascular invasion/extrahepatic metastases were randomly assigned to either a dexamethasone regimen (day 1, intravenous dexamethasone [20 mg] and granisetron [3 mg] before TACE; days 2 and 3, intravenous dexamethasone [8 mg]) or a control regimen (day 1, intravenous placebo [saline] and granisetron [3 mg]; days 2 and 3, intravenous placebo). The primary endpoint was complete response, defined as the absence of grade ≥1 fever, anorexia, or nausea/vomiting according to the Common Terminology Criteria for Adverse Events (version 4.0) and no use of rescue therapy for 120 hours after TACE. A total of 120 patients between October 2010 and June 2013 were randomly assigned to treatment groups. Overall the complete response rate was greater with the dexamethasone regimen than with the control regimen (47.5%, 95% confidence interval 34.3%-60.9%, versus 10.2%, 95% confidence interval 3.8%-20.8%; P < 0.001). Cumulative incidences of fever, anorexia, and nausea/vomiting were higher in the control regimen group compared with the dexamethasone group (P < 0.001, P < 0.001, and P = 0.095, respectively). The dexamethasone regimen was generally well tolerated by HCC patients including those with well-controlled diabetes mellitus and those with hepatitis B virus infection. Conclusion: The dexamethasone regimen was more effective than the control regimen at preventing TACE-induced fever, anorexia, and nausea/vomiting in patients with HCC. (Hepatology 2018;67:575-585).
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http://dx.doi.org/10.1002/hep.29403DOI Listing
February 2018

Prognostic Significance of Concurrent Hypovascular and Hypervascular Nodules in Patients with Hepatocellular Carcinoma.

PLoS One 2016 20;11(9):e0163119. Epub 2016 Sep 20.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Hypovascular nodules often occur together with hypervascular hepatocellular carcinoma (HCC). However, it remains controversial whether hypovascular nodules associated with hypervascular HCC have any prognostic value. This study evaluated the prognostic impact of hypovascular nodules co-existing with hypervascular HCC as diagnosed by computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), which can sensitively capture the dynamic changes in blood flow through the portal vein and hepatic artery in patients with early stage HCC.

Methods: A total of 152 patients with hypervascular HCC (≤ 30 mm, ≤ 3 nodules), who underwent initial local ablation, were analyzed retrospectively. All patients received CTAP and CTHA prior to treatment. Overall survival (OS) was compared among group A (hypervascular HCC only, 107 patients) and group B (hypovascular nodules and hypervascular HCC, 45 patients).

Results: Among all hypovascular nodules, 81% (46 of 57) developed hypervascularization within the follow-up period. The 1- and 2-year hypervascularization rates were 17% and 51%, respectively. OS was significantly longer for group A than for group B (P < 0.001). A Cox proportional-hazards model identified the presence of hypovascular nodules concurrent with hypervascular HCC as an independent poor prognostic factor.

Conclusion: The prognosis of hypervascular HCC patients with hypovascular nodules detected during CTAP and CTHA is poor. Clinical HCC categories seem to be dissimilar between patients with and without hypovascular nodules.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029907PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163119PLOS
August 2017

Post-progression survival in patients with advanced hepatocellular carcinoma resistant to sorafenib.

Invest New Drugs 2016 Apr 14;34(2):255-60. Epub 2016 Jan 14.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background: Since the approval of sorafenib, no other agent has been proven to show survival benefits in clinical trials involving patients with advanced hepatocellular carcinoma (HCC) resistant to sorafenib. Prognostic factors for survival after tumor progression in sorafenib-treated patients are critical for designing second-line trials.

Methods: To determine the factors affecting the post-progression survival (PPS) after sorafenib treatment, additional analyses were conducted using fixed data obtained from our previous prospective study. Data on patients with advanced HCC treated with sorafenib were analyzed in view of patient characteristics at the time of tumor progression and the progression pattern (intra-/extrahepatic growth or emergence of new intra-/extrahepatic lesions).

Results: Of the 89 enrolled patients, 70 were diagnosed with disease progression according to the Response Evaluation Criteria in Solid Tumors version 1.1. Multivariate Cox's regression analysis revealed that Child-Pugh scores of ≥7, macrovascular invasion (MVI), and alpha-fetoprotein of >400 ng/mL were independent predictors of poor PPS. Although both extrahepatic metastasis (EHM) and MVI were characteristics of advanced HCC, EHM was not determined as a prognostic factor. Additionally, the emergence of new extrahepatic lesions also served as an independent indicator of a poor prognosis. The PPS of the patients was well stratified according to the index based on the sum of these prognostic factors, ranging from 0 to 4.

Conclusions: Child-Pugh score of ≥7, AFP of >400 ng/mL, MVI, and new extrahepatic lesions at the time of progression may be utilized to assess the prognosis and taken into consideration when designing second-line trials.
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http://dx.doi.org/10.1007/s10637-016-0323-1DOI Listing
April 2016

Liver function assessment according to the Albumin-Bilirubin (ALBI) grade in sorafenib-treated patients with advanced hepatocellular carcinoma.

Invest New Drugs 2015 Dec 14;33(6):1257-62. Epub 2015 Oct 14.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background: The Albumin-Bilirubin (ALBI) grade has been proposed as a new, simple, and objective method of assessing liver function. However, there is lack of data in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC).

Methods: We evaluated the correlations between the ALBI grade and Child-Pugh score, adverse events, and survival in 89 patients with advanced HCC who were prospectively treated with sorafenib.

Results: Majority of patients with ALBI grade 1 (14/15 patients, 93%) had a Child-Pugh score of 5. Patients with ALBI grade 2 had a wide range of liver function according to the Child-Pugh scores, with scores of 5, 6, 7, and ≥ 8. We divided ALBI grade 2 patients into ALBI grade 2A and 2B groups according to the median ALBI score among patients with ALBI grade 2. Although no significant difference was observed, the incidence of liver dysfunction in sorafenib-treated patients with ALBI grades 1, 2A, and 2B was 7%, 19%, and 35%, respectively. Overall survival in the ALBI grade 2B group was significantly shorter than that in the ALBI grade 1 and 2A groups. Thus, ALBI grade 2B was an independent predictor of poor prognosis in addition to elevated serum aspartate aminotransferase levels, increased serum alpha-fetoprotein level, and macrovascular invasion.

Conclusion: Sorafenib may be indicated for all patients with advanced HCC and ALBI grade 1 and for some with ALBI grade 2. The subdivision of patients with ALBI grade 2 increases the utility of ALBI in identifying patients indicated for sorafenib therapy.
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http://dx.doi.org/10.1007/s10637-015-0292-9DOI Listing
December 2015

Transcatheter arterial infusion for advanced hepatocellular carcinoma: Who are candidates?

World J Gastroenterol 2015 Aug;21(29):8888-93

Eiichiro Suzuki, Tetsuhiro Chiba, Yoshihiko Ooka, Sadahisa Ogasawara, Akinobu Tawada, Tenyu Motoyama, Naoya Kanogawa, Tomoko Saito, Masaharu Yoshikawa, Osamu Yokosuka, Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.

Aim: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy (TAI) in patients with hepatocellular carcinoma (HCC).

Methods: Data from a total of 95 patients with HCC who received TAI were analyzed retrospectively. The efficacy of TAI was evaluated according to the Response Evaluation Criteria in Cancer of the Liver. Overall survival was calculated from the date of initial treatment to the date of death or last follow-up. Survival curves were calculated by the Kaplan-Meier method, and differences in survival were evaluated by the log rank test. Clinical variables that were identified as statistically different by a univariate analysis were included into the Cox proportional hazard regression model for multivariate analysis. A prognostic index based on the regression coefficients derived from variables identified by the multivariate analysis was constructed. Stratification of the patients was conducted using this prognostic index.

Results: The patient group was comprised of 76 men and 19 women with an average age of 68 years (range: 37-82 years). Six patients (6.3%) showed complete response and 18 patients (18.9%) showed partial response, for an overall response rate of 25.2%. The median overall survival was 27.6 mo, and the proportions of survivors at 1, 2, and 5 years were 67.4%, 54.0%, and 17.4%, respectively. Multivariate analysis demonstrated that no prior transcatheter arterial chemoembolization, lactate dehydrogenase < 230 IU/L, and performance status of 0 were the independent favorable prognostic factors. The development of a 0-3-point prognostic score index was based on the sum of these three prognostic factors. Subsequently, the patients were categorized into three groups: those with a good (prognostic index = 0-1; n = 54), intermediate (prognostic index = 2; n = 26), or poor (prognostic index = 3; n = 15) prognosis. The median survival times in these three groups were 41.0, 21.2, and 6.8 mo, respectively (P < 0.01).

Conclusion: Our simple prognostic index may be helpful for management of patients in determining treatment strategies for advanced HCC in the era of molecularly targeted therapy.
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http://dx.doi.org/10.3748/wjg.v21.i29.8888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528031PMC
August 2015

Fatal Diaphragmatic Hernia following Radiofrequency Ablation for Hepatocellular Carcinoma: A Case Report and Literature Review.

Case Rep Oncol 2015 May-Aug;8(2):238-45. Epub 2015 May 28.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

An 81-year-old man was admitted to our hospital because of right quadrant abdominal pain. On admission, his liver function was Child-Pugh grade C (10 points). Computed tomography (CT) revealed a diaphragmatic herniation of bowel loops into the right thoracic cavity, accompanied by pleural effusion. Although diaphragmatic hernia was successfully repaired by emergency surgery, he died of liver failure 23 days after the surgery. A retrospective reading of CT images revealed the presence of diaphragmatic injury after radiofrequency ablation (RFA) which had been conducted 33 months before the development of diaphragmatic hernia. Of importance, the lesion of the diaphragmatic injury was located on the estimated needle track of RFA for hepatocellular carcinomas in segment 5 and segment 5/8, but not adjacent to their ablation areas. Subsequently, diaphragmatic perforation had been observed 24 months before admission. This suggests that diaphragmatic hernia caused by RFA is not necessarily due to thermal damage of ablation and is possibly life-threatening, at least in some patients with an impaired liver function.
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http://dx.doi.org/10.1159/000431310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478306PMC
June 2015

A prognostic score for patients with intermediate-stage hepatocellular carcinoma treated with transarterial chemoembolization.

PLoS One 2015 28;10(4):e0125244. Epub 2015 Apr 28.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE.

Methods: Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; n = 187) and two affiliated hospitals (validation cohort; n = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child-Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions.

Results: The number of lesions and the Child-Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0-7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child-Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0-2 points, 3 points, 4 points, 5 points, and 6-7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; p < 0.0001). These results were confirmed in the external validation cohort (p < 0.0001).

Conclusions: The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125244PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412579PMC
April 2016

Sorafenib treatment in Child-Pugh A and B patients with advanced hepatocellular carcinoma: safety, efficacy and prognostic factors.

Invest New Drugs 2015 Jun 12;33(3):729-39. Epub 2015 Apr 12.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background: We aimed to evaluate the safety, efficacy and prognostic impact of baseline and early clinical markers in both Child-Pugh A and B patients with advanced hepatocellular carcinoma (HCC).

Methods: We prospectively studied 89 Japanese patients with HCC (Child-Pugh A, n = 59; Child-Pugh B, n = 30) who were started with sorafenib between May 2010 and July 2013.

Results: Frequency of sorafenib-related adverse events was almost similar between Child-Pugh score 5, 6, and 7 patients. The rate of liver dysfunction, including any grade encephalopathy, ≥ grade 3 ascites, or ≥ grade 3 bilirubin increased, in Child-Pugh score ≥8 group was significantly higher than that in the other groups. The median overall survival of Child-Pugh score 5, 6, 7 and ≥8 patients were 14.5, 11.1, 8.7 and 4.6 months, respectively. Patients in Child-Pugh score 6 had significantly longer OS than those in Child-Pugh score 7 (P = 0.049). Multivariate analysis identified macrovascular invasion (MVI), alpha-fetoprotein (AFP), Child-Pugh score and aspartate aminotransferase (AST) as baseline predictors of survival. However, extrahepatic metastasis (EHM) was not a significant prognostic factor. In addition, decrease in AFP level and development of hand-foot skin reaction within 4 weeks after sorafenib initiation were closely associated with favorable survival.

Conclusion: It is possible that not only Child-Pugh score 5 and 6 but also 7 patients are eligible for future clinical trials with sorafenib or similar drugs. Various survival predictors identified in this study might be considered as stratification factor. Although both MVI and EHM is a phenotype of advanced HCC, MVI should be discriminated from EHM because of the prognostic impact on survival in sorafenib-treated advanced HCC patients.
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http://dx.doi.org/10.1007/s10637-015-0237-3DOI Listing
June 2015

Successful interventional treatment for arterioportal fistula caused by radiofrequency ablation for hepatocellular carcinoma.

Case Rep Oncol 2014 Sep-Dec;7(3):833-9. Epub 2014 Dec 19.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Radiofrequency ablation (RFA) is commonly used as a treatment for small hepatocellular carcinoma (HCC). Although several complications such as intraperitoneal bleeding are often observed after RFA, hepatic arterioportal fistula (APF) is a less frequently occurring complication. In this study, we describe two cases of APF caused by RFA, which was successfully occluded by an interventional approach. Case 1 involved a 68-year-old man with solitary HCC in segment VIII of the liver. Both contrast-enhanced computed tomography and color Doppler sonography indicated an APF between the anterosuperior branch of the right hepatic artery (A8) and the portal branch (P8). Concordant with these findings, digital subtraction angiography (DSA) revealed an APF in segment VIII of the liver. Subsequently, the APF was successfully occluded by transarterial embolization (TAE) using gelatin sponge particles. Case 2 involved a 67-year-old man with solitary HCC in segment VII of the liver. Although he developed obstructive jaundice because of hemobilia after RFA, it was improved by endoscopic nasobiliary drainage and the systemic administration of antibiotics. In addition, color Doppler sonography revealed a disturbed flow of the right branch of the portal vein. Similar to case 1, DSA showed an APF between A8 and P8. The APF was successfully embolized by TAE using microcoils. In conclusion, it appears that the formation of APF should be checked after RFA. It is preferable to treat RFA-induced APF promptly by an interventional approach to avoid secondary complications such as portal hypertension and liver dysfunction.
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http://dx.doi.org/10.1159/000370305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307006PMC
February 2015

Sustained virologic response achieved after curative treatment of hepatitis C virus-related hepatocellular carcinoma as an independent prognostic factor.

J Gastroenterol Hepatol 2015 Jul;30(7):1197-204

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background And Aim: Whether an antiviral interferon (IFN)-based therapy (IBT) after curative treatment of hepatocellular carcinoma (HCC) improves the prognosis in patients with hepatitis C virus (HCV)-related HCC remains to be elucidated.

Methods: A total of 178 patients within the Milan criteria underwent curative treatment for HCV-related HCC. Both the time to beyond the Milan criteria (TTBMC) and overall survival (OS) were compared between the sustained virologic response (SVR) (IFN with SVR, n = 22), non-SVR (IFN without SVR, n = 19), and non-IBT (control, n = 82) groups using propensity score matching analysis. Prognostic factors to predict survival were also determined by the Cox proportional-hazards model.

Results: TTBMC in the IFN with SVR group was significantly longer than those in the control and IFN without SVR groups (P < 0.001 and P = 0.006, respectively), although no significant difference existed between the IFN without SVR and control groups. Similarly, OS of the IFN with SVR group was significantly longer than that of the control and IFN without SVR groups (P < 0.001 and P = 0.029, respectively), although no significant difference existed between the IFN without SVR and control groups. The Cox proportional-hazards model identified SVR as an independent prognostic factor in these patients. The IFN with SVR group showed a 0.096-fold decrease in mortality risk compared with the control group (95% confidence intervals = 0.023-0.405; P = 0.001).

Conclusion: Elimination of HCV after curative treatment of patients with HCC within the Milan criteria inhibits recurrence and contributes to a preferential prognosis.
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http://dx.doi.org/10.1111/jgh.12925DOI Listing
July 2015

Transarterial chemoembolization with miriplatin plus epirubicin in patients with hepatocellular carcinoma.

Anticancer Res 2015 Jan;35(1):549-54

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Aim: We aimed to evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using miriplatin plus epirubicin in unresectable hepatocellular carcinoma (HCC).

Patients And Methods: The efficacy of TACE was evaluated by dynamic computed tomography (CT) or magnetic resonance imaging (MRI) three months after the procedure according to the Response Evaluation Criteria in Cancer Study Group of Japan. Adverse events (AEs), including clinical symptoms, hematological toxicities and blood chemistry toxicities, were assessed using Common Terminology Criteria Version 4.0.

Results: Thirty patients with HCC received TACE with miriplatin (miriplatin group) and 29 patients received TACE with miriplatin plus epirubicin (miriplatin-plus-epirubicin group). AEs, such as anorexia and neutropenia, were observed more frequently in the miriplatin-plus-epirubicin group than in the miriplatin group (p=0.028 and 0.014, respectively). However, there was no significant difference in the incidence of these AEs (grade 3/4) between groups. The objective response rate (ORR), including the complete response (CR) and partial response (PR), was 76.7% in the miriplatin group and 58.6% in the miriplatin-plus-epirubicin group (p=0.224). The median time to progression (TTP) in the miriplatin group and the miriplatin-plus-epirubicin group was 8.2 and 6.1 months, respectively (p=0.123).

Conclusion: Although TACE with miriplatin plus epirubicin was safe and tolerable, no additional anti-tumor effects were observed compared to TACE with miriplatin. Further analysis is required to refine the efficacy of TACE using miriplatin plus epirubicin.
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January 2015

Incidental tumor necrosis caused by the interventional alteration of hepatic arterial flow in patients with advanced hepatocellular carcinoma.

Clin J Gastroenterol 2015 Feb 7;8(1):41-6. Epub 2014 Dec 7.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Hepatic arterial infusion chemotherapy (HAIC) is one of the approaches used to treat advanced hepatocellular carcinoma (HCC). Here, we describe 2 cases involving unexpected tumor necrosis after interventional alteration of the hepatic arterial flow during implantation of a port-catheter system for HAIC. Case 1 involved a 42-year-old man with diffuse HCC accompanied by a tumor thrombus in the main trunk of the portal vein. After the right hepatic artery (RHA) derived from the superior mesenteric artery (SMA) was occluded by coils, a port-catheter system was successfully implanted using the gastroduodenal artery (GDA) coil method. The next day, he developed a fever and had right upper abdominal pain. A marked increase in transaminase and lactate dehydrogenase levels was observed. Contrast-enhanced computed tomography (CT) showed tumor necrosis in both the parenchymal tumor and portal vein tumor thrombus. Case 2 involved a 62-year-old man diagnosed with a large HCC located in segments VII and VIII of the liver and abdominal lymph node metastasis. As in case 1, angiography revealed the RHA branched from the SMA. After the replaced RHA and right gastric artery were embolized with coils, a port-catheter system was successfully implanted. Although he showed neither clinical symptoms nor abnormal laboratory data the next day, contrast-enhanced CT revealed tumor necrosis in a large part of the HCC lesion. In conclusion, careful attention is required in the interventional alteration of hepatic arterial flow for implantation of a port-catheter system for HAIC against advanced HCC.
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http://dx.doi.org/10.1007/s12328-014-0542-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331596PMC
February 2015

Partial splenic embolization with transarterial chemoembolization in patients with hepatocellular carcinoma accompanied by thrombocytopenia.

Biomed Res Int 2014 15;2014:960628. Epub 2014 Sep 15.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Background: Thrombocytopenia often makes the introduction of systemic treatment difficult in patients with cirrhosis and hepatocellular carcinoma (HCC). We retrospectively evaluated the long-term effects of partial splenic embolization (PSE) with transarterial chemoembolization (TACE) in patients with HCC patients accompanied by thrombocytopenia.

Patients And Methods: Twenty-one patients with HCC complicated by severe thrombocytopenia (platelet count, <5.0 × 10(4)/mm(3)) were treated with PSE and TACE. Both the safety and platelet-increasing effect was evaluated in these patients.

Results: Seventeen of 21 patients (81.0%) showed increased platelet counts to ≥5.0 × 10(4)/mm(3). Subsequently, 13 patients (61.9%) successfully received systemic chemotherapy. Platelet counts and serum levels of total bilirubin, as well as neutrophil counts, improved significantly one month after treatment. However, serum levels of albumin and hemoglobin decreased significantly one month after treatment. Severe adverse events, including acute liver failure and portal vein thrombus, were observed in two patients.

Conclusion: PSE with selective TACE made it possible for patients with HCC and severe thrombocytopenia to receive systemic chemotherapy. Although PSE with TACE was safe and tolerable for most patients, the extent of PSE with TACE in a wide area of the liver may increase the risk for fatal liver failure.
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http://dx.doi.org/10.1155/2014/960628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4179942PMC
May 2016

Efficacy of sorafenib in intermediate-stage hepatocellular carcinoma patients refractory to transarterial chemoembolization.

Oncology 2014 6;87(6):330-41. Epub 2014 Sep 6.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Objective: We compared the benefits of sorafenib therapy with continued transarterial chemoembolization (TACE) in TACE-refractory patients with intermediate-stage hepatocellular carcinoma (HCC).

Methods: This retrospective study reviewed intermediate-stage HCC patients who underwent the first TACE. Patients were defined as TACE-refractory and divided into two cohorts: (1) patients who switched from TACE to sorafenib and (2) those who continued TACE. We evaluated the patient overall survival (OS) and time to disease progression (TTDP; the time patients reached Child-Pugh C or developed advanced-stage HCC).

Results: A total of 509 patients with HCC underwent TACE. Of 249 intermediate-stage HCC patients undergoing the first TACE, 122 were deemed refractory. At the time they were identified as refractory, 20 patients converted to sorafenib, whereas 36 patients continued TACE. We excluded patients with Child-Pugh scores of ≥ 8, those with advanced-stage HCC, those who had undergone hepatic arterial infusion chemotherapy or other systemic therapy, and those treated with best supportive care alone. The median TTDP and OS were 22.3 and 25.4 months, respectively, in the conversion group, and 7.7 and 11.5 months, respectively, in the continued group (p = 0.001 and p = 0.003, respectively).

Conclusions: It is possible that sorafenib conversion might prolong OS and TTDP in TACE-refractory patients with intermediate-stage HCC.
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http://dx.doi.org/10.1159/000365993DOI Listing
January 2015

Efficacy of transarterial chemoembolization targeting portal vein tumor thrombus in patients with hepatocellular carcinoma.

Anticancer Res 2014 Aug;34(8):4231-7

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Aim: We aimed to retrospectively examine the tolerability and efficacy of transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).

Patients And Methods: Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 4.0. The efficacy of TACE in parenchymal tumors (parenchymal response) and PVTT (PVTT response) was separately evaluated by dynamic computed tomography 1 to 2 months after TACE according to the Response Evaluation Criteria in Cancer of the Liver (RECICL). Patients with complete remission plus partial response in parenchymal tumors and PVTT were assessed as parenchymal response-positive and PVTT response-positive, respectively.

Results: A total of 33 HCC patients with PVTT were analyzed. Grade 3/4 toxicities included elevated aspartate aminotransferase levels (69.7%), elevated alanine aminotransferase levels (54.5%), hyponatremia (6.1%), thrombocytopenia (6.1%), hyperbilirubinemia (3.0%), leukopenia (3.0%) and anemia (3.0%). All these findings returned to the pre-treatment levels within 1 month after TACE. The number of parenchymal response-positive/negative and PVTT response-positive/negative patients was 20/13 and 13/20, respectively. Kaplan-Meier analyses revealed that the cumulative survival rate was significantly higher in parenchymal response-positive (p=0.04) and PVTT response-positive (p<0.01) patients than in their negative counterparts. PVTT response was a favorable prognostic factor for overall survival in multivariate analysis (p=0.03).

Conclusion: TACE was feasible in HCC patients with PVTT and could improve their survival by showing direct therapeutic effect against PVTT.
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August 2014

Histone lysine methyltransferase SUV39H1 is a potent target for epigenetic therapy of hepatocellular carcinoma.

Int J Cancer 2015 Jan 30;136(2):289-98. Epub 2014 May 30.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.

Histone H3 lysine 9 trimethylation (H3K9me3) is associated with transcriptional repression and regulated by histone lysine methyltransferases such as SUV39H1 and ESET. However, the functional roles of these enzymes in hepatocellular carcinoma (HCC) remain uncertain. In this study, we conducted loss-of-function assays for HCC cells. SUV39H1 knockdown but not ESET knockdown reduced H3K9me3 levels and impaired HCC cell growth and sphere formation. The pharmacological inhibition of SUV39H1 by chaetocin resulted in cell growth inhibition and inducing cellular apoptosis in culture and xenograft subcutaneous tumors. Real-time polymerase chain reaction analysis indicated high levels of SUV39H1 expression in 24 of 42 (57.1%) HCC surgical samples compared with corresponding nontumor tissues. Immunohistochemistry identified high levels of H3K9me3 and ESET proteins in 23 (54.8%) and 29 (69.0%) tumor tissues, respectively. However, these proteins' expressions were only observed in biliary epithelial cells and periportal hepatocytes of nontumor tissues. Expression levels of SUV39H1 but not those of ESET were significantly correlated with H3K9me3 levels. The cumulative HCC recurrence rate was significantly higher for patients with elevated SUV39H1 expression and H3K9me3 levels. In conclusion, our data indicate that elevated SUV39H1 expression and high levels of H3K9me3 have important roles in HCC development and progression. Therefore, the pharmacological inhibition of SUV39H1 may be a promising therapeutic approach for HCC treatment.
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http://dx.doi.org/10.1002/ijc.28985DOI Listing
January 2015

Effect of previous interferon-based therapy on recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma.

Int J Med Sci 2014 7;11(7):707-12. Epub 2014 May 7.

1. Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan;

Previous reports have shown that interferon (IFN)-based therapy decreases the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection. However, it remains to be fully elucidated whether elimination of HCV by IFN-based therapy inhibits HCC recurrence after curative treatment, such as surgical resection and local ablation therapies. In this study, we aimed to clarify the influence of a sustained virological response (SVR) after IFN-based therapy on recurrence and survival after curative treatment of HCC. Fifty-one patients who underwent curative treatment of HCV-related HCC after receiving IFN-based therapy were analyzed retrospectively. They were classified into SVR (N = 14) and non-SVR groups (N = 37). In the SVR group, serum levels of aspartate aminotransferase and alanine aminotransferase, the indocyanine green retention rate at 15 min, and the percentages of patients with liver cirrhosis and HCV serotype 1 were significantly lower, whereas serum albumin level and platelet count were significantly higher upon HCC occurrence. Recurrence-free survival (RFS) for the first recurrence was significantly higher in the SVR group (P < 0.01). Multivariate analysis showed that SVR at initial HCC treatment (P < 0.01) and multiple tumors (P < 0.01) are prognostic factors for RFS. Moreover, RFS for the second recurrence showed a similar trend to that for the first recurrence. In conclusion, patients who underwent IFN-based therapy before initial curative treatment of HCC had a favorable clinical outcome compared with non-SVR patients.
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http://dx.doi.org/10.7150/ijms.8764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025170PMC
December 2014

Intracranial metastasis in a patient with hepatocellular carcinoma and gastric cancer.

Case Rep Oncol 2014 Jan 14;7(1):199-203. Epub 2014 Mar 14.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

A 76-year-old man was referred to our hospital with visual disturbance, weakness of the left upper and lower limbs, and gait disturbance. He had previously received transarterial chemoembolization for hepatocellular carcinoma (HCC) 3 and 10 years ago. When he had received radiofrequency ablation for HCC recurrence 2 years ago, total gastrectomy was also performed for his gastric cancer. Subsequently, sorafenib had been administrated for concomitant lung metastatic tumors. On admission, MRI revealed an intra-axial tumor with perifocal edema. The level of carcinoembryonic antigen, but not alpha-fetoprotein, markedly increased. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of adenocarcinoma, which was consistent with the primary gastric cancer. After surgery, his neurological disturbances rapidly resolved. Additional gamma-knife treatment was also performed for another small brain metastasis detected after craniotomy. Subsequently, sorafenib administration was discontinued and S-1 was administered postoperatively. Successful treatment of intracranial metastasis of gastric cancer is important and meaningful, even in patients with multiple primary malignancies.
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http://dx.doi.org/10.1159/000360982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985793PMC
January 2014

A phase I/II trial of capecitabine combined with peginterferon α-2a in Patients with sorafenib-refractory advanced hepatocellular carcinoma.

Invest New Drugs 2014 Aug 16;32(4):762-8. Epub 2014 Apr 16.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background: Several pilot studies have demonstrated the effectiveness of combination therapy with pyrimidine fluoride and interferon for advanced hepatocellular carcinoma.This study aimed to determine the recommended dose of capecitabine combined with peginterferon α-2a (Phase I) and evaluate its safety and efficacy for sorafenib-refractory advanced hepatocellular carcinoma (Phase II).

Methods: Capecitabine was administered daily on days 1-14, while peginterferon α-2a was administered on days 1, 8, and 15. The cycle was repeated every 21 days. The patients were scheduled to receive capecitabine [mg/(m(2)∙day)] and peginterferon α-2a (μg/week) at 3 dose levels in phase I: 1200 and 90 (level 1), 1600 and 90 (level 2), and 2000 and 90 (level 3), respectively.

Results: A total of 30 patients were enrolled. The recommended dose was level 3. Among the 24 patients receiving the drug at the recommended dosage, 2 (8 %) exhibited a partial response, 9 (38 %) exhibited stable disease, 10 (42 %) exhibited progressive disease, and 3 (13 %) were not evaluated. The median time to progression and overall survival were 3.0 months and 7.2 months, respectively. The most common toxicities were decreased white blood cell (88 %), neutrophil (88 %), and platelet counts (58 %); fatigue (50 %); and palmar-plantar erythrodysesthesia syndrome (42 %). Four patients (17 %) discontinued treatment because of severe adverse events.

Conclusion: Capecitabine at 2000 mg/(m(2)∙day) combined with peginterferon α-2a (90 μg/week) exhibited moderate, albeit manageable, toxicity and was declared as the recommended phase II dose. Further research is required to refine the efficacy of this combination.
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http://dx.doi.org/10.1007/s10637-014-0097-2DOI Listing
August 2014

Is intra-patient sorafenib dose re-escalation safe and tolerable in patients with advanced hepatocellular carcinoma?

Int J Clin Oncol 2014 Dec 13;19(6):1029-36. Epub 2014 Feb 13.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background: Although sorafenib improves survival in patients with hepatocellular carcinoma (HCC), doses have to be reduced in quite a few patients because of adverse events. We investigated whether intra-patient sorafenib dose re-escalations were safe and tolerable in patients with advanced HCC.

Methods: Of the 73 advanced HCC patients treated with sorafenib, 42 achieved a tolerable dose with a dose reduction. We evaluated safety and tolerability in patients who attempted intra-patient dose re-escalations from the reduced dose.

Results: Thirteen of 42 patients increased the sorafenib dose from the reduced dose. Ten patients had a tolerable dose of 400 mg on alternate days, and 3 patients had a tolerable dose of 400 mg daily. Dose-limiting toxicity (DLT), defined as toxicity resulting in a dose reduction, was observed in 8 of 13 patients as a hand-foot skin reaction (HFSR), and DLT was noted in 2 of 13 patients as an increase in alanine aminotransferase/aspartate aminotransferase levels. Seven of 13 patients did not exhibit DLT after dose re-escalations. Although 6 patients exhibited DLT, the cause of the adverse event was HFSR in all cases. The median escalation dose ratio, which was calculated as the ratio of the real cumulative dose to the cumulative dose when continued at the tolerable dose after dose re-escalation, was 1.84.

Conclusions: The results of the present study indicated that intra-patient sorafenib dose re-escalations were safe and tolerable. Further prospective analyses are needed to determine in more detail the safety and efficacy of intra-patient sorafenib dose re-escalations.
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http://dx.doi.org/10.1007/s10147-014-0668-4DOI Listing
December 2014

Disulfiram eradicates tumor-initiating hepatocellular carcinoma cells in ROS-p38 MAPK pathway-dependent and -independent manners.

PLoS One 2014 13;9(1):e84807. Epub 2014 Jan 13.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Tumor-initiating cells (TICs) play a central role in tumor development, metastasis, and recurrence. In the present study, we investigated the effect of disulfiram (DSF), an inhibitor of aldehyde dehydrogenase, toward tumor-initiating hepatocellular carcinoma (HCC) cells. DSF treatment suppressed the anchorage-independent sphere formation of both HCC cells. Flow cytometric analyses showed that DSF but not 5-fluorouracil (5-FU) drastically reduces the number of tumor-initiating HCC cells. The sphere formation assays of epithelial cell adhesion molecule (EpCAM)(+) HCC cells co-treated with p38-specific inhibitor revealed that DSF suppresses self-renewal capability mainly through the activation of reactive oxygen species (ROS)-p38 MAPK pathway. Microarray experiments also revealed the enrichment of the gene set involved in p38 MAPK signaling in EpCAM(+) cells treated with DSF but not 5-FU. In addition, DSF appeared to downregulate Glypican 3 (GPC3) in a manner independent of ROS-p38 MAPK pathway. GPC3 was co-expressed with EpCAM in HCC cell lines and primary HCC cells and GPC3-knockdown reduced the number of EpCAM(+) cells by compromising their self-renewal capability and inducing the apoptosis. These results indicate that DSF impaired the tumorigenicity of tumor-initiating HCC cells through activation of ROS-p38 pathway and in part through the downregulation of GPC3. DSF might be a promising therapeutic agent for the eradication of tumor-initiating HCC cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084807PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890271PMC
September 2014

Coronal reformatted CT images contribute to the precise evaluation of the radiofrequency ablative margin for hepatocellular carcinoma.

Abdom Imaging 2014 Apr;39(2):262-8

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Objective: The purpose of the present study was to evaluate the usefulness of coronal reformatted images obtained from 64-slice multi-detector computed tomography to assess the ablative margin (AM) in hepatocellular carcinoma (HCC) treated with radio frequency ablation (RFA).

Methods: Ninety-five HCC nodules were analyzed in 66 HCC patients treated with RFA. Two radiologists and one hepatologist independently reviewed axial CT images with or without coronal reformatted images in HCC treated with RFA. Nodules were determined as AM-sufficient (≥5 mm) or AM-insufficient (<5 mm). The level of interobserver agreement was measured using the weighted kappa test. The sensitivity, specificity, and positive and negative predictive values (NPVs) of an insufficient AM (<5 mm) to predict local recurrence were evaluated.

Results: The numbers of AM-sufficient nodules judged by readers 1-3 based on axial images and both axial and coronal images were 56, 49, and 58, and 47, 33, and 48, respectively. Excellent agreement and good to excellent agreement were obtained among the three readers on axial image readings and both axial and coronal image readings, respectively. The mean sensitivity, specificity, and positive and NPVs of an insufficient AM on axial images and both axial and coronal images to predict local recurrence were 64%, 60%, 17%, and 93%, and 95%, 50%, 20%, and 97%, respectively.

Conclusions: Coronal reformatted CT images should be utilized to evaluate the AM in HCC treated with RFA in order to decrease the risk of local recurrence following treatment.
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http://dx.doi.org/10.1007/s00261-013-0054-0DOI Listing
April 2014

Efficacy of transcatheter arterial chemoembolization with miriplatin-lipiodol water-soluble contrast agent emulsion in patients with hepatocellular carcinoma.

Anticancer Res 2013 Dec;33(12):5603-9

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Aim: To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using miriplatin emulsion in unresectable hepatocellular carcinoma (HCC).

Patients And Methods: The efficacy of TACE was evaluated by dynamic computed tomography or magnetic resonance imaging three months after TACE, according to the Response Evaluation Criteria in Cancer Study Group of Japan (RECICL). Adverse events were assessed using Common Terminology Criteria, version 4.0.

Results: Eighteen patients with 48 lesions received TACE with miriplatin-lipiodol (LPD) suspension (miriplatin suspension) and 53 patients with 114 HCC tumors received TACE with miriplatin-LPD water-soluble contrast agent emulsion (miriplatin emulsion). TACE with miriplatin emulsion enabled for administration of a higher dose of miriplatin compared to TACE with miriplatin suspension (p=0.016), although there were no significant differences in the frequency of adverse events between the two groups. The treatment effect per tumor was significantly higher in the emulsion group than in the suspension group (p=0.001). The time-to-progression per tumor was significantly shorter in the suspension group than in the emulsion group (p=0.001).

Conclusion: TACE with miriplatin emulsion is more effective than that with miriplatin suspension.
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December 2013

Successful non-surgical treatment of ruptured pyogenic liver abscess.

Intern Med 2013 ;52(23):2619-22

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Japan.

A 72-year-old man with a fever and abdominal pain was referred to our hospital. On admission, the patient exhibited the clinical signs of septic shock. Computed tomography revealed a rim-and septal-enhanced lesion in the left lobe of the liver with hemorrhage along the hepatic capsule. Because Klebsiella pneumoniae was detected in both the blood and aspirated abdominal fluid, the patient was diagnosed with a ruptured pyogenic liver abscess. He was successfully treated with percutaneous abscess drainage and the systemic administration of antibiotics. Non-surgical treatment for a ruptured pyogenic liver abscess is therefore effective in at least some cases.
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http://dx.doi.org/10.2169/internalmedicine.52.0980DOI Listing
August 2014

Clinical features and natural history of portal vein thrombosis after radiofrequency ablation for hepatocellular carcinoma in Japan.

Hepatol Int 2013 Oct 28;7(4):1030-9. Epub 2013 Aug 28.

Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan.

Purpose: Little is known about portal vein thrombosis (PVT) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to determine the incidence, background, and natural history of RFA-related PVT.

Methods: This is a retrospective study of 317 patients (219 males and 98 females) with HCC treated by RFA. Clinical data were compared between patients with and without PVT detected by ultrasound/CT. The median follow-up period after RFA was 15.8 months.

Results: PVT was detected in 6 (1.9 %) of 317 patients, 6 (0.8 %) of 802 treatments for HCC, and 6 (0.6 %) of 964 sessions of RFA. Body mass index was significantly higher in patients with PVT (26.9 ± 3.1 kg/m(2)) than in those without (22.9 ± 3.5 kg/m(2), p = 0.0075). PVT was significantly more frequent in RFA for the left lobe of the liver (2.7 %) than for the other sites (0 %, p < 0.0001). Five of the six patients received no treatment for PVT, with natural outcomes of disappearance in one patient, improvement in one patient, and unchanged appearance in three patients. Anticoagulation was applied in the one remaining patient and resulted in a successful recanalization. In the six patients, there was no significant difference in hepatic functional reserve between baseline and time of detection of PVT.

Conclusions: These results indicated that a high body mass index and RFA for HCC in the left lobe might be significant risk factors for PVT and that RFA-related PVT was rarely progressive with little influence on liver function.
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http://dx.doi.org/10.1007/s12072-013-9470-zDOI Listing
October 2013

Metformin, a diabetes drug, eliminates tumor-initiating hepatocellular carcinoma cells.

PLoS One 2013 29;8(7):e70010. Epub 2013 Jul 29.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Metformin has been widely used as an oral drug for diabetes mellitus for approximately 60 years. Interestingly, recent reports showed that metformin exhibited an anti-tumor action in a wide range of malignancies including hepatocellular carcinoma (HCC). In the present study, we investigated its impact on tumor-initiating HCC cells. Metformin suppressed cell growth and induced apoptosis in a dose-dependent manner. Flow cytometric analysis showed that metformin treatment markedly reduced the number of tumor-initiating epithelial cell adhesion molecule (EpCAM)(+) HCC cells. Non-adherent sphere formation assays of EpCAM(+) cells showed that metformin impaired not only their sphere-forming ability, but also their self-renewal capability. Consistent with this, immunostaining of spheres revealed that metformin significantly decreased the number of component cells positive for hepatic stem cell markers such as EpCAM and α-fetoprotein. In a xenograft transplantation model using non-obese diabetic/severe combined immunodeficient mice, metformin and/or sorafenib treatment suppressed the growth of tumors derived from transplanted HCC cells. Notably, the administration of metformin but not sorafenib decreased the number of EpCAM(+) cells and impaired their self-renewal capability. As reported, metformin activated AMP-activated protein kinase (AMPK) through phosphorylation; however its inhibitory effect on the mammalian target of rapamycin (mTOR) pathway did not necessarily correlate with its anti-tumor activity toward EpCAM(+) tumor-initiating HCC cells. These results indicate that metformin is a promising therapeutic agent for the elimination of tumor-initiating HCC cells and suggest as-yet-unknown functions other than its inhibitory effect on the AMPK/mTOR pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0070010PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726625PMC
March 2014

Initial response to sorafenib by using enhancement criteria in patients with hepatocellular carcinoma.

Hepatol Int 2013 Jun 12;7(2):703-13. Epub 2013 Feb 12.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Purpose: Sorafenib induces early vascularity reduction in patients with hepatocellular carcinoma (HCC). We sought to identify differences in radiological assessment approaches and to evaluate their usefulness for the prediction of the initial response to sorafenib.

Methods: Forty-eight patients with advanced HCC treated with sorafenib were evaluated by four-phase contrast-enhanced computed tomography. All target lesions were analyzed using the Response Evaluation Criteria in Solid Tumors (RECIST), the EASL criteria, and modified RECIST (mRECIST).

Results: At the initial evaluation at 4-6 weeks, rates of objective response (OR) (including both complete and partial responses), stable disease (SD), and progressive disease (PD) were 2, 71, and 27 %, respectively, according to RECIST; 15, 56, and 29 %, respectively, according to the EASL criteria; and 15, 58, and 27 %, respectively, according to mRECIST. Patients who achieved an OR according to the EASL criteria also achieved an OR according to mRECIST. Patients who achieved an OR according to the EASL criteria or mRECIST had better predicted overall survival (OS) than did patients who achieved SD (p = 0.033 and 0.028, respectively). Patients with SD according to RECIST had different outcomes depending on the response according to enhancement criteria. Patients classified as responders (complete and partial) had better predicted OS than those classified as non-responders (those classified as SD and PD) (p = 0.048).

Conclusions: The enhancement criteria could be useful for prediction of the initial response to sorafenib in patients with HCC. Moreover, mRECIST appears to be simple and convenient.
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http://dx.doi.org/10.1007/s12072-013-9425-4DOI Listing
June 2013

Successful resection of intracranial metastasis of hepatocellular carcinoma.

Case Rep Gastroenterol 2013 Jan 28;7(1):182-7. Epub 2013 Mar 28.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Intracranial metastasis of hepatocellular carcinoma (HCC) is rare, but has an extremely poor prognosis. We report a case with successful surgical removal of intracranial metastasis of HCC. A 32-year-old man was admitted to our hospital with severe vomiting. He had been followed for liver cirrhosis due to hepatitis B virus infection and received a right hepatic trisectionectomy for HCC 1 year earlier. For the recurrence of HCC, sorafenib had been administered 6 months before admission. On admission, he exhibited consciousness disturbance, which gradually worsened. Two days later, both computed tomography and magnetic resonance imaging revealed an intra-axial tumor with perifocal edema and hemorrhage in the left frontal lobe. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of moderately differentiated HCC cells. The day after surgical resection of the tumor, his consciousness returned to normal. Subsequently, he was treated with hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin using an implanted port-catheter system. Surgical resection of intracranial metastasis of HCC would be important and meaningful in some cases.
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http://dx.doi.org/10.1159/000350673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635693PMC
January 2013