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Masaya Sato,
Naoya Kato,
Ryosuke Tateishi,
Ryosuke Muroyama,
Norie Kowatari,
Wenwen Li,
Kaku Goto,
Motoyuki Otsuka, Shuichiro Shiina,
Haruhiko Yoshida,
Masao Omata,
Kazuhiko Koike
[show abstract]
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ABSTRACT: BACKGROUND: IL28B polymorphisms were shown to be associated with a response to peg-interferon-based treatment in chronic hepatitis C (CHC) and spontaneous clearance. However, little is known about how this polymorphism affects the course of CHC, including the development of hepatocellular carcinoma (HCC). We evaluated the influence of IL28B polymorphisms on hepatocarcinogenesis in CHC patients. METHODS: We genotyped the rs8099917 single-nucleotide polymorphism in 351 hepatitis C-associated HCC patients without history of IFN-based treatment, and correlated the age at onset of HCC in patients with each genotype. RESULTS: Frequencies of TT, TG, and GG genotypes were 74.3 % (261/351), 24.8 % (87/351), and 0.9 % (3/351), respectively. The mean ages at onset of HCC for TT, TG, and GG genotypes were 69.9, 67.5 and 66.8, respectively. In multivariate analysis, IL28B minor allele (TG and GG genotypes) was an independent risk factor for younger age at onset of HCC (P = 0.02) in males (P < 0.001) with higher body mass index (BMI; P = 0.009). The IL28B minor allele was also associated with a lower probability of having aspartate aminotransferase-to-platelet ratio index (APRI) >1.5 (minor vs. major, 46.7 vs. 58.6 %; P = 0.01), lower AST (69.1 vs. 77.7 IU/L, P = 0.02), lower ALT (67.8 vs. 80.9 IU/L, P = 0.002), higher platelet count (12.8 vs. 11.2 × 10(4)/μL, P = 0.002), and higher prothrombin time (79.3 vs. 75.4 %, P = 0.002). CONCLUSIONS: The IL28B minor allele was associated with lower inflammatory activity and less progressed fibrosis of the liver; however, it constituted a risk factor for younger-age onset of HCC in CHC patients.
Journal of Gastroenterology 05/2013; · 4.16 Impact Factor
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Takamasa Ohki,
Ryosuke Tateishi,
Masaaki Akahane,
Shintaro Mikami,
Masaya Sato,
Koji Uchino,
Toru Arano,
Kenichiro Enooku,
Yuji Kondo,
Noriyo Yamashiki,
Tadashi Goto, Shuichiro Shiina,
Haruhiko Yoshida,
Yutaka Matsuyama,
Masao Omata,
Kuni Ohtomo,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVES:The combination of computed tomography with hepatic arteriography and arterial portography (CTHA/CTAP) can detect additional hepatocellular carcinoma (HCC) nodules undetected by conventional dynamic CT.METHODS:In this single-center, randomized, open-label, controlled trial, we randomly assigned 280 patients who were diagnosed as having HCC by conventional dynamic CT, and eligible for radiofrequency ablation (RFA), to undergo CTHA/CTAP before treatment, or to the control group. Newly detected HCC nodules by CTHA/CTAP were intended to be ablated completely. The primary end point was recurrence-free survival and the key secondary end point was overall survival. The analysis was conducted on an intention-to-treat basis. Those with nonablated nodules were treated as for recurrence.RESULTS:A total of 75 nodules were newly diagnosed as HCC by CTHA/CTAP in 45 patients. Three patients (one in the CTHA/CTAP group and two in the control group) who refused treatment were excluded from all analyses. The cumulative recurrence-free survival rates at 1, 2, and 3 years were 60.1, 29.0, and 18.9% in the CTHA/CTAP group and 52.2, 29.7, and 23.1% in the control group, respectively (P=0.66 by log-rank test; hazard ratio, 0.94 for CTHA/CTAP vs. control; 95% confidence interval (CI), 0.73-1.22). The cumulative overall survival rates at 3 and 5 years were 79.7 and 56.4% in the CTHA/CTAP group and 86.8 and 60.1% in the control group, respectively (P=0.50; hazard ratio, 1.15, 95% CI, 0.77-1.71).CONCLUSIONS:CTHA/CTAP may detect recurrent lesions earlier. However, CTHA/CTAP before RFA did not improve cumulative recurrence-free survival or overall survival.Am J Gastroenterol advance online publication, 30 April 2013; doi:10.1038/ajg.2013.109.
The American Journal of Gastroenterology 04/2013; · 7.28 Impact Factor
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Nippon Geka Gakkai zasshi 03/2013; 114(2):107-11.
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Ryosuke Tateishi, Shuichiro Shiina,
Masaaki Akahane,
Jiro Sato,
Yuji Kondo,
Ryota Masuzaki,
Hayato Nakagawa,
Yoshinari Asaoka,
Tadashi Goto,
Kuni Otomo,
Masao Omata,
Haruhiko Yoshida,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: In the treatment of hepatocellular carcinoma (HCC), hepatic resection has the advantage over radiofrequency ablation (RFA) in terms of systematic removal of a hepatic segment.
We enrolled 303 consecutive patients of a single naïve HCC that had been treated by RFA at The University of Tokyo Hospital from 1999 to 2004. Recurrence was categorized as either intra- or extra-subsegmental as according to the Couinaud's segment of the original nodule. To assess the relationship between the subsegments of the original and recurrent nodules, we calculated the kappa coefficient. We assessed the risk factors for intra- and extra-subsegmental recurrence independently using univariate and multivariate Cox proportional hazard regression. We also assessed the impact of the mode of recurrence on the survival outcome.
During the follow-up period, 201 patients in our cohort showed tumor recurrence distributed in a total of 340 subsegments. Recurrence was categorized as exclusively intra-subsegmental, exclusively extra-subsegmental, and simultaneously intra- and extra-subsegmental in 40 (20%), 110 (55%), and 51 (25%) patients, respectively. The kappa coefficient was measured at 0.135 (95% CI, 0.079-0.190; P<0.001). Multivariate analysis revealed that of the tumor size, AFP value and platelet count were all risk factors for both intra- and extra-subsegmental recurrence. Of the patients in whom recurrent HCC was found to be exclusively intra-subsegmental, extra-subsegmental, and simultaneously intra- and extra-subsegmental, 37 (92.5%), 99 (90.8%) and 42 (82.3%), respectively, were treated using RFA. The survival outcomes after recurrence were similar between patients with an exclusively intra- or extra-subsegmental recurrence.
The effectiveness of systematic subsegmentectomy may be limited in the patients with both HCC and chronic liver disease who frequently undergo multi-focal tumor recurrence.
PLoS ONE 01/2013; 8(4):e59040. · 4.09 Impact Factor
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The American Journal of Gastroenterology 10/2012; 107(10):1590. · 7.28 Impact Factor
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Kazuya Okushin,
Yoshinari Asaoka,
Izumi Fukuda,
Naoto Fujiwara,
Tatsuya Minami,
Masaya Sato,
Shintaro Mikami,
Koji Uchino,
Kenichiro Enooku,
Yuji Kondo,
Ryosuke Tateishi,
Tadashi Goto, Shuichiro Shiina,
Haruhiko Yoshida,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: Hypoglycemia is a rare paraneoplastic manifestation of patients with neoplasms. Hypoglycemia can be induced by several causes, including an aberrant increase of hypoglycemic agents and adrenal insufficiency. Sorafenib is the first agent to demonstrate a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC). This small molecule inhibits serine/threonine kinase RAF in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature and decreases tumor growth and angiogenesis. In this paper, we report a case of HCC who was treated with sorafenib and showed severe hypoglycemia. This hypoglycemia might be induced by two causes, both adrenal insufficiency as an adverse effect of sorafenib and activation of the insulin-like growth factor (IGF) signal by excessive secretion of incompletely processed precursors of IGF-II. Although the IGF signal is suggested to be involved in aberrant growth of HCC in some cases, there is no other report showing the influence of sorafenib on HCC with active IGF signal. Unfortunately, the effect of sorafenib was limited in the present case. However, emerging drugs that directly inhibit the IGF signal can be expected to be highly effective in the treatment of HCC with hypoglycemia.
Case Reports in Gastroenterology 09/2012; 6(3):784-9.
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Shuichiro Shiina,
Ryosuke Tateishi,
Masatoshi Imamura,
Takuma Teratani,
Yukihiro Koike,
Shinpei Sato,
Shuntaro Obi,
Fumihiko Kanai,
Naoya Kato,
Haruhiko Yoshida,
Masao Omata,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: Ethanol injection is the best-known image-guided percutaneous ablation for hepatocellular carcinoma (HCC) and a well-tolerated, inexpensive procedure with few adverse effects. However, there have been few reports on its long-term results.
We report a 20-year consecutive case series at a tertiary referral centre.
We performed 2147 ethanol injection treatments on 685 primary HCC patients and analysed a collected database.
Final computed tomography demonstrated complete ablation of treated tumours in 2108 (98.2%) of the 2147 treatments. With a median follow-up of 51.6 months, 5-, 10- and 20-year survival rates were 49.0% [95% confidence interval (CI) = 45.3-53.0%], 17.9% (95% CI = 15.0-21.2%) and 7.2% (95% CI = 4..5-11.5%) respectively. Multivariate analysis demonstrated that age, Child-Pugh class, tumour size, tumour number and serum alpha-fetoprotein level were significant prognostic factors for survival. Five-, 10- and 20-year local tumour progression rates were 18.2% (95% CI = 15.0-21.4%), 18.4% (95% CI = 15.2-21.6%) and 18.4% (95% CI = 15.2-21.6%) respectively. Five-, 10- and 20-year distant recurrence rates were 53.5% (95% CI = 49.4-57.7%), 60.4 (95% CI = 56.3-64.5%) and 60.8% (95% CI = 56.7-64.9%) respectively. There were 45 complications (2.1%) and two deaths (0.09%).
Ethanol injection was potentially curative for HCC, resulting in survival for more than 20 years. This study suggests that new ablation therapies will achieve similar or even better long-term results in HCC.
Liver international: official journal of the International Association for the Study of the Liver 06/2012; 32(9):1434-42. · 3.82 Impact Factor
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[show abstract]
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ABSTRACT: Three tumor markers for hepatocellular carcinoma (HCC) are available in Japan: alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonists-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). Although AFP has drawbacks in its specificity, it is widely utilized in treatment evaluation and prognosis prediction. PIVKA-II is a unique marker that does not correlate with AFP value and can predict microvascular invasion. AFP-L3 is a highly specific marker and strong predictor of poor prognosis. These three markers are indispensable in every aspect of clinical practice of hepatocellular carcinoma including surveillance, diagnosis, treatment evaluation, and prognosis prediction.
Nippon rinsho. Japanese journal of clinical medicine 05/2012; 70(5):821-7.
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Yoko Soroida,
Ryunosuke Ohkawa,
Hayato Nakagawa,
Yumiko Satoh,
Haruhiko Yoshida,
Hiroto Kinoshita,
Ryosuke Tateishi,
Ryota Masuzaki,
Kenichiro Enooku, Shuichiro Shiina,
Takahisa Sato,
Shuntaro Obi,
Tadashi Hoshino,
Ritsuko Nagatomo,
Shigeo Okubo,
Hiromitsu Yokota,
Kazuhiko Koike,
Yutaka Yatomi,
Hitoshi Ikeda
[show abstract]
[hide abstract]
ABSTRACT: Mitochondrial isoenzyme of creatine kinase (MtCK) is reportedly highly expressed in hepatocellular carcinoma (HCC). Clinical relevance of serum MtCK activity in patients with HCC was assessed using a novel immuno-inhibition method.
Among patients with cirrhosis caused by hepatitis B or C virus, 147 patients with HCC (12 with the first occurrence and 135 with recurrence) and 92 patients without HCC were enrolled.
Serum MtCK activity was higher in cirrhotic patients with HCC than in those without HCC or healthy subjects. Elevated serum MtCK activity in HCC patients decreased after radiofrequency ablation. In case of prediction of HCC, MtCK had a sensitivity of 62.6% and a specificity of 70.7% at a cut-off point of 8.0 U/L, with an area under the receiver operating curve of 0.722 vs. 0.713 for alpha-fetoprotein (AFP) and 0.764 for des-gamma-carboxy prothrombin (DCP). Among the HCC patients, serum MtCK activity was elevated in 52.9% individuals with serum AFP level < 20 ng/ml and 63.2% individuals with serum DCP level < 40 mAu/ml. Even in patients with a single HCC ≤ 2 cm, the sensitivity of serum MtCK activity for the prediction of HCC was 64.4%, which was comparable to the overall sensitivity. This increased activity was due to an increase in ubiquitous MtCK, not sarcomeric MtCK, and the enhanced mRNA expression of ubiquitous MtCK was observed in cell lines originating from HCCs in contrast to healthy liver tissues.
Serum MtCK activity merits consideration as a novel marker for HCC to be further tested as for its diagnostic and prognostic power.
Journal of Hepatology 04/2012; 57(2):330-6. · 9.26 Impact Factor
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Ryota Masuzaki,
Ryosuke Tateishi,
Haruhiko Yoshida,
Toru Arano,
Koji Uchino,
Kenichiro Enooku,
Eriko Goto,
Hayato Nakagawa,
Yoshinari Asaoka,
Yuji Kondo,
Tadashi Goto,
Hitoshi Ikeda, Shuichiro Shiina,
Masao Omata,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC).
Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled. Liver stiffness was obtained noninvasively by using Fibroscan (Echosens, Paris, France). The date of blood transfusion was obtained by interview. Duration of infection was derived from the interval between the date of blood transfusion and the date of liver stiffness measurement (LSM). Patients were stratified into four groups based on the duration of infection (17-29 years; 30-39 years; 40-49 years; and 50-70 years). The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness.
A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis (225 with HCC and 291 without). The patients were 244 men and 272 women, with a mean age of 67.8 ± 9.5 years. The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in non-HCC group). The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC (r = 0.132, P = 0.024) but not in patients with HCC (r = -0.103, P = 0.123). Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001). The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001), duration of infection (P = 0.0015), and heavy alcohol consumption (P = 0.043).
Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.
World Journal of Gastroenterology 03/2012; 18(12):1385-90. · 2.47 Impact Factor
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Koji Uchino,
Shuntaro Obi,
Ryosuke Tateishi,
Shinpei Sato,
Miho Kanda,
Takahisa Sato,
Toru Arano,
Kenichiro Enooku,
Eriko Goto,
Ryota Masuzaki,
Hayato Nakagawa,
Yoshinari Asaoka,
Yuji Kondo,
Noriyo Yamashiki,
Tadashi Goto, Shuichiro Shiina,
Masao Omata,
Haruhiko Yoshida,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: In Japan, sorafenib is now the first-line therapy for individuals with advanced hepatocellular carcinoma (HCC), but no other treatment is available for such patients. The aim of this study was to assess the efficacy and safety of combination therapy with systemic continuous intravenous infusion of 5-fluorouracil (5-FU) and subcutaneous peginterferon alfa-2a, which was used before sorafenib was introduced to Japan.
Two hundred and twenty-three HCC patients, who were not amenable to curative surgery, percutaneous ablation, or transarterial chemoembolization (TACE), and for whom intraarterial chemotherapy was not indicated because of the presence of extrahepatic metastasis or stenosis of the common hepatic artery, received peginterferon alfa-2a (90 μg subcutaneously on days 1, 8, 15, and 22) and 5-FU (500 mg/day intravenously given continuously on days 1-5 and 8-12). We assessed their response to treatment and survival, and treatment safety.
The response rate was 9.4 % (including six patients with complete response) and the disease-control rate was 32.7 %. The median time to progression was 2.0 months. The overall median survival time was 6.5 months (Child-Pugh class A: 9.2 months vs. Child-Pugh class B: 2.8 months). In a multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status >0, Child-Pugh class B, and the presence of macroscopic vascular invasion were independent predictors of poor prognosis. The major grade 3-4 adverse events were leucopenia (13.9 %) and thrombocytopenia (5.8 %). No treatment-related deaths occurred.
This combination therapy was well tolerated and showed promising efficacy. Further studies are needed to establish the usefulness of this treatment.
Journal of Gastroenterology 03/2012; 47(10):1152-9. · 4.16 Impact Factor
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Eriko Goto,
Ryota Masuzaki,
Ryosuke Tateishi,
Yuji Kondo,
Jun Imamura,
Tadashi Goto,
Hitoshi Ikeda,
Masaaki Akahane, Shuichiro Shiina,
Masao Omata,
Haruhiko Yoshida,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: We evaluated the sensitivity and specificity of post-vascular phase (Kupffer imaging) by contrast-enhanced ultrasonography (CEUS) using perflubutane microbubbles (Sonazoid) in comparison with conventional B-mode ultrasonography (US) for the detection of hepatocellular carcinoma (HCC) nodules.
A total of 100 treatment-naïve HCC patients admitted at our hospital between December 2007 and June 2009 were consecutively enrolled. The sensitivity and specificity of conventional and contrast-enhanced US were evaluated on a liver segment basis using dynamic CT as a reference standard. Movie files of conventional and enhanced US were stored separately for each segment (e.g., lateral, medial, anterior, and posterior) and reviewed randomly by two blinded readers.
A total of 138 HCC nodules (mean diameter 20.3 mm) were detected in 123 of 400 segments. Detection sensitivity of B-mode US was 0.837 for reader A and 0.846 for reader B, and that of CEUS was 0.732 for reader A and 0.831 for reader B. Specificity of B-mode US was 0.902 for reader A and 0.949 for reader B, and that of CEUS was 0.986 for reader A and 0.978 for reader B. CEUS false positives were mainly due to misidentification of hepatic cysts. A significant proportion of false-negative nodules are hyperechoic in B-mode US, likely because echogenicity hampers visualization of the defect in Kupffer imaging.
Kupffer imaging by CEUS with Sonazoid showed very high specificity but rather mediocre sensitivity for HCC detection. CEUS is highly suitable for confirmatory diagnosis of HCC; however, caution should be exercised in reaching a diagnosis based only on CEUS.
Journal of Gastroenterology 12/2011; 47(4):477-85. · 4.16 Impact Factor
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Shuichiro Shiina,
Ryosuke Tateishi,
Toru Arano,
Koji Uchino,
Kenichiro Enooku,
Hayato Nakagawa,
Yoshinari Asaoka,
Takahisa Sato,
Ryota Masuzaki,
Yuji Kondo,
Tadashi Goto,
Haruhiko Yoshida,
Masao Omata,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: Radiofrequency ablation (RFA) is widely performed for hepatocellular carcinoma (HCC). However, there has been no report on 10-year outcome of RFA. The objective of this study was to report a 10-year consecutive case series at a tertiary referral center.
We performed 2,982 RFA treatments on 1,170 primary HCC patients and analyzed a collected database.
Final computed tomography images showed complete tumor ablation in 2,964 (99.4%) of 2,982 treatments performed for the 1,170 primary HCC patients. With a median follow-up of 38.2 months, 5- and 10-year survival rates were 60.2% (95% confidence interval (CI): 56.7-63.9%) and 27.3% (95% CI: 21.5-34.7%), respectively. Multivariate analysis demonstrated that age, antibody to hepatitis C virus (anti-HCV), Child-Pugh class, tumor size, tumor number, serum des-γ-carboxy-prothrombin (DCP) level, and serum lectin-reactive α-fetoprotein level (AFP-L3) were significantly related to survival. Five- and 10-year local tumor progression rates were both 3.2% (95% CI: 2.1-4.3%). Serum DCP level alone was significantly related to local tumor progression. Five- and 10-year distant recurrence rates were 74.8% (95% CI: 71.8-77.8%) and 80.8% (95% CI: 77.4-84.3%), respectively. Anti-HCV, Child-Pugh class, platelet count, tumor size, tumor number, serum AFP level, and serum DCP level were significantly related to distant recurrence. There were 67 complications (2.2%) and 1 death (0.03%).
RFA could be locally curative for HCC, resulting in survival for as long as 10 years, and was a safe procedure. RFA might be a first-line treatment for selected patients with early-stage HCC.
The American Journal of Gastroenterology 12/2011; 107(4):569-77; quiz 578. · 7.28 Impact Factor
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Shuichiro Shiina,
Ryosuke Tateishi,
Toru Arano,
Koji Uchino,
Kenichiro Enooku,
Hayato Nakagawa,
Yoshinari Asaoka,
Takahisa Sato,
Ryota Masuzaki,
Yuji Kondo,
Tadashi Goto,
Haruhiko Yoshida,
Masao Omata,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVES: Radiofrequency ablation (RFA) is widely performed for hepatocellular carcinoma (HCC). However, there has been no report on 10-year outcome of RFA. The objective of this study was to report a 10-year consecutive case series at a tertiary referral center.
The American Journal of Gastroenterology 12/2011; 107(4):569-577. · 7.28 Impact Factor
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[show abstract]
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ABSTRACT: We evaluated the usefulness of tumor marker doubling time (DT) as an efficacy indicator of a molecular targeted anticancer agent.
Twenty-five patients with advanced hepatocellular carcinoma (HCC) received TSU-68, a multiple tyrosine kinase inhibitor. Exponential increase in HCC-specific tumor marker levels (alpha-fetoprotein or des-gamma-carboxyprothrombin) was seen in 15 of them prior to TSU-68 administration. The relationship between tumor marker DT and tumor volume DT was evaluated. Next, tumor marker DT in the first 8 weeks of TSU-68 administration was compared with tumor marker DT before treatment. Efficacy evaluation based on changes in tumor marker DT was compared with Response Evaluation Criteria In Solid Tumors (RECIST).
Tumor marker DT and tumor volume DT were almost identical (r(2) = 0.94, P < 0.001) in each patient before TSU-68 administration. Efficacy evaluation based on changes in tumor marker DT on TSU-68 administration was in accordance with RECIST in 12/15 cases. Discordance was observed in three cases, for which RECIST indicated disease progression in spite of elongated tumor marker DT. Those cases showed substantial tumor necrosis without volume shrinkage or appearance of new lesions in spite of apparent effects on target lesions.
Serum tumor marker DT can be used to evaluate viable tumor burden irrespective of the presence of tumor necrosis which can compromise radiographic evaluation. This approach may be applicable to the evaluation of responses to chemotherapy, particularly to cytostatic agents (ClinicalTrials.gov number, NCT00784290).
Journal of Gastroenterology 09/2011; 47(1):71-8. · 4.16 Impact Factor
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[show abstract]
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ABSTRACT: A 64-year-old man with 6-year history of hepatocellular carcinoma (HCC) was referred to us regarding bone metastasis to the right proximal femur. Although he underwent radiotherapy for pain palliation and local tumor control, the pain persisted and the tumor relapsed 3 months after the radiotherapy and he was thought to be at high risk of pathologic fracture. Given hypervascularity and large tumor size, a prophylactic internal fixation combined with adjuvant radiofrequency ablation (RFA) was proposed to reduce blood loss and prevent viable tumor cells being disseminated. His postoperative course was uneventful without requiring blood transfusion and preoperative symptoms immediately disappeared after surgery. He became capable of weight-bearing walk with a single cane and was almost asymptomatic without local progression on the plain radiographs when he died 14 months after surgery. Combination therapy of RFA and internal fixation using intramedullary nailing for metastases of the long bones from HCC seems to be a very promising technique both for sufficient pain relief and for local control of the tumor. Adjuvant RFA may become a potential option for patients with metastases of the long bones for the purpose of prevention of tumor dissemination and reduction of intraoperative blood loss.
International Journal of Clinical Oncology 09/2011; 17(4):417-21. · 1.41 Impact Factor
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Takamasa Ohki,
Ryosuke Tateishi,
Masaaki Akahane, Shuichiro Shiina,
Noriyo Yamashiki,
Shintaro Mikami,
Kenichiro Enooku,
Eriko Goto,
Ryota Masuzaki,
Yuji Kondo,
Tadashi Goto,
Shinichi Inoo,
Kuni Ohtomo,
Masao Omata,
Haruhiko Yoshida,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND AND AIMS: This study was part of an on-going randomized controlled trial to investigate the utility of computed tomography (CT) during hepatic arteriography and arterial portography (CTHA/CTAP) as a pre-treatment examination for patients with small hepatocellular carcinoma (HCC). METHODS: A total of 137 patients with HCC who were diagnosed by dynamic CT showing hyperattenuation in the arterial phase and hypoattenuation in the equilibrium phase, were Child-Pugh class A, and had three or less tumors with diameters ≤ 3.0 cm were randomly assigned to undergo CTHA/CTAP. We compared the diagnostic utilities of CTHA/CTAP and dynamic CT. Univariate and multivariate logistic regression analyses with stepwise variable selection were performed to identify factors related to the detection of additional nodules. RESULTS: The total number of HCCs at the time of diagnosis with contrast-enhanced dynamic CT was 197. 75 nodules with a mean diameter of 8.7 mm (range 2-20) in 45 patients (32.8%) were additionally diagnosed as definite HCC on CTHA/CTAP compared with dynamic CT. A retrospective review revealed that 54 nodules could have been identified on arterial or equilibrium phase of the previous dynamic CT, whereas 21 were indiscernible. Multivariate logistic regression analysis revealed that multinodularity on dynamic CT [odds ratio (OR) = 5.35, P = 0.002], recurrent case as opposed to initial case (OR = 2.16, P = 0.06), and seronegativity for hepatitis B surface antigen (OR = 10.0, P = 0.03) were associated with the detection of additional nodules. CONCLUSION: CTHA/CTAP may be useful for detecting additional nodules prior to percutaneous ablation in patients with multinodular HCC on dynamic CT, in recurrent cases, and in hepatitis B surface antigen-negative cases.
Hepatology International 08/2011; · 2.64 Impact Factor
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Hitoshi Ikeda,
Ryosuke Tateishi,
Kenichiro Enooku,
Haruhiko Yoshida,
Hayato Nakagawa,
Ryota Masuzaki,
Yuji Kondo,
Tadashi Goto, Shuichiro Shiina,
Yukio Kume,
Tomoaki Tomiya,
Yukiko Inoue,
Takako Nishikawa,
Natsuko Ohtomo,
Yasushi Tanoue,
Tomoko Ono,
Kazuhiko Koike,
Yutaka Yatomi
[show abstract]
[hide abstract]
ABSTRACT: Chronic liver injury evokes a wound healing response, promoting fibrosis and finally hepatocellular carcinoma (HCC), in which hepatic stellate cells play an important role. Although a blood marker of hepatic stellate cells is not known, those cells importantly contribute to the regulation of plasma a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) activity, a defect of which causes thrombotic thrombocytopenic purpura.
Plasma ADAMTS13 was evaluated in chronic hepatitis B or C patients with or without HCC.
Plasma ADAMTS13 activity significantly correlated with serum aspartate aminotransferase and alanine aminotransferase, liver stiffness value, and aspartate aminotransferase-to-platelet ratio index, irrespective of the presence of HCC, suggesting that it may reflect hepatocellular damage and subsequent wound healing and fibrosis as a result of hepatic stellate cell action. During the three-year follow-up period for patients without HCC, it developed in 10 among 81 patients. Plasma ADAMTS13 activity was significantly higher in patients with HCC development than in those without and was a significant risk for HCC development by univariate and multivariate analyses. Furthermore, during the one-year follow-up period for patients with HCC treated with radiofrequency ablation, HCC recurred in 55 among 107 patients. Plasma ADAMTS13 activity or antigen level was significantly higher in patients with HCC recurrence than in those without and was retained as a significant risk for HCC recurrence by multivariate analysis.
Higher plasma ADAMTS13 activity and antigen level was a risk of HCC development in chronic liver disease.
Plasma ADAMTS13 as a potential marker of hepatic stellate cells may be useful in the prediction of hepatocarcinogenesis.
Cancer Epidemiology Biomarkers & Prevention 08/2011; 20(10):2204-11. · 4.12 Impact Factor
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Yotaro Kudo,
Yasuo Tanaka,
Keisuke Tateishi,
Keisuke Yamamoto,
Shinzo Yamamoto,
Dai Mohri,
Yoshihiro Isomura,
Motoko Seto,
Hayato Nakagawa,
Yoshinari Asaoka, [......],
Yoshihiro Hirata,
Motoyuki Otsuka,
Tsuneo Ikenoue,
Shin Maeda, Shuichiro Shiina,
Haruhiko Yoshida,
Osamu Nakajima,
Fumihiko Kanai,
Masao Omata,
Kazuhiko Koike
[show abstract]
[hide abstract]
ABSTRACT: Some clinical findings have suggested that systemic metabolic disorders accelerate in vivo tumor progression. Deregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is implicated in both metabolic dysfunction and carcinogenesis in humans; however, it remains unknown whether the altered metabolic status caused by abnormal activation of the pathway is linked to the protumorigenic effect.
We established hepatocyte-specific Pik3ca transgenic (Tg) mice harboring N1068fs*4 mutation.
The Tg mice exhibited hepatic steatosis and tumor development. PPARγ-dependent lipogenesis was accelerated in the Tg liver, and the abnormal profile of accumulated fatty acid (FA) composition was observed in the tumors of Tg livers. In addition, the Akt/mTOR pathway was highly activated in the tumors, and in turn, the expression of tumor suppressor genes including Pten, Xpo4, and Dlc1 decreased. Interestingly, we found that the suppression of those genes and the enhanced in vitro colony formation were induced in the immortalized hepatocytes by the treatment with oleic acid (OA), which is one of the FAs that accumulated in tumors.
Our data suggest that the unusual FA accumulation has a possible role in promoting in vivo hepato-tumorigenesis under constitutive activation of the PI3K pathway. The Pik3ca Tg mice might help to elucidate molecular mechanisms by which metabolic dysfunction contributes to in vivo tumor progression.
Journal of Hepatology 05/2011; 55(6):1400-8. · 9.26 Impact Factor
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Haruhiko Yoshida,
Yasushi Shiratori,
Masatoshi Kudo, Shuichiro Shiina,
Toshihiko Mizuta,
Masamichi Kojiro,
Kyosuke Yamamoto,
Yukihiro Koike,
Kenichi Saito,
Nozomu Koyanagi, [......],
Shotaro Sakisaka,
Hiroshi Ikeda,
Hidekatsu Kuroda,
Hiroyuki Kokuryu,
Tatsuya Yamashita,
Isao Sakaida,
Tetsuo Katamoto,
Kentaro Kikuchi,
Minoru Nomoto,
Masao Omata
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ABSTRACT: Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even after curative treatment. Vitamin K2, which has been reported to reduce HCC development, may be effective in preventing HCC recurrence. Patients who underwent curative ablation or resection of HCC were randomly assigned to receive placebo, 45 mg/day, or 90 mg/day vitamin K2 in double-blind fashion. HCC recurrence was surveyed every 12 weeks with dynamic computed tomography/magnetic resonance imaging, with HCC-specific tumor markers monitored every 4 weeks. The primary aim was to confirm the superiority of active drug to placebo concerning disease-free survival (DFS), and the secondary aim was to evaluate dose-response relationship. Disease occurrence and death from any cause were treated as events. Hazard ratios (HRs) for disease occurrence and death were calculated using a Cox proportional hazards model. Enrollment was commenced in March 2004. DFS was assessed in 548 patients, including 181 in the placebo group, 182 in the 45-mg/day group, and 185 in the 90-mg/day group. Disease occurrence or death was diagnosed in 58, 52, and 76 patients in the respective groups. The second interim analysis indicated that vitamin K2 did not prevent disease occurrence or death, with an HR of 1.150 (95% confidence interval: 0.843-1.570, one-sided; P=0.811) between the placebo and combined active-drug groups, and the study was discontinued in March 2007. CONCLUSION: Efficacy of vitamin K2 in suppressing HCC recurrence was not confirmed in this double-blind, randomized, placebo-controlled study.
Hepatology 05/2011; 54(2):532-40. · 11.66 Impact Factor
