Masao Omata

Publications (565)2301.06 Total impact

• Article: CT With Hepatic Arterioportography as a Pretreatment Examination for Hepatocellular Carcinoma Patients: A Randomized Controlled Trial.

  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
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  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
• Article: Treatment of hepatitis C virus infection in the future.

  Tatsuo Kanda, Osamu Yokosuka, Masao Omata
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  ABSTRACT: Two direct-acting antivirals (DAAs) against hepatitis C virus (HCV): telaprevir and boceprevir, are now available in combination with peginterferon plus ribavirin for the treatment of chronic hepatitis C infection. Although these drugs are potent inhibitors of HCV replication, they occasionally result in severe adverse events. In the present clinical trials, in their stead, several second-generation DAAs are being investigated. Most of them are being viewed with high expectations, but they also require the combination with peginterferon plus ribavirin. In the near future, we might be using all-oral DAAs and interferon-free regimens for the treatment of HCV-infected patients, and these would be potent inhibitors of HCV and have less adverse events.
  Clinical and translational medicine. 04/2013; 2(1):9.
• Article: Erlotinib prolongs survival in pancreatic cancer by blocking gemcitabine-induced MAPK signals.

  Koji Miyabayashi, Hideaki Ijichi, Dai Mohri, Motohisa Tada, Keisuke Yamamoto, Yoshinari Asaoka, Tsuneo Ikenoue, Keisuke Tateishi, Yousuke Nakai, Hiroyuki Isayama, Yasuyuki Morishita, Masao Omata, Harold L Moses, Kazuhiko Koike
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  ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers worldwide. Although many regimens have been used for PDAC treatment, the combination of the epidermal growth factor receptor (EGFR) inhibitor, erlotinib with gemcitabine has been the only molecular targeted drug tested so far which has been superior to gemcitabine alone. The mechanism underlying this effective combinational regimen remains unknown. Here we demonstrate that the combination is superior to gemcitabine alone in blocking progression and prolonging survival in a murine model of PDAC (Kras activation with Tgfbr2 knockout). We found that gemcitabine induced MAPK signaling, which was dramatically inhibited by erlotinib even in the Kras-activated PDAC cells in the mouse model. Mechanistic investigations suggested that gemcitabine induces EGFR ligand expression and ERBB2 activation by increasing heterodimer formation with EGFR, thereby maintaining high levels of ERBB2 protein in PDAC cells. Overall, our findings suggest a significant role of ERBB in PDAC treatment.
  Cancer Research 02/2013; · 7.86 Impact Factor
• Article: A genome-wide association study of HCV induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at MHC region.

  Yuji Urabe, Hidenori Ochi, Naoya Kato, Vinod Kumar, Atsushi Takahashi, Ryosuke Muroyama, Naoya Hosono, Motoyuki Otsuka, Ryosuke Tateishi, Paulisally Hau Yi Lo, [......], Kazuhiko Koike, Daiki Miki, Hiromi Abe, Naoyuki Kamatani, Joji Toyota, Hiromitsu Kumada, Michiaki Kubo, Kazuaki Chayama, Yusuke Nakamura, Koichi Matsuda
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  ABSTRACT: BACKGROUND&AIM: We performed a genome-wide association study (GWAS) of hepatitis C virus (HCV)-induced liver cirrhosis (LC) to identify predictive biomarkers for the risk of LC in patients with chronic hepatitis C (CHC). METHOD: A total of 682 HCV-induced LC cases and 1,045 CHC patients of Japanese origin were genotyped by Illumina Human Hap 610-Quad bead Chip. RESULT: Eight SNPs which showed possible associations (P < 1.0 x 10(-5)) in the GWAS stage were further genotyped using 936 LC cases and 3,809 CHC patients. We found that two SNPs within the major histocompatibility complex (MHC) region on chromosome 6p21, rs910049 and rs3135363, were significantly associated with the progression from CHC to LC (P(combined) = 9.15 x 10(-11) and 1.45 x 10(-10), odds ratio (OR) = 1.46 and 1.37, respectively). We also found that HLA-DQA1∗0601 and HLA-DRB1∗0405 were associated with progression from CHC to LC (P = 4.53 x 10(-4) and 1.54 x 10(-4) with OR = 2.80 and 1.45, respectively). Multiple logistic regression analysis revealed that rs3135363, rs910049, and HLA-DQA1∗0601 were independently associated with the risk of HCV-induced LC. In addition, individuals with four or more risk alleles for these three loci have a 2.83-fold higher risk for LC than those with no risk allele, indicating the cumulative effects of these variations. CONCLUSION: Our findings elucidated the crucial roles of multiple genetic variations within the MHC region as prognostic/predictive biomarkers for CHC patients.
  Journal of Hepatology 01/2013; · 9.26 Impact Factor
• Article: Improvement of prognosis for unresectable biliary tract cancer.

  Takashi Sasaki, Hiroyuki Isayama, Yousuke Nakai, Naminatsu Takahara, Naoki Sasahira, Hirofumi Kogure, Suguru Mizuno, Hiroshi Yagioka, Yukiko Ito, Natsuyo Yamamoto, Kenji Hirano, Nobuo Toda, Minoru Tada, Masao Omata, Kazuhiko Koike
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  ABSTRACT: To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer. A total of 186 consecutive patients with unresectable biliary tract cancer, who had been treated with chemotherapy between 2000 and 2009 at five institutions in Japan, were retrospectively analyzed. These patients were divided into three groups based on the year beginning chemotherapy: Group A (2000-2003), Group B (2004-2006), and Group C (2007-2009). The data were fixed at the end of December 2011. Overall survival and time-to-progression were analyzed and compared chronologically. No patient characteristics were significantly different among the three groups. The gallbladder was involved in about half of the patients in each group, and metastatic biliary tract cancer was present in three quarters of the enrollees. In Group A, 5-fluorouracil-based chemotherapies were primarily selected as first-line chemotherapy, and only 24% were treated with second-line chemotherapy. In Group B, gemcitabine or S-1 monotherapy was mainly introduced as first-line chemotherapy, and 51% of the patients who were refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with monotherapy. In Group C, the combination therapy with gemcitabine and S-1 was mainly chosen as first-line chemotherapy, and 53% of the patients refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with combination therapy. The median time-to-progressions were 4.4 mo, 3.5 mo and 5.9 mo in Groups A, B and C, respectively (4.4 mo vs 3.5 mo vs 5.9 mo, P < 0.01). The median overall survivals were 7.1, 7.3, and 11.7 mo in Groups A, B and C (7.1 mo vs 7.3 mo vs 11.7 mo, P = 0.03). Induction rates of all three drugs (gemcitabine, platinum analogs, and fluoropyrimidine) in Groups A, B and C were 4%, 2% and 27% (4% vs 2% vs 27%, P < 0.01). The prognosis of unresectable biliary tract cancer has improved recently. Using three effective drugs (gemcitabine, platinum analogs, and fluoropyrimidine) may improve the prognosis of this cancer.
  World Journal of Gastroenterology 01/2013; 19(1):72-7. · 2.47 Impact Factor
• Article: Frequency, Risk Factors and Survival Associated with an Intrasubsegmental Recurrence after Radiofrequency Ablation for Hepatocellular Carcinoma.

  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
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  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
• Article: Corrigendum: MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma.

  Kentaro Kojima, Akemi Takata, Charles Vadnais, Motoyuki Otsuka, Takeshi Yoshikawa, Masao Akanuma, Yuji Kondo, Young Jun Kang, Takahiro Kishikawa, Naoya Kato, Zhifang Xie, Weiping J Zhang, Haruhiko Yoshida, Masao Omata, Alain Nepveu, Kazuhiko Koike
  Nature Communications 09/2012; 3:985. · 7.40 Impact Factor
• Article: MiRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity via directly targeting Dnmt1 expression.

  Akemi Takata, Motoyuki Otsuka, Takeshi Yoshikawa, Takahiro Kishikawa, Yohko Hikiba, Shuntaro Obi, Tadashi Goto, Young Jun Kang, Shin Maeda, Haruhiko Yoshida, Masao Omata, Hiroshi Asahara, Kazuhiko Koike
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  ABSTRACT: MicroRNAs (miRNAs) are small RNAs that regulate the expression of specific target genes. While deregulated miRNA expression levels have been detected in many tumors, whether miRNA functional impairment is also involved in carcinogenesis remains unknown. We investigated whether deregulation of miRNA machinery components and subsequent functional impairment of miRNAs are involved in hepatocarcinogenesis. Among miRNA-containing ribonucleoprotein complex components, reduced expression of DDX20 was frequently observed in human hepatocellular carcinomas, in which enhanced NF-κB activity is believed to be closely linked to carcinogenesis. Because DDX20 normally suppresses NF-κB activity by preferentially regulating the function of the NF-κB-suppressing miRNA-140, we hypothesized that impairment of miRNA-140 function may be involved in hepatocarcinogenesis. Dnmt1 was identified as a direct target of miRNA-140, and increased Dnmt1 expression in DDX20-deficient cells hypermethylated the promoters of metallothionein genes, resulting in decreased metallothionein expression leading to enhanced NF-κB activity. MiRNA-140-knockout mice were prone to hepatocarcinogenesis and had a phenotype similar to that of DDX20 deficiency, suggesting that miRNA-140 plays a central role in DDX20 deficiency-related pathogenesis. CONCLUSION: These results indicate that miRNA-140 acts as a liver tumor suppressor, and that impairment of miRNA-140 function due to a deficiency of DDX20, a miRNA machinery component, could lead to hepatocarcinogenesis. (HEPATOLOGY 2012.).
  Hepatology 08/2012; · 11.66 Impact Factor
• Article: New serum markers of hepatocellular carcinoma.

  Ryota Masuzaki, Seth J Karp, Masao Omata
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  ABSTRACT: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, usually develops in a liver already suffering from chronic damages, often cirrhosis. There has been marked progress in the treatment of HCC. However, effective treatments are limited to patients with less advanced HCC. The detection of HCC at an early stage is still a prerequisite for improved prognosis. To address this problem, a variety of screening modalities are used, including measurement of alpha-fetoprotein (AFP) and ultrasonography (US) at regular intervals in high-risk populations. Unfortunately, poor sensitivity and specificity of AFP and the operator-dependency of US limit the value of either test to diagnose early-stage lesions. Other tests, including Lens culinaris agglutinin-reactive AFP and des-gamma carboxyprothrombin (DCP), are currently being evaluated and may be superior to current tests. Recent developments in gene-expressing microarrays and proteomics promise even more potential diagnostic options. The strict application of the Early Detection Research Network methodology will aid in the assessment of their diagnostic utility, and provide an objective basis for the assessment of their clinical utility.
  Seminars in Oncology 08/2012; 39(4):434-9. · 3.50 Impact Factor
• Article: Perihepatic lymph node enlargement is a negative predictor of liver cancer development in chronic hepatitis C patients.

  Hiromi Hikita, Hayato Nakagawa, Ryosuke Tateishi, Ryota Masuzaki, Kenichiro Enooku, Haruhiko Yoshida, Masao Omata, Yoko Soroida, Mamiko Sato, Hiroaki Gotoh, Atsushi Suzuki, Tomomi Iwai, Hiromitsu Yokota, Kazuhiko Koike, Yutaka Yatomi, Hitoshi Ikeda
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  ABSTRACT: BACKGROUND: Perihepatic lymph node enlargement (PLNE) is a common ultrasound finding in chronic hepatitis C patients. Although PLNE is considered to reflect the inflammatory response to hepatitis C virus (HCV), its clinical significance remains unclear. METHODS: Between December 2004 and June 2005, we enrolled 846 chronic hepatitis C patients in whom adequate ultrasound examinations had been performed. PLNE was defined as a perihepatic lymph node that was at least 1 cm in the longest axis by ultrasonography. We analyzed the clinical features of patients with PLNE and prospectively investigated the association between PLNE and hepatocellular carcinoma (HCC) development. RESULTS: We detected PLNE in 169 (20.0 %) patients. Female sex, lower body mass index (BMI), and HCV serotype 1 were independently associated with the presence of PLNE. However, there were no significant differences in liver function tests, liver stiffness, and hepatitis C viral loads between patients with and without PLNE. During the follow-up period (mean 4.8 years), HCC developed in 121 patients. Unexpectedly, patients with PLNE revealed a significantly lower risk of HCC development than those without PLNE (p = 0.019, log rank test). Multivariate analysis revealed that the presence of PLNE was an independent negative predictor of HCC development (hazard ratio 0.551, p = 0.042). In addition, the sustained viral response rate in patients who received interferon (IFN) therapy was significantly lower in patients with PLNE than in patients without PLNE. CONCLUSIONS: Patients with PLNE had a lower risk of HCC development than those without PLNE. This study may provide new insights into daily clinical practice and the pathophysiology of HCV-induced hepatitis and hepatocarcinogenesis.
  Journal of Gastroenterology 07/2012; · 4.16 Impact Factor
• Article: Feasibility of a New Self-Expandable Metallic Stent for Patients with Malignant Colorectal Obstruction.

  Shuntaro Yoshida, Hirotsugu Watabe, Hiroyuki Isayama, Hirofumi Kogure, Yousuke Nakai, Natsuyo Yamamoto, Takashi Sasaki, Kazumichi Kawakubo, Tsuyoshi Hamada, Yukiko Ito, Yoko Yashima, Naoki Sasahira, Kenji Hirano, Yutaka Yamaji, Minoru Tada, Masao Omata, Kazuhiko Koike
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  ABSTRACT: AIM: Stent migration due to peristalsis of the colon is one of the unresolved complications of colonic self-expandable metallic stent (SEMS) placement. Axial force (AF), a recovery force of the stent to a straight position after bending, has been considered a factor influencing the conformability of the digestive tract. An uncovered SEMS (Niti-S Enteral Colonic Uncovered Stent, D-type; Taewoong, Inc., Gimpo, South Korea) with improved conformability is considered to decrease migration. METHODS: Thirty three consecutive patients with symptomatic colorectal obstruction between March 2006 and December 2011 underwent endoscopic stent placement for palliation to estimate the efficacy and safety of Niti-S stents prospectively in four tertiary referral centers. RESULTS: Technical and clinical success rates were 100% and 97%, respectively. Seventeen patients had the following complications: ingrowth (n = 6), overgrowth (n = 1), collapse of the SEMS (n = 1), stool impaction (n = 2), migration (n = 1), bleeding (n = 3), and tenesmus (n = 3). The patient with migration had no recurrent symptoms until death. Of these 17 patients, 10 required re-interventions. Seven patients underwent an additional SEMS implantation. One patient underwent surgery for stoma creation. Two patients had stool impaction, and they underwent endoscopic cleaning. The median duration of patency was 347.0 ± 65.5 days. The mean survival time after stent insertion was 240.1 ± 39.9 days. CONCLUSION: The new SEMS effectively relieves malignant colorectal obstruction. Good conformability, according to the very low AF, may contribute to the low incidence of migration.
  Digestive Endoscopy 07/2012; · 1.19 Impact Factor
• Article: A randomized controlled trial of sodium phosphate tablets and polyethylene glycol solution for polyp detection.

  Haruka Kambe, Yutaka Yamaji, Takafumi Sugimoto, Atsuo Yamada, Hirotsugu Watabe, Haruhiko Yoshida, Masao Omata, Kazuhiko Koike
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  ABSTRACT: The study was aimed to assess the efficacy of sodium phosphate (NaP) tablets and polyethylene glycol (PEG) on colon cleansing. A prospective, randomized trial was conducted at the Graduate School of Medicine, University of Tokyo. Participants who were scheduled for colonoscopy were included and randomized into either the NaP or PEG group. An interim analysis was programmed into the study design when approximately 50% of the enrolments were completed. The primary outcome was the detection rate of polyps with a diameter ≤5 mm. A total of 92 patients were included in the analysis, of whom 44 were in the NaP group and 48 in the PEG group. The quality of colonic preparation was similar in both groups. The NaP group showed a higher detection rate of polyps with a diameter ≤5 mm than the PEG group (38.6% vs 18.8%, P = 0.004). A multivariate analysis showed that NaP and the withdrawal time of the colonoscope were independent factors associated with the detection of polyps with a diameter ≤5 mm. NaP is certainly not inferior to PEG. In fact, the results suggest that diminutive polyp detection using NaP might be superior to that using PEG.
  Journal of Digestive Diseases 07/2012; 13(7):374-80. · 1.59 Impact Factor
• Article: Predictive factors of solid food intake in patients with malignant gastric outlet obstruction receiving self-expandable metallic stents for palliation.

  Takashi Sasaki, Hiroyuki Isayama, Yousuke Nakai, Osamu Togawa, Hirofumi Kogure, Kazumichi Kawakubo, Suguru Mizuno, Yoko Yashima, Yukiko Ito, Natsuyo Yamamoto, Naoki Sasahira, Kenji Hirano, Takeshi Tsujino, Nobuo Toda, Minoru Tada, Masao Omata, Kazuhiko Koike
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  ABSTRACT: As for self-expandable metallic stents (SEMS) for malignant gastric outlet obstruction (GOO), some predictive factors of stent patency have been reported, although re-canalization of GOO by SEMS does not necessarily lead to favorable food intake. Therefore, we analyzed the predictive factors of oral food intake following SEMS placement. A total of 97 consecutive patients in whom SEMS were placed for malignant GOO in five hospitals were included in this retrospective study. Clinical outcomes and predictive factors influencing solid food intake were analyzed. The technical and clinical success rates were 97.9% and 87.6%, respectively. The mean gastric outlet obstruction scoring system (GOOSS) improved from 0.39 to 2.24 after SEMS placement (P<0.01). The median eating period was 2.1 months (95% CI, 1.1-3.0 months), and the median survival time was 3.1 months (95% CI, 2.0-4.2 months). A Karnofsky performance status of ≤ 50 (odds ratio, 3.65; 95% CI, 1.17-13.1; P=0.03) and ascites (odds ratio, 3.28; 95% CI, 1.23-9.05; P=0.02) were identified as statistically significant independent poor predictive factors of solid food intake. SEMS is an effective treatment for patients with malignant GOO. Ascites and a poor performance status were poor predictive factors of solid food intake.
  Digestive Endoscopy 07/2012; 24(4):226-30. · 1.19 Impact Factor
• Article: Percutaneous ethanol injection for hepatocellular carcinoma: 20-year outcome and prognostic factors.

  Shuichiro Shiina, Ryosuke Tateishi, Masatoshi Imamura, Takuma Teratani, Yukihiro Koike, Shinpei Sato, Shuntaro Obi, Fumihiko Kanai, Naoya Kato, Haruhiko Yoshida, Masao Omata, Kazuhiko Koike
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  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
• Article: Incidental pancreatic cysts found by magnetic resonance imaging and their relationship with pancreatic cancer.

  Saburo Matsubara, Minoru Tada, Masaaki Akahane, Hiroshi Yagioka, Hirofumi Kogure, Takashi Sasaki, Toshihiko Arizumi, Osamu Togawa, Yousuke Nakai, Naoki Sasahira, Kenji Hirano, Takeshi Tsujino, Hiroyuki Isayama, Nobuo Toda, Takao Kawabe, Kuni Ohtomo, Masao Omata
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  ABSTRACT: We examined whether the presence of pancreatic cysts could be a risk for pancreatic cancer by comparing the incidence and characteristics of cysts found by magnetic resonance (MR) imaging in patients with and without pancreatic cancer. Half-Fourier rapid acquisition with relaxation enhancement images and MR cholangiopancreatography were performed in 116 patients with pancreatic cancer (PC group) and 1226 with nonpancreatic disease (NP group). Incidence and characteristics of cysts were analyzed. Pancreatic cysts were detected in 65 patients (56%) of the PC group and in 123 patients (10%) of the NP group. According to the multivariate analysis, cyst presence was a significant risk factor for pancreatic cancer (odds ratio [OR], 10.27; P < 0.01), especially cysts larger than 10 mm (OR, 4.718; P < 0.01). When the definition of cyst presence in the PC group was restricted to the 33 cases with cysts considered to have existed before the development of cancer, the incidence was still high (OR, 2.976; P < 0.01) and size remained significant (OR, 4.428; P < 0.01). Patients with pancreatic cysts, especially larger than 10 mm, were considered to be at an increased risk of pancreatic cancer over the entire pancreas.
  Pancreas 06/2012; 41(8):1241-6. · 2.39 Impact Factor
• Article: Effectiveness of IκB kinase inhibitors in murine colitis-associated tumorigenesis

  Yoku Hayakawa, Shin Maeda, Hayato Nakagawa, Yohko Hikiba, Wataru Shibata, Kei Sakamoto, Ayako Yanai, Yoshihiro Hirata, Keiji Ogura, Susumu Muto, Akiko Itai, Masao Omata
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  ABSTRACT: PurposeNuclear factor κB (NF-κB) activation is involved in various inflammatory illnesses, for example inflammatory bowel disease, and is thought to be a key factor in the tumor-promoting mechanism of inflammation-associated tumorigenesis. This study investigated whether inhibitors of IKKβ, which is a critical kinase for NF-κB activation, reduce colitis-associated tumorigenesis in mice. MethodsWe used a mouse model of the disease whereby administration of azoxymethane (AOM) followed by repeated dextran sulfate sodium (DSS) ingestion causes severe colonic inflammation and the subsequent development of multiple tumors. Effects of IKKβ inhibitors, NBD peptide, and IMD-0354 were examined. ResultsIn a colitis-associated cancer model, treatment with the IKKβ inhibitors NBD peptide and IMD-0354 significantly reduced the number of tumors compared with the untreated group. The tumors were also significantly smaller in the inhibitor-treated mice than in the untreated mice. Macrophage and neutrophil infiltration decreased with the inhibitor treatment. NF-κB activation and the expression of Cox-2 and iNOS were observed in tumor tissues, and the inhibitors ameliorated their expression. These inhibitors blocked NF-κB activation and the expression of proinflammatory cytokines mediated by the culture supernatant of inflamed colon in murine primary macrophages. In-vitro and in-vivo experiments showed that these drugs, especially NBD peptide, could also inhibit the proliferation of colonic epithelial cells. ConclusionThese results imply that IKKβ-targeted NF-κB blockade is an attractive therapeutic approach for the prevention of colitis-associated tumors.
  Journal of Gastroenterology 04/2012; 44(9):935-943. · 4.16 Impact Factor
• Article: Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography.

  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
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  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
• Article: Systemic combination therapy of intravenous continuous 5-fluorouracil and subcutaneous pegylated interferon alfa-2a for advanced hepatocellular carcinoma.

  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
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  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
• Article: Risk factors for pancreatitis following transpapillary self-expandable metal stent placement.

  Kazumichi Kawakubo, Hiroyuki Isayama, Yousuke Nakai, Osamu Togawa, Naoki Sasahira, Hirofumi Kogure, Takashi Sasaki, Saburo Matsubara, Natsuyo Yamamoto, Kenji Hirano, Takeshi Tsujino, Nobuo Toda, Minoru Tada, Masao Omata, Kazuhiko Koike
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  ABSTRACT: Pancreatitis is one of complications after self-expandable metal stent (SEMS) placement. The purpose of this study was to evaluate risk factors for pancreatitis after endoscopic SEMS placement for malignant biliary obstruction (MBO). We retrospectively reviewed 370 consecutive patients who underwent initial transpapillary SEMS placement for biliary decompression. The characteristics of inserted SEMSs were classified according to axial and radial force. Pancreatitis following SEMS insertion was observed in 22 patients (6%). All of them were mild according to consensus criteria. Univariate analysis indicated that injections of contrast into the pancreatic duct (frequency of pancreatitis, 10.3%), the placement of an SEMS with high axial force (8.3%), and nonpancreatic cancer (16.1%) significantly contributed to the development of pancreatitis, whereas female gender, a younger age, a covered SEMS, and a SEMS with high radial force or without a biliary sphincterotomy did not. In a multivariate risk model, SEMSs with high axial force (odds ratio [OR], 3.69; p = 0.022) and nonpancreatic cancer (OR, 5.52; p < 0.001) were significant risk factors for pancreatitis. SEMSs with high axial force and an etiology of MBO other than pancreatic cancer were strongly associated with a high incidence of pancreatitis following transpapillary SEMS placement in patients with distal MBO.
  Surgical Endoscopy 03/2012; 26(3):771-6. · 4.01 Impact Factor
• Article: Endoscopic papillary balloon dilation for bile duct stones in patients on hemodialysis.

  Naminatsu Takahara, Hiroyuki Isayama, Takashi Sasaki, Takeshi Tsujino, Nobuo Toda, Naoki Sasahira, Suguru Mizuno, Kazumichi Kawakubo, Hirofumi Kogure, Natsuyo Yamamoto, Yousuke Nakai, Kenji Hirano, Minoru Tada, Masao Omata, Kazuhiko Koike
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  ABSTRACT: Endoscopic papillary balloon dilation (EPBD) is a less hazardous alternative to endoscopic sphincterotomy for managing bile duct stones in patients with a coagulopathy. However, little information on EPBD is available for patients with bile duct stones who are undergoing hemodialysis (HD). We aimed to evaluate the safety and efficacy of EPBD for such patients. This was a retrospective cohort study with prospectively collected data for 37consecutive patients with bile duct stones who were undergoing HD and who also underwent EPBD between December 1995 and April 2010 at four institutions in Tokyo, Japan. The main outcome was the safety and efficacy of EPBD for managing bile duct stones in patients undergoing HD. The bile duct stones were completely removed in one session in 24 patients (64.8%). Overall success was achieved using EPBD alone in all patients. Complications occurred in five patients (13.5%), including two with hemorrhage (5.4%). No hemorrhage developed in any of the 33 patients who had no additional bleeding risk except for HD. Pancreatitis and perforation developed in two (5.4%) and one (2.7%) patient, respectively. EPBD seems to be a safe and effective treatment to extract bile duct stones in patients undergoing HD. However, EPBD should be performed carefully in patients with additional bleeding risk factors, such as Child-Pugh class C liver cirrhosis and those taking anti-platelet agents at the time of EPBD.
  Journal of Gastroenterology 02/2012; 47(8):918-23. · 4.16 Impact Factor