Faculty Profiles - TAKAKI Akinobu

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Low peripheral blood treg and high HCV specific interferon gamma production achieved after eradication of HCV after liver transplantation

Kazuko Koike, Akinobu Takaki, Masashi Utsumi, Tetsuya Yasunaka, Yasuhiro Miyake, Takahiro Yagi, Kazuhide Yamamoto

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 27 275 - 275 2012.12

Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement

Masaya Iwamuro, Hiroyuki Okada, Katsuyoshi Takata, Katsuji Shinagawa, Shigeatsu Fujiki, Junji Shiode, Atsushi Imagawa, Masashi Araki, Toshiaki Morito, Mamoru Nishimura, Motowo Mizuno, Tomoki Inaba, Seiyu Suzuki, Yoshinari Kawai, Tadashi Yoshino, Yoshiro Kawahara, Akinobu Takaki, Kazuhide Yamamoto

WORLD JOURNAL OF GASTROENTEROLOGY 18 ( 44 ) 6427 - 6436 2012.11

Language：English Publisher：BAISHIDENG PUBL GRP CO LTD

AIM: To investigate the capacity for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma.
METHODS: This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011. Data for endoscopic, radiological, and biological examinations performed were retrospectively reviewed from clinical records. A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value (SUVmax). Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed, patients were subdivided into two groups. To identify potential predictive factors for 18F-FDG positivity, these two groups were compared with respect to gender, age at diagnosis of lymphoma, histopathological grade, pattern of follicular dendritic cells, mitotic rate, clinical stage, soluble interleukin-2 receptor levels detected by 18F-FDG-PET, lactate dehydrogenase (LDH) levels, hemoglobin levels, bone marrow involvement, detectability of gastrointestinal lesions by computed tomography (CT) scanning, and follicular lymphoma international prognostic index (FLIPI) risk.
RESULTS: Involvement of follicular lymphoma in the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum was identified in 1, 34, 6, 3, 2, 3, and 6 patients, respectively. No patient had esophageal involvement. In total, 19/41 (46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract. In contrast, false-negative 18F-FDG uptake was detected in 24 patients (58.5%), while false-positive 18F-FDG uptake was detected in 5 patients (12.2%). In the former case, 2/19 patients had both 18F-FDG-positive lesions and 18F-FDG-negative lesions in the gastrointestinal tract. In patients with 18F-FDG avidity, the SUVmax value of the involved gastrointestinal tract ranged from 2.6 to 17.4 (median: 4.7). For the 18F-FDG-negative (n = 22) and -positive (n = 19) groups, there were no differences in the male to female ratios (10/12 vs 4/15, P = 0.186), patient age (63.6 +/- 2.4 years vs 60.1 +/- 2.6 years, P = 0.323), presence of histopathological grade 1 vs 2 (20/2 and 17/2, P = 1.000), follicular dendritic cell pattern (duodenal/nodal: 13/5 vs 10/3, P = 1.000), mitotic rate (low/ partly high, 14/1 vs 10/3, P = 0.311), clinical stage according to the Ann Arbor system (stages I E and II E/other, 15/7 vs 15/4, P = 0.499), clinical stage according to the Lugano system (stages I and II-1/other, 14/8 vs 14/5, P = 0.489), soluble interleukin-2 receptor levels (495 +/- 78 vs 402 +/- 83, P = 0.884), LDH levels (188 +/- 7 vs 183 +/- 8, P = 0.749), hemoglobin levels (13.5 +/- 0.3 vs 12.8 +/- 0.4, P = 0.197), bone marrow involvement (positive/negative, 1/8 vs 1110, P = 1.000), detectability by CT scanning (positive/negative, 1/16 vs 4/13, P = 0.335), and FLIPI risk (low risk/other, 16/6 vs 13/6, P = 0.763), respectively in each case.
CONCLUSION: These findings indicate that it is not feasible to predict 18F-FDG-avidity. Therefore, 18F-FDG-PET scans represent a complementary modality for the detection of gastrointestinal involvements in follicular lymphoma patients, and surveillance of the entire gastrointestinal tract by endoscopic examinations is required. (C) 2012 Baishideng. All rights reserved.

DOI： 10.3748/wjg.v18.i44.6427

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Hepatitis B e antigen predicts delayed reduction of HBV DNA without viral breakthrough with adefovir dipivoxil and lamivudine: A 5-year study of patients with hepatitis B with lamivudine resistance

Fusao Ikeda, Nobuyuki Baba, Koichi Takaguchi, Junichi Kubota, Kenji Miyoshi, Shin-ichi Fujioka, Yuki Moritou, Yasuto Takeuchi, Tetsuya Yasunaka, Yasuhiro Miyake, Akinobu Takaki, Yoshiaki Iwasaki, Haruhiko Kobashi, Kazuhide Yamamoto

JOURNAL OF MEDICAL VIROLOGY 84 ( 10 ) 1562 - 1570 2012.10

Language：English Publisher：WILEY-BLACKWELL

To clarify the factors associated with delayed reduction of HBV DNA during combination treatment with adefovir dipivoxil (ADV) and lamivudine (LAM) for patients with LAM-resistant hepatitis B virus (HBV), factors including patient characteristics, viral mutations, and drug metabolism were investigated during a 5-year observation period. Delayed reduction of HBV DNA was defined as delayed viral response of detectable HBV DNA after 3 years of combination therapy. Of 67 consecutive patients, 47 attained undetectable HBV DNA after 3 years of combination therapy, and the mean therapeutic duration was 5 years (range: 3.08.4 years). The patients with delayed viral response had high levels of HBV DNA and HBe antigen, while those with negative or low levels of HBe antigen were also negative for HBV DNA, even if they had high levels of HBV DNA. In the multivariate analysis with the proportional hazards model, a high baseline level of HBe antigen was negatively associated with viral decline to an undetectable level (P?=?0.013). A higher baseline of HBe antigen corresponded to a lower annual decline in HBV DNA (R?=?-0.38, P?=?0.004). No patients showed ADV-resistant mutations in the HBV reverse transcriptase region. Trough concentrations of LAM and ADV showed no clear associations with viral response. HBe antigen levels at the initiation of therapy, and reductions in these levels during therapy are predictive of the therapeutic response to combination therapy with ADV and LAM for patients with LAM-resistant HBV. J. Med. Virol. 84:15621570, 2012. (c) 2012 Wiley Periodicals, Inc.

DOI： 10.1002/jmv.23371

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Des-gamma-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma

Minoru Matsubara, Hidenori Shiraha, Jyunro Kataoka, Masaya Iwamuro, Shigeru Horiguchi, Shin-ichi Nishina, Nobuyuki Takaoka, Masayuki Uemura, Akinobu Takaki, Shinichiro Nakamura, Yoshiyuki Kobayashi, Kazuhiro Nouso, Kazuhide Yamamoto

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 27 ( 10 ) 1602 - 1608 2012.10

Language：English Publisher：WILEY-BLACKWELL

Background and Aim: Hepatocellular carcinoma (HCC) is a hypervascular tumor, and angiogenesis plays an important role in its development. Previously, we demonstrated that des-?-carboxyl prothrombin (DCP) promotes both cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) by inducing the autophosphorylation of kinase insert domain receptor (KDR). In the present study, DCP-associated tumor angiogenesis was assessed by comparing hypovascular and common hypervascular HCC. Methods: The solitary HCCs of 827 patients were classified into two groups according to the tumor density at the arterial phase of a dynamic computed tomography scan; the initial clinical data of patients with the hyper- and hypovascular types were compared. The HCC tissues from 95 tumors were analyzed by immunohistochemical staining for DCP and phosphorylated KDR, and intratumoral microvessel density (MVD) was analyzed to evaluate microvessel angiogenesis. Results: The serum DCP levels (320 +/- 3532 mAU/mL) and tumor size (18.4 +/- 9.0 mm) of patients with hypervascular HCC were significantly greater than those with hypovascular HCC (38.7 +/- 80 mAU/mL and 14.6 +/- 5.2 mm, P < 0.001). Immunohistochemical analysis revealed that the expressions of DCP and phospho-KDR were significantly greater in hypervascular HCC (71.4% and 31.0%, respectively) than in hypovascular HCC (7.6% and 5.7%, respectively). Intratumoral MVD was significantly correlated with DCP (r = 0.48, P < 0.0001). Conclusions: des-?-carboxyl prothrombin production is associated with tumor angiogenesis in HCC.

DOI： 10.1111/j.1440-1746.2012.07173.x

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Peritoneovenous shunting for refractory ascites results in worsening of nephrotic syndrome

Akinobu Takaki, Yohei Maeshima, Takahito Yagi, Akihiro Katayama, Norikazu Hinamoto, Shigeru Akagi, Hitoshi Sugiyama, Takeshi Tomoda, Yoshiaki Iwasaki, Tetsuya Yasunaka, Fusao Ikeda, Yasuhiro Miyake, Haruhiko Kobashi, Atsushi Hirano, Hirofumi Makino, Kazuhide Yamamoto

HEPATOLOGY RESEARCH 42 ( 10 ) 1048 - 1053 2012.10

Language：English Publisher：WILEY-BLACKWELL

Peritoneovenous shunt (PVS) is accepted as a treatment for refractory ascites due to liver cirrhosis. Infection is a well-known complication of shunting. However, the effects of PVS in terms of complications for renal disease are unclear. We encountered a case involving a 52-year-old man with alcoholic liver cirrhosis and complications of nephrotic syndrome that were worsened by PVS. He received PVS for refractory ascites due to alcoholic liver cirrhosis before coming to our hospital for evaluation for liver transplantation. Nephrotic syndrome was then identified due to cirrhosis-related membranoproliferative glomerulonephritis (MPGN). Prednisolone was administrated at 60 mg/day for MPGN. On day 5, he showed grade IV hepatic encephalopathy (West Haven criteria). Tapering prednisolone and intestinal cleansing with lactulose treatment improved hepatic encephalopathy, but hyperammonemia persisted and the PVS was removed. After shunt removal, urinary protein levels decreased from 46 g/day to 0.30.5 g/day and ammonia levels decreased. PVS may increase the excretion of urinary protein and increase ammonia levels in patients with complications of glomerulonephritis.

DOI： 10.1111/j.1872-034X.2012.01012.x

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Low frequency of Tr1 in peripheral blood correlated with persistent normal ALT in chronic hepatitis C after liver transplantation

Akinobu Takaki, Kazuko Koike, Masashi Utsumi, Takahito Yagi, Hirsohi Sadamori, Tetsuya Yasunaka, Kazuhide Yamamoto

HEPATOLOGY 56 527A - 528A 2012.10

Laparoscopic Findings of Reddish Markings Predict Hepatocellular Carcinoma in HBeAg Positive Chronic Hepatitis B Patients

Tetsuya Yasunaka, Fusao Ikeda, Yasuhiro Miyake, Akinobu Takaki, Shin-ichi Fujioka, Haruhiko Kobashi, Kazuhide Yamamoto

AMERICAN JOURNAL OF GASTROENTEROLOGY 107 S145 - S145 2012.10

Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice

Daisuke Kawai, Akinobu Takaki, Atsuko Nakatsuka, Jun Wada, Naofumi Tamaki, Tetsuya Yasunaka, Kazuko Koike, Ryuichiro Tsuzaki, Kazuyuki Matsumoto, Yasuhiro Miyake, Hidenori Shiraha, Manabu Morita, Hirofumi Makino, Kazuhide Yamamoto

HEPATOLOGY 56 ( 3 ) 912 - 921 2012.9

Language：English Publisher：WILEY-BLACKWELL

Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Molecular hydrogen is an effective antioxidant that reduces cytotoxic reactive oxygen species. In this study, we investigated the effects of hydrogen-rich water and the drug pioglitazone on the progression of NASH in mouse models. A methionine-cholinedeficient (MCD) diet mouse model was prepared. Mice were divided into three experimental groups and fed for 8 weeks as follows: (1) MCD diet + control water (CW group); (2) MCD diet + hydrogen-rich water (HW group); and (3) MCD diet mixed with pioglitazone (PGZ group). Plasma alanine aminotransferase levels, hepatic expression of tumor necrosis factor-a, interleukin-6, fatty acid synthesisrelated genes, oxidative stress biomarker 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis marker terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling (TUNEL)positive cells in the liver were decreased in the HW and PGZ groups. The HW group showed a smaller decrease in hepatic cholesterol; however, stronger antioxidative effects in serum and lower peroxisome proliferator-activated receptor-a expression in the liver were seen in comparison with the PGZ group. We then investigated the effects of hydrogen in the prevention of hepatocarcinogenesis in STAM mice, known as the NASH-related hepatocarcinogenesis model. Eight-week-old male STAM mice were divided into three experimental groups as follows: (1) control water (CW-STAM); (2) hydrogen-rich water (HW-STAM); and (3) pioglitazone (PGZ-STAM). After 8 weeks, hepatic tumors were evaluated. The number of tumors was significantly lower in the HW-STAM and PGZ-STAM groups than in the CW-STAM group. The maximum tumor size was smaller in the HW-STAM group than in the other groups. Conclusion: Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis. (HEPATOLOGY 2012;56:912921)

DOI： 10.1002/hep.25782

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Diagnostic usefulness of precise examinations with intraductal ultrasonography, peroral cholangioscopy and laparoscopy of immunoglobulin G4-related sclerosing cholangitis

Shigeru Horiguchi, Fusao Ikeda, Hidenori Shiraha, Naoki Yamamoto, Ichiro Sakakihara, Yasuhiro Noma, Koichiro Tsutsumi, Hironari Kato, Hiroaki Hagihara, Tetsuya Yasunaka, Shinichiro Nakamura, Haruhiko Kobashi, Hirofumi Kawamoto, Kazuhide Yamamoto

DIGESTIVE ENDOSCOPY 24 ( 5 ) 370 - 373 2012.9

Language：English Publisher：WILEY-BLACKWELL

Herein, a case of immunoglobulin G4 (IgG4)-related sclerosing cholangitis is reported. IgG4 was diagnosed based on observations from peroral cholangioscopy and laparoscopy, and these methods are proposed for definitive and precise diagnosis of this disease. A 76-year-old male patient with inguinal Paget's disease had intrahepatic bile duct dilatations detected with computed tomography at his periodic check-up. Magnetic resonance cholangiography showed stenosis of the upper common bile duct and poststenotic dilatation of left intrahepatic bile ducts. The portal tract and bilateral intrahepatic bile ducts were surrounded by a low-density area, facing a tumor-like lesion at segment 2. Cytological examinations of the stenotic and dilated lesions revealed no cellular atypia. Histological examination of the tumor showed normal liver tissue with infiltration of lymphocytes, indicating an inflammatory pseudotumor. Peroral cholangioscopy excluded the possibility of biliary cancer and indicated that the stenotic legion was of submucosal, not mucosal, origin. Laparoscopic observations showed discoloration with wide yellowish-white lobular markings and wide depressed lesions at segments 2 and 7. Liver histology showed mild cholangitis with infiltration of IgG4-positive plasma cells around the bile ducts. Serum IgG4 levels were elevated. From these findings, the patient was diagnosed with IgG4-related sclerosing cholangitis. After treatment with prednisolone, blood liver enzymes and IgG4 rapidly normalized, bile duct dilatations improved, and the hepatic pseudotumor disappeared. The cholangitis did not recur. In this case, biliary cancer was ruled out by observation with peroral cholangioscopy, and the spread of cholangitis in the liver periphery was verified with laparoscopy; this information could not be obtained with other modalities.

DOI： 10.1111/j.1443-1661.2012.01300.x

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非B非C肝癌の予後及び特徴

竹内康人, 能祖一裕, 萩原宏明, 安中哲也, 桑木健志, 大西秀樹, 池田房雄, 中村進一郎, 白羽英則, 三宅康広, 高木章乃夫, 山本和秀

肝臓 53 ( Suppl.2 ) A765 - A765 2012.9

当院における肝細胞癌に対する生体肝移植症例の検討

高木章乃夫, 八木孝仁, 貞森裕, 安中哲也, 篠浦先, 楳田祐三, 吉田龍一, 佐藤太祐, 信岡大輔, 内海方嗣, 中村進一郎, 能祖一裕, 保田裕子, 三浦公, 藤原俊義, 山本和秀

移植 47 ( 4-5 ) 340 - 340 2012.9

移植後B型肝炎に対するHBVワクチンの有用性についての検討

高木章乃夫, 八木孝仁, 安中哲也, 貞森裕, 小池和子, 篠浦先, 楳田祐三, 吉田龍一, 佐藤太祐, 信岡大輔, 内海方嗣, 吉田一博, 三宅康広, 保田裕子, 藤原俊義, 山本和秀

移植 47 ( 4-5 ) 341 - 341 2012.9

B型肝炎ウイルスに対して免疫寛容状態にある移植後患者でのHBVワクチンの効果

高木章乃夫, 八木孝仁, 安中哲也, 貞森裕, 篠浦先, 楳田祐三, 保田裕子, 山本和秀

移植 47 ( 総会臨時 ) 264 - 264 2012.9

Streptozotocin投与NASH発癌モデルマウスにおける病態進行と水素水投与の有効性の検討

河合大介, 高木章乃夫, 山本和秀, 中司敦子, 和田淳, 玉木直文, 安中哲也, 小池和子, 津崎龍一郎, 松本和幸, 三宅康広, 白羽英則, 森田学, 槇野博史

日本消化器病学会雑誌 109 ( 臨増大会 ) A708 - A708 2012.9

改正臓器移植法後の脳死肝移植の現状と問題点

楳田祐三, 八木孝仁, 貞森裕, 高木章乃夫, 篠浦先, 吉田龍一, 信岡大輔, 佐藤太祐, 内海方嗣, 保田裕子, 藤原俊義

移植 47 ( 総会臨時 ) 254 - 254 2012.9

C型慢性肝炎の肝脂肪化におけるPNPLA3の関与についての検討

和田望, 池田房雄, 竹内康人, 森藤由紀, 湧田暁子, 安中哲也, 三宅康広, 馬場伸介, 狩山和也, 妹尾知典, 高木章乃夫, 永野拓也, 高口浩一, 岩崎良章, 山本和秀

肝臓 53 ( Suppl.2 ) A743 - A743 2012.9

C型慢性肝炎に対するペグインターフェロン・リバビリン併用療法におけるテプレノン併用の無作為化比較試験による検討

岩崎良章, 荒木康之, 橋本訓招, 下江俊成, 高口浩一, 石田清隆, 岡本良一, 坂口孝作, 狩山和也, 小橋春彦, 難波真太郎, 池田房雄, 三宅康広, 高木章乃夫, 山本和秀

肝臓 53 ( Suppl.2 ) A750 - A750 2012.9

当院における急性・慢性肝不全に対する脳死肝移植の現状

安中哲也, 高木章乃夫, 保田裕子, 八木孝仁, 吉田龍一, 楳田祐三, 三宅康広, 篠浦先, 貞森裕, 山本和秀

日本門脈圧亢進症学会雑誌 18 ( 3 ) 157 - 157 2012.8

膵癌において、CD44の発現は、RUNX3発現は逆相関する(CD44 expression correlates negatively with runt-related transcription factor 3 in pancreatic ductal adenocarcinoma)

堀口繁, 白羽英則, 内田大輔, 永原照也, 岩室雅也, 片岡淳朗, 加藤博也, 高木章乃夫, 能祖一裕, 山本和秀

日本癌学会総会記事 71回 179 - 180 2012.8

C型肝硬変症例に対するペグインターフェロン・リバビリン併用療法の成績

安中哲也, 池田房雄, 岩崎良章, 三宅康広, 高木章乃夫, 山本和秀

日本門脈圧亢進症学会雑誌 18 ( 3 ) 150 - 150 2012.8

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