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| 1.
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Okazaki, Mitsuyoshi ; Makino, Isamu ; Kitagawa, Hirohisa ; Nakanuma, Shinichi ; Hayashi, Hironori ; Nakagawara, Hisatoshi ; Miyashita, Tomoharu ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Ohta, Tetsuo ; 岡崎, 充善 ; 牧野, 勇 ; 北川, 裕久 ; 中沼, 伸一 ; 林, 泰寛 ; 中川原, 寿俊 ; 宮下, 知治 ; 田島, 秀浩 ; 高村, 博之 ; 太田, 哲生
概要:
金沢大学医薬保健研究域医学系<br />We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor gr
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owth into the main pancreatic duct. A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor. Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas, accompanied with severe dilatation of the main pancreatic duct, which was diagnosed as an intraductal papillary-mucinous neoplasm. We performed distal pancreatectomy and splenectomy. The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma (giant cell type) and adenocarcinoma in the pancreas. There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct. The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery. In this case, we could observe a remarkable intraductal tumor growth into the main pancreatic duct. We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
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| 2.
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Onishi, Ichiro ; Kitagawa, Hirohisa ; Harada, Kenichi ; Maruzen, Syogo ; Sakai, Seisyo ; Makino, Isamu ; Hayashi, Hironori ; Nakagawara, Hisatoshi ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Fujimura, Takashi ; Kayahara, Masato ; Ikeda, Hiroko ; Ohta, Tetsuo ; Nakanuma, Yasuni ; 北川, 裕久 ; 原田, 憲一 ; 牧野, 勇 ; 林, 泰寛 ; 中川原, 寿俊 ; 田島, 秀浩 ; 高村, 博之 ; 藤村, 隆 ; 萱原, 正都 ; 池田, 博子 ; 太田, 哲生 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />We present the first case of an intraductal papillary neoplasm of the bile duct (IPNB) accompanying
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a mixed adenoneuroendocrine carcinoma (MANEC). A 74-yearold woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET. © 2013 Baishideng. All rights reserved.
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| 3.
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Hattori, Yuki ; Gabata, Toshifumi ; Matsui, Osamu ; Mochizuki, Kentaro ; Kitagawa, Hirohisa ; Kayahara, Masato ; Ohta, Tetsuo ; Nakanuma, Yasuni ; 蒲田, 敏文 ; 松井, 修 ; 北川, 裕久 ; 萱原, 正都 ; 太田, 哲生 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />Aim: To evaluate retrospectively the correlation between enhancement patterns on dynamic computed to
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mography (CT) and angiogenesis and fibrosis in pancreatic adenocarcinoma. Methods: Twenty-three patients with pancreatic adenocarcinoma underwent dynamic CT and tumor resection. In addition to the absolute and relative enhanced value that was calculated by subtracting the attenuation value on pre-contrast from those on contrast-enhanced CT in each phase, we defined one parameter, "tumor-aorta enhancement ratio", which was calculated by dividing enhancement of pancreatic cancer by enhancement of abdominal aorta in each phase. These enhancement patterns were correlated with the level of vascular endothelial growth factor (VEGF), microvessel density (MVD), and extent of fibrosis. Results: The absolute enhanced value in the arterial phase correlated with the level of VEGF and MVD (P = 0.047, P = 0.001). The relative enhanced value in arterial phase and tumor-aorta enhancement ratio (arterial) correlated with MVD (P = 0.003, P = 0.022). Tumor-aorta enhancement ratio (arterial) correlated negatively with the extent of fibrosis (P = 0.004). The tumors with greater MVD and higher expression of VEGF tended to show high enhancement in the arterial dominant phase. On the other hand, the tumors with a larger amount of fibrosis showed a negative correlation with the grade of enhancement during the arterial phase. Conclusion: Enhancement patterns on dynamic CT correlated with angiogenesis and may be modified by the extent of fibrosis. © 2009 The WJG Press and Baishideng. All rights reserved.
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Yoshikawa, Seiichi ; Zen, Yoh ; Fujii, Takahiko ; Sato, Yasunori ; Ohta, Tetsuo ; Aoyagi, Yutaka ; Nakanuma, Yasuni ; 全, 陽 ; 佐藤, 保則 ; 太田, 哲生 ; 中沼, 安二
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金沢大学医薬保健研究域医学系<br />AIM: To reveal the characteristics of CD133+ cells in the liver. METHODS: This study examined the hi
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stological characteristics of CD133 + cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133 + cells derived from human hepatocellular carcinoma (HCC) or cholangiocarcinoma cell lines. RESULTS: Immunostaining revealed constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium, and these cells had the immunophenotype CD133+/CK19+/HepPar -1-. A smal l number of CD133+/CK19-/HepPar-1+ cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma. In addition, small ductal structures, resembling the canal of Hering, partly surrounded by hepatocytes were positive for CD133. CD133 expression was observed in three HCC (HuH7, PLC5 and HepG2) and two cholangiocarcinoma cell lines (HuCCT1 and CCKS1). Fluorescence-activated cell sorting (FACS) revealed that CD133+ and CD133-cells derived from HuH7 and HuCCT1 cells similarly produced CD133+ and CD133- cells during subculture. To examine the relationship between CD133+ cells and the side population (SP) phenotype, FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133. The ratios of CD133+/CD133-cells were almost identical in the SP and non-SP in HuH7. In addition, four different cellular populations (SP/CD133+, SP/CD133-, non-SP/CD133+, and non-SP/CD133-) could similarly produce CD133+ and CD133- cells during subculture. CONCLUSION: This study revealed that CD133 could be a biliary and progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect tumor-initiating cells in cell lines. © 2009 The WJG Press and Baishideng. All rights reserved.
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| 5.
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Fujimura, Takashi ; Ohta, Tetsuo ; Oyama, Katsunobu ; Miyashita, Tomoharu ; Miwa, Koichi ; 藤村, 隆 ; 太田, 哲生 ; 尾山, 勝信 ; 宮下, 知治 ; 三輪, 晃一
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金沢大学医薬保健研究域医学系<br />Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were developed as one of the anti-inflammatory
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drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs (NSAIDs). However, coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis (FAP), which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration (FDA) immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum, and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors. © 2006 The WJG Press. All rights reserved.
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| 6.
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中沼, 伸一 ; 萱原, 正都 ; 中川原, 寿俊 ; 伊藤, 博 ; 田島, 秀浩 ; 藤田, 秀人 ; 北川, 裕久 ; 藤村, 隆 ; 太田, 哲生 ; Nakanuma, Shinichi ; Kayahara, Masato ; Nakagawara, Hisatoshi ; Ito, Hiroshi ; Tajima, Hidehiro ; Fujita, Hideto ; Kitagawa, Hirohisa ; Fujimura, Takashi ; Ohta, Tetsuo
概要:
金沢大学附属病院肝胆膵・移植外科<br />症例は30歳の男性で，体重120 kg，BMI 41の高度肥満であった．重症急性膵炎と診断され当院に紹介された．CTでは両側胸水，膵実質の不明瞭化，後腎傍腔に及ぶ滲出液が認められた（Grade I
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V）．また，SIRS，急性循環不全の状態であった．入院後4病日，炎症反応の持続とCTにて膵頭部の血流障害が認められ，感染性膵壊死と判断し，necrosectomyを行った．腸管・組織浮腫のため，閉腹によるabdominal compartment syndromeが危ぐされたため，術後zipper techniqueとして衣類圧縮用袋を腹壁に固定し，腹腔内洗浄を伴うplanned necrosectomyを継続し，残存膵壊死組織の除去を行った．退院1年目の現在，患者は職場復帰している．衣類圧縮用袋を用いたzipper techniqueは高度肥満を有する感染性膵壊死の術後に有用な処置と考えられ若干の文献を加え報告する．<br />A severely obese 30-year-old male (BMI 41) weighing 120 kg and referred based on a diagnosis of severe acute pancreatitis was found in computed tomography (CT) to have bilateral hydrothorax, unclear pancreatic parenchyma, and exudate spreading to the posterior pararenal spacer (Grade IV). He also had SIRS and acute circulatory failure. On hospital day 4, persistent inflammatory reactions and a CT finding of pancreatic-head necrosis were noted. Based on a diagnosis of infectious pancreatic necrosis, he underwent necrosectomy. It was difficult to close the abdominal wall because of intestinal and tissue edema. Postoperatively, we attached a vacuum storage bag to the abdominal wall by a zipper. The planned necrosectomy, accompanied by intraperitoneal lavage, was continued to remove residual pancreatic necrotic tissue. No sign of abdominal compartment syndrome was noted. The patient has been discharged and resumed his previous work. The zipper technique and vacuum storage bag thus proved useful in providing postoperative care to a patient with infectious pancreatic necrosis accompanied by severe obesity.
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| 7.
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Nakanuma, Shinichi ; Miyashita, Tomoharu ; Hayashi, Hironori ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Makino, Isamu ; Oyama, Katsunobu ; Nakagawara, Hisatoshi ; Fushida, Sachio ; Ohta, Tetsuo ; 中沼, 伸一 ; 宮下, 知治 ; 高村, 博之 ; 林, 泰寛 ; 田島, 秀浩 ; 牧野, 勇 ; 尾山, 勝信 ; 中川原, 寿俊 ; 伏田, 幸夫 ; 太田, 哲生
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金沢大学附属病院肝胆膵・移植外科<br />Objectives: Continuous thrombocytopenia after liver transplant is associated with a less favorable
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prognosis, but this pathogenesis remains unclear. We focused on the consumption of platelets in the allograft. We assessed platelet consumption in allografts, and evaluated the pathology of platelet aggregation in an allograft tissue and its involve-ment in clinical outcomes.Materials and Methods: We took biopsy specimens from 20 patients. To examine the localization of platelet aggregation, CD42b was assayed immuno-histochemically, and its level of expression correlated with clinical data and outcomes.Results: Platelet aggregation in zone 3 was 70%, compared with 30% in zone 1 and 50% in zone 2. Platelets were found mainly as extravasated platelet aggregates in local microenvironments. Patients were stratified according to the extent of extravasated platelet aggregates in zone 3 into extravasated platelet aggregate-negative and -positive groups. Graft weight/recipient body weight ratio with the extravasated platelet aggregate-positive group was significantly lower than that of the extravasated platelet aggregate-negative group. Platelet count after surgery was lower, while total bilirubin and prothrombin time/international normalized ratio were higher in the extravasated platelet aggregate-positive than they were in the extravasated platelet aggregate-negative group.Conclusions: Extravasated platelet aggregates in the zone 3 of allograft tissue cause the consumption of platelets and continuous thrombocytopenia after transplant, and may be the clinical marker for deterioration of graft function. Platelet activation and degranulation following the release by platelets of some negative regulators may be involved partially in liver damage.
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| 8.
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Nakanuma, Shinichi ; Takamura, Hiroyuki ; Shoji, Masatoshi ; Hayashi, Hironori ; Tajima, Hidehiro ; Nakagawara, Hisatoshi ; Miyashita, Tomoharu ; Kitagawa, Hirohisa ; Tani, Takashi ; Ohta, Tetsuo ; 中沼, 伸一 ; 高村, 博之 ; 林, 泰寛 ; 田島, 秀浩 ; 中川原, 寿俊 ; 宮下, 知治 ; 北川, 裕久 ; 太田, 哲生
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金沢大学附属病院肝胆膵・移植外科<br />Liver transplant is a treatment for familial amyloid polyneuropathy. Few cases of ABO-incompatible
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living-donor liver transplant for familial amyloid polyneuropathy exist. The outcome of an ABO-incompatible living-donor liver transplant has improved recently, using local infusion therapy and rituximab prophylaxis. Here, we describe a successful ABO-incompatible living-donor liver transplant in a patient with familial amyloid polyneuropathy in whom disease progression ceased at 2 years’ follow-up. Additionally, no evidence of acute or chronic rejection, or adverse events of the immuno-suppressive therapy, was seen. As a postoperative complication, fatty changes in the grafted liver because of malnutrition or adverse events of corticosteroids were confirmed by a liver biopsy taken early after transplant. The main cause of malnutrition was considered to be gastrointestinal dysfunction caused by familial amyloid poly-neuropathy. Therefore, before deterioration of digestive function, liver transplants should be considered for familial amyloid polyneuropathy. This case suggests that an ABO-incompatible living-donor liver transplant may provide greater opportunities for familial amyloid polyneuropathy patients.
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| 9.
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太田, 哲生 ; 米田, 貢 ; 菊池, ゆひ ; 少作, 隆子
概要:
Motor performance depends on feedback and feedforward motor control systems, and can be improved through learning proces
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ses. According to the “feedback error learning” model, the feedback of error signals improves “internal models” and refines the feedforward motor control. Thus, feedforward motor control plays a key role in improving motor performance. Feedforward motor control has been evaluated by measuring predictive components of movement in several tasks, including ball-catching, grasping, and weight-loading tasks. In the loading task, hand movement just before the start of loading （anticipatory response） is observed only when the timing of loading is predictable. Thus, this anticipatory response is assumed to reflect prediction-based feedforward motor control. On the other hand, a multi-lever-pressing task has been used to evaluate motor performance and its improvement by analyzing accelerometer signals. Correlation coefficients of accelerometer signals have been reported to increase with the number of trials, indicating that this measure can be used as an index of motor learning. In the present study, we examined the relationship between feedforward motor control and motor learning in 18 healthy volunteers using anticipatory responses in a loading task and correlation coefficients of accelerometer signals in a three-lever-pressing task. For the loading task, we used the Space Interface Device for Artificial Reality （SPIDAR）. The subject was asked to hold the ball-shaped grip of SPIDAR. When the subject pressed the start button, a force of 4.9 N was applied to the grip. The subject was instructed to maintain the initial position during loading. The loading task was repeated 10 times, and the amplitude of upward deflection （anticipatory response） just before the start of loading was measured. In the three-lever-pressing task, the subject was instructed to press three levers as rapidly as possible using the left hand （hand）, the left hand loaded with a weight （weight）, and a stick attached to the left hand （stick）. The three-lever-pressing task was repeated 11 times in sequence under each condition （hand, weight, stick）. The hand movement was monitored using an accelerometer attached to the dorsal surface of the left hand. We found that correlation coefficients of accelerometer signals were lower in the stick condition than in the other two conditions, indicating that the stick variation of the task requires more learning. We also found that the amplitude of anticipatory response was correlated with the correlation coefficients of accelerometer signals only in case of the stick variation. These results provide evidence for a relationship between prediction-based feedforward motor control and motor learning.<br />運動をなめらかに行うためには、フィードバックおよびフィードフォワードの運動制御が必要である。運動学習と運動制御の仕組みを説明する現在の仮説は、誤差情報をフィードバックすることにより内部モデルを修正し、フィードフォワード制御の精度を上げる、というものであり、運動の上達においてフィードフォワード制御は重要な要素と考えられている。 フィードフォワード制御を評価する課題の１つとして、重りの負荷課題がある。予測が可能な条件で見られる、負荷の直前の手の動き（先行反応）は、予測に基づくフィードフォワード制御を反映するものと考えられている。一方、マルチレバー押し課題は、レバーを押す上肢の動きを加速度計で計測することで、上肢の運動制御を客観的に評価できる課題である。また、レバー押しを繰り返した時の加速度波形の類似性（波形間の相関係数）は、動作の習熟に伴い高くなることが報告されており、動作の習熟度を評価する指標として用いることができる。本研究では、健常者 18 名を対象とし、重りの負荷課題と３レバー押し課題の手の動きを解析し、フィードフォワード制御と運動の習熟との関係を調べた。左手で直接レバーを押す場合は、先行反応の大きさと加速度波形の類似性との間には相関はみられなかったが、左手に取り付けた棒でレバーを押す課題では、左右軸の動きに関して中程度の正の相関がみられた。以上の結果は、フィードフォワード制御と不慣れな運動の習熟との間に関係がある可能性を示唆している。
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| 10.
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Ohta, Tetsuo ; Yamamoto, Miyuki ; Numata, Masayuki ; Iseki, Shoichi ; Tsukioka, Yuhji ; Miyashita, Tomoharu ; Kayahara, Masato ; Nagakawa, Takukazu ; Miyazaki, Itsuo ; Nishikawa, Katsuzo ; Yoshitake, Yoshino ; 太田, 哲生 ; 山本, 美由紀 ; 井関, 尚一 ; 宮下, 知治 ; 萱原, 正都 ; 永川, 宅和 ; 宮崎, 逸夫 ; 西川, 克三
概要:
金沢大学医薬保健研究域医学系<br />We examined the expression of basic fibroblast growth factor (FGF) and FGF receptor by immunohistoch
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emistry in 32 human pancreatic ductal adenocarcinomas. Mild to marked basic FGF immunoreactivity was noted in 19 (59.4%) of the 32 tumours examined, and 30 (93.3%) of the tumours exhibited a cytoplasmic staining pattern against FGF receptor. The tumours were divided into two groups according to the proportion of positively stained tumour cells: A low expression group (positive cells ≪ 25%) and a high expression group (positive cells > or = 25%). No statistically significant difference in tumour size, differentiation, metastases or stage was found between the low and high basic FGF expression groups. However, a significant correlation was found between FGF receptor expression level and the presence of retroperitoneal invasion, lymph node metastasis, and tumour stage. In addition, low FGF receptor expression was significantly associated with a longer post-operative survival as compared with high FGF receptor expression, whereas there was no significant difference in post-operative survival between the low and high basic FGF expression groups. Increased expression of FGF receptor is correlated with the extent of malignancy and post-operative survival in human pancreatic ductal adenocarcinomas. Thus, overexpression of FGF receptor may prove to be a more useful prognostic marker than basic FGF expression level in pancreatic cancer patients. © 1995 Stockton Press. All rights reserved.<br />Embargo Period 12 months
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