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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
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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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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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| 4.
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Okamoto, Koichi ; Tajima, Hidehiro ; Nakanuma, Shinichi ; Sakai, Seisho ; Makino, Isamu ; Kinoshita, Jun ; Hayashi, Hironori ; Nakamura, Keishi ; Oyama, Katsunobu ; Nakagawara, Hisatoshi ; Fujita, Hideto ; Takamura, Hiroyuki ; Ninomiya, Itasu ; Kitagawa, Hirohisa ; Fushida, Sachio ; Fujimura, Takashi ; Harada, Shinichi ; Wakayama, Tomohiko ; Iseki, Shoichi ; Ohta, Tetsuo ; 岡本, 浩一 ; 田島, 秀浩 ; 中村, 信一 ; 牧野, 勇 ; 木下, 淳 ; 林, 泰寛 ; 中村, 慶史 ; 尾山, 勝信 ; 中川原, 寿俊 ; 藤田, 秀人 ; 高村, 博之 ; 二宮, 致 ; 北川, 裕久 ; 伏田, 幸夫 ; 藤村, 隆 ; 原田, 真市 ; 若山, 友彦 ; 井関, 尚一 ; 太田, 哲生
概要:
金沢大学医薬保健研究域医学系<br />We previously reported that hepatic stellate cells (HSCs) activated by angiotensin II (AngII) facili
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tate stromal fibrosis and tumor progression in intrahepatic cholangiocarcinoma (ICC). AngII has been known as a growth factor which can promote epithelial-to-mesenchymal transition (EMT) in renal epithelial cells, alveolar epithelial cells and peritoneal mesothelial cells. However, in the past, the relationship between AngII and stromal cell-derived factor-1 (SDF-1) in the microenvironment around cancer and the role of AngII on EMT of cancer cells has not been reported in detail. SDF-1 and its specific receptor, CXCR4, are now receiving attention as a mechanism of cell progression and metastasis. In this study, we examined whether activated HSCs promote tumor fibrogenesis, tumor progression and distant metastasis by mediating EMT via the AngII/AngII type 1 receptor (AT-1) and the SDF-1/CXCR4 axis. Two human ICC cell lines and a human HSC line, LI-90, express CXCR4. Significantly higher concentration of SDF-1αwas released into the supernatant of LI-90 cells to which AngII had been added. SDF-1α increased the proliferative activity of HSCs and enhanced the activation of HSCs as a growth factor. Furthermore, addition of SDF-1α and AngII enhanced the increase of the migratory capability and vimentin expression, reduced E-cadherin expression, and translocated the expression of β-catenin into the nucleus and cytoplasm in ICC cells. Co-culture with HSCs also enhanced the migratory capability of ICC cells. These findings suggest that SDF-1α, released from activated HSCs and AngII, play important roles in cancer progression, tumor fibrogenesis, and migration in autocrine and paracrine fashion by mediating EMT. Our mechanistic findings may provide pivotal insights into the molecular mechanism of the AngII and SDF-1α-initiated signaling pathway that regulates fibrogenesis in cancerous stroma, tumor progression and metastasis of tumor cells expressing AT-1 and CXCR4.<br />Embargo Period 6 months
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| 5.
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Tajima, Hidehiro ; Takamura, Hiroyuki ; Kitagawa, Hirohisa ; Nakayama, Akira ; Shoji, Masatoshi ; Watanabe, Toshifumi ; Tsukada, Tomoya ; Nakanuma, Shinichi ; Okamoto, Koichi ; Sakai, Seisho ; Kinoshita, Jun ; Makino, Isamu ; Nakamura, Keishi ; Hayashi, Hironori ; Oyama, Katsunobu ; Inokuchi, Masafumi ; Nakagawara, Hisatoshi ; Miyashita, Tomoharu ; Ninomiya, Itasu ; Fushida, Sachio ; Fujimura, Takashi ; Wakayama, Tomohiko ; Iseki, Shoichi ; Ikeda, Hiroko ; Ohta, Tetsuo ; 田島, 秀浩 ; 高村, 博之 ; 北川, 裕久 ; 中村, 信一 ; 岡本, 浩一 ; 木下, 淳 ; 牧野, 勇 ; 中村, 慶史 ; 林, 泰寛 ; 尾山, 勝信 ; 井口, 雅史 ; 中川原, 寿俊 ; 宮下, 知治 ; 二宮, 致 ; 若山, 友彦 ; 藤村, 隆 ; 井関, 尚一 ; 池田, 博子 ; 太田, 哲生
概要:
金沢大学医薬保健研究域医学系<br />A 33-year-old female was diagnosed with a solid pseudopapillary tumor (SPT) of the pancreas and mult
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iple liver metastases at the Department of Gastroenterological Surgery, Ishikawa Prefectural Central Hospital (Kanazawa, Japan). Distal pancreatectomy and postoperative systemic chemotherapy with gemcitabine (GEM) and S-1, an oral fluoropyrimidine derivative, was administered, however, liver metastases became enlarged and local recurrence occurred. Therefore, the patient was referred to the Department of Gastroenterologic Surgery at the Graduate School of Medicine (Kanazawa, Japan) for hepatic arterial infusion (HAI) chemotherapy. Oral S-1 (80 mg/m2) was administered as well as HAI chemotherapy with GEM (1,000 mg/standard liver volume). Following 18 cycles, tumor sizes were reduced and 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) examination revealed obvious reduction of tumor FDG uptake. Transarterial tumor embolization (TAE) was performed for the previously unresectable right subphrenic liver tumor, and the other tumors were surgically resected. The resected tumors were diagnosed as liver metastases and a local recurrence of SPT in the postoperative pathological examination, which revealed that the resected tumors were composed of sheets of bland cells, which were positive for CD10, CD56, vimentin, neuron-specific enolase and α-antitrypsin. The postoperative course was uneventful, and the patient is currently under observation at an outpatient clinic; postoperative adjuvant chemotherapy with oral S-1 has continued, and additional TAE is planned. In the future, if the middle segment of the liver becomes enlarged, surgery for the residual right lobe tumor may be possible. This case demonstrates one method of SPT treatment: Preoperative HAI chemotherapy with GEM, plus oral S-1 and TAE. If complete resection can be achieved, the majority of patients with SPT have a favorable prognosis. In patients with unresectable metastases from SPT, it is crucial to conduct systematic multimodal treatment to maximize treatment success. © 2015, Spandidos Publications. All Rights Reserved.<br />Embargo Period 6 months
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Yoshimoto, Katsuhiro ; Tajima, Hidehiro ; Ohta, Tetsuo ; Okamoto, Koichi ; Sakai, Seisho ; Kinoshita, Jun ; Furukawa, Hiroyuki ; Makino, Isamu ; Hayashi, Hironori ; Nakamura, Keishi ; Oyama, Katsunobu ; Inokuchi, Masafumi ; Nakagawara, Hisatoshi ; Itoh, Hiroshi ; Fujita, Hideto ; Takamura, Hiroyuki ; Ninomiya, Itasu ; Kitagawa, Hirohisa ; Fushida, Sachio ; Fujimura, Takashi ; Wakayama, Tomohiko ; Iseki, Shoichi ; Shimizu, Koichi ; 田島, 秀浩 ; 太田, 哲生 ; 岡本, 浩一 ; 木下, 淳 ; 古川, 裕之 ; 牧野, 勇 ; 林, 泰寛 ; 中村, 慶史 ; 尾山, 勝信 ; 井口, 雅史 ; 中川原, 寿俊 ; 藤田, 秀人 ; 高村, 博之 ; 二宮, 致 ; 藤村, 隆 ; 若山, 友彦 ; 井関, 尚一 ; 清水, 康一
概要:
金沢大学医薬保健研究域医学系<br />Several recent studies have reported that selectins are produced during ischemia-reperfusion injury,
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and that selectin ligands play an important role in cell binding to the endothelium and in liver metastasis. Portal clamping during pancreaticoduodenectomy with vessel resection for pancreatic head cancer causes hepatic ischemia-reperfusion injury, which might promote liver metastasis. We investigated the liver colonization of pancreatic cancer cells under hepatic ischemia-reperfusion and examined the involvement of E-selectin and its ligands. A human pancreatic cancer cell line (Capan-1) was injected into the spleen of mice after hepatic ischemia-reperfusion (I/R group). In addition, to investigate the effect of an anti-E-selectin antibody on liver colonization in the IR group, mice received an intraperitoneal injection of the anti-E-selectin antibody following hepatic ischemia-reperfusion and tumor inoculation (IR+Ab group). Four weeks later, mice were sacrificed and the number of tumor nodules on the liver was compared to mice without hepatic ischemia-reperfusion (control group). The incidence of liver metastasis in the I/R group was significantly higher (16 of 20, 80%) than that in the control group (6 of 20, 30%) (P<0.01). Moreover, mice in the I/R group had significantly more tumor nodules compared to those in the control group (median, 9.9 vs. 2.7 nodules) (P<0.01). In the I/R+Ab group, only 2 of 5 (40%) mice developed liver metastases. RT-PCR and southern blotting of the liver extracts showed that the expression of IL-1 and E-selectin mRNA after hepatic ischemia-reperfusion was significantly higher than the basal levels. Hepatic ischemia-reperfusion increases liver metastases and E-selectin expression in pancreatic cancer. These results suggest that E-selectin produced due to hepatic ischemia-reperfusion is involved in liver metastasis.<br />Embargo Period 6 months
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| 7.
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牧野, 勇 ; 北川, 裕久 ; 太田, 哲生 ; 萱原, 正都 ; 西村, 元一 ; 藤村, 隆 ; 清水, 康一 ; 三輪, 晃一 ; 佐藤, 勝明 ; 小田, 惠夫
概要:
症例は74歳の男性で,眼球黄染と褐色尿を主訴とし入院した.胆道直接造影検査にて下部胆管内腔に乳頭状に突出する腫瘍を認め,胆汁細胞診ではclass V (adenocarcinoma)であったため下部胆管癌と診断した.画像診断上は膵,十二指腸
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への浸潤はなく,明らかなリンパ節転移,肝転移の所見もなかった.入院当初はendoscopic nasobiliary drainageを行っていたが減黄不良のためpercutaneous transhepatic cholangial drainageに変更し減黄改善を図ったが,次第に肝機能が悪化し,同年7月に肝不全死した.病理解剖の結果,下部胆管内腔に黄色調,乳頭膨張型の腫瘍を認め,肝内に3か所,大網に1か所の転移巣が存在した.病理組織像では,未分化な細胞が充実性に増殖し,免疫染色ではchromogranin A染色,Grimelius染色,CD56染色,CAM染色が陽性で胆管原発小細胞癌と診断された.胆管原発小細胞癌は極めてまれであり,文献的考察を加えて報告した. A 74 year-old man admitted for jaundice was found in diagnostic imaging to have a growing papillary tumor occupying the lumen of the lower bile duct. We diagnosed it as lower bile duct cancer without invasion to other organs, lymph node metastasis, liver metastasis, or distant metastasis, suggesting it could be curatively resected. Though we attempted to improve jaundice before surgery with PTCD, it was persisted and his liver function gradually worsened. He died of liver failure 3 months after admission. Autopsy showed a yellowish expanded papillary tumor in the lower bile duct, 3 metastatic nodules in the liver, and one on the omentum. Histopathological specimens showed undifferentiated round cells arranged crowded or in uncertain gland pattern. In immunohistological studies, granules stained with chromogranin A, Grimelius, CD56, or CAM in the cytoplasm of the cancer cells, and the tumor was diagnosed as small cell carcinoma arising primarily in the common bile duct.
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| 8.
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山崎, 祐樹 ; 伏田, 幸夫 ; 尾山, 勝信 ; 木下, 淳 ; 牧野, 勇 ; 中村, 慶史 ; 藤田, 秀人 ; 二宮, 致 ; 藤村, 隆 ; 太田, 哲生
概要:
We report a case of advanced gastric cancer with para-aortic lymph node metastasis that underwent radical gastrectomy af
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ter neoadjuvant chemotherapy, and in this case, thoracoscopy was useful in excluding mediastinal lymph node metastasis. The patient was a 70-year-old man in whom a large type 2 advanced gastric cancer accompanied with para-aortic and mediastinal lymph node metastasis was diagnosed. We attempted combination therapy of Docetaxel, CDDP and TS-1. After 2 courses of treatment, the primary lesion and regional and para-aortic lymph nodes were significantly reduced in size, suggesting that this therapy had induced a partial response (PR). However, the size of mediastinal lymph node did not change. FDG-PET showed accumulation of FDG located in the mediastinal lymph node, in which metastasis was suspected. To judge the possibility of radical excision, we performed tho-racoscopic biopsy of the mediastinal lymph node. No metastasis was shown in the mediastinal lymph node biopsy, so we performed curative total gastrectomy with D3 lymph node dissection and cholecys-tectomy with curative intent. The pathological findings showed that there were very few cancer cells either in the primary lesion and only one lymph node (No.3). There has been no recurrence for two years after the operation. © 2012 The Japanese Society of Gastroenterological Surgery. 術前DCS（docetaxel，cisplatin，TS-1併用）療法が著効した大動脈周囲リンパ節転移を伴う進行胃癌を経験した．また，胸腔鏡下生検が縦隔リンパ節転移の除外診断に有用であったので報告する．症例は70歳の男性で，噴門直下から角上部に及ぶ大型の2型腫瘍を認めた．大動脈周囲・縦隔を含め多数のリンパ節腫大を認めた．DCS療法を2コース行い，原発巣・リンパ節転移巣ともに著明に縮小した．しかし，縦隔リンパ節に変化はなくPET-CTでも淡い集積を認め転移も否定できないため，胸腔鏡下に縦隔リンパ節生検を行ったところ，転移を認めなかった．根治切除可能と判断し大動脈周囲リンパ節郭清を伴う胃全摘術を行った．組織学的に腫瘍の大部分は壊死に陥り，原発巣の一部と壁在リンパ節1個にごく僅かに腫瘍細胞が残存していた．現在，術後2年が経過しているが，無再発生存中である．
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| 9.
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牧野, 勇 ; 谷, 卓 ; 高村, 博之 ; 中川原, 寿俊 ; 田島, 秀浩 ; 大西, 一朗 ; 北川, 裕久 ; 伏田, 幸夫 ; 藤村, 隆 ; 西村, 元一 ; 萱原, 正都 ; 太田, 哲生 ; 湊, 宏 ; 蒲田, 敏文 ; 松井, 修 ; 清水, 康一
概要:
症例は52歳の女性,褐色尿を主訴として来院した,画像診断にて肝門部に2つの嚢胞性病変を認め,一方は主に肝内側区域に存在し肝門部で左右のグリソン鞘を圧排する単房性嚢胞性病変で,他方はこの病変と接して肝外に突出し内部に壁在結節を伴う多房性嚢胞性
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病変であった.後者の病変は肝外胆管に接し,これを圧排しており,肝外胆管が狭窄を呈していた.拡大肝左葉切除,肝外胆管切除にて切除しえた.切除標本では肝内側区域に存在する単房性嚢胞性腫瘍と,これと連続して肝外に突出し総肝管を圧排する多房性嚢胞性腫瘍を認め,後者の嚢胞壁には乳頭状腫瘍が存在した.病理組織所見では2つの嚢胞性病変は一連の腫瘍と考えられ,現行の規約に従い胆管嚢胞腺癌と診断した.一方で,この嚢胞性腫瘍は標本造影で胆管との交通が証明され,組織学的に卵巣様間質を認めないことから,近年提唱されている胆管内乳頭状腫瘍に分類できると考えられた.
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齋藤, 裕人 ; 尾山, 勝信 ; 伏田, 幸夫 ; 柄田, 智也 ; 岡本, 浩一 ; 中沼, 伸一 ; 木下, 淳 ; 牧野, 勇 ; 中村, 慶史 ; 林, 泰寛 ; 井口, 雅史 ; 中川原, 寿俊 ; 宮下, 知治 ; 藤田, 秀人 ; 田島, 秀浩 ; 高村, 博之 ; 二宮, 致 ; 北川, 裕久 ; 藤村, 隆 ; 太田, 哲生
概要:
We report a case of gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor (G-CSF). A 60-year-o
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ld man was admitted to our hospital complaining of upper abdominal pain. Endoscopic examination revealed a large type 5 advanced gastric cancer with bleeding from the low body of stomach to the antrum, accompanied with para-aortic and mesenteric lymph node metastasis. He had marked leukocytosis, and serum levels of G-CSF were elevated. Histological diag-nosis of the biopsy specimen was adenosquamous carcinoma producing G-CSF. We attempted combination chemotherapy with docetaxel, cisplatin and S-1 (DCS). After 1 course of treatment, the primary lesion was reduced in size. However, the size of the metastatic lymph node was larger. Chemotherapy was not effective enough, and the patient died 3 months after ending chemotherapy. 症例は60歳、男性。上腹部痛を主訴に受診。上部消化管内視鏡で胃体下部から前庭部の小弯後壁に易出血性の5型胃癌を認め、画像所見で傍大動脈・腸間膜リンパ節転移を認めた。生検にて腺癌成分と扁平上皮癌成分の混在を認めた。来院時より白血球数が著明に増多し、血清G-CSF高値、生検組織の免疫組織染色で腫瘍組織のG-CSF発現を認めた。以上よりG-CSF産生胃腺扁平上皮癌と診断し、化学療法（DCS (docetaxel/ cisplatin/ S-1併用)療法）を1コース行ったところ原発巣の縮小を認めたが、転移リンパ節の増大を認めた。急激な病状悪化により3ヶ月の経過で死亡した。
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