Researchers Database

fukushima noriyoshi

    DepartmentofDiagnosticPathology Professor
Last Updated :2021/12/04

Researcher Information

URL

J-Global ID

Research Interests

  • 膵癌   前駆病変   腫瘍   前癌病変   膵管癌   病理学   

Research Areas

  • Life sciences / Human pathology

Academic & Professional Experience

  • 2009/09 - Today  Jichi Medical UniversityDepartment of PathologyProfessor・Director
  • 2014  Jichi Medical UniversitySchool of Medicine教授

Published Papers

  • Atsushi Kihara, Yusuke Amano, Daisuke Matsubara, Noriyoshi Fukushima, Hiroyuki Fujiwara, Toshiro Niki
    Human Pathology 116 12 - 21 0046-8177 2021/10
  • Mio Tamba-Sakaguchi, Hisashi Oshiro, Naoko Mato, Ichiro Kikkawa, Teruaki Endo, Miki Yanagita, Tomoko Suzuki, Maho Akimoto, Naota Okabe, Masahiro Hiruta, Eriko Ikeda, Noriyoshi Fukushima
    Diagnostic cytopathology 2021/09 
    Cytological detection of chordoma cells in the serosal cavity is challenging because of its rare presentation. Herein, we report a case of chordoma showing malignant pleural effusion accompanied by pleuropulmonary metastases in a 68-year-old woman. Cytological analysis was performed using pleural fluid obtained following thoracentesis. Conventional cytological staining demonstrated few clusters of large, atypical cells characterized by epithelial cell-like connectivity and rich cytoplasm with foamy and/or multivacuolar changes. The nuclei of these atypical cells were large and either round or oval with no conspicuous irregularities in the nuclear membrane. Periodic acid-Schiff staining of these atypical cells revealed fine granules in the cytoplasm. Giemsa staining showed foamy and/or multivacuolar cytoplasm in these cells, with metachromatic mucoid stroma in the surroundings. Immunocytochemistry analysis using cellblock showed these cells to be positive for broad cytokeratins, epithelial membrane antigen, S100 protein, vimentin, and Brachyury. To the best of our knowledge, this is the first case report in which chordoma cells were cytologically detected in pleural effusions. Our findings also suggest that conventional cytology combined with cellblock immunocytochemistry can increase the accuracy of chordoma cell detection in the serosal cavity.
  • Masafumi Kitamura, Yoshimasa Miura, Satoshi Shinozaki, Hirotsugu Sakamoto, Yoshikazu Hayashi, Mio Sakaguchi, Noriyoshi Fukushima, Alan Kawarai Lefor, Hironori Yamamoto
    Endoscopy international open 9 (7) E1062-E1069  2021/07 
    Background and study aims  Endoscopic submucosal dissection (ESD) of superficial gastric lesions involving the pyloric ring is difficult. The pocket-creation method (PCM) with a small-caliber-tip transparent hood can overcome this difficulty by compressing the pyloric sphincter applying both traction and counter-traction. The aim of this study is to clarify the usefulness of the PCM for ESD of superficial gastric neoplasms involving the pyloric ring compared to the conventional method (CM). Patients and methods  From October 2006 to August 2019, 66 gastric lesions requiring duodenal submucosal dissection beyond the pyloric ring in 66 patients were resected. The CM was mainly performed in the first period (CM group, n = 46) and the PCM in the second period (PCM group, n = 20). We retrospectively reviewed their medical records. Results  Although no significant differences were observed in en bloc resection rates between the two groups, the PCM group had a significantly higher R0 resection rate than the CM group ( P  = 0.047). There were no holes in resected specimens in the PCM group while three specimens in the CM group had a hole. The dissection speed in the PCM group tended to be higher than in the CM group, although it did not reach statistical significance ( P  = 0.148). No significant differences were observed for the incidence of adverse events. Conclusions  This is the first study reporting the advantages of the PCM over the CM for ESD of gastric lesions involving the pyloric ring. We believe that the PCM is an effective strategy to compress the pyloric sphincter and facilitates R0 resection.
  • Ryuji Komine, Motohiro Kojima, Genichiro Ishi, Masashi Kudo, Motokazu Sugimoto, Shin Kobayashi, Shinichiro Takahashi, Masaru Konishi, Tatsushi Kobayashi, Tetsuo Akimoto, Ayumi Murakami, Motoko Sasaki, Mariko Tanaka, Akiko Matsuzaki, Nobuyuki Ohike, Katsunori Uchida, Tomoko Sugiyama, Kenichi Hirabayashi, Takuma Tajiri, Kazuyuki Ishida, Keita Kai, Yuko Omori, Kenji Notohara, Hiroshi Yamaguchi, Yoko Matsuda, Yoshiki Naito, Yuki Fukumura, Yoshihiro Hamada, Yumi Mihara, Yohei Masugi, Naoto Gotohda, Kenichi Harada, Noriyoshi Fukushima, Toru Furukawa
    Cancer Medicine 10 (11) 3499 - 3510 2045-7634 2021/06
  • Keiko Yamaoka, Shuichi Nagashima, Nobukazu Okada, Nagisa Sawayama, Shinsuke Saito, Manabu Takahashi, Kenta Okada, Kazuhiro Endo, Masaru Koizumi, Hideki Sasanuma, Ken Ebihara, Atsuko Kasajima, Noriyoshi Fukushima, Naohiro Sata, Shun Ishibashi
    Clinical case reports 9 (5) e04118  2021/05 
    Long-acting somatostatin analogs, including lanreotide slow release (LAN-SR) and octreotide long-acting release (OCT-LAR), can improve hypoglycemia in insulinoma. LAN-SR may be more beneficial in some patients with insulinoma than OCT-LAR.
  • 池田 恵理子, 牛尾 純, 安藤 梢, 谷川 雅彦, 坂口 美織, 三輪田 哲郎, 長井 洋樹, 多田 大和, 横山 健介, 菅野 敦, 森嶋 計, 笹沼 英紀, 玉田 喜一, 佐田 尚宏, 福嶋 敬宜
    胆と膵 医学図書出版(株) 42 (5) 393 - 400 0388-9408 2021/05 
    胆膵領域に発生する腫瘍は、しばしば画像診断に難渋する。画像診断精度を向上させるためには、術前画像で異常所見を拾い上げる所見のための根拠を病理組織学的に検証していくことが重要である。当施設では、詳細な術前画像と病理像の対比のために、臨床医と病理医が協力して「検体造影検査」に加え「術後検体超音波検査」を行っている。とくに、「術後検体超音波検査」は、簡便で、病理像・画像対比に適した病理組織標本を作ることができ、画像所見へのフィードバックや診療科横断的なコミュニケーションツールとしても有意義な検査である。(著者抄録)
  • Yoshiki Naito, Masayuki Tsuneki, Noriyoshi Fukushima, Yutaka Koga, Michiyo Higashi, Kenji Notohara, Shinichi Aishima, Nobuyuki Ohike, Takuma Tajiri, Hiroshi Yamaguchi, Yuki Fukumura, Motohiro Kojima, Kenichi Hirabayashi, Yoshihiro Hamada, Tomoko Norose, Keita Kai, Yuko Omori, Aoi Sukeda, Hirotsugu Noguchi, Kaori Uchino, Junya Itakura, Yoshinobu Okabe, Yuichi Yamada, Jun Akiba, Fahdi Kanavati, Yoshinao Oda, Toru Furukawa, Hirohisa Yano
    Scientific reports 11 (1) 8454 - 8454 2021/04 
    Histopathological diagnosis of pancreatic ductal adenocarcinoma (PDAC) on endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) specimens has become the mainstay of preoperative pathological diagnosis. However, on EUS-FNB specimens, accurate histopathological evaluation is difficult due to low specimen volume with isolated cancer cells and high contamination of blood, inflammatory and digestive tract cells. In this study, we performed annotations for training sets by expert pancreatic pathologists and trained a deep learning model to assess PDAC on EUS-FNB of the pancreas in histopathological whole-slide images. We obtained a high receiver operator curve area under the curve of 0.984, accuracy of 0.9417, sensitivity of 0.9302 and specificity of 0.9706. Our model was able to accurately detect difficult cases of isolated and low volume cancer cells. If adopted as a supportive system in routine diagnosis of pancreatic EUS-FNB specimens, our model has the potential to aid pathologists diagnose difficult cases.
  • Taku Uchiyama, Akira Gomi, Sumihito Nobusawa, Noriyoshi Fukushima, Daisuke Matsubara, Kensuke Kawai
    Brain tumor pathology 2021/04 
    Rosette-forming glioneuronal tumors (RGNTs) are benign WHO grade 1 tumors that occur in the ventricular system, particularly the fourth ventricle. RGNTs and dysembryoplastic neuroepithelial tumors (DNTs) are both categorized as neuronal and mixed neuronal-glial tumors and may be difficult to distinguish. Coexistence of the two tumor types has been reported. Here, we report a pediatric case of RGNT with DNT-like features showing intraventricular dissemination. The tumor occurred in the medial temporal lobe and presented with specific pathological glioneuronal elements including floating neurons, which are typical in DNTs, but was diagnosed as RGNT because of the presence of neurocytic rosettes. Genetic analysis detected fibroblast growth factor receptor 1 internal tandem duplication (FGFR1-ITD) of the tyrosine kinase domain, which was previously reported to be specific for DNT. RGNTs with FGFR1-ITD may show atypical clinical presentation and pathological features.
  • Daishi Naoi, Hisanaga Horie, Koji Koinuma, Yuko Kumagai, Gaku Ota, Mineyuki Tojo, Yuji Kaneda, Shuji Hishikawa, Ai Sadatomo, Yoshiyuki Inoue, Noriyoshi Fukushima, Alan Kawarai Lefor, Naohiro Sata
    Surgery today 2021/03 
    PURPOSE: The aim of this study was to evaluate both the intestinal mucosa staple line integrity and anastomotic leak pressure after healing in a porcine survival model. METHODS: We used two suture models using two different size staples (incomplete mucosal closure model: group G [staple height 0.75 mm], complete mucosal closure model: group B [staple height 1.5 mm]) in the porcine ileum. Five staple lines were created in each group made in the ileum for each model, and the staple sites harvested on days 0, 2, and 7. The leak pressure at the staple site was measured at each time point. RESULTS: On day 0, the leak pressure for group G (79.5 mmHg) was significantly lower than that for group B (182.3 mmHg) (p < 0.01). On days 2 and 7, there was no significant difference between groups G and B (171 mmHg and 175.5 mmHg on day 2, 175.5 mmHg and 175.5 mmHg on day 7, p > 0.05). The histological findings in both groups showed similar healing at postoperative days 2 and 7. CONCLUSION: The integrity of the mucosal staple lines was associated with the postoperative leak pressure on day 0. However, there was no association with the leak pressure at two days or more postoperatively in a porcine model.
  • Yusuke Amano, Kentaro Tsuji, Atshushi Kihara, Daisuke Matsubara, Noriyoshi Fukushima, Hiroshi Nishino, Toshiro Niki
    Medicine 100 (2) e24011  2021/01 
    RATIONALE: Salivary duct carcinoma (SDC) is a rare and highly aggressive cancer with a poor prognosis. SDC demonstrates a potential for invasive growth with early regional and distant metastasis to organs, such as bone, lung, liver, and brain. Because, adrenal gland metastasis from SDC is rare, its treatment options are not well established. Herein, we report a case of SDC metastasis from the parotid gland to the adrenal gland, which was successfully treated by surgery. PATIENT CONCERNS: The patient had an abnormal but painless lump on the right parotid gland. The size of the mass had increased over a period of 3 years. The patient underwent complete removal of the right parotid gland and radical neck dissection followed by adjuvant radiotherapy and chemotherapy. Two years later, a mass was identified in the left adrenal gland by computed tomography. As no local recurrence or metastasis to other organs was observed, the patient underwent adrenalectomy. DIAGNOSES: Metastasis of SDC in the adrenal gland was confirmed by histopathological examination of the adrenalectomized specimen. INTERVENTIONS: After adrenalectomy, the patient was followed-up without adjuvant therapy. OUTCOMES: The patient was well and alive during the 13-month postoperative follow-up period without any complications. LESSONS: Surgical resection of solitary metastatic lesion may show a survival benefit with metastatic SDC.
  • Boris V Janssen, Faik Tutucu, Stijn van Roessel, Volkan Adsay, Olca Basturk, Fiona Campbell, Claudio Doglioni, Irene Esposito, Roger Feakins, Noriyoshi Fukushima, Anthony J Gill, Ralph H Hruban, Jeffrey Kaplan, Bas Groot Koerkamp, Seung-Mo Hong, Alyssa Krasinskas, Claudio Luchini, Johan Offerhaus, Arantza Fariña Sarasqueta, Chanjuan Shi, Aatur Singhi, Thomas F Stoop, Eline C Soer, Elizabeth Thompson, Geertjan van Tienhoven, Marie-Louise F Velthuysen, Johanna W Wilmink, Marc G Besselink, Lodewijk A A Brosens, Huamin Wang, Caroline S Verbeke, Joanne Verheij
    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 34 (1) 4 - 12 2021/01 
    Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands. Here, we provide an overview of the outcomes and consensus statements that originated from this meeting. Consensus (≥80% agreement) was reached on a total of seven statements: (1) TRS is important because it provides information about the effect of neoadjuvant treatment that is not provided by other histopathology-based descriptors. (2) TRS for resected PDAC following neoadjuvant therapy should assess residual (viable) tumor burden instead of tumor regression. (3) The CAP scoring system is considered the most adequate scoring system to date because it is based on the presence and amount of residual cancer cells instead of tumor regression. (4) The defining criteria of the categories in the CAP scoring system should be improved by replacing subjective terms including "minimal" or "extensive" with objective criteria to evaluate the extent of viable tumor. (5) The improved, consensus-based system should be validated retrospectively and prospectively. (6) Prospective studies should determine the extent of tissue sampling that is required to ensure adequate assessment of the residual cancer burden, taking into account the heterogeneity of tumor response. (7) In future scientific publications, the extent of tissue sampling should be described in detail in the "Materials and methods" section.
  • Atsushi Kihara, Yusuke Amano, Daisuke Matsubara, Noriyoshi Fukushima, Hiroyuki Fujiwara, Toshiro Niki
    The American journal of surgical pathology 44 (12) 1712 - 1724 2020/12 
    Switch/sucrose nonfermenting complex subunits, such as BRG1, INI1, and ARID1B, are inactivated in a subset of endometrial undifferentiated carcinoma and dedifferentiated carcinoma (DC). Limited information is currently available on their prevalence in other subtypes or the nosological status of endometrial carcinoma with their deficiencies. This study immunohistochemically examined the expression status of BRG1, INI1, and ARID1B using 570 archived cases of endometrial carcinoma and carcinosarcoma resected at a single institution. We identified 1 BRG1-deficient undifferentiated carcinoma, 8 BRG1/INI1/ARID1B-deficient DC, and 3 BRG1-deficient clear-cell carcinomas. None of the cases of endometrioid and serous carcinomas or carcinosarcoma showed deficiencies of these subunits. We then compared 8 BRG1/INI1/ARID1B-deficient DC with 6 BRG1/INI1/ARID1B-intact DC and 28 carcinosarcomas, the latter of which was often confused with DC. Histologically, BRG1/INI1/ARID1B-intact and BRG1/INI1/ARID1B-deficient DC shared a monotonous solid appearance with rhabdoid and epithelioid cells and a myxoid stroma; however, abrupt keratinization and cell spindling was absent in BRG1/INI1/ARID1B-deficient tumors. The median overall survival of patients with BRG1/INI1/ARID1B-deficient DC was 3.8 months, which was worse than those with BRG1/INI1/ARID1B-intact DC (P=0.008) and with carcinosarcoma (P=0.004). BRG1/INI1/ARID1B-deficient DC may be a separate entity with an aggressive behavior to be distinguished from BRG1/INI1/ARID1B-intact DC and carcinosarcoma. Regarding clear-cell carcinoma (n=12), BRG1 deficiency appeared to be mutually exclusive with abnormal ARID1A, BRM, and p53 expression. Further studies are needed to clarify whether BRG1 deficiency plays a role in the pathogenesis of clear-cell carcinoma.
  • 膵細胞診の可能性と将来展望 膵組織透明化技術を併用した3D画像解析技術の膵細胞診への応用と展望
    池田 恵理子, 牛尾 純, 鈴木 智子, 中村 香織, 織田 智博, 二階堂 貴章, 郡 俊勝, 柳田 美樹, 小野寺 宏, 福嶋 敬宜
    日本臨床細胞学会雑誌 (公社)日本臨床細胞学会 59 (Suppl.2) 482 - 482 0387-1193 2020/11
  • Toshihide Komatsubara, Yasunaru Sakuma, Naohiro Sata, Noriyoshi Fukushima
    Pathology international 70 (11) 857 - 864 2020/11 
    Extrahepatic bile duct (EHBD) cancer is a devastating cancer, and more common in Asian countries than in Western countries. Histological grading continues to be a highly relevant factor in prognosis and management of many kinds of cancer, however no uniform histological grading system exists for EHBD cancer. Histological heterogeneity within tumors is a problem in the evaluation of EHBD cancer. We developed an EHBD histological grading scheme to evaluate tumor differentiation pattern, and statistically analyzed its relationship with prognosis. In the present study, 257 surgically resected EHBD cancers were reviewed and their histological glandular differentiation (HGD) pattern was scored, and then we summed up the most and second most predominant scores. These scores were statistically analyzed for their relationship with patient prognosis. Patients showed a trend of shortening recurrence-free survival (RFS) and overall survival (OS) in association with higher HGD scores. In multivariate analyses, HGD score was determined to be an influential factor in RFS (P = 0.00041) and OS (P < 0.0001). In addition, combining HGD score and lymph node status correctly stratified patient prognosis in RFS. In conclusion, this new HGD scoring system is highly practical and has powerful prognostic value for EHBD cancer.
  • Yusuke Amano, Mio Sakaguchi-Tamba, Yumiko Sasaki, Hisashi Oshiro, Noriyoshi Fukushima, Takashi Fujita, Shinobu Masuda, Toshiro Niki
    Medicine 99 (42) e22665  2020/10 
    INTRODUCTION: Breast adenomyoepithelioma (AME) is a rare tumor composed of myoepithelial cells and ductal or luminal cells. Most cases of AME are benign, but rare cases in which either or both cell types exhibited malignant features have been reported. Due to its rarity, no diagnostic criteria for malignancy have been established for AME. PATIENT CONCERNS: A 64-year-old woman presented with a mass in her right breast. Fine-needle aspiration cytology and biopsy examinations revealed lesions composed of spindle-shaped cells and round epithelial cells. AME was suspected, and partial mastectomy was performed. DIAGNOSIS: The tumor specimen showed AME, which mainly consisted of spindle-shaped myoepithelial cells with slight atypia, admixed with tubular luminal cells and small areas of atypical intraductal proliferative lesions. No apparent features of malignancy, such as necrosis or invasion, were seen in the myoepithelial cells or the luminal or intraductal component. However, the atypical intraductal component exhibited focal nuclear atypia, a cribriform pattern, and moderate to strong membranous human epidermal growth factor receptor 2 (HER2) immunoreactivity. HER2 amplification was detected in focal regions of the atypical intraductal component by fluorescence in situ hybridization (FISH), which resulted in a diagnosis of AME with ductal carcinoma in situ. OUTCOMES: The patient did not receive further therapy and was free from tumor recurrence at 23 months after the operation. CONCLUSION: HER2 FISH might be useful for evaluating suspected AME tumors for malignancy when an atypical ductal lesion that lacks definitive features of malignancy is encountered.
  • Kenji Notohara, Terumi Kamisawa, Noriyoshi Fukushima, Toru Furukawa, Takuma Tajiri, Hiroshi Yamaguchi, Shinichi Aishima, Yuki Fukumura, Kenichi Hirabayashi, Eisuke Iwasaki, Atsushi Kanno, Satomi Kasashima, Atsuhiro Kawashima, Motohiro Kojima, Kensuke Kubota, Yasuhiro Kuraishi, Tomoko Mitsuhashi, Yoshiki Naito, Itaru Naitoh, Hiroshi Nakase, Takayoshi Nishino, Nobuyuki Ohike, Junichi Sakagami, Kyoko Shimizu, Masahiro Shiokawa, Takeshi Uehara, Tsukasa Ikeura, Shigeyuki Kawa, Kazuichi Okazaki
    Pathology international 70 (10) 699 - 711 2020/10 [Refereed][Not invited]
     
    The biopsy-based diagnosis of autoimmune pancreatitis (AIP) is difficult but is becoming imperative for pathologists due to the increased amount of endoscopic ultrasound-guided biopsy tissue. To cope with this challenge, we propose guidance for the biopsy diagnosis of type 1 AIP. This guidance is for pathologists and comprises three main parts. The first part includes basic issues on tissue acquisition, staining, and final diagnosis, and is intended for gastroenterologists as well. The second part is a practical guide for diagnosing type 1 AIP based on the AIP clinical diagnostic criteria 2018. Inconsistent histological findings, tips for evaluating IgG4 immunostaining and key histological features including the ductal lesion and others are explained. Storiform fibrosis and obliterative phlebitis are diagnostic hallmarks but are sometimes equivocal. Storiform fibrosis is defined as spindle-shaped cells, inflammatory cells and fine collagen fibers forming a flowing arrangement. Obliterative phlebitis is defined as fibrous venous obliteration with inflammatory cells. Examples of each are provided. The third part describes the differentiation of AIP from pancreatic ductal adenocarcinoma (PDAC), focusing on histological features of acinar-ductal metaplasia in AIP, which is an important mimicker of PDAC. This guidance will help standardize pathology reports of pancreatic biopsies for diagnosing type 1 AIP.
  • Keiichi Kubota, Jin-Young Jang, Yasuni Nakanuma, Kee-Taek Jang, Yasuo Haruyama, Noriyoshi Fukushima, Toru Furukawa, Seung-Mo Hong, Yuhki Sakuraoka, Haeryoung Kim, Takatsugu Matsumoto, Kyung Bun Lee, Yoh Zen, Jaeri Kim, Masaru Miyazaki, Dong Wook Choi, Jin Seok Heo, Itaru Endo, Shin Hwang, Masafumi Nakamura, Ho-Seong Han, Shinji Uemoto, Sang Jae Park, Eun Kyung Hong, Atsushi Nanashima, Dong-Sik Kim, Joo Young Kim, Tetsuo Ohta, Koo Jeong Kang, Takumi Fukumoto, Yang Won Nah, Hyung Il Seo, Kazuo Inui, Dong-Sup Yoon, Michiaki Unno
    Journal of hepato-biliary-pancreatic sciences 27 (9) 581 - 597 2020/09 [Refereed][Not invited]
     
    BACKGROUND: The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location. METHODS: IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid-tubular components. Medical data were evaluated. RESULTS: Among 694 IPNB patients, 520 and 174 had Type 1 and Type 2, respectively. The levels of AST, ALT, ALP, T. Bil, and CEA were significantly higher in patients with Type 2 than in those with Type 1. Type 1 IPNB was more frequently located in the intrahepatic bile duct than Type 2, whereas Type 2 was more frequently located in the distal bile duct than Type 1 IPNB (P < 0.001). There were significant differences in 5-year cumulative survival rates (75.2% vs 50.9%; P < 0.0001) and 5-year cumulative disease-free survival rates (64.1% vs 35.3%; P < 0.0001) between the two groups. CONCLUSION: Type 1 and Type 2 IPNBs differ in their clinicopathological features and prognosis. This classification may help to further understand IPNB.
  • Atsushi Kihara, Kazuya Takahashi, Ayataka Ishikawa, Yusuke Amano, Daisuke Matsubara, Hiroaki Kanda, Naohiro Sata, Noriyoshi Fukushima, Toshiro Niki
    Medical molecular morphology 53 (3) 177 - 182 2020/09 [Refereed][Not invited]
     
    We herein report a variant case of desmoplastic small round cell tumor (DSRCT) showing limited desmoplasia and confusing immunohistochemical findings. A 26-year-old male was referred for multiple abdominal masses. Laparoscopic biopsy showed only the solid proliferation of small round cells, and he was initially diagnosed with small cell carcinoma. At autopsy, the tumor spread diffusely throughout the abdominal and pelvic cavities. Although the tumor was composed of a predominantly solid pattern of small round cells, multiple samples revealed a fibrous stroma in limited areas only. While immunohistochemistry showed the diffuse expression of desmin, CD99, and bcl-2, epithelial differentiation was unclear with few cytokeratin-positive cells and no staining for the epithelial membrane antigen. Although fluorescence in situ hybridization analysis indicated the EWSR1 gene rearrangement, we were unable to exclude Ewing sarcoma considering the morphological and immunohistochemical findings. The diagnosis of DSRCT was confirmed with a reverse transcription-polymerase chain reaction for EWSR1-WT1 fusion transcripts. DSRCT must be included in a differential diagnosis of small round cell tumors even if desmoplasia is not immediately detected, and thorough sampling and a molecular analysis are mandatory.
  • Yuya Hiroshima, Soki Kurumisawa, Kei Aizawa, Noriyoshi Fukushima, Koji Kawahito
    Surgical case reports 6 (1) 128 - 128 2020/06 [Refereed][Not invited]
     
    BACKGROUND: Aspergillus endocarditis (AE) is a rare and lethal cardiac infection with a high rate of mortality. AE most commonly presents in immunocompromised patients and is associated with various co-morbidities. Herein, we present a case of AE associated with lung, brain, and cervical abscesses after chemotherapy for malignant lymphoma that was successfully treated by a combination of antifungal and surgical therapy. CASE PRESENTATION: A 29-year-old man was admitted to our hospital with an unidentified fever. He was diagnosed with malignant lymphoma (extra-nodal NK/T cell lymphoma nasal type), and chemotherapy was administered. After chemotherapy, nodular lung shadows along with new brain, cervical, and myocardial abscesses appeared, despite anti-bacterial/fungal therapy. Gene analysis of the cervical abscess biopsy revealed the presence of Aspergillus fumigatus species, and the transesophageal echocardiogram showed a mobile mural vegetation in the left ventricle (22 × 8 mm). He underwent surgical resection of this mural vegetation. His postoperative course was uneventful. He remains healthy at 28 months after surgery with continued oral antifungal therapy. CONCLUSION: Although AE associated with immunosuppression is a fatal clinical presentation, combined treatment with surgical resection and antifungal therapy was effective.
  • Olca Basturk, Britta Weigelt, Volkan Adsay, Jamal K Benhamida, Gokce Askan, Lu Wang, Maria E Arcila, Giuseppe Zamboni, Noriyoshi Fukushima, Rodrigo Gularte-Mérida, Arnaud Da Cruz Paula, Pier Selenica, Rahul Kumar, Fresia Pareja, Christopher A Maher, John Scholes, Yoshinao Oda, Donatella Santini, Leona A Doyle, Iver Petersen, Uta Flucke, Christian Koelsche, Samuel J Reynolds, Aslihan Yavas, Andreas von Deimling, Jorge S Reis-Filho, David S Klimstra
    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 33 (3) 456 - 467 0893-3952 2020/03 [Refereed][Not invited]
     
    We have encountered pancreatic tumors with unique histologic features, which do not conform to any of the known tumors of the pancreas or other anatomical sites. We aimed to define their clinicopathologic features and whether they are characterized by recurrent molecular signatures. Eight cases were identified; studied histologically and by immunohistochemistry. Selected cases were also subjected to whole-exome sequencing (WES; n = 4), RNA-sequencing (n = 6), Archer FusionPlex assay (n = 5), methylation profiling using the Illumina MethylationEPIC (850k) array platform (n = 6), and TERT promoter sequencing (n = 5). Six neoplasms occurred in females. The mean age was 43 years (range: 26-75). Five occurred in the head/neck of the pancreas. All patients were treated surgically; none received neoadjuvant/adjuvant therapy. All patients are free of disease after 53 months of median follow-up (range: 8-94). The tumors were well-circumscribed, and the median size was 1.8 cm (range: 1.3-5.8). Microscopically, the unencapsulated tumors had a geographic pattern of epithelioid cell nests alternating with spindle cell fascicles. Some areas showed dense fibrosis, in which enmeshed tumor cells imparted a slit-like pattern. The predominant epithelioid cells had scant cytoplasm and round-oval nuclei with open chromatin. The spindle cells displayed irregular, hyperchromatic nuclei. Mitoses were rare. No lymph node metastases were identified. All tumors were positive for vimentin, CD99 and cytokeratin (patchy), while negative for markers of solid pseudopapillary neoplasm, neuroendocrine, acinar, myogenic/rhabdoid, vascular, melanocytic, or lymphoid differentiation, gastrointestinal stromal tumor as well as MUC4. Whole-exome sequencing revealed no recurrent somatic mutations or amplifications/homozygous deletions in any known oncogenes or tumor suppressor genes. RNA-sequencing and the Archer FusionPlex assay did not detect any recurrent likely pathogenic gene fusions. Single sample gene set enrichment analysis revealed that these tumors display a likely mesenchymal transcriptomic program. Unsupervised analysis (t-SNE) of their methylation profiles against a set of different mesenchymal neoplasms demonstrated a distinct methylation pattern. Here, we describe pancreatic neoplasms with unique morphologic/immunophenotypic features and a distinct methylation pattern, along with a lack of abnormalities in any of key genetic drivers, supporting that these neoplasms represent a novel entity with an indolent clinical course. Given their mesenchymal transcriptomic features, we propose the designation of "sclerosing epithelioid mesenchymal neoplasm" of the pancreas.
  • Kentaro Tsuji, Takeo Nakaya, Kentaro Ashizawa, Fumihiro Arai, Noriyoshi Fukushima, Akira Gomi, Shintaro Sugita, Tadashi Hasegawa, Akira Tanaka
    Pathology international 70 (2) 123 - 125 1320-5463 2020/02 [Refereed][Not invited]
  • 中枢神経原発と考えられ、その後他臓器浸潤がみられた悪性リンパ腫の一例
    柳田 美樹, 二階堂 貴章, 郡 俊勝, 鈴木 智子, 渡邊 温子, 天野 雄介, 大城 久, 福嶋 敬宜
    自治医科大学臨床検査技師年報 自治医科大学附属病院臨床検査技師会 (42) 52 - 55 0919-3448 2019/12 
    症例は60歳代女性で、2週間程度で亜急性進行性の多発脳神経障害と錐体路・小脳・全感覚路の障害を認めた。頭部MRI所見より中枢神経系原発悪性リンパ腫(PCNSL)と考えられたが、脳幹部位であったため生検による組織診断が不可能で、脳脊髄液細胞診においても確定には至らなかった。ステロイド治療により病変の縮小と造影効果の消失を認めたが、約半年後に症状の急速な悪化がみられた。MRIで病変の広がりを認め、鎖骨上窩や腹腔内リンパ節の腫大、右腎周囲・脾・膵・腸管周囲の腫瘤、胸腹水貯留がみられ、再発/浸潤が疑われた。その後の治療で寛解になっている。当院の過去10年間において脳生検または手術を施行したPCNSLは34例で、全脳腫瘍に対して4.9%と少なく、全例においてDLBCLであった。さらに脳脊髄液細胞診を行い、悪性リンパ腫が疑われた症例は2例であった。脳生検または手術を施行しなかったPCNSLの症例は今回の症例のみで、他臓器転移があった症例は他に1例みられた。
  • 病理解剖室・臓器保管倉庫におけるホルマリン対策
    小瀬川 順幸, 二階堂 貴章, 本望 一昌, 飛田野 清美, 芳賀 美子, 天野 雄介, 福嶋 敬宜
    自治医科大学臨床検査技師年報 自治医科大学附属病院臨床検査技師会 (42) 56 - 63 0919-3448 2019/12 
    当院では開院当初(1974年)からの旧病理解剖室と2016年にリニューアル移転した現在の新病理解剖室において、ホルマリン濃度が0.1ppm以下の第1管理区分を目標とした環境改善対策を旧剖検室で1回、新剖検室で3回、合わせて4回実施した。本稿では、対策前後の作業環境改善結果について報告した。当院の旧剖検室はホルマリン環境対策を一切行っていなかった。旧倉庫は病理レポートの保管棚と同じスペースにあり、切り出し台、ホルマリン原液ストック場と床に直置きした臓器保管用ホルマリンバケツ置き場が混在していた。2013年に旧解剖室と旧倉庫のホルマリン対策を初めて行い、それを参考に2016年に新解剖室・臓器保管倉庫のリニューアルが実施され、1階の旧剖検室から地下1階の新剖検室に場所を移した。リニューアル移転時のホルマリン環境測定結果は、第1管理区分に至らなかった。新解剖室では切り出し臓器時にホルマリン吸収シートを使用したり、新倉庫で保管容器のビニール袋使用による二重密閉・パッキン付き容器への変更・ホルマリン吸着ビーズを使用したりと工夫を重ね、最終的には何とか第1管理区分を達成できた。旧剖検室では、ホルマリン臭がするのが当たり前との意識で剖検業務をこなしていた。現在の新剖検室は旧剖検室に比べてホルマリン臭はかなり軽減されてはいる。しかし現在第1管理区分を達成していても、ホルマリン臭がきつくなる場面も多々あり、ホルマリン濃度の低減への根本的な解決にはなっていないと思われる。
  • Atsushi Kihara, Yusuke Amano, Taichiro Yoshimoto, Daisuke Matsubara, Noriyoshi Fukushima, Hiroyuki Fujiwara, Toshiro Niki
    The American journal of surgical pathology 43 (11) 1526 - 1535 0147-5185 2019/11 [Refereed][Not invited]
     
    Atypical polypoid adenomyoma (APA) is a polypoid lesion that is comprised of atypical endometrial glands and fibromuscular stroma, which pathologists often confuse with myoinvasive endometrioid carcinoma. Here, we characterized the immunohistochemical and molecular features of the stromal components of APA to find distinct markers between APA and myoinvasive endometrioid carcinoma. First, we examined the immunohistochemical expression and gene mutations that were previously investigated in uterine and breast fibroepithelial lesions using 12 cases of APA. α-smooth muscle actin was diffusely positive in the stromal component in all cases, whereas desmin and h-caldesmon were focally expressed in 8 cases. Positive expression was also observed in 9 cases for CD10, 12 cases for estrogen receptor, 3 cases for HMGA2, and 3 cases for MDM2. All cases showed normal p53 expression and negative staining of HMGA1 and nuclear β-catenin. No mutations in MED12 exon 2 and the TERT promoter were found in any cases. p16 was positive in all cases and showed diffuse expression in 10 cases. We assessed stromal p16 expression in 84 cases of myoinvasive endometrioid carcinoma. The stromal p16 status was negative in all myoinvasive carcinomas, but there was 1 case with focal staining. There was a significant difference in stromal p16 expression between APA and myoinvasive endometrioid carcinoma (P<0.001). Stromal p16 expression was more suggestive of APA than myoinvasive endometrioid carcinoma among endometrial fibroepithelial lesions.
  • 上紙 航, 堀 隆, 桝澤 容子, 佐藤 奈緒美, 松本 信雄, 角田 敏一, 下岡 友子, 小山 芳徳, 砂川 恵伸, 福嶋 敬宜, 福岡 順也
    日本臨床細胞学会雑誌 (公社)日本臨床細胞学会 58 (Suppl.2) 653 - 653 0387-1193 2019/10 [Refereed][Not invited]
  • Chieko Miyazaki, Mikio Shiozawa, Rintaro Koike, Kasumi Ogihara, Yumiko Sasaki, Satomi Shiba, Saki Nishida, Masako Sakuragi, Hirofumi Mizunuma, Takashi Fujita, Noriyoshi Fukushima, Alan K Lefor, Joji Kitayama, Naohiro Sata
    Journal of medical case reports 13 (1) 289 - 289 2019/09 [Refereed][Not invited]
     
    BACKGROUND: Primary sarcoma of the breast is rare. Surgery has been the only curative treatment available. Recently, neoadjuvant chemotherapy including anthracycline/ifosfamide has been reported effective for patients with high-risk sarcomas in a prospective trial. CASE PRESENTATION: A 52-year-old Japanese woman presented with a mass in her left breast. The 10 cm tumor was fixed to her chest wall on examination. A skin biopsy was performed which showed leiomyosarcoma. Neoadjuvant chemotherapy was given and the tumor became mobile. A mastectomy and axillary dissection were performed with surgically negative margins. After neoadjuvant chemotherapy, the amount of necrosis was profoundly influenced by chemotherapy, and the histological effect of neoadjuvant chemotherapy was assessed in reference to pre-neoadjuvant chemotherapy magnetic resonance imaging. CONCLUSION: In contrast to many other cancers, the evaluation of various treatments and of the histological effect of neoadjuvant chemotherapy for sarcoma has been difficult due to the rarity of these tumors. We report the case of a patient with a breast sarcoma, treated with neoadjuvant chemotherapy and discuss the appropriate pathological evaluation and therapeutic management.
  • Kentaro Tsuji, Atsushi Ito, Shinsuke Kurokawa, Takeo Nakaya, Taichiro Yoshimoto, Hirotoshi Kawata, Mio Tamba-Sakaguchi, Noriyoshi Fukushima, Hisashi Oshiro
    Medicine 98 (32) e16643  0025-7974 2019/08 [Refereed][Not invited]
     
    RATIONALE: Primary carcinosarcoma of the upper urinary tract is rare. Ureteral duplication is one of the most common urinary tract malformations. Additionally, the association between ureteral duplication and malignancy is unknown. To the best of our knowledge, no cases of malignant tumors diagnosed as carcinosarcoma with ureteral duplication have been reported. We herein report the case of a patient with carcinosarcoma of the ureteropelvic junction associated with incomplete ureteral duplication. PATIENT CONCERNS: A 60-year-old Japanese woman presented with painless gross hematuria. She had a history of total hysterectomy and chemotherapy for endometrioid carcinoma 5 years before. She had no history of occupational chemical exposure. DIAGNOSES: Radiographic imaging revealed right incomplete ureteral duplication, hydronephrosis, and a polypoid tumor in the ureteropelvic junction of the lower moiety of the right kidney. Urine cytology showed a small amount of degenerated atypical epithelial and nonepithelial cells. The transureteral biopsy specimen showed dysplastic urothelial cells and atypical myoid spindle cells. These findings were indefinite for malignancy. INTERVENTIONS: The patient underwent right nephroureterectomy. Pathological examination of the resected tumor showed a biphasic neoplasm composed of carcinomatous and sarcomatous components. The sarcomatous component was immunohistochemically positive for vimentin, desmin, h-caldesmon, and α-SMA and negative for pancytokeratin (AE1/AE3), low molecular weight cytokeratin (CAM 5.2), EMA, E-cadherin, GATA3, uroplakin 2, and p63. Based on these findings, we diagnosed the tumor as carcinosarcoma. OUTCOMES: The postoperative course was uneventful. No additional therapy was administered. The patient has remained alive without recurrence for 21 months since surgery. LESSONS: Carcinosarcoma can arise from ureteral duplication. Although the majority of carcinosarcomas of the upper urinary tract are diagnosed at an advanced stage and have a poor prognosis, some can have a less aggressive course. Further studies are needed to determine the association between ureteral duplication and malignancy.
  • Kumiko Mito, Michihiro Saito, Kohei Morita, Iruru Maetani, Naohiro Sata, Makiko Mieno, Noriyoshi Fukushima
    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 19 (5) 793 - 793 1424-3903 2019/07 [Refereed][Not invited]
  • Takao Nagashima, Yasuyuki Kamata, Masahiro Iwamoto, Hitoaki Okazaki, Noriyoshi Fukushima, Seiji Minota
    Rheumatology international 39 (5) 901 - 909 0172-8172 2019/05 [Refereed][Not invited]
     
    The objective was to investigate the clinical and histological features of liver dysfunction in patients with polymyositis (PM) or dermatomyositis (DM).A total of 115 patients (38 with PM and 77 with DM), who were admitted to our hospital between 2001 and 2012, were retrospectively reviewed. Liver dysfunction was defined as an alanine transaminase (ALT) level ≥ 60 U/l and a disproportionate ALT elevation relative to the creatine kinase level. The histological findings from liver biopsies were also assessed.The frequencies of liver dysfunction were 3% and 17% in the patients with PM and DM, respectively. Liver dysfunction was not observed in the patients who had malignancies. Among the patients with DM with no malignancies (n = 50), 20% had liver dysfunction, and all of the patients with liver dysfunction were positive for the anti-melanoma differentiation-associated gene 5 (MDA5) antibody. Compared with those in the patients who did not have liver dysfunction, the ALT, alkaline phosphatase, γ-glutamyl transferase, and KL-6 levels were significantly elevated in the patients who had liver dysfunction. Six patients, comprising four with DM and two with PM, underwent liver biopsies, and the common histological findings associated with DM were steatosis, hepatocyte ballooning, increases in the pigmented macrophage numbers, and glycogenated nuclei. Hemophagocytosis was detected in two of three patients with DM who underwent liver biopsies and bone marrow aspirations. In conclusion, Liver dysfunction might be an extramuscular manifestation in patients with DM who are anti-MDA5 antibody-positive. Steatosis and hepatocyte ballooning could be common histological features.
  • Toru Furukawa, Noriyoshi Fukushima, Takao Itoi, Nobuyuki Ohike, Tomoko Mitsuhashi, Toshio Nakagohri, Kenji Notohara, Michio Shimizu, Takuma Tajiri, Mariko Tanaka, Hiroshi Yamaguchi, Akio Yanagisawa, Masanori Sugiyama, Kazuichi Okazaki
    Pancreas 48 (4) 480 - 487 0885-3177 2019/04 [Refereed][Not invited]
     
    OBJECTIVE: The grading and typing of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are challenging for pathologists. We aimed to clarify the points of consistency and disagreement in assessing the grades and types of IPMNs. METHODS: Digital slide images of 20 IPMNs were independently assessed by 10 Japanese pathologists, who then held a consensus meeting to discuss the points of disagreement and develop a consensus and recommendations. RESULTS: The average agreement rates for grade and type were 83.5% (range, 100%-40%) and 82.5% (range, 100%-50%) and the Fleiss' κ values were 0.567 and 0.636, respectively. CONCLUSIONS: The disagreement points and recommendations were as follows: destructed ductal walls with desquamated neoplastic epithelia or mucin lakes partially lined with neoplastic cells could be invasion; intraductal stromal invasion could be dismissed unless vascular or lymphatic invasion existed; elastica staining may help visualize ducts in colloidal nodules; high-grade can be distinguished from low/intermediate grade by marked nuclear disarrangements and complex architecture in the intestinal papillae; oncocytic papillae are characterized by eosinophilic cells with round disoriented nuclei; high-grade gastric papillae can be distinguished from pancreatobiliary papillae by relatively low but complex architecture; and the most dysplastic papillae should be used to assess type in mixed papillae types.
  • Shizu Watanabe, Kishio Kuroda, Takashi Yao, Tomoo Itoh, Hajime Aoyama, Yukio Kashima, Andrey Bychkov, Naoko Tsuyama, Yoshiki Mikami, Toshitaka Nagao, Daisuke Niino, Tohru Ikeda, Noriyoshi Fukushima, Oi Harada, Takako Kiyokawa, Naoki Yoshimi, Yoshinao Oda, Shinichi Aishima, Ichiro Maeda, Ichiro Mori, Koji Yamanegi, Koichi Tsuneyama, Ryohei Katoh, Miki Izumi, Bungo Furusato, Shota Fujimura, Junya Fukuoka
    MODERN PATHOLOGY 32 0893-3952 2019/03 [Refereed][Not invited]
  • Shizu Watanabe, Kishio Kuroda, Takashi Yao, Tomoo Itoh, Hajime Aoyama, Yukio Kashima, Andrey Bychkov, Naoko Tsuyama, Yoshiki Mikami, Toshitaka Nagao, Daisuke Niino, Tohru Ikeda, Noriyoshi Fukushima, Oi Harada, Takako Kiyokawa, Naoki Yoshimi, Yoshinao Oda, Shinichi Aishima, Ichiro Maeda, Ichiro Mori, Koji Yamanegi, Koichi Tsuneyama, Ryohei Katoh, Miki Izumi, Bungo Furusato, Shota Fujimura, Junya Fukuoka
    LABORATORY INVESTIGATION 99 0023-6837 2019/03 [Refereed][Not invited]
  • Toshihide Komatsubara, Hisashi Oshiro, Yasunaru Sakuma, Naohiro Sata, Toshiro Niki, Noriyoshi Fukushima
    Pathology international 69 (2) 86 - 93 1320-5463 2019/02 [Refereed][Not invited]
     
    Bile duct cancer is known to contain numerous fibroblasts, and reported to recruit cancer- associated fibroblasts by secreting platelet-derived growth factor-D (PDGF-D) which needs serine proteases, such as matriptase, to behave as a ligand. However, their expression pattern, and prognostic value have not been clarified. In this study, we investigated the clinicopathological significance of PDGF-D and matriptase expression in patients with extrahepatic bile duct cancer. The samples were obtained from 256 patients who underwent the surgical resection between 1991 and 2015, and the expression levels of PDGF-D and matriptase were evaluated immunohistochemically. Staining intensities and distribution were scored, and finally classified into low and high expression groups in cancer cells and stroma respectively. High expression of matriptase in the cancer stroma was detected in 91 tumors (40%). The high stromal matriptase expression was significantly associated with shorter recurrence-free survival (RFS) and overall survival (OS) (P = 0.0027 and 0.0023, respectively). Multivariate analyses also demonstrated that the stromal matriptase expression level was an independent influential factor in RFS (P = 0.0050) and OS (P = 0.0093). Our findings suggest that the high stromal matriptase expression was strongly associated with tumor progression, recurrence and poor outcomes in patients with extrahepatic bile duct cancer.
  • Kumiko Mito, Yusuke Amano, Hisashi Oshiro, Daisuke Matsubara, Noriyoshi Fukushima, Shigeru Ono
    Medicine 98 (4) e14211  0025-7974 2019/01 [Refereed][Not invited]
     
    RATIONALE: Liver heterotopia associated with congenital diaphragmatic hernia (CDH) is a rare condition; to the best of our knowledge, only 17 cases have been reported to date. The histogenesis and clinicopathological features are largely unknown. We herein report 2 cases of liver heterotopia associated with CDH along with 17 cases described in the literature to shed light on their clinicopathological characteristics. PATIENT CONCERNS: Case 1 was a vaginally delivered male newborn who presented with respiratory distress immediately after birth. Case 2 was a female fetus who was found to have left-sided CDH during gestation. DIAGNOSIS: In case 1, a chest X-ray revealed left-sided CDH. In case 2, magnetic resonance imaging performed at 33 weeks of gestation revealed left-sided CDH. INTERVENTIONS: Case 1 underwent diaphragmatic patch repair surgery 3 days after birth. Histopathological examination following surgery in case 1 revealed the presence of ectopic liver tissue in the hernia sac. Case 2 was delivered by Cesarean section, and diaphragmatic patch surgery was performed 3 days after birth. During surgery, an isolated nodule was identified on the peritoneal side of the border of the defective foramen of the diaphragm. Histopathological examination following surgery in case 2 confirmed the presence of an epidermal cyst in the hernia sac. In addition, the isolated nodule was histopathologically found to be ectopic liver tissue. OUTCOMES: In Case 1, CDH recurred at 6 months after surgery, and a second patch repair surgery was performed. The surgically removed hernia sac was found to contain microscopic ectopic liver tissue on histopathology. Case 1 recovered well after surgery, and there was no critical change during the 10-month postoperative period. Case 2 recovered well after surgery, and there was no critical change during the 20-month postoperative period. LESSONS: There were no secondary pathological conditions associated with the presence of ectopic liver in CDH, such as torsion, infarction, rupture, intra-abdominal bleeding, or tumorization. Our observations suggest that liver heterotopia is a rare but asymptomatic condition in patients with CDH.
  • Yuichi Aoki, Atsushi Miki, Tomoyuki Nakano, Hideki Sasanuma, Yasunaru Sakuma, Hisanaga Horie, Yoshinori Hosoya, Noriyoshi Fukushima, Alan Kawarai Lefor, Naohiro Sata
    BMC cancer 18 (1) 1249 - 1249 2018/12 [Refereed][Not invited]
     
    BACKGROUND: Thymomas are typically slow-growing tumors and AB type thymomas are considered no/low risk tumors with a better prognosis. Extra-thoracic metastases are extremely rare. To the best of our knowledge, no patient with an isolated splenic metastasis from a thymoma has been reported. We report a patient who underwent laparoscopic splenectomy for a slow-growing, isolated splenic metastasis, eight years after thymectomy. CASE PRESENTATION: The patient is a 78-year-old man. Eight years previously, the patient underwent extended thymectomy and postoperative radiation therapy for a thymoma. Five years after thymectomy, a nodule appeared in the spleen, and the lesion enlarged gradually for three years thereafter. The patient was referred for further examination and treatment. Computed tomography scan showed a sharply circumscribed 50 mm tumor slightly hypodense and heterogeneous lesion in the spleen. On T2-weighted images on Magnetic Resonance Imaging, the tumor had high intensity, equivalent to or slightly lower than that on T1-weighted images, and no decrease on diffusion-weighted images. The tumor was multinodular and showed a low-signal spoke-wheel sign in the margin, enhanced gradually in the dynamic study. Positron emission tomography-CT scan, showed relatively low accumulation. Surgical resection was undertaken, and pathological examination showed metastatic thymoma. The patient is without recurrence and has no other symptoms three years after splenectomy. CONCLUSIONS: This is the first report of an isolated splenic metastasis from a thymoma. Further cases are needed to standardize this surgery for such lesions.
  • Mio Tamba-Sakaguchi, Hisashi Oshiro, Daisuke Minakata, Miki Yanagita, Toshikatsu Kohri, Takaaki Nikaido, Midori Kikuchi, Tomoko Suzuki, Taichiro Yoshimoto, Noriyoshi Fukushima
    DIAGNOSTIC CYTOPATHOLOGY 46 (12) 1077 - 1080 8755-1039 2018/12 [Refereed][Not invited]
  • Kohei Morita, Hisashi Oshiro, Kumiko Mito, Makiko Naka Mieno, Mio Tamba-Sakaguchi, Toshiro Niki, Atsushi Miki, Masaru Koizumi, Yasunaru Sakuma, Toshihide Komatsubara, Naohiro Sata, Noriyoshi Fukushima
    Medicine 97 (49) e13466  0025-7974 2018/12 [Refereed][Not invited]
     
    Little is known concerning the prognostic significance of the degree of lymphatic vessel invasion in pancreatic head cancer. To address this gap in knowledge, we retrospectively examined 60 patients with locally advanced, surgically resectable pancreatic head cancer who underwent pancreaticoduodenectomy and lymph node (LN) dissection.All cases were histopathologically diagnosed as ductal adenocarcinoma, stage II (25 pT3N0 cases, 35 pT3N1 cases). The following variables were investigated: age; sex; neoadjuvant therapy; adjuvant therapy; tumor size; tumor grade; invasion into the serosa, retropancreatic tissue, duodenum, bile duct, portal venous system and perineural area; cut margins; LN metastasis; and the number of invaded lymphatic vessels (LVI-score).Univariate analysis demonstrated that LN metastasis and an LVI-score ≥5 were significantly associated with poor disease-free survival. Multivariate Cox regression analysis confirmed that LN metastasis and an LVI-score ≥7 were significantly associated with poor disease-free survival. Additionally, LVI-scores ≥9 and ≥10 were comparable to or surpassed the significance of LN metastasis based on the hazard ratio. Univariate analysis demonstrated that tumor size >30 mm, duodenal invasion, LN metastasis and an LVI-score ≥2 were significantly associated with poor overall survival. Multivariate Cox regression analysis confirmed that LN metastasis and LVI-scores ≥9 and ≥10 were significantly associated with poor overall survival, and an LVI-score ≥10 was comparable to or surpassed the significance of LN metastasis based on the hazard ratio.Our study strongly suggests that a high degree of lymphatic vessel invasion is associated with a poor prognosis in patients with locally advanced, surgically resectable pancreatic head cancer.
  • Keiji Hanada, Keisuke Kurihara, Takao Itoi, Akio Katanuma, Tamito Sasaki, Kazuo Hara, Masafumi Nakamura, Wataru Kimura, Yutaka Suzuki, Masanori Sugiyama, Nobuyuki Ohike, Noriyoshi Fukushima, Michio Shimizu, Kousei Ishigami, Toshifumi Gabata, Kazuichi Okazaki
    Pancreas 47 (8) 1019 - 1026 0885-3177 2018/09 [Refereed][Not invited]
     
    OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of solid pseudopapillary neoplasms (SPNs). METHODS: In this retrospective study, 288 SPNs were analyzed. RESULTS: Overall, 214 patients (74%) were female. Distant metastases occurred in 4 patients, and splenic vein tumor thrombus occurred in 1 patient. Although imaging findings showed large (>2.0 cm) SPNs with clear, regular border, and heterogeneous internal structure, small SPNs appeared as almost entirely solid. Surgical resection was performed in 278 cases. The 5-year survival rate was 98.8%. Six patients had tumor recurrence after the initial resection. The detection rate in typical pathological findings was low for small SPNs. Tumor extension to the pancreatic parenchyma was detected in greater than 70% of the cases. Tumor invasion to adjacent organs was detected in 13 cases. One was given a diagnosis of apparent high-grade malignant transformation. CONCLUSIONS: The proportion of male cases was higher than that in previous studies, and there were statistically significant differences in the onset age and tumor diameter between male and female patients. Therefore, women seemed to have an early occurrence of SPNs, suggesting a difference in the developmental stage between men and women. Images and pathological findings of SPNs varied according to tumor size. Our findings indicated that SPN patients have excellent survival after margin-negative surgical resection.
  • Mariko Tanaka, Tetsuo Ushiku, Masako Ikemura, Yutaka Takazawa, Toru Igari, Michio Shimizu, Hiroshi Yamaguchi, Noriyoshi Fukushima, Kei Sakuma, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Takeyuki Watadani, Yousuke Nakai, Kazuhiko Koike, Masashi Fukayama
    AMERICAN JOURNAL OF SURGICAL PATHOLOGY 42 (7) 891 - 897 0147-5185 2018/07 [Refereed][Not invited]
     
    Pancreatic masses consisting of lipomatous components clinically include lipoma, liposarcoma, lipomatous pseudohypertrophy of the pancreas, fat-containing neoplasms such as perivascular epithelioid cell tumor, and malignant neoplasm with lipoid degeneration. We present pancreatic lipomatous hamartoma, which has not been reported hitherto. A solid pancreatic mass was detected from a computed tomographic scan check-up in each of 3 cases of Japanese men. Macroscopically, well-demarcated solid lipomatous masses were detected at the uncus, body, and tail of the pancreas, respectively. Microscopically, the masses predominantly consisted of mature adipocytes with no atypia, but contained characteristics components of pancreatic hamartoma, such as small ducts, a well-preserved acinar structure, and/or fibrous stroma. On the basis of the unique features, lack of islets and absence of periductal elastic fibers, these tumors are a distinct variant of pancreatic hamartoma. Furthermore, high-mobility group AT-hook 2 expression in the fibro-adipocytes of this tumor indicated that these cells are an integral component of the pancreatic lipomatous hamartoma. Consequently, the unique tumors described herein are pancreatic lipomatous hamartoma, which must be discriminated from other lipomatous lesions of the pancreas.
  • Taku Uchiyama, Rie Nagayama, Junji Shibahara, Noriyoshi Fukushima, Daisuke Matsubara, Kensuke Kawai, Akira Gomi
    NEURO-ONCOLOGY 20 146 - 146 1522-8517 2018/06 [Refereed][Not invited]
  • Kumiko Mito, Michihiro Saito, Kohei Morita, Iruru Maetani, Naohiro Sata, Makiko Mieno, Noriyoshi Fukushima
    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 18 (4) 407 - 412 1424-3903 2018/06 [Refereed][Not invited]
     
    BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a primary pancreatic ductal epithelial neoplasm with the potential to develop into an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic and prognostic significance of four potential biomarkers for the preoperative evaluation of patients with IPMN. MATERIALS AND METHODS: Clinicopathologic materials from 104 patients with IPMN who underwent surgical resection at Jichi Medical University Hospital were analyzed. IPMNs (110 lesions in total) were histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n = 26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and FXYD3, which were previously reported to be overexpressed in pancreatic ductal adenocarcinoma. RESULTS: The expression of MUC13 was more common in Group 3 compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor location, histological subtype, lymphatic or vascular invasion, or neural invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show an association with tumor recurrence and poorly differentiated histology of invasive carcinoma; however, this association was not statistically significant. The expressions of FUT8 and FXYD3were not associated with the clinicopathological features of IPMNs. CONCLUSIONS: The results suggest that MUC13 overexpression and loss of expression of AGR2 may predict the progression of IPMN and an unfavorable prognosis in patients with IPMN.
  • Kohei Morita, Kumiko Mito, Toshiro Niki, Noriyoshi Fukushima
    Pathology international 1320-5463 2018/04 [Refereed][Not invited]
  • Basturk Olca, Weigelt Britta, Askan Gokce, Wang Lu, Arcila Maria, Zamboni Giuseppe, Fukushima Noriyoshi, Pareja Fresia, Selenica Pier, Kumar Rahul, Doyle Leona, Reynolds Samuel J, Adsay N. Volkan, Reis-Filho Jorge, Klimstra David
    MODERN PATHOLOGY 31 671  0893-3952 2018/03 [Refereed][Not invited]
  • Komatsubara Toshihide, Fukushima Noriyoshi, Oshiro Hisashi, Niki Toshiro, Sakuma Yasunaru, Sata Naohiro
    MODERN PATHOLOGY 31 681 - 682 0893-3952 2018/03 [Refereed][Not invited]
  • Yasuni Nakanuma, Kee-Taek Jang, Noriyoshi Fukushima, Toru Furukawa, Seung-Mo Hong, Haeryoung Kim, Kyung Bun Lee, Yoh Zen, Jin-Young Jang, Keiichi Kubota
    Journal of hepato-biliary-pancreatic sciences 25 (3) 181 - 187 1868-6974 2018/03 [Refereed][Not invited]
     
    Intraductal papillary neoplasm of bile duct (IPNB) was described as a preinvasive neoplastic lesion of the biliary tract in the 2010 World Health Organization (WHO) classification. Although a number of studies have since been conducted on IPNBs, controversy remains, particularly regarding the standardization of its definition. Meetings by Japanese and Korean expert pathologists were held twice to resolve the pathological diagnostic aspects of IPNB. Through round-table discussions and histological reviews, we reached the common understanding that IPNBs diagnosed according to the criteria of WHO 2010 are characterized by intraductal predominant papillary or villous biliary neoplasms covering delicate fibrovascular stalks and are classified into two types pathologically. One type (type 1 IPNB) is histologically similar to intraductal papillary mucinous neoplasms of pancreas, and typically develops in the intrahepatic bile ducts, while the other (type 2 IPNB) has a more complex histological architecture with irregular papillary branching or with foci of solid-tubular components and typically involves the extrahepatic bile ducts. This report states the diagnostic pathologic features of IPNB proposed by WHO 2010. Since currently, the concept of IPNB is still confusing, the proposed diagnostic pathologic features stated here will be of use for future clinicopathological and molecular analyses toward consensus building of IPNB.
  • Hirotaka Waki, Kazuo Eguchi, Shinichi Toriumi, Tomokazu Ikemoto, Tsukasa Suzuki, Noriyoshi Fukushima, Kazuomi Kario
    INTERNAL MEDICINE 57 (6) 835 - 839 0918-2918 2018 [Refereed][Not invited]
     
    The diagnosis of cardiac sarcoidosis (CS) has become easier due to advances in imaging modalities, but we sometimes encounter difficult-to-diagnose patients. We herein report the case of a 60-year-old Japanese woman who was diagnosed with isolated CS, although she also met the diagnostic criteria of arrhythmogenic right ventricular cardiomyopathy (ARVC). A histological examination by an endomyocardial biopsy of the right ventricle revealed the typical findings of granulomatous change for CS. Although she did not show any characteristics of systemic sarcoidosis, oral prednisolone treatment was introduced, and she achieved a good response. This case shows that the characteristics of CS can overlap with the diagnostic criteria of ARVC, and that a histological examination is essential for the correct diagnosis of CS.
  • Kensuke Yokoyama, Jun Ushio, Norikatsu Numao, Kiichi Tamada, Noriyoshi Fukushima, Alan Kawarai Lefor, Hironori Yamamoto
    ENDOSCOPY INTERNATIONAL OPEN 5 (9) E913 - E917 2364-3722 2017/09 [Refereed][Not invited]
     
    Background and study aims Tumor seeding after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is rare. A 53-year-old man underwent transesophageal EUS-FNA for diagnosis of a 6-cm mass in the mediastinum as seen by computed tomography (CT). Four weeks later, repeat CT scan revealed a mass in the esophageal wall. Upper gastrointestinal endoscopy confirmed a lesion in the mid-esophagus, which was biopsied and found to be consistent with needle tract seeding after EUS-FNA. Tumor seeding in the gastrointestinal wall or peritoneum after EUS-FNA is rare, but may adversely affect the prognosis. Indications for EUS-FNA must be carefully considered.
  • Shin Saito, Takao Nagashima, Daisuke Matsubara, Noriyoshi Fukushima, Masahiro Iwamoto, Seiji Minota, Hisanaga Horie, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata
    INTERNATIONAL SURGERY 102 (5-6) 210 - 215 0020-8868 2017/05 [Refereed][Not invited]
     
    Eosinophilic granulomatosis with polyangiitis (EGPA) is a vascular disorder of unknown etiology characterized by severe asthma, eosinophilia, and granulomatous vasculitis. It is sometimes associated with gastrointestinal lesions, although perforations are uncommon. Corticosteroids are commonly used in the treatment of patients with EGPA; however, they may impair tissue repair and induce fibrotic changes in the vascular intima, which can lead to vascular occlusion, ischemia, and perforation. The anti-inflammatory properties of corticosteroids may mask symptoms of gastroduodenal ulcers or other intra-abdominal conditions, which can lead to a delay in diagnosis. From January 1, 2001 to December 31, 2014, 71 patients underwent surgery for small intestinal perforations. Of these, 4 operations were performed on 3 patients with EGPA who were receiving corticosteroids. We retrospectively reviewed the clinical and pathologic features of these patients. All 3 patients with EGPA were men, with a mean age of 56 years. The length of resected intestine ranged from 10 to 60 cm. Histopathologic examination revealed ulcers and perforations of the small intestine associated with vasculitis, compatible with EGPA. All patients had an uneventful postoperative course. Patients with EGPA presenting with abdominal pain must be carefully evaluated for possible intestinal perforation, especially those receiving corticosteroid therapy.
  • Atsushi Ito, Yuto Yamazaki, Hironobu Sasano, Daisuke Matsubara, Noriyoshi Fukushima, Mio Tamba, Kenichi Tabata, Kentaro Ashizawa, Akihito Takei, Masaru Koizumi, Yasunaru Sakuma, Naohiro Sata, Hisashi Oshiro
    PATHOLOGY INTERNATIONAL 67 (4) 214 - 221 1320-5463 2017/04 [Refereed][Not invited]
     
    Unilateral multiple adrenocortical micronodules (UMNs) constitute a rare subset of primary aldosteronism (PA) characterized by the hypersecretion of aldosterone derived from multiple small nodules in the zona glomerulosa of the unilateral adrenal grand. This case study describes a 49-year-old man with PA and UMNs who presented with muscle cramps at rest due to hypokalemia. The patient had a 6-year history of hypertension treated with antihypertensive drugs. Imaging studies revealed bilateral adrenal nodules as large as 5mm. Adrenal venous sampling confirmed unilateral PA; therefore, the patient underwent the removal of the affected adrenal gland. Macroscopically, the removed adrenal gland exhibited irregular adrenocortical thickening accompanied by ill-defined, adrenocortical macronodules as large as 6mm. The zona glomerulosa was histologically hyperplastic. However, an immunohistochemistry test of the steroidogenic enzymes revealed that these macronodules and the hyperplastic glomerular layer tested negative for CYB11B2. Moreover, we observed adrenocortical micronodules as large as 0.5mm that tested immunohistochemically positive for CYP11B2 and HSD3B2 but negative for CYP17A1 and CYP11B1. Thus, UMNs were diagnosed. This case instructively indicates that a grossly or histologically detectable nodular lesion is not necessarily a culprit lesion for PA. Therefore, functional histopathology is indispensable for the correct subclassification of PA.
  • Hideyuki Ohzawa, Atsushi Miki, Takumi Teratani, Satomi Shiba, Yasunaru Sakuma, Wataru Nishimura, Yasuko Noda, Noriyoshi Fukushima, Hirofumi Fujii, Yasuo Hozumi, Hirofumi Mukai, Yoshikazu Yasuda
    ONCOLOGY LETTERS 13 (3) 1731 - 1740 1792-1074 2017/03 [Refereed][Not invited]
     
    Pathological complete response (pCR) is considered to be a useful prognostic marker for neoadjuvant chemotherapy to improve the survival rate of patients with operable breast cancer. In the present study, we identified differentially expressed microRNAs (miRNAs) between pCR and non-pCR groups of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who received neoadjuvant chemotherapy with trastuzumab. Expression profiles were examined by miRNA microarrays using total RNA extracted from formalin-fixed, paraffin-embedded tissues from pretreatment biopsy specimens. Significant differences were observed in miRNAs associated with pCR between the luminal B-like (HER2-positive) and HER2posi-tive (nonluminal) subtypes, which were further classified according to their estrogen receptor (ER) status. Prediction models constructed with differentially expressed miRNAs performed well. In conclusion, the combination of miRNA profiles and ER status may improve the accuracy of pCR prediction in patients with HER2-positive breast cancer and enable the development of personalized treatment regimens.
  • Kumiko Mito, Michihiro Saito, Kohei Morita, Iruru Maetani, Naohiro Sata, Noriyoshi Fukushima
    LABORATORY INVESTIGATION 97 447A - 447A 0023-6837 2017/02 [Refereed][Not invited]
  • Kohei Morita, Kumiko Mito, Hisashi Oshiro, Naohiro Sata, Toshiro Niki, Noriyoshi Fukushima
    MODERN PATHOLOGY 30 447A - 448A 0893-3952 2017/02 [Refereed][Not invited]
  • Kumiko Mito, Michihiro Saito, Kohei Morita, Iruru Maetam, Naohiro Sata, Noriyoshi Fukushima
    MODERN PATHOLOGY 30 447A - 447A 0893-3952 2017/02 [Refereed][Not invited]
  • Kohei Morita, Kumiko Mito, Hisashi Oshiro, Naohiro Sata, Toshiro Niki, Noriyoshi Fukushima
    LABORATORY INVESTIGATION 97 447A - 448A 0023-6837 2017/02 [Refereed][Not invited]
  • Yasunaru Sakuma, Naohiro Sata, Kazuhiro Endo, Yoshikazu Yasuda, Shinichiro Yokota, Yoshinori Hosoya, Atsushi Shimizu, Hirofumi Fujii, Daisuke Matsubara, Noriyoshi Fukushima, Shoko Asakawa, Yuuki Kawarai Shimada, Chieko Kawarai Lefor, Alan Kawarai Lefor
    INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS 41 169 - 173 2210-2612 2017 [Refereed][Not invited]
     
    INTRODUCTION: Pancreatic neuroendocrine tumors are rare. Treatment includes aggressive local management of the primary lesion and metastases, and systemic somatostatin. This is the first report of an isolated metachronous metastasis to the adrenal gland from a pancreatic neuroendocrine tumor that presented 90 months after the primary tumor.PRESENTATION OF CASE: The patient presented as a 53yo man with a left upper quadrant mass and synchronous metastases to the spleen and liver (pancreatic neuroendocrine tumor T4NOM1, Stage IV), which were resected (CD56-, synaptophysin+, chromogranin+, Ki-67 < 1%). Over the next 90 months, he underwent five procedures to treat hepatic recurrences (2 liver resections and 3 percutaneous radiofrequency ablations). Serum PIVKA levels were elevated prior to treatment of four of six lesions and returned to baseline after therapy. He presents now, asymptomatic, with a right adrenal mass found on routine imaging and no other lesions. Serum PIVKA was elevated to 44 mg/dL. The adrenal gland was resected and shown to be a metastasis (CD56+, synaptophysin+, chromogranin+, Ki-67 15-20%).DISCUSSION: This patient's clinical course reflects aggressive local therapy of the primary lesion and multiple metastatic lesions to three organs (liver, spleen, adrenal) over nearly eight years. The utility of serum PIVKA levels in patients with pancreatic neuroendocrine tumors is not previously reported and needs further investigation.CONCLUSION: This patient has a pancreatic neuroendocrine tumor with metastases to the spleen, liver and adrenal gland and elevated PIVKA levels with recurrent disease. These unique clinical features add to the diversity of clinical presentation of these rare tumors. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license.
  • Tsuneo Ikenoue, Yumi Terakado, Hayato Nakagawa, Yohko Hikiba, Tomoaki Fujii, Daisuke Matsubara, Rei Noguchi, Chi Zhu, Keisuke Yamamoto, Yotaro Kudo, Yoshinari Asaoka, Kiyoshi Yamaguchi, Hideaki Ijichi, Keisuke Tateishi, Noriyoshi Fukushima, Shin Maeda, Kazuhiko Koike, Yoichi Furukawa
    SCIENTIFIC REPORTS 7 39567  2045-2322 2017/01 [Refereed][Not invited]
  • Yuki Imaizumi, Kazuo Eguchi, Hiroki Imada, Kiyomi Hidano, Satoshi Niijima, Hirotoshi Kawata, Noriyoshi Fukushima, Tsunenori Saito, Michiaki Hiroe, Kazuomi Kario
    CANADIAN JOURNAL OF CARDIOLOGY 32 (12) 1577.e19 - 1577.e20 0828-282X 2016/12 [Refereed][Not invited]
  • Hisashi Fukuda, Yoshikazu Hayashi, Yoshimasa Miura, Satoshi Shinozaki, Masahiro Okada, Hirotsugu Sakamoto, Keijiro Sunada, Noriyoshi Fukushima, Alan Kawarai Lefor, Hironori Yamamoto
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31 316 - 316 0815-9319 2016/11 [Refereed][Not invited]
  • Takahiro Koyanagi, Hiroyuki Fujiwara, Hirokazu Usui, Haruko Ariga, Shizuo Machida, Yuji Takei, Yasushi Saga, Makio Shozu, Noriyoshi Fukushima, Toshiro Niki, Shigeki Matsubara, Mitsuaki Suzuki
    PATHOLOGY INTERNATIONAL 66 (9) 529 - 534 1320-5463 2016/09 [Refereed][Not invited]
     
    Ovarian non-gestational choriocarcinomas co-existing with adenocarcinoma are extremely rare and have been reported as epithelial ovarian carcinomas of a "non-germ cell origin" with "choriocarcinomatous differentiation". Although the cellular origin of non-gestational choriocarcinoma may be post-meiotic ovarian germ cells or the dedifferentiation of epithelial ovarian carcinoma, detailed genetic evidence has not yet been obtained to support this. We herein present a case of ovarian non-gestational choriocarcinoma co-existing with adenocarcinoma in a 29-year-old woman. The tumor rapidly increased in size and lung metastases appeared soon after parturition. We genetically demonstrated that the cellular origin of ovarian non-gestational choriocarcinoma was a post-meiotic germ cell derivation using a short tandem repeat analysis. The co-existing adenocarcinoma component was also shown to be of the same germ cell origin. These tumors showed the same homozygous pattern. A molecular genetic approach may be important for understanding the clinicopathological features of such tumors.
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • Tsuneo Ikenoue, Yumi Terakado, Hayato Nakagawa, Yohko Hikiba, Tomoaki Fujii, Daisuke Matsubara, Rei Noguchi, Chi Zhu, Keisuke Yamamoto, Yotaro Kudo, Yoshinari Asaoka, Kiyoshi Yamaguchi, Hideaki Ijichi, Keisuke Tateishi, Noriyoshi Fukushima, Shin Maeda, Kazuhiko Koike, Yoichi Furukawa
    SCIENTIFIC REPORTS 6 2045-2322 2016/04 [Refereed][Not invited]
     
    Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis and its incidence is increasing worldwide. Recently, several types of cells have been considered as the origin of ICC, namely cholangiocytes, liver progenitor cells, and hepatocytes. Here, we have established a novel mouse model of ICC by liver-specific Kras activation and Pten deletion. An activating mutation of Kras in combination with deletion of Pten was introduced in embryonic hepatic bipotential progenitor cells (so-called hepatoblasts) and mature hepatocytes using the Cre-loxP system. As a result, liver-specific Kras activation and homozygous Pten deletion cooperated to induce ICCs exclusively. In contrast, Kras activation in combination with heterozygous Pten deletion induced both ICCs and HCCs, whereas Kras activation alone resulted in HCCs but not ICCs. Furthermore, a cell-lineage visualization system using tamoxifen-inducible Cre-loxP demonstrated that the ICCs did not originate from hepatocytes but from cholangiocytes. Our data suggest that mice carrying liver-specific Kras activation in combination with homozygous Pten deletion should be useful for the investigation of therapeutic strategies for human ICC.
  • 川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳
    Gastroenterological Endoscopy (一社)日本消化器内視鏡学会 58 (Suppl.1) 798  0387-1207 2016/04 [Not refereed][Not invited]
  • 三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 522  0300-9181 2016/04 [Not refereed][Not invited]
  • 蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 439  0300-9181 2016/04 [Not refereed][Not invited]
  • 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎
    日本病理学会会誌 (一社)日本病理学会 105 (1) 391  0300-9181 2016/04 [Not refereed][Not invited]
  • 森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 367  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    日本病理学会会誌 (一社)日本病理学会 105 (1) 249  0300-9181 2016/04 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • Yoshikazu Hayashi, Satoshi Shinozaki, Keijiro Sunada, Hiroyuki Sato, Yoshimasa Miura, Yuji Ino, Hisanaga Horie, Noriyoshi Fukushima, Alan K. Lefor, Hironori Yamamoto
    GASTROINTESTINAL ENDOSCOPY 83 (3) 602 - 607 0016-5107 2016/03 [Refereed][Not invited]
     
    Background and Aims: The feasibility of endoscopic submucosal dissection (ESD) for large superficial colorectal tumors is undefined. The aim of this study was to assess the outcomes for patients undergoing ESD of superficial colorectal tumors larger than 50 mm. Methods: A total of 472 patients who underwent ESD for superficial colorectal tumors from 2010 to 2014 were enrolled. We retrospectively reviewed their records. Results: We compared patients with 20-mm to 50-mm lesions and those with lesions >50 mm regarding demographics, the ESD procedure, and histopathology. Among patients with lesions >50 mm, laterally spreading tumors nongranular and protruded types were uncommon. Histopathologically, deeply invasive (>= 1000 mm) submucosal carcinomas were more frequent in lesions >50 mm (14% [10/70] vs 5% [20/402], P <.01). Technically, en bloc resection was successfully accomplished in 99% of patients (69/70). Although the total dissection time for lesions >50 mm was significantly longer than for lesions 20 mm to 50 mm (mean +/- SD, 157 +/- 114 minutes vs 68 +/- 50 min; P <.01), dissection speed for lesions >50 mm was significantly faster than for lesions 20 mm to 50 mm (P <.01). There were no significant differences in en bloc R0 resection rate comparing both groups (>50 mm, 83% vs 20 mm to 50 mm, 87%; P = .31). No perforations or postoperative bleeding occurred in patients with lesions >50 mm. Post-ESD colorectal strictures requiring intervention did not develop in any patient. Conclusions: ESD for superficial colorectal tumors >50 mm is feasible. ESD of these lesions had a high R0 resection rate and a low adverse event rate. En bloc resection by ESD provides adequate pathological specimens and may limit the need for surgical intervention.
  • 福嶋 敬宜
    内科 (株)南江堂 117 (3) 503  0022-1961 2016/03 [Not refereed][Not invited]
  • 内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜
    日本内科学会関東地方会 日本内科学会-関東地方会 622回 39  2016/03 [Not refereed][Not invited]
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜
    臨床検査栃木 (一社)栃木県臨床検査技師会 11 (2) 24  1881-2961 2016/03 [Not refereed][Not invited]
  • Shin Saito, Kentaro Kurashina, Shiro Matsumoto, Yasunaru Sakuma, Seiji Minota, Masahiro Iwamoto, Daisuke Matsubara, Noriyoshi Fukushima, Hisanaga Horie, Yoshinori Hosoya, Alan K. Lefor, Naohiro Sata
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 137 (2) AB165 - AB165 0091-6749 2016/02 [Refereed][Not invited]
  • Toshihide Komatsubara, Koji Koinuma, Yasuyuki Miyakura, Hisanaga Horie, Mitsuaki Morimoto, Homare Ito, Alan K. Lefor, Naohiro Sata, Noriyoshi Fukushima
    Clinical Journal of Gastroenterology 9 (1) 1 - 6 1865-7265 2016/02 [Refereed][Not invited]
     
    Purpose: Endocrine cell carcinoma, according to the Japanese classification criteria for colorectal cancer, corresponds to neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC), as defined in the 2010 World Health Organization (WHO) classification. We retrospectively reviewed the clinical features of patients with these tumors diagnosed and treated at our institution. Methods: The clinicopathological features of endocrine cell carcinomas of the colon and rectum diagnosed by neuroendocrine markers from January 2000 to December 2012 were retrospectively evaluated in 12 patients. Results: Surgical specimens were obtained from eight of the 12 patients. MANEC was diagnosed in six patients and NEC in one. One tumor was unclassifiable. The tumors were not resected in four patients, and all died within 3 months. Of the eight patients who underwent resection, four received an R0 resection, two of whom underwent adjuvant chemotherapy and survived more than 5 years. One patient who underwent an R2 resection and continuous chemotherapy survived for 53 months. One patient with NEC underwent surgery and radiotherapy, and died 17 months later. Conclusion: Most endocrine cell carcinomas of the colon and rectum reviewed were MANECs. Though their prognosis was generally poor, chemotherapy may be effective in some patients.
  • Kazuma Rifu, Koji Koinuma, Hisanaga Horie, Mitsuaki Morimoto, Yoshihiko Kono, Makiko Tahara, Yasunaru Sakuma, Yoshinori Hosoya, Joji Kitayama, Alan Kawarai Lefor, Naohiro Sata, Tsukasa Suzuki, Noriyoshi Fukushima
    International Journal of Surgery Case Reports 23 151 - 156 2210-2612 2016 [Refereed][Not invited]
     
    Introduction Neuroendocrine tumors of the colon and rectum are relatively rare compared to sporadic colorectal carcinoma. There are few reports of neuroendocrine tumors of the colon and rectum in patients with ulcerative colitis. Presentation of case A patient with sigmoid colon carcinoma with focal neuroendocrine features is presented. A 32-year-old man, who had been followed for ulcerative colitis for 14 years, was found to have carcinoma of the sigmoid colon on routine annual colonoscopy, and he underwent laparoscopic total colectomy. Pathologic examination showed sigmoid colon adenocarcinoma with focal neuroendocrine features. Discussion Most colorectal carcinomas associated with inflammatory bowel disease are histologically similar to the sporadic type, and tumors with neuroendocrine features are very unusual. Conclusion Very rare case of sigmoid colon carcinoma with neuroendocrine features arising in a patient with UC was described.
  • Tomoyuki Nakano, Shunsuke Endo, Kenji Tetsuka, Noriyoshi Fukushima
    JOURNAL OF THORACIC DISEASE 8 (1) E157 - E160 2072-1439 2016/01 [Refereed][Not invited]
     
    We herein report an asymptomatic 65-year-old male with localized pleural amyloidosis mimicking malignant pleural mesothelioma. He had a history of exposure to asbestos and was admitted for investigation of an abnormal pleural thickness detected by chest radiography. Positron emission tomography showed elevation of standardized uptake value corresponding to the pleural thickness. Partial pleurectomy including the tumor was performed for the purpose of diagnosis and local disease control. The pathological examination showed that the tumor was pleural amyloidosis. The tumor was diagnosed as localized primary amyloidosis, because serum monoclonal protein concentration did not increase. Pleural amyloidosis should be considered as a differential diagnosis from pleural mesothelioma.
  • Kogawara Haruna, Naoko Mato, Hiroyoshi Yamauchi, Testuro Sawata, Masashi Sata, Masayuki Nakayama, Takakiyo Nakaya, Shinichiro Fujiwara, Hideaki Yamasawa, Masashi Bando, Noriyoshi Fukushima, Yukihiko Sugiyama
    RESPIROLOGY 20 24 - 24 1323-7799 2015/12 [Refereed][Not invited]
  • Olca Basturk, Seung-Mo Hong, Laura D. Wood, N. Volkan Adsay, Jorge Albores-Saavedra, Andrew V. Biankin, Lodewijk A. A. Brosens, Noriyoshi Fukushima, Michael Goggins, Ralph H. Hruban, Yo Kato, David S. Klimstra, Guenter Kloeppel, Alyssa Krasinskas, Daniel S. Longnecker, Hanno Matthaei, G. Johan A. Offerhaus, Michio Shimizu, Kyoichi Takaori, Benoit Terris, Shinichi Yachida, Irene Esposito, Toru Furukawa
    AMERICAN JOURNAL OF SURGICAL PATHOLOGY 39 (12) 1730 - 1741 0147-5185 2015/12 [Refereed][Not invited]
     
    International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade. Thus, high-grade dysplasia is to be reserved for only the uppermost end of the spectrum (carcinoma in situ-type lesions). (2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined. (3) Intraductal lesions 0.5 to 1 cm can be either large PanINs or small IPMNs. The term incipient IPMN should be reserved for lesions in this size with intestinal or oncocytic papillae or GNAS mutations. (4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the associated group) ought to be genetically distinct from an IPMN elsewhere in the gland. (5) Intraductal spread of invasive carcinoma (aka, colonization) is recommended to describe lesions of invasive carcinoma invading back into and extending along the ductal system, which may morphologically mimic high-grade PanIN or even IPMN. (6) Simple mucinous cyst is recommended to describe cysts >1 cm having gastric-type flat mucinous lining at most minimal atypia without ovarian-type stroma to distinguish them from IPMN. (7) Human lesions resembling the acinar to ductal metaplasia and atypical flat lesions of genetically engineered mouse models exist and may reflect an alternate pathway of carcinogenesis; however, their biological significance requires further study. These revised recommendations are expected to improve our management and understanding of precursor lesions in the pancreas.
  • Yoshihiko Kono, Kazutomo Togashi, Kenichi Utano, Hisanaga Horie, Yasuyuki Miyakura, Noriyoshi Fukushima, Alan T. Lefor, Yoshikazu Yasuda
    AMERICAN SURGEON 81 (12) 1263 - 1271 0003-1348 2015/12 [Refereed][Not invited]
     
    Although size criteria have been proposed to identify lymph node metastases in patients with rectal cancer, size may not be an accurate predictor. Specimens from consecutive rectal cancer patients who underwent curative-intent radical surgery were examined. The long and short axes of lymph nodes were measured on the glass slides using micrometer calipers. The pathologic diagnosis was used as the reference. The diagnostic accuracy of metastatic status according to lymph node size was evaluated. Overall, 1283 lymph nodes from 78 patients were reviewed. The metastatic rate correlates with the length of both the long and short axes. However, metastases were present even in 1-mm lymph nodes, and the metastatic rate exceeds 5 per cent in lymph nodes measuring 3 mm along both axes. Cutoff values of >= 4 mm and >= 3 mm for the long and short axes result in a sensitivity of 76 per cent and 79 per cent, and a specificity of 36 per cent and 33 per cent, respectively, for each axis. Size criteria alone do not accurately predict the N-stage of rectal cancer. Diminutive lymph nodes, which are not seen on imaging studies, can contain metastatic disease.
  • Rina Nakajima, Mayumi Komine, Yukiko Miyamoto, Takayuki Fusumae, Yurika Fujita, Takeo Maekawa, Satoru Murata, Noriyoshi Fukushima, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 42 (11) 1083 - 1086 0385-2407 2015/11 [Refereed][Not invited]
     
    We report a case of sarcomatoid carcinoma of the skin in a 63-year-old man who was treated with the carbon dioxide snow freezing method for a huge congenital pigmented nevus that extended from the right upper extremity to the right trunk during childhood. He had an exophytic red tumor on the nevus in the right upper extremity that grew slowly for 4years and rapidly recently. Histological and immunohistochemical studies revealed both epithelial and mesenchymal malignancy in the same tumor. The epithelial component was composed of basaloid cells forming multiple nests with peripheral palisading, positive for keratins and BerEP4, implying basal cell carcinoma. The mesenchymal component was composed of spindle-shaped cells negative for keratins and positive for vimentin, suggesting sarcoma. This is, to our knowledge, the first report of sarcomatoid carcinoma arising in the primary pigmented nevus that had been treated by the carbon dioxide snow freezing method.
  • Hiroki Imada, Takashi Sakatani, Mikio Sawada, Tohru Matsuura, Noriyoshi Fukushima, Imaharu Nakano
    PATHOLOGY INTERNATIONAL 65 (10) 549 - 553 1320-5463 2015/10 [Refereed][Not invited]
     
    Rosai-Dorfman disease (RDD) is a benign histiocytic proliferative disorder characterized by the accumulation of histiocytes in lymph nodes and various other organs. RDD seldom involves the central nervous system, and cases of purely intracranial RDD are particularly rare. We report a case of purely intracranial RDD involving the brainstem that was diagnosed at autopsy. A 68-year-old woman visited our hospital because of visual disturbances and loss of energy. Magnetic resonance imaging revealed an obscure mass in the brainstem. Despite exhaustive work-ups, the etiology of the intracranial mass remained unclear. The patient died of respiratory depression, and an autopsy was performed for pathological investigation. Macroscopically, a pink pale mass 2.5cm in diameter was found in the brainstem, with no attachment to the dura. Histologically, it was composed of histiocytic cells with incorporation of small lymphocytes (emperipolesis). Immunohistochemical staining revealed that the cells were positive for CD68 and S100 and negative for CD1a, consistent with a diagnosis of RDD. Purely intracranial RDD is extremely rare and considered benign. To date, nine cases (including ours) have been reported. To our knowledge, this is the first case of intracranial RDD with autopsy. Although generally considered benign, RDD involving the brainstem might be lethal.
  • Michihiro Saito, Hiroki Imada, Tsukasa Suzuki, Naohiro Sata, Yoshikazu Yasuda, Iruru Maetani, Noriyoshi Fukushima
    ANNALS OF DIAGNOSTIC PATHOLOGY 19 (5) 347 - 352 1092-9134 2015/10 [Refereed][Not invited]
     
    Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are primary pancreatic neoplasms that can act as precursors to invasive adenocarcinoma of the pancreas. The peritumoral stroma has been increasingly recognized to play an important role in many types of tumors. Therefore, to investigate the clinicopathological significance of the peritumoral stroma in IPMNs, we examined the histological features of the peritumoral stroma in each subtype and histological grade of IPMNs. Eighty-two patients with IPMN, who underwent surgical resection, were reviewed clinicopathologically. Intraductal papillary mucinous neoplasms (86 lesions in total) were histologically subclassified into gastric (n = 51), intestinal (n = 22), pancreatobiliary (n = 11), and oncocytic (n = 2) subtypes. Peritumoral histological features between the gastric and intestinal subtypes were evaluated by each histological grade. The results showed that subepithelial edema and inflammatory cell infiltration were more commonly observed in the gastric subtype (74% and 79%, respectively) than in the intestinal subtype (12% and 25%, respectively) of low-grade IPMNs. On the other hand, mucus lakes were more commonly observed in the intestinal subtype (100%) than in the gastric subtype (0%) of high-grade IPMNs. In addition, pancreatobiliary subtype IPMNs tended to exhibit acute inflammation such as neutrophil predominance. This study showed that peritumoral histological features differed among subtypes of IPMNs from low-grade tumors. These differences suggest the possibility that each subtype of IPMNs has a distinct mechanism from an early stage of tumor progression, which is reflected in the properties of the peritumoral stroma. (C) 2015 Elsevier Inc. All rights reserved.
  • Chizu Saito, Kotaro Ishikawa, Ken-ichi Nakamura, Akifumi Fujita, Michio Shimizu, Noriyoshi Fukushima, Hiroshi Nishino, Keiichi Ichimura
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY 124 (8) 609 - 613 0003-4894 2015/08 [Refereed][Not invited]
     
    Background: Blue nevus is a benign dermal melanocyte tumor that mainly arises from the skin. We report an extremely rare case of blue nevus in a pediatric patient with extensive progression from the middle ear and inner ear to the nasopharynx through the Eustachian tube. Case Report: A 2-year-old girl with blue tympanum was referred to our department. Computed tomography scans and magnetic resonance imaging were performed, followed by a tissue biopsy and histopathologic evaluations. Radiologic examinations revealed that the lesion had progressed beyond the middle ear into the inner ear and the nasopharynx through the Eustachian tube. Subsequent histopathologic examinations indicated dermal dendritic melanocytic proliferations, but no evidence of malignancy. Based on the clinical and histopathologic findings, we concluded that the lesion was consistent with blue nevus. Discussion: Blue nevus is a relatively common skin lesion. However, no prior reports have described the extension of blue nevus from the auditory organ to the nasopharynx in a pediatric patient. Despite the benign nature of the lesion, the patient experienced profound hearing loss in the affected ear, which necessitates continued monitoring as the lesion may expand with patient growth.
  • 横隔膜上食道憩室内癌の1切除例
    松本 志郎, 細谷 好則, 安部 望, 春田 英律, 宇井 崇, 倉科 憲太郎, 齋藤 心, 佐田 尚宏, 安田 是和, 福島 敬宜
    日本食道学会学術集会プログラム・抄録集 (NPO)日本食道学会 69回 197 - 197 2015/07
  • Mitsuaki Morimoto, Yasuyuki Miyakura, Alan T. Lefor, Kazuya Takahashi, Hisanaga Horie, Koji Koinuma, Hiroyuki Tanaka, Homare Ito, Tetsuichiro Shimizu, Yoshihiko Kono, Naohiro Sata, Noriyoshi Fukushima, Takashi Sakatani, Yoshikazu Yasuda
    SURGERY TODAY 45 (7) 834 - 840 0941-1291 2015/07 [Refereed][Not invited]
     
    We hypothesized that a reduction in the size of the lymph nodes after neoadjuvant therapy for locally advanced rectal carcinoma would be associated with decreased lymph node metastases and/or a better prognosis. Between March 2006 and April 2012, 71 patients with primary rectal cancer received neoadjuvant chemoradiation therapy (CRT). For all lymph nodes 5 mm or larger in size, the major and minor axes were measured on CT scan images, and the product was calculated. The lymph node size was determined before and after CRT. The patients were divided into three groups based on the lymph node size before and after treatment. Group A exhibited a reduction in size of 60 % or more, Group B a reduction of less than 60 % and Group C had no lymph node enlargement before treatment. The incidence of lymph node metastases on pathological examination was 15 % in Group A and 50 % in Group B (p = 0.006). The five-year disease-free survival in Group A was 84 % compared with 78 % in Group B (log rank p = 0.34). The five-year overall survival in Group A was 92 % compared with 74 % in Group B (log rank p = 0.088). A reduction in the size of enlarged lymph nodes after neoadjuvant therapy may be a useful prognostic factor for recurrence and survival.
  • Fukushima N
    Nihon rinsho. Japanese journal of clinical medicine 73 Suppl 3 11 - 15 0047-1852 2015/03 [Refereed][Not invited]
  • Takeo Maekawa, Mayumi Komine, Satoru Murata, Noriyoshi Fukushima, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 42 (3) 318 - 321 0385-2407 2015/03 [Refereed][Not invited]
     
    Intravascular large B-cell lymphoma (IVLBCL) is classified as a rare type of non-Hodgkin's B-cell lymphoma by the World Health Organization. It is characterized by the presence of lymphoma cells in the lumens of the small vessels of several organs, most notably the skin. Diagnosis of IVLBCL is difficult because of the lack of lymphadenopathy and because lesions need to be histologically confirmed via a biopsy of the affected organs. Random skin biopsy (RSB) of normal-appearing skin is a useful and apparently safe means of evaluating IVLBCL. However, patients with IVLBCL often exhibit thrombocytopenia, and we describe a case in which a patient with thrombocytopenia experienced hemorrhagic shock and died shortly after RSB. For this reason, we reviewed cases of RSB performed at our hospital and found that the middle adipose tissue contained a higher percentage of atypical lymphoid cells than other layers of the skin. On the basis of our findings, we propose a strategy for the safer performance of RSB in IVLBCL patients with thrombocytopenia and coagulation abnormalities.
  • Olca Basturk, Seung-Mo Hong, Laura Wood, Volkan Adsay, Jorge Albores-Saavedra, Andrew Biankin, Lodewijk Brosens, Noriyoshi Fukushima, Michael Goggins, Ralph Hruban, Yo Kato, Scott Kern, David Klimstra, Gunter Kloppel, Alyssa Krasinskas, Daniel Longnecker, Anirban Maitra, Hanno Matthei, Michio Shimizu, Kyoichi Takaori, Benoit Terris, Shinichi Yachida, Irene Esposito, Toru Furukawa
    LABORATORY INVESTIGATION 95 440A - 440A 0023-6837 2015/02 [Refereed][Not invited]
  • Olca Basturk, Seung-Mo Hong, Laura Wood, Volkan Adsay, Jorge Albores-Saavedra, Andrew Biankin, Lodewijk Brosens, Noriyoshi Fukushima, Michael Goggins, Ralph Hruban, Yo Kato, Scott Kern, David Klimstra, Gunter Kloppel, Alyssa Krasinskas, Daniel Longnecker, Anirban Maitra, Hanno Matthei, G. Johan Offerhaus, Michio Shimizu, Kyoichi Takaori, Benoit Terris, Shinichi Yachida, Irene Esposito, Toru Furukawa
    MODERN PATHOLOGY 28 440A - 440A 0893-3952 2015/02 [Refereed][Not invited]
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi
    Japanese Journal of Medical Technology Japanese Association of Medical Technologists 64 (4) 468 - 474 0915-8669 2015 [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinat
  • Imayoshi S, Kanazawa T, Fukushima N, Kikuchi H, Hasegawa M, Nagatomo T, Nishino H
    Case reports in otolaryngology 2015 846832  2090-6765 2015 [Refereed][Not invited]
  • Noriyoshi Fukushima, Giuseppe Zamboni
    SEMINARS IN DIAGNOSTIC PATHOLOGY 31 (6) 467 - 474 0740-2570 2014/11 [Refereed][Not invited]
     
    Mucinous cystic neoplasms (MCNs) of the pancreas are primary pancreatic cyst-forming neoplasms that can be a precursor to invasive adenocarcinoma of the pancreas. MCNs occur almost exclusively in the distal pancreas of middle-aged women. MCNs typically show a "cyst-in-cyst" pattern of growth and are well encapsulated by a thick fibrous wall. MCNs are composed of mucin-producing neoplastic epithelial cells and "ovarian-type" subepithelial stroma. The epithelium is dysplastic and the grade can range from low to high grade; some MCNs have an associated invasive carcinoma. It is this associated invasive carcinoma that determines prognosis. MCNs harbor several characteristic genetic and epigenetic alterations, some of which are shared with conventional invasive pancreatic ductal adenocarcinoma. Furthermore, several studies reveal characteristic patterns of gene expression in the ovarian-type stroma that suggest steroidogenesis in the ovarian-type stroma. Better knowledge of the molecular alterations could help in the management of patients with this type of precursor of invasive carcinoma. (C) 2014 Elsevier Inc. All rights reserved.
  • Yoshiyuki Meguro, Noriyoshi Fukushima, Masaru Koizumi, Naoya Kasahara, Masanobu Hydo, Kazue Morishima, Naohiro Sata, Alan T. Lefor, Yoshikazu Yasuda
    PATHOLOGY INTERNATIONAL 64 (9) 465 - 471 1320-5463 2014/09 [Refereed][Not invited]
     
    A 54-year-old Japanese woman was referred with a gallbladder tumor. Based on the results of the computed tomography scan, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography, a mucin-producing neoplasm of the gallbladder associated with pancreaticobiliary maljunction was diagnosed. Extended cholecystectomy, extrahepatic bile duct resection, and choledochojejunostomy were performed, and she remains free of recurrence 24 months after resection. Histopathological examination revealed that the papillary component of the lesion was an intracystic papillary neoplasm with diverse characteristics of pancreaticobiliary epithelium and intestinal epithelium including mucin. In this component, most of the papillary lesion was a high-grade intraepithelial neoplasm, but also showed slight invasion into the muscular layer. The nodular component consisted of both poorly differentiated biliary type adenocarcinoma and large cell neuroendocrine carcinoma. We report a rare case of a mixed adenoneuroendocrine carcinoma arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction. As for the histogenesis of this tumor, based on the histopathologic appearance, transdifferentiation from poorly differentiated biliary type adenocarcinoma to large cell neuroendocrine carcinoma is considered the most possible histogenesis of this tumor.
  • Yuta Kawahara, Akira Morimoto, Akinori Onoue, Yoshifumi Kashii, Noriyoshi Fukushima, Yuji Gunji
    EUROPEAN JOURNAL OF PEDIATRICS 173 (8) 1107 - 1110 0340-6199 2014/08 [Refereed][Not invited]
     
    Adrenocortical oncocytomas are rarely reported, occur almost exclusively in adults, and are mostly nonfunctional. Here, we report an interleukin-6 (IL-6)-producing adrenocortical oncocytoma in an 11-year-old girl presenting with fever, body weight loss, and increased levels of inflammatory markers and serum IL-6. Imaging studies revealed a 4-cm mass in the left adrenal gland. After complete resection, laboratory findings returned to normal. Histology was consistent with adrenocortical oncocytoma, and the tumor cells stained positive for IL-6. Conclusion: IL-6-producing adrenocortical oncocytoma should be included in the differential diagnosis and imaging studies should be performed in patients presenting with persistent fever of unknown origin and high levels of inflammatory markers.
  • Harumi Koibuchi, Kiyoka Omoto, Noriyoshi Fukushima, Tomonori Toyotsuji, Nobuyuki Taniguchi, Mikihiko Kawano
    JOURNAL OF ULTRASOUND IN MEDICINE 33 (7) 1299 - 1303 0278-4297 2014/07 [Refereed][Not invited]
     
    This report documents 3 pediatric papillary thyroid carcinoma cases with associated Hashimoto thyroiditis. In all 3 cases, hypoechoic nodules accompanied by multiple echogenic spots were noted on sonography of the thyroid. Hashimoto thyroiditis was suspected on the basis of positive thyroid autoantibody test results and pathologic examinations of thyroidectomy specimens, which revealed chronic thyroiditis with lymphocytic infiltration as the background of papillary thyroid carcinoma development. The potential for papillary carcinoma development warrants close follow-up, and meticulous sonographic examinations must be performed in children with Hashimoto thyroiditis.
  • Kyoko Yamada, Yasuyuki Miyakura, Koji Koinuma, Hisanaga Horie, Alan T. Lefor, Yoshikazu Yasuda, Noriyoshi Fukushima, Yusuke Oyama, Yuta Nemoto, Hiroshi Azuma
    SURGERY TODAY 44 (5) 888 - 896 0941-1291 2014/05 [Refereed][Not invited]
     
    The purpose of this study was to evaluate the clinical features, pathology, and etiology of adenocarcinoma in patients with anal fistulae.We identified seven patients diagnosed with adenocarcinoma associated with anal fistulae from a retrospective chart review.Five patients were diagnosed with primary adenocarcinoma associated with anal fistulae. Two patients were diagnosed with secondary adenocarcinoma associated with anal fistulae originating from rectal cancer on the proximal side. The primary adenocarcinomas included cancers arising from long-standing anal fistulae fulfilling established diagnostic criteria in two patients, and cancer arising from short-duration anal fistulae in three patients. Excision of the fistula was performed based on the initial diagnosis of the anal fistula for all five patients. Increased suspicion of cancer was due to the existence of gelatinous material in the anal fistula in three patients and induration in the resected specimens in two patients. The etiologies of the secondary adenocarcinomas associated with anal fistulae included implantation in the anal fistula from rectal cancer and fistula formation originating due to the progression of rectal cancer.Anal fistulae are commonly seen in the coloproctology clinic, but special attention to similar conditions associated with malignant disease is needed.
  • Fumio Kurosaki, Masashi Bando, Masayuki Nakayama, Naoko Mato, Takakiyo Nakaya, Hideaki Yamasawa, Taichiro Yoshimoto, Noriyoshi Fukushima, Yukihiko Sugiyama
    INTERNAL MEDICINE 53 (12) 1299 - 1306 0918-2918 2014 [Refereed][Not invited]
     
    Objective We retrospectively investigated the clinical features of pulmonary aspergillosis associated with interstitial pneumonia. Methods We reviewed the medical records of all patients treated for interstitial pneumonia with or without pulmonary aspergillosis at our institution between April 2006 and August 2012 and evaluated the clinical features as well as risk and prognostic factors for pulmonary aspergillosis associated with interstitial pneumonia. Results Among 539 patients with interstitial pneumonia, 15 who suffered from pulmonary aspergillosis were identified. The median age was 69.2 +/- 7.0 years, and fourteen patients were men. The subtypes of pulmonary aspergillosis were chronic pulmonary aspergillosis (n=14) and invasive pulmonary aspergillosis (n=1). The forms of interstitial pneumonia included idiopathic pulmonary fibrosis (n=9), rheumatoid arthritisrelated interstitial pneumonia (n=4) and pleuroparenchymal fibroelastosis (n=2). The underlying conditions were emphysema (n=9) and a history of oral corticosteroid and/or immunosuppressive use (n=4). Home oxygen therapy (HOT) was administered in 11 patients. Following the diagnosis of pulmonary aspergillosis, all patients were treated with antifungal drugs. Ten patients (66.6%) died. A comparison of the interstitial pneumonia patients with and without pulmonary aspergillosis showed that the presence of emphysema, use of HOT and death were significantly associated with pulmonary aspergillosis. Conclusion Pulmonary aspergillosis is one of the major complications of interstitial pneumonia and its prognosis is poor. Therefore, providing careful monitoring and proper treatment is extremely important.
  • Yoko T. Katsuragi, Akira Gomi, Ataru Sunaga, Kunio Miyazaki, Hideaki Kamochi, Fumihiro Arai, Noriyoshi Fukushima, Yasushi Sugawara
    JOURNAL OF NEUROSURGERY-PEDIATRICS 12 (6) 622 - 625 1933-0707 2013/12 [Refereed][Not invited]
     
    Numerous reports have demonstrated the usefulness of bioresorbable materials, but few have described severe complications caused by delayed degradation. The authors present the case of an intracranial foreign body granuloma caused by plates made of unsintered hydroxyapatite (uHA) particles and poly-L-lactide (PLLA; Super Fixsorb MX, Takiron) after cranioplasty. This 1-month-old boy presented to the authors' department with Pfeiffer syndrome. He had multiple-suture synostosis causing turribrachycephaly, Chiari malformation Type 1, and obstructive sleep apnea syndrome. At 6 months old, the child was treated with multidirectional cranial distraction osteogenesis. The uHA-PLLA plates were applied as base stones to reinforce the pins. After 16 days of distraction and 3 weeks of consolidation, the pins were removed. Seventeen months postoperatively, the plate on the right temporal bone showed passive intraosseous translocation (PIT), and by 2 years postoperatively, the plate was completely left behind in the cerebrum. At 3.5 years postoperatively, MRI disclosed a contrast-enhanced mass with surrounding brain edema at the site of the plate. The lesion was resected. The clinical history and histological specimens led to a diagnosis of foreign body granuloma surrounding the nonabsorbed resorbable plate in the dura mater. Resorbable plates are clearly useful resources in cases in which delayed absorption will not prove problematic, but careful application and follow-up is required when dealing with the growing skull given the possibility of intracranial displacement after PIT.
  • Chiemi Saigo, Yoshinobu Hirose, Nami Asano, Manabu Takamatsu, Noriyoshi Fukushima, Ichiro Yasuda, Satoshi Goshima, Michio Ozeki, Shinji Osada
    ONCOLOGY LETTERS 6 (4) 871 - 874 1792-1074 2013/10 [Refereed][Not invited]
     
    A solid pseudopapillary neoplasm (SPN) of the pancreas has distinct histopathological features. A solid pattern of growth with pseudopapillary structures that result from degeneration is observed. On rare occasions, the tumor may vary from being entirely solid to completely cystic. The present study describes two unique cases of SPN. A 25-year-old male presented with a pancreatic tumor showing a predominantly solid pattern with no degenerative change, although the pre-operative cytological specimens that were obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) revealed pseudopapillary structures. The second case was of an 11-year-old female who presented with a pancreatic tumor with prominent degeneration. Nests and cords of the remaining neoplastic cells were located only at the periphery, with perineural invasion. An immunohistochemical analysis revealed that the tumor cells in the two cases were positive for CD10 and beta-catenin and negative for trypsin. An awareness of the broad morphological variability of SPN and an immunohistochemical panel that includes CD10, beta-catenin and trypsin are useful for establishing an accurate diagnosis.
  • Mikio Shiozawa, Yasuyuki Miyakura, Makiko Tahara, Kazue Morishima, Hidetoshi Kumano, Koji Koinuma, Hisanaga Horie, Alan T. Lefor, Naohiro Sata, Yoshikazu Yasuda, Kenji Gonda, Seiichi Takenoshita, Akihiko Tamura, Noriyoshi Fukushima, Kokichi Sugano
    JOURNAL OF GASTROENTEROLOGY 48 (6) 770 - 776 0944-1174 2013/06 [Refereed][Not invited]
     
    Lynch syndrome, also referred to as hereditary nonpolyposis colorectal cancer, is the most common form of hereditary colorectal cancer, and is associated with a high incidence of multiple primary neoplasms in various organs.A 79-year-old woman (patient 1) diagnosed with ascending colon cancer had a history of previous carcinomas of the uterus, stomach, uroepithelial tract, and colon. One year later, she developed a brain tumor (glioblastoma). A 54-year-old female (patient 2) was diagnosed with endometrial cancer and sigmoid colon cancer. Both patients underwent genetic evaluations independently.No mutations were found in an exon-by-exon analysis of genomic DNA by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR. However, multiplex ligation-dependent probe amplification (MLPA) identified genomic duplication spanning from exon 7 to exon 14 of the MSH2 gene in both patients. Due to the presence of this characteristic gene duplication, their pedigrees were investigated further, and these showed that they are paternal half-sisters, consistent with paternal inheritance.Large genomic duplication from intron 6 through intron 14 in MSH2 is a very rare cause of Lynch syndrome and is difficult to identify with conventional methods. MLPA may be an alternative approach for detecting large-scale genomic rearrangements.
  • 食道癌肉腫手術症例の検討
    瑞木 亨, 細谷 好則, 齋藤 心, 倉科 憲太郎, 宇井 崇, 春田 英律, 松本 志郎, 佐田 尚宏, 安田 是和, 福島 敬宜
    日本食道学会学術集会プログラム・抄録集 (NPO)日本食道学会 67回 319 - 319 2013/06
  • Takeharu Kanazawa, Noriyoshi Fukushima, Shoichiro Imayoshi, Takafumi Nagatomo, Kazumi Kawada, Hiroshi Nishino, Kiyoshi Misawa, Keiichi Ichimura
    SpringerPlus 2 (1) 2193-1801 2013 [Refereed][Not invited]
     
    Recurrent respiratory papillomatosis (RRP), a chronic upper respiratory condition characterized by diffuse multiple recurring papillomas, is thought to result from human papillomavirus (HPV) type 6 or 11 infection. Although RRP is an intractable disease, malignant transformation of RRP is rare. The underlying mechanism, however, has not been elucidated. We describe the clinical course of a patient who underwent more than 130 operations for RRP associated with HPV type 6 infection and subsequently suffered spontaneous malignant transformation to squamous cell carcinoma. Immunohistochemical analysis revealed that malignant transformation might result from a genomic defect, such as p53 inactivation, leading to stimulation of uncontrolled cell proliferation by HPV type 6 for an extended period, but not directly because of HPV itself. Our results could help in the development of novel therapeutic strategies for severe RRP, although further studies are required before clinical application of molecular targeted therapies. © 2013 Kanazawa et al.
  • Kazuhito Ichikawa, Takahiro Fujimori, Takuya Moriya, Atsushi Ochiai, Shigetaka Yoshinaga, Ryouji Kushima, Ryuji Nagahama, Yasuo Ohkura, Shinji Tanaka, Yoichi Ajioka, Ichiro Hirata, Masanori Tanaka, Yoshio Hoshihara, Yoshikazu Kinoshita, Hironobu Sasano, Akinori Iwashita, Shigeki Tomita, Seiichi Hirota, Takashi Yao, Shigehiko Fujii, Takahisa Matsuda, Hideki Ueno, Yuichi Ishikawa, Kaiyo Takubo, Noriyoshi Fukushima, Tamotsu Sugai, Mitsuya Iwafuchi, Jhoji Imura, Toshiaki Manabe, Masahisa Fukayama
    DIGESTION 88 (3) 153 - 160 0012-2823 2013 [Refereed][Not invited]
     
    The 6th Diagnostic Pathology Summer Fest, held in Tokyo on August 25-26, 2012, opened its gates for everyone in the medical profession. Basic pathology training can contribute to the improvement of algorithms for diagnosis and treatment. The 6th Summer Fest with the theme 'Pathology and Clinical Treatment of Gastrointestinal Diseases' was held at the Ito International Research Center, The University of Tokyo. On August 25, Treatment of Early Gastrointestinal Cancer and New Guidelines' was discussed in the first session, followed by 'Biopsy Diagnosis of Digestive Tract: Key Points of Pathological Diagnosis for Inflammation and Their Clinical Significance' in the second session. On August 26, cases were discussed in the third session, and issues on pathological diagnosis and classification of neuroendorcrine tumor in the fourth session. The summaries of speeches and discussions are introduced along with the statements of each speaker. This meeting was not a formal evidence-based consensus conference, and 20 experts gave talks on their areas of specialty. Discussion was focused on how the management strategy should be standardized on the algorithm of patient care. (C) 2013 S. Karger AG, Basel
  • Yasuyuki Miyakura, Shinichiro Yokota, Hisanaga Horie, Kazutomo Togashi, Alan Lefor, Yoshikazu Yasuda, Noriyoshi Fukushima
    SURGERY TODAY 42 (12) 1215 - 1218 0941-1291 2012/12 [Refereed][Not invited]
     
    Intestinal strangulation caused by a mucocele of the appendix is extremely rare and difficult to diagnose. It is not usually suspected pre-operatively. This report presents a case of intestinal strangulation due to a mucous containing cystic lesion that was wrapped around the base of a loop of the small bowel. An 89-year-old female was transferred after an acute onset of abdominal pain. A physical examination revealed severe tenderness with guarding in the right upper quadrant. CT of the abdomen showed a loop of dilated small bowel with edema on the right side of the abdominal cavity suggesting a closed loop obstruction. In addition, a low-density thin-walled mass measuring 5 cm in diameter was also seen in the pelvis. Intestinal strangulation was suspected and emergency laparotomy was thus performed. A loop of terminal ileum 25 cm in length was strangulated by a dilated appendix, and ileocecal resection was performed. The resected appendix measured 9 x 3 cm in size and contained mucus. A histopathological examination showed a mucous containing cystic appendix without mucin-producing, neoplastic epithelial cells. A mucocele of the appendix can present in various ways and it is important to recognize this entity at the time of surgery.
  • Yoshitaka Iwazu, Tetsu Akimoto, Sayoko Izawa, Makoto Inoue, Shigeaki Muto, Yasuhiro Ando, Kana Iwazu, Noriyoshi Fukushima, Wako Yumura, Eiji Kusano
    CLINICAL AND EXPERIMENTAL NEPHROLOGY 16 (3) 485 - 489 1342-1751 2012/06 [Refereed][Not invited]
     
    We describe a case of an adult female who presented with nephrotic syndrome. She was diagnosed with systemic lupus erythematosus with serum antinuclear antibodies, leucopenia with lymphopenia, butterfly erythema, and nephrotic syndrome. Renal biopsy revealed normal glomeruli with diffuse effacement of the foot processes, consistent with lupus podocytopathy. Although human albumin replacement was performed initially, acute renal failure developed rapidly. Therefore, she was treated with double filtration plasmapheresis (DFPP) in addition to oral steroid. After steroid therapy combined with DFPP, the renal function and proteinuria improved rapidly. Although the impact of DFPP on the treatment of lupus nephritis remains to be delineated, our observations suggest that DFPP in lupus podocytopathy played a pivotal role in facilitating the early recovery from renal injuries. Because of the rapid improvement of renal function without any change in body weight by DFPP, acute renal failure in the setting of lupus podocytopathy might contribute to an alternative pathophysiological factor for the diminished glomerular filtration rate, similar to that observed in the setting of idiopathic minimal change glomerulopathy.
  • Eriko Maeda, Masaaki Akahane, Naoki Yoshioka, Hidemasa Takao, Izuru Matsuda, Kouhei Kamiya, Kenji Hirano, Minoru Tada, Hiroshi Ohtsu, Noriyoshi Fukushima, Kuni Ohtomo
    JAPANESE JOURNAL OF RADIOLOGY 30 (3) 227 - 234 1867-1071 2012/04 [Refereed][Not invited]
     
    Purpose To retrospectively evaluate criteria for differentiating biliary tract changes in autoimmune pancreatitis (AIP-BTC) from extrahepatic cholangiocarcinoma (ECCA) based on CT findings and to determine predictors for differentiation between the two disorders. Materials and methods CT findings of 22 patients with AIP-BTC and 45 patients with ECCA, both with positive CT findings in the biliary system, were retrospectively assessed. The images were assessed for presence of biliary obstruction, diameter of the maximally dilated biliary duct, maximum thickness of the involved duct, presence of masses inside or around the involved ducts, lengths of the biliary lesions, concentricity of wall thickening, multifocality of the lesion, and degree of lesion enhancement. Results Compared with AIP-BTC, ECCA was significantly more frequently associated with biliary obstruction (p = 0.0037), shorter lengths of the biliary lesions (p = 0.0036), and masses (p < 0.001). No significant differences were found for other items. Conclusion Presence of obstructive dilatation of the bile ducts and intraluminal or peri-ductal masses and length of the thickened wall may help differentiate between AIP-BTC and ECCA.
  • Wataru Kimura, Toshiyuki Moriya, Keiji Hanada, Hideki Abe, Akio Yanagisawa, Noriyoshi Fukushima, Nobuyuki Ohike, Michio Shimizu, Takashi Hatori, Naotaka Fujita, Hiroyuki Maguchi, Yasuhiro Shimizu, Kenji Yamao, Tamito Sasaki, Yoshiki Naito, Satoshi Tanno, Kosuke Tobita, Masao Tanaka
    PANCREAS 41 (3) 380 - 387 0885-3177 2012/04 [Refereed][Not invited]
     
    Objectives: There have been only a few reports on follow-up results of serous cystic neoplasm (SCN) of the pancreas. The frequency of malignancy and surgical indication of SCN are not determined yet. Methods: In this multi-institutional study of the Japan Pancreas Society, a total of 172 patients with SCN were enrolled. The mean follow-up period was 4.5 years. Surgical resection was performed in 90 patients, whereas the remaining 82 were simply observed. Results: Of all patients, 20% were symptomatic. The tumor was located in the pancreatic head (39%), body (35%), and tail (22%). The mean diameter of the tumor was 4.1 cm. None of the patients showed distant or lymph node metastasis except for liver metastasis found in 2 patients (1.2%). No patient died during the follow-up. The preoperative diagnosis did not correctly identify SCN in 57 (63%) of 90 resected cases. A honeycomb appearance, which is one of the most characteristic findings of SCN, could be diagnosed better by endoscopic ultrasonography than by other imaging diagnostic modalities. Conclusions: Surgical resection should be considered only when clear distinction from other surgical diseases is difficult, when symptoms or mass effects are present, and when the tumor size is large.
  • Naoko Otani, Tetsu Akimoto, Wako Yumura, Daisuke Matsubara, Yoshitaka Iwazu, Akihiko Numata, Takuya Miki, Fumi Takemoto, Noriyoshi Fukushima, Shigeaki Muto, Eiji Kusano
    DIAGNOSTIC PATHOLOGY 7 (1) 1746-1596 2012/04 [Refereed][Not invited]
     
    Glomerular crescents are most commonly associated with rapidly progressive crescentic glomerulonephritis; however, they also develop in response to a wide range of primary and secondary glomerular injuries. Since various kind of glomerulopathies occasionally overlay diabetic glomerular injuries, the presence of crescents in renal biopsy specimens of diabetics may have stimulated a search for etiologies other than diabetes. In this report, we describe an unusual case of diabetic glomerulosclerosis with peculiar extracapillary proliferation. Although such a relationship has so far been ignored in most of the literature, the etiological linkage between diabetic glomerulosclerosis and the development of crescents may not be exceptional. We have reviewed the previous literature and herein discuss the pathological implications of the development of crescents in patients with diabetic glomerulosclerosis. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3950457896920255.
  • Dai Mohri, Yoshinari Asaoka, Hideaki Ijichi, Koji Miyabayashi, Yotaro Kudo, Motoko Seto, Miki Ohta, Motohisa Tada, Yasuo Tanaka, Tsuneo Ikenoue, Keisuke Tateishi, Hiroyuki Isayama, Fumihiko Kanai, Noriyoshi Fukushima, Minoru Tada, Takao Kawabe, Masao Omata, Kazuhiko Koike
    JOURNAL OF GASTROENTEROLOGY 47 (2) 203 - 213 0944-1174 2012/02 [Refereed][Not invited]
     
    Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes. Surgically resected IPMNs (n = 25) were classified into four subtypes by hematoxylin and eosin (H&E) and mucin immunostaining. Mutations in KRAS, BRAF, and PIK3CA genes and expression of CDKN2A, TP53, SMAD4, phospho-ERK, and phospho-SMAD1/5/8 proteins were examined. There were 11 gastric, 11 intestinal, one pancreatobiliary, and two oncocytic types in this study. We then compared the two major subtypes, gastric-type and intestinal-type IPMN. Gastric-type IPMN showed a significantly higher incidence of KRAS mutations (9/11, 81.8%) compared with intestinal type (3/11, 27.3%; p < 0.05), although the intestinal type showed a higher grade of dysplasia than gastric type (p < 0.01). All cases with KRAS mutations showed phospho-ERK immunostaining. In contrast, intestinal type (9/11, 81.8%) showed more frequent SMAD1/5/8 phosphorylation compared with gastric-type IPMN (3/11, 27.3%; p < 0.05%). There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN. In particular, KRAS mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreatic cancer in IPMN patients.
  • Noriyoshi Fukushima
    Journal of Japanese Society of Gastroenterology 109 (2) 173 - 177 0446-6586 2012/02 [Refereed][Not invited]
  • Yuasa M, Fujiwara S, Oh I, Yamaguchi T, Fukushima N, Morimoto A, Ozawa K
    Journal of clinical and experimental hematopathology : JCEH 2 52 (2) 121 - 126 1346-4280 2012 [Refereed][Not invited]
  • Oka S, Muroi K, Sato K, Fujiwara S, Oh I, Matsuyama T, Ohmine K, Suzuki T, Ozaki K, Mori M, Nagai T, Fukushima N, Fukushima N, Tanaka A, Ozawa K
    Journal of clinical and experimental hematopathology : JCEH 2 52 (2) 127 - 131 1346-4280 2012 [Refereed][Not invited]
  • Takeharu Kanazawa, Noriyoshi Fukushima, Hidetaka Tanaka, Juntaro Shiba, Hiroshi Nishino, Hiroyuki Mineta, Keiichi Ichimura
    Journal of Medical Case Reports 6 431  1752-1947 2012 [Refereed][Not invited]
     
    Introduction. Primary involvement of the salivary glands in small cell carcinoma is rare, and has one of the worst prognoses of salivary gland neoplasms. However, it has been reported that some cases have a favorable outcome, although the prognostic factors are still under consideration. Multidisciplinary therapy was usually required to achieve long-term survival. Recently, a resemblance of some small cell carcinomas of the salivary gland to cutaneous Merkel cell carcinoma was suggested the latter have the potential for spontaneous regression, which is related to a favorable clinical outcome. Case presentation. We present a locoregional advanced parotid small cell carcinoma with multiple lymph node metastases in an 87-year-old Asian woman. The tumor was controlled by surgery alone, and nine-year disease-free survival was achieved without any adjunctive therapy. To the best of our knowledge, this is the longest reported follow-up of head and neck small cell carcinoma. Conclusion: We believe this to be the first case of small cell carcinoma with involvement of the salivary glands reported in the literature with a good outcome after surgery alone without any adjunctive therapy. © 2012 Kanazawa et al. licensee BioMed Central Ltd.
  • Mariko Tanaka, Junji Shibahara, Noriyoshi Fukushima, Aya Shinozaki, Makoto Umeda, Shumpei Ishikawa, Norihiro Kokudo, Masashi Fukayama
    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY 59 (10) 942 - 952 0022-1554 2011/10 [Refereed][Not invited]
     
    Pancreatic ductal neoplasms exhibit gastric epithelium-like characteristics. In this study, we evaluated the expression of claudin-18 (CLDN18), a gastric epithelium-associated claudin, in pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and pancreatic ductal adenocarcinomas (PDACs) using immunohistochemistry. We observed a high level of expression of CLDN18 in PanINs (31/32, 97%), IPMNs (61/65, 95%), and MCNs (4/5, 80%) using ordinary tissue section analysis. Furthermore, we observed a high level of CLDN18 expression in PDACs (109/156, 70%) using tissue microarray analysis. However, the normal pancreatic duct or the ductal metaplasia of the acinar cells was not immunoreactive. Comparative analysis of CLDN18 and phenotypic markers in IPMNs revealed that simultaneous expression of CLDN18 and intestinal markers frequently occurred, even in intestinal-type IPMNs. CLDN18 variant 2 mRNA was expressed and was similarly upregulated by phorbol 12-myristate 13-acetate (PMA) treatment in pancreatic cancer cell lines and in a gastric cancer cell line. An inhibitor of pan-PKC (GF109203X) completely suppressed this upregulation in pancreatic cancer cells. These results indicate that CLDN18, a marker for the early carcinogenetic process, is commonly expressed in precursor lesions of PDAC. Activation of the PKC pathway might be involved in CLDN18 expression associated with pancreatic carcinogenesis. (J Histochem Cytochem 59:942-952, 2011)
  • Aya Tatsuta, Mayumi Komine, Yoshiko Taguchi, Hideto Yokokura, Yumiko Koike, Satoru Murata, Noriyoshi Fukushima, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 38 (7) 730 - 732 0385-2407 2011/07 [Refereed][Not invited]
  • Kenji Yamao, Akio Yanagisawa, Kuniyuki Takahashi, Wataru Kimura, Ryuichiro Doi, Noriyoshi Fukushima, Nobuyuki Ohike, Michio Shimizu, Takashi Hatori, Bunsei Nobukawa, Michio Hifumi, Yuji Kobayashi, Kosuke Tobita, Satoshi Tanno, Masanori Sugiyama, Yoshihiro Miyasaka, Toshio Nakagohri, Taketo Yamaguchi, Keiji Hanada, Hideki Abe, Minoru Tada, Naotaka Fujita, Masao Tanaka
    PANCREAS 40 (1) 67 - 71 0885-3177 2011/01 [Refereed][Not invited]
     
    Objective: The aim of this study was to elucidate the clinicopathological features and prognosis of mucinous cystic neoplasms (MCNs).Materials and Methods: We performed a multi-institutional, retrospective study on a collected series of patients with MCN pathologically defined by ovarian-type stroma. Clinicopathological features and prognosis were investigated.Result: Mucinous cystic neoplasm was confirmed in 156 cases, including 129 adenomas (82.7%) and 21 noninvasive (13.4%) and 6 invasive carcinomas (3.9%). Patients with MCN were exclusively women (98.1%) with the mean age of 48.1 years. All but 1 MCN were in the pancreatic body/tail region with a mean size of 65.3 mm. Communication between the cyst and the pancreatic duct was found in 18.1%. The 3-, 5-, and 10-year survival rates were 97.6%, 96.6%, and 96.6%, respectively. A significant difference in the survival rates was observed between adenomas and carcinomas and between minimally invasive carcinomas and invasive carcinomas. Cyst diameter and presence of mural nodule were predictive of malignant MCN.Conclusions: Mucinous cystic neoplasm is a rare but distinctive pancreatic cystic neoplasm with a favorable overall prognosis. All MCNs should be resected to prevent malignant changes but can be observed an appropriate time when the lesion is small without the presence of mural nodules.
  • Makoto Komura, Yutaka Kanamori, Masahiko Sugiyama, Noriyoshi Fukushima, Tadashi Iwanaka
    PEDIATRIC RADIOLOGY 40 (9) 1569 - 1571 0301-0449 2010/09 [Refereed][Not invited]
     
    Most patients with thymic cysts complain of a slowly enlarging, asymptomatic cervical mass. Only 6-10% suffer dysphagia, dyspnoea, stridor, cervical pain or vocal paralysis. In some rare cases sudden onset of severe dyspnoea or asphyxia is the first symptom, especially in neonates and small infants. We report a unique case of a 20-month-old child, who required emergency tracheal intubation due to asphyxia. Cervicomediastinal thymic cyst might need to be included in causes of life-threatening airway obstruction in young children.
  • Mariko Tanaka, Noriyoshi Fukushima, Naohiro Noda, Junji Shibahara, Norihiro Kokudo, Masashi Fukayama
    HUMAN PATHOLOGY 40 (11) 1543 - 1552 0046-8177 2009/11 [Refereed][Not invited]
     
    Intraductal oncocytic papillary neoplasm is known as a distinct subtype of intraductal papillary mucinous neoplaSm of the pancreas. Similar neoplasms of the bile duct are rarely reported, and their disease characteristics are not well established. In this study, we examined 6 cases of biliary neoplasms consisting of oncocytic cells with almost exclusively intraductal growth. The patients were 5 women and I mail of 51 to 68 years. Grossly, 4 appeared to be cystic neoplasms with papillary projections located in the liver and the other two were papillary neoplasms of the dilated hilar bile duct that ranged from 1.5 to 16 cm in size. The most prominent neoplastic cells were cuboidal epithelial cells that showed abundant eosinophilic granular cytoplasm with strongly positive staining for antimitochondrial antibody. Four neoplasms were mixed with minor components of nononcocytic cells. All neoplasms showed arborized papillary and/or cribriform formations except one, which showed a villous architecture. All neoplasms were adenocarcinomas accompanied by a microscopic minimally invasive carcinoma. The oncocytic neoplastic cells, as well as the nononcocytic cells, produced gastric-type mucin (MUC5AC and MUC6) and showed claudin18 and HepPar-1 positivity. Five patients lived disease-free for 10 to 112 months after resection, and I died of tumor recurrence at 26 months postoperatively. The present series of biliary tumors are intraductal papillary neoplasms with oncocytic features and call be clinicopathologically regarded as counterparts of pancreatic intraductal oncocytic papillary neoplasm. Our results also Suggest that oncocytic changes occur in epithelial cells of biliary tracts that show a predominant gastric phenotype. (C) 2009 Elsevier Inc. All rights reserved.
  • Kenji Hirano, Noriyoshi Fukushima, Minoru Tada, Hiroyuki Isayama, Suguru Mizuno, Keisuke Yamamoto, Yoko Yashima, Hiroshi Yagioka, Takashi Sasaki, Hirofumi Kogure, Yousuke Nakai, Naoki Sasahira, Takeshi Tsujino, Takao Kawabe, Masashi Fukayama, Masao Omata
    JOURNAL OF GASTROENTEROLOGY 44 (7) 765 - 773 0944-1174 2009/07 [Refereed][Not invited]
     
    Background and aims Infiltration of IgG4-positive plasma cells in the pancreas and other organs is characteristic of autoimmune pancreatitis (AIP). However, it is undetermined whether needle or forceps biopsy of pancreas or other organs is indeed useful for the diagnosis of AIP. We aimed to clarify this point. Methods Among 39 AIP patients, tissue sampling without laparotomy was performed in 27. Biopsy of pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was performed in 15, 17, 11, 5 and 7, respectively. The obtained specimens were examined for IgG4-positive plasma cells. We also examined gastric mucosa of 18 patients with pancreatic cancer as controls. When the number of IgG4-positive plasma cells was more than 10 per high-power field, we regarded it as diagnostic. Results Diagnostic sensitivity in pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was 47% (7/15), 47% (8/17), 36% (4/11), 0% (0/5), and 57% (4/7), respectively. Conclusions Sensitivity of IgG4 immunostaining was unsatisfactory when tissue sampling was performed by needle or forceps biopsy. Biopsy of gastric mucosa might be a good subsidiary diagnostic tool.
  • Takeaki Ishizawa, Noriyoshi Fukushima, Junji Shibahara, Koichi Masuda, Surnihito Tamura, Taku Aoki, Kiyoshi Hasegawa, Yoshifumi Beck, Masashi Fukayama, Norihiro Kokudo
    CANCER 115 (11) 2491 - 2504 0008-543X 2009/06 [Refereed][Not invited]
     
    BACKGROUND: We have often encountered difficulties in identifying small liver cancers during surgery. Fluorescent imaging using indocyanine green (ICG) has the potential to detect liver cancers through the visualization of the disordered biliary excretion of ICG in cancer tissues and noncancerous liver tissues compressed by the tumor. METHODS: ICG had been intravenously injected for a routine liver function test in 37 patients with hepatocellular carcinoma (HCC) and 12 patients with metastasis of colorectal carcinoma (CRC) before liver resection. Surgical specimens were investigated using a near-infrared light camera system. Among the 49 subjects, the 26 patients examined during the latter period of the study (20 with HCC and 6 with metastasis) underwent ICG-fluorescent imaging of the liver surfaces before resection. RESULTS: ICG-fluorescent imaging identified all of the microscopically confirmed HCCs (n=63) and CRC metastases (n=28) in surgical specimens. Among the 63 HCCs, 8 tumors (13%, including 5 early HCCs) were not evident grossly unless observed by ICG-fluorescent imaging. Five false-positive nodules (4 large regenerative nodules and 1 bile duct proliferation) were identified among the fluorescent lesions. Well-differentiated HCCs appeared as uniformly fluorescing lesions with higher lesion-to-liver contrast than that of moderately or poorly differentiated HCCs (162.6 [71.1-218.2] per pixel vs 67.7 [-6.3-211.2] per pixel, P<.001), while CRC metastases were delineated as rim-fluorescing lesions. Fluorescent microscopy confirmed that fluorescence originated in the cytoplasm and pseudoglands of HCC cells and in the noncancerous liver parenchyma surrounding metastases. ICG-fluorescent imaging before resection identified 21 of the 41 HCCs (51%) and all of the 16 metastases that were examined. CONCLUSIONS: ICG-fluorescent imaging enables the highly sensitive identification of small and grossly unidentifiable liver cancers in real time, enhancing the accuracy of liver resection and operative staging. Cancer 2009;115:2491-504. (C) 2009 American Cancer Society.
  • Takeaki Ishizawa, Noriyoshi Fukushima, Junji Shibahara, Koichi Masuda, Sumihito Tamura, Taku Aoki, Kiyoshi Hasegawa, Yoshifumi Beck, Yasutsugu Bandai, Masashi Fukayama, Norihiro Kokudo
    GASTROENTEROLOGY 136 (5) A855 - A856 0016-5085 2009/05 [Refereed][Not invited]
  • Noriyoshi Fukushima, Yoshinao Kikuchi, Takashi Nishiyama, Akira Kudo, Masashi Fukayama
    MODERN PATHOLOGY 21 (8) 1044 - 1053 0893-3952 2008/08 [Refereed][Not invited]
     
    Desmoplasia is a common feature of infiltrating ductal adenocarcinoma of the pancreas. This process is intricately interacted between the host and neoplastic cells. Recently, by transcriptome analysis, periostin was identified as a significantly highly expressed gene in pancreatic stellate cells. To investigate the characteristics of periostin immunodeposition in pancreatic ductal neoplasms, we performed immunohistochemistry and in situ hybridization, focusing on tumor -stromal cells interactions. Eighty-one surgically resected pancreatic lesions, including 35 pancreatic ductal adenocarcinoma, 26 intraductal papillary-mucinous neoplasms, 11 mucinous cystic neoplasms and 9 chronic pancreatitis, were studied. In all ductal adenocarcinomas, periostin deposition was observed in the stroma around the infiltrating cancer on immunohistochemistry. Cellular stroma of mucinous cystic neoplasm, called 'ovarian-type' stroma, did not show periostin deposition. In chronic pancreatitis, most of the staining patterns of periostin were perilobular and meshwork-like. Periostin gene expression was detected solely in the stromal cells on in situ hybridization. Intraductal papillary-mucinous neoplasms were classified into four groups on the basis of the histological grade, namely, adenoma, non-invasive adenocarcinoma, adenocarcinoma with microscopical invasion and with macroscopically evident invasion. In intraductal papillary-mucinous neoplasm, periostin deposition in the periductal stroma increased in frequency and intensity in adenocarcinoma compared with adenomas (P = 0.014). Furthermore, our results showed that a higher frequency of periostin deposition was correlated with a higher frequency of ` intestinal phenotype' of proliferating epithelium (P = 0.036) and laminin-5 gamma 2 chain expression (P<0.001) in intraductal papillary-mucinous neoplasm, the latter of which is frequently expressed in invasive carcinoma. This is the first report to describe the periostin immunohistochemistry in intraductal papillary mucinous neoplasm of the pancreas.
  • Hisashi Oshiro, Yohei Miyagi, Yoshiaki Kawaguchi, Yasushi Rino, Hiromasa Arai, Mikiko Asai-Sato, Hiroki Nakayama, Shoji Yamanaka, Yoshiaki Inayama, Noriyoshi Fukushima
    PATHOLOGY INTERNATIONAL 58 (7) 456 - 461 1320-5463 2008/07 [Refereed][Not invited]
     
    Reported herein is a case of endometrial adenocarcinoma without myometrial invasion that metastasized to the pancreas in a 69-year-old Japanese woman who had a history of hysterectomy. Although systemic radiography could not detect any metastasis in the whole body before hysterectomy, imaging performed 2 months after the hysterectomy consisting of CT, magnetic resonance imaging, gallium scintigraphy and positron emission tomography identified a solitary pancreatic tumor. Imaging demonstrated an intracystic papillary growth in the pancreas, suggesting intraductal papillary mucinous neoplasm or mucinous cystic neoplasm. Excised in distal pancreatectomy, the tumor was diagnosed as a pancreatic primary, an invasive papillary adenocarcinoma at first, but both the endometrial tumor and the pancreatic tumor demonstrated similar morphology and immunohistochemistry. Furthermore, the identical nucleotide mutation of TP53 gene was observed from both the endometrial and pancreatic tumors. The pancreatic tumor was therefore confirmed to be a metastasis from the primary endometrial adenocarcinoma. Metastasis to the pancreas from endometrial carcinoma is extremely rare but must be considered even if the previous cancer was treated at an early stage. Histopathological comparison study and genetic analysis are important for the correct diagnosis of metastasis.
  • Ralph H. Hruban, Noriyoshi Fukushima
    Diagnostic Histopathology 14 (6) 260 - 265 1756-2317 2008/06 [Refereed][Not invited]
     
    In contrast to the relatively uniform pathology and the unyielding dismal outcome associated with infiltrating ductal adenocarcinoma of the pancreas, cystic lesions have a broad spectrum of gross and microscopic pathologies, and a range of clinical outcomes. The common cystic lesions of the pancreas are reviewed with emphasis on practical tips for distinguishing between the main entities. © 2008 Elsevier Ltd. All rights reserved.
  • Kenji Hirano, Noriyoshi Fukushima, Minoru Tada, Hiroyuki Isayama, Yoko Yashima, Hiroshi Yagioka, Takashi Sasaki, Hirofumi Kogure, Osamu Togawa, Toshihiko Arizumi, Saburo Matsubara, Yousuke Nakai, Naoki Sasahira, Takeshi Tsujino, Takao Kawabe, Masashi Fukayama, Masao Omata
    GASTROENTEROLOGY 134 (4) A223 - A223 0016-5085 2008/04 [Refereed][Not invited]
  • Chanjuan Shi, Noriyoshi Fukushima, Tadayoshi Abe, Yansong Bian, Li Hua, Brian J. Wendelburg, Charles J. Yeo, Ralph H. Hruban, Michael G. Goggins, James R. Eshleman
    CANCER BIOLOGY & THERAPY 7 (3) 353 - 360 1538-4047 2008/03 [Refereed][Not invited]
     
    KRAS2 gene mutations are found in 75-90% of infiltrating pancreatic ductal adenocarcinomas but can also be present with other nonneoplastic pancreatic diseases. We recently developed a novel sensitive assay for point mutation detection, called "LigAmp", which can detect one mutant molecule in the presence of 10,000 wild-type molecules and can quantify mutant DNA over a wide dynamic range. We analyzed KRAS2 mutations in surgically-collected pancreatic duct juice samples from patients with pancreatic adenocarcinoma ( n = 27) and chronic pancreatitis ( n = 9). DNA sequencing demonstrated that 17 of the 27 pancreatic cancers harbored KRAS2 mutations at codon 12, including G12D ( GGT -> GAT), G12V ( GTT), and G12R ( CGT). We determined the relative amounts of each KRAS2 mutant by simultaneously quantifying wild-type and mutant KRAS2 DNA. For all pancreatic adenocarcinoma patients, the dominant KRAS2 mutation detected in the pancreatic juice corresponded to that found in the primary cancer. Mutation levels were substantially higher in patients with pancreatic cancer ( 0.05 to 82% of total KRAS2 molecules) compared to those with chronic pancreatitis ( 0 to 0.7%). Among patients with mutant KRAS2 positive cancers, all but one ( 94%) had mutant KRAS2 DNA concentrations of more than 0.5% in their pancreatic juice samples, whereas only 1 of 9 ( 11%) pancreatic juice samples from patients with chronic pancreatitis had more than 0.5% mutant KRAS2 DNA, corresponding to a sensitivity of 94% and a specificity of 89%. LigAmp quantification of mutant KRAS2 in pancreatic juice differentiates pancreatic adenocarcinoma from chronic pancreatitis, and may be a useful early detection tool for pancreatic cancer.
  • Norihiro Sato, Noriyoshi Fukushima, Ralph H. Hruban, Michael Goggins
    MODERN PATHOLOGY 21 (3) 238 - 244 0893-3952 2008/03 [Refereed][Not invited]
     
    Infiltrating adenocarcinoma of the pancreas is thought to develop through well-defined precursor lesions called pancreatic intraductal neoplasia (PanIN). Despite the exponential growth in our understanding of genetic events that characterize the progression of PanINs to invasive carcinoma, little is known about the role of epigenetic alterations in these precursor lesions. To define the timing and prevalence of methylation abnormalities during early pancreatic carcinogenesis, we investigated the CpG island methylation profile in the various grades of PanINs. Using methylation-specific PCR, we analyzed DNA samples from 65 PanIN lesions for methylation status of eight genes recently identified by microarray approach as aberrantly hypermethylated in invasive pancreatic cancer. Aberrant methylation at any of the eight genes was identified in 68% of all the PanIN lesions examined, and, notably, aberrant methylation was identified in more than 70% of the earliest lesions (PanIN-1A). The average number of methylated loci was 1.1 in PanIN-1A, 0.8 in PanIN-1B, 1.1 in PanIN-2, and 2.9 in PanIN-3 lesions (P = 0.01 for PanIN -3 vs earlier PanINs). Among the genes analyzed, NPTX2 demonstrated an increase in methylation prevalence from PanIN-1 to PanIN-2 (P = 0.0008), and from PanIN-2 to PanIN-3 for SARP2 (P = 0.001), Reprimo (P = 0.01), and LHX1 (P = 0.03). These results suggest that aberrant CpG island hypermethylation begins in early stages of PanINs, and its prevalence progressively increases during neoplastic progression.
  • Hashimoto T, Kitayama J, Hidemura A, Ishigami H, Kaizaki S, Fukushima N, Miyata T, Nagawa H
    Case reports in gastroenterology 1 1 (1) 184 - 189 2007/12 [Refereed][Not invited]
  • Taclayoshi Abe, Noriyoshi Fukushima, Kieran Brune, Corinne Boehm, Norihiro Sato, Hiroyuki Matsubayashi, Marcia Canto, Gloria M. Petersen, Ralph H. Hruban, Michael Goggins
    CLINICAL CANCER RESEARCH 13 (20) 6019 - 6025 1078-0432 2007/10 [Refereed][Not invited]
     
    Purpose: Most familial cancer susceptibility genes are tumor suppressor genes that are biallelically inactivated in familial neoplasms through somatic deletion of the wild-type allele. Identifying the genomic losses that occur in pancreatic neoplasms, particularly those that occur in familial and precursor neoplasms, may help localize the genes responsible for pancreatic cancer susceptibility. Experimental Design: Normal and neoplastic tissue DNA was isolated from fresh-frozen surgically resected tissues from 20 patients with primary familial pancreatic adenocarcinoma (defined as having at least one first-degree relative with pancreatic cancer), 31 with sporadic intraductal papillary mucinous neoplasms (IPMN), and 7 with familial IPMNs using laser capture microdissection. Microdissected DNA was whole genome amplified using multiple strand displacement. Genome-wide allelotypes were determined using 391 microsatellite markers. The accuracy of microdissection and fidelity of the whole genome amplification were determined by comparing the genotypes of microdissected primary pancreatic cancers to the genotypes of xenografts derived from these cancers and by comparing the results of amplified to nonamplified specimens. Results: The concordance of genotypes between LCM whole genome amplified primary pancreatic cancers and their corresponding pancreatic cancer xenograft DNAs was 98%. Among the 20 primary familial pancreatic adenocarcinomas, we found a high prevalence of loss of heterozygosity (LOH) with an average fractional allelic loss (FAL) of 49.9% of an aggregate of 2,378 informative markers. The level of FAL in the IPMNs (10%) was significantly lower than in the pancreatic adenocarcinomas. The most common locus of LOH in the IPMNs was at 19p (LOH at 24% of markers). The regions of frequent allelic loss observed in the familial pancreatic cancers were similar to those found in sporadic pancreatic cancers. Conclusions: The allelic loss patterns of familial and sporadic pancreatic cancers and IPMNs provide clues as to the genomic locations of tumor suppressor genes inactivated in these neoplasms.
  • Noriyoshi Fukushima, Masashi Fukayama
    JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 14 (3) 238 - 242 0944-1166 2007/05 [Refereed][Not invited]
     
    Mucinous cystic neoplasm (MCN) of the pancreas is a distinct clinicopathological entity characterized by mucin-producing epithelial and cyst-forming neoplasm with "ovarian-type" stroma beneath the epithelial component. It is clearly distinguished from ductal adenocarcinoma and intraductal papillary mucinous neoplasm (IPMN). However, MCN can progress to infiltrating carcinoma, and frequently shows a similar histological pattern to ductal adenocarcinoma. Several genetic alterations such as K-ras oncogene mutation, and epigenetic alterations such as hypermethylation of p16 in the invasive component of MCN are also common with ductal adenocarcinoma. Furthermore, recent technologies, including a laser-assisted microdissection system for histological slides and global gene expression profilings using DNA microarrays, made possible to identify more information about molecular abnormalities of MCNs. It is important to diagnose the lesions before they progress to an invasive carcinoma. MCN is one of the precursors of invasive pancreatic carcinoma.
  • Takao Itoi, Atsushi Sofuni, Noriyoshi Fukushima, Fumihide Itokawa, Takayoshi Tsuchiya, Toshio Kurihara, Fuminori Moriyasu, Akihiko Tsuchida, Kazuhiko Kasuya
    JOURNAL OF GASTROENTEROLOGY 42 (5) 389 - 394 0944-1174 2007/05 [Refereed][Not invited]
     
    Background. Gemcitabine is an efficacious cytotoxic agent used in the treatment of unresectable pancreatic carcinoma (PC). Recently, gemcitabine resistance has been associated with the ribonucleotide reductase subunit M2 (RRM2). In this prospective study, we hypothesized that RRM2 expression in PC biopsy specimens would be a significant predictor of outcome. Methods. RRM2 mRNA expression in 35 endoscopic ultrasonography-guided fine needle aspiration biopsy (EUS-FNAB) samples was quantified using real-time quantitative reverse transcription -polymerase chain reaction. Results. Thirty-one of 35 biopsy specimens could be assessed for RRM2 expression levels. The mean RRM2 expression relative to glyceraldehyde-3-phcsphate dehydrogenase was 0.248 (range, 0.00739 to 0.858). Eighteen patients (64.5%) had low RRM2 levels, and 13 patients (35.5%) had high RRM2 levels with a cutoff of 0.1. The median survival was 8.8 months for patients with low RRM2 levels and 5.0 months for patients with high levels (P < 0.05). In the low RRM2 expression group, a complete response (CR) was observed in one patient, and a partial response (PR) was observed in eight patients. In contrast, in the high RRM2 expression group, PR was observed in one patient, and CR was not observed. The overall response rate between the high and low expression groups was significantly different (50.0% vs. 7.7%, P < 0.05). Conclusions. RRM2 mRNA expression of EUS-FNAB specimens is a key predictive marker of survival in gemcitabine-treated patients with PC.
  • Yasuhiro Hibi, Noriyoshi Fukushima, Akihiko Tsuchida, Atsushi Sofuni, Takao Itoi, Fuminori Moriyasu, Kiyoshi Mukai, Tatsuya Aoki
    PANCREAS 34 (2) 197 - 204 0885-3177 2007/03 [Refereed][Not invited]
     
    Objectives: Histological subclassification of intraductal papillary mucinous neoplasms (IPMNs) is important because the malignant potential of each subtype is different. We investigated whether pancreatic juice cytology can be used to define the subtypes of IPMNs preoperatively. Methods: The cytological findings and pathological parameters in 19 cases of IPMN were analyzed for correlations. Pancreatic juice cytology specimens were reviewed and classified into 4 types according to the criteria previously described for histological diagnosis: intestinal (Int), gastric foveolar (GF), oncocytic (Onc), and pancreatobiliary (PB), and the resected IPMNs were classified histologically using the same criteria for comparison. Immunochemical testing for MUC proteins was also performed. Results: fit 15 cases (79%), the cytological and histological subclassifications were in agreement. The cytology specimens displayed different features corresponded to their histological subtypes. The sensitivities of the cytological diagnosis of each subtype were 80.0% (Int), 72.7% (GF), and 100% (Onc/PB); and the specificities were 85.7% (Int), 87.5% (GF), and 93.8% (Onc/PB). The cytoplasm of the Int-type cells in the pancreatic juice cytology specimens was positive for MUC2. Conclusions: Most of the cytological findings of IPMNs corresponded to the histological findings. The use of MUC2 immunocytochemistry in IPMN subtyping was also demonstrated. Subtyping of IPMNs is useful for preoperative evaluation in addition to cytomorphological grading.
  • Ralph H. Hruban, Noriyoshi Fukushima
    MODERN PATHOLOGY 20 S61 - S70 0893-3952 2007/02 [Refereed][Not invited]
     
    Pancreatic cancer is the fourth leading cause of cancer death in the US. Most pancreatic cancers are infiltrating ductal adenocarcinomas. The careful application of well-defined morphologic criteria can be used to differentiate between infiltrating ductal adenocarcinoma and reactive glands. While most pancreatic cancers are ductal adenocarcinomas, a number of histologically defined variants have been described. These are important to recognize because they have distinct clinical pathologic features. Pancreatic intraepithelial neoplasia (PanIN) is the presumed precursor lesion to infiltrating ductal adenocarcinoma, and PanIN lesions can mimic infiltrating cancer.
  • Carmelle D. Rogers, Noriyoshi Fukushima, Norihiro Sato, Chanjuan Shi, Nijaguna Prasad, Steven R. Hustinx, Hiroyuki Matsubayashi, Marcia Canto, James R. Eshleman, Ralph H. Hruban, Michael Goggins
    CANCER BIOLOGY & THERAPY 5 (10) 1383 - 1389 1538-4047 2006/10 [Refereed][Not invited]
     
    Background: The gene expression profile of pancreatic cancer is significantly different from that of normal pancreas. Differences in gene expression are detectable using microarrays, but microarrays have traditionally been applied to pancreatic cancer tissue obtained from surgical resection. We hypothesized that gene expression alterations indicative of pancreatic cancer can be detected by profiling the RNA of pancreatic juice. Methods: We performed oligonucleotide microarray analysis on RNA isolated from pancreatic juice obtained endoscopically after secretin stimulation from six patients with pancreatic cancer and ten patients with nonneoplastic diseases of the pancreas or upper gastrointestinal tract. Extracted RNA was subjected to two rounds of linear RNA amplification, and then hybridized with U133A or X3P gene chips (Affymetrix). Results: Using the U133A or X3P chips, 37 and 133 gene fragments respectively, were identified as being at least 3-fold more abundant in the pancreatic juice of patients with pancreatic cancer compared to the noncancer controls ( p < 0.05, Mann-Whitney test). For example, pancreatic juice from patients with pancreatic cancer contained increased levels of IL8, IFITM1, fibrinogen, osteopontin, CXCR4, DAF and NNMT RNA, genes that have been previously reported as overexpressed in primary pancreatic cancers or pancreatic cancer cell lines relative to control tissues. Conclusions: These results demonstrate that RNA analysis of pancreatic juice can reveal some of the same RNA alterations found in invasive pancreatic cancers. RNA analysis of pancreatic juice deserves further investigation to determine its utility as a tool for the evaluation of pancreatic lesions.
  • Norihiro Sato, Noriyoshi Fukushima, Hiroyuki Matsubayashi, Christine A. Iacobuzio-Donahue, Charles J. Yeo, Michael Goggins
    CANCER 107 (2) 251 - 257 0008-543X 2006/07 [Refereed][Not invited]
     
    BACKGROUND. The p53-dependent G2/M checkpoint plays a key role in the maintenance of genomic integrity, thereby protecting cells from neoplastic progression. Reprimo, a gene involved in the p53-induced G2 cell cycle arrest, has been recently identified as a novel target for aberrant methylation in pancreatic and other cancers. The biological and clinical relevance of Reprimo methylation in pancreatic cancer was investigated.METHODS. The methylation status of Reprimo CpG island was analyzed by methylation-specific polymerase chain reaction in a large series of pancreatic cancers and was correlated with p53 mutation status, genetic instability (as measured by the fractional allelic loss), and clinicopathologic features.RESULTS. Aberrant methylation of Reprimo was identified in 60% (75 of 125) of pancreatic cancer xenografts and primary pancreatic adenocarcinomas. Reprimo methylation was also detectable in 30% (19 of 63) of pancreatic intraepithelial neoplasias (PanIN), known precursors to infiltrating carcinoma. Reprimo methylation was unrelated to the p53 mutation status and associated with the increased degree of genetic instability (P=.04). Furthermore, we found that patients with Reprimo methylation in their primary pancreatic cancers have significantly worse prognosis than those without Reprimo methylation (P=.007). In contrast, other methylation targets in pancreatic cancers (SPARC and CXCR4) did not correlate with prognosis.CONCLUSIONS. These results suggest that aberrant methylation of Reprimo is a common event in pancreatic carcinogenesis and is associated with genetic instability and unfavorable outcome after surgical resection.
  • N Sato, N Fukushima, R Chang, H Matsubayashi, M Goggins
    GASTROENTEROLOGY 130 (2) 548 - 565 0016-5085 2006/02 [Refereed][Not invited]
     
    Background & Aims: Recently described genome-wide approaches robustly detect many candidate genes that are regulated by DNA methylation, but many of these genes do not represent important targets for functional inactivation. Here we used a microarray-based strategy to identify biologically relevant genes associated with epigenetic silencing in pancreatic cancer. Methods: We compared information from differential gene expression analysis with the transcriptional responses to epigenetic modifiers. Results: Using this approach, we identified 7 novel targets for aberrant methylation in pancreatic cancer. One of the genes identified, RELN (Reelin), a key regulator of neuronal migration, is frequently silenced in pancreatic cancers, as are several of its downstream mediators. Importantly, small interfering RNA-mediated knockdown of RELN in pancreatic cancer cells that retain RELN expression resulted in greatly enhanced cell motility, invasiveness, and colony-forming ability. Increased cell motility was also induced by knockdown of downstream components of the RELN pathway, including ApoER2, VLDLR, and DAB1. Treatment of pancreatic cancer cells with histone deacetylase inhibitors, valproic acid and suberoylanilide hydroxamic acid, restored the expression of RELN and DAB1 and markedly inhibited their migration. Conclusions: The high prevalence of the silencing of RELN pathway components and its reversal by histone deacetylase inhibitors suggest the importance of this pathway as a diagnostic and therapeutic target for pancreatic cancer.
  • T Furukawa, G Kloppel, NV Adsay, J Albores-Saavedra, N Fukushima, A Horii, RH Hruban, Y Kato, DS Klimstra, DS Longnecker, J Luttges, GJA Offerhaus, M Shimizu, M Sunamura, A Suriawinata, K Takaori, S Yonezawa
    VIRCHOWS ARCHIV 447 (5) 794 - 799 0945-6317 2005/11 [Refereed][Not invited]
     
    Now that more than two decades have passed since the first reports of intraductal papillary-mucinous neoplasms (IPMNs), it has become clear that IPMN consists of a spectrum of neoplasms with both morphological and immunohistochemical variations. At a meeting of international experts on pancreatic precursor lesions held in 2003, it was agreed that a consensus classification of IPMN subtypes should be established to enable a more detailed analysis of the clinicopathological significance of the variations. Based on our experience and on information from the literature, we selected representative histological examples of IPMNs and defined a consensus nomenclature and criteria for classifying variants as distinctive IPMN subtypes including gastric type, intestinal type, pancreatobiliary type, and oncocytic type. These definitions can be used for further analyses of the clinicopathological significance of the variations of IPMN.
  • N Sato, H Matsubayashi, T Abe, N Fukushima, M Goggins
    CLINICAL CANCER RESEARCH 11 (13) 4681 - 4688 1078-0432 2005/07 [Refereed][Not invited]
     
    Purpose: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is an increasingly identified precursor to infiltrating ductal adenocarcinoma. Although our knowledge of the clinical and pathologic features of IPMNs is increasing, the molecular mechanisms underlying these neoplasms remain poorly understood. Experimental Designs: To provide further insight into the molecular pathobiology of IPMNs, global expression profiling was done to determine genes that are inactivated/down-regulated in IPMNs using oligonucleotide microarrays (Affymetrix). Results: In total, 300 unique transcripts (217 known genes) were identified as highly underexpressed in 12 IPMNs (< 10-fold lower and P < 0,05) compared with five normal pancreatic ductal epithelium samples obtained by laser capture microdissection. The differential expression of a selection of genes was confirmed using reverse-transcription PCR. One of the genes underexpressed at both the transcriptional and protein level in a significant proportion of IPMNs was the cyclin-dependent kinase inhibitor, CDKN1C/p57K1P2. CDKN1C expression was also decreased in many pancreatic cancer cell lines and was restored following treatment with a DNA methylation inhibitor (5-aza-2'-deoxycitidine) or, more potently, with a histone deacetylase inhibitor (trichostatin A), Partial methylation of the CDKN1C promoter CpG island was found in most, but not all, pancreatic cancer cell lines with reduced CDKN1C expression, and was also detectable in IPMNs. Furthermore, a subset of pancreatic cancers showed complete hypornethylation of LIT1, an imprinting control region important for the regulation of CDKN1C expression. Complete hypornethylation in these cancers was the result of deletion of the methylated LIT1 allele at 11p15.5 rather than loss of imprinting. dConclusions: These findings suggest that CDKN1C is commonly down-regulated in pancreatic ductal neoplasms through a combination of promoter hypermethylation, histone deacetylation, and loss of the maternal allele expressing CDKN1C.
  • N Fukushima, J Koopmann, N Sato, N Prasad, R Carvalho, SD Leach, RH Hruban, M Goggins
    MODERN PATHOLOGY 18 (6) 779 - 787 0893-3952 2005/06 [Refereed][Not invited]
     
    The non-neoplastic pancreatic parenchyma adjacent to infiltrating ductal adenocarcinoma demonstrates inflammation, fibrosis, acinar cell loss and small duct-like metaplasia of acinar cells. Similar morphologic changes are also observed in the setting of chronic pancreatitis. In addition, peritumoral acini have been shown to have alterations in gene expression even in the absence of morphological changes. To better understand the pancreatic acinar responses to infiltrating pancreatic ductal adenocarcinoma, we characterized gene expression patterns of pancreatic acinar tissue adjacent to infiltrating pancreatic ductal adenocarcinomas and compared them to gene expression patterns of acinar tissue affected by chronic pancreatitis as well as to those of normal pancreatic acini. Fresh-frozen pancreatic acinar tissue was microdissected from nine patients ( three with pancreatic cancer, three with chronic pancreatitis, three with normal pancreata) using laser capture microdissection, and extracted RNA from each microdissection was subjected to two rounds of linear amplification and hybridized to oligonucleotide microarrays. Gene expression patterns were confirmed using quantitative RT-PCR and/or immunohistochemistry. A total of 20 genes was found to be overexpressed in peritumoral acinar tissue compared to normal acinar tissue and to acini affected by chronic pancreatitis. These 20 genes included pancreatitis-associated protein (HIP/PAP), a gene known to be overexpressed in acini adjacent to infiltrating pancreatic cancer, and the gene cartilage glycoprotein-39 (HC gp-39 or TKL-40). Serum HC gp-39 protein levels were significantly higher in patients with pancreatic cancer and in those with chronic pancreatitis than in controls without pancreatic disease. There was no significant difference in the levels of serum HC gp-39 in patients with pancreatic cancer and those with chronic pancreatitis. Our results demonstrate some of the molecular alterations in acinar cells that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma and reveal that such alterations can provide a rich source of markers of pancreatic cancer.
  • Hustinx, SR, N Fukushima, ML Zahurak, TS Riall, A Maitra, L Brosens, JL Cameron, CJ Yeo, GJA Offerhaus, RH Hruban, M Goggins
    CANCER BIOLOGY & THERAPY 4 (5) 596 - 601 1538-4047 2005/05 [Refereed][Not invited]
     
    Aberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5' region of 14-3-3 sigma (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers. We investigated the prognostic significance of aberrant expression of 14-3-3 sigma and the ERM proteins (Ezrin, radixin, Moesin) in a series of invasive periampullary adenocarcinomas including 300 infiltrating pancreatic adenocarcinomas, 54 ampullary adenocarcinomas, and 33 noninvasive intraductal papillary mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003. Two-hundred fourty-four (82%) primary infiltrating adenocarcinomas of the pancreas demonstrated positive expression of the 14-3-3 sigma, 45 (15%) showed weak immunolabelling, and 9 (3%) were negative. 201 (68%) showed positive immunolabeling of the ERM proteins, 75 (25%) demonstrated weak expression and 20 (7%) no expression. A similar proportion of ampullary cancers showed 14-3-3 sigma and ERM protein expression. Expression of 14-3-3 sigma and ERM protein was more likely in poorly differentiated cancers (p = 0.00005), and their expression was associated with poor survival in univariate analysis (p = 0.09). By multivariate analysis, patients whose cancers expressed 14-3-3 sigma, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p = 0.14). Aberrant expression of 14-3-3 sigma may contribute to the outcome of patients with pancreatic ductal adenocarcinoma.
  • Fukushima N, Mukai K
    Gan to kagaku ryoho. Cancer & chemotherapy 5 32 599 - 604 0385-0684 2005/05 [Refereed][Not invited]
  • A Maitra, N Fukushima, K Takaori, RH Hruban
    ADVANCES IN ANATOMIC PATHOLOGY 12 (2) 81 - 91 1072-4109 2005/03 [Refereed][Not invited]
     
    Pancreatic cancer, once invasive, is almost uniformly fatal. In order to alleviate the dismal prognosis associated with this disease, it is imperative that pancreatic cancer be recognized and treated prior to invasion. Understanding the morphology and biology of precursor lesions of invasive pancreatic cancer has therefore become an issue of paramount importance. In the last decade, significant progress has been in the recognition and appropriate classification of these precursor lesions, and the current review will focus on our state-of-the-art knowledge on this topic. Mucinous cystic neoplasms (MCNs), intraductal papillary mucinous neoplasms (IPMNs), and pancreatic intraepithelial neoplasia (PanIN) encompass the three known morphologically distinct precursors to invasive pancreatic cancer. In addition to discussion of the "classic" precursor entities, this review will also address some of the recent diagnostic controversies for these lesions, in particular features that distinguish IPMNs from PanIN lesions. Finally, the potential clinical impact of recognizing these precursor lesions in the context of early detection of pancreatic cancer will be discussed.
  • NB Prasad, AV Biankin, N Fukushima, A Maitra, S Dhara, AG Elkahloun, RH Hruban, N Goggins, SD Leach
    CANCER RESEARCH 65 (5) 1619 - 1626 0008-5472 2005/03 [Refereed][Not invited]
     
    Invasive pancreatic cancer is thought to develop through a series of noninvasive duct lesions known as pancreatic intraepithelial neoplasia (PanIN). We used cDNA microarrays interrogating 15,000 transcripts to identify 49 genes that were differentially expressed in microdissected early PanIN lesions (PanIN-1B/2) compared with microdissected normal duct epithelium. In this analysis, a cluster of extrapancreatic foregut markers, including pepsinogen C, MUC6, KLF4, and TFF1, was found to be up-regulated in PanIN. Up-regulation of these genes was further validated using combinations of real-time reverse transcription-PCR, in situ hybridization, and immunohistochemistry in a total of 150 early PanIN lesions from 81 patients. Identification of these gastrointestinal transcripts in human PanIN prompted assessment of other foregut markers by both semiquantitative and realtime reverse transcription-PCR, revealing similar upregulation of Sox-2, Gastrin, HoxA5, GATA4/5/6, Villin and Forkbead 6 (FoxI1). In contrast to frequent expression of multiple gastric epithelial markers, the intestinal markers intestinal fatty acid binding protein, CDX1 and CDX2 were rarely expressed either in PanIN lesions or in invasive pancreatic cancer. Hedgehog pathway activation induced by transfection of immortalized human pancreatic ductal epithelial cells with Gli1 resulted in up-regulation of the majority of foregut markers seen in early PanIN lesions. These data show frequent up-regulation of foregut markers in early PanIN lesions and suggest that PanIN development may involve Hedgehog-mediated conversion to a gastric epithelial differentiation program.
  • N Sato, AR Parker, N Fukushima, Y Miyagi, C Iacobuzio-Donahue, Eshleman, JR, M Goggins
    ONCOGENE 24 (5) 850 - 858 0950-9232 2005/01 [Refereed][Not invited]
     
    Using microarrays, we have screened for genes reactivated by drugs that modify epigenetic mechanisms in pancreatic cancer cells. One of the genes identified was tissue factor pathway inhibitor 2 (TFPI-2), which encodes for a broad-spectrum serine proteinase inhibitor that negatively regulates the extracellular matrix degradation, an essential step in tumor invasion and metastasis. We therefore investigated the expression and methylation patterns of the TFPI-2 gene in pancreatic adenocarcinoma, and determined its role in tumor growth and invasion. In contrast to its abundant expression in normal pancreas, TFPI-2 mRNA was undetectable in a high fraction of pancreatic cancer cell lines and in primary pancreatic ductal neoplasms (IPMNs). Loss of TFPI-2 expression was associated with aberrant hypermethylation of its promoter CpG island. Treatment with the phorbol ester (PMA), known to stimulate the TFPI-2 promoter activity, augmented the TFPI-2 expression in cell lines with unmethylated or partially methylated TFPI-2, but failed to induce the expression in cell lines that harbored fully methylated TFPI-2. Aberrant methylation of TFPI-2 was also detected in 73% (102/140) of pancreatic cancer xenografts and primary pancreatic adenocarcinomas, was more likely in older patients with pancreatic cancer, and significantly correlated with progression of IPMNs (P = 0.0002). Restored expression of the TFPI-2 gene in nonexpressing pancreatic cancer cells resulted in marked suppression in their proliferation, migration, and invasive potential in vitro. We thus conclude that epigenetic inactivation of TFPI-2 is a common mechanism that contributes to the aggressive phenotype of pancreatic ductal adenocarcinoma.
  • Hustinx, SR, RH Hruban, LM Leoni, C Iacobuzio-Donahue, JL Cameron, CJ Yeo, PN Brown, P Argani, R Ashfaq, N Fukushima, M Goggins, SE Kern, AA Maitra
    CANCER BIOLOGY & THERAPY 4 (1) 83 - 86 1538-4047 2005/01 [Refereed][Not invited]
     
    Methylthioadenosine phosphorylase (MTAP) plays an important role in the salvage pathway for the synthesis of adenosine. Novel chemotherapeutic strategies exploiting the selective loss of MTAP function in cancers have been proposed. The MTAP gene, on chromosome 9p21, is frequently included within homozygous deletions of the p16(INK4A)/CDKN2A gene. Biallelic deletions of the p16(INK4A)/CDKN2A gene are found in 40% of pancreatic cancers, suggesting that the MTAP gene may be frequently inactivated in pancreatic cancer and that selected patients with pancreatic cancer may benefit from therapies targeting this loss. We immunolabeled six xenografted pancreatic cancers with known MTAP and p16(INK4A)/CDKN2A gene status and found that immunolabeling mirrored gene status. Loss of expression of both MTAP and p16 was observed only in those pancreatic cancers with homozygous deletions that encompassed both the MTAP and p16(INK4A)/CDKN2A genes. We then immunolabeled a series of 320 microarrayed infiltrating pancreatic adenocarcinomas, 35 biliary adenocarcinomas, 54 ampullary cancers, and 35 noninvasive intraductal papillary mucinous neoplasms. Immunolabeling for MTAP was lost in 91 of the 300 (30%) evaluable pancreatic cancers, nine of 54 (17%) ampullary cancers, four of 33 (12%) biliary cancers, and in one of 35 (3%) IPMNs. All neoplasms with loss of MTAP labeling also demonstrated loss of p16 labeling. These results suggest that MTAP expression is lost in similar to 30% of infiltrating pancreatic cancers and in a lower percentage of other periampullary neoplasms, that this loss is the result of homozygous deletions encompassing both the MTAP and p16(INK4A)/CDKN2A genes. Thus, pancreatic cancer is a promising cancer type in which to explore novel chemotherapeutic strategies to exploit the selective loss of MTAP function.
  • N Sato, H Matsubayashi, N Fukushima, M Goggins
    CANCER BIOLOGY & THERAPY 4 (1) 70 - 76 1538-4047 2005/01 [Refereed][Not invited]
     
    Despite the biological and clinical importance of the interaction between the chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1 alpha) in human cancers, little is known about transcriptional regulation of the CXCR,4 gene. Although aberrant hypermethylation in cancer has been described typically in genes with tumor-suppressor properties, this epigenetic alteration has also been observed to affect potential cancer-promoting genes. We now demonstrate that DNA methylation influences CXCR4 expression in human pancreatic cancer. Gene expression profiling and reverse transcription-PCR identified a significant proportion of pancreatic cancer cell lines that displayed little or no CXCR4 mRNA expression. Using methylation-specific PCR, combined bisulfite restriction analysis, and bisulfite sequencing, we found the 5' CpG islands of the CXCR4 gene to be unmethylated in normal pancreas, whereas promoter hypermethylation was detected in 45% (9 of 20) of pancreatic cancer cell lines and in 46% (46 of 100) of primary pancreatic adenocarcinomas. There was a significant inverse correlation between methylation and mRNA expression level of CXCR4 (P = 0.008) in a large panel of pancreatic cancer cell lines. Constitutive as well as inducible expression of CXCR,4 could be restored in methylated cell lines pharmacologically using epigenetic modifying drugs. These findings demonstrate the first evidence for epigenetic regulation of CXCR4 in human cancers, providing new insights into the role of CXCR4/CXCL12 interactions in tumor progression.
  • N Fukushima, N Sato, N Prasad, SD Leach, RH Hruban, M Goggins
    ONCOGENE 23 (56) 9042 - 9051 0950-9232 2004/12 [Refereed][Not invited]
     
    Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon neoplasms usually located in the body or tail of the pancreas and usually in females (>90% of cases). Clinically, they are often misdiagnosed as non-neoplastic pseudocysts leading to failed opportunities for curative resection. To better understand the biology of MCNs and to identify markers of the disease, we performed global gene expression profiling of MCNs using oligonucleotide microarrays. Using laser capture microdissection applied to frozen sections, RNA was extracted from the neoplastic epithelium of MCNs, from the adjacent 'ovarian-type' stroma of MCNs, from histologically normal pancreatic ductal epithelium, from pancreatic acinar tissue and from fibrous stroma in pancreata affected by chronic pancreatitis. Each RNA sample was subjected to two rounds of linear amplification followed by hybridization with U133A gene chips (Affymetrix). The expression patterns of selected genes were confirmed by quantitative RT-PCR and by immunohistochemistry using tissue microarrays containing 19 resected MCNs. A total of 114 known genes were overexpressed in the neoplastic epithelium compared to normal pancreatic ductal epithelium (>3-fold) including S100P, PSCA, c-myc, STK6/STKI5, cathepsin E and pepsinogen C. Activation of the Notch pathway in the epithelial component of MCNs was evident by the demonstration of overexpression of Jagged1 and the downstream Notch pathway member Hes1. In the 'ovarian-type' stroma, several genes involved in estrogen metabolism were overexpressed including STAR and ESR1 genes. Some of the genes identified as overexpressed in these neoplasms may be useful as markers that can distinguish MCNs from non-neoplastic pancreatic cystic lesions.
  • CJ Shi, SH Eshleman, D Jones, N Fukushima, L Hua, AR Parker, CJ Yeo, RH Hruban, MG Goggins, Eshleman, JR
    NATURE METHODS 1 (2) 141 - 147 1548-7091 2004/11 [Refereed][Not invited]
     
    We developed the LigAmp assay for sensitive detection and accurate quantification of viruses and cells with single-base mutations. In LigAmp, two oligonucleotides are hybridized adjacently to a DNA template. One oligonucleotide matches the target sequence and contains a probe sequence. If the target sequence is present, the oligonucleotides are ligated together and detected using real-time PCR. LigAmp detected KRAS2 mutant DNA at 0.01% in mixtures of different cell tines. KRAS2 mutations were also detected in pancreatic duct juice from patients with pancreatic cancer. LigAmp detected the K103N HIV-1 drug resistance mutation at 0.01% in plasmid mixtures and at similar to0.1% in DNA amplified from plasma HIV-1. Detection in both systems is linear over a broad dynamic range. Preliminary evidence indicates that reactions can be multiplexed. This assay may find applications in the diagnosis of genetic disorders and the management of patients with cancer and infectious diseases.
  • RH Hruban, K Takaori, DS Klimstra, NV Adsay, J Albores-Saavedra, AV Biankin, SA Biankin, C Compton, N Fukushima, T Furukawa, M Goggins, Y Kato, G Kloppel, DS Longnecker, J Luttges, A Maitra, GJA Offerhaus, M Shimizu, S Yonezawa
    AMERICAN JOURNAL OF SURGICAL PATHOLOGY 28 (8) 977 - 987 0147-5185 2004/08 [Refereed][Not invited]
     
    Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs.
  • Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, Lillemoe KD
    Annals of surgery 6 239 (6) 788 - 97; discussion 797 0003-4932 2004/06 [Refereed][Not invited]
  • A Maitra, Y Cohen, SED Gillespie, E Mambo, N Fukushima, MO Hoque, N Shah, M Goggins, J Califano, D Sidransky, A Chakravarti
    GENOME RESEARCH 14 (5) 812 - 819 1088-9051 2004/05 [Refereed][Not invited]
     
    Somatic mitochondrial mutations are common in human cancers, and can be used as a tool for early detection of cancer. We have developed a mitochondrial Custom Reseq(TM) microarray as an array-based sequencing platform for rapid and high-throughput analysis of mitochondrial DNA. The MitoChip contains oligonucleotide probes synthesized using standard photolithography and solid-phase synthesis, and is able to sequence >29 kb of double-stranded DNA in a single assay. Both strands of the entire human mitochondrial coding sequence (15,451 bp) are arrayed on the MitoChip; both strands of an additional 12,935 bp (84% of coding DNA) are arrayed in duplicate. We used 300 ng of genomic DNA to amplify the mitochondrial coding sequence in three overlapping long PCR fragments. We then sequenced >2 million base pairs of mitochondrial DNA, and successfully assigned base calls at 96.0% of nucleotide positions. Replicate experiments demonstrated >99.99% reproducibility. In matched fluid samples (urine and pancreatic juice, respectively) obtained from five patients with bladder cancer and four with pancreatic cancer, the MitoChip detected at least one cancer-associated mitochondrial mutation in six (66%) of nine samples. The MitoChip is a high-throughput sequencing tool for the reliable identification of mitochondrial DNA Mutations from primary tumors in clinical samples.
  • J Koopmann, P Buckhaults, DA Brown, ML Zahurak, N Sato, N Fukushima, LJ Sokoll, DW Chan, CJ Yeo, RH Hruban, SN Breit, KW Kinzler, B Vogelstein, M Goggins
    CLINICAL CANCER RESEARCH 10 (7) 2386 - 2392 1078-0432 2004/04 [Refereed][Not invited]
     
    Purpose: Patients with pancreatic ductal adenocarcinoma usually present with advanced-stage disease and a dismal prognosis. One effective strategy likely to improve the morbidity and mortality from pancreatic cancer would be the identification of accurate, noninvasive diagnostic markers that would enable earlier diagnosis of symptomatic patients and earlier detection of cancer in asymptomatic individuals at high risk for developing pancreatic cancer. In this study, we evaluated serum macrophage inhibitory cytokine-1 (MIC-1) as a marker of pancreatic cancer. Experimental Design: MIC-1 expression in primary pancreatic cancers, intraductal papillary mucinous neoplasms, and pancreatic cancer cell lines was determined using the National Center for Biotechnology Information serial analysis of gene expression database, oligonucleotide microarrays analysis, in situ hybridization, and immunohistochemistry. Serum MIC-1 levels were determined by ELISA in 80 patients with pancreatic adenocarcinomas, in 30 patients with ampullary and cholangiocellular carcinomas, in 42 patients with benign pancreatic tumors, in 76 patients with chronic pancreatitis, and in 97 healthy control subjects. The diagnostic performance of serum MIC-1 as a marker of pancreatic cancer was compared with that of serum CA19-9. Results: Oligonucleotide microarray and serial analysis of gene expression data demonstrated that MIC-1 RNA levels were higher in primary pancreatic cancers, intraductal papillary mucinous neoplasms, and pancreatic cancer cell lines than in nonneoplastic pancreatic ductal epithelium. MIC-1 expression was localized to the malignant epithelium in pancreatic adenocarcinomas by in situ hybridization. MIC-1 protein was expressed in 14 of 16 primary pancreatic adenocarcinomas (88%) by inummohistochemistry and was also expressed in some pancreata affected by pancreatitis but not in normal pancreas. Serum MIC-1 levels were significantly higher in patients with pancreatic ductal adenocarcinoma (mean +/- SD, 2428 +/- 2324 pg/ml) and in patients with ampullary and cholangiocellular carcinomas (2123 +/- 2387 pg/ml) than in those with benign pancreatic neoplasms (940 +/- 469 pg/ml), chronic pancreatitis (1364 +/- 1236 pg/ml), or in healthy controls (546 +/- 262 pg/ml). An elevated serum MIC-1 (defined as 2 SD above the mean for healthy controls) performed as well as CA19-9 (area under the receiver operating characteristic curve, 0.81 and 0.77, respectively), and the combination of MIC-1 and CA19-9 significantly improved diagnostic accuracy (P < 0.05; area under the receiver operating characteristic curve, 0.87; sensitivity, 70%; specificity, 85%). Conclusion: Serum MIC-1 measurement can aid in the diagnosis of pancreatic adenocarcinoma.
  • N Sato, N Fukushima, A Maitra, CA Iacobuzio-Donahue, NT van Heek, JL Cameron, CJ Yeo, RH Hruban, M Goggins
    AMERICAN JOURNAL OF PATHOLOGY 164 (3) 903 - 914 0002-9440 2004/03 [Refereed][Not invited]
     
    The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of an associated invasive carcinoma in IPMNs. Using oligonucleotide microarrays, we performed a large-scale gene expression profiling of 12 IPMNs with or without an associated invasive carcinoma. A subset of genes identified was validated for the gene expression patterns in a large panel of IPMNs by reverse-transcription polymerase chain reaction and/or imimmohistochemistry. A total of 673 transcripts were identified as expressed at significantly higher levels (P < 0.05 and at fivefold or greater) in IPMNs relative to normal pancreatic ductal epithelial samples. Of interest, many of the genes identified as overexpressed in IPMNs have also been previously reported to be highly expressed in infiltrating ductal adenocarcinoma. of the pancreas. By analyzing genes overexpressed selectively in IPMNs with an associated invasive carcinoma (n = 7), we also identified a panel of genes potentially associated with the invasive phenotype of the neoplasms. Immunohistochemical validation revealed that claudin 4, CXCR4, S100A4, and mesothelin were expressed at significantly high frequency in invasive IPMNs than in noninvasive IPMNs. Notably, the expression of at least two of the four proteins was observed in 73% of 22 invasive IPMNs but in none of 16 noninvasive EPMNs (P < 0.0001). Our findings suggest that preoperative assessment of gene expression profiles may be able to differentiate invasive from noninvasive EPMNs.
  • N Sato, N Fukushima, H Matsubayashi, M Goggins
    ONCOGENE 23 (8) 1531 - 1538 0950-9232 2004/02 [Refereed][Not invited]
     
    DNA hypomethylation is one of the major epigenetic alterations in human cancers. We have previously shown that genes identified as hypomethylated in pancreatic cancer are expressed in pancreatic cancer cell lines, but not in normal pancreatic ductal epithelium and can be reexpressed in nonexpressing cells using 'epigenetic modifying agents' such as DNA methyltransferase inhibitors. To identify additional targets for aberrant hypomethylation in pancreatic cancer, we used oligonucleotide microarrays to screen for genes that displayed expression patterns associated with hypomethylation. This analysis identified a substantial number of candidates including previously reported hypomethylated genes. A subset of eight genes were selected for further methylation analysis, and two cancer-related genes, maspin and S100P, were found to be aberrantly hypomethylated in a large fraction of pancreatic cancer cell lines and primary pancreatic carcinomas. Combined treatment with 5-aza-2'-deoxycytidie and trichostatin A resulted in synergistic induction of maspin and S100P mRNA in MiaPaCa2 cells where both genes were methylated. Furthermore, there was an inverse correlation between methylation and mRNA expression level for maspin and S100P in a large panel of pancreatic cancer cell lines. We also found a significant difference in the methylation patterns of maspin and two previously identified hypomethylated genes (trefoil factor 2 and lipocalin 2) between pancreatic and breast cancer cell lines, suggesting cancer-type specificity for some hypomethylation patterns. Thus, our present results confirm that DNA hypomethylation is a frequent epigenetic event in pancreatic cancer, and suggest that gene expression pro. ling may help to identify potential targets affected by this epigenetic alteration.
  • H Matsubayashi, N Fukushima, N Sato, K Brune, M Canto, CJ Yeo, RH Hruban, SE Kern, M Goggins
    CANCER BIOLOGY & THERAPY 2 (6) 652 - 655 1538-4047 2003/11 [Refereed][Not invited]
     
    Long standing chronic pancreatitis is a risk factor for developing pancreatic cancer. Inheritance of polymorphisms in SPINK1 and CFTR are associated with an increased risk of developing pancreatitis. The aim of this study was to determine if patients who carry polymorphisms in SPINK1 and CFTR are at increased risk of developing pancreatic cancer through the development of chronic pancreatitis. DNA from patients with histologically confirmed surgically-treated chronic pancreatitis, familial and sporadic pancreatic adenocarcinoma and controls were analyzed for the N34S polymorphism of SPINK1 and the two commonest polymorphisms of the CFTR gene, the DeltaF508 mutation and the 5T polymorphism. These polymorphisms were determined using restriction fragment length polymorphism, PCR and cycle sequencing methods. The SPINK1 N34S polymorphism was detected in 5 of 172 (2.9%) patients with chronic pancreatitis, in 4 of 200 (2.0%) patients with sporadic pancreatic adenocarcinoma, in 0 of 36 (0%) of patients with familial pancreatic cancer and in 3 of 177 (1.7%) controls of chronic cholecystitis. The CFTR 5T polymorphism was identified in 31 of 334 (9.3%) patients of sporadic pancreatic cancer, in 5 of 43 (11.6%) patients with familial pancreatic cancer and in 10 of 112 (8.9%) controls with colorectal cancer. The CFTR DeltaF508 mutation was recognized in 6 of the 240 (2.5%) patients with pancreatic adenocarcinoma, a prevalence similar to that of control populations. We conclude that the N345 polymorphism of SPINK1 and the 5T and DeltaF508 CFTR polymorphisms do not predispose to the development of pancreatic adenocarcinoma. Furthermore, the N34S polymorphism is rarely found in patients with severe idiopathic chronic pancreatitis.
  • N Sato, N Fukushima, N Maehara, H Matsubayashi, J Koopmann, GH Su, RH Hruban, M Goggins
    ONCOGENE 22 (32) 5021 - 5030 0950-9232 2003/08 [Refereed][Not invited]
     
    Deregulated expression of SPARC/osteonectin, a secreted glycoprotein with multiple biological functions, has been associated with the progression of various cancers. Using microarrays, we previously identified SPARC as one of the genes induced by treatment with a DNA methylation inhibitor in pancreatic cancer cells. We therefore analysed the expression pattern and methylation status of the SPARC gene in pancreatic cancer. Gene expression profiting by oligonucleotide microarray and reverse transcription-PCR analyses demonstrated that SPARC mRNA was expressed in non-neoplastic pancreatic ductal epithelial cells, but was not expressed in a majority of pancreatic cancer cell lines. The loss of SPARC expression was associated with aberrant hypermethylation of its CpG island. Immunohistochemical labeling revealed that the SPARC protein was overexpressed in the stromal fibroblasts immediately adjacent to the neoplastic epithelium in primary pancreatic cancers, but rarely expressed in the cancers themselves. Primary fibroblasts derived from pancreatic cancer strongly expressed SPARC mRNA and secreted SPARC protein into the conditioned media, and treatment of pancreatic cancer cells with exogenous SPARC resulted in growth suppression. SPARC expression in fibroblasts from noncancerous pancreatic tissue was augmented by coculture with pancreatic cancer cells. These findings suggest that SPARC is a frequent target for aberrant methylation in pancreatic cancer and that SPARC expression in fibroblasts adjacent to pancreatic cancer cells is regulated through tumor-stromal interactions.
  • N Sato, N Fukushima, A Maitra, H Matsubayashi, CJ Yeo, JL Cameron, RH Hruban, M Goggins
    CANCER RESEARCH 63 (13) 3735 - 3742 0008-5472 2003/07 [Refereed][Not invited]
     
    To identify potential targets for aberrant methylation in pancreatic cancer, we analyzed global changes in gene expression profiles of four pancreatic cancer cell lines after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) and/or the histone deacetylase inhibitor trichostatin A. A substantial number of genes were induced 5-fold or greater by 5Aza-dC alone (631 transcripts), trichostatin A alone (1196 transcripts), and by treatment with both agents (857 transcripts). Four hundred and seventy-five genes were markedly (>5-fold) induced after 5Aza-dC treatment in pancreatic cancer cell lines but not in a nonneoplastic pancreatic epithelial cell line. The methylation status of 11 of these 475 genes was examined in a panel of 42 pancreatic cancers, and all 11 of these genes were aberrantly methylated in pancreatic cancer but rarely, if any, methylated in 10 normal pancreatic ductal epithelia. These genes include UCHL1 (methylated in 100% of 42 pancreatic cancers), NPTX2 (98%), SARP2 (95%), CLDN5 (93%), reprimo (86%), LHX1 (76%), WNT7A (71%), FOXE1 (69%), TJP2 (64%), CDH3 (19%), and ST14 (10%). Three of these 11 genes (NPTX2, SARP2, and CLDN5) were selected for further analysis in a larger panel of specimens, and aberrant methylation of at least one of these three genes was detectable in 100% of 43 primary pancreatic cancers and in 18 of 24 (75%) pancreatic juice samples obtained from patients with pancreatic cancer. Thus, a substantial number of genes are induced by 5Aza-dC treatment of pancreatic cancer cells, and many of them may represent novel targets for aberrant methylation in pancreatic carcinoma.
  • N Sato, A Maitra, N Fukushima, NT van Heek, H Matsubayashi, CA Iacobuzio-Donahue, C Rosty, M Goggins
    CANCER RESEARCH 63 (14) 4158 - 4166 0008-5472 2003/07 [Refereed][Not invited]
     
    To investigate the relationship between DNA hypomethylation and gene overexpression in pancreatic cancer, we analyzed the methylation status of a subset of 18 genes previously identified by global gene expression studies as overexpressed in pancreatic cancer tissues compared with normal pancreas. For comparison, we determined the methylation status of 14 genes not known to be overexpressed in pancreatic cancer. Methylation-specific PCR analysis revealed that 19 of these 32 genes were methylated at their 5' CpGs in normal pancreas. We then analyzed these 19 genes for their methylation pattern in pancreatic cancers and found that all 7 of the genes (claudin4, lipocalin2, 14-3-3sigma,, trefoil factor2, S100A4, mesothelin, and prostate stem cell antigen) that were overexpressed in the neoplastic cells of pancreatic cancers and not expressed in normal pancreatic duct displayed a high prevalence of hypomethylation in pancreatic cancer cell lines and primary pancreatic carcinomas. By contrast, only 1 of 12 genes not overexpressed in pancreatic cancer demonstrated hypomethylation (P = 0.0002). In pancreatic cancer cell lines that retained methylation of 1 or more of the 7 aforementioned overexpressed and hypomethylated genes, treatment with 5-aza-2'-deoxycytidine or with trichostatin A, either alone or in combination, almost invariably reactivated the transcription of each of these 7 genes. These results indicate that gene hypomethylation is a frequent epigenetic event in pancreatic cancer and is commonly associated with the overexpression of affected genes.
  • NUNOBE SOUYA, FUKUSHIMA NORIYOSHI, YACHIDA SHINICHI, SHIMADA KAZUAKI, KOSUGE TOMOO, SAKAMOTO MICHIIE
    Surgery today : the Japanese journal of surgery 33 (6) 470 - 474 0941-1291 2003/06 [Refereed][Not invited]
     
    We describe the case of a pancreatic endocrine tumor with marked clear cell changes. The patient, a 56-year-old woman, presented with appetite loss and nausea but no evidence of either von Hippel-Lindau disease, or a family history of the disease. A radiological examination revealed a hypervascular tumor measuring 5.2 cm in diameter located in the pancreatic head. The patient underwent a pylorus-preserving pancreatoduodenectomy. The cut surface of the tumor was yellowish and well demarcated. Histologically, the tumor was composed of cuboidal cells with clear cytoplasm, thus forming trabecular and insular nests. Immunohistochemically, the tumor cells were strongly positive for chromogranin. An electron microscopic examination revealed the tumor cells to contain neuroendocrine secretory granules, abundant lipid droplets, and some crystalloid bodies in the cytoplasm. We conclusively diagnosed it to be a pancreatic clear cell endocrine tumor. Such tumors not associated with von Hippel-Lindau disease are extremely rare.
  • S Yachida, N Fukushima, Y Nakanishi, T Akasu, H Kitamura, M Sakamoto, T Shimoda
    DISEASES OF THE COLON & RECTUM 46 (6) 826 - 831 0012-3706 2003/06 [Refereed][Not invited]
     
    PURPOSE: We describe a rare case of an alpha-fetoprotein-producing carcinoma originating in the transverse colon of a 59-year-old Japanese male. METHODS: The patient reported an abdominal mass and weight loss. On examination, a tumor of the transverse colon and multiple masses in the liver were found. The serum alpha-fetoprotein level was extremely high (12,873 ng/ml). The patient underwent right hemicolectomy and intraoperative biopsy of a liver mass. RESULTS: Histologically, the colon cancer was composed of three different components: a well-differentiated tubular adenocarcinoma, a tubulopapillary carcinoma consisting of cells with clear cytoplasms, and a "hepatoid carcinoma." The hepatoid carcinoma was composed of large polygonal cells with abundant eosinophilic or clear cytoplasms, arranged in a trabecular or solid pattern, and showing marked vascular invasion. Immunohistochemically, alpha-fetoprotein was strongly expressed, largely in the hepatoid carcinoma and partially in the tubulopapillary carcinoma. The liver biopsy specimen showed morphologic and immunohistochemical features similar to those of the hepatoid carcinoma of the colon and was therefore diagnosed as a metastasis. The patient died of the cancer two months after surgery. CONCLUSION: Based on our experience of this patient and a review of the literature, alpha-fetoprotein-producing colorectal carcinomas are generally associated with a poor prognosis because of the frequent occurrence of blood-borne metastases.
  • H Matsubayashi, N Sato, N Fukushima, CJ Yeo, KM Walter, K Brune, F Sahin, RH Hruban, M Goggins
    CLINICAL CANCER RESEARCH 9 (4) 1446 - 1452 1078-0432 2003/04 [Refereed][Not invited]
     
    Purpose: Hypermethylation of CpG islands in the promoters of selected genes is a common feature of neoplasia. Aberrant methylation of cyclin D2 has been observed in several cancers. We investigated the methylation of cyclin D2 in aging and pancreatic neoplastic development, and the utility of cyclin D2 methylation as a marker of pancreatic adenocarcinoma. Experimental Design: Methylation-specific PCR was performed on DNA from 165 resected pancreatic exocrine neoplasms [109 adenocarcinomas, 46 intraductal papillary-mucinous neoplasms (IPMNs), and 10 mucinous cystic neoplasms], 14 pancreatic intraepithelial neoplasms, 13 micro-dissected-normal pancreatic ductal epithelia, 25 normal pancreatic parenchyma, 51 specimens of pancreatic juice obtained perioperatively, 15 pancreatic cancer xenografts, 22 pancreatic cancer cell lines, 59 specimens of normal duodenum, and 49 gallbladders affected by cholecystitis. Cyclin D2 RNA expression was determined in pancreatic cancer cell lines, before and after 5-AZA-2'-deoxycytidine treatment, by reverse transcription-PCR. Results: Methylation of cyclin D2 was identified in 65.1% (71 of 109) of primary pancreatic adenocarcinomas, in 50% (23 of 46) of IPMNs, and in 70% (7 of 10) of mucinous cystic neoplasms, but was detected infrequently in microdissected samples of normal pancreatic epithelia [7.7% (1 of 13)] and in pancreatic intraepithelial neoplasms [14.3% (2 of 14)]. Cyclin D2 methylation was also recognized in 10 of 15 (66.7%) pancreatic cancer xenografts; and in 19 of 22 (86.4%) pancreatic cancer cell lines. All of 10 pancreatic cancer cell lines completely methylated at cyclin D2 showed no expression by reverse transcription-PCR. Four of these 10 cell lines were treated with 5-AZA-2'-deoxycytidine, and all 4 showed increased RNA expression of cyclin D2 after treatment. In pancreatic juice, cyclin D2 methylation was detected in 9 of 22 (40.9%) samples from patients with pancreatic cancer and in 6 of 9 (66.7%) patients with IPMNs, but in none of 20 non-neoplastic controls, respectively (P = 0.0013 and P < 0.0001, respectively). Methylation of cyclin D2 was also observed more in non-neoplastic tissues and with increasing age (P = 0.041 in the pancreas, P = 0.047 in the duodenum, and P = 0.0008 in the gallbladder). Conclusions: The promoter region of cyclin D2 undergoes age-related methylation in multiple tissues, but aberrant methylation is more often detected in tissues and juice samples of pancreatic cancer than in normal tissues. The detection of cyclin D2 methylation in pancreatic juice may aid in the diagnosis of pancreatic adenocarcinoma.
  • N Fukushima, KM Walter, T Ueki, N Sato, H Matsubayashi, JL Cameron, RH Hruban, M Canto, CJ Yeo, M Goggins
    CANCER BIOLOGY & THERAPY 2 (1) 78 - 83 1538-4047 2003/01 [Refereed][Not invited]
     
    The aim of this study was to determine the utility of detecting methylated ppENK and p16 in pancreatic juice by methylation specific PCR as a marker of pancreatic adenocarcinoma. Pancreatic juice samples were collected either intraoperatively, from 92 patients undergoing pancreaticoduodenectomy for benign (n = 20) and malignant periampullary disease (n = 72) or endoscopically (by duodenal aspiration after secretin infusion), from 13 patients undergoing investigation for pancreatic disease. Methylated ppENK was detected in the pancreatic juice of 30 (66.7%) of 45 patients with pancreatic ductal adenocarcinoma, in A (44.4%) of 9 patients with intraductal papillary-mucinous adenocarcinoma, and in 7 (41.2%) of 17 patients with other periampullary carcinomas, using methylation specific PCR. Methylated p 16 was detected in a lower percentage of these patients (11.1%, 11.1% and 23.5%, respectively). In contrast, methylated ppENK and p16 were not detected in 20 patients with non-malignant periampullary disease including 12 patients with chronic pancreatitis. Methylated ppENK was detected in 30 of 33 (90.9%) primary pancreatic adenocarcinoma and methylated p16 was in 6/33 (18.2%). Despite the absence of ppENK and p 16 methylation in normal pancreas, methylated ppENK and p 16 was present in the duodenum of 90.5% and 28.6%, respectively of patients without cancer. Further, methylated ppENK and p 16 was seen in 88.9% and 11.1%, respectively of pancreatic juice samples obtained by duodenal aspiration from patients without cancer. We conclude that since ppENK and p16 are not normally methylated in pancreatic secretions, detection of methylated ppENK and p 16 in pure pancreatic juice obtained by direct cannulation of the pancreatic duct to avoid duodenal secretions may suggest the presence of pancreatic adenocarcinoma
  • T Okusaka, S Okada, H Ueno, M Ikeda, K Shimada, J Yamamoto, T Kosuge, S Yamasaki, N Fukushima, M Sakamoto
    CANCER 95 (9) 1931 - 1937 0008-543X 2002/11 [Refereed][Not invited]
     
    BACKGROUND. It is not rare to find satellite lesions in patients with small hepatocellular carcinoma (HCC). The purpose of this study was to elucidate the factors associated with satellite lesions in these patients. METHODS. We investigated the prevalence of satellite lesions, the relationship of clinicopathologic factors to satellite lesions, and the distance from the main tumor to the satellite lesion in 149 patients. Patients, who had a solitary HCC of 3.0 cm or less in diameter but no satellite lesions on preoperative imaging procedures, underwent potentially curative resection. The main tumors were macroscopically classified into four groups: early HCC, a vaguely nodular type showing preservation of the preexisting liver structure; single nodular type; single nodular type with extranodular growth; and confluent multinodular type. RESULTS. Of 149 resected specimens, 28 (19%) showed satellite lesions. Of the clinicopathologic factors investigated, the macroscopic type and tumor differentiation were significantly associated with the prevalence of satellite lesions. Both the single nodular type with extranodular growth and the confluent multinodular type showed satellite lesions more frequently than the early HCC and the single nodular type. A significantly higher prevalence of satellite lesions was observed in poorly differentiated HCC than in well and moderately differentiated HCC. The satellite lesions were located 0.5 cm or less from the main tumor in 8 (33%) specimens, 0.6-1.0 cm in 12 (50%), and 1.1-2.0 cm in 4 (17%). No identifiable factors were significantly related to the distance from the main tumor to the satellite lesion. However, all satellite lesions located more than 1.0 cm from the main tumor coexisted with poorly differentiated HCC, which were the single nodular type with extranodular growth or the confluent multinodular type. CONCLUSION. In the single nodular type with extranodular growth, confluent multinodular type, and poorly differentiated HCC, extensive treatment achieving a large safety margin and/or frequent posttreatment follow-up examinations may be needed because of the high prevalence of satellite lesions. (C) 2002 American Cancer Society.
  • YACHIDA Shinichi, FUKUSHIMA Noriyoshi, NAKANISHI Kazuaki, SHIMADA Kazuaki, KOSUGE Tomoo, SAKAMOTO Michiie
    Pathol Int 52 (9) 607 - 611 1320-5463 2002/09 [Refereed][Not invited]
     
    We describe a case of minute pancreatic ductal adenocarcinoma featuring stenosis of the main pancreatic duct (MPD) and associated with histological findings of periductal elastosis and fibroblast proliferation. A 53-year-old Japanese man with preoperative radiological evidence of MPD stricture and dilation of the distal MPD, and suspected of having pancreatic cancer, underwent successful resection. Neither radiological nor macroscopic examination directly disclosed any tumorous lesions, and a small focus of carcinoma (8 x 8 mm) was only revealed on microscopic examination. The tumor was a poorly differentiated, invasive ductal adenocarcinoma that had invaded the intrapancreatic nerves and veins. Interestingly, the MPD located at the edges of the tumor had not been destroyed by the carcinoma, but its wall had been thickened by elastic tissue and fibroblast proliferation, resulting in stenosis. The peripheral pancreas exhibited secondary obstructive pancreatitis. To date, the detection of small pancreatic tumor masses using imaging procedures remains difficult, and most patients are diagnosed on the basis of pancreatic ductal changes. However, the published work on small pancreatic cancers contains little information about the histological features of the affected MPD. The present findings suggest that MPD strictures are not always provoked by destruction or filling with cancer cells, and that they can be caused by periductal elastosis and fibroblast proliferation in a minute carcinoma. Such changes in the MPD may therefore be of clinical importance in the detection of early stage cancers.
  • KUBO Makoto, SAKAMOTO Michiie, FUKUSHIMA Noriyoshi, YACHIDA Shinichi, NAKANISHI Yukihiro, SHIMODA Tadakazu, YAMAMOTO Junji, MORIYA Yoshihiro, HIROHASHI Setsuo
    Pathol Int 52 (8) 514 - 518 1320-5463 2002/08 [Refereed][Not invited]
     
    We have previously reported the frequent occurrence of bile duct invasion by liver metastases from colorectal cancer. We found that patients with macroscopic intrabiliary cancer growth survive longer after hepatectomy than those without this feature. In the present study, we analyzed the clinicopathological features of primary colorectal cancer showing macroscopic intrabiliary extension of liver metastases. We reviewed 217 patients who underwent initial hepatic resection for colorectal liver metastasis between 1992 and 1998, and analyzed the corresponding primary colorectal cancers clinicopathologically. Microscopic bile duct invasion was found in 89 of 217 cases (40.6%) and, of these cases, 23 (10.6%) had macroscopic intrabiliary extension. Histological sections of the corresponding primary colorectal cancer were available in eight (group A) of these 23 cases. These were compared with 20 cases, selected randomly, of colorectal cancer that did not show bile duct invasion and were diagnosed as liver metastases. These patients underwent hepatectomy during the same period as group A and were used as a control (group B). The histology of the primary tumors revealed well-differentiated adenocarcinoma in 100% of group A and in 25% of group B. The average maximum diameter of the primary tumor was 5.32 cm in group A and 3.61 cm in group B. Venous invasion was detected in 25% of group A and in 90% of group B (P < 0.01), while the incidences of lymphatic vessel invasion and lymph node metastases were similar between the groups. These data suggest that macroscopic intrabiliary extension could be a good indicator of a unique subgroup of colorectal cancers showing less aggressive features even though they develop liver metastases. Careful histological evaluation is important even for metastatic tumors.
  • S Yachida, N Fukushima, Y Kanai, S Nimura, K Shimada, J Yamamoto, M Sakamoto
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 32 (8) 315 - 317 0368-2811 2002/08 [Refereed][Not invited]
     
    While metastasis to the pancreas is uncommon, it may occur from renal cell carcinomas (RCCs). We here present a case of pancreatic metastasis from RCC extending into the main pancreatic duct (MPD) in a 66-year-old Japanese man. The patient had a history of RCC treated with a radical nephrectomy 17 years previously and was found to have a mass similar to2 cm in diameter in the body of the pancreas on radiological images. The patient was suspected of having pancreatic metastasis from RCC and underwent a distal pancreatectomy with splenectomy. Histologically, the tumor consisted of cells arranged in trabecular and alveolar structures with clear or eosinophilic granular cytoplasm, compatible with a metastatic RCC. The pancreatic tumor extended into the MPD with the stream of pancreatic juice. This condition is similar to RCC extension into the renal vein and the inferior vena cava. In conclusion, although extension into the MPD may be rare, such a growth pattern may be characteristic of metastases from RCCs.
  • N Sato, T Ueki, N Fukushima, CA Iacobuzio-Donahue, CJ Yeo, JL Cameron, RH Hruban, M Goggins
    GASTROENTEROLOGY 123 (1) 365 - 372 0016-5085 2002/07 [Refereed][Not invited]
     
    Background & Aims: The functional abrogation of several tumor suppressor genes, including p16, DPC4, and p53, is a major mechanism underlying pancreatic ductal carcinogenesis. However, mutational inactivation of these genes is relatively uncommon in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. We hypothesized that an alternative mechanism for gene inactivation (notably, transcriptional silencing by promoter methylation) could be important in the pathogenesis of IPMNs. Methods: Using methylation-specific polymerase chain reaction, we analyzed the methylation status of 7 CpG islands previously identified as aberrantly methylated in pancreatic adenocarcinoma (including preproenkephalin [ppENK], p16, and thrombospondin 1) in 51 IPMNs of different histologic grades. The relationship between methylation status and expression was evaluated using reverse-transcription polymerase chain reaction for ppENK and immunohistochemistry for p16. Results: We found that more than 80% of the IPMNs exhibited hypermethylation of at least one of these CpG islands. Hypermethylation of ppENK and p16 was detected at a significant higher frequency in high-grade (in situ carcinoma) IPMNs than in low-grade (adenoma/borderline) IPMNs (ppENK, 82% vs. 28%, P = 0.0002; p16, 21% vs. 0%, P = 0.04). Furthermore, the average number of methylated loci was significantly higher in high-grade IPMNs than in low-grade IPMNs (2.4 vs. 0.9; P = 0.0008). Aberrant methylation of ppENK and p16 was associated with loss of expression. Conclusions: These results suggest that de novo methylation of multiple CpG islands is one of the critical pathways that contributes to the malignant progression of IPMNs.
  • S Yachida, N Fukushima, Y Nakanishi, S Nimura, M Sato, K Shimada, K Miura, M Sakamoto
    DIGESTIVE DISEASES AND SCIENCES 47 (6) 1413 - 1418 0163-2116 2002/06 [Refereed][Not invited]
  • N Fukushima, N Sato, T Ueki, C Rosty, KM Walter, RE Wilentz, CJ Yeo, RH Hruban, M Goggins
    AMERICAN JOURNAL OF PATHOLOGY 160 (5) 1573 - 1581 0002-9440 2002/05 [Refereed][Not invited]
     
    Pancreatic intraductal neoplasia (PanIN) is thought to be the precursor to infiltrating pancreatic ductal adenocarcinoma. We have previously shown that the preproenkephalin (ppENK) and p16 genes are aberrantly methylated in pancreatic adenocarcinoma. In this study we define the methylation status of the ppENK and p16 genes in various grades of PanINs. One hundred seventy-four samples (28 nonneoplastic pancreatic epithelia, 7 reactive epithelia, 29 PanIN-1A, 48 PanIN-1B, 27 PanIN-2, 14 PanIN-3, 15 invasive ductal adenocarcinomas, and 6 miscellaneous pancreatic neoplasms) were microdissected from 29 formalin-fixed paraffin-embedded surgically resected pancreata, and were analyzed by methylation-specific polymerase chain reaction. Fourteen of 15 (93.3%) invasive pancreatic ductal adenocarcinomas showed methylation of the ppENK gene and 4 of 15 (26.7%) showed methylation of the p16 gene. Nonneoplastic pancreatic epithelia did not harbor methylation of either gene. The prevalence of methylation of the ppENK gene increased significantly with increasing PanIN grade. A similar nonsignificant trend was noted for p16 methylation. Aberrant methylation of the ppENK gene was found in 7.7% of PanIN-1A, 7.3% of PanIN-1B, 22.7% of PanIN-2, and 46.2% of PanIN-3. Aberrant methylation of the p16 gene was found in 12% of PanIN-1A, 2.6% of PanIN-1B, 4.5% of PanIN-2, and 21.4% of PanIN-3. All but one of the PanINs from the 14 pancreata without pancreatic carcinoma was unmethylated with respect to either the p16 or ppENK gene. Our results suggest that methylation-related inactivation of the ppENK and p16 genes is an intermediate or late event during pancreatic carcinogenesis. Because aberrant methylation of ppENK or p16 was more often detected in similar grade PanINs from patients with pancreatic carcinoma than in those with other pancreatic diseases, it may be a useful indicator of the potential malignancy of epithelial cells of the pancreas.
  • M Jansen, N Fukushima, C Rosty, K Walter, R Altink, T van Heek, R Hruban, JG Offerhaus, M Goggins
    CANCER BIOLOGY & THERAPY 1 (3) 293 - 296 1538-4047 2002/05 [Refereed][Not invited]
     
    The recently identified tumor-suppressor gene TSLC1 on chromosome 11q23.2 is frequently inactivated in human non-small cell lung adenocarcinoma by DNA methylation-associated silencing. The aim of this study was to determine if TSLC1 is inactivated in adenocarcinoma of the pancreas. We analyzed 17 pancreatic cancer cell lines, 91 primary pancreatic adenocarcinoma, 46 pancreatic intraepithelial (PanIN) precursor lesions and 15 microscopically normal pancreata for methylation of the 5' CpG island of the TSLC1 gene through methylation-specific PCR. We observed 5' CpG methylation of TSLC1 in 4 of 17 cell lines (24%). In each cell line the aberrant methylation was associated with loss of TSLC1 expression by RT-PCR that was reversible after treatment with the DNA methyltransferase inhibitor 5-aza-2'- deoxycytidine. Furthermore, we observed that TSLC1 was methylated in 25 of 91 primary pancreatic adenocarcinomas (27%), and in 2 of 7 high-grade PanIN-3 lesions (29%), but not in low-grade PanIN (0 of 9 PanIN-2 and 0 of 30 PanIN-1) lesions or in normal pancreata (n=15). We conclude that epigenetic silencing of TSLC1 expression through 5' CpG island associated methylation is common in pancreatic adenocarcinoma and is a late event in pancreatic neoplastic development.
  • J Murakami, N Fukushima, H Ueno, T Saito, T Watanabe, R Tanosaki, Y Kobayashi, Y Matsuno, K Tobinai
    INTERNATIONAL JOURNAL OF HEMATOLOGY 75 (1) 85 - 90 0925-5710 2002/01 [Refereed][Not invited]
     
    Primary hepatic lymphoma, mostly diffuse large B-cell lymphoma, is a rare disease. We describe an extremely rare case of low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type occurring in the liver. A 61-year-old man with a history of hepatitis A presented with early gastric cancer and a liver mass. Needle biopsy of the liver tumor suggested low-grade B-cell lymphoma by histology and polymerase chain reaction of the immunoglobulin heavy chain gene. The tumor (3.4 X 2.8 X 2.4 cm) was completely resected from the anterior segment of the right lobe of the liver. Atypical lymphoid cells of small to intermediate size proliferated in the tumor, and lymphoepithelial lesions were recognized. Immunohistochemically, lymphoma cells were positive for CD20 and negative for CD5, CD10, and cyclin D1. Staging procedures showed no lymphoma lesion other than the liver tumor. Thus, the patient was diagnosed with low-grade hepatic marginal zone B-cell lymphoma of the MALT type. The patient has been followed up for 1.5 years since surgical resection with no recurrence. The clinicopathologic characteristics and management of this rare disease are discussed. Int J Hematol. 2002;75:85-90. (C)2002 The Japanese Society of Hematology.
  • N Fukushima, K Mukai
    INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY 8 (4) 271 - 278 1066-8969 2000/10 [Refereed][Not invited]
     
    Mucinous cystic tumors (MCTs) and intraductal papillary-mucinous tumors (IPMTs) are often confused with each other. However, clinicopathological studies have shown that these are two distinct entities. In this review clinicopathological differences and important features for differential diagnosis are presented. MCTs are cyst-forming tumors in the body or tail of the pancreas seen almost exclusively in females. IPMTs show distinct duct ectasia in the pancreatic head with male predominance. Histologically both tumors consist of mucin secreting tall columnar epithelium. MCTs are often accompanied by characteristic "ovarian-type stroma.'' Recent immunohistochemical and gene analysis have not demonstrated significant differences between two tumor types. These tumors should be clearly separated from ordinary ductal adenocarcinomas of the pancreas as they follow indolent course.

Books etc

MISC

  • 福嶋 敬宜  胆と膵  42-  (6)  501  -505  2021/06  
    膵管の上皮内腫瘍/腫瘍性病変には、膵管内乳頭粘液性腫瘍(IPMN)、膵管内管状乳頭腫瘍(ITPN)、膵管内オンコサイト型乳頭状腫瘍(IOPN)そして膵上皮内腫瘍性病変(pancreatic intraepithelial neoplasia:PanIN)がある。IPMNは、大橋、高木らが1982年に粘液産生膵癌(mucous secreting pancreatic cancer)の4例を報告したことに始まる。それから約40年の間に、その名称、概念、異型度分類、亜型分類など、さまざまな議論がなされてきた。その過程で、国際がん研究機関(IARC)が発行する国際保健機関(WHO)分類は、第2版(1996年)ではじめてIPMNを取り上げ、第4版(2010年)では、IPMNからITPNを独立させ、さらに第5版(2019年)ではIPMNからIOPNを独立させて現在に至る。PanINは、WHO分類第3版(2000年)に初登場し、以来、膵管癌の前駆病変として定着してきた。本稿では、膵管の上皮内腫瘍の変遷と用語の取り扱いについて、病理学的視点からこれらを整理する。(著者抄録)
  • 谷川 雅彦, 福嶋 敬宜  臨床消化器内科  36-  (6)  595  -600  2021/05  
    <文献概要>近年,内視鏡検査,検体採取の質的向上により,膵胆道領域のIgG4関連疾患の生検診断が可能となりつつある.しかし,生検検体は微小であり,必ずしも特徴的な所見が得られるとは限らない.また,検体採取時にアーチファクトを伴いやすく診断に影響を与える場合もある.組織所見においては,時に腺癌との鑑別を要する腺房組織の導管上皮化生がみられることなどにも注意が必要である.本稿では,膵胆道領域におけるIgG4関連疾患の生検診断について,病理所見とその課題について概説する.
  • 池田 恵理子, 牛尾 純, 安藤 梢, 谷川 雅彦, 坂口 美織, 三輪田 哲郎, 長井 洋樹, 多田 大和, 横山 健介, 菅野 敦, 森嶋 計, 笹沼 英紀, 玉田 喜一, 佐田 尚宏, 福嶋 敬宜  胆と膵  42-  (5)  393  -400  2021/05  
    胆膵領域に発生する腫瘍は、しばしば画像診断に難渋する。画像診断精度を向上させるためには、術前画像で異常所見を拾い上げる所見のための根拠を病理組織学的に検証していくことが重要である。当施設では、詳細な術前画像と病理像の対比のために、臨床医と病理医が協力して「検体造影検査」に加え「術後検体超音波検査」を行っている。とくに、「術後検体超音波検査」は、簡便で、病理像・画像対比に適した病理組織標本を作ることができ、画像所見へのフィードバックや診療科横断的なコミュニケーションツールとしても有意義な検査である。(著者抄録)
  • 【消化管悪性リンパ腫のすべて】稀な消化管原発悪性リンパ腫 狭窄を伴う小腸濾胞性リンパ腫
    北村 昌史, 矢野 智則, 岡田 昌浩, 坂口 美織, 福嶋 敬宜, 山本 博徳  消化器内視鏡  33-  (5)  911  -915  2021/05
  • 安藤 梢, 福嶋 敬宜  病理と臨床  39-  (臨増)  116  -123  2021/04
  • 【これだけは知っておきたい胆膵疾患の診断・治療up-to-date】膵癌早期発見・診断はどこまで進歩したか?
    安藤 梢, 菅野 敦, 池田 恵理子, 三輪田 哲郎, 長井 洋樹, 川崎 佑輝, 多田 大和, 横山 健介, 沼尾 規且, 牛尾 純, 福嶋 敬宜, 玉田 喜一, 山本 博徳  消化器クリニカルアップデート  2-  (2)  203  -208  2021/04  
    膵癌は予後不良な悪性腫瘍であり、膵癌の予後を改善するためには、早期診断が極めて重要である。近年、膵癌のリスク因子や、早期に診断された膵癌の臨床的な特徴、画像の特徴などが報告されるようになり、リスク因子を有する症例の集積や経過観察の方法などが注目されている。本稿では、膵癌早期診断における活動の現状について概説する。(著者抄録)
  • 高橋 礼, 笹沼 英紀, 池田 恵理子, 三木 厚, 森嶋 計, 吉田 淳, 遠藤 和洋, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 瓦井Lefor Alan, 福嶋 敬宜, 佐田 尚宏  膵臓  36-  (2)  142  -149  2021/04  
    症例は37歳,女性.25歳で偶発的に膵体尾部に嚢胞性病変を指摘され,精査目的に当院消化器内科に紹介された.腹部造影CTとMRI検査では膵尾部に約5cmの嚢胞性腫瘤を認め膵粘液性嚢胞腫瘍(mucinous cystic neoplasm:MCN)が疑われたが,経過観察の方針となった.32歳時の第2子妊娠を契機に経過観察が一時中断となり,5年後の37歳に再診した.嚢胞性腫瘤は多房化し,大きさ6cmへの増大を認め,血清CA19-9の上昇を伴ったことから手術目的に消化器外科紹介となった.腹腔鏡下膵体尾部脾摘術を施行し,術後経過は良好で術後11日目に退院した.病理組織像では卵巣様間質を認め,微小浸潤を伴った膵粘液性嚢胞腺癌の診断であった.MCNの自然史を解明するには長期経過観察例の集積が必要である.(著者抄録)
  • 福嶋 敬宜  病理と臨床  39-  (3)  254  -262  2021/03
  • 病理診断におけるAI〜研究開発から社会実装へ〜 消化器内視鏡分野における医療画像AIの現状 上部消化管内視鏡AIを中心に
    多田 智裕, 河内 洋, 中野 薫, 福嶋 敬宜, 坂口 美織  日本病理学会会誌  110-  (1)  137  -137  2021/03
  • 口腔扁平上皮癌における腫瘍間質の組織学的評価
    天野 雄介, 木原 淳, 長谷川 雅世, 三浦 珠希, 松原 大祐, 福嶋 敬宜, 仁木 利郎  日本病理学会会誌  110-  (1)  240  -240  2021/03
  • 膵切除検体の病理学的検索における超音波撮像法併用の有用性
    池田 恵理子, 牛尾 純, 安藤 梢, 谷川 雅彦, 坂口 美織, 福嶋 敬宜  日本病理学会会誌  110-  (1)  244  -244  2021/03
  • 直腸原発杯細胞カルチノイド(goblet cell adenocarcinoma)の1例
    辻 賢太郎, 河田 浩敏, 安藤 梢, 三浦 珠希, 仁木 利郎, 田中 亨, 福嶋 敬宜  日本病理学会会誌  110-  (1)  305  -305  2021/03
  • 子宮間葉系腫瘍におけるSMARCA4とSMARCB1の発現の検討
    木原 淳, 天野 雄介, 長谷川 雅世, 三浦 珠希, 松原 大祐, 福嶋 敬宜, 仁木 利郎  日本病理学会会誌  110-  (1)  340  -340  2021/03
  • 【悪性腫瘍と誤りやすい疾患】肝胆膵領域
    福嶋 敬宜  病理と臨床  39-  (3)  254  -262  2021/03
  • 谷川 雅彦, 福嶋 敬宜  病理と臨床  38-  (12)  1113  -1118  2020/12
  • 福嶋 敬宜  病理と臨床  38-  (12)  1142  -1144  2020/12
  • 福嶋 敬宜  胆と膵  41-  (臨増特大)  1153  -1158  2020/11  
    膵管内乳頭粘液性腫瘍(intraductal papillary mucinous neoplasm:IPMN)は、大橋、高木らが1982年に粘液産生膵癌(mucous secreting pancreatic cancer)の4例を報告してから約40年の間に、その名称、概念、異型度分類、亜型分類など、さまざまな議論がなされ今日に至る。国際がん研究機関(International Agency for Research on Cancer:IARC)が発行する国際保健機関(WHO)分類は、1996年第2版ではじめて現IPMNを取り上げて以来、この分野の腫瘍の整理に常に新たな指針を示してきた。日本の膵癌取扱い規約は、WHO分類の変更に合わせるように少しずつ用語なども変更してきたが、両者間でもっとも混乱がみられたのは異型度分類であった。細胞形態だけでも「悪性」と診断できるとする日本の病理診断の考え方と、浸潤しないと悪性と診断しない両者の考え方の違いも影響していると思われるが、最近は各方面の努力もあり、用語は異なるが、基準は同じというところまできた。組織異型度分類は臨床予後に直結するものであり、同じ基準で診断されるようになることが望ましく、今後も歩み寄りの努力が必要であろう。(著者抄録)
  • 膵細胞診の可能性と将来展望 膵組織透明化技術を併用した3D画像解析技術の膵細胞診への応用と展望
    池田 恵理子, 牛尾 純, 鈴木 智子, 中村 香織, 織田 智博, 二階堂 貴章, 郡 俊勝, 柳田 美樹, 小野寺 宏, 福嶋 敬宜  日本臨床細胞学会雑誌  59-  (Suppl.2)  482  -482  2020/11
  • 福嶋 敬宜  日本消化器病学会雑誌  117-  (臨増大会)  A424  -A424  2020/10
  • 膵管の上皮内腫瘍性病変 WHO分類第5版での変更点を中心に
    福嶋 敬宜  Gastroenterological Endoscopy  62-  (Suppl.2)  1874  -1874  2020/10
  • 膵管の上皮内腫瘍性病変 WHO分類第5版での変更点を中心に
    福嶋 敬宜  日本消化器がん検診学会雑誌  58-  (Suppl大会)  716  -716  2020/10
  • 福嶋 敬宜  日本消化器病学会雑誌  117-  (臨増大会)  A424  -A424  2020/10
  • 膵管の上皮内腫瘍性病変 WHO分類第5版での変更点を中心に
    福嶋 敬宜  肝臓  61-  (Suppl.2)  A551  -A551  2020/09
  • 膵管の上皮内腫瘍性病変 WHO分類第5版での変更点を中心に
    福嶋 敬宜  肝臓  61-  (Suppl.2)  A551  -A551  2020/09
  • 福嶋 敬宜  膵臓  35-  (4)  242  -249  2020/08  
    WHOの消化器腫瘍分類第5版が2019年に改訂されたが,膵腫瘍の90%以上を占める膵管癌については,浸潤性微小乳頭状癌が亜型に加えられ,未分化癌が再整理された以外は大きな変更はない.しかし,病理学的役割は,当然その腫瘍分類の整理にとどまるものではなく,膵管癌にもいくつもの側面があり,病理学的研究も臨床〜基礎まで多方向性に進め統合させていく必要がある.本稿では,膵管癌について病理学的視点から,その病理像,亜型,前駆病変,癌間質の特徴などについて概説し,また日常診療に直結するEUS-FNA,TNM分類そして術前治療後の評価などについても現状と今後の課題について述べる.(著者抄録)
  • 膵癌取り扱い規約変更に関する説明会 病理組織分類の変更点
    福嶋 敬宜  膵臓  35-  (3)  A126  -A126  2020/07
  • 10mm以下の非機能性膵神経内分泌腫瘍における診断と治療成績
    池田 恵理子, 牛尾 純, 三輪田 哲郎, 長井 洋樹, 川崎 佑輝, 横山 健介, 沼尾 規且, 玉田 喜一, 佐田 尚宏, 福嶋 敬宜, 山本 博徳  膵臓  35-  (3)  A366  -A366  2020/07
  • 「自己免疫性膵炎生検診断のためのガイダンス」の作成
    能登原 憲司, 神澤 輝実, 田尻 琢磨, 福嶋 敬宜, 古川 徹, 山口 浩, 川茂 幸, 岡崎 和一  膵臓  35-  (3)  A422  -A422  2020/07
  • 福嶋 敬宜  胆と膵  41-  (6)  541  -545  2020/06  
    膵癌の多くは、浸潤性膵管癌であり、膵臓腫瘍のなかで約60%を占める。その他には、膵管内乳頭粘液性腫瘍や粘液性嚢胞腫瘍に由来する浸潤癌や腺房細胞癌、神経内分泌細胞癌などがあり、これらも広い意味では膵癌である。また膵管癌にも腺扁平上皮癌などのような亜型が数種類存在する。膵管癌の遺伝子異常としては、癌遺伝子のKRAS、癌抑制遺伝子であるp16(CDKN2A)、TP53、SMAD4(DPC4)が以前からよく知られているが、遺伝子解析機器の進歩もあり、腫瘍細胞のみならず間質の分子異常も含めた解析もなされてきている。(著者抄録)
  • 多田 大和, 池田 恵理子, 三輪田 哲郎, 長井 洋樹, 川崎 佑輝, 横山 健介, 沼尾 規且, 牛尾 純, 玉田 喜一, 福嶋 敬宜, 山本 博徳  Progress of Digestive Endoscopy  96-  (1)  57  -60  2020/06  
    富士フイルムメディカル社から2019年11月に発売されたインフィニティ細胞診ブラシミニの細胞採取能力を評価した。本製品の特徴は、通常のブラシよりも硬めのブラシをブラシの両端に備えていることである。2019年5月から11月に胆管狭窄の質的診断として胆管擦過細胞診を施行した9例を対象とし、診断能とカテーテルの挿入性能を後方視的に評価した。カテーテルの挿入性は高く、全例で目的部位を擦過できた。悪性狭窄を疑った6例は擦過細胞診で良好な検体が採取されており、正診率は100%であった。一方で、胆汁細胞診の正診率は33.3%、胆管生検は66.7%であった。我々の検討は、この製品の有用性を示した。(著者抄録)
  • 福嶋 敬宜  日本臨床細胞学会雑誌  59-  (Suppl.1)  115  -115  2020/05
  • 池田 恵理子, 牛尾 純, 鈴木 智子, 柳田 美樹, 中村 香織, 織田 智博, 二階堂 貴章, 郡 勝, 福嶋 敬宜  日本臨床細胞学会雑誌  59-  (Suppl.1)  225  -225  2020/05
  • 「自己免疫性膵炎生検診断のためのガイダンス」の作成
    能登原 憲司, 神澤 輝実, 田尻 琢磨, 福嶋 敬宜, 古川 徹, 山口 浩, 川 茂幸, 岡崎 和一  日本病理学会会誌  109-  (1)  357  -357  2020/03
  • 子宮体癌におけるSWI/SNF複合体発現異常の免疫組織化学的検討
    木原 淳, 天野 雄介, 松原 大祐, 福嶋 敬宜, 仁木 利郎  日本病理学会会誌  109-  (1)  371  -371  2020/03
  • 小児の終糸脂肪腫にmyxopapillary ependymoma様の上衣成分を伴った1例
    辻 賢太郎, 仁木 利郎, 大城 久, 柴原 純二, 廣田 由佳, 仲矢 丈雄, 河田 浩敏, 田中 亨, 福嶋 敬宜  日本病理学会会誌  109-  (1)  385  -385  2020/03
  • 膵病変の臨床病理学的特徴とその診断のポイント
    福嶋 敬宜  Japanese Journal of Diagnostic Imaging  38-  (1)  44  -44  2020/01  [Refereed][Not invited]
  • 【IPMN・MCN国際診療ガイドライン総まとめ】IPMNの病理組織分類
    池田 恵理子, 福嶋 敬宜  胆と膵  41-  (1)  27  -31  2020/01  [Refereed][Not invited]
     
    膵管内乳頭粘液性腫瘍(IPMN)は、膵管内に増殖する上皮性腫瘍である。WHO分類第4版および膵癌取扱い規約第7版では、膵管内腫瘍を、粘液産生の有無と組織構築によってIPMNと膵管内管状乳頭腫瘍(ITPN)に分けていたが、WHO分類第5版(2019年発行)では、ゲノム解析からの知見を背景にIPMNから、膵管内オンコサイト型乳頭状腫瘍(IOPN)が別の疾患概念として独立した。IPMNは、細胞分化による組織亜型の他、腫瘍の主座や異型度による分類などもよく知られており、組織型も含めた臨床病理学的所見とも関連性がある。(著者抄録)
  • 池田 恵理子, 牛尾 純, 川崎 佑輝, 多田 大和, 横山 健介, 玉田 喜一, 福嶋 敬宜, 山本 博徳  Progress of Digestive Endoscopy  96-  (Suppl.)  s146  -s146  2019/12  [Refereed][Not invited]
  • 池田 恵理子, 福嶋 敬宜  臨床消化器内科  34-  (12)  1445  -1451  2019/10  [Refereed][Not invited]
     
    <文献概要>膵管内乳頭粘液性腫瘍(intraductal papillary mucinous neoplasm;IPMN)の病理学的概念は,多くの症例,議論を基に確立してきた.IPMNは腫瘍上皮の異型性による異型度分類と腫瘍の組織分化の種類による組織亜型分類がある.異型度分類は低異型度(low-grade)と高異型度(high-grade)の2段階であり,低異型度は腺腫(adenoma),高異型度は非浸潤癌(non-invasivecarcinoma)に相当する.組織亜型は,胃型,腸型,胆膵型,オンコサイト型に分類される.組織亜型の補助診断は,MUCシリーズ染色が有用である.IPMNに関わる遺伝子異常としてGNAS変異,KRAS変異,RNF43変異が判明している.とくにGNAS変異はIPMNに特異的な遺伝子異常であり,IPMN由来膵癌の鑑別診断にも有用である.また,良悪性の鑑別や治療方針決定の補助診断として,膵液を用いてGNAS変異の検出や組織亜型の判別を行う試みがされている.
  • 福嶋 敬宜  日本臨床細胞学会雑誌  58-  (Suppl.2)  519  -519  2019/10  [Refereed][Not invited]
  • 上紙 航, 堀 隆, 桝澤 容子, 佐藤 奈緒美, 松本 信雄, 角田 敏一, 下岡 友子, 小山 芳徳, 砂川 恵伸, 福嶋 敬宜, 福岡 順也  日本臨床細胞学会雑誌  58-  (Suppl.2)  653  -653  2019/10  [Refereed][Not invited]
  • 山崎 正博, 亀田 智弘, 森田 侑平, 竹嶋 咲, 田畑 憲一, 池 大官, 田代 絢亮, 亀井 潤, 杉原 亨, 藤崎 明, 安東 聡, 高山 達也, 福嶋 敬宜, 藤村 哲也  泌尿器外科  32-  (7)  971  -974  2019/07  [Refereed][Not invited]
     
    48歳男性。陰嚢腫大、陰嚢皮膚からの出血のため救急搬送された。精査にて骨盤内、鼠径リンパ節転移を伴う右精巣腫瘍(cT4N3M1aS2)と診断した。また右下肢に蜂窩織炎を認め、炎症反応が著しく高かった。局所進行が強く高位精巣摘除術が困難であり、リンパ節生検を施行した上で化学療法を施行した。生検結果はセミノーマであった。腫瘍の縮小が得られ、高位精巣摘除術、リンパ節郭清術、腹直筋皮弁による閉創を施行した。術後10ヵ月再発なく経過している。(著者抄録)
  • 池田 恵理子, 牛尾 純, 横山 健介, 多田 大和, 川崎 佑輝, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏  膵臓  34-  (3)  A120  -A120  2019/06  [Refereed][Not invited]
  • 腎病理所見からみたループス腎炎の病態
    岩津 加奈, 岩津 好隆, 福嶋 敬宜, 仁木 利郎, 湯村 和子, 小野 祐子, 上田 善彦, 長田 太助  日本腎臓学会誌  61-  (3)  345  -345  2019/05  [Refereed][Not invited]
  • 腎疾患におけるTubuloreticular inclusionの臨床病理学的検討
    岩津 加奈, 岩津 好隆, 福嶋 敬宜, 仁木 利郎, 湯村 和子, 小野 祐子, 上田 善彦, 長田 太助  日本腎臓学会誌  61-  (3)  345  -345  2019/05  [Refereed][Not invited]
  • 池田 恵理子, 鈴木 智子, 中村 香織, 織田 智博, 二階堂 貴章, 郡 俊勝, 柳田 美樹, 吉本 多一郎, 天野 雄介, 福嶋 敬宜  日本臨床細胞学会雑誌  58-  (Suppl.1)  294  -294  2019/05  [Refereed][Not invited]
  • 中村 香織, 天野 雄介, 織田 智博, 鈴木 智子, 柳田 美樹, 郡 勝俊, 池田 恵理子, 大城 久, 仁木 利郎, 福嶋 敬宜  日本臨床細胞学会雑誌  58-  (Suppl.1)  295  -295  2019/05  [Refereed][Not invited]
  • DNTの病理学的特徴を持つ、播種した側頭葉腫瘍の1例
    内山 拓, 永山 理恵, 柴原 純二, 福嶋 敬宜, 松原 大祐, 川合 謙介, 五味 玲  Brain Tumor Pathology  36-  (Suppl.)  124  -124  2019/05  [Refereed][Not invited]
  • 坂口 美織, 大城 久, 笹島 ゆう子, 吉本 多一郎, 小柳 貴裕, 竹井 裕二, 藤原 寛行, 松原 大祐, 仁木 利郎, 福嶋 敬宜  日本臨床細胞学会雑誌  58-  (Suppl.1)  277  -277  2019/05  [Refereed][Not invited]
  • EUSによる10mm以下の非機能性膵神経内分泌腫瘍の描出能とgrade診断
    池田 恵理子, 牛尾 純, 横山 健介, 多田 大和, 川崎 佑輝, 坂口 美織, 玉田 喜一, 福嶋 敬宜  超音波医学  46-  (Suppl.)  S543  -S543  2019/04  [Refereed][Not invited]
  • 膵切除検体の病理学的検索における「検体超音波描画法」併用の有用性
    池田 恵理子, 牛尾 純, 川崎 佑輝, 横山 健介, 多田 大和, 坂口 美織, 玉田 喜一, 福嶋 敬宜  超音波医学  46-  (Suppl.)  S654  -S654  2019/04  [Refereed][Not invited]
  • ヘリコバクターピロリ除菌後発見胃癌の臨床病理学的特徴
    坂口 美織, 三浦 義正, 池田 恵理子, 大澤 博之, 福嶋 敬宜  日本病理学会会誌  108-  (1)  370  -371  2019/04  [Refereed][Not invited]
  • 膵切除検体における超音波検査を併用した病理組織学的診断の試み
    池田 恵理子, 牛尾 純, 坂口 美織, 多田 大和, 福嶋 敬宜  日本病理学会会誌  108-  (1)  385  -385  2019/04  [Refereed][Not invited]
  • Atypical polypoid adenomyomaの間質成分の免疫組織化学的検討
    木原 淳, 天野 雄介, 吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎  日本病理学会会誌  108-  (1)  411  -411  2019/04  [Refereed][Not invited]
  • 膵神経内分泌腫瘍組織のEUS-FNA検体における組織透明化を併用した3D-Gradingの試み
    池田 恵理子, 牛尾 純, 坂口 美織, 福嶋 敬宜  日本病理学会会誌  108-  (1)  479  -479  2019/04  [Refereed][Not invited]
  • ヘリコバクターピロリ除菌後発見胃癌の臨床病理学的特徴
    坂口 美織, 三浦 義正, 池田 恵理子, 大澤 博之, 福嶋 敬宜  日本病理学会会誌  108-  (1)  370  -371  2019/04  [Not refereed][Not invited]
  • 12年の長期経過観察中に悪性化したと考えられる膵粘液嚢胞性腫瘍の一例
    高橋 礼, 笹沼 英紀, 三木 厚, 森嶋 計, 吉田 淳, 遠藤 和洋, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏, 池田 恵理子, 福島 敬宜  日本消化器病学会関東支部例会プログラム・抄録集  354回-  49  -49  2019/04  [Not refereed][Not invited]
  • 【肉眼病理-症例から探る鑑別のヒント-】 (第5章)食道 癌肉腫
    福嶋 敬宜  病理と臨床  37-  (臨増)  135  -137  2019/04  [Not refereed][Not invited]
  • 【肉眼病理-症例から探る鑑別のヒント-】 (第7章)小腸・大腸 炎症性類線維ポリープ
    福嶋 敬宜  病理と臨床  37-  (臨増)  167  -169  2019/04  [Not refereed][Not invited]
  • 【肉眼病理-症例から探る鑑別のヒント-】 (第7章)小腸・大腸 潰瘍性大腸炎による中毒性巨大結腸症
    福嶋 敬宜  病理と臨床  37-  (臨増)  180  -182  2019/04  [Not refereed][Not invited]
  • 【肉眼病理-症例から探る鑑別のヒント-】 (第8章)肝胆脾 胆管内乳頭状腫瘍
    福嶋 敬宜  病理と臨床  37-  (臨増)  218  -220  2019/04  [Not refereed][Not invited]
  • 【肉眼病理-症例から探る鑑別のヒント-】 (第9章)膵 膵腺房細胞癌
    福嶋 敬宜  病理と臨床  37-  (臨増)  245  -247  2019/04  [Not refereed][Not invited]
  • 【肉眼病理-症例から探る鑑別のヒント-】 (第16章)乳腺・腹膜 腸間膜リンパ管腫
    福嶋 敬宜  病理と臨床  37-  (臨増)  374  -376  2019/04  [Not refereed][Not invited]
  • 透過型電子顕微鏡検査の基礎と実際 腎生検検査の必須アイテム
    飛田野 清美, 二階堂 貴章, 本望 一昌, 小瀬川 順幸, 芳賀 美子, 福嶋 敬宜  臨床検査栃木  14-  (2)  19  -26  2019/04  [Not refereed][Not invited]
  • 骨盤内リンパ節転移を伴う巨大精巣腫瘍の1例
    山崎 正博, 黒川 真輔, 亀田 智弘, 金子 侑平, 竹嶋 咲, 田畑 憲一, 池 大官, 田代 絢亮, 亀井 潤, 杉原 亨, 藤崎 明, 安東 聡, 高山 達也, 福嶋 敬宜, 藤村 哲也  泌尿器外科  32-  (3)  305  -305  2019/03  [Not refereed][Not invited]
  • サルコイドーシスに合併した気管支内アスペルギローマの1例
    水品 佳子, 坂東 政司, 中山 雅之, 高崎 俊和, 間藤 尚子, 金井 信行, 福嶋 敬宜, 遠藤 俊輔, 鈴木 拓児, 萩原 弘一  気管支学  41-  (2)  181  -186  2019/03  [Not refereed][Not invited]
     
    背景. 肺サルコイドーシスにアスペルギルス感染を併発する頻度が高いことが報告されているが、限局性拡張気管支内腔に生じたアスペルギローマは稀である。症例. 69歳、男性。胸部異常陰影の精査目的に来院した。胸部CTで舌区に単発の結節影を認め、気管支鏡下生検でアスペルギルス感染が示唆された。根治治療目的に胸腔鏡下舌区域切除術を施行し、病理学的にサルコイドーシスを背景とした気管支拡張症とその内部のアスペルギローマと診断した。結論. 単発の肺結節影を呈し、サルコイドーシスを背景とした限局性拡張気管支内腔に生じたアスペルギローマの1例を経験した。背景疾患を含めた診断および治療に外科的切除が有用であった。(著者抄録)
  • 【膵神経内分泌腫瘍-診断と治療のパラダイムシフト-】 病理と基礎 WHO2017分類改訂の要点
    池田 恵理子, 福嶋 敬宜  肝・胆・膵  78-  (1)  9  -15  2019/01  [Not refereed][Not invited]
  • 無治療で20年間の経過を観察しえている肝原発類上皮血管内皮腫の1例
    山口 将太, 津久井 舞未子, 三浦 光一, 森本 直樹, 大竹 俊哉, 高岡 良成, 村山 梢, 渡邊 俊司, 野本 弘章, 福嶋 敬宜, 礒田 憲夫, 山本 博徳  肝臓  59-  (12)  692  -699  2018/12  [Not refereed][Not invited]
     
    症例は61歳女性。1998年に近医で肝腫瘤を指摘され、2001年に精査目的に当科紹介。画像所見で多発する肝腫瘍を認めた。診断目的に行った肝生検で腫瘍細胞は血管内皮系マーカーであるCD31、Factor VIII、CD34が陽性より、類上皮血管内皮腫(Epithelioid hemangioendothelioma:EHE)と診断した。肺にも小結節を複数認め、経過から肝原発で肺転移を疑った。手術適応はなく、また有効な化学療法も存在しなかったため、十分なインフォームドコンセントのもと、経過観察とした。経過観察中、腫瘍の進展はほとんど見られず、また造影CT検査で当初認められた腫瘍のリング状エンハンスメントも現在は消失している。近医での初診を起点とすると、無治療で20年間の経過観察しえているEHEの1例であり、貴重な症例と考え報告する。(著者抄録)
  • 【EUSによる消化管疾患の診断-現状と最新の話題】 小腸腫瘍・十二指腸腫瘍のEUS診断
    三浦 義正, 矢野 智則, 坂口 美織, 井野 裕治, 角田 真人, Khurelbaatar Tsevelnorov, 小林 泰俊, 坂本 博次, 林 芳和, 砂田 圭二郎, 大澤 博之, 福嶋 敬宜, 山本 博徳  胃と腸  53-  (13)  1747  -1755  2018/12  [Not refereed][Not invited]
     
    <文献概要>小腸腫瘍の治療前評価における超音波内視鏡(EUS)の役割は,質的診断と腫瘍深度診断であり,内視鏡治療に直結するため重要である.しかし,小腸腫瘍は上皮性腫瘍,非上皮性腫瘍共に発見時に内視鏡治療になる可能性は低いため,臨床でのEUSの使用は限られる.一方,Helicobacter pylori陰性者が増加する中で,十二指腸腫瘍を発見・治療する機会が増えている.特に表在性非乳頭部十二指腸上皮性腫瘍(SNADET)の治療においては,腫瘍のサイズ,形態,リスク・ベネフィットを考慮して治療法を選択するが,EUSは手技の安全性を確保する上で重要である.本稿では,小腸腫瘍に対する診断・治療について,実臨床で比較的遭遇する疾患を中心に解説する.
  • 腎生検における透過型電子顕微鏡観察所見の捉え方
    飛田野 清美, 二階堂 貴章, 本望 一昌, 芳賀 美子, 福嶋 敬宜  自治医科大学臨床検査技師年報  (41)  41  -52  2018/12  [Not refereed][Not invited]
     
    生検電顕観察所見の捉え方について、各種腎炎の電顕像とともに供覧した。腎生検をグルタールアルデヒドで前固定、オスミウム酸による後固定、脱水、置換、エポキシ樹脂包埋後に準超薄切切片作製、超薄切片作製、電子染色、透過型電子顕微鏡を使用し、所見観察・写真撮影を行った。微小変化群、良性家族性血尿(菲薄基底膜病)、アルポート症候群、Fabry病、イムノタクトイド腎症、微量アミロイド沈着(アミロイドーシス)について、それぞれの腎炎に対する特徴となる所見を撮影した。糸球体において、上皮細胞・足突起、メサンギウム細胞、沈着物の有無やその存在場所、糸球体基底膜、内皮細胞などの観察を行った。尿細管間質において間質内傍尿細管毛細血管、近位尿細管、遠位尿細管および集合管などを観察し、電顕写真撮影後に所見レポートを作成、電顕写真とともに病理医に提出した。
  • 【膵嚢胞診療最前線-IPMN国際診療コンセンサスガイドライン改訂を踏まえて-】 IPMN国際診療コンセンサスガイドライン最新版(2017年) 病理診断改訂の要点・意義
    福嶋 敬宜  肝・胆・膵  77-  (5)  933  -938  2018/11  [Not refereed][Not invited]
  • サルコイドーシスに合併した気管支内アスペルギルス菌球症の1例
    水品 佳子, 坂東 政司, 中山 雅之, 高崎 俊和, 間藤 尚子, 金井 信行, 福嶋 敬宜, 遠藤 俊輔, 鈴木 拓児, 萩原 弘一  日本サルコイドーシス/肉芽腫性疾患学会雑誌  38-  (サプリメント号)  76  -76  2018/10  [Not refereed][Not invited]
  • 膵腫瘍組織型と悪性度 細胞診結果をどう伝えるか
    福嶋 敬宜  日本臨床細胞学会雑誌  57-  (Suppl.2)  496  -496  2018/10  [Not refereed][Not invited]
  • 肝胆道系疾患における細胞診の役割 胆汁細胞診における免疫細胞化学的染色の有用性について
    織田 智博, 渡邊 温子, 中村 香織, 二階堂 貴章, 柳田 美樹, 郡 俊勝, 鈴木 智子, 芳賀 美子, 池田 恵理子, 小松原 利英, 大城 久, 福嶋 敬宜  日本臨床細胞学会雑誌  57-  (Suppl.2)  568  -568  2018/10  [Not refereed][Not invited]
  • 重複尿管の腎盂尿管移行部に発生した癌肉腫の尿細胞診所見
    辻 賢太郎, 大城 久, 伊藤 淳史, 田畑 憲一, 丹波 美織, 吉本 多一郎, 天野 雄介, 木原 淳, 河田 浩敏, 二階堂 貴章, 柳田 美樹, 郡 俊勝, 鈴木 智子, 仁木 利郎, 福嶋 敬宜  日本臨床細胞学会雑誌  57-  (Suppl.2)  622  -622  2018/10  [Not refereed][Not invited]
  • 【ここまで来た!膵癌の早期診断】 浸潤性膵管癌の前駆病変
    森田 剛平, 福嶋 敬宜  胆と膵  39-  (9)  813  -818  2018/09  [Not refereed][Not invited]
     
    膵癌の前駆病変としては、膵上皮内腫瘍性病変(PanIN)、膵管内乳頭粘液性腫瘍(IPMN)、粘液性嚢胞腫瘍(MCN)などがその候補としてしばしばあげられる。一方、腺房細胞の導管上皮様化生(ADM)は、動物実験では膵癌のもとになる病変ではないかと比較的古くから報告されている病変であるが、ヒト膵癌では否定的な意見が多い。また、比較的最近報告された異型平坦状病変(atypical flat lesions:AFLs)は、ADMとも類似した病変だが、膵癌家系の膵癌の背景膵にもみられると報告され、膵癌の新たな前駆病変である可能性が論じられている。(著者抄録)
  • 肺病変を呈する悪性リンパ腫気管支鏡診断に影響する因子の検討
    古川原 春菜, 間藤 尚子, 藤城 泰麿, 瀧上 理子, 中山 雅之, 山沢 英明, 坂東 政司, 福嶋 敬宜, 杉山 幸比古, 萩原 弘一  気管支学  40-  (4)  293  -299  2018/07  [Not refereed][Not invited]
     
    背景. 悪性リンパ腫(malignant lymphoma:ML)の肺病変は気管支鏡での診断率が約30%と低いが、なぜ気管支鏡による診断が困難なのか検討した報告はない。目的. MLの肺病変に対して気管支鏡下生検を施行した症例を解析し、診断に関与する因子を検討した。方法. 2009〜2014年に当科で気管支鏡下生検を施行した肺病変を伴う初発のML9例において、診断群と非診断群とで臨床所見、画像所見、生検時の情報、病理学的所見を比較検討した。結果. 9例の生検部位は、気管支生検(endobronchial biopsy:EBB)2例、経気管支肺生検(transbronchial lung biopsy:TBLB)7例であった。確定診断が得られたのはEBBで2例中2例、TBLBで7例中4例であった。診断群6例の病理診断はびまん性B細胞リンパ腫(diffuse large B-cell lymphoma:DLBCL)4例、mucosa-associated lymphoid tissue(MALT)リンパ腫2例であった。診断群は非診断群と比較し、炎症反応およびsoluble interleukin-2 receptor(sIL-2R)が高値であり、発熱などの臨床症状を伴い、CT上肺病変は広範囲に進展し多彩であった。一方、非診断群は最終的にvideo-assisted thoracic surgery(VATS)で診断し、DLBCLが1例、MALTリンパ腫が2例であった。CT上肺病変は限局的であったが、TBLB時には診断群と同様、全例で超音波気管支鏡(endobronchial ultrasonography:EBUS)で病変への到達が確認され、さらに全例で病理所見上リンパ球浸潤が認められていた。しかし、組織検体が微小であり、採取時の挫滅により細胞形態の観察が妨げられ確定診断に至らなかったこと、術前診断で他疾患が想定された例では、病理診断医への診療情報提供が不十分であったことが判明した。結語. MLのTBLBに際しては、十分な検体量を確保し組織の挫滅を避けるため、より大きなカップ径の鉗子を使用することが望ましいと考えられた。また、MLを疑う症例で病理学的にリンパ球浸潤を認めた場合には、生検方法の工夫と病理診断医への適切な診療情報提供により、気管支鏡での診断率が向上する可能性が示唆された。(著者抄録)
  • 食道神経内分泌癌(NEC)6例の治療経験
    齋藤 心, 細谷 好則, 藤井 博文, 山口 博紀, 森 美鈴, 福嶋 敬宜, 金丸 理人, 松本 志郎, 三浦 義正, 佐田 尚宏  日本食道学会学術集会プログラム・抄録集  72回-  281  -281  2018/06  [Not refereed][Not invited]
  • 【膵癌update】 疫学・基礎 病理
    福嶋 敬宜  臨床消化器内科  33-  (7)  733  -739  2018/05  [Not refereed][Not invited]
  • 早期膵癌発見への道筋
    伊佐山 浩通, 福嶋 敬宜, 大塚 隆生, 蘆田 玲子, 潟沼 朗生  日本消化器病学会雑誌  115-  (4)  357  -376  2018/04  [Not refereed][Not invited]
  • 【膵嚢胞性腫瘍の診断と治療-up-to-date-】 膵嚢胞性病変の病理
    福嶋 敬宜  膵臓  33-  (2)  94  -100  2018/04  [Not refereed][Not invited]
     
    画像診断の発展も相まって、膵臓の嚢胞性病変の検出数は増加している。嚢胞状の病変には、上皮に裏打ちされた嚢胞を形成する病変、内部が崩壊して嚢胞状を示す病変とその他があり、それぞれに腫瘍性病変と非腫瘍性病変がある。前者には、膵管の嚢胞状拡張性病変も含まれ、貯留嚢胞、膵管内乳頭粘液性腫瘍(IPMN)、粘液嚢胞性腫瘍(MCN)、漿液性嚢胞腫瘍(SCN)、リンパ上皮性嚢胞などが、後者には充実性偽乳頭状腫瘍(SPN)の他、転移性腫瘍も含め様々な充実性腫瘍があり、非腫瘍性病変としては仮性(偽)嚢胞がある。これらの嚢胞性病変には、非腫瘍性病変から悪性腫瘍まで、様々な性質の病変が含まれることからその見極めに注意が必要である。(著者抄録)
  • IPMN診療における内視鏡の役割 病理からみたIPMNと背景膵
    福嶋 敬宜  Gastroenterological Endoscopy  60-  (Suppl.1)  580  -580  2018/04  [Not refereed][Not invited]
  • 膵IPMNの病理診断と細胞診
    福嶋 敬宜  日本臨床細胞学会雑誌  57-  (Suppl.1)  120  -120  2018/04  [Not refereed][Not invited]
  • 胸水中への脊索腫細胞の出現を証明しえた1例
    丹波 美織, 大城 久, 柳田 美樹, 郡 俊勝, 鈴木 智子, 芳賀 美子, 織田 智博, 二階堂 貴章, 仁木 利郎, 福嶋 敬宜  日本臨床細胞学会雑誌  57-  (Suppl.1)  248  -248  2018/04  [Not refereed][Not invited]
  • 中枢神経系原発と考えられ、その後他臓器浸潤がみられた悪性リンパ腫の一例
    柳田 美樹, 二階堂 貴章, 郡 俊勝, 鈴木 智子, 渡邊 温子, 天野 雄介, 大城 久, 福嶋 敬宜  日本臨床細胞学会雑誌  57-  (Suppl.1)  264  -264  2018/04  [Not refereed][Not invited]
  • 田畑 憲一, 大城 久, 柳田 美樹, 郡 俊勝, 鈴木 智子, 天野 雄介, 木原 淳, 松原 大祐, 仁木 利郎, 福嶋 敬宜  日本臨床細胞学会雑誌  57-  (Suppl.1)  327  -327  2018/04  [Not refereed][Not invited]
  • 乳頭状胆道腫瘍を再整理する IPNB overview 概要と課題
    福嶋 敬宜  日本病理学会会誌  107-  (1)  541  -541  2018/04  [Not refereed][Not invited]
  • 腎生検・蛍光抗体法直接法の所見から糸球体腎炎を推測する 臨床検査技師としてのチャレンジ
    飛田野 清美, 渡邊 温子, 中村 香織, 菊地 みどり, 本望 一昌, 二階堂 貴章, 芳賀 美子, 福嶋 敬宜  臨床検査栃木  13-  (2)  51  -56  2018/03  [Not refereed][Not invited]
     
    蛍光抗体法により推測できる糸球体腎炎について、各種抗体の組み合わせ所見と電顕所見を合わせて提示した。免疫グロブリンのIgG、IgM、IgAと補体のC3c、C1q、C4ならびにFibrinogenの各種抗体を1種類1プレパラートに搭載し、湿潤箱中で室温に1時間、蛍光抗体法、直接法による反応を行った。蛍光抗体法で免疫グロブリンや補体などの沈着パターンの組み合わせを観察し、各種腎炎(IgA腎症、紫斑病性腎炎、膜性腎症、ループス腎炎など)について、その種類を推測した。沈着パターンは沈着物の大きさや形(細顆粒状、粗顆粒状、線状、沈着部位、基底膜係蹄末梢部、間質など)について観察した。同症例の電顕所見も確認した。症例1(IgA腎症、20歳男性)、症例2(紫斑病性腎炎、65歳女性)、症例3(膜性腎症、48歳女性)、症例4(ループス腎炎、78歳男性)、症例5(ループス腎炎、44歳男性)について蛍光抗体法所見、電顕所見、最終病理診断を提示した。
  • 右耳後部に異所性の呼吸器粘膜上皮がみられた稀な1例
    二階堂 貴章, 飛田野 清美, 本望 一昌, 小瀬川 順幸, 芳賀 美子, 福嶋 敬宜  臨床検査栃木  13-  (2)  57  -61  2018/03  [Not refereed][Not invited]
     
    症例は1歳女性で、出生時より低体重、口蓋裂、両唇顎口蓋裂、哺乳不全、難聴、胃食道逆流症、誤嚥性肺炎、皮膚感染症、新生児ビタミンK欠乏症を認めた。今回、右耳後部に赤いびらんを認めた。皮膚のびらんに対し、ゲンタシン軟膏等の外用薬で経過観察したが上皮化は得られず、先天性皮膚欠損症等が疑われ、パンチ生検を施行した。病理組織にて線毛を有する上皮細胞が確認された。後日、口唇口蓋裂の手術と併せて皮膚のびらんを全切除した。免疫染色所見では、表層の細胞はCK7陰性で、真皮内にある小さな嚢胞部のみ陽性で、染色性は一様ではなかった。ほかの抗体CDX-2、CK20、TTF-1は陰性であった。電顕では表層部にわずかな管腔形成がみられ、重層扁平上皮とは明らかに違う線毛上皮が確認された。本症例は、先天性表皮水疱症や先天性皮膚欠損症などいくつかの疾患が候補に上がったが、どれもあてはまるものがなく確定診断には至らなかった。最終病理診断は、線毛を有する気管支上皮細胞と扁平上皮化生が交互に分布する異所性の呼吸器粘膜となった。
  • 電顕観察で傍尿細管毛細血管に糸球体同様の病変を認めたSLE腎炎の一例
    飛田野 清美, 本望 一昌, 二階堂 貴章, 山本 昌代, 中村 香織, 渡邊 温子, 芳賀 美子, 福嶋 敬宜  自治医科大学臨床検査技師年報  (40)  46  -53  2018/01  [Not refereed][Not invited]
     
    症例は14歳女性で、38℃台の発熱、乏尿、関節の腫脹・関節痛を認め、血圧130〜140台、血液検査でアルブミン2.6g/dl、尿検査で蛋白定量3.79mg/gCr、尿中赤血球50-99HPFを呈し、ネフローゼ症候群を疑った。抗核抗体陽性、低補体血症があり、各種自己抗体が陽性で、全身性エリテマトーデス(SLE)、シェーグレン症候群と臨床診断し、腎生検を施行した。腎生検・光顕所見は係蹄にWire-loop lesionが目立ち、糸球体の血管内に硝子様血栓を疑う像もあり、好中球や核片も散見された。電顕所見はメサンギウム領域、内皮下、上皮下にdense deposit沈着、Wire-loop lesion、内皮細胞質内にtubuloreticular inclusionを観察した。さらに尿血管間質内やPTCの基底膜にdeposit沈着がみられ、PTCの内皮細胞質内にもTRIを認めた。病理最終診断は、IV-G(A)相当のループス腎炎であった。
  • 乳腺腺筋上皮腫の一例
    郡 俊勝, 天野 雄介, 鈴木 智子, 柳田 美樹, 伊藤 聡史, 田中 裕美子, 藤田 崇史, 大城 久, 福嶋 敬宜  自治医科大学臨床検査技師年報  (40)  54  -56  2018/01  [Not refereed][Not invited]
     
    症例は64歳女性で、10年前に右乳腺腫瘍を指摘され、経過観察していた。マンモグラフィーでFADカテゴリー3、超音波で右乳腺D領域に20mmの範囲で低エコー領域を認め、MRIで右CD領域に20mmの範囲で小結節性病変の集簇を認めた。乳腺腫瘤の疑いで、穿刺吸引細胞診、針生検および右乳腺部分切除術を施行した。細胞所見により推定診断として紡錘形細胞腫瘍を疑った。針生検で採取した組織には紡錘形細胞が主体に増殖し、一部では腺管構造を認めた。組織像と免疫染色の結果において腺筋上皮腫と診断した。摘出検体は、肉眼像で腫瘍は境界明瞭で白色多結節性に認めた。組織学的に病変は多結節性で充実性に認め、一部では腺管構造を観察した。組織像は紡錘形細胞が主体に増殖し、一部において腺管構造を観察した。組織像と免疫染色の結果において、腺筋上皮腫と診断した。
  • Ugajin Takuhiro, Watanabe Miho, Tsudo Naoki, Fujinuma Sumio, Sasanuma Hideki, Fukushima Noriyoshi  Official Journal of Japan Society of Ningen Dock  33-  (1)  69  -75  2018  [Not refereed][Not invited]
     

      A 64-year-old woman had been positive for fecal occult blood for three consecutive years in occupational health check-ups, but this was not followed up. She developed orthostatic dizziness and pain upon defecation, but did not consult a physician. Thereafter, she was diagnosed with anemia and consulted a doctor who diagnosed advanced rectal cancer and early colon cancer. Pretreatment examination also revealed gallbladder cancer. She developed ileus due to bowel preparation for endoscopic therapy to be performed for early colon cancer and required construction of an artificial anus. The colon and gallbladder cancers were treated endoscopically and surgically, respectively. Chemotherapy is currently being administered for the rectal cancer.

      Although rates of colorectal cancer have recently increased, rates for secondary testing following colorectal cancer screening are generally low, and they are lower for occupational health check-ups than for local health check-ups. Education on colorectal cancer would lead to enhanced awareness of the need for examination and it would be important to combine this with appropriate encouragement to undergo it.

      Rates of multiple primary cancers have been tending to increase together with the aging of the population and advances in diagnostic imaging. Although multiple primary cancers of the colon and gallbladder are rare, there is a visible increasing trend. In cancer screening, it is important to confirm whether cancer predilection and multiple factors are present or not through history taking, physical and other examinations. Knowledge of multiple primary cancers is required even for medical staff engaged in general health check-ups.

  • 胆管癌間質におけるmatriptase発現とその臨床的意義
    小松原 利英, 福嶋 敬宜, 大城 久, 佐田 尚宏, 佐久間 康成  日本消化器外科学会雑誌  50-  (Suppl.2)  222  -222  2017/10
  • 不正子宮出血を契機に再発が確認された急性骨髄性白血病の一例
    丹波 美織, 大城 久, 柳田 美樹, 郡 俊勝, 鈴木 智子, 芳賀 美子, 蘆澤 健太郎, 田畑 憲一, 伊藤 淳史, 松原 大祐, 吉本 多一郎, 木原 淳, 天野 雄介, 仁木 利郎, 福嶋 敬宜  日本臨床細胞学会雑誌  56-  (Suppl.2)  715  -715  2017/10  [Not refereed][Not invited]
  • ブラシを用いた横隔腹膜擦過・液状化細胞診断法の細胞採取量の検討 綿棒法との比較
    蘆澤 健太郎, 大城 久, 丹波 美織, 田畑 憲一, 伊藤 淳史, 鈴木 智子, 渡邊 温子, 柳田 美樹, 郡 俊勝, 二階堂 貴章, 藤原 寛行, 芳賀 美子, 福嶋 敬宜  日本臨床細胞学会雑誌  56-  (Suppl.2)  800  -800  2017/10  [Not refereed][Not invited]
  • HAYAKAWA Morisada, SAKATA Asuka, FUKUSHIMA Noriyoshi, NISHIMURA Satoshi, SAKATA Yoichi, OHMORI Tsukasa  臨床血液  58-  (9)  1456  2017/09  [Not refereed][Not invited]
  • 集学的治療が有効であった肺原発Ewing's sarcoma/primitive neuroectodermal tumorの一例
    瀧上 理子, 山沢 英明, 内山 歩, 佐多 将史, 長井 良昭, 福嶋 敬宜, 仁木 利郎, 坂東 政司, 萩原 弘一  肺癌  57-  (5)  590  -590  2017/09  [Not refereed][Not invited]
  • 部分血栓化巨大右椎骨動脈瘤に対するコイル塞栓術後に右側Wallenberg症候群を呈して死亡した一剖検例
    田畑 憲一, 大城 久, 檜垣 鮎帆, 難波 克成, 河合 謙介, 蘆澤 健太郎, 丹波 美織, 伊藤 淳史, 福嶋 敬宜  日本病理学会会誌  106-  (2)  75  -75  2017/09  [Not refereed][Not invited]
  • 集学的治療が有効であった肺原発Ewing's sarcoma/primitive neuroectodermal tumorの一例
    瀧上 理子, 山沢 英明, 内山 歩, 佐多 将史, 長井 良昭, 福嶋 敬宜, 仁木 利郎, 坂東 政司, 萩原 弘一  肺癌  57-  (5)  590  -590  2017/09  [Not refereed][Not invited]
  • 異型ポリープ様腺筋腫(APAM)8例の検討
    成見 莉紗, 森澤 宏行, 森田 剛平, 竹井 裕二, 町田 静生, 高橋 詳史, 高橋 寿々代, 種市 明代, 嵯峨 泰, 福嶋 敬宜, 藤原 寛行, 松原 茂樹  日本婦人科腫瘍学会雑誌  35-  (3)  672  -672  2017/06  [Not refereed][Not invited]
  • 飛田野清美, 佐藤さなえ, 鈴木智子, 本望一昌, 二階堂貴章, 小瀬川順幸, 芳賀美子, 福嶋敬宜  臨床検査栃木  12-  (2)  140‐143  2017/03  [Not refereed][Not invited]
  • 肝胆膵疾患 病態の病理学的境界を考える 膵臓の神経内分泌腫瘍 いわゆる"NET G3"とMANECの境界
    福嶋 敬宜  日本病理学会会誌  106-  (1)  210  -210  2017/03  [Not refereed][Not invited]
  • 膵頭部膵癌における、D2-40染色を用いたリンパ管侵襲数の測定の意義
    森田 剛平, 三登 久美子, 大城 久, 仁木 利郎, 福嶋 敬宜  日本病理学会会誌  106-  (1)  317  -317  2017/03  [Not refereed][Not invited]
  • IPMNにおけるMUC13とAGR2の発現の臨床病理学的意義と予後予測に関する検討
    三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜  日本病理学会会誌  106-  (1)  318  -318  2017/03  [Not refereed][Not invited]
  • 広範な胸膜進展を伴う肺胞上皮置換性優位型肺腺癌の1例
    田畑 憲一, 森田 剛平, 大城 久, 吉本 多一郎, 松原 大祐, 仁木 利郎, 福嶋 敬宜  日本病理学会会誌  106-  (1)  371  -371  2017/03  [Not refereed][Not invited]
  • 異所性胃粘膜を伴うブルンナー腺の増殖性病変からなる十二指腸ポリポーシスの一例
    蘆澤 健太郎, 大城 久, 三登 久美子, 丹波 美織, 田畑 憲一, 伊藤 淳史, 福嶋 敬宜  日本病理学会会誌  106-  (1)  436  -436  2017/03  [Not refereed][Not invited]
  • 悪性の診断にFISH法が有用であった乳管内癌を伴う乳腺腺筋上皮腫の一例
    丹波 美織, 天野 雄介, 増田 しのぶ, 森田 剛平, 仁木 利郎, 福嶋 敬宜  日本病理学会会誌  106-  (1)  490  -490  2017/03  [Not refereed][Not invited]
  • 膵癌診療新時代 病理医が知っておくべき膵癌取扱い規約新改訂版のポイント 膵癌取扱い規約改訂の概要
    福嶋 敬宜  日本病理学会会誌  106-  (1)  582  -582  2017/03  [Not refereed][Not invited]
  • 飛田野 清美, 佐藤 さなえ, 鈴木 智子, 本望 一昌, 二階堂 貴章, 小瀬川 順幸, 芳賀 美子, 福嶋 敬宜  臨床検査栃木 = Journal of Tochigi Society of Medical Technology : 栃木県臨床衛生検査技師会雑誌  12-  (2)  140  -143  2017  [Not refereed][Not invited]
  • 飛田野清美, 二階堂貴章, 本望一昌, 芳賀美子, 今泉悠希, 江口和男, 福嶋敬宜  自治医科大学臨床検査技師年報  (39)  55‐62  -62  2017/01  [Not refereed][Not invited]
  • EUS-FNAにより診断し化学療法奏功後に切除を行ったが、術後に脳転移、髄膜播種を来たした膵神経内分泌細胞癌の1例
    山本 修平, 齋藤 倫寛, 権 勉成, 徳久 順也, 成木 良瑛子, 齋藤 智明, 松清 大, 浅井 浩司, 榎本 泰典, 三登 久美子, 福嶋 敬宜, 渡邉 学, 前谷 容  Progress of Digestive Endoscopy  90-  (Suppl.)  s140  -s140  2016/12  [Not refereed][Not invited]
  • 福嶋 敬宜  膵臓  31-  (6)  818  -824  2016/12  [Not refereed][Not invited]
     
    日本膵臓学会発行の膵癌取扱い規約第7版において、病理診断に関連した主な改訂点は、局所進展度因子の判定基準の明確化、組織型分類の見直し、生検、細胞診の診断報告様式についての指針の新設、術前化学療法や放射線照射の組織学的な効果判定法の新設などである。膵腫瘍の診療において、膵癌取扱い規約はその診療方針決定における基盤でありまた診療科を越えた共通語でもある。したがって、腫瘍の病理組織型や病理診断の判定基準などについても、診療科を問わずその概要は知っておく必要がある。(著者抄録)
  • 福嶋敬宜  消化器内視鏡  28-  (11)  1722‐1727  -1727  2016/11  [Not refereed][Not invited]
     
    WHOの腫瘍分類は、消化器臓器の神経内分泌腫瘍について、2010年にそのグレード分類基準を大きく改定した。その主な内容は、(1)従来の「carcinoid(カルチノイド)」「endocrine neoplasm(内分泌腫瘍)」という名称を、臓器によらず、すべて「neuroendocrine neoplasm(神経内分泌腫瘍)」に変更し統一した、(2)核分裂像数とKi-67指数のみを基準とした組織グレード分類を提示した、(3)消化管、肝胆膵も含め、消化器臓器発生の神経内分泌腫瘍のグレード分類をすべて同じ診断基準とした、などである。これにより、グレード分類がシンプルにはなったが、いくつかの問題点も指摘されている。(1)増殖能のみによるグレード分類の妥当性について、(2)腫瘍内のheterogeneityについて、(3)臓器特異性について、などである。腫瘍分類は人が作るものであり、それによって腫瘍の本質が変わるわけではないが、治療方針にも影響を及ぼすため、その妥当性は、常に病理学的にも臨床上も丹念に検証され進められていくべきだろう。(著者抄録)
  • 胸骨後経路胃管癌に対して胸壁吊り上げ式鏡視下胃管切除・空腸再建を行なった3例の経験
    齋藤 心, 宇井 崇, 倉科 憲太郎, 金丸 理人, 松本 志郎, 堀江 久永, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏, 永井 秀雄, 福嶋 敬宜  日本消化器外科学会雑誌  49-  (Suppl.2)  126  -126  2016/11
  • 伊藤淳史, 山崎有人, 笹野公伸, 松原大祐, 福嶋敬宜, 丹波美織, 田畑憲一, 武井暁一, 小泉大, 大城久  日本病理学会会誌  105-  (2)  112  -112  2016/09  [Not refereed][Not invited]
  • 安部望, 細谷好則, 金丸理人, 松本志郎, 春田英律, 倉科憲太郎, 佐田尚宏, 安田是和, 今田浩生, 福嶋敬宜  日本臨床外科学会雑誌  77-  (9)  2375‐2376  -2376  2016/09  [Not refereed][Not invited]
  • 片側性多発副腎皮質微小結節による原発性アルドステロン症の一例
    伊藤 淳史, 山崎 有人, 笹野 公伸, 松原 大祐, 福嶋 敬宜, 丹波 美織, 田畑 憲一, 武井 暁一, 小泉 大, 大城 久  日本病理学会会誌  105-  (2)  112  -112  2016/09  [Not refereed][Not invited]
  • 特発性血小板減少性紫斑病(ITP)と胃癌を合併した自己免疫性膵炎(AIP)の1例
    安部 望, 細谷 好則, 金丸 理人, 松本 志郎, 春田 英律, 倉科 憲太郎, 佐田 尚宏, 安田 是和, 今田 浩生, 福嶋 敬宜  日本臨床外科学会雑誌  77-  (9)  2375  -2376  2016/09  [Not refereed][Not invited]
  • 福嶋敬宜  病理と臨床  34-  (8)  805‐809  -809  2016/08  [Not refereed][Not invited]
  • MORITA Kohei, MITO Kumiko, FUKUSHIMA Noriyoshi  すい臓  31-  (3)  519‐520  2016/07  [Not refereed][Not invited]
  • FUKUSHIMA Noriyoshi  すい臓  31-  (3)  385  2016/07  [Not refereed][Not invited]
  • MITO Kumiko, SAITO Michihiro, MORITA Kohei, MAETANI Iruru, SATA Naohiro, FUKUSHIMA Noriyoshi  すい臓  31-  (3)  518  2016/07  [Not refereed][Not invited]
  • Biliary; Diagnosis and Treatment of cystic duct cancer in comparison of gallbladder or extrahepatic bile duct cancer 胆嚢管癌 臨床病理学的特徴とその課題(Biliary: Diagnosis and Treatment of cystic duct cancer in comparison of gallbladder or extra-hepatic bile duct cancer C
    福嶋 敬宜  日本肝胆膵外科学会・学術集会プログラム・抄録集  28回-  347  -347  2016/06  [Not refereed][Not invited]
  • 蘆澤健太郎, 河田浩敏, 金井信行, 仁木利郎, 福嶋敬宜  日本病理学会会誌  105-  (1)  439  -439  2016/04  [Not refereed][Not invited]
  • 吉本多一郎, 松原大祐, 福嶋敬宜, 仁木利郎  日本病理学会会誌  105-  (1)  391  -391  2016/04  [Not refereed][Not invited]
  • 福嶋敬宜  日本病理学会会誌  105-  (1)  249  -249  2016/04  [Not refereed][Not invited]
  • 森田剛平, 森田剛平, 三登久美子, 仁木利郎, 福嶋敬宜  日本病理学会会誌  105-  (1)  367  -367  2016/04  [Not refereed][Not invited]
  • 三登久美子, 齋藤倫寛, 森田剛平, 前谷容, 福嶋敬宜  日本病理学会会誌  105-  (1)  522  -522  2016/04  [Not refereed][Not invited]
  • 膵管内腫瘍栓を形成した退形成性膵管癌の3例
    川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳  Gastroenterological Endoscopy  58-  (Suppl.1)  798  -798  2016/04  [Not refereed][Not invited]
  • 膵管内腫瘍性病変の概要と改訂ボルチモア・コンセンサス
    福嶋 敬宜  日本病理学会会誌  105-  (1)  249  -249  2016/04  [Not refereed][Not invited]
  • 膵癌前癌病変としてのAtypical flat lesion(AFL)の病理組織学的検討
    森田 剛平, 三登 久美子, 仁木 利郎, 福嶋 敬宜  日本病理学会会誌  105-  (1)  367  -367  2016/04  [Not refereed][Not invited]
  • 肺癌の上皮間葉転換におけるクロマチンリンモデリング因子異常の解析
    吉本 多一郎, 松原 大祐, 福嶋 敬宜, 仁木 利郎  日本病理学会会誌  105-  (1)  391  -391  2016/04  [Not refereed][Not invited]
  • 子宮頸癌切除術後に大腿皮下に発生した血管肉腫(Stewart-Treves症候群)の一剖検例
    蘆澤 健太郎, 河田 浩敏, 金井 信行, 仁木 利郎, 福嶋 敬宜  日本病理学会会誌  105-  (1)  439  -439  2016/04  [Not refereed][Not invited]
  • 主膵管内にポリープ状に発育する破骨細胞様巨細胞(OGCs)を伴う退形成癌の臨床病理学的検討
    三登 久美子, 齋藤 倫寛, 森田 剛平, 前谷 容, 福嶋 敬宜  日本病理学会会誌  105-  (1)  522  -522  2016/04  [Not refereed][Not invited]
  • 膵管内腫瘍栓を形成した退形成性膵管癌の3例
    川崎 佑輝, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 福嶋 敬宜, 佐田 尚宏, 山本 博徳  Gastroenterological Endoscopy  58-  (Suppl.1)  798  -798  2016/04  [Not refereed][Not invited]
  • 飛田野清美, 二階堂貴章, 本望一昌, 中村啓子, 大木麻衣, 細田健太, 猪山和美, 越智利佳, 河野哲也, 芳賀美子, 山田茂樹, 福嶋敬宜  臨床検査栃木  11-  (2)  24  -29  2016/03  [Not refereed][Not invited]
  • キサンチンオキシダーゼ阻害作用を持つ既存薬のラットL-アルギニン急性膵炎モデルに対する効果(第2報)
    綾部 秀範, 真板 桜子, 濱本 知之, 山本 健, 小林 茂樹, 福嶋 敬宜  日本薬学会年会要旨集  136年会-  (4)  208  -208  2016/03  [Not refereed][Not invited]
  • キサンチンオキシダーゼ阻害作用を持つ既存薬のラットL-アルギニン急性膵炎モデルに対する効果(第2報)
    綾部 秀範, 真板 桜子, 濱本 知之, 山本 健, 小林 茂樹, 福嶋 敬宜  日本薬学会年会要旨集  136年会-  (4)  208  -208  2016/03  [Not refereed][Not invited]
  • 甲状腺クリーゼにより死亡した重症肺動脈性肺高血圧症の1例
    内山 歩, 久保田 香菜, 永井 道明, 今井 靖, 新保 昌久, 苅尾 七臣, 上野 修市, 吉本 多一郎, 福嶋 敬宜  日本内科学会関東地方会  622回-  39  -39  2016/03  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  117-  (3)  503  -507  2016/03  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.20)(最終回) 細胞診で使われることば
    福嶋 敬宜  内科  117-  (3)  503  -507  2016/03  [Not refereed][Not invited]
  • Toshihide Komatsubara, Koji Koinuma, Yasuyuki Miyakura, Hisanaga Horie, Mitsuaki Morimoto, Homare Ito, Alan K. Lefor, Naohiro Sata, Noriyoshi Fukushima  Clinical Journal of Gastroenterology  9-  (1)  1  -6  2016/02  [Not refereed][Not invited]
     
    Purpose: Endocrine cell carcinoma, according to the Japanese classification criteria for colorectal cancer, corresponds to neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC), as defined in the 2010 World Health Organization (WHO) classification. We retrospectively reviewed the clinical features of patients with these tumors diagnosed and treated at our institution. Methods: The clinicopathological features of endocrine cell carcinomas of the colon and rectum diagnosed by neuroendocrine markers from January 2000 to December 2012 were retrospectively evaluated in 12 patients. Results: Surgical specimens were obtained from eight of the 12 patients. MANEC was diagnosed in six patients and NEC in one. One tumor was unclassifiable. The tumors were not resected in four patients, and all died within 3 months. Of the eight patients who underwent resection, four received an R0 resection, two of whom underwent adjuvant chemotherapy and survived more than 5 years. One patient who underwent an R2 resection and continuous chemotherapy survived for 53 months. One patient with NEC underwent surgery and radiotherapy, and died 17 months later. Conclusion: Most endocrine cell carcinomas of the colon and rectum reviewed were MANECs. Though their prognosis was generally poor, chemotherapy may be effective in some patients.
  • 福嶋 敬宜  内科  117-  (2)  313  -317  2016/02  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.19) 膵臓の非腫瘍性病変
    福嶋 敬宜  内科  117-  (2)  313  -317  2016/02  [Not refereed][Not invited]
  • FUKUSHIMA Noriyoshi  日本肝胆膵外科学会学術集会プログラム・抄録集(CD-ROM)  28th-  ROMBUNNO.IP1‐2  2016  [Not refereed][Not invited]
  • FUKUSHIMA Noriyoshi  Suizo  31-  (6)  818  -824  2016  [Not refereed][Not invited]
     

    The Japan Pancreas Society published the 7th Edition of the General Rules for the Study of Pancreatic Cancer in 2016. Revised points in pathology-related matters were as follows: 1) histological criteria for local tumor extension were clarified, 2) histological classification of pancreatic neoplasms was revised on the basis of the WHO histological typing. In addition, sessions for: "criteria of histological response to drug therapy and/or radiotherapy", "pancreatic biopsy reporting formats" and "pancreas related cytology reporting formats" were newly proposed. Here we summarize principal points of revision and its concepts.

  • CPC解説(第78回) 高度な骨髄癌腫症とPulmonary tumor thrombotic microangiopathyを合併した胃癌の一剖検例
    吉本 多一郎, 田野 茂夫, 福嶋 敬宜, 仁木 利郎  病理と臨床  34-  (1)  83  -87  2016/01  [Not refereed][Not invited]
  • 鈴木智子, 坂谷貴司, 伊藤聡史, 柳田美樹, 郡俊勝, 芳賀美子, 福嶋敬宜  自治医科大学臨床検査技師年報  (38)  38  -41  2016/01  [Not refereed][Not invited]
  • 飛田野清美, 二階堂貴章, 本望一昌, 中村啓子, 大木麻衣, 細田健太, 猪山和美, 越智利佳, 河野哲也, 芳賀美子, 野首光弘, 山田茂樹, 福嶋敬宜  自治医科大学臨床検査技師年報  (38)  33  -37  2016/01  [Not refereed][Not invited]
  • 吉本多一郎, 田野茂夫, 福嶋敬宜, 仁木利郎  病理と臨床  34-  (1)  83  -87  2016/01  [Not refereed][Not invited]
  • Tahara Makiko, Fukushima Noriyoshi, Hojyo Nobuyuki, Morishima Kazue, Sakuma Yasunari, Horie Hisanaga, Hosoya Yoshinori, Lefor Alan, Sata Naohiro, Yasuda Yoshikazu  Nihon Gekakei Rengo Gakkaishi (Journal of Japanese College of Surgeons)  41-  (1)  52  -57  2016  [Not refereed][Not invited]
     
    A 76-year-old woman presented with right upper quadrant pain. Upper gastrointestinal endscopy showed a small depressed lesion on the greater curvature in the upper gastric body, and biopsy showed signet-ring cell carcinoma. Abdominal computed tomography scan revealed gastric wall thickening with enlarged lymph nodes. Total gastrectomy with lymph node dissection was performed. Mesenteric nodules were seen and two biopsied. The final histological diagnosis was poorly-differentiated adenocarcinoma/signet ring cell carcinoma, pT1a (M), ly0, v0, n (18/69) (#4sa, #7, #8a, #10). The tumor was intramucosal, measuring approximately 10 mm×10 mm. The mesenteric nodules were metastatic gastric cancer. We report a rare case of intramucosal gastric cancer with peritoneal dissemination.
  • 飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 山田 茂樹, 福嶋 敬宜  臨床検査栃木  11-  (2)  24  -29  2016  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  117-  (1)  135  -139  2016/01  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.18) EUS-FNA 充実性膵病変の病理学的鑑別
    福嶋 敬宜  内科  117-  (1)  135  -139  2016/01  [Not refereed][Not invited]
  • CPC解説(第78回) 高度な骨髄癌腫症とPulmonary tumor thrombotic microangiopathyを合併した胃癌の一剖検例
    吉本 多一郎, 田野 茂夫, 福嶋 敬宜, 仁木 利郎  病理と臨床  34-  (1)  83  -87  2016/01  [Not refereed][Not invited]
  • 光顕・電顕所見からFabry病を疑った心筋生検の一例
    飛田野 清美, 二階堂 貴章, 本望 一昌, 中村 啓子, 大木 麻衣, 細田 健太, 猪山 和美, 越智 利佳, 河野 哲也, 芳賀 美子, 野首 光弘, 山田 茂樹, 福嶋 敬宜  自治医科大学臨床検査技師年報  (38)  33  -37  2016/01  [Not refereed][Not invited]
     
    63歳男。失神して救急搬送された。心肺停止蘇生後にCRT-D(心臓再同期療法+除細動機能)システムの埋め込みと同時の心筋生検を行った。病理組織所見では炎症細胞の浸潤や壊死、類上皮細胞、アミロイド沈着を疑う所見はなく、光顕的所見では細胞の淡明化と空胞状変化を認めた。また、透過型電子顕微鏡所見では筋原線維の萎縮、消失や層状ミエリン様構造を示すZebra like structure沈着を認め、Fabry病に類似した像であった。遺伝子検査や酵素活性の検査を行ったが、Fabry病やミトコンドリア心筋症は否定的であり、Fabry病に類似した原因不明の脂質沈着症と推測された。
  • フィルター転写法(ThinPrep 5000)による腺癌細胞の検出性能の検討
    鈴木 智子, 坂谷 貴司, 伊藤 聡史, 柳田 美樹, 郡 俊勝, 芳賀 美子, 福嶋 敬宜  自治医科大学臨床検査技師年報  (38)  38  -41  2016/01  [Not refereed][Not invited]
     
    ThinPrep 5000を用いて扁平上皮細胞混在下における腺癌細胞の検出性能を検討した。陰性喀痰沈渣を混合した腺癌細胞の等倍希釈検査検体(x2〜x32)について、フィルター転写法による液状化検体細胞診(LBC法)を行い、腺癌細胞集塊の出現性と検出率を評価した。その結果、各希釈倍率および連続作製標本における腺癌細胞の検出率は、扁平上皮細胞混在下でも共存する細胞の影響を受けることなく13〜18%程度の一定の値を示した。また、腺癌細胞数の少ない高倍希釈(x32)検体では標本作製の連続操作によって集塊が減少し、フィルター転写法の原理である回転攪拌操作によって集塊が崩れた可能性が示された。
  • 【病理像から読みとる膵・胆道画像診断のコツ】 病理像を画像診断に反映させるために 病理像のバリエーションはどのように画像に反映するか
    三登 久美子, 福嶋 敬宜  胆と膵  36-  (12)  1291  -1297  2015/12  [Not refereed][Not invited]
     
    画像に反映され得る病理像として、肉眼レベルでは病変の形状、病変内部や境界部の性状があり、組織学的には、血管の増生、腫瘍細胞と線維組織のバランス、壊死、石灰沈着、膵萎縮、脂肪置換などがある。本稿では、画像(主にCT画像)に反映される病理組織学的な所見について概説する。(著者抄録)
  • 【病理像から読みとる膵・胆道画像診断のコツ】 病理像を画像診断に反映させるために 病理像のバリエーションはどのように画像に反映するか
    三登 久美子, 福嶋 敬宜  胆と膵  36-  (12)  1291  -1297  2015/12  [Not refereed][Not invited]
     
    画像に反映され得る病理像として、肉眼レベルでは病変の形状、病変内部や境界部の性状があり、組織学的には、血管の増生、腫瘍細胞と線維組織のバランス、壊死、石灰沈着、膵萎縮、脂肪置換などがある。本稿では、画像(主にCT画像)に反映される病理組織学的な所見について概説する。(著者抄録)
  • 福嶋 敬宜  内科  116-  (5)  873  -877  2015/11  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.17) 膵管内腫瘍
    福嶋 敬宜  内科  116-  (5)  873  -877  2015/11  [Not refereed][Not invited]
  • 【胆嚢・胆管と膵臓の画像診断update:病理・画像・治療のtriangle】 膵臓腫瘍の病理
    森田 剛平, 福嶋 敬宜  臨床画像  31-  (11)  1334  -1349  2015/11  [Not refereed][Not invited]
  • 心内膜下心筋生検の電顕標本作製法と将来への展望
    飛田野 清美, 二階堂 貴章, 本望 一昌, 芳賀 美子, 福嶋 敬宜, 江口 和男  臨床検査栃木  11-  (1)  31  -31  2015/10  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  116-  (4)  687  -691  2015/10  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.16) Vater乳頭部とその腫瘍
    福嶋 敬宜  内科  116-  (4)  687  -691  2015/10  [Not refereed][Not invited]
  • 悪性との鑑別を要したAtypical polypoid adenomyomaの2例
    福島 愛理, 伊藤 聡史, 鈴木 智子, 郡 俊勝, 森田 剛平, 河田 浩敏, 森澤 宏行, 藤原 寛行, 福嶋 敬宜  日本臨床細胞学会雑誌  54-  (Suppl.2)  561  -561  2015/10  [Not refereed][Not invited]
  • 膵液中に腫瘍細胞が出現した破骨細胞様巨細胞型退形成癌の3例
    伊藤 聡史, 福島 愛理, 鈴木 智子, 郡 俊勝, 森田 剛平, 福嶋 敬宜  日本臨床細胞学会雑誌  54-  (Suppl.2)  685  -685  2015/10  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  116-  (3)  506  -510  2015/09  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.15) 胆嚢炎あれこれ
    福嶋 敬宜  内科  116-  (3)  506  -510  2015/09  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.14) 針生検による肝腫瘍診断へのアプローチ
    福嶋 敬宜  内科  116-  (2)  325  -329  2015/08  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.13) 慢性肝障害における所見のオーバーラップ
    福嶋 敬宜  内科  116-  (1)  131  -135  2015/07  [Not refereed][Not invited]
  • 胃粘膜黄色腫の病態・発生機序と脂質異常症との関連
    福嶋 敬宜  日本医事新報  (4756)  65  -65  2015/06  [Not refereed][Not invited]
  • 急速な発育を示した膵管内腫瘍栓を伴う破骨巨細胞型退形成性膵管癌の1例
    吉田 友直, 牛尾 純, 横山 健介, 沼尾 規且, 畑中 恒, 玉田 喜一, 斉藤 倫寛, 福嶋 敬宜, 佐田 尚宏, 山本 博徳  Progress of Digestive Endoscopy  87-  (Suppl.)  s109  -s109  2015/06  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.12) 肝生検標本の見方の基本
    福嶋 敬宜  内科  115-  (5)  843  -847  2015/05  [Not refereed][Not invited]
  • 嚢胞状を示す膵病変の病理学的理解
    福嶋 敬宜  膵臓  30-  (3)  220  -220  2015/05  [Not refereed][Not invited]
  • 三木 厚, 佐久間 康成, 眞田 幸広, 森嶋 計, 笹沼 秀紀, 福嶋 敬宜, 田久保 海誉, 佐田 尚宏, 安田 是和  膵臓  30-  (3)  269  -269  2015/05  [Not refereed][Not invited]
  • 当科で切除術を施行した膵神経内分泌腫瘍についての検討
    石黒 保直, 佐久間 康成, 笹沼 英紀, 森嶋 計, 佐田 尚宏, 安田 是和, 齋藤 倫寛, 福嶋 敬宜  膵臓  30-  (3)  516  -516  2015/05  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  115-  (5)  843  -847  2015/05  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.11) 食道胃接合部とはどこか
    福嶋 敬宜  内科  115-  (4)  659  -663  2015/04  [Not refereed][Not invited]
  • 【病理診断クイックリファレンス】 (第8章)胆膵 腺房細胞癌
    福嶋 敬宜  病理と臨床  33-  (臨増)  126  -126  2015/04  [Not refereed][Not invited]
  • 【病理診断クイックリファレンス】 (第8章)胆膵 コレステロールポリープ
    福嶋 敬宜  病理と臨床  33-  (臨増)  127  -127  2015/04  [Not refereed][Not invited]
  • 【病理診断クイックリファレンス】 (第8章)胆膵 自己免疫性膵炎
    福嶋 敬宜  病理と臨床  33-  (臨増)  128  -128  2015/04  [Not refereed][Not invited]
  • 【病理診断クイックリファレンス】 (第8章)胆膵 胆嚢腺筋(腫)症
    福嶋 敬宜  病理と臨床  33-  (臨増)  129  -129  2015/04  [Not refereed][Not invited]
  • 小林 由香子, 森澤 宏行, 郡 俊勝, 福嶋 敬宜, 竹井 裕二, 町田 静生, 佐藤 尚人, 嵯峨 泰, 藤原 寛行, 鈴木 光明  日本臨床細胞学会雑誌  54-  (Suppl.1)  164  -164  2015/04  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  115-  (4)  659  -663  2015/04  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.10) 食道上皮内病変のキモ
    福嶋 敬宜  内科  115-  (3)  468  -472  2015/03  [Not refereed][Not invited]
  • 【膵癌・胆道癌-基礎と臨床の最新研究動向-】 膵癌 基礎編 膵癌発症の分子異常
    福嶋 敬宜  日本臨床  73-  (増刊3 膵癌・胆道癌)  11  -15  2015/03  [Not refereed][Not invited]
  • 膜性腎症症例の中で超微形態にて糸球体基底膜にうねりを示す20例の臨床病理学的検討(Ultrastructural study of the undulated epithelial side of glomerular basement membrane in membranous nephropathy: clinicopathological study of 20 patients)
    鈴木 司, 前田 真之, 吉本 多一郎, 福嶋 敬宜  自治医科大学紀要  37-  11  -18  2015/03  [Not refereed][Not invited]
     
    膜性腎症は成人ネフローゼ症候群の代表的な原因疾患であり、糸球体基底膜(GBM)領域にみられる高電子密度沈着物(EDD)が特徴的所見である。一方で、膜性腎症例においてEDDとは無関係にGBMのうねる構造(undulation)が時に観察される。膜性腎症の病期分類でもこの点について十分に検討されていない。我々はこの変化に注目し、陽性の20症例について、undulationを示さない膜性腎症20例を対照として比較検討した。undulation群では緻密層が有意に肥厚していた(962.4±309.1 vs.604.0±296.5nm;p=0.001)。また、蛍光抗体ではC3cの糸球体沈着例が少なく(n=4 vs.n=12;p=0.009)、血清補体値も保たれる傾向にあった。一般的に膜性腎症では補体の関与が報告されるが、undulation群では異なる機序を有することが示唆された。(著者抄録)
  • アドステロールシンチグラフィ陰性の副腎black adenomaによるCushing症候群の1例
    高橋 学, 長坂 昌一郎, 小太刀 豪, 若林 徹治, 齋藤 奈緒子, 野口 仁麗, 岡田 健太, 今田 浩生, 福嶋 敬宜, 佐久間 康成, 佐田 尚宏, 石橋 俊  自治医科大学紀要  37-  19  -23  2015/03  [Not refereed][Not invited]
     
    40歳女性。満月様顔貌、中心性肥満、赤色皮膚線条といったCushing徴候あり、血中ACTH抑制、コルチゾール高値で、左副腎に28mm大の腫瘍を認め、副腎性Cushing症候群と診断された。しかし、アドステロールシンチグラフィで集積なく、また尿中カテコラミンが軽度上昇し、MIBGシンチグラフィで甲状腺右側に有意に集積があり、精査目的で当院紹介となった。シンチグラフィ陰性の原因として副腎癌やblack adenomaが鑑別として考えられた。MIBGシンチグラフィの集積は、甲状腺髄様癌や傍神経節腫瘍は否定的で、腺腫様甲状腺腫による影響と考えられた。当院外科にて腹腔鏡下左副腎摘除術が施行された。腫瘍の割面は暗褐色調を呈し、病理組織所見からblack adenomaと診断された。アドステロールシンチグラフィ陰性で、副腎癌との鑑別を要した副腎black adenomaの症例を経験したので報告する。(著者抄録)
  • 肺病変を呈する悪性リンパ腫に対する気管支鏡的診断に関する検討
    古川原 春菜, 間藤 尚子, 佐多 将史, 中山 雅之, 中屋 孝清, 藤原 慎一郎, 山沢 英明, 坂東 政司, 福嶋 敬宜, 杉山 幸比古  日本呼吸器学会誌  4-  (増刊)  310  -310  2015/03  [Not refereed][Not invited]
  • 膵IPMN周囲間質におけるMast cell数の増加と間質所見の関連
    齋藤 倫寛, 今田 浩生, 鈴木 司, 福嶋 敬宜  日本病理学会会誌  104-  (1)  420  -420  2015/03  [Not refereed][Not invited]
  • 多彩な形態を示した肺原発Invasive mucinous adenocarcinomaの2例
    吉本 多一郎, 中野 智之, 遠藤 俊輔, 杉山 幸比古, 福嶋 敬宜, 仁木 利郎  日本病理学会会誌  104-  (1)  472  -472  2015/03  [Not refereed][Not invited]
  • Suzuki Tsukasa, Maeda Masayuki, Yoshimoto Taichiro, Fukushima1 Noriyoshi  自治医科大学紀要  37-  (37)  11  -18  2015/03  [Not refereed][Not invited]
     
    Introduction: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults and is characterized by electron-dense deposits (EDD) in the glomerular basement membrane (GBM). On the other hand, undulations, which are formed on the epithelial side of the GBM irrelevant to EDD, are observed in some cases; these findings were not considered in the Ehrenreich and Churg (EC) classification in MN. Methods: Twenty adult patients with MN formed long segments of undulations on the epithelial side of the GBM without reactions to subepithelial EDD by EM were enrolled. We compared the clinicopathological findings of these cases with 20 control cases of MN patients who did not have this undulation. These two patient groups were matched for gender, age, and class of disease stage in the EC classification of MN. Results: In the study group, the lamina densa thickened in many areas in comparison with the control group (962.4±309.1 vs. 604.0±296.5 nm; p=0.001). In addition, the number of C3c positive cases were less in the immunofluorescence (IF) study, (n=4 vs. n=12; p=0.009), and serum complement levels tended to be higher than those in the control group. Conclusion: In our study, the pathogenesis of GBM undulation was not determined. Nevertheless, these results indicate that diverse immune responses, in addition to the complement system, may be involved differently from usual cases of MN.
  • Suzuki Tsukasa, Maeda Masayuki, Yoshimoto Taichiro, Fukushima Noriyoshi, Noriyoshi  自治医科大学紀要 = Jichi Medical University Journal  37-  11  -18  2015/03  [Not refereed][Not invited]
     
    Introduction:Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adultsand is characterized by electron-dense deposits (EDD) in the glomerular basement membrane (GBM).On the other hand, undulations, which are formed on the epithelial side of the GBM irrelevant to EDD,are observed in some cases; these findings were not considered in the Ehrenreich and Churg (EC)classification in MN.Methods:Twenty adult patients with MN formed long segments of undulations on the epithelialside of the GBM without reactions to subepithelial EDD by EM were enrolled. We compared theclinicopathological findings of these cases with 20 control cases of MN patients who did not have thisundulation. These two patient groups were matched for gender, age, and class of disease stage in the ECclassification of MN.Results:In the study group, the lamina densa thickened in many areas in comparison with the controlgroup (962.4±309.1 vs. 604.0±296.5 nm; p = 0.001). In addition, the number of C3c positive cases wereless in the immunofluorescence( IF) study,( n = 4 vs. n = 12; p = 0.009), and serum complement levelstended to be higher than those in the control group.Conclusion:In our study, the pathogenesis of GBM undulation was not determined. Nevertheless, theseresults indicate that diverse immune responses, in addition to the complement system, may be involveddifferently from usual cases of MN.
  • 福嶋 敬宜  内科  115-  (3)  468  -472  2015/03  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.9) 鋸歯状ポリープ
    福嶋 敬宜  内科  115-  (2)  313  -317  2015/02  [Not refereed][Not invited]
  • 大腸内分泌細胞癌の臨床病理学的検討
    小松原 利英, 鯉沼 広治, 宮倉 安幸, 田中 宏幸, 伊藤 誉, 直井 大志, 井上 賢之, 森本 光昭, 安田 是和, 福嶋 敬宜  日本大腸肛門病学会雑誌  68-  (2)  140  -140  2015/02  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  115-  (2)  313  -317  2015/02  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.8) 病理診断にいたるまでのもろもろ
    福嶋 敬宜  内科  115-  (1)  149  -153  2015/01  [Not refereed][Not invited]
  • 病理組織標本作製におけるキシレン代替品の有用性
    福島 愛理, 星野 真紀子, 佐藤 さなえ, 山本 昌代, 小瀬川 順幸, 芳賀 美子, 今田 浩生, 福嶋 敬宜  自治医科大学臨床検査技師年報  (37)  44  -47  2015/01  [Not refereed][Not invited]
     
    病理組織標本作製におけるキシレン代替品の有用性について検討した。通常の標本作製で使用する中間剤として、キシレンとキシレン代替品のクリアプラスを用いた。乳腺など脂肪の多い臓器は細織との親和性が悪く不良ブロックになると懸念されていたが、作製した範囲内では不良ブロックは見られなかった。肝臓ではクリアプラス、キシレンいずれにおいても細網線維が明瞭に見られ、類洞構築も確認できた。肺胞も同様で、いずれにおいても全体的な構築は保たれた。腎動脈は内膜・中膜・外膜の構造が明瞭に区分され、大腸の粘膜構造は保たれ、腺管構造のゆがみは見られなかった。肝Azan染色では線維性結合組織が紫色に染色された。脾臓のAg染色では細網線維を確認でき、キシレン・クリアプラスで明らかな差は見られなかった。糸球体PAS染色では基底膜やメサンギウムが赤紫色に染色され、また周辺の尿細管基底膜も確認できた。
  • MATSUMOTO Yuya, IMADA Hiroki, HOSHINO Makiko, HAGA Yoshiko, FUKUSHIMA Noriyoshi  Japanese Journal of Medical Technology  64-  (4)  468  -474  2015  [Not refereed][Not invited]
     
    Direct fast scarlet 4BS (DFS) is a commonly used staining reagent for amyloid. It stains amyloid relatively specifically, but we sometimes experience insufficient amyloid staining and undesirable positive staining of collagen fiber. To prevent such inappropriate staining, several methods of adding salt to the DFS reagent had been reported so far. In this study, we focused on the types and combinations of salts added to the DFS reagent. We prepared seven types of DFS reagent using the following salts: sodium chloride, sodium carbonate, sodium sulfate, a combination of two out of these three types of salt. The reagent without salt was used as a control. Then, we serially sectioned a paraffin block of liver tissue obtained from an autopsy case of systemic amyloidosis (type AA). The slides were stained with the seven DFS reagents mentioned above. On each slide, staining of amyloid and collagen fiber was evaluated. In the assessment of staining quality, we adopted not only the conventional visual method, but also the quantification of stained color using the CIE 1976 L*a*b* color difference formula. There was neither visual nor numerical difference in amyloid staining among the different types of added salt. However, staining of collagen fiber was significantly reduced in the reagents with sodium carbonate. These results suggest that the addition of sodium carbonate to the DFS reagent could be valuable in reducing undesirable staining while maintaining favorable amyloid staining.
  • Fujiki Yasumaro, Fukushima Noriyoshi, Niki Toshiro, Sugiyama Yukihiko, Yamauchi Hiroyoshi, Sawata Tetsuro, Sata Masafumi, Mato Naoko, Hidano Kiyomi, Matsubara Daisuke, Yamasawa Hideaki, Bando Masashi  The Journal of the Japan Society for Respiratory Endoscopy  37-  (5)  508  -513  2015  [Not refereed][Not invited]
     
    Background. Pulmonary fibrosis of Hermansky-Pudlak syndrome is usually distributed diffusely and symmetrically; asymmetrical progression of pulmonary fibrosis is rarely seen. Case. A 47-year-old man, given a diagnosis of pulmonary fibrosis based on his chest radiograph of February 2010, was admitted in December 2011. On admission, a chest radiograph showed bilateral interstitial infiltrates, and a chest computed tomography image revealed that the distribution of fibrosis had progressively worsened. From childhood, the patient had oculocutaneous albinism, horizontal nystagmus, and bleeding diathesis. Abnormal platelets with empty dense granules were observed by electron microscopy, and those findings led us to diagnose his disease as Hermansky-Pudlak syndrome. Although we treated with N-acetyl cysteine and pirfenidone, dyspnea has worsened. Moreover, ventilation/perfusion lung scintigraphy showed both ventilation and perfusion deficits on the left lung, in addition to progressive left lung dominant fibrosis. Conclusion. We encountered a Hermansky-Pudlak syndrome patient with asymmetrically progressed pulmonary fibrosis.
  • Takaoka Yoshinari, Sanada Yukihiro, Yasuda Yoshikazu, Fukushima Noriyoshi, Isoda Norio, Yamamoto Hironori, Morimoto Naoki, Watanabe Shunji, Hirosawa Takuya, Tsukui Mamiko, Otake Toshiya, Miyata Natsumi, Hujieda Takeshi, Nagamine Nobuhiko  Kanzo  56-  (6)  289  -295  2015  [Not refereed][Not invited]
     
    Hepatic angiomyolipoma (HAML) is a rare hepatic mesenchymal tumor and is composed of a heterogeneous mixture of adipose cells, smooth muscle cells and vessels. HAML is difficulty in distinguishing from other hepatic tumors because of the variety of imaging according to the coustituent. We reported the case of a 22-year old woman presenting a liver tumor with a diameter of 12 cm in left lobe. Liver function was within normal limit and serum surface antigens for hepatitis B and anti-hepatitis C virus antibodies were negative. We suspected that the liver tumor was hepatic adenoma, hemangioma, focal nodular hyperplasia or angiomyoliopoma and the extended left hepatic lobectomy was performed. Histopathologically, the tumor tissue was mainly composed eosinophilic smooth muscle cells, a few blood vessels and adipocytes and was positively stained with HMB-45 by immunohistochemistry. Multiple nodular lesions shown in the resected specimen were stained with HMB-45 and this case was diagnosed multiple HAML.
  • 福嶋 敬宜  内科  115-  (1)  149  -153  2015/01  [Not refereed][Not invited]
  • 肺アスペルギルス症による左気胸の他、多彩な感染症を合併した顕微鏡的多発血管炎の一例
    伊藤 千春, 湯村 和子, 高橋 秀明, 松原 大祐, 福嶋 敬宜, 草野 英二  脈管学  54-  (12)  206  -206  2014/12  [Not refereed][Not invited]
  • パーキンソン病の遺伝子治療 AADC発現の5年間の評価
    小野 さやか, 村松 慎一, 藤本 健一, 斉藤 純一, 佐藤 俊彦, 福嶋 敬宜, 中野 今治  臨床神経学  54-  (Suppl.)  S44  -S44  2014/12  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.7) 大腸SM癌の評価
    福嶋 敬宜  内科  114-  (5)  845  -849  2014/11  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  114-  (5)  845  -849  2014/11  [Not refereed][Not invited]
  • 森澤宏行, 藤原寛行, 伊藤聡史, 郡俊勝, 小柳貴裕, 高橋詳史, 高橋寿々代, 佐藤尚人, 種市明代, 町田静生, 竹井裕二, 嵯峨泰, 福嶋敬宜, 鈴木光明  日本臨床細胞学会雑誌  53-  (Suppl.2)  564  -564  2014/10  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.6) 炎症性腸疾患
    福嶋 敬宜  内科  114-  (4)  683  -687  2014/10  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  114-  (4)  683  -687  2014/10  [Not refereed][Not invited]
  • 山口涼, 真板桜子, 綾部秀範, 小林茂樹, 福嶋敬宜, 浜本知之  日本薬学会関東支部大会講演要旨集  58th-  277  2014/09  [Not refereed][Not invited]
  • 沼尾規且, 牛尾純, 横山健介, 畑中恒, 冨山剛, 玉田喜一, 山本博徳, 斉藤倫寛, 福嶋敬宜  Gastroenterol Endosc  56-  (Supplement 2)  3057  -3057  2014/09  [Not refereed][Not invited]
  • PATHO-Words講座 病理の言葉を読み解こう(Vol.5) 消化管NET(カルチノイド腫瘍) 「oid」はやめよう
    福嶋 敬宜  内科  114-  (3)  503  -507  2014/09  [Not refereed][Not invited]
  • 非小細胞肺がんにおけるクロマチンリモデリング因子(BRG1、BRM、ARID1A、ARID1B、BAF47)の発現異常について(Altered Expressions of Chromatin Remodeling Factors (BRG1, BRM, ARID1A, ARID1B, BAF47) in Non-small Cell Lung Cancer)
    吉本 多一郎, 松原 大祐, 坂谷 貴司, 福嶋 敬宜, 仁木 利郎  日本癌学会総会記事  73回-  P  -1335  2014/09  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.4) 胃粘膜下腫瘍/腫瘤(SMT)の診断
    福嶋 敬宜  内科  114-  (2)  309  -312  2014/08  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  114-  (2)  309  -312  2014/08  [Not refereed][Not invited]
  • PATHO-Words講座 病理の言葉を読み解こう(Vol.3) 胃MALTリンパ腫
    福嶋 敬宜  内科  114-  (1)  141  -145  2014/07  [Not refereed][Not invited]
  • 水疱性類天疱瘡を契機に診断された乳癌の1例
    加藤 昌弘, 坂谷 貴司, 福嶋 敬宜, 甲斐崎 祥一  日本乳癌学会総会プログラム抄録集  22回-  683  -683  2014/07  [Not refereed][Not invited]
  • 福嶋 敬宜  内科  114-  (1)  141  -145  2014/07  [Not refereed][Not invited]
  • 森澤宏行, 藤原寛行, 堀江健司, 有賀治子, 葭葉貴弘, 鈴木達也, 町田静生, 竹井裕二, 嵯峨泰, 福嶋敬宜, 鈴木光明  日本婦人科腫よう学会雑誌  32-  (3)  594  -594  2014/06  [Not refereed][Not invited]
  • PATHO-Words講座 病理のことばを読み解こう(Vol.2) 胃ESD標本 病理像から細胞の動きを読む
    福嶋 敬宜  内科  113-  (5)  927  -931  2014/05  [Not refereed][Not invited]
  • 今田浩生, 福嶋敬宜  病理と臨床  32-  132  -138  2014/04  [Not refereed][Not invited]
  • 福嶋 敬宜  医学のあゆみ  249-  (2)  150  -155  2014/04  [Not refereed][Not invited]
  • 福嶋敬宜  医学のあゆみ  249-  (2)  150  -155  2014/04  [Not refereed][Not invited]
     
    膵管内乳頭粘液性腫瘍(IPMN)は、"粘液産生膵癌"の報告から組織亜型分類まで、多くの知見が日本人研究者からもたらされてきた。IPMNは膵管内での腫瘍上皮の乳頭状発育と粘液の過剰産生を特徴とするが、それぞれの所見や程度はさまざまである。粘液産生に乏しいものもあり、その一部は2010年のWHO分類で膵管内管状乳頭腫瘍(ITPN)として分離された。IPMNの増殖細胞にはその細胞分化に応じたいくつかの亜型があり、病変の主座やその他の臨床病理学的所見との相関もある程度示されてきている。IPMN由来の浸潤癌と膵管癌の鑑別は、画像診断上、また病理診断上もしばしば問題になるが、従来の病理組織学的所見に加え、SMAD4発現の消失やGNAS遺伝子変異の有無が両者の鑑別法として有力な手段となる可能性がある。さらに最近、IPMNの発育進展に間質反応や免疫細胞など周囲環境が関与していることが示されつつあり、治療法開発の面からも注目されてきている。(著者抄録)
  • PATHO-Words講座 病理のことばを読み解こう(Vol.1) 胃生検レポートにこめられた病理医の思い
    福嶋 敬宜  内科  113-  (4)  735  -739  2014/04  [Not refereed][Not invited]
  • 【免疫組織化学 診断と治療選択の指針】 (第2部)腫瘍の鑑別に用いられる抗体(各臓器別) 胆、膵
    今田 浩生, 福嶋 敬宜  病理と臨床  32-  (臨増)  132  -138  2014/04  [Not refereed][Not invited]
  • 吉本多一郎, 村上明子, 大竹俊哉, 坂谷貴司, 福嶋敬宜, 仁木利郎  病理と臨床  32-  (4)  425  -430  2014/04  [Not refereed][Not invited]
  • 今田浩生, 山口岳彦, 仁木利郎, 福嶋敬宜  日本病理学会会誌  103-  (1)  379  -379  2014/03  [Not refereed][Not invited]
  • 齋藤倫寛, 今田浩生, 鈴木司, 坂谷貴司, 福嶋敬宜  日本病理学会会誌  103-  (1)  355  -355  2014/03  [Not refereed][Not invited]
  • 鈴木司, 吉本多一郎, 吉本多一郎, 福嶋敬宜  日本病理学会会誌  103-  (1)  305  -305  2014/03  [Not refereed][Not invited]
  • 川野寿子, 中野智之, 峯岸健太郎, 山本真一, 手塚憲志, 長谷川剛, 遠藤俊輔, 佐久間裕司, 福嶋敬宜  気管支学  36-  (1)  98  -98  2014/01  [Not refereed][Not invited]
  • 高橋 学, 長坂 昌一郎, 小太刀 豪, 若林 徹治, 齋藤 奈緒子, 野口 仁麗, 岡田 健太, 今田 浩生, 福嶋 敬宜, 佐久間 康成, 佐田 尚宏, 石橋 俊  自治医科大学紀要  37-  19  -23  2014  [Not refereed][Not invited]
     
    40歳女性。満月様顔貌,中心性肥満,赤色皮膚線条といったCushing徴候あり,血中ACTH抑制,コルチゾール高値で,左副腎に28mm大の腫瘍を認め,副腎性Cushing症候群と診断された。しかし,アドステロールシンチグラフィで集積なく,また尿中カテコラミンが軽度上昇し,MIBGシンチグラフィで甲状腺右側に有意に集積があり,精査目的で当院紹介となった。シンチグラフィ陰性の原因として副腎癌やblack adenomaが鑑別として考えられた。MIBGシンチグラフィの集積は,甲状腺髄様癌や傍神経節腫瘍は否定的で,腺腫様甲状腺腫による影響と考えられた。当院外科にて腹腔鏡下左副腎摘除術が施行された。腫瘍の割面は暗褐色調を呈し,病理組織所見からblack adenomaと診断された。アドステロールシンチグラフィ陰性で,副腎癌との鑑別を要した副腎black adenomaの症例を経験したので報告する。
  • YOSHIMOTO Taichiro, MATSUBARA Daisuke, SAKATANI Takashi, FUKUSHIMA Noriyoshi, NIKI Toshiro  日本癌学会学術総会抄録集(Web)  73rd-  P-1335 (WEB ONLY)  2014  [Not refereed][Not invited]
  • Kurosaki Fumio, Fukushima Noriyoshi, Tetsuka Kenji, Endo Shunsuke, Sugiyama Yukihiko, Bando Masashi, Shinoda Sachi, Nakayama Masayuki, Mato Naoko, Yamasawa Hideaki, Kawai Akira, Shinozaki Takeshi, Yoshimoto Taichiro  The Journal of the Japan Society for Respiratory Endoscopy  36-  (2)  153  -157  2014  [Not refereed][Not invited]
     
    Background. Solitary fibrous tumor (SFT) is a rare tumor of mesenchymal origin that occurs preferentially in the pleura. When a solitary thoracic nodule is detected in a patient suffering from any type of cancer, it is difficult to determine whether the nodule is a metastatic lesion or a de novo primary thoracic tumor. Case. A 62-year-old man, previously treated for stage IB renal cell carcinoma by nephrectomy, was admitted to our hospital for further examination following detection of a solitary thoracic nodule, which was suspected to be thoracic metastasis. The patient underwent computed tomography (CT)-guided lung biopsy and SFT was subsequently diagnosed, although hemothorax occurred due to intercostal artery laceration. Video-assisted thoracoscopic surgery (VATS) was performed and no recurrence has occurred thus far. Conclusion. When a solitary thoracic nodule is detected in a patient suffering from any type of cancer, SFT should be considered in the differential diagnosis, and surgical resection may be considered as initial treatment if the primary tumor is controlled, no extrathoracic metastases are present, and the patient is in good enough condition to undergo the operation.
  • 川野 寿子, 中野 智之, 峯岸 健太郎, 山本 真一, 手塚 憲志, 長谷川 剛, 遠藤 俊輔, 佐久間 裕司, 福嶋 敬宜  気管支学  36-  (1)  98  -98  2014  [Not refereed][Not invited]
  • 小松原利英, 鯉沼広治, 宮倉安幸, 田中宏幸, 伊藤誉, 直井大志, 直井大志, 井上賢之, 森本光昭, 安田是和, 福嶋敬宜  大腸癌研究会プログラム・抄録集  80th-  87  2014  [Not refereed][Not invited]
  • 村松慎一, 藤本健一, 加藤正哉, 浅利さやか, 水上浩明, 中村優子, 池口邦彦, 川上忠孝, 卜部匡司, 久米晃啓, 福嶋敬宜, 佐藤俊彦, 渡辺英寿, 小澤敬也, 中野今治  機能的脳神経外科  52-  38  -42  2013/12  [Not refereed][Not invited]
     
    Parkinson病に対する遺伝子治療として、L-dopaをドパミンに変換する芳香族アミノ酸脱炭酸酵素(AADC)の遺伝子をアデノ随伴ウイルス(AAV)ベクターで両側の被殻に導入する遺伝子治療の臨床研究を実施した。対象者は51〜68歳の6人で、平均罹患期間は10年間、治療開始時のHoehn & Yahrの重症度はIV度であった。遺伝子導入6ヵ月後の評価では、振戦、筋強剛、動作緩慢などの運動症状の改善が認められた(L-dopaオフ時のUPDRS運動スコアで46%)。また、AADCに結合する[18F]fluoro-L-m-tyrosine(FMT)をトレーサーとして使用したPET計測では治療前より56%集積が増加した。遺伝子導入後3〜5年の長期観察で、2年後より認知機能障害が増悪し運動機能も低下した一人を除く5人で運動症状の改善効果が持続していた。5年後にもPET検査を実施した3人では両側被殻でFMT集積の増加は持続していた。41ヵ月後に急性心不全で亡くなった例の剖検脳で被殻内にAADC陽性細胞を確認した。AADC遺伝子治療は、運動症状の長期改善効果が期待できる。(著者抄録)
  • T. Nagashima, N. Fukushima, S. Minota  Scandinavian journal of rheumatology  42-  510  -511  2013/12  [Not refereed][Not invited]
  • 村松慎一, 藤本健一, 浅利さやか, 中村優子, 池口邦彦, 川上忠孝, 佐藤俊彦, 福嶋敬宜, 中野今治  日本神経学会学術大会プログラム・抄録集  54th-  (12)  415  -1526  2013/12  [Not refereed][Not invited]
  • 田村聖月, 鈴木智子, 郡俊勝, 柳田美樹, 芳賀美子, 山口岳彦, 坂谷貴司, 福嶋敬宜  日本臨床細胞学会雑誌  52-  (Suppl.2)  670  -670  2013/10  [Not refereed][Not invited]
  • 齋藤こよみ, 藤原寛行, 竹井裕二, 町田静生, 嵯峨泰, 種市明代, 吉田智香子, 森澤宏行, 高橋寿々代, 高橋詳史, 伊藤聡史, 鈴木智子, 山口岳彦, 福嶋敬宜, 鈴木光明  日本臨床細胞学会雑誌  52-  (Suppl.2)  536  -536  2013/10  [Not refereed][Not invited]
  • 病理組織標本作製におけるキシレン代替品の有用性
    福島 愛理, 星野 真紀子, 佐藤 さなえ, 山本 昌代, 小瀬川 順幸, 芳賀 美子, 今田 浩生, 福嶋 敬宜  臨床検査栃木  9-  (1)  65  -65  2013/10  [Not refereed][Not invited]
  • Direct fast scarlet 4BS(DFS)染色液によるアミロイド染色法の検討
    松本 祐弥, 星野 真紀子, 佐藤 さなえ, 伊藤 聡史, 菊地 みどり, 芳賀 美子, 今田 浩生, 福嶋 敬宜  臨床検査栃木  9-  (1)  69  -69  2013/10  [Not refereed][Not invited]
  • 齋藤倫寛, 福嶋敬宜  膵・胆道癌Frontier  3-  (2)  98  -101  2013/09  [Not refereed][Not invited]
  • 齋藤 倫寛, 福嶋 敬宜  膵・胆道癌Frontier  3-  (2)  98  -101  2013/09  [Not refereed][Not invited]
  • 牛尾純, 沼尾規且, 畑中恒, 遠藤和洋, 鈴木司, 玉田喜一, 佐田尚宏, 福嶋敬宜, 菅野健太郎  日本消化器画像診断研究会プログラム・抄録集  59th-  22  2013/08  [Not refereed][Not invited]
  • TAGUCHI Masanobu, HYODO Masanobu, MORISHIMA Kazue, SHIMIZU Atsushi, SATA Naohiro, FUKUSHIMA Noriyoshi, YASUDA Yoshikazu  Kanzo  54-  (7)  479  -485  2013/07  [Not refereed][Not invited]
     
    A 50-year-old woman with a liver mass on abdominal ultrasonography was referred for further evaluation. HBs antigen and HCV antibody were negative, but HBs antibody and HBc antibody were positive. Liver function tests were normal. A 24×15 mm low echoic mass was seen in segment 4 of the liver on ultrasonography. Enhanced sonography showed early enhancement with drainage via the hepatic vein. In the Kupffer phase, the tumor appeared as a defect. Abdominal enhanced CT and MRI demonstrated a high-density mass in the arterial phase and wash out in the portal phase. Based on these imaging findings and the possibility of occult HBV, we suspected hepatocellular carcinoma and a segment 4 resection was performed. Histopathologically, perivascular epithelioid cells and a few fat cells were seen. Immunohistochemically, HMB-45, MelanA and αSMA were positive. The tumor was diagnosed as a hepatic angiomyolipoma, which may be difficult to distinguish from hepatocellular carcinoma.
  • 膵Intraductal Papillary Mucinous Neoplasm(IPMN)の手術適応と至適術式 膵切離断端からみた膵IPMN切除術式の検討
    笹沼 英紀, 佐田 尚宏, 兼田 裕司, 石黒 保直, 遠藤 和洋, 小泉 大, 佐久間 康成, 福嶋 敬宜, 安田 是和  日本消化器外科学会総会  68回-  WS  -8  2013/07  [Not refereed][Not invited]
  • FUKUSHIMA NORIYOSHI  画像診断  33-  (8)  857  -867  2013/06  [Not refereed][Not invited]
  • Masanobu Taguchi, Masanobu Hyodo, Kazue Morishima, Atsushi Shimizu, Naohiro Sata, Noriyoshi Fukushima, Yoshikazu Yasuda  Acta Hepatologica Japonica  54-  (7)  479  -485  2013/05  [Not refereed][Not invited]
     
    A 50-year-old woman with a liver mass on abdominal ultrasonography was referred for further evaluation. HBs antigen and HCV antibody were negative, but HBs antibody and HBc antibody were positive. Liver function tests were normal. A 24×15 mm low echoic mass was seen in segment 4 of the liver on ultrasonography. Enhanced sonography showed early enhancement with drainage via the hepatic vein. In the Kupffer phase, the tumor appeared as a defect. Abdominal enhanced CT and MRI demonstrated a high-density mass in the arterial phase and wash out in the portal phase. Based on these imaging findings and the possibility of occult HBV, we suspected hepatocellular carcinoma and a segment 4 resection was performed. Histopathologically, perivascular epithelioid cells and a few fat cells were seen. Immunohistochemically, HMB-45, MelanA and αSMA were positive. The tumor was diagnosed as a hepatic angiomyolipoma, which may be difficult to distinguish from hepatocellular carcinoma. © 2013 The Japan Society of Hepatology.
  • 篠田 沙智, 黒崎 史朗, 坂東 政司, 瀧上 理子, 堂嶽 洋一, 大圃 美穂, 澤田 哲郎, 佐多 将史, 水品 佳子, 開 陽子, 平野 利勝, 水谷 英明, 中山 雅之, 間藤 尚子, 山沢 英明, 河合 陽, 篠崎 健史, 吉本 多一郎, 福嶋 敬宜, 手塚 憲志, 遠藤 俊輔, 杉山 幸比古  気管支学 : 日本気管支研究会雑誌  35-  (3)  349  -350  2013/05  [Not refereed][Not invited]
  • 伊藤聡史, 鈴木智子, 郡俊勝, 柳田美樹, 山口岳彦, 坂谷貴司, 藤原寛行, 福嶋敬宜  日本臨床細胞学会雑誌  52-  (Suppl.1)  264  -264  2013/05  [Not refereed][Not invited]
  • 鈴木智子, 坂谷貴司, 伊藤聡史, 柳田美樹, 郡俊勝, 芳賀美子, 福嶋敬宜  日本臨床細胞学会雑誌  52-  (Suppl.1)  189  -189  2013/05  [Not refereed][Not invited]
  • 福嶋敬宜  日本病理学会会誌  102-  (1)  267  -267  2013/04  [Not refereed][Not invited]
  • 鈴木司, 吉本多一郎, 福嶋敬宜  日本病理学会会誌  102-  (1)  404  -404  2013/04  [Not refereed][Not invited]
  • 今田浩生, 坂谷貴司, 福嶋敬宜  日本病理学会会誌  102-  (1)  392  -392  2013/04  [Not refereed][Not invited]
  • 福嶋敬宜, 田中雅夫, 大塚隆生, 真口宏介, 山雄健次  日本病理学会会誌  102-  (1)  201  2013/04  [Not refereed][Not invited]
  • FUKUSHIMA Noriyoshi  Suizo  28-  (2)  156  -162  2013/04  [Not refereed][Not invited]
     
    In the international consensus guidelines 2012 for the management of IPMN and MCN of the pancreas, six histological aspects are discussed, (1) Types of invasive carcinoma of malignant IPMN, (2) Pathologic definition of minimally invasive carcinoma derived from IPMN, (3) Distinction and clinical relevance of gastric, intestinal, pancreatobiliary, and oncocytic forms of IPMNs, (4) Role of intraoperative frozen section evaluation in the surgical management of IPMNs, (5) Special instructions for specimen processing to differentiate BD-IPMN from MD-IPMN, (6) Distinction of carcinoma derived from and concomitant with an IPMN. According to these, there are two important points. One is a standardization of histopathological criteria of each pathologist, and the other is a standardization of pathological specimen-processing. It is necessary to approach to these aspects by cross-sectional effort.
  • 福嶋 敬宜  膵臓  28-  (2)  156  -162  2013/04  [Not refereed][Not invited]
     
    IPMN/MCN国際診療ガイドライン2012では、病理組織学的事項について、(1)浸潤癌組織型、(2)「微小浸潤癌」、(3)腫瘍組織亜型、(4)術中迅速診断、(5)主膵管型、分枝型の判別と病理学的検索、(6)浸潤性膵管癌とIPMN由来癌の鑑別などの各問題を取り上げ、現時点での推奨内容が述べられている。そして、それぞれにはさらに細かな問題が内在している。一方で、これらを突き詰めて考えると、病理組織学的課題は、組織標本上でどのような基準を用いて評価判定すべきか、ということと、その評価判定の問題を検討するための検体処理や標本作製の問題からなっていることがわかる。とくに検体処理の問題は、ある意味で組織診断基準の設定より標準化の難しい側面であり、今後、病理医のみならず、科横断的な取り組みが必要である。(著者抄録)
  • 膵臓・胆道癌の発癌機構と病理診断の展望 早期膵癌・前駆病変研究における多分野連携の重要性と病理医の役割 国際CAPSサミットからの考察
    福嶋 敬宜, 田中 雅夫, 大塚 隆生, 真口 宏介, 山雄 健次  日本病理学会会誌  102-  (1)  201  -201  2013/04  [Not refereed][Not invited]
  • 西河真美, 市田勝, 上野修市, 苅尾七臣, 弘中貢, 福嶋敬宜  診断と治療  101-  (3)  337  -341  2013/03  [Not refereed][Not invited]
  • V. Adsay, K-T Jang, N. Ohike, J. Albores-Saavedra, P. Argani, N. Fukushima, T. Furukawa, R. Hruban, H. Kijima, D. Klimstra, G. Kloppel, G. Lauwers, A. Ochiai, J. C. Roa, M. Shimizu, B. Terris, G. Zamboni, Y. Zen, T. Tajiri, O. Basturk, B. Saka, N. Dursun, P. Bagci, M. Goodman  MODERN PATHOLOGY  26-  422A  -422A  2013/02  [Not refereed][Not invited]
  • 【外科医必読 膵管内乳頭粘液性腫瘍(IPMN)のすべて】 IPMNの組織亜型(サブタイプ)分類の臨床病理学的意義
    福嶋 敬宜  外科  75-  (2)  122  -128  2013/02  [Not refereed][Not invited]
     
    膵管内乳頭粘液性腫瘍(IPMN)の組織亜型分類は腫瘍組織・細胞の形態や分化方向から腫瘍を細分類するものである.Intestinal type,gastric type,pancreatobiliary type,oncocytic typeの4型に分けられることが多いが,同一症例内に二つ以上の亜型が混在して認められることもある.これらは粘液コア蛋白を検出する免疫組織化学でかなり明瞭に同定することが可能になり,臨床病理学的意義も明らかにされつつある.一方,膵管内腫瘍には粘液産生を示さないものがあり,最新のWHO分類では膵管内管状乳頭腫瘍(ITPN)としてIPMNと並列する概念として位置づけられた.ITPNも含め,組織亜型分類をもとにした分子メカニズムの解明もすすめられており,今後,臨床病理学的位置づけも明確化してくると考えられる.(著者抄録)
  • 福嶋 敬宜  外科  75-  (2)  122  -128  2013/02  [Not refereed][Not invited]
  • FUKUSHIMA Noriyoshi  Suizo  28-  (2)  156  -162  2013  [Not refereed][Not invited]
     
    In the international consensus guidelines 2012 for the management of IPMN and MCN of the pancreas, six histological aspects are discussed, (1) Types of invasive carcinoma of malignant IPMN, (2) Pathologic definition of minimally invasive carcinoma derived from IPMN, (3) Distinction and clinical relevance of gastric, intestinal, pancreatobiliary, and oncocytic forms of IPMNs, (4) Role of intraoperative frozen section evaluation in the surgical management of IPMNs, (5) Special instructions for specimen processing to differentiate BD-IPMN from MD-IPMN, (6) Distinction of carcinoma derived from and concomitant with an IPMN. According to these, there are two important points. One is a standardization of histopathological criteria of each pathologist, and the other is a standardization of pathological specimen-processing. It is necessary to approach to these aspects by cross-sectional effort.
  • 村松慎一, 藤本健一, 浅利さやか, 中村優子, 池口邦彦, 佐藤俊彦, 福嶋敬宜, 中野今治  神経変性疾患に関する調査研究 平成24年度 総括・分担研究報告書  110  -112  2013  [Not refereed][Not invited]
  • 前田恵理子, 赤羽正章, 吉岡直紀, 高尾英正, 松田出, 神谷昂平, 平野健二, 多田稔, 大田洋, 福嶋敬宜, 大友邦  日本消化器癌発生学会総会プログラム・抄録集  24th-  76  2013  [Not refereed][Not invited]
  • 篠田沙智, 黒崎史朗, 坂東政司, 瀧上理子, 堂嶽洋一, 大圃美穂, 澤田哲郎, 佐多将史, 水品佳子, 開陽子, 平野利勝, 水谷英明, 中山雅之, 間藤尚子, 山沢英明, 河合陽, 篠崎健史, 吉本多一郎, 福嶋敬宜, 手塚憲志, 遠藤俊輔, 杉山幸比古  気管支学  35-  (3)  349  -350  2013  [Not refereed][Not invited]
  • 村上明子, 廣澤拓也, 大竹俊哉, 渡邊俊司, 礒田憲夫, 田中亨, 福嶋敬宜, 菅野健太郎  日本内科学会関東支部関東地方会  593rd-  29  -29  2012/12  [Not refereed][Not invited]
  • 福嶋敬宜  胆とすい  33-  (11)  1137  -1140  2012/11  [Not refereed][Not invited]
     
    膵管内乳頭粘液性腫瘍(IPMN)が"粘液産生膵癌"として我が国から最初に報告されて以来、国内では病理・画像相関を含む詳細な検討から多くの知見が蓄積されてきている。これを追うように欧米からのIPMNに関する研究報告も次第に増えていき、結果として、WHO分類は粘液性嚢胞腫瘍(MCT)との区別を明確にした"膵管内乳頭粘液性腫瘍(IPMT)"を採用した。その後、15年以上を経た最近では、ある程度の国際的なコンセンサスは得られてきたといえるが、一部の病変の捉え方や用語には依然として違いがみられる。このような違いは、日本と欧米での腫瘍に関する根本的な考え方の違いやその基になる病理学的検索法の違いなどからきていると考えられる。(著者抄録)
  • 高岡良成, 礒田憲夫, 東澤俊彦, 渡邊俊司, 廣澤拓也, 津久井舞未子, 大竹俊哉, 宮田なつ美, 藤枝毅, 長嶺伸彦, 眞田幸弘, 安田是和, 田中亨, 福嶋敬宜, 菅野健太郎  肝臓  53-  (Supplement 3)  A979  -A979  2012/10  [Not refereed][Not invited]
  • 笹沼英紀, 佐田尚宏, 小泉大, 田口昌延, 森嶋計, 笠原尚哉, 兼田裕司, 三木厚, 佐久間康成, 清水敦, 福嶋敬宜, 安田是和  日本臨床外科学会雑誌  73-  (増刊)  459  -459  2012/10  [Not refereed][Not invited]
  • 中屋孝清, 中山雅之, 草野彩, 大圃美穂, 山内浩義, 小松有, 平野利勝, 間藤尚子, 山沢英明, 坂東政司, 福嶋敬宜, 杉山幸比古  日本サルコイドーシス/肉芽腫性疾患学会雑誌  32-  (1)  153  -159  2012/09  [Not refereed][Not invited]
     
    症例は21歳の時に関節リウマチの既往がある52歳,女性.2007年12月に経気管支肺生検にて器質化肺炎と診断され,ステロイド療法を導入された.以後,肺野の陰影は消失したため,2009年8月にステロイドは中止となった.2010年2月の胸部CTにて縦隔リンパ節腫大,4月から霧視,12月上旬からは心不全に伴う労作時呼吸困難が出現した.2011年1月に入院後,TBLB検体の再評価,心臓超音波,心臓造影MRI,ガリウムシンチグラフィなどの所見より,心サルコイドーシスによる心不全と診断した.プレドニゾロン30mg/日とフロセミド20mg/日を開始後,速やかに心不全による呼吸不全は改善し,縦隔リンパ節腫大の縮小も認めた.器質化肺炎で発症したサルコイドーシスは稀であり,また再燃時の病態が異なることからサルコイドーシスの病態を解明する上で有用であると考えられた.(著者抄録)
  • 種市明代, 藤原寛行, 廣瀬典子, 竹井裕二, 町田静生, 嵯峨泰, 高橋寿々代, 金井信行, 福嶋敬宜, 鈴木光明  日本臨床細胞学会雑誌  51-  (Suppl.2)  794  -794  2012/09  [Not refereed][Not invited]
  • KUROSAKI Fumio, BANDO Masashi, NAKAYAMA Masayuki, YAMASAWA Hideaki, FUKUSHIMA Noriyoshi, SUGIYAMA Yukihiko  日本呼吸器学会誌 = Annals of the Japanese Respiratory Society  1-  (6)  520  -525  2012/09  [Not refereed][Not invited]
     
    症例は55歳、女性。33歳時に肺門リンパ節腫大と間質性肺炎を指摘され、経気管支肺生検にて非乾酪性類上皮細胞肉芽腫を認め、眼病変とあわせてサルコイドーシス(サ症)と診断された。新規の他臓器病変の出現はなく、眼病変は経過観察され、肺病変も進行は認められなかった。48歳時に非ホジキンリンパ腫を発症、約2年の化学療法により完全寛解となった。55歳時に左肺下葉に径20mmほどの結節が出現し、CTガイド下生検にて肺小細胞癌と診断、化学療法で部分寛解が得られたが、肺小細胞癌の診断から約2年で死亡した。サ症の悪性腫瘍合併の報告として悪性リンパ腫または肺癌の報告は散見されるが、両者を合併した報告はまれであり、貴重な症例と考え報告する。(著者抄録)
  • Toru Furukawa, Guenter Kloeppel, Adsay, V, Jorge Albores-Saavedra, Noriyoshi Fukushima, Akira Horii, Ralph H. Hruban, Yo Kato, David S. Klimstra, Daniel S. Longnecker, Jutta Luettges, G. Johan A. Offerhaus, Michio Shimizu, Makoto Sunamura, Arief Suriawinata, Kyoichi Takaori, Suguru Yonezawa  VIRCHOWS ARCHIV  461-  (3)  351  -351  2012/09  [Not refereed][Not invited]
  • 木村 理, 森谷 敏幸, 花田 敬士, 阿部 秀樹, 柳澤 昭夫, 福嶋 敬宜, 大池 信之, 清水 道生, 羽鳥 隆, 藤田 直孝, 真口 宏介, 清水 泰博, 山雄 健次, 佐々木 民人, 内藤 嘉紀, 丹野 誠志, 飛田 浩輔, 田中 雅夫  膵臓 = The Journal of Japan Pancreas Society  27-  (4)  572  -583  2012/08  [Not refereed][Not invited]
  • 副膵管由来と考えられた膵管内乳頭粘液性腫瘍(IPMN)の一例
    伊藤 誉, 高橋 大二郎, 笹沼 英紀, 佐久間 康成, 佐田 尚宏, 安田 是和, 今田 浩生, 福島 敬宜  日本消化器外科学会総会  67回-  2  -2  2012/07  [Not refereed][Not invited]
  • 松本志郎, 佐田尚宏, 伊藤誉, 森本光昭, 遠藤和洋, 小泉大, 安田是和, 福嶋敬宜  すい臓  27-  (3)  431  -431  2012/05  [Not refereed][Not invited]
  • 笹沼英紀, 佐田尚宏, 小泉大, 田口昌延, 森嶋計, 笠原尚哉, 兼田裕司, 三木厚, 遠藤和洋, 佐久間康成, 清水敦, 福嶋敬宜, 安田是和  すい臓  27-  (3)  307  2012/05  [Not refereed][Not invited]
  • 卵巣型間質を伴うMCNの臨床病理学的特徴と予後 日本膵臓学会多施設共同研究から
    山雄 健次, 柳澤 昭夫, 高橋 邦幸, 木村 理, 土井 隆一郎, 福島 敬宜, 大池 信之, 清水 道生, 羽鳥 隆, 信川 文誠, 一二三 倫郎, 小林 祐次, 飛田 浩輔, 丹羽 誠志, 杉山 政則, 宮坂 義浩, 中郡 聡夫, 山口 武人, 花田 敬士, 阿部 秀樹, 多田 稔, 藤田 直孝, 田中 雅夫  膵臓  27-  (3)  365  -365  2012/05  [Not refereed][Not invited]
  • IPMNの画像と手術適応と病理 膵IPMN切除後残膵再発症例の画像および病理学的検討
    笹沼 英紀, 佐田 尚宏, 小泉 大, 田口 昌延, 森嶋 計, 笠原 尚哉, 兼田 裕司, 三木 厚, 遠藤 和洋, 佐久間 康成, 清水 敦, 福嶋 敬宜, 安田 是和  膵臓  27-  (3)  307  -307  2012/05  [Not refereed][Not invited]
  • KIKUCHI Hisashi, NISHINO Hiroshi, SASAMURA Yoshimi, FUKUSHIMA Noriyoshi, ICHIMURA Keiichi  Practica Oto-Rhino-Laryngologica  105-  (5)  489  -494  2012/05  [Not refereed][Not invited]
     
    Recently, partial glossectomy is likely to be chosen for early tongue cancer. In our hospital, we have used the CO2 laser or electrosurgery for this procedure, but post-operative pain was severe and, as a result, oral intake was hampered.
    So as to lessen the postoperative pain, we experimented with a coblation system in partial glossectomy for early tongue cancer and got a good healing course. We would like to report on a case together with the pathological findings. A 34-year-old woman complained of glossal pain. She had a small mass at the right side of the tongue. Biopsy revealed squamous cell carcinoma. Under the clinical diagnosis of a tongue cancer (T1 N0 M0) the patient underwent a partial glossectomy using the coblation system (Evac 70®) under general anesthesia. Postoperative pain was milder than that associated with electrosurgery. The pathological examination revealed that, in descending order, tissue damage was electrosurgery>CO2 laser>coblation system. Partial glossectomy for early tongue cancer using a coblation system seems to be a useful operation for reducing post-operative pain.
  • 鈴木司, 福嶋敬宜  日本病理学会会誌  101-  (1)  270  -270  2012/03  [Not refereed][Not invited]
  • 福嶋敬宜  日本病理学会会誌  101-  (1)  223  2012/03  [Not refereed][Not invited]
  • 福嶋敬宜  日本消化器病学会雑誌  109-  A166  2012/03  [Not refereed][Not invited]
  • 畑中恒, 福嶋敬宜, 間野博行, 菅野健太郎  日本消化器病学会雑誌  109-  (臨増総会)  A218  -A218  2012/03  [Not refereed][Not invited]
  • IPMNの国際診療ガイドラインを巡って IPMNについての日本と欧米での考え方・取扱いの違い 病理の立場から
    福嶋 敬宜  日本消化器病学会雑誌  109-  (臨増総会)  A166  -A166  2012/03  [Not refereed][Not invited]
  • 膵腫瘍を見直す 2010年WHO新分類を踏まえて 新WHO分類の概要
    福嶋 敬宜  日本病理学会会誌  101-  (1)  223  -223  2012/03  [Not refereed][Not invited]
  • 田村聖月, 郡俊勝, 鈴木智子, 久保野幸子, 弘中貢, 川井俊郎, 福嶋敬宜  自治医科大学臨床検査技師年報  (34)  23  -26  2012/03  [Not refereed][Not invited]
     
    81歳男性。健診の胸部レントゲンにて右下肺野における異常陰影を指摘され近医を受診、器質化肺炎として経過観察となったが、陰影の増大を認めたため、精査目的で著者らの施設へ紹介となった。気管支洗浄細胞診で肺腺癌が疑われ、右中葉切除術を施行したところ、病理組織学的に大型核の異型リンパ球が比較的混在した肺MALTomaであることが判明した。術後、化学療法は行われなかったが、現在まで再発はみられていない。
  • FUKUSHIMA Noriyoshi  Nippon Shokakibyo Gakkai Zasshi  109-  (2)  173  -177  2012/02  [Not refereed][Not invited]
     
    膵管内腫瘍は,膵管内に増殖する上皮性腫瘍の総称でありいくつかに亜分類できる.まず,粘液産生の有無と組織構築によって膵管内乳頭粘液性腫瘍(IPMN)と膵管内管状乳頭腫瘍(ITPN)に分けられる.次にIPMNは,腫瘍発生部位や異型度による分類の他,細胞分化をもとにした組織亜型分類が提唱されてきており,WHO分類にも採用されている.それぞれの亜分類は臨床病理学的にもそれらの意義が明らかになりつつあり,病変に応じたきめ細かい診断,治療に向けて,今後ますます重要性が増すと考えられる.
  • 卵巣型間質を伴うMCNの臨床病理学的特徴と予後 日本膵臓学会多施設共同研究から
    山雄 健次, 柳澤 昭夫, 高橋 邦幸, 木村 理, 土井 隆一郎, 福島 敬宜, 大池 信之, 清水 道生, 羽鳥 隆, 信川 文誠, 一二三 倫郎, 小林 祐次, 飛田 浩輔, 丹野 誠志, 杉山 政則, 宮坂 義浩, 中郡 聡夫, 山口 武人, 花田 敬士, 阿部 秀樹, 多田 稔, 藤田 直孝, 田中 雅夫  膵臓  27-  (1)  9  -16  2012/02  [Not refereed][Not invited]
     
    目的:本研究はMCNの臨床病理学的特徴と長期予後について明らかにすることを目的とした。対象と方法:多施設共同、後ろ向き試験で、病理学的に卵巣型間質を有すると判断された膵嚢胞性疾患のみをMCNと定義して集計し、その臨床病理学的所見と長期予後を検討した。成績:156例がMCNと診断され集計された。156例の組織型の内訳は、腺腫129例(82.7%)、非浸潤癌21例(13.4%)、浸潤癌6例(3.9%)であった。平均年齢は48.1歳で、殆どの症例(98.1%)が女性であった。腫瘍は1例を除き全例が体尾部にあり、平均嚢胞径は65.3mmであった。主膵管との交通は18.1%(25/138)に認められた。MCNの術後3年、5年、10年生存率は各々、97.6%、96.6%、96.6%であった。腺腫と腺癌、微少浸潤と(高度)浸潤癌では生存率に有意差を認めた。癌と非癌の間に有意差が認められたのは、嚢胞径と結節の有無であった。(著者抄録)
  • 福嶋 敬宜  日本消化器病学会雑誌  109-  (2)  173  -177  2012/02  [Not refereed][Not invited]
     
    膵管内腫瘍は、膵管内に増殖する上皮性腫瘍の総称でありいくつかに亜分類できる。まず、粘液産生の有無と組織構築によって膵管内乳頭粘液性腫瘍(IPMN)と膵管内管状乳頭腫瘍(ITPN)に分けられる。次にIPMNは、腫瘍発生部位や異型度による分類の他、細胞分化をもとにした組織亜型分類が提唱されてきており、WHO分類にも採用されている。それぞれの亜分類は臨床病理学的にもそれらの意義が明らかになりつつあり、病変に応じたきめ細かい診断、治療に向けて、今後ますます重要性が増すと考えられる。(著者抄録)
  • 前田恵理子, 赤羽正章, 吉岡直紀, 高尾英正, 松田出, 平野賢二, 多田稔, 福嶋敬宜, 大友邦  日本医学放射線学会総会抄録集  71回-  S133  -S133  2012/02  [Not refereed][Not invited]
  • 木村 理, 森谷 敏幸, 花田 敬士, 阿部 秀樹, 柳澤 昭夫, 福嶋 敬宜, 大池 信之, 清水 道生, 羽鳥 隆, 藤田 直孝, 真口 宏介, 清水 泰博, 山雄 健次, 佐々木 民人, 内藤 嘉紀, 丹野 誠志, 飛田 浩輔, 田中 雅夫, 日本膵臓学会膵嚢胞性腫瘍委員会  膵臓  27-  (4)  572  -583  2012  [Not refereed][Not invited]
     
    「背景」膵漿液性嚢胞腫瘍(SCN)は本邦以外では経過観察例の報告がほとんどなく、経過観察例を多数抱える本邦との違いは明白である。SCNに悪性例はどの程度存在するのか、SCNは手術すべき疾患なのかどうか、解決されていないのが現状である。日本膵臓学会によるSCNの全国施設調査を分析することで、SCNの治療指針を考察した。「対象と方法」嚢胞性腫瘍委員会に登録されている施設15施設を対象にSCNに関してアンケート調査を実施した。集積した症例数は172例で経過観察例82例・外科的切除例90例であった。男性50例(29%)・女性122例(71%)、平均年齢は60.8歳、平均観察期間は4.5年であった。「結果」有症状例は20%で腹痛・背部痛・糖尿病の増悪・腫瘤触知・黄疸などであった。腫瘍の存在部位は膵頭部39%・体部35%・尾部22%。平均腫瘍径は4.1cmであった。本腫瘍による死亡例はなかったが、肝転移を2例(1.2%)に認めた。肝転移以外の遠隔転移やリンパ節転移は認めなかった。画像診断においては、切除例中57例(63%)で術前にSCNの診断を得られなかった。SCNの画像診断で最大の特徴である蜂巣状所見はEUS77.5%・MRI63%・CT60%・体外式超音波検査60%・IDUS45%で描出されており、EUSでの描出率が高かった。「結語」確定診断が得られず、診断に迷う場合、圧迫による機能障害を示す症例や腫瘍サイズが大きい場合には外科切除をすべきである。(著者抄録)
  • 浅利さやか, 中村優子, 川上忠孝, 池口邦彦, 佐藤俊彦, 村松慎一, 福嶋敬宜, 藤本健一, 中野今治  パーキンソン病・運動障害疾患コングレスプログラム・抄録集  6th-  84  2012  [Not refereed][Not invited]
  • FUKUSHIMA NORIYOSHI  日本消化器病学会雑誌  109-  (2)  173-177 (J-STAGE)  2012  [Not refereed][Not invited]
  • 小太刀豪, 高橋学, 若林徹治, 高橋仁麗, 齋藤奈緒子, 野牛宏晃, 大須賀淳一, 長坂昌一郎, 今田浩生, 福嶋敬宜, 佐久間康成, 金澤曉太郎, 石橋俊  日本内分泌学会関東甲信越支部学術集会プログラム抄録集  13th-  78  2012  [Not refereed][Not invited]
  • 福嶋敬宜  胆とすい  32-  (12)  1273  -1278  2011/12  [Not refereed][Not invited]
     
    各種癌取扱い規約は、腫瘍の診断・治療における基盤として、また異なる分野の専門家をつなぐ共通言語としても各現場で日常的に使われている。一方、国際的には、WHOの腫瘍組織分類やUICCステージ分類が用いられることが多く、最近では国内の学会・研究会でもその影響力は以前にも増して大きくなり、癌取扱い規約がそれらを追随している部分もある。しかし、腫瘍分類一つを取り上げても、それぞれの見解に相容れないものも散見され、実際にそれらの分類を用いるわれわれがその場その場で使い分けている実情がある。本稿では膵胆管癌の前駆病変、膵胆管内腫瘍、粘液性嚢胞腫瘍、神経内分泌腫瘍などを取り上げ、それぞれの分類間の相違や動向の整理を試みる。腫瘍組織型分類の理想は、それぞれに客観的エビデンスが存在することであるが、人という生物に起こる事象を相手にしている限り、経験則でしかものを言えないことが多いのも事実であろう。日々の診療における事実の蓄積から真に患者に有益なデータが抽出され、今後の分類作りに生かされていくことを願いたい。(著者抄録)
  • 今田浩生, 福嶋敬宜  病理と臨床  29-  (12)  1355  -1358  2011/12  [Not refereed][Not invited]
  • 福嶋敬宜  病理と臨床  29-  (11)  1251  -1254  2011/11  [Not refereed][Not invited]
  • 伊藤誉, 三木厚, 小泉大, 佐田尚宏, 安田是和, 山口岳彦, 坂谷貴司, 福島敬宜  日本臨床外科学会雑誌  72-  869  2011/10  [Not refereed][Not invited]
  • 今田浩生, 福嶋敬宜  病理と臨床  29-  (10)  1131  -1134  2011/10  [Not refereed][Not invited]
  • 飛田野清美, 二階堂貴章, 本望一昌, 山本昌代, 星野真紀子, 芳賀美子, 櫻井達夫, 福嶋敬宜  臨床検査栃木  7-  (1)  41  -41  2011/10  [Not refereed][Not invited]
  • 鈴木孝雄, 大澤博之, 樋之口真, 三浦義正, 新畑博英, 砂田圭二郎, 佐藤博之, 佐藤貴一, 山本博徳, 菅野健太郎, 福嶋敬宜  日本消化器病学会雑誌  108-  (臨増大会)  A822  -A822  2011/09  [Not refereed][Not invited]
  • 今田浩生, 福嶋敬宜  病理と臨床  29-  (9)  987  -990  2011/09  [Not refereed][Not invited]
  • 福嶋敬宜  肝胆膵  63-  (2)  213  -218  2011/08  [Not refereed][Not invited]
  • 長友孝文, 菊池恒, 市村恵一, 坂谷貴司, 福嶋敬宜  口腔・咽頭科  24-  (3)  357  -357  2011/08  [Not refereed][Not invited]
  • 福嶋敬宜  内科  108-  (2)  317  -323  2011/08  [Not refereed][Not invited]
  • 今田浩生, 福嶋敬宜  病理と臨床  29-  (8)  869  -872  2011/08  [Not refereed][Not invited]
  • 大池信之, 伊達博三, 河原正明, 福嶋敬宜  日本臨床  303  -306  2011/07  [Not refereed][Not invited]
  • 【膵臓症候群(第2版)-その他の膵臓疾患を含めて-】 膵腫瘍 膵癌 膵退形成癌
    大池 信之, 伊達 博三, 河原 正明, 福嶋 敬宜  日本臨床  別冊-  (膵臓症候群)  303  -306  2011/07  [Not refereed][Not invited]
  • 肉腫様成分を認めた肝癌4例の検討
    森嶋 計, 俵藤 正信, 小泉 大, 藤原 岳人, 佐久間 康成, 太田 真, 清水 敦, 福嶋 敬宜, 佐田 尚宏, 安田 是和  日本消化器外科学会総会  66回-  738  -738  2011/07  [Not refereed][Not invited]
  • 福嶋敬宜  内科  108-  (1)  137  -143  2011/07  [Not refereed][Not invited]
  • 福嶋敬宜  病理と臨床  29-  (7)  739  -741  2011/07  [Not refereed][Not invited]
  • NAKASONE ETSUKO, BANDO MASASHI, NAKAYA TAKAKIYO, YAMASAWA HIDEAKI, FUKUSHIMA NORIYOSHI, NISHIMURA NAOYUKI, SUNADA KEIJIRO, SUGIYAMA YUKIHIKO  日本胸部臨床  70-  (5)  520  -525  2011/05  [Not refereed][Not invited]
     
    The patient was a 66-year-old man who complained of general malaise and constipation. A mass shadow in the lower lobe of the right lung was detected by chest CT. He was diagnosed with large cell lung cancer by transbronchial lung biopsy. His 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal uptake in the small bowel and the pulmonary mass. Double-balloon enteroscopy (DBE) was performed, and detected multiple ulcers in the small bowel, which pathologically showed large cell carcinoma. We diagnosed small bowel metastasis from large cell lung cancer. This is a rare case that enabled the detection of small bowel metastases from the lung cancer by DBE.
  • 福嶋 敬宜  内科  107-  (5)  917  -921  2011/05  [Not refereed][Not invited]
  • 福嶋敬宜  内科  107-  (5)  917  -921  2011/05  [Not refereed][Not invited]
  • 森嶋計, 佐田尚宏, 横田真一郎, 笠原尚哉, 志村国彦, 小泉大, 藤原岳人, 佐久間康成, 太田真, 清水敦, 俵藤正信, 喜舎場由香, 福嶋敬宜, 安田是和  日本臨床外科学会雑誌  72-  (4)  1087  -1087  2011/04  [Not refereed][Not invited]
  • 福嶋敬宜  病理と臨床  29-  387  2011/04  [Not refereed][Not invited]
  • 福嶋敬宜  病理と臨床  29-  388  -391  2011/04  [Not refereed][Not invited]
  • 【病理診断に役立つ分子生物学】 (第2部)病理診断医になじみのある疾患関連分子 Ras family 解説編
    福嶋 敬宜  病理と臨床  29-  (臨増)  387  -387  2011/04  [Not refereed][Not invited]
  • 【病理診断に役立つ分子生物学】 (第2部)病理診断医になじみのある疾患関連分子 Ras family 診断編
    福嶋 敬宜  病理と臨床  29-  (臨増)  388  -391  2011/04  [Not refereed][Not invited]
  • 福嶋敬宜  日本病理学会会誌  100-  (1)  282  2011/03  [Not refereed][Not invited]
  • 根本大樹, 玉田喜一, 牛尾純, 畑中恒, 冨山剛, 和田伸一, 山口岳彦, 坂谷貴司, 福嶋敬宜, 菅野健太郎  Gastroenterol Endosc  53-  (Supplement 1)  839  -839  2011/03  [Not refereed][Not invited]
  • 【早期膵癌の病態解明】 【早期膵癌の病態解明】
    多田 稔, 江川 新一, 立石 敬介, 福嶋 敬宜  肝・胆・膵  62-  (3)  591  -605  2011/03  [Not refereed][Not invited]
  • 膵腫瘍 新WHO分類の概要と問題点 症例検討を含めて 新WHO分類(膵腫瘍)の問題点と今後の課題
    福嶋 敬宜  日本病理学会会誌  100-  (1)  282  -282  2011/03  [Not refereed][Not invited]
  • FUKUSHIMA NORIYOSHI  肝胆膵  62-  (1)  39  -43  2011/01  [Not refereed][Not invited]
  • 福嶋敬宜  肝胆膵画像  12-  (6)  687  -692  2010/11  [Not refereed][Not invited]
     
    膵の漿液性嚢胞腫瘍(SCN)と粘液性嚢胞腫瘍(MCN)は,膵嚢胞性腫瘍の代表格であるが,女性に多いという共通点以外は,肉眼像(嚢胞の大きさ,嚢胞壁の厚さ,ほか),組織像(腫瘍細胞形態,間質組織の特徴,ほか),分子異常など,その違いは明確である.消化器腫瘍の新WHO分類(2010年発行予定)では,SCNの亜型や悪性例について,MCNでは異型度分類や卵巣様間質の由来に関する言及もなされる.(著者抄録)
  • Mariko Tanaka, Masashi Fukayama, Noriyoshi Fukushima  Pathology Case Reviews  15-  (6)  210  -214  2010/11  [Not refereed][Not invited]
     
    Undifferentiated carcinoma of the pancreas is a rare malignant epithelial neoplasm with a significant component showing no particular differentiation such as keratinization, glandular structure, or mucin production. Clinical recognition of this neoplasm is important because of its poor prognosis with a mean survival of 5 months. The primary diagnostic challenge for surgical pathologists is to distinguish undifferentiated carcinoma from poorly differentiated epithelial, mesenchymal, germ cell, hematopoietic, and other neoplasms. In addition to the morphological characteristics, immunohistochemical analyses are useful for differential diagnosis. In this article, we present a case of undifferentiated carcinoma of the pancreas, followed by a discussion focused on the differential diagnosis of undifferentiated carcinoma, as well as histomorphologic/cytomorphologic, ultrastructural, and immunophenotypic findings helpful for the diagnosis. © 2010 by Lippincott Williams & Wilkins.
  • FUKUSHIMA NORIYOSHI  肝胆膵  61-  (3)  383  -389  2010/09  [Not refereed][Not invited]
  • 田村聖月, 郡俊勝, 鈴木智子, 久保野幸子, 弘中貢, 川井俊郎, 福嶋敬宜  日本臨床細胞学会雑誌  49-  (Suppl.2)  592  -592  2010/09  [Not refereed][Not invited]
  • 種市明代, 藤原寛行, 竹井裕二, 町田静生, 嵯峨泰, 高橋寿々代, 森澤宏行, 仁木利郎, 福嶋敬宜, 鈴木光明  日本臨床細胞学会雑誌  49-  (Suppl.2)  721  -721  2010/09  [Not refereed][Not invited]
  • 福嶋敬宜  胆とすい  31-  (9)  815  -818  2010/09  [Not refereed][Not invited]
     
    胆膵領域の生検・細胞診は、手術適応などの治療方針決定に欠かせないものであるが、患者への侵襲などを考えれば決して満足できる正診率とは言いがたい。また、確定的な診断が難しく"atypical"とされる場合も少なくない。病理・細胞診断が確診に至らない理由には、主に、(1)採取された組織・細胞量の少なさ、(2)中間的病変の存在、(3)非腫瘍性病態でのバリエーションの多彩さ、(4)検体へのアーティファクトなどがあげられ、さらに、(5)きわめて稀な病変である場合や診断者の経験なども影響しえる。これらを改善するためには、臨床サイド、病理サイドの情報交換が何よりも重要である。病変や病態、採取部位に関する情報はもちろんであるが、検体量や標本の状態から観察される像までを情報として共有することで、検査医はより適切な検体採取や検体処理を行えるようになり、一方病理医は必要性に応じて適切な免疫組織化学検査も選択することもできる。胆膵領域の生検・細胞診にも、正診率を上げる余地はまだ残されていると考えられる。(著者抄録)
  • 牛尾純, 玉田喜一, 矢野智則, 畑中恒, 大橋明, 和田伸一, 阿藤一志, 志村国彦, 佐田尚宏, 弘中貢, 福嶋敬宜, 菅野健太郎  日本消化器病学会雑誌  107-  (臨増大会)  A971  -A971  2010/09  [Not refereed][Not invited]
  • 【膵嚢胞性疾患の新展開】 Mucous cystic neoplasm Mucinous cystic neoplasmの定義 ovarian-type stromaとは
    福嶋 敬宜  肝・胆・膵  61-  (3)  383  -389  2010/09  [Not refereed][Not invited]
  • 清水敦, 森嶋計, 佐久間康成, 藤原岳人, 太田真, 志村国彦, 笠原尚哉, 俵藤正信, 仁平芳人, 小泉大, 山下圭輔, 佐田尚宏, 川井俊郎, 福嶋敬宜, 服部照夫, 安田是和  日本肝胆膵外科学会・学術集会プログラム・抄録集  22nd-  333  -333  2010/05  [Not refereed][Not invited]
  • 田中麻理子, 福嶋敬宜  病理と臨床  28-  184  -185  2010/04  [Not refereed][Not invited]
  • 福嶋敬宜  病理と臨床  28-  174  -175  2010/04  [Not refereed][Not invited]
  • 三澤知子, 畑中恒, 牛尾純, 大橋明, 和田伸一, 玉田喜一, 菅野健太郎, 志村国彦, 太田真, 佐田尚宏, 安田是和, 河田浩敏, 山口岳彦, 川井俊郎, 福嶋敬宜  Gastroenterol Endosc  52-  (Supplement 1)  1098  -1098  2010/04  [Not refereed][Not invited]
  • 【病理形態学キーワード】 胆・膵 Intraepithelial neoplasia
    福嶋 敬宜  病理と臨床  28-  (臨増)  174  -175  2010/04  [Not refereed][Not invited]
  • 【病理形態学キーワード】 胆・膵 Microcystic/macrocystic(oligocystic)
    田中 麻理子, 福嶋 敬宜  病理と臨床  28-  (臨増)  184  -185  2010/04  [Not refereed][Not invited]
  • 福嶋敬宜  日本病理学会会誌  99-  (1)  155  2010/03  [Not refereed][Not invited]
  • 山本諭, 風間伸介, 川合一茂, 須並英二, 北山丈二, 名川弘一, 石川俊平, 福嶋敬宜  日本臨床外科学会雑誌  71-  (3)  890  -890  2010/03  [Not refereed][Not invited]
  • 福嶋敬宜  肝胆膵画像  12-  (2)  161  -166  2010/03  [Not refereed][Not invited]
     
    膵癌の早期診断のためには,その早期像,初期像,前駆病変などを解明していくことが必須である.現在膵癌の前駆病変で直系と考えられているのは,膵上皮性腫瘍性病変(PanIN)であるが,膵管内乳頭粘液性腫瘍(IPMN),粘液性嚢胞腫瘍(MCN)も浸潤性腺癌に進展することがあり,前駆病変ととらえることもできる.ほかに比較的以前から膵癌の内分泌細胞発生説があり,また最近ではacinar-to-ductal metaplasiaや膵癌幹細胞の存在が話題になってきている.これらの早期病変を画像でとらえることは必ずしも容易ではないが,実像とともに二次的所見などの理解も画像の読みに役立つ可能性がある.(著者抄録)
  • 膵腫瘍update(新WHO分類に基づく病理診断) 膵腫瘍WHO分類(第4版)の概要と改訂のポイント
    福嶋 敬宜  日本病理学会会誌  99-  (1)  155  -155  2010/03  [Not refereed][Not invited]
  • Yoshinori Hosoya, Takashi Ui, Kentaro Kurashina, Hidenori Haruta, Shin Saito, Toru Zuiki, Masanobu Hyodo, Kiichi Sato, Norihiro Yamamoto, Kentaro Sugano, Michitaka Nagase, Hirohumi Hujii, Chiaki Shibayama, Masanori Nakazawa, kazuhide Misawa, Masahiko Wada, Shin Nunomiya, Yoshihiro Hirabayashi, Hiroshi Nishino, Kunio Miyazaki, Shunji Sarukawa, Noriyoshi Fukushima, Toshiro Niki, Kaichiro Tanba, Naohiro Sata, Hideo Nagai, Yoshikazu Yasuda  Jichi Medical University journal  33-  29  -36  2010  [Not refereed][Not invited]
     
    Jichi Medical University Hospital from 1999 through 2009 were reviewed. Long-term outcome, prognosis, and postoperative complications were analyzed. Multi-modality treatment regimens, including surgery, varied over three time intervals for patients with advanced cancer: 1) 1999-2006, preoperative chemo-radiotherapy: low-dose 5FU (300 mg/m2) and cisplatin (3 mg/m2) days 1-5/three courses with concurrent radiotherapy (40 Gy); 2) 2006-2007, postoperative standard FP chemotherapy: 5FU (800 mg/m2) day 1 and cisplatin (80 mg/m2) days 1-5/two courses; and 3) 2008-2009, preoperative chemotherapy: standard FP/two courses. The 3-year cumulative survival rate was calculated using the Kaplan-Meier method for each stage: Stage 0, 86% (n=25); Stage I, 91% (n=54); Stage II, 79% (n=94); Stage III, 56% (n=106); and Stage IV, 11% (n=38). Postoperative complications included respiratory failure (6%) and anastomotic leakage (4%). The hospital mortality rate was 0.6%. The present multi-modality regimen, with surgery before or after chemotherapy, radiotherapy, or both, is inadequate to improve outcomes for patients with advanced esophageal carcinoma. However, there is a need for advanced staging to develop more effective multidisciplinary treatment regimens.
  • 竹内裕子, 坂谷貴司, 瀬田章, 福嶋敬宜, 深山正久  日本臨床細胞学会雑誌  48-  (Suppl.2)  551  -551  2009/09  [Not refereed][Not invited]
  • 瀬田章, 福嶋敬宜, 竹内裕子, 松田つばさ, 深山正久  日本臨床細胞学会雑誌  48-  418  2009/09  [Not refereed][Not invited]
  • 各領域に於けるLBCの応用と工夫 YM液状喀痰に於けるThinPrep処理の応用と工夫
    瀬田 章, 福嶋 敬宜, 竹内 裕子, 松田 つばさ, 深山 正久  日本臨床細胞学会雑誌  48-  (Suppl.2)  418  -418  2009/09  [Not refereed][Not invited]
  • 山雄健次, 柳澤昭夫, 福嶋敬宜, 大池信之, 清水道生, 土井隆一郎, 高橋邦幸, 木村理  すい臓  24-  (3)  331  -331  2009/06  [Not refereed][Not invited]
  • FUKUSHIMA NORIYOSHI, TANAKA MARIKO, NODA NAOHIRO  肝胆膵  58-  (6)  747  -754  2009/06  [Not refereed][Not invited]
  • 【胆管上皮内腫瘍に関する話題】 胆管内乳頭状腫瘍の病理学的特徴
    福嶋 敬宜, 田中 麻理子, 野田 直宏  肝・胆・膵  58-  (6)  747  -754  2009/06  [Not refereed][Not invited]
  • 【胆管上皮内腫瘍に関する話題】 胆管上皮内腫瘍に関する話題
    全 陽, 福嶋 敬宜, 野田 裕, 近藤 哲  肝・胆・膵  58-  (6)  831  -848  2009/06  [Not refereed][Not invited]
  • 福嶋敬宜  病理と臨床  27-  (6)  518  -524  2009/06  [Not refereed][Not invited]
  • 永井美和子, 甲賀かをり, 平田哲也, 平池修, 藤本晃久, 廣井久彦, 大須賀穣, 矢野哲, 上妻志郎, 武谷雄二, 福嶋敬宜  日本産科婦人科学会関東連合地方部会誌  46-  (2)  206  -206  2009/05  [Not refereed][Not invited]
  • 瀬田章, 福嶋敬宜, 竹内裕子, 松田つばさ, 深山正久  日本臨床細胞学会雑誌  48-  147  2009/03  [Not refereed][Not invited]
  • 坂谷貴司, 福嶋敬宜, 深山正久  日本病理学会会誌  98-  (1)  305  -305  2009/03  [Not refereed][Not invited]
  • 田中麻理子, 福嶋敬宜, 野田直宏, 深山正久  日本病理学会会誌  98-  (1)  384  -384  2009/03  [Not refereed][Not invited]
  • 柴原純二, 福嶋敬宜, 野田直宏, 田中麻理子, 深山正久  日本病理学会会誌  98-  (1)  356  -356  2009/03  [Not refereed][Not invited]
  • 柴原純二, 福嶋敬宜, 野田直宏, 田中麻理子, 深山正久  日本病理学会会誌  98-  (1)  356  -356  2009/03  [Not refereed][Not invited]
  • LBC標本の細胞形態学的検討 従来法との比較を通して ThinPrepを用いた液状喀痰処理の有効性
    瀬田 章, 福嶋 敬宜, 竹内 裕子, 松田 つばさ, 深山 正久  日本臨床細胞学会雑誌  48-  (Suppl.1)  147  -147  2009/03  [Not refereed][Not invited]
  • 肝外胆管癌におけるリンパ転移の臨床病理学的規定因子の検討
    野田 直宏, 福嶋 敬宜, 柴原 純二, 田中 麻理子, 深山 正久  日本病理学会会誌  98-  (1)  380  -380  2009/03  [Not refereed][Not invited]
  • Ralph H. Hruban, Noriyoshi Fukushima, Robb E. Wilentz  Modern Surgical Pathology  1-  867  -901  2009  [Not refereed][Not invited]
  • 石沢武彰, 増田晃一, 田村純人, 青木琢, 長谷川潔, 今村宏, 別宮好文, 國土典宏, 福嶋敬宜, 柴原純二, 深山正久  肝臓  49-  (Suppl.3)  A755  -A755  2008/10  [Not refereed][Not invited]
  • 福嶋敬宜  日本病理学会会誌  97-  (2)  17  -17  2008/09  [Not refereed][Not invited]
  • 松田 つばさ, 福嶋 敬宜, 竹内 裕子, 瀬田 章, 田中 麻理子, 深山 正久  日本臨床細胞学会雑誌  47-  (2)  504  -504  2008/09  [Not refereed][Not invited]
  • 松田つばさ, 福嶋敬宜, 竹内裕子, 瀬田章, 田中麻理子, 深山正久  日本臨床細胞学会雑誌  47-  (Suppl.2)  504  -504  2008/09  [Not refereed][Not invited]
  • 松原三郎, 伊佐山浩通, 小俣政男, 脊山泰治, 今村宏, 國土典宏, 福嶋敬宜, 赤羽正章  胆道  22-  (3)  376  -376  2008/08  [Not refereed][Not invited]
  • TANAKA Masami, SHUKUYA Kenichi, KANNO Nobuko, YOKOTA Hiromitsu, SHIMOSAWA Tatsuo, KIKUCHI Yoshinao, FUKUSHIMA Noriyoshi, YATOMI Yutaka  医学検査  57-  (8)  1063  -1065  2008/08  [Not refereed][Not invited]
     
    症例は78歳男性で、血清クレアチニンの上昇前より尿細管上皮細胞を1〜9/HPFから10〜19/HPFの範囲で認めていた。また、尿細管上皮細胞は約2年間継続的に認められ、核が濃縮状で細胞の表面構造は不規則型顆粒状を呈し、中には細胞の大きさ100μm以上の顆粒円柱型や大型の鋸歯型の特殊型尿細管上皮細胞が観察された。剖検では拡張した尿細管腔を認め、尿沈渣検査と同様の円柱状の尿細管上皮細胞が確認された。尿細管上皮細胞の形態は尿細管腔の状態を反映し、特殊型尿細管上皮細胞の出現は尿細管腔の閉塞、或いは拡張を示唆する所見となる。尿沈渣から得られる細胞の形態所見は、病態解析の新たな付加的情報になると考えられた。
  • 【膵管内乳頭粘液性腫瘍(IPMN)の最新知見】 膵管内乳頭粘液性腫瘍(IPMN)膵上皮内腫瘍性病変(PanIN)および浸潤性膵管癌(IDC)の組織発生
    福嶋 敬宜  外科  70-  (5)  476  -482  2008/05  [Not refereed][Not invited]
     
    膵管内乳頭粘液性腫瘍(IPMN)と浸潤性膵管癌(IDC)は組織発生上の類似性がうかがわれるものの、完成された病変における臨床病理学的特徴には大きな相違がある。IDCの前駆病変と考えられている膵上皮内腫瘍性病変(PanIN)とIPMNの高異型度病変との分子レベルの違いは、SMAD4,MUC1,MUC2などにみられるが、低異型度病変では必ずしもその区別は明確ではない。それぞれの組織発生に関する知見を集積し、分子レベルでの両者の異同を明確にすることが、今後の新たな治療戦略につながるものと考えられる。(著者抄録)
  • 福嶋敬宜  病理と臨床  26-  179  -184  2008/04  [Not refereed][Not invited]
  • 生検標本の読み方 膵臓の生検標本の読み方
    福嶋 敬宜  G.I.Research  16-  (2)  170  -176  2008/04  [Not refereed][Not invited]
  • 【外科病理マニュアル】 各論 膵臓
    福嶋 敬宜  病理と臨床  26-  (臨増)  179  -184  2008/04  [Not refereed][Not invited]
  • 福嶋敬宜  GI Res  16-  (2)  170  -176  2008/04  [Not refereed][Not invited]
  • 野田直宏, 福嶋敬宜, 柴原純二, 深山正久  日本病理学会会誌  97-  (1)  272  -272  2008/03  [Not refereed][Not invited]
  • 金子伸行, 福嶋敬宜, 深山正久  日本病理学会会誌  97-  (1)  283  -283  2008/03  [Not refereed][Not invited]
  • 福嶋敬宜, 深山正久  日本病理学会会誌  97-  (1)  153  2008/03  [Not refereed][Not invited]
  • 福嶋敬宜  日本病理学会会誌  97-  (1)  135  2008/03  [Not refereed][Not invited]
  • 大橋多美, 金子伸行, 福嶋敬宜, 深山正久  日本病理学会会誌  97-  (1)  282  -282  2008/03  [Not refereed][Not invited]
  • 田中麻理子, 福嶋敬宜, 野田直宏, 柴原純二, 深山正久  日本病理学会会誌  97-  (1)  272  -272  2008/03  [Not refereed][Not invited]
  • 胆管・膵管のIPMNと上皮内病変 膵上皮内腫瘍性病変(PanIN)分類と膵管癌の発生
    福嶋 敬宜  日本病理学会会誌  97-  (1)  135  -135  2008/03  [Not refereed][Not invited]
  • 「ワンデイ・パソロジー」の現状と将来展望 保険適応の動向も含めて 病理診断の迅速化が目指すもの
    福嶋 敬宜, 深山 正久  日本病理学会会誌  97-  (1)  153  -153  2008/03  [Not refereed][Not invited]
  • 福嶋敬宜, 菊地良直, 西山尚志, 工藤明, 深山正久  日本病理学会会誌  97-  (1)  252  -252  2008/03  [Not refereed][Not invited]
  • 【自己免疫性膵炎の最近の進展】 Lymphoplasmacytic sclerosing pancreatitis(LPSP)とidiopathic duct-centric chronic pancreatitis(IDCP)からみた自己免疫性膵炎
    福嶋 敬宜, 能登原 憲司  肝・胆・膵  56-  (2)  247  -252  2008/02  [Not refereed][Not invited]
  • 福嶋敬宜  Pharma Med  26-  (1)  13  -16  2008/01  [Not refereed][Not invited]
  • R. H. Hruban, A. Maitra, N. Fukushima  Diseases of the Pancreas: Current Surgical Therapy  497  -511  2008  [Not refereed][Not invited]
     
    A thorough understanding of the pathology of the pancreas is critical to the proper surgical management of patients with pancreatic disease. Some neoplasms of the pancreas are entirely benign and can be managed conservatively, while others are highly lethal malignancies that are best treated by aggressive surgical resection. This chapter provides a broad overview of the pathology of pancreatic neoplasia with emphasis on features important for the surgical management of patients with pancreatic disease. Recent developments in our understanding of pancreatic neoplasia will also be discussed, particularly the growing recognition that a variety of noninvasive precursor lesions can give rise to invasive pancreatic cancer. These noninvasive precursor lesions create an opportunity to cure pancreatic neoplasia before an invasive cancer develops. At the same time they present a significant clinical management problem because there is precious little evidence-based medicine on which to judge when the benefit of removing a precursor lesion outweighs the risks of surgery. In this chapter we will broadly divide our discussion of neoplasms of the pancreas into a description of those with predominantly exocrine differentiation and those with predominantly endocrine differentiation. The discussion of exocrine neoplasms will be further subdivided into those that are cystic and those that are solid. © Springer-Verlag Berlin Heidelberg 2008.
  • 大嶽雄也, 金子伸行, 福嶋敬宜, 深山正久  関東甲信地区医学検査学会講演集  44th-  133  -133  2007/11  [Not refereed][Not invited]
  • 日比康太, 向井清, 土田明彦, 祖父尼淳, 糸井隆夫, 森安史典, 青木達哉, 福嶋敬宜  日本消化器病学会雑誌  104-  (臨増大会)  A742  -A742  2007/09  [Not refereed][Not invited]
  • 平野賢二, 福嶋敬宜, 多田稔, 伊佐山浩通, 八島陽子, 有住俊彦, 外川修, 松原三郎, 中井陽介, 笹平直樹, 辻野武, 川邊隆夫, 深山正久, 小俣政男  日本消化器病学会雑誌  104-  (臨増大会)  A732  -A732  2007/09  [Not refereed][Not invited]
  • HIBI Yasuhiro, FUKUSHIMA Noriyoshi, TSUCHIDA Akihiko, SOFUNI Atsushi, ITOI Takao, MORIYASU Fuminori, MUKAI Kiyoshi, AOKI Tatsuya  Suizo  22-  (4)  519  -520  2007/08  [Not refereed][Not invited]
  • 辻英一, 倉林理恵, 神森眞, 金内一, 小川利久, 三村芳和, 小野稔, 福嶋敬宜, 上西紀夫  日本乳癌学会学術総会プログラム・抄録集  15th-  536  -536  2007/06  [Not refereed][Not invited]
  • 大池信之, 福嶋敬宜  胆とすい  28-  (4)  313  -318  2007/04  [Not refereed][Not invited]
  • 福嶋敬宜, 大池信之  胆とすい  28-  (4)  307  -311  2007/04  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 臨床・病理の良好な関係がもたらすWIN-WIN-WIN
    福嶋 敬宜, 大池 信之  胆と膵  28-  (4)  307  -311  2007/04  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 稀な症例にぶつかった。さて診断はどうする?
    大池 信之, 福嶋 敬宜  胆と膵  28-  (4)  313  -318  2007/04  [Not refereed][Not invited]
  • 瀬田 章, 福嶋 敬宜, 竹内 裕子, 佐藤 孝夫, 角田 千能, 深山 正久  日本臨床細胞学会雑誌  46-  (1)  170  -170  2007/03  [Not refereed][Not invited]
  • 瀬田章, 福嶋敬宜, 竹内裕子, 佐藤孝夫, 角田千能, 深山正久  日本臨床細胞学会雑誌  46-  (Suppl.1)  170  -170  2007/03  [Not refereed][Not invited]
  • 福嶋敬宜  病理と臨床  25-  81  -88  2007/03  [Not refereed][Not invited]
  • 【診断に役立つ免疫組織化学】 各臓器、疾患で用いられる抗体とその応用 胆、膵(内分泌含む)
    福嶋 敬宜  病理と臨床  25-  (臨増)  81  -88  2007/03  [Not refereed][Not invited]
  • 西田裕哉, 北山丈二, 石神浩徳, 秀村晃生, 川崎普司, 武井純子, 甲斐崎祥一, 名川弘一, 山内稚佐子, 福嶋敬宜  日本臨床外科学会雑誌  68-  (2)  503  -503  2007/02  [Not refereed][Not invited]
  • 大池信之, 福嶋敬宜  胆とすい  28-  (2)  143  -148  2007/02  [Not refereed][Not invited]
  • 野田直宏, 福嶋敬宜, 柴原純二, 深山正久  日本病理学会会誌  96-  (1)  273  -273  2007/02  [Not refereed][Not invited]
  • 菱沼美千代, 柴原純二, 山内直子, 太田聡, 福嶋敬宜, 油谷浩幸, 深山正久  日本病理学会会誌  96-  (1)  232  -232  2007/02  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 病理形態を基盤にした研究の展開
    福嶋 敬宜, 大池 信之  胆と膵  28-  (2)  137  -142  2007/02  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 膵癌はどこから発生するか
    大池 信之, 福嶋 敬宜  胆と膵  28-  (2)  143  -148  2007/02  [Not refereed][Not invited]
  • OIKE NOBUYUKI, FUKUSHIMA NORIYOSHI  胆とすい  27-  (12)  943  -949  2006/12  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 初めての症例報告
    福嶋 敬宜, 大池 信之  胆と膵  27-  (12)  935  -942  2006/12  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 百の顔をもつ膵内分泌腫瘍の病理像
    大池 信之, 福嶋 敬宜  胆と膵  27-  (12)  943  -949  2006/12  [Not refereed][Not invited]
  • OIKE NOBUYUKI, FUKUSHIMA NORIYOSHI  胆とすい  27-  (10)  759  -764  2006/10  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 特殊染色はこの目的で行う
    福嶋 敬宜, 大池 信之  胆と膵  27-  (10)  753  -758  2006/10  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 免疫染色の落とし穴 染色して逆に困った!
    大池 信之, 福嶋 敬宜  胆と膵  27-  (10)  759  -764  2006/10  [Not refereed][Not invited]
  • 竹内 裕子, 太田 聡, 瀬田 章, 福嶋 敬宜, 深山 正久  日本臨床細胞学会雑誌  45-  (2)  469  -469  2006/09  [Not refereed][Not invited]
  • 瀬田 章, 福嶋 敬宜, 竹内 裕子, 室田 由里, 宇於 崎宏, 深山 正久  日本臨床細胞学会雑誌  45-  (2)  488  -488  2006/09  [Not refereed][Not invited]
  • 瀬田章, 福嶋敬宜, 竹内裕子, 室田由里, 宇於崎宏, 深山正久  日本臨床細胞学会雑誌  45-  (Suppl.2)  488  -488  2006/09  [Not refereed][Not invited]
  • 竹内裕子, 太田聡, 瀬田章, 福嶋敬宜, 深山正久  日本臨床細胞学会雑誌  45-  (Suppl.2)  469  -469  2006/09  [Not refereed][Not invited]
  • MIYATA Yuki, ITOI Takao, SOFUNI Atsushi, ITOKAWA Fumihide, OSIMA Toshihiro, TUTIYA Takayoshi, KURIHARA Toshio, MORIYASU Fuminori, KASUYA Kazuhiko, FUKUSHIMA Noriyoshi  日本消化器内視鏡学会雑誌 = Gastroenterological endoscopy  48-  (8)  1592  -1597  2006/08  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 顕微鏡観察の前に大切なこと
    福嶋 敬宜, 大池 信之  胆と膵  27-  (8)  571  -576  2006/08  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 胆膵病変の迅速標本はこう読む
    大池 信之, 福嶋 敬宜  胆と膵  27-  (8)  577  -582  2006/08  [Not refereed][Not invited]
  • FUKUSHIMA NORIYOSHI, SHIBAHARA JUNJI  胆とすい  27-  (7)  437  -442  2006/07  [Not refereed][Not invited]
     
    胆道内の乳頭状腫瘍,肝内の嚢胞性腫瘍や粘液産生性腫瘍への関心が高まってきており,それぞれの特徴も少しずつ明らかになりつつある.しかし,これらの病変には,粘液産生,嚢胞状病変,胆管内発育などがさまざまな程度で混在していることが多く,個々の腫瘍の特徴を充分に包括するような広くコンセンサスの得られた定義や分類はまだない.今後,そのような疾患概念の整理にあたり,癌取扱い規約を含む腫瘍分類の多くが,その基盤を病理組織学的な所見に置いていることや,膵臓の粘液産生腫瘍がIPMNとMCNに整理されてきた経緯などは参考になるだろう.もちろん膵臓腫瘍の分類をそのまま適用すればよいというものではなく,それらとの異同を考えながら,腫瘍の本質を大局的に捉える努力をしていかなければならない.また,それと同時に国際的コンセンサス構築の試みも必要と考えられる(著者抄録)
  • ぼくは病理学研究生 診断ときどきリサーチ 病理組織標本はこんなふうに診る
    福嶋 敬宜, 大池 信之  胆と膵  27-  (6)  413  -418  2006/06  [Not refereed][Not invited]
  • ぼくは病理学研究生 診断ときどきリサーチ 胆膵上皮の病理形態変化はこう表現する
    大池 信之, 福嶋 敬宜  胆と膵  27-  (6)  419  -422  2006/06  [Not refereed][Not invited]
  • 病理学各論教育のあり方 参加型臨床実習教育(BSL)の中での病理実習(肉眼および組織)の効果
    清水 道生, 前田 盛, 山田 健人, 田村 浩一, 福嶋 敬宜  日本病理学会会誌  95-  (1)  156  -156  2006/04  [Not refereed][Not invited]
  • 腎細胞癌膵転移切除例の臨床病理学的検討
    山田 薫, 福嶋 敬宜, 森川 鉄平, 牛久 哲男, 深山 正久  日本病理学会会誌  95-  (1)  366  -366  2006/04  [Not refereed][Not invited]
  • 山田薫, 福嶋敬宜, 森川鉄平, 牛久哲男, 深山正久  日本病理学会会誌  95-  (1)  366  2006/03  [Not refereed][Not invited]
  • 栗原俊夫, 糸井隆夫, 中村和人, 祖父尼淳, 糸川文英, 土屋貴愛, 青木貴哉, 宮田祐樹, 森安史典, 福嶋敬宜  消化器画像  8-  (2)  216  -226  2006/03  [Not refereed][Not invited]
  • 栗原 俊夫, 糸井 隆夫, 中村 和人, 祖父尼 淳, 糸川 文英, 土屋 貴愛, 青木 貴哉, 宮田 祐樹, 森安 史典, 福嶋 敬宜  消化器画像  8-  (2)  216  -226  2006/03  [Not refereed][Not invited]
     
    69歳男.5年前に心窩部痛と全身倦怠感の増強を主訴に,近医にて肝胆道系酵素の上昇と腹部エコー・CTで総胆管の拡張・壁肥厚を指摘され初回入院となった.画像所見・胆管生検・胆汁細胞診では悪性所見を認めず,患者がステロイド投与を拒否したため下部胆管にステント留置し,3ヵ月後の第2回入院でも悪性所見は認めなかった.初回入院から約2年後の第3回入院では胆管生検で間質に強い線維化と慢性炎症細胞浸潤を認め,IgG4が高値を示し,画像所見と併せて自己免疫性膵炎による胆管病変と考えステロイド療法を開始した.3週間後の画像所見では上中部胆管の偏側性狭窄は認めるが隆起性病変は改善傾向を示した.初回入院から5年後の画像所見では胆管壁の肥厚・上中部胆管の偏側性狭窄は軽度残存し,現在プレドニゾロン5mg投与で経過観察中である.以上より自己免疫性膵炎と診断した.本症例では胆管病変は異時性・異所性に出現しており,画像と病理学的検討,IgG4による診断が有用であった
  • 福嶋敬宜  Annual Review 消化器  2006-  47  -53  2006/01  [Not refereed][Not invited]
  • N Fukushima, S Ban, M Fukayama, T Furukawa, Y Hibi, Y Kato, T Morohoshi, K Mukai, K Nagata, B Nobukawa, K Notohara, N Ohike, K Suda, S Yonezawa, M Shimizu  LABORATORY INVESTIGATION  86-  272A  -272A  2006/01  [Not refereed][Not invited]
  • N Fukushima, S Ban, M Fukuyama, T Furukawa, Y Hibi, Y Kato, T Morohoshi, K Mukai, K Nagata, B Nobukawa, K Notohara, N Ohike, K Suda, S Yonezawa, M Shimizu  MODERN PATHOLOGY  19-  272A  -272A  2006/01  [Not refereed][Not invited]
  • トピックス 肝・胆・膵 PanIN分類と膵癌の発生
    福嶋 敬宜  Annual Review消化器  2006-  47  -53  2006/01  [Not refereed][Not invited]
  • 膵粘液性嚢胞腺腫(MCA)の1例
    青木 貴哉, 祖父尼 淳, 糸井 隆夫, 土屋 貴愛, 栗原 俊夫, 森安 史典, 小澤 隆, 斉藤 準, 青木 達哉, 山岸 哲也, 河合 隆, 日比 康太, 福嶋 敬宜, 向井 清  Progress of Digestive Endoscopy  67-  (1)  88  -88  2005/06  [Not refereed][Not invited]
  • 膵管癒合不全に合併した膵癌の1例
    土屋 貴愛, 糸井 隆夫, 祖父尼 淳, 栗原 俊夫, 宮田 祐樹, 森安 史典, 粕谷 和彦, 井上 敬一郎, 北村 慶一, 青木 達哉, 福嶋 敬宜, 日比 康太, 向井 清, 河合 隆  Progress of Digestive Endoscopy  67-  (1)  89  -89  2005/06  [Not refereed][Not invited]
  • 土屋貴愛, 糸井隆夫, 祖父尼淳, 小沢隆, 斉藤準, 山岸哲也, 福嶋敬宜, 日比康太, 向井清  消化器画像  7-  (3)  401  -408  2005/05  [Not refereed][Not invited]
  • 福嶋敬宜  臨床検査  49-  (5)  503  -507  2005/05  [Not refereed][Not invited]
  • FUKUSHIMA NORIYOSHI, MUKAI KIYOSHI  癌と化学療法  32-  (5)  599  -604  2005/05  [Not refereed][Not invited]
  • 工藤幸正, 釜本寛之, 杉本勝俊, 目時亮, 小熊一豪, 鈴木史朗, 福嶋敬宜, 向井清, 佐久間正祥  Liver Cancer  11-  (1)  63  -72  2005/05  [Not refereed][Not invited]
  • 【膵癌の診断と治療の進歩】 膵癌の病理像と病理学的評価
    福嶋 敬宜, 向井 清  癌と化学療法  32-  (5)  599  -604  2005/05  [Not refereed][Not invited]
     
    膵管癌は膵腫瘍のなかで最も頻度が高く,一般に境界不明瞭な灰白色〜白色調の硬い結節を形成する.組織学的には中〜高分化型管状腺癌で,強い線維増生を伴っていることが多い.浸潤性膵癌(腺癌)の前駆病変として膵粘液性嚢胞腫瘍(MCNs),膵管内乳頭粘液性腫瘍(IPMNs)と膵上皮内腫瘍性病変(PanINs)が知られている.このなかで分子生物学的知見を根拠にPanINを膵管癌の前駆病変とする考えが広まりつつあるが,まだ膵管癌の発育進展過程が十分に解明されたわけではない.たとえば,概念的には別とされるIPMNと膵管癌,IPMNとPanINの鑑別ですら,病理学的には時に困難である.膵癌の病理学的検索・診断においては,腫瘍病理像に加え組織異型度や進展度の評価が重要である.その結果の解釈に当たっては,検索の方法や診断基準についても注意を払う必要がある(著者抄録)
  • 土屋 貴愛, 糸井 隆夫, 祖父尼 淳, 栗原 俊夫, 大島 敏裕, 宮田 祐樹, 森安 史典, 小澤 隆, 斉藤 準, 池田 隆久, 青木 達哉, 山岸 哲也, 福嶋 敬宜, 日比 康太, 向井 清  消化器画像  7-  (3)  401  -408  2005/05  [Not refereed][Not invited]
     
    37歳男.扁桃腺炎の加療中,膵頭体移行部に経26mm大の低エコー腫瘤を指摘された.腫瘍は充実性成分のみで構成され,膵Solid-pseudopapillary tumor(SPT),乏血性内分泌腫瘍,腺房細胞癌を鑑別診断に挙げ,幽門輪温存膵頭十二指腸切除術を施行し,術後病理診断で膵SPTと診断された.手術に際し,バルーンEndoscopic retrograde pancreatography(ERP)下Multidetector-row CT(MDCT)と,バルーンERP下MDCTから得た情報からのmalti planer reconstruction(MPR)法を試み,主膵管と腫瘍との位置関係を把握することが可能であった.SPTの術前鑑別診断は困難であり,SPTの診断および手術方法の選択にバルーンERP下MDCTおよびMPRは有用と考えられた
  • 【局所療法後,増殖,転移が誘発された症例】 膵頭十二指腸切除後肝転移を来し局所療法などで5年間の治療経過を有する膵腺房細胞癌の1例
    工藤 幸正, 釜本 寛之, 杉本 勝俊, 目時 亮, 小熊 一豪, 鈴木 史朗, 柳沢 京介, 清水 雅文, 宮原 健夫, 横井 正人, 堀部 俊哉, 飯島 尋子, 森安 史典, 福嶋 敬宜, 向井 清, 佐久間 正祥  Liver Cancer  11-  (1)  63  -72  2005/05  [Not refereed][Not invited]
     
    49歳女.2年前に膵頭部腫瘍で幽門輪温存膵頭十二指腸切除術を施行され,病理診断はacinar cell carcinomaであった.肝内転移巣に対し経カテーテル的肝動注化学療法を施行されたが,腫瘍は増大傾向を示した.画像所見で10〜30mmの肝両葉に多発する多血性腫瘍を認め,経カテーテル肝動脈塞栓術を行ったが,術後に肝腫瘍以外の部位に肝膿瘍が発生した.肝動脈内抗生剤注入療法および経皮的膿瘍ドレナージを行い,3ヵ月後に治癒した.肝腫瘍はCRの状態となったが,1年後S4に再発を認め,術前に絶食および抗生剤投与を行った後,ラジオ波熱凝固療法(RFA)を行った.肝膿瘍の合併はなく,寛解が続いたが,1年後に肝左葉外側区に10mm大の再発結節を2ヶ所認めた.同様のRFAを施行したが,その半年後に肝内に多発する結節を認め,絶食および抗生剤投与の上,超選択的TAEを施行した.腫瘍は消失し,肝膿瘍の合併もなかった
  • SUGIMOTO Katsutoshi, METOKI Ryo, YOSHIDA Masahiro, KAMIYAMA Naohisa, IIJIMA Hiroko, MORIYASU Fuminori, FUKUSHIMA Noriyoshi, MUKAI Kiyoshi  Journal of medical ultrasonics = 超音波医学  32-  S393  2005/04  [Not refereed][Not invited]
  • SUGIMOTO Katsutoshi, METOKI Ryo, YOSHIDA Masahiro, KAMIYAMA Naohisa, IIJIMA Hiroko, MORIYASU Fuminori, FUKUSHIMA Noriyoshi, MUKAI Kiyoshi  Japanese journal of medical ultrasonics = 超音波医学  32-  S393  2005/04  [Not refereed][Not invited]
  • 栗原俊夫, 糸井隆夫, 祖父尼淳, 粕谷和彦, 井上敬一郎, 北村慶一, 芹沢博美, 福嶋敬宜, 向井清  Gastroenterol Endosc  47-  (Supplement 1)  845  2005/04  [Not refereed][Not invited]
  • 膵胆管高位合流に合併した胆嚢腺筋症の1例
    栗原 俊夫, 糸井 隆夫, 祖父尼 淳, 大島 敏裕, 土屋 貴愛, 宮田 祐樹, 森安 史典, 粕谷 和彦, 井上 敬一郎, 北村 慶一, 芹沢 博美, 福嶋 敬宜, 向井 清  Gastroenterological Endoscopy  47-  (Suppl.1)  845  -845  2005/04  [Not refereed][Not invited]
  • 片桐 仁子, 福嶋 敬宜, 日比 康太, 青木 達哉, 松林 純, 横山 明子, 三宅 真司, 室井 昭, 向井 清  日本臨床細胞学会雑誌  44-  (1)  222  -222  2005/03  [Not refereed][Not invited]
  • 片桐仁子, 福嶋敬宜, 日比康太, 青木達哉, 松林純, 横山明子, 三宅真司, 室井昭, 向井清  日本臨床細胞学会雑誌  44-  222  2005/03  [Not refereed][Not invited]
  • 膵臓のSolid-pseudopapillary tumor/neoplasmの細胞学的検討
    片桐 仁子, 福嶋 敬宜, 日比 康太, 青木 達哉, 松林 純, 横山 明子, 三宅 真司, 室井 昭, 向井 清  日本臨床細胞学会雑誌  44-  (Suppl.1)  222  -222  2005/03  [Not refereed][Not invited]
  • FUKUSHIMA NORIYOSHI  胆とすい  26-  (2)  99  -104  2005/02  [Not refereed][Not invited]
     
    膵管上皮の形態分類であるpancreatic intraepithelial neoplasia(PanIN)分類(2001年)には,改訂版(2004年)が発表された後も,依然いくつかの問題点や疑問点が指摘されている. 1)膵管上皮の変化のほとんどをneoplasiaと呼んでよいのか?, 2)PanIN-2の診断基準は分かりにくい, 3)PanIN-3とcancerization of the ductsは判別可能か?, 4)PanINと膵管内乳頭粘液性腫瘍(IPMN)の早期像は鑑別可能か?, 5)PanIN分類をIPMNの異型度の表現に使用してよいか?, 6)膵切除断端にPanINが見られた場合は追加切除すべきか, 7)PanIN分類を浸潤性膵管癌の発育進展モデルと考えてよいのか,などが主なものである.これらの事項はPanIN分類の欠陥を突いているともいえるが,むしろPanIN分類に基づく今後の詳細な解析で解明されていくものではないかと考えられる(著者抄録)
  • 土屋貴愛, 糸井隆夫, 祖父尼淳, 栗原俊夫, 粕谷和彦, 井上敬一郎, 福嶋敬宜, 日比康太, 河合隆  Prog Dig Endosc  67-  (1)  89  2005  [Not refereed][Not invited]
  • FUKUSHIMA Noriyoshi, MUKAI Kiyoshi  膵臓 = The Journal of Japan Pancreas Society  19-  (6)  617  -625  2004/12  [Not refereed][Not invited]
  • 【膵癌の早期診断へのアプローチ】 血液,膵液などによる膵癌の分子生物学的診断の可能性
    福嶋 敬宜, 向井 清  膵臓  19-  (6)  617  -625  2004/12  [Not refereed][Not invited]
  • 日比 康太, 福嶋 敬宜, 三宅 真司, 渡部 顕章, 五百部 浩昭, 高橋 俊二, 青木 達哉, 向井 清  日本臨床細胞学会雑誌  43-  (2)  368  -368  2004/09  [Not refereed][Not invited]
  • 日比康太, 福嶋敬宜, 三宅真司, 渡部顕章, 五百部浩昭, 高橋俊二, 青木達哉, 向井清  日本臨床細胞学会雑誌  43-  368  2004/09  [Not refereed][Not invited]
  • 乳癌の浸潤形態とArp2/3複合体の発現
    岩屋 啓一, 及川 恒輔, 堂本 英治, 泉 美貴, 福嶋 敬宜, 長尾 俊孝, 松林 純, 芹沢 博美, 向井 保雄, 望月 眞, 黒田 雅彦, 向井 清  日本癌学会総会記事  63回-  258  -258  2004/09  [Not refereed][Not invited]
  • 膵管内乳頭粘液性腫瘍(IPMT)の細胞診 膵管内乳頭粘液性腫瘍(IPMNs)の細胞像 組織亜型を踏まえた細胞観察の重要性について
    日比 康太, 福嶋 敬宜, 三宅 真司, 渡部 顕章, 五百部 浩昭, 高橋 俊二, 青木 達哉, 向井 清  日本臨床細胞学会雑誌  43-  (Suppl.2)  368  -368  2004/09  [Not refereed][Not invited]
  • 岩屋啓一, 及川恒輔, 堂本英治, 泉美貴, 福嶋敬宜, 長尾俊孝, 松林純, 望月真, 黒田雅彦  日本癌学会総会記事  63rd-  258  2004/08  [Not refereed][Not invited]
  • 福嶋敬宜, 佐藤典宏, GOGGINS M, SOHN T A, YEO C J, HRUBAN R H, 向井清  日本病理学会会誌  93-  (1)  162  2004/05  [Not refereed][Not invited]
  • 膵管内乳頭粘液性腫瘍 膵管内乳頭粘液性腫瘍(IPMNs)由来の浸潤癌の臨床病理と遺伝子発現プロファイリング
    福嶋 敬宜, 佐藤 典宏, Goggins Michael, Sohn Taylor A, Yeo Charles J, Hruban Ralph H, 向井 清  日本病理学会会誌  93-  (1)  162  -162  2004/05  [Not refereed][Not invited]
  • NB Prasad, AV Biankin, N Fukushima, A Maitra, AG Elkahloun, M Goggins, RH Hruban, SD Leach  GASTROENTEROLOGY  126-  (4)  A593  -A593  2004/04  [Not refereed][Not invited]
  • 福嶋 敬宜, 野元 三治  消化器画像  6-  (1)  123  -130  2004/01  [Not refereed][Not invited]
  • 二村聡, 福嶋敬宜  消化器画像  5-  (6)  914  -917  2003/11  [Not refereed][Not invited]
  • 福嶋 敬宜  消化器画像  5-  (6)  909  -913  2003/11  [Not refereed][Not invited]
  • HORINOUCHI Michiko, NAGATA Kohji, NAKAMURA Akiko, GOTO Masamichi, TAKAO Sonshin, SAKAMOTO Michiie, FUKUSHIMA Noriyoshi, MIWA Atsuo, IRIMURA Tatsuro, IMAI Kohzoh, SATO Eiichi, YONEZAWA Suguru  ACTA HISTOCHEMICA ET CYTOCHEMICA  36-  (5)  443  -453  2003/10  [Not refereed][Not invited]
     
    Our previous studies of pancreatic tumors have demonstrated that invasive ductal carcinoma (IDC) usually showed expression of MUC1 (membrane bound type mucin) detected by monoclonal antibody DF3, whereas intraductal papillary-mucinous neoplasm (IPMN) showed no expression of MUC1. In the present study, we examined 50 IDCs, and 63 IPMNs which were morphologically classified into two histological subtypes, "dark cell type" (IPMN-D, 27 cases) and "clear cell type" (IPMN-C, 36 cases). Patients with either type of IPMN showed significantly better survival than those with IDC. To clarify the relationship of the expression patterns of mucins with their biological behavior, we examined the expression profiles of various glycoforms of membrane mucin (MUC1) and secretory mucin (MUC2, MUC5AC and MUC6) in the neoplasms using immunohistochemistry. IDCs showed high expression of all the glycoforms of MUC1 (66%-98%). In contrast, IPMNs-D showed no or low expression of all the glycoforms of MUC1 (0%-4%), while IPMNs-C showed low expression of poorly glycosylated MUC1 (3%-6%), but expression of sialylated MUC1 (41%) and fully glycosylated MUC1 (69%). Expression of MUC2 was negative (0%) in IDC, high (96%) in IPMN-D and low (3%) in IPMN-C. MUC5AC was highly expressed in all types. MUC6 expression was higher in IPMNs-C (92%) than in IDCs (56%) and IPMNs-D (37%). In conclusion, the present study demonstrated that IDCs showed high expression of all the glycoforms of MUC1, and also that two types of IPMNs showed different expression patterns of glycosylated MUC1 as well as MUC2 and MUC6. These different expression patterns of mucins may be related with the malignancy potential of pancreatic neoplasms.
  • 福嶋敬宜  消化器画像  5-  (5)  754  -761  2003/09  [Not refereed][Not invited]
  • 福嶋 敬宜  消化器画像  5-  (5)  754  -761  2003/09  [Not refereed][Not invited]
  • N Fukushima, N Sato, F Sahin, GH Su, RH Hruban, M Goggins  BRITISH JOURNAL OF CANCER  89-  (2)  338  -343  2003/07  [Not refereed][Not invited]
     
    The suppressor of cytokine signalling-1 (SOCS-1) gene is frequently silenced in human hepatocellular carcinoma by aberrant methylation. The aim of this study was to determine if SOCS-1 is inactivated in pancreatic ductal neoplasms, and to investigate if aberrant methylation of this gene affected the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. Aberrant methylation in the CpG island of the SOCS-1 gene was detected in six of 19 (31.6%) human pancreatic cancer cell lines using methylation-specific PCR, and was associated with a loss or reduction of gene expression in five of the six methylated cell lines. Thirteen of 60 pancreatic ductal adenocarcinomas (21.7%) and two of 34 intraductal papillary mucinous neoplasms (IPMNs) (5.9%) had methylated SOCS-1. In contrast, SOCS-1 methylation was not seen in pancreatic normal ductal epithelia (zero out of 15), in pancreatic intraepithelial neoplasia (PanINs) (zero out of 49) or in the IPMNs without infiltrating cancer (zero out of 20). 5-Aza-2'-deoxycytidine treatment of the SOCS-1-methylated pancreatic cancer cell lines led to restoration of SOCS-1 gene expression. Interleukin-6, which has been shown to act through the JAK/STAT pathway to increase cell growth, induced modest time and dose-dependent cell proliferation in a SOCS-1-methylated cell line (PL10, P = 0.015) but not in two unmethylated cell lines. These results indicate that loss of SOCS-1 gene is associated with transcriptional silencing and may have growth-promoting effects, and that its methylation is a useful marker of pancreatic cancer.
  • S Yachida, N Fukushima, Y Nakanishi, T Akasu, H Kitamura, M Sakamoto, T Shimoda  DISEASES OF THE COLON & RECTUM  46-  (6)  826  -831  2003/06  [Not refereed][Not invited]
     
    PURPOSE: We describe a rare case of an alpha-fetoprotein-producing carcinoma originating in the transverse colon of a 59-year-old Japanese male. METHODS: The patient reported an abdominal mass and weight loss. On examination, a tumor of the transverse colon and multiple masses in the liver were found. The serum alpha-fetoprotein level was extremely high (12,873 ng/ml). The patient underwent right hemicolectomy and intraoperative biopsy of a liver mass. RESULTS: Histologically, the colon cancer was composed of three different components: a well-differentiated tubular adenocarcinoma, a tubulopapillary carcinoma consisting of cells with clear cytoplasms, and a "hepatoid carcinoma." The hepatoid carcinoma was composed of large polygonal cells with abundant eosinophilic or clear cytoplasms, arranged in a trabecular or solid pattern, and showing marked vascular invasion. Immunohistochemically, alpha-fetoprotein was strongly expressed, largely in the hepatoid carcinoma and partially in the tubulopapillary carcinoma. The liver biopsy specimen showed morphologic and immunohistochemical features similar to those of the hepatoid carcinoma of the colon and was therefore diagnosed as a metastasis. The patient died of the cancer two months after surgery. CONCLUSION: Based on our experience of this patient and a review of the literature, alpha-fetoprotein-producing colorectal carcinomas are generally associated with a poor prognosis because of the frequent occurrence of blood-borne metastases.
  • 福嶋敬宜  消化器画像  5-  (3)  417  -423  2003/05  [Not refereed][Not invited]
  • 福嶋 敬宜  消化器画像  5-  (3)  417  -423  2003/05  [Not refereed][Not invited]
  • 【膵癌の研究・診療における新たな展開 ゲノム医学の導入】 ゲノム医学に基づく膵癌早期診断への取り組み 米国ジョンズ・ホプキンス大学からのレポート
    福嶋 敬宜  胆と膵  24-  (5)  341  -348  2003/05  [Not refereed][Not invited]
     
    米国での膵癌発症数は年間約30,000人で,人種差はあるものの人口比,切除率,5年生存率などは日本とほぼ同様と見なされる.根治が難しい膵癌の現状における対膵癌戦略の要の1つに早期診断を目指したバイオマーカーの開発がある.異常検出のアプローチとしてDNAレベル,RNAレベル,タンパク質レベルがあるが,DNAマイクロアレイの出現やプロテオミクス技術の開発が膵癌早期診断に向けてのゲノムスケールでの遺伝子発現解析を可能にした.一方,これらの「ゲノム医学の導入」を活かすための研究環境の整備やネットワークの構築なども重要である.ジョンズ・ホプキンス大学の対膵癌チームの戦略はその1つのモデルである
  • 福嶋敬宜  消化器画像  5-  (2)  269  -276  2003/03  [Not refereed][Not invited]
  • 福嶋 敬宜  消化器画像  5-  (2)  269  -276  2003/03  [Not refereed][Not invited]
  • 福嶋敬宜  消化器画像  5-  (1)  119  -125  2003/01  [Not refereed][Not invited]
  • N Fukushima, N Sato, F Sahin, G Su, RH Hruban, M Goggins  MODERN PATHOLOGY  16-  (1)  273A  -273A  2003/01  [Not refereed][Not invited]
  • N Fukushima, N Sato, F Sabin, G Su, RH Hruban, M Goggins  LABORATORY INVESTIGATION  83-  (1)  273A  -273A  2003/01  [Not refereed][Not invited]
  • 福嶋 敬宜  消化器画像  5-  (1)  119  -125  2003/01  [Not refereed][Not invited]
  • S Yachida, N Fukushima, M Sakamoto, Y Matsuno, T Kosuge, S Hirohashi  BRITISH JOURNAL OF SURGERY  89-  (5)  573  -578  2002/05  [Not refereed][Not invited]
     
    Background: The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer. Methods: Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated. Results: One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence. Conclusions: Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.
  • S Jagannath, H Niiyama, M Yeatman, N Fukushima, C Rosty, MI Canto, M Goggins  GASTROENTEROLOGY  122-  (4)  A122  -A122  2002/04  [Not refereed][Not invited]
  • 【膵嚢胞性疾患の取り扱い】 膵管内乳頭腫瘍と膵粘液性嚢胞腫瘍の臨床病理学的特徴と問題点
    福嶋 敬宜  臨床消化器内科  17-  (3)  351  -359  2002/02  [Not refereed][Not invited]
     
    膵管内乳頭腫瘍(IPMN)と膵粘液性嚢胞腫瘍(MCN)とは,形態的に類似している場合があり混同されてきた.ところがMCNの嚢胞壁に卵巣様間質(OS)が存在することが知られるようになり,改めて両者の違いに関心がもたれている.IPMNとMCNの病理学的鑑別には,膵管系との交通やそれに付随する所見の有無,OSの有無などが重要である.IPMN症例の蓄積に伴い,その浸潤癌への関心も高まっている.IPMNと通常の浸潤性膵管癌とは臨床病理学的に異なる疾患概念であるが,両者の発生・発育の違いに関しての分子生物学的説明は必ずしも十分にはなされておらず,形態的にも両者の中間に位置するような浸潤癌が存在する
  • N Fukushima, N Sato, RH Hruban, C Rosty, CJ Yeo, JL Cameron, M Goggins  LABORATORY INVESTIGATION  82-  (1)  285A  -285A  2002/01  [Not refereed][Not invited]
  • N Fukushima, N Sato, RH Hruban, C Rosty, CJ Yeo, JL Cameron, M Goggins  MODERN PATHOLOGY  15-  (1)  285A  -285A  2002/01  [Not refereed][Not invited]
  • N Sato, C Rosty, M Jansen, N Fukushima, T Ueki, CJ Yeo, JL Cameron, CA Iacobuzio-Donahue, RH Hruban, M Goggins  AMERICAN JOURNAL OF PATHOLOGY  159-  (6)  2017  -2022  2001/12  [Not refereed][Not invited]
     
    Despite the growing awareness of intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas among clinicians, the molecular features of IPMNs have not been well characterized. Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartomas as weft as several cancers, including pancreatic adenocarcinoma. Using polymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1 gene, we analyzed DNA from 22 IPMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 of 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lacking features of PJS (7 of 22, 32% overall). Sequencing analysis of the STK11/LKB1 gene in these IPMNs with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS and a somatic mutation in 1 of the 20 sporadic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LKB1 gene. These results suggest that the STK11/LKB1 gene is involved in the pathogenesis of som IPMNs.
  • 税所俊光, 奥坂拓志, 岡田周市, 栗山仁, 島田和明, 山本順司, 山崎晋, 福嶋敬宜, 坂元亨宇  日本消化器病学会雑誌  98-  A625  2001/09  [Not refereed][Not invited]
  • OKUSAKA T, OKADA S, UENO H, IKEDA M, SHIMADA K, YAMAMOTO J, KOSUGE T, YAMASAKI S, FUKUSHIMA N, SAKAMOTO M  膵臓 = The Journal of Japan Pancreas Society  16-  (4)  416  -417  2001/08  [Not refereed][Not invited]
  • N Fukushima, K Mukai, M Sakamoto, T Hasebe, K Shimada, T Kosuge, T Kinoshita, S Hirohashi  VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY  439-  (1)  6  -13  2001/07  [Not refereed][Not invited]
     
    Most intraductal papillary-mucinous carcinomas (IPMCs) of the pancreas are resectable and curable. but some develop into frankly invasive carcinomas. We studied the clinicopathologic features of eight cases of invasive carcinoma derived from IPMC (IC-IPMC) of the pancreas. The patients were aged 54-75 years (mean, 66.6 years); six were male and two were female. The mean tumor size was 7.7 cm (range 5.5-10.5 cm). Two patients without lymph node metastasis had no peripancreatic invasion, and survived longer (115 and 20 months). Three out of four patients with extrapancreatic invasion died of their tumors or developed tumor recurrence within a year. One patient with evidence of liver and lymph node metastasis at the time of first surgery again showed metastatic tumor 21 months later. One patient died of another cause. We also performed a comparative study of the immunohistochemical features of IC-IPMCs in 9 IPMCs (including minimally invasive cases) and 15 ductal adenocarcinomas. CEA cytoplasmic positivity was observed in most of the IC-IPMCs (87.5%) and ductal adenocarcinomas (93.3%), but in only I IPMC (11.1%). The frequency of p53 nuclear staining in ductal adenocarcinoma (73.3%) was higher than in IPMC (33.3%) or IC-IPMC (37.5%). In conclusion, IC-IPMC with extrapancreatic invasion should be treated as ductal carcinoma because of its aggressive behavior after resection. Some IPMCs might progress to invasive carcinoma via pathways that are different from those followed by ductal adenocarcinomas.
  • 【膵管内乳頭腫瘍と粘液性嚢胞腫瘍の鑑別】 膵管内乳頭(粘液性)腫瘍と膵粘液性嚢胞腫瘍の病理学的分類とその鑑別
    福嶋 敬宜, 向井 清  消化器画像  3-  (3)  307  -312  2001/05  [Not refereed][Not invited]
     
    膵の粘液性嚢胞腫瘍(MCN)と膵管内乳頭(粘液性)腫瘍(IPMN)は臨床病理学的に区別されるべき病変である.MCNは嚢胞形成性腫瘍であり,中年女性の膵体尾部に好発する.一方,IPMNは膵管拡張を伴い膵管内を進展増殖する傾向の強い腫瘍で,高齢男性の膵頭部に多い.両者の上皮成分は類似しているが,MCNの殆どには上皮下に"卵巣様間質"が見られ,WHO分類ではこの所見を定義の中に取り入れている.画像診断上の両者の鑑別には,膵管枝との連絡の有無,嚢胞状病変の壁の性状,腫瘍全体の形状などが役立つ
  • N Fukushima, M Sakamoto, S Hirohashi  MODERN PATHOLOGY  14-  (5)  404  -409  2001/05  [Not refereed][Not invited]
     
    The laminin-5-gamma -2 chain is expressed in various invasive carcinoma cells. To clarify the relationship between laminin-5 expression and the development of intraductal papillary-mucinous tumors (IPMTs), we performed an immunohistochemical study of 26 IPMTs and 30 invasive ductal adenocarcinomas, Cases were classified into five groups: intraductal papillary-mucinous adenoma (Group A; n = 8), adenocarcinoma without invasion (Group B; n = 3), adenocarcinoma with minimal invasion (Group C; n = 5), adenocarcinoma with macroscopically evident invasion (Group D; n = 10), and invasive ductal adenocarcinoma (conventional type; Group E; rt = 30). In the invasive components of Groups D and E, laminin-5 was expressed in 80% and 100% of cases, respectively. In the intraductal components of IPMTs, expression of laminin-5 was not seen in Groups A and B, whereas they were seen in one case in Group C (20%) and in seven in Group D (70%). Most of the staining patterns of the intraductal components were focal and scattered. Laminin-5-gamma -2 expression in the intraductal components of IPMTs tends to increase as tumors develop and may be a indicator of the potential invasiveness of the tumor cells.
  • T Okusaka, S Okada, H Ueno, M Ikeda, H Kuriyama, K Shimada, J Yamamota, T Kosuge, S Yamasaki, N Fukushima, M Sakamoto  GASTROENTEROLOGY  120-  (5)  A556  -A556  2001/04  [Not refereed][Not invited]
  • OKUSAKA Takuji, OKADA Shuichi, UENO Hideki, IKEDA Masafumi, SHIMADA Kazuaki, YAMAMOTO Junji, KOSUGE Tomoo, YAMASAKI Susumu, FUKUSHIMA Noriyoshi, SAKAMOTO Michiie  Pancreas  22-  (3)  279  -284  2001/04  [Not refereed][Not invited]
     
    Abdominal and/or back pain is one of the most common symptoms in patients with pancreatic cancer. However, the cause of the pain and the clinicopathologic features of patients with pain have not been fully elucidated. We retrospectively determined the factors related to preoperative abdominal and/or back pain in 95 patients with resectable pancreatic cancer. Pancreatic tumor size, invasion of the intrapancreatic nerves, invasion of the anterior pancreatic capsule, and lymph node metastasis were determined to be variables related to the pain. Pancreatic tumor size, invasion of anterior pancreatic capsule, and lymph node metastasis were also variables significantly correlating to pain intensity. Survival also correlated with pain intensity: the median survival periods were 29 months in patients without pain, 19 months in those with mild pain, and 9 months in those with severe pain who required analgesics. Larger pancreatic tumors, invasion of the intrapancreatic nerves, and invasion of the anterior pancreatic capsule may cause abdominal and/or back pain in patients with resectable pancreatic cancer. This study also suggests clinical implications of the pain intensity as a prognostic factor in patients with resectable pancreatic cancer.
  • 岡田智志, 福嶋敬宜, 長谷川匡, 前沢直樹, 渡部庸一, 豊島壮介, 沢田守男, 松野吉宏, 笠松高弘  日本臨床細胞学会雑誌  40-  191  2001/03  [Not refereed][Not invited]
  • 子宮頸部腺癌初期病変の細胞診断学的検討
    岡田 智志, 福嶋 敬宜, 長谷川 匡, 前沢 直樹, 渡部 庸一, 豊島 壮介, 澤田 守男, 松野 吉宏, 笠松 高弘  日本臨床細胞学会雑誌  40-  (Suppl.1)  191  -191  2001/03  [Not refereed][Not invited]
  • 尾島英知, 長谷川匡, 福嶋敬宜, 坂元亨宇, 松野吉宏, 下田忠和  日本病理学会会誌  90-  (1)  269  -269  2001/03  [Not refereed][Not invited]
  • Noriyoshi Fukushima, Michiie Sakamoto, Kiyoshi Mukai, Yae Kanai, Kazuaki Shimada, Tomoo Kosuge, Setsuo Hirohashi  Human Pathology  32-  (8)  834  -841  2001  [Not refereed][Not invited]
     
    Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P = .002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression. Copyright © 2001 by W.B. Saunders Company.
  • H Furukawa, N Fukushima, K Shimada  AMERICAN JOURNAL OF GASTROENTEROLOGY  95-  (12)  3659  -3660  2000/12  [Not refereed][Not invited]
  • 福嶋敬宜, 向井清  胆とすい  21-  (7)  533  -537  2000/07  [Not refereed][Not invited]
  • 岡田 智志, 津田 均, 長谷川 匡, 前沢 直樹, 當銘 良也, 福嶋 敬宜, 松野 吉宏, 澤田 守男, 笠松 高弘  日本臨床細胞学会雑誌  39-  (1)  87  -87  2000/03  [Not refereed][Not invited]
  • 岡田 智志, 津田 均, 長谷川 匡, 前沢 直樹, 當銘 良也, 福嶋 敬宜, 松野 吉宏, 澤田 守男, 笠松 高弘  日本臨床細胞学会雑誌  39-  (1)  2000/03  [Not refereed][Not invited]
  • 澤田 守男, 恒松 隆一郎, 笠松 高弘, 樋田 一英, 岡田 智志, 長谷川 匡, 津田 均, 福嶋 敬宜, 松野 吉宏  日本臨床細胞学会雑誌  39-  (1)  247  -247  2000/03  [Not refereed][Not invited]
  • 沢田守男, 恒松隆一郎, 笠松高弘, 樋田一英, 岡田智志, 長谷川匡, 津田均, 福嶋敬宜, 松野吉宏  日本臨床細胞学会雑誌  39-  247  2000/03  [Not refereed][Not invited]
  • 岡田智志, 津田均, 長谷川匡, 前沢直樹, 当銘良也, 福嶋敬宜, 松野吉宏, 沢田守男, 笠松高弘  日本臨床細胞学会雑誌  39-  87  2000/03  [Not refereed][Not invited]
  • 福嶋敬宜, 坂元亨宇, 広橋説雄  日本病理学会会誌  89-  (1)  139  2000/03  [Not refereed][Not invited]
  • 澤田 守男, 恒松 隆一郎, 笠松 高弘, 樋田 一英, 岡田 智志, 長谷川 匡, 津田 均, 福嶋 敬宜, 松野 吉宏  日本臨床細胞学会雑誌  39-  (Suppl.1)  247  -247  2000/03  [Not refereed][Not invited]
  • 膵乳頭状粘液産生癌 浸潤性膵管癌における膵管内乳頭状成分の意義
    福嶋 敬宜, 坂元 亨宇, 廣橋 説雄  日本病理学会会誌  89-  (1)  139  -139  2000/03  [Not refereed][Not invited]
  • Hideo Ozaki, Taira Kinoshita, Tomoo Kosuge, Kazuaki Shimada, Junji Yamamoto, Koichi Tokuuye, Noriyoshi Fukushima, Kiyoshi Mukai  International Journal of Pancreatology  27-  (3)  217  -224  2000  [Not refereed][Not invited]
     
    Background. The prognosis of pancreatic adenocarcinoma after radical pancreatectomy is poor, especially in advanced-stage disease. Study Aim. To determine the survival rates and evaluate the effectiveness of multimodality treatment for advanced pancreatic cancer. Methods. From November 1983 to January 1993, 30 patients with pancreatic adenocarcinoma including 9 with carcinoma of the body and tail were treated by a multimodal approach consisting of extended pancreatectomy, intraoperative radiotherapy (IORT), and hepatic artery or portal vein infusion of mitomycin C (MMC) followed by systemic bolus injection. All surviving patients were followed for more than 8 yr and survival rates were calculated by the Kaplan-Meier method. Results. There were no operative or hospital deaths. Eight patients survived for more than 5 yr, 3 of whom survived more than 10 yr. The 5-yr survival rate for 27 patients excluding 3 with metastasis to the liver, peritoneum, or lung was 31%, with a median survival of 31.1 mo. Among them, the 1-, 3-, and 5-yr survival rates for 19 patients with regional nodal metastasis were 95, 50, and 28%, respectively, with a median survival of 36.0 mo. Conclusion. The multimodality treatment combined with IORT and MMC chemotherapy appeared to have a benefit for prognosis of advanced pancreatic adenocarcinoma.
  • Noriyoshi Fukushima, Kiyoshi Mukai  International Journal of Surgical Pathology  8-  (4)  271  -278  2000  [Not refereed][Not invited]
     
    Mucinous cystic tumors (MCTs) and intraductal papillary-mucinous tumors (IPMTs) are often confused with each other. However, clinicopathological studies have shown that these are two distinct entities. In this review, clinicopathological differences and important features for differential diagnosis are presented. MCTs are cyst-forming tumors in the body or tail of the pancreas seen almost exclusively in females. IPMTs show distinct duct ectasia in the pancreatic head with male predominance. Histologically both tumors consist of mucin secreting tall columnar epithelium. MCTs are often accompanied by characteristic "ovarian-type stroma." Recent immunohistochemical and gene analysis have not demonstrated significant differences between two tumor types. These tumors should be clearly separated from ordinary ductal adenocarcinomas of the pancreas as they follow indolent course.
  • FUKUSHIMA NORIYOSHI, MUKAI KIYOSHI  胆とすい  20-  (12)  1077  -1082  1999/12  [Not refereed][Not invited]
  • 【膵粘液性嚢胞腫瘍(MCT)をめぐる新展開】 膵粘液性嚢胞腫瘍の病理診断と問題点 膵管内乳頭腫瘍との鑑別を中心に
    福嶋 敬宜, 向井 清  胆と膵  20-  (12)  1077  -1082  1999/12  [Not refereed][Not invited]
  • H Furukawa, Y Muramatsu, N Fukushima, T Kosuge  AMERICAN JOURNAL OF ROENTGENOLOGY  173-  (4)  1141  -1141  1999/10  [Not refereed][Not invited]
  • Adenoma malignumの細胞学的検討
    當銘 良也, 渡部 庸一, 沼田 正男, 山崎 茂樹, 前沢 直樹, 野本 清明, 福嶋 敬宜, 松野 吉宏, 笠松 高弘, 津田 均  日本臨床細胞学会雑誌  38-  (Suppl.2)  385  -385  1999/09  [Not refereed][Not invited]
  • 肺のLarge cell neuroendocrine carcinomaの細胞学的検討
    沼田 正男, 當銘 良也, 山崎 茂樹, 前沢 直樹, 野本 清明, 大貫 敬司, 渡部 庸一, 福嶋 敬宜, 松野 吉宏  日本臨床細胞学会雑誌  38-  (Suppl.2)  549  -549  1999/09  [Not refereed][Not invited]
  • 當銘 良也, 渡部 庸一, 沼田 正男, 山崎 茂樹, 前沢 直樹, 野本 清明, 福嶋 敬宜, 松野 吉宏, 笠松 高弘, 津田 均  日本臨床細胞学会雑誌  38-  (2)  385  -385  1999/09  [Not refereed][Not invited]
  • 沼田 正男, 當銘 良也, 山崎 茂樹, 前沢 直樹, 野本 清明, 大貫 敬司, 渡部 庸一, 福嶋 敬宜, 松野 吉宏  日本臨床細胞学会雑誌  38-  (2)  549  -549  1999/09  [Not refereed][Not invited]
  • 子宮頸部Minimal Deviation Adenocarcinomaにおける治療前診断の臨床病理学的検討
    笠松 高弘, 澤田 守男, 樋田 一英, 山田 拓郎, 恒松 隆一郎, 近江 和夫, 福嶋 敬宜, 林 勇, 長谷川 匡, 津田 均  日本婦人科腫瘍学会雑誌  17-  (1)  35  -35  1999/06  [Not refereed][Not invited]
  • 乳癌の子宮頸部転移の1例
    澤田 守男, 笠松 高弘, 樋田 一英, 山田 拓郎, 恒松 隆一郎, 近江 和夫, 長谷川 匡, 津田 均, 福嶋 敬宜, 松野 吉宏  日本婦人科腫瘍学会雑誌  17-  (1)  59  -59  1999/06  [Not refereed][Not invited]
  • N Fukushima, K Mukai  ADVANCES IN ANATOMIC PATHOLOGY  6-  (2)  65  -77  1999/03  [Not refereed][Not invited]
     
    The clinicopathologic features and problems in classification and diagnosis of the pancreatic neoplasms with abundant mucus production are presented. In this article, the various reported concepts and terminology of these mucus-producing pancreatic tumors are summarized, and the differences between intraductal papillary-mucinous tumors and mucinous cystic tumors are specifically discussed. Intraductal papillary-mucinous tumors show diffuse or segmental dilatation of the pancreatic ducts with intraductal papillary growth. Mucinous cystic tumors are mucus-producing tumors showing cyst formation, which is often accompanied by intracystic papillary projections and "ovarian-type" stroma. Intraductal papillary-mucinous tumors occur most often in the pancreatic Plead of elderly men, whereas mucinous cystic tumors typically occur in the pancreatic tail or body of middle-aged women. Histologically, these tumors show a wide cytologic spectrum from benign to borderline to malignant. These tumors pursue an indolent clinical course compared with conventional ductal carcinoma of the pancreas. Mucinous cystadenocarcinomas have a higher malignant potential than intraductal papillary-mucinous adenocarcinomas, yet these turners recur infrequently if they are excised completely. Because of the differences in clinicopathologic features, these tumors should be clearly separated from conventional ductal carcinoma of the pancreas.
  • 【浸潤性膵管内乳頭腺癌の病理・臨床と予後】 膵管内乳頭腺癌の膵管外進展機序 他臓器穿破機序も含めて
    福嶋 敬宜, 向井 清  胆と膵  20-  (1)  17  -20  1999/01  [Not refereed][Not invited]
  • 子宮頸部細胞診で上皮内腺癌(Adenocarcinoma in situ)を疑った症例
    澤田 守男, 笠松 高弘, 樋田 一英, 山田 拓郎, 種村 健二郎, 恒松 隆一郎, 近江 和夫, 福嶋 敬宜, 松野 吉宏, 長谷川 匡, 津田 均  日本産科婦人科学会東京地方部会会誌  47-  (4)  442  -445  1998/12  [Not refereed][Not invited]
  • SAWADA MORIO, KASAMATSU TAKAHIRO, HIDA KAZUHIDE, YAMADA TAKURO, OUMI KAZUO, FUKUSHIMA NORIYOSHI, MATSUNO YOSHIHIRO, HASEGAWA TADASHI, TSUDA HITOSHI  日本産科婦人科学会東京地方部会会誌  47-  (4)  442  -445  1998/12  [Not refereed][Not invited]
  • 転移再発を示しながらも,手術治療にて13年生存し得た肝原発カルチノイドの1例
    佐藤 弘, 坂元 亨宇, 中西 幸浩, 福嶋 敬宜, 山本 順司, 島田 和明, 小菅 智男, 山崎 晋  Liver Cancer  4-  (2)  152  -156  1998/10  [Not refereed][Not invited]
     
    脾転移を認める等,経過が肝細胞癌としては非典型的であるために,再検討し肝原発カルチノイドと診断された症例.本症例のように転移再発に対しても,積極的に切除することにより,長期生存が期待できる症例もある
  • 石井 浩, 福嶋 敬宜  Chiba medical journal  74-  (4)  330  -330  1998/08
  • 石井 浩, 福嶋 敬宜  千葉医学雑誌  74-  (4)  330  -330  1998/08  [Not refereed][Not invited]
  • MIYAMOTO Shin'ichi, SATO Atsushi, MUKAI Kiyoshi, FUKUSHIMA Noriyoshi  Med Imaging Technol  16-  (4)  485  -486  1998/07  [Not refereed][Not invited]
  • MIYAMOTO SHIN'ICHI, SATO ATSUSHI, MUKAI KIYOSHI, FUKUSHIMA NORIYOSHI  画像センシングシンポジウム講演論文集  4th-  151  -156  1998/06  [Not refereed][Not invited]
  • 福嶋 敬宜  日本臨床細胞学会雑誌  37-  (1)  224  -224  1998/03  [Not refereed][Not invited]
  • 日吾 雅宜, 渡部 庸一, 沼田 正男, 福嶋 敬宜, 島村 香也子, 松野 吉宏  日本臨床細胞学会雑誌  37-  (1)  191  -191  1998/03  [Not refereed][Not invited]
  • 福嶋 敬宜, 沼田 正男, 渡部 庸一, 日吾 雅宜, 島村 香也子  日本臨床細胞学会雑誌  37-  (1)  1998/03  [Not refereed][Not invited]
  • 松野 吉宏, 柴田 雅彦, 長谷川 達朗, 渡部 庸一, 福嶋 敬宜, 島村 香也子  日本臨床細胞学会雑誌  37-  (1)  270  -270  1998/03  [Not refereed][Not invited]
  • Miyamoto Shin-ichi, Sato Atsushi, Mukai Kiyoshi, Fukushima Noriyoshi  Proceedings of the IEICE General Conference  1998-  (2)  282  -282  1998/03  [Not refereed][Not invited]
  • 膵管内乳頭腺癌由来の浸潤癌
    福嶋 敬宜  日本病理学会会誌  87-  (1)  497  -497  1998/03  [Not refereed][Not invited]
  • Noriyoshi Fukushima  Pathology International  48-  (1)  33  -40  1998  [Not refereed][Not invited]
     
    To develop an objective reference for the cytological evaluation of atypical cells in bile and pancreatic juice, we analyzed K-ras oncogene mutation In atypical cell clusters, which were collected directly from cytological smear slides 50 samples (cell clusters) from 31 smear slides of 21 patients with carcinomas of the pancreatic head region, and nine samples from eight cases of benign disease. These cell clusters (5-1000 cells/cluster) were selectively suspended in buffer containing proteinase K, and subjected to DNA extraction. K-ras codon 12 mutation was determined by polymerase chain reaction amplification, followed by digestion with BstNI. The K-ras gene was amplified in 20 of 21 cases with carcinoma (34/50 samples), and in seven of eight cases with non-neoplastic disease (8/9 samples). Among the cases of which primary tumors showed K-ras mutation, amplification was successful in 10 of 11 cases mutation was demonstrated in three of seven cases with cytologically atypical cells (4/11 samples), and in three of three cases with cytologically malignant cells (5/7 samples). No mutation was identified in the 10 cases of carcinoma without K-ras mutation (0/15 samples), or in eight cases of non-neoplastic disease (0/8 samples). Cytological details could be comparatively evaluated between atypical cell clusters with or without mutation on the same smear slides in two cases. This type of direct analysis of atypical cell clusters may be useful in the self-assessment of cytological diagnosis of bile and pancreatic juice.
  • FUKUSHIMA Noriyoshi, SUZUKI Miwako, FUKAYAMA Masashi  Pathology International  48-  (1)  33  -40  1998/01  [Not refereed][Not invited]
     
    To develop an objective reference for the cytological evaluation of atypical cells in bile and pancreatic juice, we analyzed K-ras oncogene mutation in atypical cell clusters, which were collected directly from cytological smear slides; 50 samples (cell clusters) from 31 smear slides of 21 patients with carcinomas of the pancreatic head region, and nine samples from eight cases of benign disease. These cell clusters (5-1000 cells/cluster) were selectively suspended in buffer containing proteinase K, and subjected to DNA extraction. K-ras codon 12 mutation was determined by polymerase chain reaction amplification, followed by digestion with BstNI. The K-ras gene was amplified in 20 of 21 cases with carcinoma (34/50 samples), and in seven of eight cases with non-neoplastic disease (8/9 samples). Among the cases of which primary tumors showed K-ras mutation, amplification was successful in 10 of 11 cases; mutation was demonstrated in three of seven cases with cytologically atypical cells (4/11 samples), and in three of three cases with cytologically malignant cells (5/7 samples). No mutation was identified in the 10 cases of carcinoma without K-ras mutation (0/15 samples), or in eight cases of non-neoplastic disease (0/8 samples). Cytological details could be comparatively evaluated between atypical cell clusters with or without mutation on the same smear slides in two cases. This type of direct analysis of atypical cell clusters may be useful in the self-assessment of cytological diagnosis of bile and pancreatic juice.
  • FUKUSHIMA Noriyoshi, MUKAI Kiyoshi  Pathology International  47-  (11)  806  -808  1997/11  [Not refereed][Not invited]
     
    'Ovarian-type' stroma of nine mucinous cystic tumors (MCT) of the pancreas, six cystadenomas and three cystadeno-carcinomas, were studied immunohistochemically. Most of the spindle cells of the 'ovarian-type' stroma were positive for smooth muscle actin and desmin, but were negative for S- 100 protein, cytochrome P450 19 and CD34. Similar stroma with smooth muscle differentiation has been described In hepatobiliary MCT. Embryologic similarity between the pancreas and liver suggests a closely related origin of MCT in both organs.
  • N Fukushima, K Mukai, Y Kanai, T Hasebe, K Shimada, H Ozaki, T Kinoshita, T Kosuge  HUMAN PATHOLOGY  28-  (9)  1010  -1017  1997/09  [Not refereed][Not invited]
     
    Clinicopathological features of 28 patients with intraductal papillary tumor (IDPT) and 10 patients with mucinous cystic tumor (MCT) of the pancreas were studied. Both IDPT and MCT showed papillary projections of the epithelium with abundant mucus secretion in the ectatic ducts or cystic spaces. The patients with IDPT comprised 19 men and 9 women with a mean age of 64.9 years. Three fourths of the IDPTs were located in the pancreatic head, and the mean tumor size was 3.5 cm. Local recurrence was observed in one patient, but none died of IDPT. In contrast, all patients with MCT were women, with a mean age of 49.4 years. None of the MCTs arose in the head, and the mean tumor size was 7.1 cm. One patient died of MCT, but all of the others survived without recurrence. Eight IDPTs and three MCTs showed invasion into the surrounding pancreatic tissue. Muconodular infiltration was mainly observed in five IDPTs and one MCTs and tubular infiltration in three IDPTs and two MCTs. A characteristic histological finding associated with the muconodular infiltration in IDPT was subepithelial ''mucin droplets'' that appeared to represent a change in polarity of mucus secretion. The formation of such subepithelial ''mucin droplets'' may be the initial step of muconodular infiltration in IDPT. Muconodular infiltration in IDPT appears different morphologically and biologically from the mucinous carcinoma subtype of conventional invasive ductal carcinoma. Copyright (C) 1997 by W.B. Saunders Company.
  • FUKUSHIMA Noriyoshi, SHINBATA Hiroyuki, HASEBE Takahiro, YOKOSE Tomoyuki, SATO Atsushi, MUKAI Kiyoshi  Japanese journal of cancer research : gann  88-  (3)  328  -333  1997/03  [Not refereed][Not invited]
     
    We studied whether a computer-assisted system using a combination of data collection by image analysis and analysis by neural networks can differentiate benign and malignant breast lesions. Forty-six intraductal lesions of the breast were studied by pathologists and by the computer-assisted system. Histological evaluation was performed independently by three pathologists, and the lesions were classified into pathologically malignant (n = 12), undetermined (n = 13), and benign (n = 21). Computerized nuclear image analysis was performed using the CAS200 (Cell Analysis Systems, Elmhurst, IL) system to obtain data on nuclear morphometric and textural features. A neural network was constructed using the morphometric and texture data obtained from teaching cases of malignant and benign lesions. Then data for unknown cases were classified by the constructed neural network into neural network-malignant (n = 11), -undetermined (n = 5), and -benign (n = 30). The agreement rate between the diagnosis by pathologists and judgement by the computer-assisted system was 75%, excluding pathologically undetermined lesions. There were four false-negative but no false-positive results. False-negative cases had nuclei that were quite different from those of the teaching cases. The agreement rate obtained using either morphometric data or texture data only was lower than that using a combination of both. Selection of appropriate teaching data and incorporation of both morphometric and textural parameters seemed important for obtaining more accurate results. The present data suggest that development of a computer-assisted histopathological diagnosis system for practical use may be possible.
  • Noriyoshi Fukushima, Hiroyuki Shinbata, Takahiro Hasebe, Tomoyuki Yokose, Atsushi Sato, Kiyoshi Mukai  Japanese Journal of Cancer Research  88-  (3)  328  -333  1997  [Not refereed][Not invited]
     
    We studied whether a computer-assisted system using a combination of data collection by image analysis and analysis by neural networks can differentiate benign and malignant breast lesions. Forty-six intraductal lesions of the breast were studied by pathologists and by the computer-assisted system. Histological evaluation was performed independently by three pathologists, and the lesions were classified into pathologically malignant (n = 12), undetermined (n = 13), and benign (n = 21). Computerized nuclear image analysis was performed using the CAS200 (Cell Analysis Systems, Elmhurst, IL) system to obtain data on nuclear morphometric and textural features. A neural network was constructed using the morphometric and texture data obtained from teaching cases of malignant and benign lesions. Then data for unknown cases were classified by the constructed neural network into neural network-malignant (n = 11), -undetermined (n = 5), and -benign (n = 30). The agreement rate between the diagnosis by pathologists and judgement by the computer-assisted system was 75%, excluding pathologically undetermined lesions. There were four false-negative but no false-positive results. False-negative cases had nuclei that were quite different from those of the teaching cases. The agreement rate obtained using either morphometric data or texture data only was lower than that using a combination of both. Selection of appropriate teaching data and incorporation of both morphometric and textural parameters seemed important for obtaining more accurate results, The present data suggest that development of a computer-assisted histopathological diagnosis system for practical use may be possible.
  • Noriyoshi Fukushima, Miwako Suzuki, Tetsuo Abe, Masashi Fukayama  Virchows Archiv  431-  (3)  219  -224  1997  [Not refereed][Not invited]
     
    Inflammatory pseudotumour of the common bile duct (CBD) is extremely rare. A 58-year-old Japanese female without choledocolithiasis underwent pancreatico-duodenectomy for constriction of the middle lower region of the CBD. A submucosal tumour protruding into the CBD, was histologically inflammatory consisting of fibroblastic cells, collagen fibres and myxoid stroma with chronic inflammatory cells. This lesion was surrounded by an irregular fibrosclerosing lesion with obliterative phlebitis which involved the neighbouring pancreas and lymph nodes. Clonal analysis of the tumour by polymerase chain reaction analysis of X chromosome inactivation patterns, confirmed the polyclonal nature of the lesion. Immunohistochemically, the fibroblastic cells in both lesions had the same phenotype [vimentin (+), desmin (-), muscle-specific actin (-) and CD34 (+)] suggesting that these lesions with different histological features represent zonation of the same inflammatory process. The outer lesion extended irregularly into adjacent pancreatic tissue and lymph nodes. This fact made it difficult to differentiate this from a malignant lesion, even if frozen sections contained no atypical cells.
  • 画像解析と人工知能による乳管内増殖性病変の良悪性判定
    福嶋 敬宜  日本癌学会総会記事  55回-  590  -590  1996/09  [Not refereed][Not invited]
  • 膵臓の管内乳頭状腫瘍及び粘液性嚢胞腫瘍38例の臨床病理学的検討
    福嶋 敬宜  日本病理学会会誌  85-  (1)  264  -264  1996/03  [Not refereed][Not invited]
  • FUKUSHIMA NORIYOSHI, SHINBATA HIROYUKI, SATO ATSUSHI, MUKAI KIYOSHI  コンピュータ支援画像診断学会大会・日本コンピュータ外科学会大会合同論文集  5th-4th-  121  -122  1995/10  [Not refereed][Not invited]
  • FUKUSHIMA Noriyoshi, OONISHI Tadahiro, YAMAGUCHI Kazuyoshi, FUKAYAMA Masashi  Pathol. Int.  45-  (2)  156  -159  1995/02  [Not refereed][Not invited]
     
    A case of mesothelium-lined cyst of the adrenal gland is reported. Although more than 300 adrenal cysts have been reported in the literature, epithelial cell-lined cysts are rare and comprise only 9% of the cases. An adrenal cyst was found, the lining cells of which had features consistent with mesothelial cells. The inner surface of the cyst was lined by a single layer of cuboidal cells, which showed alcian blue positive cellular outline. Immunohistochemically, the lining cells were positively stained for keratin, epithelial membrane antigen and CA-125. Electron microscopic examination revealed many long complex microvilli and desmosomes in the lining cells. There was a basal lamina beneath the cell layer. These morphological and immunohistochemical findings indicated that the lining cell is derived from mesothelium.
  • Noriyoshi Fukushima, Tadahiro Oonishi, Kazuyoshi Yamaguchi, Masashi Fukayama  Pathology International  45-  (2)  156  -159  1995  [Not refereed][Not invited]
     
    A case of mesothelium‐lined cyst of the adrenal gland is reported. Although more than 300 adrenal cysts have been reported in the literature, epithelial cell‐lined cysts are rare and comprise only 9% of the cases. An adrenal cyst was found, the lining cells of which had features consistent with mesothelial cells. The inner surtace of the cyst was lined by a single layer of cuboidal cells, which showed alcian blue positive cellular outline. Immunohistochemically, the lining cells were positively stained for keratin, epithelial membrane antigen and CA‐125. Electron microscopic examination revealed many long complex microvilli and desmosomes in the lining cells. There was a basal lamina beneath the cell layer. These morphological and immunohistochemical findings indicated that the lining cell is derived from mesothelium. © 1995 Cambridge Philosophical Society
  • Tsukada Shinko, Kamisaka Kazuaki, Abe Takashi, Ikegami Fumiaki, Fukushima Noriyoshi, Fukayama Masashi, Kida Tsuyoshi, Ishiguchi Tadashi, Yamato Taro, Ohyama Takanori, Baba Toshiyuki, Ohta Masahiro, Terada Mitsuhiro, Itoh Masayoshi, Sakurai Yukihiro  Progress of Digestive Endoscopy(1972)  46-  (0)  164  -165  1995  [Not refereed][Not invited]
     
    A 60-year-old man was admitted to our hospital because of a flat lesion at the anal side of supra duodenal angle. This lesion was pointed out by screening upper GI endoscopy. The follow-up examination showed the adenoma with severe atypia.
    Tumor was 15×10mm in size with eroded surface. After spraying indigocalmin, this lesion was clearly identified. Endoscopic ultrasonograpy revealed the adenoma was located within duodenal mucosa.
    The endoscopic mucosal resection (EMR) was successfully done, the resected specimen was 18×15×3mm in size and histological examination revealed 7×3mm flat type of adenoma. The over expression of p53 by using immunohistochemistry was not observed in the tissue.
    Reported case of flat adenoma was relatively rare. There was 6 cases in Japanese literature (during 1956-1993 period) .
  • 荒井 政和, 福嶋 敬宜, 望月 眞, 原田 弥生, 畔川 一郎, 松本 荻乃, 牛島 友則, 島田 素子, 原田 美貴, 深山 正久  日本臨床細胞学会雑誌  33-  (5)  917  -917  1994/09  [Not refereed][Not invited]
  • 福嶋 敬宜, 大西 忠博, 原田 弥生, 荒井 政和, 末松 直美, 山口 和克  日本臨床細胞学会雑誌  32-  (5)  831  -831  1993/09  [Not refereed][Not invited]
  • FUKUSHIMA NORIYOSHI  診断と治療  81-  (2)  537  -539  1993/02  [Not refereed][Not invited]
  • M. Shimoyama, K. Minato, K. Tobinai, M. Nagai, T. Setoya, S. Watanabe, H. Hoshino, M. Miwa, H. Nagoshi, N. Ichiki, N. Fukushima, K. Sugiura, N. Funaki  Japanese Journal of Clinical Oncology  13 Suppl 2-  245  -256  1983/01  [Not refereed][Not invited]
     
    Five cases of adult T-cell leukemia-lymphoma (ATL) having typical clinicohematologic and morphologic features but negative for anti-ATLA [antibody to ATL virus (ATLV)-associated antigen (ATLA)] are presented. Some differences in immunologic, epidemiologic, and serologic data between anti-ATLA-positive and -negative ATLs are also described. Expression of ATLA in early primary cultured leukemic cells was found to be negative in three patients tested (Cases 1, 2 and 4), however, a long-term cultured cell line, ATL-6A, derived from peripheral blood leukemia cells from Case 1, was found to express ATLA. Mother of Case 1 and a daughter of Case 2 were anti-ATLA negative. These results indicate that ATLV was involved in certain anti-ATLA-negative ATL patients, at least in Case 1, and that the patient had no detectable immune response against ATLV and ATLA. However, in other cases in which no ATLA reactivity of serum and no ATLA expression in cultured leukemic cells were observed, another possibility such as activation of an unknown cellular oncogene specific for ATL without ATLV involvement may be considered. In order to prove these possibilities definitely, it is necessary to elucidate whether or not proviral DNA of ATLV is integrated into chromosomal DNA of ATL cells and to find a cellular oncogene specific for ATL in the future.
  • M. Shimoyama, K. Minato, K. Tobinai, M. Nagai, T. Setoya, T. Takenaka, K. Ishihara, S. Watanabe, H. Hoshino, M. Miwa, M. Kinoshita, S. Okabe, N. Fukushima, N. Inada  Japanese Journal of Clinical Oncology  13 Suppl 2-  165  -187  1983/01  [Not refereed][Not invited]
     
    The diverse clinical manifestations of 10 cases of so-called adult T-cell leukemia-lymphoma (ATL)-related T-cell malignancies are described. These cases were anti-ATLA [antibody to ATL virus (ATLV)-associated antigen (ATLA)] positive, and tumor cells had the inducer/helper T-cell phenotype and expressed ATLA when cultured, indicating that these diseases are the same as typical ATL, even though their clinical diagnoses were different from ATL. Accordingly, they are called atypical ATL. Clinically, they could be divided into two subtypes, smoldering type and lymphoma type. In the smoldering type, the disease usually started with skin lesions and rarely with lung lesions. After a prodromal stage of several years, the disease progressed insidiously to the leukemic stage without additional manifestations. The flower cells characteristic of typical ATL were observed in only a small percentage of peripheral lymphoid cells. In two of the five patients the disease progressed to typical ATL after several years from onset. All five patients are alive with a long survival time, more than 6 yr in four, and had high titers of anti-ATLA, suggesting that anti-ATLA might have some role in regulating the proliferation of ATL cells in vivo. In the lymphoma type, morphological diagnosis was not always specific for discriminating ATL-related from ATL-unrelated T-cell lymphomas. Detection of anti-ATLA in the patient's serum and of ATLA in cultured tumor cells, examination of the sera of members of the patient's family for anti-ATLA, and observation of typical flower cells in the peripheral blood though the patients had neither lymphocytosis nor leukemic changes, seem to be useful for the discrimination, especially in an ATL-nonendemic area. Members of the family of a patient with anti-ATLA positive T-lymphoma in an ATL-nonendemic area were also anti-ATLA positive, indicating that healthy ATLV carriers in an ATL-nonendemic area exist as a family colony. This is responsible for sporadic outbreaks of ATL in an ATL-nonendemic area. In summary, the disease entity of ATL is considered, at present, to be a malignancy of inducer/helper T-cells transformed by ATLV or HTLV (human T-cell leukemia virus). In this sense, diverse clinical manifestations of ATL should be recognized as events of viral oncogenesis and host immune response.

Research Grants & Projects

  • Establishment of Integrated Molecular Subtyping Method for Bile Duct Cancer
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2018/04 -2021/03 
    Author : 福嶋 敬宜
     
    本課題(胆道癌の統合分子サブタイピングの確立)の最初の検討として、受容体型チロシンキナーゼの一種で、正常組織では細胞の増殖、分化、遊走、胎生期の発達に関連しているplatelet-derived growth factor-D (PDGF-D)を候補分子の一つとして解析した。胆管癌では、豊富な癌間質を伴うが、その主たる構成要素である癌関連線維芽細胞を誘導する因子の一つとしてもPDGF-Dが報告されている。また、PDGF-Dがリガンドとして作用するためにはmatriptaseなどのプロテアーゼが必要であり,これらも同時に検討した。その結果,肝外胆管癌においては、多くの腫瘍細胞がPDGF-Dおよびmatriptaseを発現していることがわかった。一方、癌間質では発現が高度な腫瘍と乏しい腫瘍が存在することを明らかにした。そして,癌間質でmatriptaseが高発現している腫瘍は無再発生存期間(RFS),全生存期間(OS)ともに不良で、多変量解析でも独立した予後規定因子となることを明らかにした。以上の結果は,Pathology International誌に投稿し受諾された。本件に関して,現在は,PDGF―D,matriptaseの発現とCAFとの関連などを培養細胞において検証中である。 また,すでに構築した組織マイクロアレイにおいて,S100P, IMP3, Maspin, MUC17, GLUT1, S100A4, CD10 などについて免疫組織化学染色で胆道癌サブタイピング法の候補になりうる分子をスクリーニング中である。
  • MicroRNAを用いた膵癌Precision Medicineの構築
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2017/04 -2020/03 
    Author : 佐田 尚宏, 三木 厚, 北山 丈二, 佐久間 康成, 福嶋 敬宜, 大澤 英之, 寺谷 工, 藤井 博文
     
    膵癌は治癒切除された症例でも5年生存率が20%程度と言われている難治性癌である。本邦で行われた膵癌手術症例の術後補助化学療法の無作為化比較試験では治療成績の向上が得られたが、その効力は十分とは言えない。一部には再発が無く長期生存が得られている症例が存在するが、どのような症例で良好な治療効果を得られるかわかっていない。良好な治療効果を予測する因子が明らかになれば、適切な薬剤の選択や、不要な有害事象の回避などを通して治療の個別化に貢献できる。本研究ではマイクロRNAの網羅的解析から膵癌の術後補助化学療法の効果と感受性に関わる分子を探索し、治療効果や予後の予測因子を見出すことで膵癌治療戦略の構築に貢献することを目的としている。 最初に条件設定とTraining studyを行う必要があり、当施設での膵臓手術症例を対象として研究を開始した。膵臓癌手術症例の術後補助化学療法の有無と種類、臨床病理学的因子、腫瘍学的予後などの情報を後方視的に収集し、対照群として膵臓癌以外の膵切除症例についても情報を収集した。倫理委員会に申請し承認を得た後に、手術標本から切片を薄切し、レーザーマイクロダイセクション法で癌部を選択的に切り出してRNAを抽出した。RNAは品質チェックを行いその後の実験に使用可能なことを確認した。今後はRNAの抽出作業を継続して行いながら、早期再発例と長期無再発例のサンプルを用いて網羅的解析を行い、それぞれに特徴的なマイクロRNAを同定していく。絞り込まれたマイクロRNAは、細胞株を用いた細胞増殖、細胞死、浸潤性などの実験を行い膵癌における機能解析を行う予定である。
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2014/04 -2017/03 
    Author : Fukushima Noriyoshi
     
    We studied tumor microenvironment in pancreatic cancer and their precursor lesions. First, we found that mast cell infiltration was significantly increased in the periductal stroma of one of the precursors of pancreatic cancer (IPMNs). Mast cells may be related to tumor progression during non-invasive stage of them. Second, MUC13 expression was more frequently observed in higher grade of IPMN, and was associated with poor prognosis of the patients. Third, using immunohistochemical method, we indicated that atypical flat lesion (AFL), recently described as a precursor of pancreatic cancer mainly in mice, was a possible precursor in human, too. Fourth, since there has been no consensus on the method and criteria for evaluation of lymph vessel invasions (LVIs), we analyzed on the whole of the largest cut sections of the pancreatic cancer specimens and determined appropriate criteria of LVIs. Furthermore, we found distribution of LVIs has a tendency to exist near the duodenum or bile duct.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2010 -2012 
    Author : FUKUSHIMA Noriyoshi
     
    The aim of this study is to develop early diagnostic system of pancreatic cancer. The analyses of the early stage of pancreatic cancer, including pancreatic intraductal neoplasm have been performed. Total RNA from tissue specimens obtained by using microd
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2006 -2008 
    Author : FUKUSHIMA Noriyoshi
     
    膵管癌の分子診断法の確立のために, その前駆病変とされている異型上皮病変(膵上皮内腫瘍性病変, 膵管内腫瘍)について, 膵管癌との関連を明らかにすべく解析を行ってきた。その結果, 膵管内腫瘍はその発育・進展過程で非浸潤癌の段階でも腫瘍周囲の環境変化(間質の筋線維芽細胞におけるペリオスチンの発現)が始まっていることを明らかにした。これにより早期癌へのアプローチは癌細胞だけでなく, 周囲組織(主に間質細胞)にもあり得ることを示した。


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