Mechanisms and predictive factors of ovarian cancer metastasis to the diaphragm

• Project/Area Number: 16K11158
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Jichi Medical University
• Principal Investigator: Oshiro Hisashi 自治医科大学, 医学部, 准教授 (60381513)
• Co-Investigator(Kenkyū-buntansha): 黒田 雅彦 東京医科大学, 医学部, 主任教授 (80251304)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 卵巣癌 / 癌性腹水 / 悪性腹水 / 横隔腹膜 / リンパ管小孔 / lymphatic stomata / リンパ行性転移 / 腹膜擦過・液状処理細胞診 / 腹膜播種 / リンパ管侵襲 / 横隔腹膜転移 / リンパ節転移 / 癌性腹膜炎 / 転移 / 細胞診 / 横隔膜 / 腹膜 / 走査型電子顕微鏡 / 漿膜 / 中皮細胞 / 機能超微形態学 / 液状化細胞診 / 腹膜擦過細胞診 / セルブロック / diaphragm / liquid-based cytology / cell block / exfoliative cytology

Outline of Final Research Achievements

We studied predictive factors of ovarian cancer metastasis to the diaphragmatic peritoneum using a method of intraoperative diaphragmatic brushing and liquid-based cytology (n=76). The rates of cancerous ascites (Odds Ratio (OR) 42.9), metastasis to the lymph node (OR 27.0), metastasis to the omentum (OR 13.7), metastasis to the peritoneum except for the omentum (OR 11.2), lymphatic vessel invasion of cancer in the primary lesion (OR 6.4), cancer exposure on the ovarian surface (OR 5.6), neoadjuvant chemotherapy (OR 4.7), high-grade serous carcinoma histology (OR 3.5), and no lymph node dissection (OR 0.3) were significantly increased in the group cytologically positive for diaphragmatic metastasis compared with the group cytologically negative for diaphragmatic metastasis (Fisher’s exact test). Rates of patients’ years of age, rapture of ovarian capsule, and blood vessel invasion of cancer in the primary lesion did not significantly differ between the two groups.

Academic Significance and Societal Importance of the Research Achievements

癌の横隔腹膜転移が癌性腹水発症の独立した予測因子となる可能性を研究代表者は既に報告している。本研究の結果は、癌の横隔腹膜転移の病態形成の上で癌のリンパ節転移が重要な予測因子となることを示唆しており、『骨盤内や傍大動脈のリンパ節に癌が転移し、腹膜や後腹膜にリンパのうっ滞が起こり、それに伴って腹水の産生速度が吸収速度を上回って腹水が貯留し、癌細胞が逆行性（あるいは経路再選択性）リンパ行性に横隔腹膜リンパ管に到達し、リンパ管小孔を介して癌細胞が腹腔へ出ていくことで癌性腹水が発生する』という研究代表者の新たな仮説をある程度支持するものと思われ、この点において本研究成果には学術的意義があると考えられる。

Research Products

• [Journal Article] Pancreaticoduodenectomy for a primary duodenal capicua transcriptional repressor (CIC) -rearranged sarcoma with severe bleeding: a case report (2020)
  • Author(s): Aoki Yuichi、Oshiro Hisashi、Yoshida Akihiko、Morishima Kazue、Miki Atsushi、Sasanuma Hideki、Sakuma Yasunaru、Lefor Alan Kawarai、Sata Naohiro
  • Journal Title: BMC Gastroenterology Volume: 20 Issue: 1 Pages: 1-6
  • DOI: 10.1186/s12876-020-01266-3
  • Peer Reviewed
• [Journal Article] Liver heterotopia associated with congenital diaphragmatic hernia (2019)
  • Author(s): Mito Kumiko、Amano Yusuke、Oshiro Hisashi、Matsubara Daisuke、Fukushima Noriyoshi、Ono Shigeru
  • Journal Title: Medicine Volume: 98 Issue: 4 Pages: e14211-e14211
  • DOI: 10.1097/md.0000000000014211
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Primary carcinosarcoma of the ureteropelvic junction associated with ureteral duplication (2019)
  • Author(s): Tsuji Kentaro、Ito Atsushi、Kurokawa Shinsuke、Nakaya Takeo、Yoshimoto Taichiro、Kawata Hirotoshi、Tamba-Sakaguchi Mio、Fukushima Noriyoshi、Oshiro Hisashi
  • Journal Title: Medicine Volume: 98 Issue: 32 Pages: e16643-e16643
  • DOI: 10.1097/md.0000000000016643
  • Peer Reviewed
• [Journal Article] TAFRO Syndrome with an Anterior Mediastinal Mass and Lethal Autoantibody-Mediated Thrombocytopenia: An Autopsy Case Report. (2019)
  • Author(s): Morita K, Fujiwara SI, Ikeda T, Kawaguchi SI, Toda Y, Ito S, Ochi SI, Nagayama T, Mashima K, Umino K, Minakata D, Nakano H, Yamasaki R, Kawasaki Y, Sugimoto M, Ashizawa M, Yamamoto C, Hatano K, Sato K, Oh I, Ohmine K, Muroi K, Ashizawa K, Yamamoto Y, Oshiro H, Kanda Y.
  • Journal Title: Acta Haematol. Volume: 141 Issue: 3 Pages: 158-163
  • DOI: 10.1159/000492743
  • Peer Reviewed
• [Journal Article] Overexpression of matriptase in tumor stroma is a poor prognostic indicator of extrahepatic bile duct cancer. (2019)
  • Author(s): Komatsubara T, Oshiro H, Sakuma Y, Sata N, Niki T, Fukushima N.
  • Journal Title: Pathol Int. Volume: 69 Issue: 2 Pages: 86-93
  • DOI: 10.1111/pin.12769
  • Peer Reviewed
• [Journal Article] Prognostic significance of the degree of lymphatic vessel invasion in locally advanced, surgically resectable pancreatic head cancer: A single center experience. (2019)
  • Author(s): Morita K, Oshiro H, Mito K, Mieno MN, Tamba-Sakaguchi M, Niki T, Miki A, Koizumi M, Sakuma Y, Komatsubara T, Sata N, Fukushima N.
  • Journal Title: Medicine. Volume: 97 Issue: 49 Pages: e13466-e13466
  • DOI: 10.1097/md.0000000000013466
  • Peer Reviewed / Open Access
• [Journal Article] Cytological detection of recurrence of acute myeloid leukemia in a postmenopausal woman presenting with abnormal uterine bleeding. (2018)
  • Author(s): Tamba-Sakaguchi M, Oshiro H, Minakata D, Yanagita M, Kohri T, Nikaido T, Kikuchi M, Suzuki T, Yoshimoto T, Fukushima N.
  • Journal Title: Diagn Cytopathol. Volume: 46 Issue: 12 Pages: 1077-1080
  • DOI: 10.1002/dc.24085
  • Peer Reviewed
• [Journal Article] A case of primary aldosteronism caused by unilateral multiple adrenocortical micronodules presenting as muscle cramps at rest: The importance of functional histopathology for identifying a culprit lesion. (2017)
  • Author(s): Ito A, Yamazaki Y, Sasano H, Matsubara D, Fukushima N, Tamba M, Tabata K, Ashizawa K, Takei A, Koizumi M, Sakuma Y, Sata N, Oshiro H.
  • Journal Title: Pathol Int. Volume: 67 Issue: 4 Pages: 214-221
  • DOI: 10.1111/pin.12521
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Giant solitary fibrous tumor of the pleura with high-grade sarcomatous overgrowth accompanied by lipid-rich, rhabdomyosarcomatous, and pleomorphic components (2017)
  • Author(s): Nakaya Takeo、Oshiro Hisashi、Takigami Ayako、Kanai Yoshihiko、Tetsuka Kenji、Hagiwara Koichi、Fujii Hirofumi、Endo Shunsuke、Tanaka Akira
  • Journal Title: Medicine Volume: 96 Issue: 50 Pages: e8926-e8926
  • DOI: 10.1097/md.0000000000008926
  • Peer Reviewed / Open Access
• [Journal Article] Liver fibrosis: noninvasive assessment using supersonic shear imaging and FIB4 index in patients with non-alcoholic fatty liver disease (2017)
  • Author(s): Hisashi Oshiro, et al
  • Journal Title: J Med Ultrason Volume: Epub ahead of print Issue: 2 Pages: 243-249
  • DOI: 10.1007/s10396-017-0840-3
  • NAID: 130007938261
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison between whole mount tissue preparations and virtual tissue microarray samples for measuring Ki-67 and apoptosis indices in human bladder cancer: A cross-sectional study (2016)
  • Author(s): Oshiro H, Czerniak BA, Sakamaki K, Tsuta K, Bondaruk J, Keyhani A, Dinney CP, Nagai T, Kamat AM
  • Journal Title: Medicine Volume: 95 Issue: 31 Pages: e4500-e4500
  • DOI: 10.1097/md.0000000000004500
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 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 (2017)
  • Author(s): 大城久、他
  • Organizer: 第56回日本臨床細胞学会秋期大会
• [Presentation] 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 (2017)
  • Author(s): 大城久、他
  • Organizer: 第56回日本臨床細胞学会秋期大会
• [Presentation] Prognostic value of quantification of lymph vessel invasions (LVIs) of cancer cells in patients with pancreatic head cancer (2017)
  • Author(s): Hisashi Oshiro, et al
  • Organizer: Annual Meeting of The United States and Canadian Academy of Pathology
  • Int'l Joint Research
• [Presentation] 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 (2016)
  • Author(s): 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
  • Organizer: 第62回日本病理学会秋期特別総会
  • Place of Presentation: 石川県金沢市，金沢市文化ホール
  • Year and Date: 2016-11-10
• [Presentation] γδ-T細胞性急性リンパ性白血病の同種移植後に悪性末梢性神経鞘腫を発症した神経線維腫症1型の一例 (2016)
  • Author(s): 和田 聖哉, 川原 勇太, 翁 由紀子, 早瀬 朋美, 田中 大輔, 柳澤 智彦, 小野 滋, 五味 玲, 相原 敏則, 古川 理恵子, 大城 久, 森本 哲
  • Organizer: 第59回日本小児血液・がん学会学術集会
  • Place of Presentation: 愛媛県松山市，愛媛県民文化会館
  • Year and Date: 2016-11-09
• [Presentation] Atypical diagnosis category of bile cytology in pancreatobilliary carcinoma and benign diseases (2016)
  • Author(s): Satoshi Ito, Daisuke Matsubara, Tomoko Suzuki, Toshikatsu Kohri, Kumiko Mito,
  • Organizer: The 19th International Congress of Cytology
  • Place of Presentation: Kanagawa, Yokohama, Pacifico Yokohama
  • Year and Date: 2016-05-28
• [Presentation] 乳腺筋上皮腫の一例 (2016)
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  • Organizer: 第30回関東臨床細胞学会学術集会
  • Place of Presentation: 山梨県甲府市，山梨県立文学館
• [Presentation] 経気腔散布像ならびに洗浄胸水中に多数の腫瘍集塊を認めた肺扁平上皮癌の一例 (2016)
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  • Organizer: 第72回日本病理学会関東支部学術集会
  • Place of Presentation: 東京都大田区，東邦大学大森キャンパス