Faculty Profiles - akihide Tanimoto

Papers - akihide Tanimoto

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赤羽俊章, 比嘉那優大, 霧島茉莉, 米澤大, 牧野隆太郎, 内田裕之, 山本淳考, 吉本幸司, 花谷亮典, 谷本昭英 . WHO新分類(WHO2021)の課題とその克服2:脳腫瘍病理形態診断と分子診断の融合の可能性脳腫瘍診断用カスタムパネルによるNot Elsewhere Classified(NEC)の再分類 . Brain Tumor Pathology41 ( Suppl. ) 088 - 088 2024.5Reviewed

比嘉那優大, 赤羽俊章, 米澤大, 横山勢也, 牧野隆太郎, 内田裕之, 霧島茉莉, 吉本幸司, 谷本昭英, 花谷亮典 . WHO新分類(WHO2021)の課題とその克服2:脳腫瘍病理形態診断と分子診断の融合の可能性グリオーマに特化したカスタムDNA/RNAパネルを用いたクリニカルシーケンス . Brain Tumor Pathology41 ( Suppl. ) 087 - 087 2024.5Reviewed

牧野隆太郎, 比嘉那優大, 赤羽俊章, 米澤大, 内田裕之, 高城朋子, 霧島茉莉, 吉本幸司, 谷本昭英, 花谷亮典 . WHO新分類(WHO2021)の課題とその克服1:脳腫瘍病理形態診断と分子診断の融合の可能性 Molecular Glioblastomaの臨床学的特徴 . Brain Tumor Pathology41 ( Suppl. ) 076 - 076 2024.5Reviewed

霧島茉莉, 寺原航, 村上未樹, 北薗育美, 信澤純人, 米永理法, 中川俊輔, 上村清央, 義岡孝子, 谷本昭英 . EWSR1::BEND2融合遺伝子を有する脊髄/脳幹Astroblastomaの1例 . 診断病理41 ( 2 ) 145 - 151 2024.4Reviewed

Language：Japanese Publisher：(一社)日本病理学会

Astroblastomaは大脳に好発する境界明瞭なグリア系腫瘍で,WHO分類第5版ではAstroblastoma,MN1-alteredとして記載されている。脊髄や脳幹のAstroblastomaはMN1再構成ではなくEWSR1::BEND2融合遺伝子を有する頻度が高い。6歳女児の頸髄から延髄に境界明瞭で嚢胞変性を伴う腫瘍を認めた。組織学的には,血管壁や間質の硝子化を伴って腫瘍細胞がastroblastic pseudorosetteや偽乳頭状構造を示して増殖し,免疫組織化学ではEMA,GFAP,Olig2陽性を示し,Fluorescence in situ hybridizationでEWSR1::BEND2融合遺伝子を確認した。大脳のAstroblastomaと異なる融合遺伝子を有する稀な脊髄/脳幹のAstroblastomaの診断にはependymomaやpiloytic astrocytoma等の鑑別と共に,特徴的なEWSR1::BEND2融合遺伝子の検索が重要である。(著者抄録)

Language：Japanese Publisher：(一社)日本病理学会

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比嘉那優大, 赤羽俊章, 米澤大, 横山勢也, 牧野隆太郎, 内田裕之, 霧島茉莉, 吉本幸司, 谷本昭英, 花谷亮典 . 脳腫瘍1 小児脳腫瘍におけるカスタムDNA/RNAパネルを用いたクリニカルシーケンス . 小児の脳神経49 ( 2 ) 168 - 168 2024.4Reviewed

Takuya Yoshimura, Yuka Hirano, Taiji Hamada, Seiya Yokoyama, Hajime Suzuki, Hirotaka Takayama, Hirono Migita, Takayuki Ishida, Yasunori Nakamura, Masahiro Ohsawa, Akihiro Asakawa, Kiyohide Ishihata, Akihide Tanimoto . Exercise Suppresses Head and Neck Squamous Cell Carcinoma Growth via Oncostatin M. . Cancers16 ( 6 ) 2024.3Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM.

DOI： 10.3390/cancers16061187

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Seiya Yokoyama, Kei Matsuo, Akihide Tanimoto . Methylation-Specific Electrophoresis . Methods in Molecular Biology2763 259 - 268 2024.2Reviewed International journal

Language：English Publishing type：Part of collection (book) Publisher：Springer US

Methylation of CpG sites in the promoter region of genomic DNA is an important epigenetic modification that plays a critical role in gene regulation, particularly in gene silencing. Epigenetic abnormalities, along with genetic alterations, are implicated in carcinogenesis and cancer progression. Numerous studies have investigated the role of epigenetics in cancer using various tools to assess DNA methylation. However, conventional analysis methods for DNA methylation require a large amount of DNA but lack higher sensitivity, making them unsuitable for analysis of samples with high heterogeneity, such as tumor tissues. In this study, we introduce a novel electrophoresis method named "methylation-specific electrophoresis (MSE)," which utilizes a denaturing gradient acrylamide gel. We demonstrate the applicability of the MSE method for DNA methylation analysis of the mucin gene as an example.

DOI： 10.1007/978-1-0716-3670-1_22

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霧島茉莉, 赤羽俊章, 横山勢也, 比嘉那優大, 米澤大, 内田裕之, 花谷亮典, 吉本幸司, 谷本昭英 . 膠芽腫の細胞形態とゲノム変化による予後推定の試み . 日本病理学会会誌113 ( 1 ) 435 - 436 2024.2Reviewed

保坂優斗, 福田皓祐, 内野祥徳, 後藤雄一, 大井秀之, 佐竹霜一, 伊地知徹也, 山崎洋一, 田上聖徳, 川崎洋太, 又木雄弘, 蔵原弘, 東美智代, 谷本昭英, 杉浦剛, 大塚隆生 . 【膵癌基礎研究の最前線RELOADED】膵管内乳頭粘液性腫瘍の腫瘍内細菌叢の病的意義 . 胆と膵45 ( 2 ) 189 - 196 2024.2Reviewed

Language：Japanese Publisher：医学図書出版(株)

膵臓は元来,腸内細菌叢(マイクロバイオータ)とは無縁と考えられていたが,近年の研究で腸内細菌や真菌が膵内に移行すること,膵癌の腫瘍内には活発な細菌が豊富に存在すること,腫瘍内細菌叢が局所の免疫機能を抑制することで癌の増殖と進展を促進していることが明らかとなった。われわれは膵癌の危険因子の一つである膵管内乳頭粘液性腫瘍(intraductal papillary mucinous neoplasm:IPMN)の発生や進展にも腫瘍内細菌叢が関与しているという仮説を立てて,IPMNの腫瘍内細菌叢を調査し,腫瘍内細菌叢が腫瘍と宿主に及ぼす影響について検証した。その結果を踏まえてIPMNにおける腫瘍内細菌叢の病的意義について概説する。(著者抄録)

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有馬直佑, 藤崎真由, 中別府聖一郎, 島晃大, 林田真衣子, 鎌田勇平, 中村大輔, 吉満誠, 橋口照人, 東美智代, 谷本昭英, 大島孝一, 石塚賢治 . 抗レトロウイルス療法による免疫再構築により消失したHIV関連EBV陽性粘膜皮膚潰瘍 . 臨床血液65 ( 1 ) 13 - 17 2024.1Reviewed

Language：Japanese Publisher：(一社)日本血液学会-東京事務局

症例は24歳男性。倦怠感や体重減少の精査のため実施した下部消化管内視鏡検査で回盲部潰瘍を認め,生検でびまん性大細胞型B細胞リンパ腫と診断された。その後の精査中にニューモシスチス肺炎を併発し,後天性免疫不全症候群(AIDS)の合併が判明した。回盲部潰瘍以外に明確な病変はなく,生検組織のin situ hybridization法により腫瘍細胞はEpstein-Barr encoding region(EBER)がびまん性に強陽性であったため,EBV陽性粘膜皮膚潰瘍(EBVMCU)と診断した。免疫再構築により病変が改善することを期待し,抗レトロウイルス療法(ART)を開始した。ART開始79日後には回盲部潰瘍の完全消失を確認し,その後3年以上にわたって寛解を維持している。EBVMUCは種々の免疫抑制状態を背景に発症することが知られておりAIDSもその一つであるが,ARTによる免疫再構築によってEBVMCUが寛解に至った初めての報告である。(著者抄録)

ARIMA Naosuke, FUJISAKI Mayu, NAKABEPPU Seiichiro, SHIMA Kodai, HAYASHIDA Maiko, KAMADA Yuhei, NAKAMURA Daisuke, YOSHIMITSU Makoto, HASHIGUCHI Teruto, HIGASHI Michiyo, TANIMOTO Akihide, OHSHIMA Kouichi, ISHITSUKA Kenji . Spontaneous regression of HIV-associated EBV-positive mucocutaneous ulcer due to immune reconstruction with antiretroviral therapy . Rinsho Ketsueki65 ( 1 ) 13 - 17 2024Reviewed

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology

A 24-year-old man was found to have an ileocecal ulcer by colonoscopy. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) with diffuse positive reaction of Epstein-Barr encoding region (EBER) by in situ hybridization was made based on analysis of the specimen. Acquired immunodeficiency syndrome (AIDS) complicated by pneumocystis jirovecii pneumonia was also diagnosed. As no other significant lymphomatous lesions were identified by further examination, a clinical diagnosis of EBV-positive mucocutaneous ulcer (EBVMCU) was made. Rather than performing systemic chemotherapy, the lesion was closely monitored and antiretroviral therapy (ART) for AIDS was started with the hope of treating the lesion through immune reconstitution. The lesion had completely disappeared by day 79 after starting ART, and has not recurred for over 3 years. EBVMCU is known to develop secondary to various immunosuppressive states including AIDS. Here we report a rare case of EBVMCU detected at diagnosis of AIDS that entered complete remission after immune reconstitution by ART.

DOI： 10.11406/rinketsu.65.13

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Tomonobu Yamada, Hiroaki Kawaguchi, Aki Matsuoka, Kohei Akioka, Naoki Miura, Hiroyuki Izumi, Akihide Tanimoto . Development of a Microminipig Model of Atherosclerosis for the Evaluation of a HMGCR Inhibitor. . In vivo (Athens, Greece)38 ( 1 ) 98 - 106 2024Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIM: Atherosclerosis is known as a major risk factor for cardiovascular disease, and development of an animal model of atherosclerosis is required to investigate its clinical pathogenesis. We studied the optimal amount of cholesterol in the diet and the optimal experimental period for development of a Microminipig model of atherosclerosis for the evaluation of a hydroxymethylglutaryl-CoA reductase (HMGCR) inhibitor (atorvastatin). MATERIALS AND METHODS: Eighteen male animals (3-4 months old) were divided into 3 groups. Group 1 consisted of control animals receiving a normal chow diet, Group 2 animals received a high fat (12% w/w) and low cholesterol (0.1% w/w) diet (HFLCD), and Group 3 animals received HFLCD+statin for 12 weeks. Animals received statin at 3 mg/kg body weight per day. HFLCD did not down-regulate the hepatic expression of HMGCR mRNA. RESULTS: HFLCD increased body, omentum, and mesenteric adipose tissue weight, and induced hypercholesterolemia and atherosclerotic lesions in the abdominal aorta. HFLCD+statin inhibited hypercholesterolemia and atherosclerotic lesions, but not obesity. CONCLUSION: A microminipig atherosclerosis model induced by HFLCD can be used in the evaluation of HMGCR inhibitors for the treatment of hypercholesterolemia and atherosclerosis.

DOI： 10.21873/invivo.13415

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Ikumi Kitazono, Toshiaki Akahane, Seiya Yokoyama, Emi Kubota, Yukari Nishida-Kirita, Hirotsugu Noguchi, Miki Murakami, Shintaro Yanazume, Hiroaki Kobayashi, Akihide Tanimoto . Cervical Cytology Preserves Histologically Detected Surface Epithelial Slackening, Unique to the POLE Mutation-subtype in Endometrial Cancer. . In vivo (Athens, Greece)38 ( 1 ) 321 - 333 2024Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIM: Among the four genomic subtypes of endometrial cancer, distinguishing between the DNA polymerase epsilon mutation (POLEmut) and no specific molecular profile (NSMP) subtypes requires genomic profiling owing to the lack of surrogate immunohistochemical markers. We have previously found that, histologically, the POLEmut-subtype exhibits surface epithelial slackening (SES). Therefore, to improve subtype identification, we aimed to extract cytological features corresponding to SES in POLEmut-subtype cervical cytology specimens. MATERIALS AND METHODS: We analyzed 104 endometrial cancer cervical cytology specimens, with integrative diagnosis confirmation via histology, immunohistochemistry, and genomic profiling. Cytological features were evaluated for the presence of atypical glandular cells, atypical cell appearance in single cells and clusters, and cytological SES and the presence of tumor-infiltrating inflammatory cells in clusters. RESULTS: Based on cervical cytology, the POLEmut- and p53mut-subtypes exhibited more frequent atypical cells in smaller clusters, giant tumor cells, and cytological SES patterns than the NSMP-subtype. Tumor-infiltrating lymphocytes were frequent in the POLEmut- and mismatch repair-deficient subtypes. CONCLUSION: Histologically-detected SES as well as other endometrial cancer features may be preserved in the atypical cell clusters observed in cervical cytology specimens. Cytological detection of SES and of smaller clusters of atypical cells and inflammatory cells with moderate atypia are suggestive of POLEmut-subtype. Integrative diagnosis including genomic profiling remains critical for diagnostic confirmation.

DOI： 10.21873/invivo.13442

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Shintaro Yanazume, Yukari Kirita, Yusuke Kobayashi, Ikumi Kitazono, Toshiaki Akahane, Mika Mizuno, Shinichi Togami, Akihide Tanimoto, Hiroaki Kobayashi . Can Endometrial Cytology Identify Patients Who Would Benefit from Immunotherapy? . Acta cytologica68 ( 2 ) 128 - 136 2024Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Patients with polymerase epsilon (POLE) mutation (POLEmut) subtype, MMR-deficient (MMR-d) subtype as classified by The Cancer Genome Atlas (TCGA), and a high tumor mutation burden (TMB-high) potentially benefit from immunotherapy. However, characteristics of the cytological morphology within these populations remain unknown. METHODS: DNA extracted from formalin-fixed paraffin-embedded tissues was subjected to next-generation sequencing analysis. Genomic mutations related to gynecological cancers, TMB, and microsatellite instability were analyzed and were placed in four TCGA classification types. The following morphological cytological investigations were conducted on endometrial cancer using a liquid-based preparation method, prior to the commencement of initial treatment: (i) cytological backgrounds; (ii) differences between each count of neutrophils and lymphocytes as described below. RESULTS: Insignificant differences in the cytological background patterns of TCGA groups and TMB status were found. Although there was no significant difference in neutrophil count (p = 0.955) in the TCGA groups, POLEmut and MMR-d had significantly higher lymphocyte counts than no specific molecular profile (NSMP) (p = 0.019 and 0.037, respectively); furthermore, p53mut also tended to be significant (p = 0.064). Lymphocyte counts in TMB-high were also significantly greater than TMB-low (p = 0.002). POLEmut showed a positive correlation between TMB levels and lymphocyte counts. For predicting patients with POLEmut plus MMR-d, lymphocyte counts demonstrated a superior diagnostic accuracy of area under the curve (AUC) (0.70, 95% CI: 0.57-0.84), with a cutoff value of 26 high-power field. CONCLUSION: Lymphocyte count using liquid-based cytology for patients with endometrial cancer may predict POLEmut plus MMR-d of TCGA groups and TMB-high in those who can benefit from immunotherapy.

DOI： 10.1159/000538288

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野口紘嗣, Baldwin William, 谷本昭英 . Role of C1q in Resolving Ischemia Reperfusion in Kidney Transplants . 移植59 ( Supplement ) s372_1 - s372_1 2024Reviewed

Language：Japanese Publisher：一般社団法人日本移植学会

[Introduction]Complement has been implicated as a pro-inflammatory mediator in ischemia reperfusion injury (IRI). However, C1q, a subcomponent of C1, functions as a pattern recognition receptor (PRR) that removes injured cells. [Method]We examined the effects of C1q in kidney allografts. A/J kidneys were transplanted to wild type C57BL6 or C1q-knockout (KO) recipients. Treated mice were euthanized from 1 day to 28 day after transplantation to see the C1q function in early to chronic phase inflammation by these tests.[Result]All kidney allografts survived more than 14 days in wild type recipients. In contrast, allografts subjected to cold or warm ischemia failed acutely in C1q-KO recipients with unresolved IRI. C1q transcripts increased in allografts from 1 day to 7 days after transplantation. nanoString analysis on flow sorted infiltrating versus resident myeloid cells isolated from transplants indicated higher C1q transcripts from resident macrophages than infiltrating macrophages.[Conclusion]These data indicate that C1q functions as a PRR to resolve IRI incurred at the time of transplantation.

DOI： 10.11386/jst.59.supplement_s372_1

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YAMANAKA Sae, TOKIMURA Hiroshi, HIGA Nayuta, IWAMOTO Hirofumi, NISHIMUTA Yosuke, SUEYOSHI Kazunobu, YONEZAWA Hajime, TAJITSU Kenichiro, AKAHANE Toshiaki, TANIMOTO Akihide, HANAYA Ryosuke . Pilocytic Astrocytoma Presenting with Spontaneous Cerebellar Hemorrhage: A Case Report . NMC Case Report Journal10 ( 0 ) 303 - 308 2023.12Reviewed

Language：English Publisher：The Japan Neurosurgical Society

Hemorrhagic pilocytic astrocytomas (PAs) are rare, accounting for 1.1%-8.0% of all PA cases. They are reported to occur more frequently in older populations, with a male predominance. In this study, we report a case of a 14-year-old boy who presented with a headache, vertigo, and diplopia. As per his brain computed tomography scan, a small hematoma was observed in the left inferior cerebellar peduncle. Follow-up magnetic resonance imaging (MRI) revealed repeated minor bleeding from the lesion and mild expansion, with no neurological deficits. Four years later, the patient developed nausea, vomiting, and left abducens palsy. MRI revealed a mulberry-shaped mass surrounded by a hypointense rim, suggesting a cavernous angioma. The lesion was surgically resected via midline occipital craniotomy with the opening of the cerebellomedullary fissure. Histopathological examination of the lesion revealed PA. Next-generation sequencing analyses revealed that PAs harbored mutations in the ARID1A, ATM, and POLE genes but not in the BRAF gene. To the best of our knowledge, there are yet no reported studies on these mutations in PAs to date. Thus, PA should be considered in the differential diagnosis of cerebellar hemorrhage, especially in young adults and children.

DOI： 10.2176/jns-nmc.2023-0152

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Yamanaka Sae, Tokimura Hiroshi, Higa Nayuta, Iwamoto Hirofumi, Nishimuta Yosuke, Sueyoshi Kazunobu, Yonezawa Hajime, Tajitsu Kenichiro, Akahane Toshiaki, Tanimoto Akihide, Hanaya Ryosuke . 自然小脳出血を呈した毛様細胞性星細胞腫　症例報告(Pilocytic Astrocytoma Presenting with Spontaneous Cerebellar Hemorrhage: A Case Report) . NMC Case Report Journal10 ( 1 ) 303 - 308 2023.12Reviewed

Language：English Publisher：(一社)日本脳神経外科学会

症例は14歳男児。バスケットボール中に頭部を負傷した後、頭痛、めまい、複視を呈した。CTで左下小脳小帯に小さな血腫を認めた。MRIによる経過観察では、血腫からの軽度の出血と軽度の拡張を繰り返されたが、神経学的障害は認められなかった。しかし、4年後に悪心、嘔吐、左外転麻痺を発症した。MRIにより腫瘤が認められ、mulberry-shaped腫瘍が示唆された。病変は外科的切除された。病変の病理組織学的検査の結果、毛様細胞性星細胞腫が認められた。次世代シーケンス解析の結果、毛様細胞性星細胞腫はARIDIA遺伝子、ATM遺伝子、POLE遺伝子変異を有していたが、BRAJ遺伝子には変異は認められなかった。

窪田恵美, 北薗育美, 岩切かおり, 切田ゆかり, 田崎貴嗣, 東美智代, 簗詰伸太郎, 小林裕明, 谷本昭英 . 液状化検体細胞診で診断した子宮頸部明細胞癌の1例 . 日本臨床細胞学会雑誌62 ( 6 ) 287 - 292 2023.11Reviewed

Language：Japanese Publisher：(公社)日本臨床細胞学会

背景:子宮頸部原発明細胞癌はまれであり,液状化検体細胞診(liquid-based cytology:LBC)の細胞像の報告はほとんどない.われわれは,LBC標本で診断しえた子宮頸部明細胞癌の1例を経験したので,塗抹標本所見との異同および他の腺癌との鑑別点について検討し報告する.症例:70歳代,女性.約1年前より持続する性器出血があり,子宮頸部のポリープ状腫瘍を指摘された.擦過細胞診および組織診で明細胞癌と診断された.LBC標本では,異型細胞が重積性のある集塊状や孤立性に認められ,腺腔構造や乳頭状構造およびhobnail状の核の突出も認めた.異型細胞の核は軽度の腫大を示す類円形を呈しており,大型で明瞭な核小体を認め,細胞質は豊富で,淡く微細顆粒状を呈していた.結論:LBC標木においても,塗抹標本と同様に明細胞癌の特徴とされる,大型で明瞭な核小体および豊富な細胞質を有する異型細胞を認め,LBC標本で明細胞癌の診断を行う際にも重要な細胞所見である.(著者抄録)

Yumisashi Riho, Saito Ryosuke, Togami Shinichi, Kobayashi Yusuke, Kitazono Ikumi, Tanimoto Akihide, Kobayashi Hiroaki . 分子生物学的解析により組織学的グレードが異なるsynchronous endometrial and ovarian cancerの症例が子宮内膜癌からの転移性卵巣癌であることが明らかになった　症例報告と文献レビュー(Molecular biological analysis revealed a case of synchronous endometrial and ovarian cancer with different histological grade as metastatic ovarian cancer from endometrial cancer: Case report and review of literature) . The Journal of Obstetrics and Gynaecology Research49 ( 11 ) 2766 - 2770 2023.11Reviewed

Language：English Publisher：John Wiley & Sons Australia, Ltd

症例は38歳の女性で、下腹部痛により来院した。超音波とMRIにて右卵巣と付属器に腫瘍を認め、腹腔鏡下にて切除した。子宮内膜及び卵巣において病理学的にグレード3の類内膜癌が認められた。進行度の検査にて子宮内膜と播種結節に腫瘍を認め、直腸への浸潤も含め切除し、卵管卵巣摘除術を行った。子宮内膜癌はグレード1、子宮漿膜内の播種結節はグレード3の類内膜腺癌と診断された。synchronous endometrial and ovarian cancer(SEOC)を疑い、DNA解析を行った。その結果、SEOCではなく子宮内膜癌の卵巣転移と診断された。パクリタキセルとカルボプラチンによるアジュバント化学療法を受け、再発は認められていない。

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