2026/06/02 更新

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写真a

トモノベ　ヒロシ
友延 寛
TOMONOBE HIROSHI
所属
九州大学病院 産科婦人科 助教
職名
助教

論文

  • High-grade Serous Carcinoma can Show Squamoid Morphology Mimicking True Squamous Differentiation 査読

    Tomonobe, H; Ohishi, Y; Hachisuga, K; Yahata, H; Kato, K; Oda, Y

    AMERICAN JOURNAL OF SURGICAL PATHOLOGY   47 ( 9 )   967 - 976   2023年9月   （ ISSN:0147-5185 eISSN:1532-0979 ）

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    担当区分：筆頭著者,　最終著者,　責任著者   記述言語：英語   掲載種別：学位論文（博士）   出版者・発行元：American Journal of Surgical Pathology  

    Tubo-ovarian high-grade serous carcinoma (HG-SC) and ovarian endometrioid carcinoma (EC) can show overlapping morphologic features, such as glandular and solid patterns. The differential diagnosis of these subtypes is thus sometimes difficult. The existence of "squamous differentiation"tends to lead to a diagnosis of EC rather than HG-SC. We noticed that HG-SC can contain a "squamoid component,"but its nature has been poorly investigated. This study was thus established to clarify the nature of this "squamoid component"in HG-SC by investigating its frequency and immunohistochemical features. We reviewed hematoxylin and eosin-stained slides of 237 primary untreated cases of tubo-ovarian HG-SC and identified 16 cases (6.7%) of HG-SC with "squamoid component."An immunohistochemical staining panel (CK5/6, CK14, CK903, p40, p63, WT1, ER, and PgR) was used to analyze all of these 16 cases. We also selected 14 cases of ovarian EC with "squamous differentiation"as a control. The "squamoid component"in HG-SC was completely p40-negative and showed significantly lower expression of CK5/6, CK14, CK903, and p63 than the "squamous differentiation"in EC. The immunophenotype of the "squamoid component"in HG-SC was concordant with the conventional HG-SC component (WT1-positive/ER-positive). Furthermore, all 16 tumors were confirmed to be truly "HG-SC"by the findings of aberrant p53 staining pattern and/or WT1/p16 positivity, and the lack of mismatch repair deficiency and POLE mutation. In conclusion, HG-SC can on rare occasions show a "squamoid component"mimicking "squamous differentiation."However, the "squamoid component"in HG-SC does not represent true "squamous differentiation."The "squamoid component"is one part of the morphologic spectrum of HG-SC, which should be interpreted carefully for the differential diagnosis of HG-SC and EC. An immunohistochemical panel including p40, p53, p16, and WT1 is a useful adjunct to achieve a correct diagnosis.

    DOI： 10.1097/PAS.0000000000002089

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  • 子宮体部癌肉腫術後に発生した閉鎖動脈仮性動脈瘤の一例 査読

    金子 夏生, 鶴地 伸宏, 友延 寛, 木下 秀一郎

    共済医報   74 ( 3 )   225 - 230   2025年8月   （ ISSN:0454-7586 ）

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    記述言語：日本語   出版者・発行元：国家公務員共済組合連合会  

    仮性動脈瘤とは,正常な動脈壁の3層構造を欠いた動脈瘤であり,非常にもろく破裂しやすい.婦人科手術後の仮性動脈瘤は非常に稀な疾患であるが,破裂すると即座に循環動態が破綻し,生命を脅かしかねない.子宮体部癌肉腫IA期に対して,子宮体癌根治術を行い,術後1日目,術中出血量に見合わない貧血があり,2日目の経腹超音波断層法で右後腹膜血腫を認めた.8日目の造影CT検査で血腫内に仮性動脈瘤を疑う結節状濃染域を認め,血管造影検査で右閉鎖動脈の仮性動脈瘤と診断し,コイルによる動脈塞栓術で治療できた.血管周囲を処理する骨盤リンパ節郭清後は血管壁の脆弱化により仮性動脈瘤が生じることがあることを念頭に置き診療にあたる必要がある.また,診断には造影CT検査や血管造影検査が有用であり,本疾患を疑った場合は速やかに検査を行い,診断・治療につなげることで救命可能である.(著者抄録)

  • 腹腔鏡手術で診断と治療を行った妊娠11週のメッケル憩室炎による絞扼性腸閉塞の1例 査読

    蒔田 真也香, 友延 寛, 上田 純二, 西田 眞

    日本周産期・新生児医学会雑誌   61 ( 1 )   141 - 146   2025年5月   （ ISSN:1348-964X ）

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    担当区分：責任著者   記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

    症例は26歳,妊娠11週0日の妊婦.腹痛を主訴に当院を救急受診した.血液検査で炎症所見があり,単純CT検査で小腸の局所的な拡張と集簇を認めたが,確定診断には至らなかった.症状の改善がなく診断目的に審査腹腔鏡を施行して,メッケル憩室と周囲組織のバンド形成,同部位への小腸の嵌頓を認め,メッケル憩室炎に伴う腸閉塞と診断した.メッケル憩室切除術を施行して症状は消失した.当院で周産期管理を継続して妊娠高血圧腎症に対して分娩誘発を施行し妊娠40週1日に頭位経腟分娩となった.妊娠中のメッケル憩室による急性腹症は稀な病態でその診断は非常に困難であるが,対応の遅れは母体および胎児の予後を悪化させる可能性がある.CT検査等の画像検査を躊躇せず施行しなければならないが,妊娠中の原因不明の急性腹症に対しては,診断目的での試験開腹術や審査腹腔鏡といった外科的介入も積極的に考慮すべきである.(著者抄録)

  • Low-Grade Endometrial Cancer with Abnormal p53 Expression as a Separate Clinical Entity: Insights from RNA Sequencing and Immunohistochemistry 査読

    Hachisuga, K; Kawakami, M; Tomonobe, H; Maenohara, S; Kodama, K; Yagi, H; Yasunaga, M; Onoyama, I; Asanoma, K; Yahata, H; Oda, Y; Kato, K

    DIAGNOSTICS   15 ( 6 )   2025年3月   （ ISSN:2075-4418 eISSN:2075-4418 ）

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    記述言語：英語   出版者・発行元：Diagnostics  

    Background: A molecular classification of endometrial cancer was developed based on an analysis of The Cancer Genome Atlas. In this classification, the group characterized by abnormal p53 immunohistochemical expression showed the poorest prognosis. However, there may be no need to apply a molecular classification in low-grade endometrial cancer. In this study, we investigated the clinical significance of abnormal p53 immunohistochemical expression in low-grade endometrial cancer. Methods: We obtained nine frozen samples of endometrial cancer [low-grade endometrial cancer with wild-type p53 expression (EC<sup>lo</sup>p53<sup>wt</sup> group): n = 3, low-grade endometrial cancer with abnormal p53 expression (EC<sup>lo</sup>p53<sup>ab</sup> group): n = 3, and high-grade endometrial cancer (EC<sup>hi</sup> group): n = 3]. RNA sequencing was performed for each sample. All the samples passed RNA quality control. In addition, an immunohistochemical analysis was performed for 44 formalin-fixed paraffin-embedded samples. Results: Differentially expressed genes were identified in the RNA sequencing results (1811 genes between the EC<sup>lo</sup>p53<sup>ab</sup> group and the EC<sup>hi</sup> group, and 1088 genes between the EC<sup>lo</sup>p53<sup>ab</sup> group and the EC<sup>lo</sup>p53<sup>wt</sup> group). In a principal component analysis, the EC<sup>lo</sup>p53<sup>ab</sup> group was more similar to the EC<sup>lo</sup>p53<sup>wt</sup> group than to the EC<sup>hi</sup> group. In the immunohistochemical analysis, L1CAM expression was significantly less frequently observed in the EC<sup>lo</sup>p53<sup>ab</sup> group than in the EC<sup>hi</sup> group. Moreover, p21 expression tended to be more frequently observed in the EC<sup>lo</sup>p53<sup>ab</sup> group than in the EC<sup>hi</sup> group. Conclusions: In this study, the RNA sequencing and immunohistochemical results revealed that the EC<sup>lo</sup>p53<sup>ab</sup> group is a separate entity from the EC<sup>hi</sup> group. While the abnormal p53 group is considered the most prognostically unfavorable in molecular classification, these findings suggest that routine molecular profiling is not necessary for patients with low-grade endometrial cancer. However, there is insufficient evidence to modify adjuvant treatment in low-grade endometrial cancer patients. Further investigation is needed on the clinical application of molecular classification to low-grade endometrial cancer.

    DOI： 10.3390/diagnostics15060671

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  • A treatment strategy for endometrial cancer focusing on KRAS mutation and DUSP6 expression 査読

    Kawakami, M; Tomonobe, H; Hachisuga, K; Maenohara, S; Kodama, K; Yagi, H; Yasunaga, M; Onoyama, I; Asanoma, K; Yahata, H; Kato, K

    CANCER SCIENCE   116   1738 - 1738   2025年1月   （ ISSN:1347-9032 eISSN:1349-7006 ）

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  • Clinical Significance of Tumor Immune Microenvironment in Endometrial Endometrioid Carcinoma, Grade 1 With DNA Mismatch Repair Protein Loss 査読

    Hachisuga, K; Kawakami, M; Tomonobe, H; Maenohara, S; Kodama, K; Yagi, H; Yasunaga, M; Onoyama, I; Asanoma, K; Yahata, H; Oda, Y; Kato, K

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY   43 ( 6 )   573 - 585   2024年11月   （ ISSN:0277-1691 eISSN:1538-7151 ）

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    出版者・発行元：International Journal of Gynecological Pathology  

    The administration of immune checkpoint inhibitors (ICIs) is increasing in endometrial cancer, especially in the mismatch repair (MMR)-deficient group. To prevent unnecessary immune-related adverse events, ICIs need to be administered to more appropriate patients. The tumor immune microenvironment has been reported to be a predictive marker of the efficacy of ICI therapies. This study evaluated CD8, FoxP3, CD68, PD-L1, and β-catenin expression in endometrial endometrioid carcinoma, grade 1 (G1) with DNA mismatch repair protein loss (MMR loss), and their association with clinicopathological features. We retrospectively analyzed tumor samples from 107 patients with endometrial endometrioid carcinoma, G1 (MMR-deficient group: n=67; MMR-proficient group: n=40). Overall, 47 cases of MLH1/PMS2 loss and 20 cases of MSH2/MSH6 loss were observed. The patients with low intraepithelial CD8 expression significantly more frequently exhibited deep myometrial invasion, and the elderly group (≥60 y) significantly more frequently showed low stromal CD8 expression. In addition, FoxP3-positive cell count and FoxP3/CD8+ ratio were significantly correlated with the International Federation of Obstetrics and Gynecology 2023 stage and lymph node metastasis. In the Kaplan-Meier analysis, the patients with low intraepithelial or stromal CD8 expression had shorter progression-free survival (PFS) than those with high intraepithelial or stromal CD8 expression, albeit not significantly. We clarified that the tumor immune microenvironment had an impact on clinicopathological features within the group with MMR loss, which is the main target for ICIs, limited to endometrioid carcinoma, G1. Further studies are needed, including on patients administered ICIs.

    DOI： 10.1097/PGP.0000000000001020

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  • 術前化学療法後に下大静脈を離断し,右腎合併切除で完全摘出できた晩期再発卵巣顆粒膜細胞腫の一例 査読

    矢幡 秀昭, 岡部 安博, 蜂須賀 一寿, 友延 寛, 前之原 章司, 小玉 敬亮, 八木 裕史, 安永 昌史, 小野山 一郎, 淺野間 和夫, 中村 雅史, 加藤 聖子

    産婦人科手術   ( 35 )   151 - 151   2024年6月   （ ISSN:0915-8375 ）

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    記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

  • Complete reduction surgery of a huge recurrent adult granulosa cell tumor after neoadjuvant chemotherapy 査読

    Tokui, H; Yahata, H; Okabe, Y; Magarifuchi, N; Maenohara, S; Hachisuga, K; Tomonobe, H; Kodama, K; Yagi, H; Yasunaga, M; Onoyama, I; Asanoma, K; Oda, Y; Nakamura, M; Kato, K

    INTERNATIONAL CANCER CONFERENCE JOURNAL   13 ( 2 )   162 - 166   2024年4月   （ ISSN:2192-3183 ）

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  • 術前補助化学療法後の巨大再発成人顆粒膜細胞腫に対して完全縮小手術を施行した1例(Complete reduction surgery of a huge recurrent adult granulosa cell tumor after neoadjuvant chemotherapy) 査読

    Tokui Hiroha, Yahata Hideaki, Okabe Yasuhiro, Magarifuchi Naomi, Maenohara Shoji, Hachisuga Kazuhisa, Tomonobe Hiroshi, Kodama Keisuke, Yagi Hiroshi, Yasunaga Masafumi, Onoyama Ichiro, Asanoma Kazuo, Oda Yoshinao, Nakamura Masafumi, Kato Kiyoko

    International Cancer Conference Journal   13 ( 2 )   162 - 166   2024年4月

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    記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

    症例は72歳女性、2妊2産であった。卵巣悪性腫瘍に対して52歳時に開腹子宮全摘術、両側卵管卵巣摘出術、大網切除術、骨盤リンパ節郭清術を施行され、最終診断はステージIaの成人型顆粒膜細胞腫(AGCT)であった。初回手術から19年後、他施設で受けたCTで後腹膜腫瘍が偶然発見された。腫瘍は直径11×10cmで、肝門部、下大静脈、右腎静脈が隆起していた。CTガイド下腫瘍生検によりAGCTの再発が確認された。腫瘍が巨大であり、完全切除を行うと出血多量による術中死亡のリスクがあると考えられた。そこで、パクリタキセル+カルボプラチン(PC)による術前化学療法を行い、再発腫瘍を縮小させた。その後、縮小手術を行った。再発腫瘍の完全切除に成功し、手術時間は12時間54分、出血量は700gであった。切除標本の病理所見からAGCTの再発と診断した。術後1年経過時点で再発は認められなかった。

  • The BHLHE40-PPM1F-AMPK pathway regulates energy metabolism and is associated with the aggressiveness of endometrial cancer 査読

    Asanoma, K; Yagi, H; Onoyama, I; Cui, L; Hori, E; Kawakami, M; Maenohara, S; Hachisuga, K; Tomonobe, H; Kodama, K; Yasunaga, M; Ohgami, T; Okugawa, K; Yahata, H; Kitao, H; Kato, K

    JOURNAL OF BIOLOGICAL CHEMISTRY   300 ( 3 )   105695   2024年3月   （ ISSN:00219258 eISSN:1083-351X ）

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    記述言語：英語   出版者・発行元：Journal of Biological Chemistry  

    BHLHE40 is a basic helix-loop-helix transcription factor that is involved in multiple cell activities including differentiation, cell cycle, and epithelial-to-mesenchymal transition. While there is growing evidence to support the functions of BHLHE40 in energy metabolism, little is known about the mechanism. In this study, we found that BHLHE40 expression was downregulated in cases of endometrial cancer of higher grade and advanced disease. Knockdown of BHLHE40 in endometrial cancer cells resulted in suppressed oxygen consumption and enhanced extracellular acidification. Suppressed pyruvate dehydrogenase (PDH) activity and enhanced lactated dehydrogenase (LDH) activity were observed in the knockdown cells. Knockdown of BHLHE40 also led to dephosphorylation of AMPKα Thr172 and enhanced phosphorylation of pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) Ser293 and lactate dehydrogenase A (LDHA) Tyr10. These results suggested that BHLHE40 modulates PDH and LDH activity by regulating the phosphorylation status of PDHA1 and LDHA. We found that BHLHE40 enhanced AMPKα phosphorylation by directly suppressing the transcription of an AMPKα-specific phosphatase, PPM1F. Our immunohistochemical study showed that the expression of BHLHE40, PPM1F, and phosphorylated AMPKα correlated with the prognosis of endometrial cancer patients. Because AMPK is a central regulator of energy metabolism in cancer cells, targeting the BHLHE40‒PPM1F‒AMPK axis may represent a strategy to control cancer development.

    DOI： 10.1016/j.jbc.2024.105695

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  • 卵巣嚢腫摘出術後の外来での経過観察中に再発を繰り返した卵巣粘液性嚢胞腺腫の1例 査読

    和田 智子, 藤 玄一郎, 清武 早紀, 野田 龍之介, 中島 京, 田中 大智, 嶋田 幸世, 前原 佳奈, 友延 寛, 貴島 雅子, 濱崎 洋一郎, 松本 恵, 西山 憲一, 遠城 幸子, 西田 眞

    日本女性医学学会雑誌   30 ( 2 )   246 - 249   2023年1月   （ ISSN:2185-8861 ）

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    記述言語：日本語   出版者・発行元：(一社)日本女性医学学会  

    良性卵巣腫瘍の嚢腫摘出術後に再発することがあるが,これについて詳細に検討した報告は少ない.また,良性卵巣腫瘍の術後の長期的な管理についても確立された考え方はない.腹腔鏡下卵巣嚢腫摘出後に同側卵巣に再発し,1年ごとに計3回手術を行った卵巣粘液性嚢胞腺腫の症例を経験したので報告する.症例は21歳1妊0産.婦人科受診で左卵巣腫瘍を指摘されX-1年6月に当科を初診した.左付属器領域に径60×47mmの内部エコーや充実部を伴わない多房性嚢胞性腫瘤を認め,腫瘍マーカーはCA125,CA19-9,CEAいずれも基準範囲内であった.左卵巣子宮内膜症性嚢胞を疑いジエノゲストを投与したが腫瘍は増大し,X年4月に腹腔鏡下左卵巣嚢腫摘出術を施行した.病理組織診断は粘液性嚢胞腺腫であった.X+1年4月,術後1年後の受診で左付属器領域に径141×102mmの多房性嚢胞性腫瘤を認め,同年6月に2回目の腹腔鏡下左卵巣嚢腫摘出術を施行し,病理組織診断は粘液性嚢胞腺腫で悪性所見はなかった.2回目の手術から5ヵ月後に同側卵巣に径10×5cmの多房性嚢胞性腫瘤の再発があり,さらに5ヵ月後には長径約18cmに増大した.短期間に再発を繰り返しており悪性腫瘍の可能性を否定できなかったため,同年8月に腹腔鏡下左付属器摘出術を施行した.左卵巣腫瘍の病理組織診断は1,2回目と同じく粘液性嚢胞腺腫であった.過去の報告では卵巣粘液性嚢胞腺腫の術後再発リスク因子として,若年,嚢腫摘出術,術中被膜破綻を挙げられており,本症例もこれらの因子を有していた.2回とも同側卵巣に再発していることから再発の原因として手術時の腫瘍組織の残存が推測された.しかしながら,嚢腫摘出時に腫瘍の遺残がないことを確認する手段はなく,術後の定期経過観察が再発を早期に発見する契機となる可能性が考えられた.(著者抄録)

  • 再発子宮頸癌に対するペムブロリズマブ療法中に内腸骨動脈-S状結腸瘻を生じた一例(Arterio-enteric fistula in a patient with recurrent cervical cancer treated with pembrolizumab) 査読

    永谷 優華, 八木 裕史, 久保 雄一郎, 牛島 泰宏, 堀 絵美子, 川上 穣, 友延 寛, 安武 伸子, 吉田 祥子, 小玉 敬亮, 安永 昌史, 大神 達寛, 小野山 一郎, 奥川 馨, 淺野間 和夫, 谷口 秀一, 嶋本 富博, 矢幡 秀昭, 石神 康生, 加藤 聖子

    宮崎県医師会医学会誌   46 ( 2 )   147 - 153   2022年9月   （ ISSN:0389-8288 ）

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    記述言語：英語   出版者・発行元：(公社)宮崎県医師会  

    動脈-腸管瘻は消化管出血の原因としてはまれであるが,初発症状が致死性の大量出血の場合もある緊急性の高い疾患である。症例は44歳,9妊7産,子宮頸癌IB3期(扁平上皮癌)に対して広汎子宮全摘出術,両側付属器摘出術,術後補助療法として同時化学放射線療法を施行した。治療終了6ヵ月後に骨盤内再発を認め,全身化学療法を施行したが奏効しなかった。MSI検査の結果,MSI-highであったためペムブロリズマブ療法を開始した。腫瘍の著明な縮小を認め,4コース後の治療効果判定はPRであった。ペムブロリズマブ療法4コース目day7,当科入院中に突然,多量の下血,意識レベルの低下を認めた。緊急造影CTの結果,左内腸骨動脈からS状結腸への造影剤の漏出を認め,左内腸骨動脈-S状結腸瘻と診断した。直ちに左内腸骨動脈塞栓術を施行し止血した。発症から止血まで3時間の間に赤血球32単位,新鮮凍結血漿28単位,血小板10単位の輸血を要した。(著者抄録)

  • A Case of Malignant Phyllodes Tumor of the Breast Metastasizing to the Ovary 査読

    Tada, Y; Yasunaga, M; Tomonobe, H; Yamada, Y; Hori, E; Okugawa, K; Yahata, H; Oda, Y; Kato, K

    INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY   30 ( 4 )   427 - 431   2022年6月   （ ISSN:1066-8969 eISSN:1940-2465 ）

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    出版者・発行元：International Journal of Surgical Pathology  

    Phyllodes tumors of the breast are uncommon, and 6.2% of phyllodes tumors behave in a malignant fashion. The metastatic spread of malignant phyllodes tumor is mainly hematogenous to lung and bone, and malignant phyllodes tumor metastasizing to the ovary is rare, with only 2 cases reported. We report the third case of metastatic malignant phyllodes tumor to the ovary with a focus on the differential diagnosis of ovarian cancer.

    DOI： 10.1177/10668969211056912

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  • Evaluation of Clinical Significance of Lymphovascular Space Invasion in Stage IA Endometrial Cancer 査読

    Okugawa, K; Yahata, H; Hachisuga, K; Tomonobe, H; Yasutake, N; Kodama, K; Kenjo, H; Yagi, H; Ohgami, T; Yasunaga, M; Onoyama, I; Asanoma, K; Hori, E; Ohishi, Y; Oda, Y; Kato, K

    ONCOLOGY   100 ( 4 )   195 - 202   2022年4月   （ ISSN:0030-2414 eISSN:1423-0232 ）

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    記述言語：英語   出版者・発行元：Oncology Switzerland  

    Introduction: The prognostic significance of lymphovascular space invasion (LVSI) in stage IA endometrial cancer remains unclear. The aim of this study was to evaluate the clinical significance of LVSI in stage IA endometrial cancer. Methods: Clinical data of patients with stage IA endometrial cancer who underwent initial surgery at our institution between January 2008 and December 2018 were reviewed retrospectively. Information of patients, surgery, and characteristics of cancer were obtained from medical records and pathological reports. Results: Two hundred ninety-seven patients were enrolled in this study. With a median follow-up of 60 months, 15 patients experienced recurrence (5.1%) and 4 patients died of endometrial cancer (1.3%). The recurrence and mortality rates did not differ significantly between the LVSI-positive and-negative groups (p = 0.07 and p = 0.41, respectively). Recurrence-free survival and endometrial cancer-specific survival also did not differ significantly between these groups (p = 0.11 and p = 0.49, respectively). The 5-year endometrial cancer-specific survival rates for tumors with and without LVSI were 97.0% and 98.9%, respectively. Among patients with low-grade tumors, recurrence-free survival and endometrial cancer-specific survival did not differ significantly between patients with tumors with and without LVSI (p = 0.92 and p = 0.72, respectively). The 5-year endometrial cancer-specific survival rates for low-grade tumors with and without LVSI were 100% and 99.3%, respectively. Conclusion: LVSI was not a prognostic factor of not only stage IA endometrial cancer but also stage IA low-grade cancer.

    DOI： 10.1159/000521382

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