Faculty Profiles - NAKAMURA Keiichiro

Papers - NAKAMURA Keiichiro

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HBOCに対するリスク低減卵管卵巣摘出術及び乳腺外科手術の合同実施に関する当院での取り組み

花谷智美, 原賀順子, 小川千加子, 長尾昌二, 杉原花子, 谷佳紀, 白河伸介, 依田尚之, 松岡敬典, 中村圭一郎, 平沢晃, 増山寿

日本産科婦人科学会雑誌 76 ( 臨増 ) S - 500 2024.2

Adenosine Deaminase Family Acting on RNA 1 (ADAR1) May Be a De Novo Target for Endometriosis Treatment. International journal

Thuy Ha Vu, Keiichiro Nakamura, Kunitoshi Shigeyasu, Kotaro Kubo, Chiaki Kashino, Hisashi Masuyama

In vivo (Athens, Greece) 38 ( 2 ) 683 - 690 2024

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

BACKGROUND/AIM: Adenosine deaminase family acting on RNA 1 (ADAR1) expression was examined to determine its correlation with endometriosis. The biological functions and inhibitory effects of ADAR1 knockdown were investigated in a human endometriotic cell line. MATERIALS AND METHODS: ADAR1 was examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR), and the apoptotic expression of ADAR1 small interfering RNA (siRNA) was confirmed using flow cytometry. The biological functions and inhibitory effects of ADAR1 knockdown were investigated using RT-PCR in a 12Z immortalized human endometriotic cell line. RESULTS: ADAR1 expression was significantly higher in patients with endometriosis than in those without (p<0.001). ADAR1 siRNA increased early and late apoptosis, compared to the mock (24.83%) and control (19.96%) cells. ADAR1 knockdown led to apoptosis through MDA5, RIG-I, IRF3, IRF7, caspase 3, caspase 7, and caspase 8 expression in the cell lines. CONCLUSION: ADAR1 is a potential novel therapeutic target in endometriosis.

DOI： 10.21873/invivo.13489

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Not taking sick leave for gynecologic cancer treatment is negatively associated with returning to the same workplace. International journal

Keiichiro Nakamura, Hirofumi Matsuoka, Kotaro Kubo, Shinsuke Shirakawa, Naoyuki Ida, Junko Haraga, Chikako Ogawa, Kazuhiro Okamoto, Shoji Nagao, Hisashi Masuyama

Japanese journal of clinical oncology 2023.11

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

BACKGROUND: Gynecologic cancers are one of the most common types of malignancies in working-age women. We aimed to determine the factors that impede women from returning to the same workplace after treatment for such cancers. METHODS: A questionnaire-based survey was conducted on 194 women who underwent treatment for gynecologic cancer at the Okayama University (≥1 year after cancer treatment and <65 years of age). We performed a logistic regression analysis to determine the relationship between returning to the same workplace and not taking sick leave. RESULTS: The median age at diagnosis was 49.0 years, and the median time from cancer treatment to questionnaire completion was 3.8 years. Not returning to the same workplace was positively associated with not being regularly employed (P = 0.018), short work time per day (P = 0.023), low personal income (P = 0.004), not taking sick leave (P < 0.001), advanced cancer stage (P = 0.018) and long treatment time (P = 0.032). Interestingly, not taking sick leave was strongly associated with not returning to the same workplace in the multivariable analysis (P < 0.001). CONCLUSIONS: Not taking sick leave likely was negatively associated with returning to the same workplace after the treatment for gynecologic cancer. Therefore, we suggest that steps be taken to formally introduce a sick leave system over and above the paid leave system in Japan.

DOI： 10.1093/jjco/hyad159

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Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the MINT study. International journal

Mamiko Onuki, Fumiaki Takahashi, Takashi Iwata, Hiroshi Nakazawa, Hideaki Yahata, Hiroyuki Kanao, Koji Horie, Katsuyuki Konnai, Ai Nio, Kazuhiro Takehara, Shoji Kamiura, Naotake Tsuda, Yuji Takei, Shogo Shigeta, Noriomi Matsumura, Hiroyuki Yoshida, Takeshi Motohara, Hiroyuki Yamazaki, Keiichiro Nakamura, Junzo Hamanishi, Nobutaka Tasaka, Mitsuya Ishikawa, Yasuyuki Hirashima, Wataru Kudaka, Mayuyo Mori-Uchino, Iwao Kukimoto, Takuma Fujii, Yoh Watanabe, Kiichiro Noda, Hiroyuki Yoshikawa, Nobuo Yaegashi, Koji Matsumoto

Cancer science 114 ( 11 ) 4426 - 4432 2023.11

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

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population-based cancer registry, the incidence of ICC among young women aged 20-29 years showed a significant decline from 3.6 to 2.8 per 100 000 women-years during 2016-2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20-29 years also decreased from 256 cases to 135 cases during 2011-2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20-29 years during 2017-2022 (90.5%-64.7%, p = 0.05; Cochran-Armitage trend test). This is the first report to suggest population-level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination.

DOI： 10.1111/cas.15943

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Efficacy and safety of olaparib, olaparib plus bevacizumab and niraparib maintenance treatment in Japanese patients with platinum-sensitive advanced ovarian cancer. International journal

Keiichiro Nakamura, Hirofumi Matsuoka, Masae Yorimitsu, Mariko Ogawa, Miho Kanemori, Kotaro Sueoka, Ayumi Kozai, Hiroko Nakamura, Tomoko Haruma, Yuko Shiroyama, Yuu Hayata, Hirokazu Sugii, Akiko Ueda, Shuichi Kurihara, Saiko Urayama, Miyuki Shimizu, Hisashi Masuyama

Japanese journal of clinical oncology 2023.9

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

OBJECTIVE: To investigate whether maintenance treatment could be safely and effectively performed with olaparib, olaparib plus bevacizumab and niraparib in platinum-sensitive advanced ovarian cancer at multiple institutions in Japan. METHODS: We investigated progression-free survival and adverse events in 117 patients with platinum-sensitive advanced ovarian cancer treated with maintenance therapy. RESULTS: The median progression-free survival of 117 patients was 20.1 months. Patients with germline BRCA pathogenic variants had a significantly better prognosis than the other groups (P < 0.001). Furthermore, in the multivariate analysis, stage IV (P = 0.016) and germline BRCA wild-type (P ≤ 0.001) were significantly associated with worse progression-free survival in patients with advanced ovarian cancer. Regarding adverse events, all three types of maintenance treatment were significantly worse than chemotherapy given before maintenance treatment with respect to renal function (olaparib, P = 0.037; olaparib plus bevacizumab, P < 0.001; and niraparib, P = 0.016). CONCLUSION: Maintenance treatment was performed effectively and safely. Renal function deterioration is likely to occur during maintenance treatment, and careful administration is important in platinum-sensitive advanced ovarian cancer.

DOI： 10.1093/jjco/hyad125

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子宮体癌卵巣転移が多彩な組織像を呈した1例

花谷智美, 原賀順子, 大石恵一, 白河伸介, 谷佳紀, 杉原花子, 入江恭平, 依田尚之, 松岡敬典, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 72 ( Suppl. ) S59 - S60 2023.9

Relationship Between Hematological Toxicities During Maintenance Treatment and During Chemotherapy Before Maintenance Treatment in Patients With Platinum-sensitive Relapsed Ovarian Cancer. International journal

Hirofumi Matsuoka, Keiichiro Nakamura, Masae Yorimitsu, Mariko Ogawa, Miho Kanemori, Kotaro Sueoka, Ayumi Kozai, Hiroko Nakamura, Tomoko Haruma, Yuko Shiroyama, Yuu Hayata, Hirokazu Sugii, Akiko Ueda, Shuichi Kurihara, Saiko Urayama, Miyuki Shimizu, Hisashi Masuyama

Anticancer research 43 ( 8 ) 3653 - 3658 2023.8

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

BACKGROUND/AIM: To determine if maintenance treatment can be performed effectively and safely in patients with platinum-sensitive relapsed ovarian cancer. PATIENTS AND METHODS: We carried out a multi-center study to investigate progression-free survival (PFS) and adverse events (AEs) in 229 patients receiving maintenance treatment for platinum-sensitive relapsed ovarian cancer. RESULTS: The median PFS in the 229 patients with maintenance treatment was 14.0 months (95% confidence interval=10.3-17.6 months). The hematological toxicities included ≥grade 3 anemia in 33.2% of cases. Anemia during maintenance treatment was significantly more common than anemia during chemotherapy given before maintenance treatment (p<0.001). Anemia during chemotherapy prior to maintenance treatment significantly increased the risk of anemia during maintenance treatment, compared with other clinical features (p<0.001). CONCLUSION: Maintenance treatment can be performed safely and effectively in patients with platinum-sensitive relapsed ovarian cancer. Anemia during chemotherapy given before maintenance treatment significantly increased the risk of developing anemia during maintenance treatment in patients with platinum-sensitive relapsed ovarian cancer.

DOI： 10.21873/anticanres.16546

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Pure abscopal effect in a patient with advanced uterine carcinosarcoma. International journal

Kazuhiro Okamoto, Kotaro Yoshio, Shinsuke Shirakawa, Kyohei Irie, Naoyuki Ida, Hirofumi Matsuoka, Junko Haraga, Chikako Ogawa, Keiichiro Nakamura, Shoji Nagao, Hisashi Masuyama

Radiology case reports 18 ( 7 ) 2447 - 2451 2023.7

Language：English

The abscopal effect is a rare phenomenon, in which tumor shrinkage in the nonirradiated metastatic region is observed after radiotherapy. Certainly, this response is sometimes reported with the combined use of immune-checkpoint inhibitors, but a pure abscopal effect is extremely rare, especially in endometrial cancer. We present the case of a 79-year-old woman with an advanced endometrial carcinosarcoma. She was treated with surgical reduction of the primary lesion, followed by radiotherapy of the metastatic regional lymph nodes. Distant metastases were detected in radiological imaging test 2 months after the completion of radiotherapy, and we carefully followed up without any treatment considering the patient's tolerability for further procedures. Six months after recurrence, she experienced cytoreduction in the metastatic lesions confirmed through imaging findings, which was believed to be an abscopal effect, and maintained this shrinking state for 15 months. Herein, we describe this pure abscopal effect from the perspective of imaging, pathological and molecular findings, and therapeutic strategies.

DOI： 10.1016/j.radcr.2023.04.031

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当院におけるMSI陽性者の遺伝外来受診に関する現状と課題

原賀順子, 小川千加子, 長尾昌二, 依田尚之, 白河伸介, 入江恭平, 松岡敬典, 中村圭一郎, 平沢晃, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 65回 374 - 374 2023.7

当院におけるcadaver surgical training(CST)を活用した,広汎子宮全摘出術の成績向上への試み

入江恭平, 白河伸介, 松岡敬典, 依田尚之, 原賀順子, 久保光太郎, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 65回 347 - 347 2023.7

Bevacizumab併用化学療法後の再発卵巣癌のプラチナ製剤free期間と化学療法効果の後方視的再検討

田中圭紀, 宇佐美知香, 石川雅子, 近藤英司, 利部正裕, 平林啓, 松村謙臣, 佐藤慎也, 西村正人, 荒川敦志, 中村圭一郎, 金野陽輔, 竹原和宏, 藤原聡枝, 末岡幸太郎, 中村紘子, 古宇家正, 伊藤公彦, 本郷淳司

日本婦人科腫瘍学会学術講演会プログラム・抄録集 65回 294 - 294 2023.7

卵巣癌治療中に皮膚筋炎を発症し治療に難渋した一例

徳本佑奈, 依田尚之, 兼森雅敏, 岡本和浩, 松岡敬典, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 71 ( 2 ) 261 - 265 2023.6

Language：Japanese Publisher：中国四国産科婦人科学会

今回,我々は卵巣癌治療中に急激な筋力低下,嚥下障害を伴った皮膚筋炎を経験した。全身状態不良の中で積極的な卵巣癌治療を優先的に行うことで皮膚筋炎の改善を認めたため報告する。【症例】68歳,女性。1ヵ月前に当院にて審査腹腔鏡手術を行い卵巣癌IIIC期(FIGO2014,pT3cN0M0)高異型度漿液性癌と診断した。MyChoice診断システムを提出した上で,結果開示までの間,術前化学療法としてddTC(Dose dense PTX+CBDCA)療法を開始した。1サイクル施行後,急激な筋力低下,嚥下障害が出現し,皮膚筋炎が疑われ当科入院となった。Gottron丘疹や著明な筋原性酵素の上昇を認め,抗TIF1γ抗体陽性であり,卵巣癌を契機に発症した皮膚筋炎と診断した。皮膚筋炎に対しステロイド投与を開始した。肝酵素の上昇を伴っていたが,筋原性酵素の低下に伴い改善したことから筋肉の崩壊に伴う肝酵素の上昇と診断し,第8病日に化学療法2サイクル目を施行した。卵巣癌の病状制御は良好であったが,皮膚筋炎に対する治療反応が乏しく免疫グロブリン療法も併用した。ステロイド投与と抗癌剤治療による低免疫状態のため全身管理に苦慮し,リハビリテーションも遅々としたものであった。化学療法5サイクル終了後,残存病変の完全切除による皮膚筋炎の改善を期待し,単純子宮全摘出術,両側附属器摘出術,大網切除術を施行し,肉眼的残存腫瘍なしとできた。その後も化学療法とリハビリテーションを継続し,術前に比して著明に四肢の筋力や嚥下機能の向上を認めた。【結語】皮膚筋炎と卵巣癌の治療を併用することは長期的で繊細な全身管理を要するが,化学療法だけでなく手術療法を伴った卵巣癌の標準治療を適切に敢行することが皮膚筋炎の改善に繋がった。(著者抄録)

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ADAR1 has an oncogenic function and can be a prognostic factor in cervical cancer. International journal

Keiichiro Nakamura, Kunitoshi Shigeyasu, Kazuhiro Okamoto, Hirofumi Matsuoka, Hisashi Masuyama

Scientific reports 13 ( 1 ) 4720 - 4720 2023.3

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

Adenosine deaminase acting on RNA 1 (ADAR1), a recently described epigenetic modifier, is believed to play a critical oncogenic role in human cancers. However, its functional role and clinical significance in cervical cancer (CC) remain unclear. ADAR1 knockdown was performed to investigate its oncogenic functions in SiHa (HPV16), HeLa (HPV18), and Yumoto (non-HPV) CC cell lines. Cytoplasmic and nuclear ADAR1 expression were examined to clarify their correlation with clinicopathological parameters and prognosis in patients with CC. This resulted in increased apoptosis and necroptosis in HPV16 -type SiHa, HPV18-type HeLa, and non-HPV-type Yumoto CC cell lines. Progression-free survival (PFS) rates of patients exhibiting high cytoplasmic and nuclear ADAR1 expression were poorer than those in the other groups (P = 0.016). Multivariate analysis indicated that the combination of higher cytoplasmic and nuclear ADAR1 expression was an independent predictor of prognosis in patients with CC (P = 0.017). ADAR1 could be a potential therapeutic target for HPV-positive or HPV-negative CC. The combination of cytoplasmic and nuclear ADAR1 comprises a better prognostic factor for CC.

DOI： 10.1038/s41598-023-30452-y

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ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer. International journal

Nanako Hata, Kunitoshi Shigeyasu, Yuzo Umeda, Shuya Yano, Sho Takeda, Kazuhiro Yoshida, Tomokazu Fuji, Ryuichi Yoshida, Kazuya Yasui, Hibiki Umeda, Toshiaki Takahashi, Yoshitaka Kondo, Hiroyuki Kishimoto, Yoshiko Mori, Fuminori Teraishi, Hideki Yamamoto, Hiroyuki Michiue, Keiichiro Nakamura, Hiroshi Tazawa, Toshiyoshi Fujiwara

Scientific reports 13 ( 1 ) 2078 - 2078 2023.2

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

Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy.

DOI： 10.1038/s41598-023-29397-z

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初回進行卵巣癌に対するPARP阻害剤維持療法の施行状況と安全性の検討

松岡敬典, 白河伸介, 入江恭平, 岡本和浩, 依田尚之, 原賀順子, 久保光太郎, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

日本産科婦人科学会雑誌 75 ( 臨増 ) S - 291 2023.2

子宮頸癌に対し放射線治療後骨盤骨折発生の多施設共同後ろ向きコホート研究

白河伸介, 長尾昌二, 入江恭平, 岡本和浩, 松岡敬典, 依田尚之, 原賀順子, 小川千加子, 中村圭一郎, 依光正枝, 児玉順一, 永坂久子, 中西美惠, 今福紀章, 山本暖, 増山寿, IPFAR

日本産科婦人科学会雑誌 75 ( 臨増 ) S - 450 2023.2

腹腔鏡下手術の適応への判断に超音波ガイド下針生検を施行した子宮腫瘤の検討

藤川淳, 久保光太郎, 兼森雅敏, 白河伸介, 岡本和浩, 依田尚之, 松岡敬典, 小川千加子, 鎌田泰彦, 中村圭一郎, 長尾昌二, 増山寿

日本産科婦人科学会雑誌 75 ( 臨増 ) S - 427 2023.2

当科におけるマイクロサテライト不安定性検査とペムブロリズマブ投与の現況

長谷井稜子, 松岡敬典, 入江恭平, 岡本和浩, 依田尚之, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 71 ( 1 ) 117 - 121 2022.12

Language：Japanese Publisher：中国四国産科婦人科学会

2018年12月,高頻度マイクロサテライト不安定性(microsatellite instability-high;MSI-H)を有する固形癌に対して免疫チェックポイント阻害剤であるペムブロリズマブが保険収載された。MSI-H症例は全固形癌の中で子宮体癌に最も多いと報告されている。そこで当科におけるMSI検査やペムブロリズマブ投与の現状,免疫関連有害事象(immune-related Adverse Events;irAE)の発症について調査した。対象は,2018から2021年に化学療法後に増悪し,MSI検査を実施した婦人科癌患者とし,当院の倫理委員会の承認を得ておこなった。MSI検査提出数は65例であり,内訳は卵巣癌24例(36.9%),子宮体癌21例(32.3%),子宮頸癌18例(27.7%),外陰癌1例(1.5%),子宮癌肉腫1例(1.5%)であった。陽性例は7例(10.8%)であり,内訳は子宮体癌6/21例(28.6%),卵巣癌1/24例(4.2%)であった。陽性7例中6例でペムブロリズマブが投与され,奏功は4/6例(66.7%),progression free survivalの中央値は24.5ヵ月(3-37)であった。ペムブロリズマブ投与サイクル数の中央値は26サイクル(3-52)であった。投与継続中は3例,一時中止・再開は1例,中止は2例であった。3/6例でirAEを発症し,Grade2が1例(甲状腺機能亢進症),Grade3が2例(自己免疫性髄膜脳炎,自己免疫性肝炎)であり,Grade3のirAE発症例は2例ともペムブロリズマブ投与を中止した。MSI-H症例は子宮体癌で有意に多く,ペムブロリズマブ使用例では半数以上が奏功している。セカンドライン以降の化学療法の有効性が低い子宮体癌においては特に,ペムブロリズマブは有効な治療となり得るため,コンパニオン診断としてMSI検査を提出することは重要である。投与に際しては臓器非特異的なirAEが起こり得るため,院内連携システムの構築が重要である。(著者抄録)

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分葉状頸管腺過形成の診断で腹腔鏡下子宮全摘出術を施行し,子宮頸部上皮内胃型腺癌が判明した1例

依田尚之, 久保光太郎, 田中佑衣, 兼森雅敏, 白河伸介, 岡本和浩, 松岡敬典, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 71 ( 1 ) 99 - 103 2022.12

Language：Japanese Publisher：中国四国産科婦人科学会

子宮頸部に胃型粘液を産生する多嚢胞性病変を認めた場合に分葉状頸管腺過形成(Lobular endocervical glandular hyperplasia:LEGH)と最小偏倚腺癌(minimal deviation adenocarcinoma:MDA)を含む胃型粘液性癌(mucinous carcinoma,gastric type:GAS)とを鑑別することは非常に困難である。LEGHと診断し,腹腔鏡下子宮全摘出術を行い子宮頸部上皮内胃型腺癌と診断した1例を経験したので報告する。症例は56歳女性,4妊2産。前医の子宮頸管細胞診にてatypical glandular cells(AGC)を認めた。その後の子宮頸管細胞診の再検や頸管内掻爬組織診では異常所見を認めないが,子宮頸部多発嚢胞がありLEGH疑いにて精査加療目的に当科紹介となった。頸管内掻爬組織診の再検にて,子宮頸管線上皮はMUC5AC陽性,MUC6陽性,HIK1083一部陽性を示し,Endocervical epithelium with gastric type mucinであり,LEGHと診断した。画像所見や子宮頸管細胞診・組織診から悪性を強く疑わず,経過観察又は,子宮摘出を提示したところ,患者は子宮摘出を希望した。腹腔鏡下子宮全摘出術,両側付属器摘出術を施行し,術後病理学的診断はAdenocarcinoma in situ(gastric type)associated with LEGHであった。その後,外来にて定期検診を施行しているが明らかな再発を認めない。MRI所見,子宮頸管細胞診異常,gastric type mucinから術前診断し,LEGHの治療戦略を立てるべきだが,腹腔鏡下子宮摘出術を選択する場合には,AISやMDAの合併している可能性に留意した術式を工夫すべきかもしれない。(著者抄録)

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Barbed sutureによる2層連続縫合は帝王切開による子宮創の菲薄化を予防する

牧尉太, 三苫智裕, 樫野千明, 依田尚之, 光井崇, 衛藤英理子, 中村圭一郎, 鎌田泰彦, 増山寿

日本女性医学学会雑誌 30 ( 1 ) 112 - 112 2022.10

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