Faculty Profiles - NAGAO Shoji

Papers - NAGAO Shoji

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Epithelioid trophoblastic tumor diagnosed during a thorough examination of recurrent implantation failure: A case report

Yasuhiko Kamada, Junko Haraga, Naoyuki Ida, Shoji Nagao, Hiroyuki Yanai, Hisashi Masuyama

Journal of Obstetrics and Gynaecology Research 2025.3

Incidence and risk factors for venous thromboembolism in gynecological cancer: the GOTIC-VTE trial. International journal

Yoshifumi Takahashi, Hiroyuki Fujiwara, Kouji Yamamoto, Satoshi Yamaguchi, Shoji Nagao, Masashi Takano, Morikazu Miyamoto, Kosei Hasegawa, Maiko Miwa, Toshiaki Yasuoka, Soichi Yamashita, Takashi Hirakawa, Tomonori Nagai, Yoshinobu Hamada, Masaya Uno, Mayuyo Mori-Uchino, Michitaka Ohwada, Akira Mitsuhashi, Toyomi Satoh, Keiichi Fujiwara, Mitsuaki Suzuki

Journal of thrombosis and thrombolysis 2024.11

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

Real-world data on venous thromboembolism (VTE) in Japanese patients with gynecological cancer are lacking. The GOTIC-VTE trial aimed to evaluate the frequency of VTE-associated events and risk factors at the time of cancer diagnosis and during 1-year follow-up. From July 2017 to February 2019, patients with endometrial, cervical, ovarian, tubal, or peritoneal cancer who underwent VTE screening within 2 months before registration, were enrolled. Of the 1008 patients enrolled, 881 were included in the analysis set, 51 (5.8%) had VTE at the time of cancer diagnosis (baseline), 7 (0.8%) had symptomatic VTE, and the majority had asymptomatic VTE (n = 44; 5.0%). Patients with ovarian, tubal, or peritoneal cancer had a higher incidence of VTE (13.7%) than those with other cancer types. During the 1-year follow-up, 0.9% (n = 8) of the patients had symptomatic VTE, 3.5% (n = 31) had composite VTE (symptomatic VTE and incidental VTE requiring treatment), 0.2% (n = 2) had bleeding events, and 4.3% (n = 38) had all-cause death, all of which were significantly higher in the VTE group at baseline. In the multivariate analysis, chemotherapy was an independent risk factor for composite VTE during the 1-year follow-up (hazard ratio 3.85, 95% confidence interval 1.39-13.63, p = 0.018). Among gynecological cancers, VTE incidence is particularly high in ovarian, tubal, or peritoneal cancer, and patients undergoing chemotherapy should be cautioned against VTE occurrence during treatment.The GOTIC-VTE trial Unique identifier, jRCTs031180124; Registration date, April 06, 2017.

DOI： 10.1007/s11239-024-03055-1

当院で施行した婦人科癌のがん遺伝子パネル検査の実施状況と課題

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

日本癌治療学会学術集会抄録集 62回 P54 - 1 2024.10

Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study.

Shoji Nagao, Shin Nishio, Kazuhiro Takehara, Shinya Sato, Toyomi Satoh, Muneaki Shimada, Satoshi Yamaguchi, Hiroshi Tanabe, Masashi Takano, Kouji Horie, Yuji Takei, Yuichi Imai, Yumi Hibino, Kosei Hasegawa, Munetaka Takekuma, Kazuto Nakamura, Hirokuni Takano, Keiichi Fujiwara, Hisashi Masuyama

International journal of clinical oncology 2024.7

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

BACKGROUND: We previously demonstrated the applicability of the concept of "platinum sensitivity" in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study. METHODS: Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data. RESULTS: In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12-23 months, 18/43 (42%); 24-35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12-23 months, 0/19 (0%); 24-35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)]. CONCLUSIONS: Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering.

DOI： 10.1007/s10147-024-02585-1

再発子宮体癌に対するプラチナ製剤再投与 SGSG012/GOTIC004研究追加報告

長尾昌二, 西尾真, 竹原和宏, 佐藤慎也, 佐藤豊実, 島田宗昭, 山口聡, 田部宏, 高野政志, 堀江弘二, 藤原寛行, 宮城悦子, 日比野佑美, 長谷川幸清, 武隈宗孝, 中村和人, 高野浩邦, 藤原恵一, 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 66回 254 - 254 2024.7

婦人科悪性手術後のアセトアミノフェン定期静脈投与に関する検討

原賀順子, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 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

日本婦人科腫瘍学会学術講演会プログラム・抄録集 66回 391 - 391 2024.7

不妊治療中に子宮内膜異型増殖症・子宮体がんと診断され妊孕性温存治療後に生児を得た2例

鎌田泰彦, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 依田尚之, 松岡敬典, 原賀順子, 光井崇, 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 66回 371 - 371 2024.7

進行上皮性卵巣癌に対する超音波ガイド下針生検

杉原花子, 谷佳紀, 白河伸介, 入江恭平, 依田尚之, 松岡敬典, 原賀順子, 小川千加子, 鎌田泰彦, 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 66回 415 - 415 2024.7

婦人科悪性手術後のアセトアミノフェン定期静脈投与に関する検討

原賀順子, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 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

日本婦人科腫瘍学会学術講演会プログラム・抄録集 66回 391 - 391 2024.7

化学療法施行中の貧血に対する静注鉄剤製剤投与に関する検討

松岡敬典, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 依田尚之, 原賀順子, 小川千加子, 鎌田泰彦, 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 66回 427 - 427 2024.7

がん対策基本法前後での離職状況の検討

谷佳紀, 中村圭一郎, 杉原花子, 白河伸介, 入江恭平, 松岡敬典, 依田尚之, 原賀順子, 小川千加子, 鎌田泰彦, 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 66回 324 - 324 2024.7

当科におけるリスク低減卵管卵巣摘出術後の女性ヘルスケアについての検討

川口優里香, 小川千加子, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 松岡敬典, 依田尚之, 原賀順子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 72 ( 2 ) 239 - 244 2024.6

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

【目的】遺伝性乳癌卵巣癌(Hereditary Brest and Ovarian Cancer:HBOC)では,卵巣癌未発症者の場合,リスク低減卵管卵巣摘出術(risk reducing salpingo-oophorectomy:RRSO)が唯一の卵巣癌予防法であり,通常35～40歳で出産完了時に行うことが推奨されている。そのため,至適時期でのRRSOは,外科的閉経を招き女性ヘルスケアに影響を与える。今回我々は,当院でRRSOを行った患者の現状と今後のヘルスケアにおけるマネジメントについて検討し,課題を抽出した。【方法】2016年4月～2023年9月にRRSOを施行された66例について,年齢,BRCA1/2バリアント,乳癌既往と治療,閉経の有無,術後更年期症状の有無,女性ヘルスケアの検査と治療などの診療情報を診療録より抽出し,検討した。【成績】RRSO実施時の年齢中央値は49歳,既閉経例は48/66例(73%)であった。7例でRRSO以前に乳癌への抗癌剤治療により早発閉経をきたしていた。術後更年期症状は,閉経患者の6/48例(12%),未閉経患者の8/18例(44%)に認めたが性機能障害などに踏み込めた問診は行われていなかった。更年期症状に対して8例で漢方療法やサプリメントなどの非ホルモン療法が,2例でホルモン補充療法(Hormone Replacement Therapy:HRT)が使用された。術後骨粗鬆症検査は16例で行われ,4例で薬物療法を要した。この4例はいずれも乳癌治療により閉経をした症例で,閉経年齢中央値は39.5歳であった。【結論】本邦のRRSO症例の多くは乳癌治療やそれに伴う閉経を経験しており,潜在的に女性ヘルスケアを必要としているが,その提供は未だ不十分である。適切に女性ヘルスケアを提供するためのシステムづくりが今後の課題と考えられた。(著者抄録)

腫瘍の自然脱落により診断に至った子宮腺肉腫の一例

田中佑衣, 依田尚之, 白河伸介, 岡本和浩, 松岡敬典, 原賀順子, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 72 ( 2 ) 333 - 336 2024.6

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

子宮腺肉腫は良性上皮性成分と肉腫成分から構成される上皮性・間葉性混合腫瘍で,子宮悪性腫瘍の約0.5%未満,肉腫の約5%を占める稀な疾患である。今回,我々は自然脱落した腫瘍組織から診断に至った子宮腺肉腫の一例を経験したので報告する。症例は69歳,2妊2産。不正性器出血を主訴に前医を受診し,子宮内膜ポリープの腟内脱出が疑われた。子宮内膜組織診で悪性所見を認めなかったが,MRIにて子宮体癌の可能性を指摘され,当科紹介となった。初診2日後,自宅にて中等量の性器出血と腟外への腫瘤の脱出を認め,緊急入院となった。入院中に手拳大の暗赤色腫瘤が自然脱落し,病理組織検査にて凝固壊死を伴う子宮腺肉腫と診断した。子宮腺肉腫IA期相当に対して腹式単純子宮全摘出術,両側付属器摘出術を施行し,術後病理学的診断は子宮腺肉腫IA期(pT1aNX)であった。術後補助療法は行わず,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。子宮腺肉腫は主症状として不正性器出血を認めるが,術前の画像診断や組織診の正診率は低く,良性疾患との鑑別が困難である。不正性器出血や子宮口からの腫瘤脱出を伴う再発性のポリープ様病変を認めた際は,本疾患を鑑別に挙げることが重要である。(著者抄録)

当科におけるリスク低減卵管卵巣摘出術後の女性ヘルスケアについての検討

川口優里香, 小川千加子, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 松岡敬典, 依田尚之, 原賀順子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 72 ( 2 ) 239 - 244 2024.6

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

【目的】遺伝性乳癌卵巣癌(Hereditary Brest and Ovarian Cancer:HBOC)では,卵巣癌未発症者の場合,リスク低減卵管卵巣摘出術(risk reducing salpingo-oophorectomy:RRSO)が唯一の卵巣癌予防法であり,通常35～40歳で出産完了時に行うことが推奨されている。そのため,至適時期でのRRSOは,外科的閉経を招き女性ヘルスケアに影響を与える。今回我々は,当院でRRSOを行った患者の現状と今後のヘルスケアにおけるマネジメントについて検討し,課題を抽出した。【方法】2016年4月～2023年9月にRRSOを施行された66例について,年齢,BRCA1/2バリアント,乳癌既往と治療,閉経の有無,術後更年期症状の有無,女性ヘルスケアの検査と治療などの診療情報を診療録より抽出し,検討した。【成績】RRSO実施時の年齢中央値は49歳,既閉経例は48/66例(73%)であった。7例でRRSO以前に乳癌への抗癌剤治療により早発閉経をきたしていた。術後更年期症状は,閉経患者の6/48例(12%),未閉経患者の8/18例(44%)に認めたが性機能障害などに踏み込めた問診は行われていなかった。更年期症状に対して8例で漢方療法やサプリメントなどの非ホルモン療法が,2例でホルモン補充療法(Hormone Replacement Therapy:HRT)が使用された。術後骨粗鬆症検査は16例で行われ,4例で薬物療法を要した。この4例はいずれも乳癌治療により閉経をした症例で,閉経年齢中央値は39.5歳であった。【結論】本邦のRRSO症例の多くは乳癌治療やそれに伴う閉経を経験しており,潜在的に女性ヘルスケアを必要としているが,その提供は未だ不十分である。適切に女性ヘルスケアを提供するためのシステムづくりが今後の課題と考えられた。(著者抄録)

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

Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial

Ana Oaknin, Laurence Gladieff, Jerónimo Martínez-García, Guillermo Villacampa, Munetaka Takekuma, Ugo De Giorgi, Kristina Lindemann, Linn Woelber, Nicoletta Colombo, Linda Duska, Alexandra Leary, Ana Godoy-Ortiz, Shin Nishio, Antoine Angelergues, Maria Jesús Rubio, Lorena Fariñas-Madrid, Satoshi Yamaguchi, Domenica Lorusso, Isabelle Ray-Coquard, Luis Manso, Florence Joly, Jesús Alarcón, Philippe Follana, Ignacio Romero, Coriolan Lebreton, J. Alejandro Pérez-Fidalgo, Mayu Yunokawa, Hanna Dahlstrand, Véronique D'Hondt, Leslie M. Randall, Sophie Abadie-Lacourtoisie, Claudia Andreetta, Nerea Anzizar, Daiseuke Aoki, Maria Pilar Barretina-Ginesta, Marco Battista, Charlotte Bellier, Anne Gry Bentzen, Dominique Berton, Bertrand Billemont, Line Bjørge, Maria Bjurberg, Destin Black, Alessandra Bologna, Elena Ioana Braicu, Claudia Casanova, Radoslav Chekerov, Annick Chevalier, Juan Fernando Cueva, Bastian Czogalla, Nicolas Delanoy, Dominik Denschlag, Oscar Derke, Michael Eichbaum, Takayuki Enomoto, Carmen Esteban, Michel Fabbro, Tanja Fehm, Annamaria Ferrero, Markus Fleisch, Anne Floquet, Antonio Frassoldati, Lydia Gaba, Angiolo Gadducci, Yolanda García, Elena Geuna, Eva Guerra, Lars Hanker, Anne Claire Hardy-Bessard, Philipp Harter, Kosei Hasegawa, Kristina Hellman, Ana Herrero, Felix Hilpert, Dionyssios Katsaros, Matthias Koegel, Anthoula Koliadi, Jean Emmanuel Kurtz, Bjoern Lampe, Andrea Alberto Lissoni, Alain Lortholary, Giorgia Mangili, Laura Mansi, Frederik Marmé, Cara Mathews, William Mina, Shinichiro Minobe, Katherine Moxley, Shoji Nagao, Ornella Nicoletto, Koji Nishino, Hiroshi Nishio, Michaela Onstad, Beatriz Pardo, Carmela Pisano, Andrés Poveda, Julia Radosa, Leslie M. Randall, Andrés Redondo, Debra Richardson

The Lancet 403 ( 10421 ) 31 - 43 2024.1

Publishing type：Research paper (scientific journal)

Background: The GOG240 trial established bevacizumab with chemotherapy as standard first-line therapy for metastatic or recurrent cervical cancer. In the BEATcc trial (ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030), we aimed to evaluate the addition of an immune checkpoint inhibitor to this standard backbone. Methods: In this investigator-initiated, randomised, open-label, phase 3 trial, patients from 92 sites in Europe, Japan, and the USA with metastatic (stage IVB), persistent, or recurrent cervical cancer that was measurable, previously untreated, and not amenable to curative surgery or radiation were randomly assigned 1:1 to receive standard therapy (cisplatin 50 mg/m2 or carboplatin area under the curve of 5, paclitaxel 175 mg/m2, and bevacizumab 15 mg/kg, all on day 1 of every 3-week cycle) with or without atezolizumab 1200 mg. Treatment was continued until disease progression, unacceptable toxicity, patient withdrawal, or death. Stratification factors were previous concomitant chemoradiation (yes vs no), histology (squamous cell carcinoma vs adenocarcinoma including adenosquamous carcinoma), and platinum backbone (cisplatin vs carboplatin). Dual primary endpoints were investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumours version 1.1 and overall survival analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03556839, and is ongoing. Findings: Between Oct 8, 2018, and Aug 20, 2021, 410 of 519 patients assessed for eligibility were enrolled. Median progression-free survival was 13·7 months (95% CI 12·3–16·6) with atezolizumab and 10·4 months (9·7–11·7) with standard therapy (hazard ratio [HR]=0·62 [95% CI 0·49–0·78]; p<0·0001); at the interim overall survival analysis, median overall survival was 32·1 months (95% CI 25·3–36·8) versus 22·8 months (20·3–28·0), respectively (HR 0·68 [95% CI 0·52–0·88]; p=0·0046). Grade 3 or worse adverse events occurred in 79% of patients in the experimental group and in 75% of patients in the standard group. Grade 1–2 diarrhoea, arthralgia, pyrexia, and rash were increased with atezolizumab. Interpretation: Adding atezolizumab to a standard bevacizumab plus platinum regimen for metastatic, persistent, or recurrent cervical cancer significantly improves progression-free and overall survival and should be considered as a new first-line therapy option. Funding: F Hoffmann-La Roche.

DOI： 10.1016/S0140-6736(23)02405-4

Niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer: final results of a multicenter phase 2 study

Hiroaki Itamochi, Nobuhiro Takeshima, Junzo Hamanishi, Kosei Hasegawa, Motoki Matsuura, Kiyonori Miura, Shoji Nagao, Hidekatsu Nakai, Naotake Tanaka, Hideki Tokunaga, Shin Nishio, Hidemichi Watari, Yoshihito Yokoyama, Yoichi Kase, Shuuji Sumino, Ai Kato, Ajit Suri, Toshiaki Yasuoka, Kazuhiro Takehara

Journal of Gynecologic Oncology 2024

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

【婦人科悪性腫瘍手術-トラブルシューティングとその予防法-】準広汎子宮全摘術

依田尚之, 長尾昌二, 増山寿

産婦人科の実際 72 ( 12 ) 1276 - 1284 2023.11

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

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

Pure abscopal effect in a patient with advanced uterine carcinosarcoma. Reviewed 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

血清TFPI-2がCA125より病勢を反映した当院卵巣明細胞癌の1例

荒武淳一, 荻本圭祐, 市田啓佑, 成田萌, 濱崎京子, 中澤浩志, 澁谷剛志, 北井美穂, 塩崎隆也, 若橋宣, 須藤保, 長尾昌二, 山口聡

日本婦人科腫瘍学会学術講演会プログラム・抄録集 65回 370 - 370 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

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)

Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study. Reviewed

Shoji Nagao, Jun Tamura, Takashi Shibutani, Maiko Miwa, Tomoyasu Kato, Ayumi Shikama, Yuji Takei, Natsuko Kamiya, Naoki Inoue, Kazuto Nakamura, Aya Inoue, Koji Yamamoto, Keiichi Fujiwara, Mitsuaki Suzuki

International journal of clinical oncology 28 ( 6 ) 804 - 815 2023.6

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice. PATIENTS AND METHODS: We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III-IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy. RESULTS: Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99-1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80-1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74-1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65-1.47, p = 0.93). CONCLUSIONS: NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

DOI： 10.1007/s10147-023-02329-7

Intraperitoneal Carboplatin for Ovarian Cancer — A Phase 2/3 Trial Reviewed

Shoji Nagao, Keiichi Fujiwara, Kouji Yamamoto, Hiroshi Tanabe, Aikou Okamoto, Kazuhiro Takehara, Motoaki Saito, Hiroyuki Fujiwara, David S.P. Tan, Satoshi Yamaguchi, Sosuke Adachi, Akira Kikuchi, Takeshi Hirasawa, Takeshi Yokoi, Tomonori Nagai, Toyomi Sato, Shoji Kamiura, Akira Fujishita, Wong Wai Loong, Karen Chan, Peter Syks, Alexsander Olawaye, Sang-Young Ryu, Hiroyuki Shigeta, Eiji Kondo, Yoshihito Yokoyama, Takashi Matsumoto, Kosei Hasegawa, Takayuki Enomoto

NEJM Evidence 2 ( 5 ) 2023.4

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

Veliparib with frontline chemotherapy and as maintenance in Japanese women with ovarian cancer: a subanalysis of efficacy, safety, and antiemetic use in the phase 3 VELIA trial. Reviewed

Mika Mizuno, Kimihiko Ito, Hidekatsu Nakai, Hidenori Kato, Shoji Kamiura, Kimio Ushijima, Shoji Nagao, Hirokuni Takano, Masao Okadome, Munetaka Takekuma, Hideki Tokunaga, Satoru Nagase, Daisuke Aoki, Robert L Coleman, Yasuko Nishimura, Christine K Ratajczak, Hideyuki Hashiba, Hao Xiong, Noriyuki Katsumata, Takayuki Enomoto, Aikou Okamoto

International journal of clinical oncology 28 ( 1 ) 163 - 174 2022.12

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

BACKGROUND: The phase 3 VELIA trial evaluated veliparib with carboplatin/paclitaxel and as maintenance in patients with high-grade serous ovarian carcinoma. METHODS: Patients with previously untreated stage III-IV high-grade serous ovarian carcinoma were randomized 1:1:1 to control (placebo with carboplatin/paclitaxel and placebo maintenance), veliparib-combination-only (veliparib with carboplatin/paclitaxel and placebo maintenance), or veliparib-throughout (veliparib with carboplatin/paclitaxel and veliparib maintenance). Randomization stratification factors included geographic region (Japan versus North America or rest of the world). Primary end point was investigator-assessed median progression-free survival. Efficacy, safety, and pharmacokinetics were evaluated in a subgroup of Japanese patients. RESULTS: Seventy-eight Japanese patients were randomized to control (n = 23), veliparib-combination-only (n = 30), and veliparib-throughout (n = 25) arms. In the Japanese subgroup, median progression-free survival for veliparib-throughout versus control was 27.4 and 19.1 months (hazard ratio, 0.46; 95% confidence interval, 0.18-1.16; p = 0.1 [not significant]). In the veliparib-throughout arm, grade 3/4 leukopenia, neutropenia, and thrombocytopenia rates were higher for Japanese (32%/88%/32%) versus non-Japanese (17%/56%/28%) patients. Grade 3/4 anemia rates were higher in non-Japanese (65%) versus Japanese (48%) patients. Early introduction of olanzapine during veliparib monotherapy maintenance phase may help prevent premature discontinuation of veliparib, via its potent antiemetic efficacy. CONCLUSIONS: Median progression-free survival was numerically longer in Japanese patients in the veliparib-throughout versus control arm, consistent with results in the overall study population. Pharmacokinetics were comparable between Japanese and non-Japanese patients. Data for the subgroup of Japanese patients were not powered to show statistical significance but to guide further investigation.

DOI： 10.1007/s10147-022-02258-x

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 Reviewed

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)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J05038&link_issn=&doc_id=20221221480017&doc_link_id=%2Fcv0mtrob%2F2022%2F007101%2F017%2F0099-0103%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2022%2F007101%2F017%2F0099-0103%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

腫瘍の自然脱落により診断に至った子宮腺肉腫の一例

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

現代産婦人科 71 ( Suppl. ) S62 - S63 2022.9

Tumor size before image-guided brachytherapy is an important factor of local control after radiotherapy for cervical squamous cell carcinoma: analysis in cases using central shielding. Reviewed International journal

Kotaro Yoshio, Hiroki Ihara, Kazuhiro Okamoto, Etsuji Suzuki, Takeshi Ogata, Soichi Sugiyama, Keiichiro Nakamura, Shoji Nagao, Hisashi Masuyama, Takao Hiraki

Journal of radiation research 2022.7

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

We analyzed the local control (LC) of cervical squamous cell carcinoma treated by computed tomography (CT)-based image-guided brachytherapy (IGBT) using central shielding (CS). We also examined the value of tumor diameter before brachytherapy (BT) as a factor of LC. In total, 97 patients were analyzed between April 2016 and March 2020. Whole-pelvic (WP) radiotherapy (RT) with CS was performed, and the total pelvic sidewall dose was 50 or 50.4 Gy; IGBT was delivered in 3-4 fractions. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions, and distribution was modified manually by graphical optimization. The median follow-up period was 31.8 months (6.3-63.2 months). The 1- and 2-year LC rates were 89% and 87%, respectively. The hazard ratio was 10.11 (95% confidence interval: 1.48-68.99) for local recurrence in those with a horizontal tumor diameter ≥ 4 cm compared to those with < 4 cm before BT. In CT-based IGBT for squamous cell carcinoma, favorable LC can be obtained in patients with a tumor diameter < 4 cm before BT. However, if the tumor diameter is ≥ 4 cm, different treatment strategies such as employing interstitial-BT for dose escalation may be necessary.

DOI： 10.1093/jrr/rrac040

卵巣未熟奇形種に併発した抗NMDA受容体脳炎の一例

松岡敬典, 白河伸介, 岡本和浩, 依田尚之, 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 64回 285 - 285 2022.7

当院で施行した婦人科癌のがんゲノム医療の現況と課題

依田尚之, 小川千加子, 入江恭平, 岡本和浩, 松岡敬典, 久保光太郎, 中村圭一郎, 長尾昌二, 増山寿, 平沢晃

日本婦人科腫瘍学会学術講演会プログラム・抄録集 64回 205 - 205 2022.7

肥満を伴う子宮体癌患者に対して腹腔鏡下手術を施行した2症例

久保光太郎, 岡本和浩, 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

日本婦人科腫瘍学会学術講演会プログラム・抄録集 64回 244 - 244 2022.7

当院で施行した婦人科癌のがんゲノム医療の現況と課題

依田尚之, 小川千加子, 入江恭平, 岡本和浩, 松岡敬典, 久保光太郎, 中村圭一郎, 長尾昌二, 増山寿, 平沢晃

日本婦人科腫瘍学会学術講演会プログラム・抄録集 64回 205 - 205 2022.7

Abscopal effectによる遠隔転移の消失と考えられた子宮癌肉腫の一例

岡本和浩, 入江恭平, 松岡敬典, 依田尚之, 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 64回 237 - 237 2022.7

Effect of prior olaparib maintenance therapy for platinum sensitive recurrent ovarian cancer on response to subsequent platinum-based chemotherapy. Reviewed International journal

Hiroshi Nakazawa, Shoji Nagao, Moyu Narita, Takashi Shibutani, Tomoatsu Jimi, Hiroko Yano, Miho Kitai, Takaya Shiozaki, Satoshi Yamaguchi

The journal of obstetrics and gynaecology research 2022.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

AIM: Several years have passed since olaparib maintenance therapy was approved in patients with platinum sensitive recurrent ovarian cancer (PSROC). We speculated that the response to platinum-based chemotherapy (PBC) would be impaired at the time of recurrence after olaparib maintenance therapy. We conducted a noninterventional retrospective study to clarify this clinical question in a single institution. METHODS: We included all patients with PSROC who received olaparib after second or later line of PBC between April 18, 2018, and August 31, 2021. We evaluated the effect of olaparib maintenance therapy on PBC after progression. RESULTS: We identified 42 patients who received olaparib maintenance therapy after second or later line of PBC. Twenty-four patients relapsed after olaparib maintenance therapy, and 17 patients received PBC again. Four of 17 patients (complete response 2, partial response 2) responded to the PBC. The median progression-free survival was longer in patients with platinum-free interval ≥12 months than platinum-free interval of 6-12 months (9.7 vs 2.6 months, hazard ratio, 0.20: 95% confidence interval, 0.04-0.90; p = 0.04). CONCLUSIONS: In the patients with PSROC who experienced disease progression after olaparib maintenance therapy, especially in those with platinum-free interval of 6-12 months, the response to subsequent PBC was extremely poor. The efficiency of re-administration of PBC for PSROC patients with a short-term recurrence after olaparib treatment may need to be reconsidered.

DOI： 10.1111/jog.15184

プラチナ抵抗性再発卵巣癌に対してプラチナ製剤を再投与し奏功した2症例

小川麻理子, 依田尚之, 入江恭平, 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

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 324 2022.2

再発卵巣癌に対するPARP阻害剤維持療法の施行状況と安全性の検討

松岡敬典, 中村圭一郎, 入江恭平, 岡本和浩, 依田尚之, 小川千加子, 長尾昌二, 増山寿

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 496 2022.2

プラチナ抵抗性再発卵巣癌に対して非プラチナ製剤を投与した後,プラチナ製剤を再投与した症例の検討

依田尚之, 入江恭平, 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

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 503 2022.2

MRI検査・FDG-PET検査で悪性を疑う所見を認め,術前に悪性外陰腫瘍と考えた結節性筋膜炎の一例

西田康平, 岡本和浩, 入江恭平, 松岡敬典, 依田尚之, 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 74 ( 臨増 ) S - 343 2022.2

MRI検査・FDG-PET検査で悪性を疑う所見を認め,術前に悪性外陰腫瘍と考えた結節性筋膜炎の一例

西田康平, 岡本和浩, 入江恭平, 松岡敬典, 依田尚之, 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 74 ( 臨増 ) S - 343 2022.2

プラチナ抵抗性再発卵巣癌に対してプラチナ製剤を再投与し奏功した2症例

小川麻理子, 依田尚之, 入江恭平, 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

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 324 2022.2

再発卵巣癌に対するPARP阻害剤維持療法の施行状況と安全性の検討

松岡敬典, 中村圭一郎, 入江恭平, 岡本和浩, 依田尚之, 小川千加子, 長尾昌二, 増山寿

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 496 2022.2

プラチナ抵抗性再発卵巣癌に対して非プラチナ製剤を投与した後,プラチナ製剤を再投与した症例の検討

依田尚之, 入江恭平, 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

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 503 2022.2

Clinical practice guideline for the treatment of malignant ascites: section summary in Clinical Practice Guideline for peritoneal dissemination (2021). Reviewed

Keisuke Matsusaki, Kuniaki Aridome, Shigenobu Emoto, Hiroaki Kajiyama, Nobumasa Takagaki, Takao Takahashi, Hiroshi Tsubamoto, Shoji Nagao, Akihiro Watanabe, Hideaki Shimada, Joji Kitayama

International journal of clinical oncology 27 ( 1 ) 1 - 6 2022.1

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

Patients with peritoneal dissemination (PD) caused by abdominal malignancies are often associated with massive ascites, which shows extremely dismal prognosis because of the discontinuation of systemic chemotherapy mostly due to poor performance status. Many treatment methods, such as simple drainage, peritoneovenous shunting (PVS) and cell-free and concentrated reinfusion therapy (CART), have been used for symptom relief. However, the clinical efficacies of these methods have not been fully investigated yet. Recently, we developed the Clinical Practice Guideline for PD caused by various malignancies according to "Minds Clinical Practice Guideline Development Guide 2017". In this guideline, we systematically reviewed information on clinical diagnosis and treatments for PD using PubMed databases (2000 - 2020), and clarified the degree of recommendation for clinical questions (CQ). The evidence level was divided into groups by study design and quality. The literature level and a body of evidence were evaluated in reference to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Based on the results of systematic review, the strength of the recommendations was evaluated at a consensus meeting of the Guideline Committee. This is the English synopsis of the part of treatment of malignant ascites in Clinical Practice Guideline for PD, 2021 in Japanese. The guidelines summarize the general aspect of the treatment of malignant ascites and statements with recommendation strengths, evidence levels, agreement rates and future perspective for four raised clinical questions.

DOI： 10.1007/s10147-021-02077-6

進行上皮性卵巣癌における主治療前化学療法および腫瘍減量手術の適用(GOTIC019試験)

長尾昌二, 田村惇, 澁谷剛志, 三輪真唯子, 加藤友康, 佐藤豊実, 竹井裕二, 紙谷菜津子, 井上直樹, 中村和人, 井上彩, 藤原恵一, 鈴木光明

日本癌治療学会学術集会抄録集 59回 O8 - 1 2021.10

Olaparib plus bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer: Japan subset from the PAOLA-1/ENGOT-ov25 trial. Reviewed International journal

Keiichi Fujiwara, Hiroyuki Fujiwara, Hiroyuki Yoshida, Toyomi Satoh, Kan Yonemori, Shoji Nagao, Takashi Matsumoto, Hiroaki Kobayashi, Hughes Bourgeois, Philipp Harter, Anna Maria Mosconi, Isabel Palacio Vazquez, Alexander Reinthaller, Tomoko Fujita, Philip Rowe, Eric Pujade-Lauraine, Isabelle Ray-Coquard

Journal of gynecologic oncology 32 ( 5 ) e82 2021.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Asian Society of Gynecologic Oncology$\mathsemicolon$ Korean Society of Gynecologic Oncology and Colposcopy

OBJECTIVE: The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. METHODS: PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). RESULTS: Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11-1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16-2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. CONCLUSION: Results in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02477644.

DOI： 10.3802/jgo.2021.32.e82

Survival impact of adjuvant concurrent chemoradiotherapy after radical hysterectomy in FIGO stage IIIC1 cervical adenocarcinoma. Reviewed

Kazuhiro Suzuki, Shoji Nagao, Moyu Narita, Hiroshi Nakazawa, Takashi Shibutani, Kasumi Yamamoto, Tomoatsu Jimi, Hiroko Yano, Miho Kitai, Takaya Shiozaki, Kazuko Matsuoka, Satoshi Yamaguchi

International journal of clinical oncology 26 ( 7 ) 1322 - 1329 2021.7

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media {LLC}

BACKGROUND: We evaluated the survival effect of adjuvant concurrent chemoradiotherapy after radical hysterectomy in patients with clinical pelvic node-positive cervical adenocarcinoma. METHODS: Patients with pelvic node-positive cervical adenocarcinoma diagnosed between 2000 and 2016 at our institution were identified. Survival was compared between patients who underwent radical hysterectomy alone and those who received concurrent chemoradiotherapy as an adjuvant treatment. Survival analysis using log-rank test and Cox proportional hazards model was performed. RESULTS: We identified 80 patients who underwent radical hysterectomy for clinical pelvic node-positive cervical adenocarcinoma; of these, four with pathological pelvic node-negative adenocarcinoma were excluded. Of the 76 patients, 27 underwent radical hysterectomy alone and 49 received radical hysterectomy followed by concurrent chemoradiotherapy. With a median follow-up of 53 months, the 5-year overall survival rate was 51.0% in patients who underwent radical hysterectomy alone versus 53.0% in patients who received additional concurrent chemoradiotherapy (log-rank p = 0.455). CONCLUSION: The addition of concurrent chemoradiotherapy after radical hysterectomy did not significantly improve survival among patients with pelvic node-positive cervical adenocarcinoma. More appropriate treatment strategies are needed to improve the survival outcomes of these patients.

DOI： 10.1007/s10147-021-01904-0

Validation of tissue factor pathway inhibitor 2 as a specific biomarker for preoperative prediction of clear cell carcinoma of the ovary. Reviewed

Etsuko Miyagi, Noriaki Arakawa, Kentaro Sakamaki, Naho Ruiz Yokota, Takeharu Yamanaka, Yuki Yamada, Satoshi Yamaguchi, Shoji Nagao, Yasuyuki Hirashima, Yuka Kasamatsu, Hisamori Kato, Tae Mogami, Yohei Miyagi, Hiroshi Kobayashi

International journal of clinical oncology 26 ( 7 ) 1336 - 1344 2021.7

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

BACKGROUND: Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinoma (CCC) from borderline ovarian tumors (BOTs) and non-clear cell epithelial ovarian cancers (EOCs). Here, we examined the performance of TFPI2 for preoperative diagnosis of CCC. METHODS: Serum samples were obtained preoperatively from patients with ovarian masses, who needed surgical treatment at five hospitals in Japan. The diagnostic powers of TFPI2 and cancer antigen 125 (CA125) serum levels to discriminate CCC from BOTs, other EOCs, and benign lesions were compared. RESULTS: A total of 351 patients including 69 CCCs were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean ± SD, 508.2 ± 812.0 pg/mL) than in patients with benign lesions (154.7 ± 46.5), BOTs (181 ± 95.5) and other EOCs (265.4 ± 289.1). TFPI2 had a high diagnostic specificity for CCC (79.5%). In patients with benign ovarian endometriosis, no patient was positive for TFPI2, but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating stage II-IV CCC from BOTs and other EOCs (AUC 0.815 for TFPI2 versus 0.505 for CA125) or endometriosis (AUC 0.957 for TFPI2 versus 0.748 for CA125). The diagnostic sensitivity of TFPI2 to discriminate CCC from BOTs and other EOCs was improved from 43.5 to 71.0% when combined with CA125. CONCLUSIONS: High specificity of TFPI2 for preoperative detection of CCC was verified with the defined cutoff level of TFPI2 in clinical practice. TFPI2 and CA125 may contribute substantially to precise prediction of intractable CCC.

DOI： 10.1007/s10147-021-01914-y

Docetaxel and carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix: a phase II study. Reviewed

Muneaki Shimada, Shinya Sato, Tadahiro Shoji, Shoji Nagao, Hideki Tokunaga, Kotaro Sueoka, Kazuhiro Takehara, Keiichiro Nakamura, Satoshi Yamaguchi, Junzo Kigawa

International journal of clinical oncology 26 ( 7 ) 1314 - 1321 2021.7

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

BACKGROUND: This phase II study evaluated the efficacy and safety of docetaxel/carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix. METHODS: A total of 50 patients with International Federation of Gynecology and Obstetrics stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix were enrolled and administered docetaxel at a dose of 60 mg/m2, followed by carboplatin at a dose based on the area under the receiver operating characteristic curve of 6. The treatments were repeated every 21 days until disease progression or unacceptable adverse events. Except for two patients, 48 were eligible for evaluation. Another patient withdrew consent before treatment; adverse events were evaluated in 47. RESULTS: The response rate was 47.9% with 5 patients achieving complete response, 18 partial response, 14 stable disease, and 6 progressive disease. The disease control rate was 77.1%. With a median follow-up duration of 368 days, the median progression-free survival and overall survival were 6.1 months (95% CI 5.5-8.6) and 15.8 months (95% CI 18.2-28.3), respectively. The most frequent grade 3 and grade 4 hematological toxicity was neutropenia, with 38 patients (81%) having grade 4 and 4 (9%) having grade 3 neutropenia. The non-hematological toxicities were mainly grade 1 or 2 in severity. CONCLUSION: Docetaxel/carboplatin chemotherapy was effective, with a higher disease control rate and well-tolerated chemotherapeutic regimen for patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix.

DOI： 10.1007/s10147-021-01903-1

Treatment strategy for locally advanced squamous cell cervical cancer with clinically positive pelvic lymph nodes metastasis. Reviewed International journal

Takashi Shibutani, Shoji Nagao, Kazuhiro Suzuki, Kasumi Yamamoto, Tomoatsu Jimi, Hiroko Yano, Miho Kitai, Takaya Shiozaki, Satoshi Yamaguchi

The journal of obstetrics and gynaecology research 47 ( 7 ) 2442 - 2448 2021.7

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

AIM: To determine the optimal treatment for locally advanced squamous cell cervical cancer with clinical positive pelvic lymph nodes metastasis (cN1). METHODS: We enrolled patients with squamous cell cervical cancer with 2008 FIGO stages IB, IIA, or IIB diagnosed with cN1, who were treated at Hyogo Cancer Center between April 2010 and December 2016. Patients with para-aortic lymph nodes metastasis were excluded. RESULTS: Of the 69 eligible patients, 24 underwent concurrent chemoradiotherapy (CCRT), 11 underwent radical hysterectomy with pelvic lymphadenectomy (RH) with or without adjuvant RT, and 34 underwent neoadjuvant chemotherapy (NAC) followed by RH as initial treatment. The regimens of NAC included dose-dense TC (paclitaxel 80 mg/m2 , days 1, 8, 15; and carboplatin at an area under the curve = 6 on day 1, every 3 weeks) and dose-dense TP (paclitaxel 80 mg/m2 on days 1, 8, 15; and cisplatin 75 mg/m2 on day 1, every 3 weeks). The median observation period was 57 (12-107) months. The 5-year disease-free survival rates of the CCRT, RH, and NAC groups were 78.7%, 63.6%, and 88.2%, respectively (p = 0.14). The 5-year overall survival rates of the CCRT, RH, and NAC groups were 78.6%, 70.1%, and 94.1%, respectively (p = 0.11). CONCLUSIONS: We recommend avoiding RH as primary treatment for cN1 with locally advanced squamous cell cervical cancer. Although CCRT should be considered for cN1, further studies are required to determine if NAC followed by RH will serve as an effective option.

DOI： 10.1111/jog.14816

Prognostic Factors of Advanced Cervical Cancer with Distant Metastasis Reviewed

Miho Kitai, Shoji Nagao, Kayoko Tsujino, Satoshi Yamaguchi

Indian Journal of Gynecologic Oncology 19 ( 2 ) 2021.6

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

Purpose: Advanced cervical cancer with distant metastases is often difficult to treat and has an extremely poor prognosis. In this study, we aimed to examine treatment modalities that may contribute to prolonging overall survival. Methods: Under institutional review board approval, we conducted a retrospective study of 91 patients with advanced cervical cancer with distant metastasis who were treated at our hospital from 2000 to 2018. Overall survival was analyzed for each of the following prognostic factors: age, local stage, histological type, metastatic morphology (hematogenous metastasis or lymphadenopathy), presence or absence of local treatment with surgery or radiotherapy, and use of bevacizumab. Results: The median age was 58 years, and the median duration of observation was 34.5 months. The most common histological type was squamous cell carcinoma (64.8%). Eighty percent of patients opted for platinum-based chemotherapy as their first treatment. Univariate analysis detected histological type, metastatic morphology, presence or absence of local treatment with surgery or radiotherapy, and use of bevacizumab as significant prognostic factors, whereas multivariate analysis detected metastatic morphology, presence or absence of local treatment with surgery or radiotherapy, and use of bevacizumab as significant prognostic factors. Conclusion: In advanced cervical cancer, distant metastases can be controlled with chemotherapy, and the prognosis is relatively good when combined with local treatment. The results suggest that combined treatment strategies may contribute to prolonged survival and that bevacizumab use may extend survival.

DOI： 10.1007/s40944-021-00509-9

Successful endoscopic treatment for high-grade cervical intraepithelial neoplasia with gross lesions of the vagina Reviewed

Koyo Yamamoto, Miho Kitai, Kasumi Yamamoto, Toshiko Sakuma, Shoji Nagao, Satoshi Yamaguchi

Gynecology and Minimally Invasive Therapy 10 ( 2 ) 124 - 126 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Wolters Kluwer Medknow Publications

We present a patient diagnosed with high-grade cervical intraepithelial neoplasia (CIN) combined with macroscopic lesions of the vaginal epithelium. There was no lesion in pelvic magnetic resonance imaging examination, and histopathological examination revealed CIN3 and vaginal intraepithelial neoplasia (VAIN) 3 without invasion. We chose minimally invasive surgery for her and total laparoscopic hysterectomy with partial resection of the vagina was carried out. To determine appropriate surgical margins, vaginal colpotomy was performed. No recurrence of VAIN has been observed to date that passed for 9 months either.

DOI： 10.4103/GMIT.GMIT_119_19

Quality of life assessment of cell-free and concentrated ascites reinfusion therapy during initial treatment for advanced ovarian cancer: A prospective cohort study. Reviewed International journal

Kasumi Yamamoto, Shoji Nagao, Tomoharu Tsu, Taeko Matsushima, Yoshimi Ishido, Moyu Narita, Kazuhiro Suzuki, Hiroshi Nakazawa, Takashi Shibutani, Tomoatsu Jimi, Hiroko Yano, Miho Kitai, Takaya Shiozaki, Kazuko Matsuoka, Satoshi Yamaguchi

The journal of obstetrics and gynaecology research 47 ( 4 ) 1536 - 1543 2021.4

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

AIM: Cell-free and concentrated ascites reinfusion therapy (CART) is applied to relieve symptoms in patients with malignant ascites. We performed a prospective cohort study to evaluate the efficacy and safety of CART performed on patients with advanced ovarian and peritoneal cancers with massive ascites during the initial treatment. METHODS: From April 2018 to July 2020, CART was performed during the initial treatment of 31 patients with advanced ovarian and peritoneal cancers with cancerous ascites. Patient characteristics and clinical information before and after CART were collected. We performed quality of life assessment using the Japanese version of the M.D. Anderson Symptom Inventory (MDASI-J) 24 h before and after CART. RESULTS: CART was performed 38 times in 24 patients before or during neoadjuvant chemotherapy and 11 times in 11 patients prior to surgery. Four patients underwent CART before primary surgery and before and/or during chemotherapy. Grade 1-2 fever was observed in 18 of 31 cases (58%), and all were controllable by nonsteroidal anti-inflammatory drugs. CART did not adversely affect the main treatment, chemotherapy, or surgery. CART significantly improved the MDASI-J symptom and interference scores within 24 h after the procedure. The symptom and interference scores decreased from 2.4 to 1.8 and from 4.8 to 3.0, respectively. CONCLUSIONS: CART can be safely performed and is useful for symptom relief and improvement of general condition prior to initial surgery and during initial chemotherapy in ovarian and peritoneal cancers. Performing CART at the time of initial treatment may facilitate initiation of the main treatment.

DOI： 10.1111/jog.14670

Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer. Reviewed International journal

Kazuhiro Takehara, Takashi Matsumoto, Junzo Hamanishi, Kosei Hasegawa, Motoki Matsuura, Kiyonori Miura, Shoji Nagao, Hidekatsu Nakai, Naotake Tanaka, Hideki Tokunaga, Kimio Ushijima, Hidemichi Watari, Yoshihito Yokoyama, Yoichi Kase, Shuuji Sumino, Ajit Suri, Hiroaki Itamochi, Nobuhiro Takeshima

Journal of gynecologic oncology 32 ( 2 ) e21 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Asian Society of Gynecologic Oncology$\mathsemicolon$ Korean Society of Gynecologic Oncology and Colposcopy

OBJECTIVE: The primary objective of this study was to evaluate the safety of niraparib 300 mg/day in Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. METHODS: Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients with platinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens. The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30 days after initial niraparib administration) was justified by the incidences of a global pivotal phase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematological adverse event of niraparib. The overall safety analysis examined other treatment-emergent adverse events (TEAEs). RESULTS: Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8-79.1) kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib 300 mg/day but this decreased in subsequent cycles (mean±standard deviation dose intensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration. Other common TEAEs included nausea, and decreased platelet or neutrophil counts. No progression-free or overall survival events occurred; only 1 of 4 response-evaluable patients had a post-baseline tumor assessment (stable disease). CONCLUSION: The incidence of grade 3 or 4 thrombocytopenia-related events in Japanese ovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall, the safety profile was acceptable and consistent with the known safety profile and previous experience with niraparib. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759587.

DOI： 10.3802/jgo.2021.32.e21

Phase II study of a new multidisciplinary therapy using once every 3 week carboplatin plus dose-dense weekly paclitaxel before and after radical hysterectomy for locally advanced cervical cancer. Reviewed

Shoji Nagao, Kasumi Yamamoto, Tetsuro Oishi, Satoshi Yamaguchi, Kazuhiro Takehara, Muneaki Shimada, Junzo Kigawa

International journal of clinical oncology 26 ( 1 ) 207 - 215 2021.1

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media {LLC}

BACKGROUND: We proposed a novel treatment strategy, consisting of triweekly cisplatin plus dose-dense weekly paclitaxel before and after radical hysterectomy without adjuvant radiation therapy to treat locally advanced cervical cancer. However, cisplatin-related severe non-hematologic toxicities were frequent during this strategy. This study aimed to assess the applicability of replacing cisplatin with carboplatin in our proposed strategy. METHODS: Women with International Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB2, IIA2, or IIB cervical cancer received three cycles of carboplatin (based on an area under the curve of six), each 21 days apart, starting on day 1, and 80 mg/m2 of paclitaxel on days 1, 8, and 15 of each 21-day cycle before undergoing radical hysterectomy. Patients with one or more high-risk factors, including lymph vascular invasion, parametrial invasion, lymph-node metastasis, or positive margins, received three additional cycles of chemotherapy after hysterectomy. Concurrent chemoradiation therapy was only applied to those patients who failed to respond to neoadjuvant chemotherapy. RESULTS: Between September 2014 and July 2016, 50 women (13 women with FIGO stage IB2, 5 with stage IIA2, and 32 with stage IIB) were enrolled in this study. The overall response rate to chemotherapy was 92%, including 22% with pathological complete response. Forty-nine women (98%) completed the planned radical hysterectomy, and 11 (22%) women with one or more high-risk factors received three additional cycles of chemotherapy. Only four women (8%) received concurrent chemoradiation therapy after surgery. The 2- and 3-year progression-free survival rates were 88.0% and 83.8%, respectively, and the 2- and 3-year overall survival rates were 98.0% and 95.4%, respectively. Only two patients reported grade 3 or higher non-hematologic toxicities including grade 3 nausea in one patient and grade 3 liver dysfunction in one patient. CONCLUSIONS: Replacement the platinum agent resulted in equivalent efficacy, with reduced toxicity, in women with locally advanced cervical cancer. This strategy could considerably diminish the application of radiation therapy without reduced survival. A study to identify those patients who will benefit from this new multidisciplinary strategy is warranted.

DOI： 10.1007/s10147-020-01787-7

Propensity score-matched analysis of systemic chemotherapy versus salvage hysterectomy for persistent cervical cancer after definitive radiotherapy/concurrent chemoradiotherapy. Reviewed International journal

Munetaka Takekuma, Fumiaki Takahashi, Seiji Mabuchi, Wataru Kudaka, Koji Horie, Mariko Ikeda, Ayumi Shikama, Akira Mitsuhashi, Shoji Nagao, Shiro Suzuki, Mika Mizuno, Shin Nishio, Hideki Tokunaga, Yukinobu Ota, Takahiro Kasamatsu, Ryo Kitagawa, Takafumi Toita, Hiroaki Kobayashi, Mitsuya Ishikawa, Nobuo Yaegashi

BMC cancer 20 ( 1 ) 1169 - 1169 2020.11

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

BACKGROUND: The aim of the current study was to evaluate oncologic outcomes of patients who were treated with salvage hysterectomy (HT), compared to systemic chemotherapy (CT) for persistent cervical cancer after definitive radiotherapy (RT)/ concurrent chemoradiotherapy (CCRT). METHODS: Patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions from 2005 to 2014 were reviewed retrospectively (n = 317). Those who underwent a HT for persistent cervical cancer after definitive RT/CCRT were matched with propensity scores for patients who underwent systemic CT. Oncologic outcomes between the two groups using a propensity score matched-cohort analysis were compared. RESULTS: A total of 142 patients with persistent cervical cancer after definitive RT/CCRT were included after matching (HT: 71, systemic CT: 71). All background factors between HT and CT groups were well balanced. Median overall survival was 3.8 and 1.5 years in the HT and CT groups, respectively (p = 0.00193, hazards ratio [HR] 0.41, 95% confidence interval [CI] 0.23-0.73), Increasing residual tumor size was significantly associated with a high incomplete resection rate (p = 0.016, Odds Ratio 1.11, 95%CI 1.02-1.22). Severe late adverse events occurred in 7 patients (9.9%) in the HT cohort. CONCLUSION: The current study demonstrated that, when compared to systemic CT, the adoption of salvage HT for patients with persistent cervical cancer after definitive RT/CCRT reduced mortality rate by about 60%. This indicates that salvage HT could be curative treatment for those patients. Further prospective clinical trials with regard to salvage HT after RT/CCRT are warranted.

DOI： 10.1186/s12885-020-07672-w

Suppressive effect upon carboplatin hypersensitivity reaction via pegylated liposomal doxorubicin combination therapy. Reviewed

Kyoko Shimada, Shoji Nagao, Kazuhiro Suzuki, Takashi Shibutani, Kasumi Yamamoto, Tomoatsu Jimi, Hiroko Yano, Miho Kitai, Takaya Shiozaki, Satoshi Yamaguchi

International journal of clinical oncology 25 ( 9 ) 1718 - 1725 2020.9

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media {LLC}

BACKGROUND: Occurrence of hypersensitivity reaction (HSR) in patients having received multiple doses of carboplatin has been reported. Several studies demonstrated reduction of carboplatin-associated HSR with in combination with pegylated liposomal doxorubicin (PLD). The objective of this study was to determine the suppressive effect on carboplatin-induced HSR via combined treatment with PLD within clinical practice. METHODS: We reviewed the medical records of women with primary or recurrent ovarian, fallopian tube, or peritoneal cancer treated with carboplatin containing regimen at our hospital between January 2009 and March 2019. We compared the incidence of carboplatin-induced HSR among patients who received more than one cycle of PLD plus carboplatin (PLD-C) therapy (i.e., PLD-C group) versus patients who never received PLD-C therapy (non-PLD-C group). RESULTS: A total of 414 women were included in this study (48: PLD-C group, 366: non-PLD-C group). Carboplatin-induced HSR occurred in 34 total patients (8.2%) [1/48 (2.1%) in the PLD-C group and 33/366 (9.0%) in the non-PLD-C group], with a median cycle number of carboplatin administration at onset of HSR being 9. Incidences of carboplatin-induced HSR within the PLD-C versus non-PLD-C group at the 8th, 12th, and 16th cycles of carboplatin administration were 2.2% vs 11.2%, 2.2% vs 28.6%, and 2.2% vs 39.1%, respectively [hazard ratio: 19.2 (95% confidence interval: 9.82-39.4), p < 0.0001]. CONCLUSION: Based on the data analyzed here, a suppressive effect on carboplatin-induced HSR via combination therapy with PLD was confirmed within clinical practice.

DOI： 10.1007/s10147-020-01706-w

Dose-dense paclitaxel and carboplatin vs. conventional paclitaxel and carboplatin as neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: a retrospective study. Reviewed

Takashi Shibutani, Shoji Nagao, Kazuhiro Suzuki, Michiko Kaneda, Kasumi Yamamoto, Tomoatsu Jimi, Hiroko Yano, Miho Kitai, Takaya Shiozaki, Kazuko Matsuoka, Tamotsu Sudo, Satoshi Yamaguchi

International journal of clinical oncology 25 ( 3 ) 502 - 507 2020.3

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media {LLC}

BACKGROUND: The purpose of this study was to determine the optimal regimen of neoadjuvant chemotherapy (NAC) for advanced epithelial ovarian, fallopian tube, and peritoneal cancers. METHODS: A clinical information survey involving 171 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer was conducted. These patients underwent NAC followed by interval debulking surgery at the Hyogo Cancer Center (Hyogo, Japan) between January 2006 and December 2015. RESULTS: The median observation period was 41 (range 4-138) months. Dose-dense paclitaxel and carboplatin (TC) was administered in 101 patients (59%); tri-weekly TC was administered 70 patients (41%). Median progression-free survival was 21 [95% confidence interval (CI) 18-23] months and 15 (95% CI 13-17) months in the dose-dense TC and conventional-TC group [hazard ratio (HR) = 0.69, 95% CI 0.46-0.96; p = 0.02], respectively. The median overall survival was 59 (95% CI 46-72) and 40 (95% CI 32-57) months in the dose-dense TC group and conventional-TC group (HR = 0.72, 95% CI 0.48-1.06; p = 0.09). Multivariate analysis for progression-free survival demonstrated that dose-dense TC represented an independent prognostic factor (HR = 0.70, 95% CI 0.50-0.99; p = 0.04). CONCLUSIONS: Dose-dense TC is a promising regimen of NAC for advanced epithelial ovarian cancer.

DOI： 10.1007/s10147-019-01567-y

A phase II study of the combination chemotherapy of bevacizumab and gemcitabine in women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. Reviewed International journal

Shoji Nagao, Ai Kogiku, Kazuhiro Suzuki, Takashi Shibutani, Kasumi Yamamoto, Tomoatsu Jimi, Miho Kitai, Takaya Shiozaki, Kazuko Matsuoka, Satoshi Yamaguchi

Journal of ovarian research 13 ( 1 ) 14 - 14 2020.2

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media {LLC}

INTRODUCTION: Bevacizumab and gemcitabine are key drugs for treating recurrent epithelial ovarian cancer. However, information about the combination of bevacizumab and gemcitabine is insufficient. We conducted a phase II study to assess the feasibility, clinical activity, and toxicity of this combination chemotherapy. METHODS: This study included women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer who received one to three regimens of platinum-based chemotherapy between April 1, 2015 and December 31, 2018. The patients received bevacizumab 15 mg/kg intravenously on day 1 and gemcitabine 1000 mg/m2 intravenously on days 1 and 8 every 21 days until disease progression or unacceptable toxicity. The primary endpoint was the completion rate of three cycles of chemotherapy. This study was registered in the University Medical Information Network (UMIN) Clinical Trials Registry (UMIN000016619). RESULTS: Among the 19 patients, 18 (95%) received ≥3 and 9 (47%) received ≥6 cycles of the study therapy. The objective response rate was 42% (complete response of 16% and partial response of 26%), and the clinical control rate was 84%. Hematological toxicity included neutropenia grade 3/4 in 9 patients (47%), anemia grade 3/4 in 2 (11%), and thrombocytopenia grade 3/4 in 1 (5%). One patient (5%) had grade 3 hypertension, and 1 (5%) had grade 3 protein urea. Possibly related grade 3 pulmonary toxicity was observed in 1 patient. Three patients needed dose reduction of gemcitabine to 800 mg/m2 due to treatment delay by 15 to 21 days on day1. There was no treatment delay more than 14 days on day 8. The median progression-free survival duration was 5.1 months and median overall survival duration was 21.3 months. CONCLUSION: The combination chemotherapy with gemcitabine and bevacizumab was feasible, effective and safe. This combination chemotherapy may be explored in a further randomized trial.

DOI： 10.1186/s13048-020-0617-y

Leptomeningeal metastases arising from gynecological cancers. Reviewed

Hiroko Yano, Shoji Nagao, Satoshi Yamaguchi

International journal of clinical oncology 25 ( 2 ) 391 - 395 2020.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Most cases of leptomeningeal metastasis (LM) arise from solid tumors, such as breast cancer, lung cancer, or malignant melanoma. LM arising from gynecological cancers are extremely rare. Longer survival owing to recent advances in chemotherapy and other treatments has contributed to the increased frequency of gynecological cancers metastasizing to the central nervous system (CNS). Detailed information regarding LM is scarce; therefore, we conducted a study concerning LM arising from primary gynecological cancers. METHODS: Among 24 patients with CNS metastases from gynecological cancer treated at our hospital between January 2011 and August 2018, those who were eventually diagnosed with LM were included in this retrospective study. RESULTS: Among 24 patients with CNS metastases, five patients (20.8%) were diagnosed with LM. The primary cancer was endometrial in two, cervical in one, and peritoneal in two patients. Of these five patients, three developed LM as a complication 1-11 months after the treatment of brain metastases; one patient had multiple brain metastases diagnosed at the same time as LM, and one had LM alone, without accompanying brain metastases. The median survival after the diagnosis of LM was 23 (12-69) days, while the median survival of 24 patients after the initial diagnosis of CNS metastases was 106 (13-959) days. CONCLUSION: Although LM arising from gynecological cancers is considered rare, identification of LM may be important to predict prognosis and develop new therapeutic strategies.

DOI： 10.1007/s10147-019-01556-1

[Ⅳ.Endometrial Cancer].

Shoji Nagao

Gan to kagaku ryoho. Cancer & chemotherapy 47 ( 2 ) 247 - 251 2020.2

Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. Reviewed International journal

Isabelle Ray-Coquard, Patricia Pautier, Sandro Pignata, David Pérol, Antonio González-Martín, Regina Berger, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Johanna Mäenpää, Frédéric Selle, Jalid Sehouli, Domenica Lorusso, Eva M Guerra Alía, Alexander Reinthaller, Shoji Nagao, Claudia Lefeuvre-Plesse, Ulrich Canzler, Giovanni Scambia, Alain Lortholary, Frederik Marmé, Pierre Combe, Nikolaus de Gregorio, Manuel Rodrigues, Paul Buderath, Coraline Dubot, Alexander Burges, Benoît You, Eric Pujade-Lauraine, Philipp Harter

The New England journal of medicine 381 ( 25 ) 2416 - 2428 2019.12

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

BACKGROUND: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS: We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS: Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644.).

DOI： 10.1056/NEJMoa1911361

Landscape of systemic therapy for ovarian cancer in 2019: Primary therapy. Reviewed International journal

Keiichi Fujiwara, Kosei Hasegawa, Shoji Nagao

Cancer 125 Suppl 24 4582 - 4586 2019.12

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

According to the statement from the 5th Ovarian Cancer Consensus Conference in 2015, the primary systemic chemotherapy for advanced ovarian cancer is a combination of paclitaxel plus carboplatin administered every 3 weeks (PCq3w). Optional alternatives include weekly dose-dense paclitaxel, in combination and maintenance therapy with bevacizumab, and intraperitoneal chemotherapy. Since then, in addition to the PCq3w strategy, there has been emerging new evidence, especially for poly(adenosine diphosphate-ribose) polymerase inhibitors. Moreover, there are multiple randomized, phase 3 trials testing the addition of antiangiogenic and/or immune checkpoint inhibitors in this patient population. In this article, current and future perspectives of systemic chemotherapy for advanced ovarian cancer are discussed.

DOI： 10.1002/cncr.32475

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer. Reviewed International journal

Koji Matsuo, James C Cripe, Katherine C Kurnit, Michiko Kaneda, Audrey S Garneau, Gretchen E Glaser, Aaron Nizam, Rachel M Schillinger, Michelle L Kuznicki, Akira Yabuno, Shiori Yanai, Denise M Garofalo, Jiro Suzuki, Jessica D St Laurent, Ting-Tai Yen, Annie Y Liu, Masako Shida, Mamoru Kakuda, Tetsuro Oishi, Shin Nishio, Jenna Z Marcus, Sosuke Adachi, Tetsuji Kurokawa, Malcolm S Ross, Max P Horowitz, Marian S Johnson, Min K Kim, Alexander Melamed, Karime K Machado, Kosuke Yoshihara, Yoshio Yoshida, Takayuki Enomoto, Kimio Ushijima, Shinya Satoh, Yutaka Ueda, Mikio Mikami, Bobbie J Rimel, Rebecca L Stone, Whitfield B Growdon, Aikou Okamoto, Saketh R Guntupalli, Kosei Hasegawa, Mian M K Shahzad, Dwight D Im, Marina Frimer, Bobbie S Gostout, Frederick R Ueland, Shoji Nagao, Pamela T Soliman, Premal H Thaker, Jason D Wright, Lynda D Roman

Gynecologic oncology 155 ( 1 ) 39 - 50 2019.10

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

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

DOI： 10.1016/j.ygyno.2019.08.007

A phase II randomized controlled study of pegylated liposomal doxorubicin and carboplatin vs. gemcitabine and carboplatin for platinum-sensitive recurrent ovarian cancer (GOTIC003/intergroup study). Reviewed

Hiroyuki Fujiwara, Kimio Ushijima, Shoji Nagao, Yuji Takei, Muneaki Shimada, Masashi Takano, Kiyoshi Yoshino, Yoshiaki Kawano, Yasuyuki Hirashima, Satoru Nagase, Shin Nishio, Tadaaki Nishikawa, Kimihiko Ito, Tadahiro Shoji, Eizo Kimura, Tadao Takano, Toru Sugiyama, Junzo Kigawa, Keiichi Fujiwara, Mitsuaki Suzuki

International journal of clinical oncology 24 ( 10 ) 1284 - 1291 2019.10

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

PURPOSE: To compare the efficacy, safety, and tolerability profiles of pegylated liposomal doxorubicin and carboplatin (PLDC) with those of gemcitabine and carboplatin (GC) for the treatment of patients with platinum-sensitive recurrent ovarian cancer. METHODS: Ovarian cancer patients with recurrence > 6 months after first-line platinum and taxane-based therapies were randomly assigned to PLDC [pegylated liposomal doxorubicin 30 mg/m2 plus carboplatin area under the curve (AUC) 5 mg/mL/min on day 1] every 4 weeks or GC (gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin AUC 4 mg/mL/min on day 1) every 3 weeks for at least 6 cycles. The primary endpoint was progression-free survival, and overall response rate, overall survival, toxicity, and dose administration were secondary endpoints. RESULTS: One-hundred patients (49 PLDC; 51 GC) were randomly assigned. Over a median follow-up of 24 months, the median progression-free survival was 12.0 months (95% CI 9.2-15.0) for PLDC and 9.8 months (8.9-12.3) for GC [HR 0.69 (0.455-1.047)] with a difference of 2.2 months. The response rate was 57.1% (41.0-72.3) for PLDC and 56.4% (39.6-72.2) for GC. No obvious differences in toxicity (G3/4) were noted between arms. The median relative dose intensity of planned dose per week was 88.9% for pegylated liposomal doxorubicin and 53.1% for gemcitabine (p < 0.0001). CONCLUSIONS: PLDC and GC are both good treatment candidates for platinum-sensitive recurrent ovarian cancer patients; however, the dose intensity was lower for GC than for PLDC. PLDC had a more favorable risk-benefit profile than that of GC for patients.

DOI： 10.1007/s10147-019-01471-5

放射線治療をうけた子宮頸部の扁平上皮癌患者の血清SCC値が予後に与える影響について

塩崎隆也, 太田真見子, 島田京子, 鈴木一弘, 澁谷剛志, 自見倫敦, 矢野紘子, 北井美穂, 松岡和子, 須藤保, 長尾昌二, 山口聡

日本癌治療学会学術集会抄録集 57回 P32 - 4 2019.10

Phase II trial of paclitaxel, carboplatin, and bevacizumab for advanced or recurrent cervical cancer. Reviewed International journal

Kazuhiro Suzuki, Shoji Nagao, Takashi Shibutani, Kasumi Yamamoto, Tomoatsu Jimi, Hiroko Yano, Miho Kitai, Takaya Shiozaki, Kazuko Matsuoka, Satoshi Yamaguchi

Gynecologic oncology 154 ( 3 ) 554 - 557 2019.9

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: We evaluated the efficacy and safety of the combination of paclitaxel, carboplatin, and bevacizumab in patients with advanced or recurrent cervical cancer. METHODS: Subjects included patients with advanced or recurrent cervical cancer not amenable to curative treatment with surgery or radiation therapy. Treatment consisted of paclitaxel 175 mg/m2, carboplatin area under the curve 6 mg/mL/min, and bevacizumab 15 mg/kg every 21 days until disease progression, complete remission, or limiting toxicity. The primary endpoint was the objective response. RESULTS: In total, 34 patients received a median of 6 treatment cycles (range 2-25). The median follow-up period was 18.5 months (range 2-29). The objective response was 88% (95% confidence interval: 72.5%-96.7%). Seventeen patients (50%) experienced complete response, whereas 13 patients experienced (38%) partial response with a median duration of 6 months. Grades 3 and 4 hematologic toxicities manifested as neutropenia in 14 (41.2%), leukopenia in 14 (41.2%), anemia in 11 (32.4%), and thrombocytopenia in 9 (26.5%) patients. One patient who underwent prior pelvic irradiation developed grade 2 rectovaginal fistula. CONCLUSION: The combination of paclitaxel, carboplatin, and bevacizumab is effective and safe in patients with advanced or recurrent cervical cancer.

DOI： 10.1016/j.ygyno.2019.05.018

Endometrial carcinoma in a 14-year-old: A case report. Reviewed International journal

Hajime Uda, Miho Kitai, Ai Kogiku, Anna Kobayashi, Toshiko Sakuma, Shoji Nagao, Satoshi Yamaguchi

Gynecologic oncology reports 29 7 - 9 2019.8

Language：English

•We present a case of endometrial carcinoma (EC) in a 14-year-old girl with no risk factors for EC.•The patient received MPA therapy and endometrial curettage.•At 47 weeks after her last MPA treatment, she has had no recurrence.•EC should be considered in diagnosing juveniles with sustained abnormal uterine bleeding, even those without risk factors.

DOI： 10.1016/j.gore.2019.05.006

鏡視下手術導入における子宮全摘術の習熟度

長尾昌二, 太田真見子, 山本幸代, 成田萌, 島田京子, 中澤浩志, 鈴木一弘, 渋谷剛志, 山本香澄, 自見倫敦, 矢野紘子, 北井美穂, 塩崎隆也, 松岡和子, 山口聡

日本産科婦人科内視鏡学会雑誌 35 ( Suppl.I ) 125 - 125 2019.8

子宮体癌の腹腔鏡下手術における系統的骨盤リンパ節郭清省略についての検討

成田萌, 太田真見子, 山本幸代, 島田京子, 鈴木一弘, 中澤浩志, 澁谷剛志, 山本香澄, 自見倫敦, 矢野紘子, 北井美穂, 塩崎隆也, 松岡和子, 長尾昌二, 山口聡

日本産科婦人科内視鏡学会雑誌 35 ( Suppl.I ) 162 - 162 2019.8

卵巣成熟嚢胞性奇形種との鑑別が困難であった子宮脂肪平滑筋腫の1例

島田京子, 北井美穂, 太田真見子, 山本幸代, 成田萌, 鈴木一弘, 中澤浩志, 渋谷剛志, 山本香澄, 自見倫敦, 矢野紘子, 塩崎隆也, 松岡和子, 長尾昌二, 山口聡

日本産科婦人科内視鏡学会雑誌 35 ( Suppl.I ) 241 - 241 2019.8

Correlation between pre-operative and final histological diagnosis on endometrial cancer. Reviewed International journal

Takaya Shiozaki, Maiko Miwa, Toshiko Sakuma, Kazuhiro Suzuki, Ai Kogiku, Kasumi Yamamoto, Tokihiro Senda, Hiroko Yano, Miho Kitai, Kazuko Matsuoka, Tamotsu Sudo, Shoji Nagao, Satoshi Yamaguchi

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 29 ( 5 ) 886 - 889 2019.6

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

OBJECTIVE: We conducted a retrospective study to evaluate the correlation between pre-operative and post-operative histological diagnoses on endometrial cancer, and to describe the treatments and outcomes when post-operative diagnoses are downgraded from pre-operative histology. METHODS: Patients who underwent surgery for endometrial cancer in our facility between 2010 and 2013 were enrolled in the study. The definition of downgrade discordance is in accordance with the following criteria: 1) the pre-operative and post-operative histological diagnoses were both endometrioid and the final pathology was a lower grade than the pre-operative pathology and 2) the pre-operative diagnosis was not endometrioid, whereas the post-operative diagnosis was endometrioid grade 2 or less. RESULTS: A total of 250 patients were enrolled, and the concordance rates were 56% for endometrioid adenocarcinoma grade 1 (EMG1), 67% for EMG2, 67% for EMG3, 82% for carcinosarcoma, 71% for serous carcinoma, and 67% for clear cell carcinoma. Eighteen cases (6.6%) were identified as downgrade discordancy. Of the 18 patients, the triage for adjuvant therapy remained the same for 15 cases (83%), all of whom had no evidence of disease at their last visit. Three cases had discordances with respect to triage for adjuvant therapy; the therapies were triaged based on post-operative diagnosis. Of these patients one had a recurrence. CONCLUSIONS: Good correlation was observed between pre-operative and final histological diagnoses of endometrioid carcinoma (56%-67%) and type 2 carcinoma (67%-82%). Approximately 7% (18/250) of patients had downgrade discordancy; however, triage for adjuvant therapy did not change for approximately 80% (15/18) of the patients with downgrade discordancy. Further studies are needed to evaluate the effectiveness of triages that are based on post-operative diagnoses.

DOI： 10.1136/ijgc-2018-000041

ハイボリュームセンターでの開腹広汎子宮全摘術の治療成績と予後

北井美穂, 宇田元, 太田真見子, 島田京子, 鈴木一弘, 澁谷剛志, 山本香澄, 自見倫敦, 矢野紘子, 塩崎隆也, 松岡和子, 長尾昌二, 山口聡

日本婦人科腫瘍学会雑誌 37 ( 3 ) 483 - 483 2019.6

[Ⅲ.Surgery for Platinum Sensitive Recurrent Epithelial Ovarian Cancer]. Reviewed

Shoji Nagao

Gan to kagaku ryoho. Cancer & chemotherapy 46 ( 2 ) 240 - 243 2019.2

Phase I Study of Multiple Epitope Peptide Vaccination in Patients With Recurrent or Persistent Cervical Cancer. Reviewed International journal

Kosei Hasegawa, Yuji Ikeda, Yuko Kunugi, Akira Kurosaki, Yuichi Imai, Shunsuke Kohyama, Shoji Nagao, Eito Kozawa, Koji Yoshida, Takuya Tsunoda, Yusuke Nakamura, Keiichi Fujiwara

Journal of immunotherapy (Hagerstown, Md. : 1997) 41 ( 4 ) 201 - 207 2018.5

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

Cancer immunotherapy has now been established as a leading standard therapeutic option in a subset of patients with cancer. In this study, we conducted a phase I dose-escalation trial using a mixture of 5 peptides to vaccinate cervical cancer patients with HLA-A*2402. The primary endpoints were safety and determination of a recommended vaccine dose, and the secondary endpoints were evaluations of immunologic responses and clinical efficacy. All patients had recurrent or persistent disease and had failed to respond to or were intolerant to prior standard chemotherapy. Peptides derived from forkhead box protein M1 (FOXM1), maternal embryonic leucine zipper kinase (MELK), Holliday junction-recognition protein, and vascular endothelial growth factor receptors 1 and 2 were administered to 9 patients in a 3 patient-cohort design, with doses of 0.5, 1, or 2 mg of each of the individual peptides in a mixture with incomplete Freund's adjuvant. The major adverse events were anemia and injection site reactions, which were seen in 77.8% (7/9) and 66.7% (6/9) of patients, respectively. Grade 3 anemia was observed in 1 patient. No dose-limiting toxicity of the vaccine was observed. Seven (78%) patients achieved stable disease, and the median progression-free survival was 3.3 months (102 d). Interferon-γ enzyme-linked immunospot assays for each of the 5 antigens showed that 8 (89%) and 7 (78%) patients had high T-cell responses to FOXM1 and MELK, respectively. In conclusion, we demonstrated that this 5-peptide vaccine was tolerable, and that FOXM1 and MELK could be promising targets for immunotherapy in patients with cervical cancer.

DOI： 10.1097/CJI.0000000000000214

[II. Chemotherapy for Small Cell Carcinoma of the Uterus].

Shoji Nagao

Gan to kagaku ryoho. Cancer & chemotherapy 45 ( 2 ) 239 - 242 2018.2

Chemoresistance of Gastric-Type Mucinous Carcinoma of the Uterine Cervix: A Study of the Sankai Gynecology Study Group. Reviewed International journal

Atsumi Kojima, Muneaki Shimada, Yoshiki Mikami, Shoji Nagao, Nobuhiro Takeshima, Toru Sugiyama, Norihiro Teramoto, Takako Kiyokawa, Junzo Kigawa, Ryuichiro Nishimura

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 28 ( 1 ) 99 - 106 2018.1

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

OBJECTIVE: Gastric-type mucinous carcinoma (GAS) is a novel variant of mucinous carcinoma of the uterine cervix, characterized by aggressive clinical behavior and absence of high-risk human papillomavirus. We conducted this study to evaluate the chemosensitivity of GAS compared with that of usual-type endocervical adenocarcinoma (UEA) in patients who had been enrolled in our previous study. METHODS: Of 52 patients from our previous phase 2 study (SGSG005) of neoadjuvant chemotherapy with docetaxel and carboplatin for stage IB2 to IIB nonsquamous cervical cancer, 47 (stage IB2, 12; stage IIA2, 7; stage IIB, 28) were enrolled in this study with written informed consent. The biopsy specimens before neoadjuvant chemotherapy and surgical specimens after chemotherapy were centrally reviewed based on the updated World Health Organization classification (2014). RESULTS: Of 47 patients with nonsquamous cell carcinoma, 20 (42.6%) were diagnosed with UEA, 13 (27.7%) with GAS, 12 (25.5%) with adenosquamous carcinoma, and 1 patient each (2%) with small cell carcinoma and serous carcinoma. Consequently, 33 patients, consisting of 20 patients with UEA and 13 patients with GAS, were eligible for the current study. The response rate of GAS was significantly lower than that of UEA (46.2% vs 85.0%, P = 0.048). Of 16 cases of stage II UEA, 11 (68.8%) were downstaged on microscopic examination of postsurgical specimens, but none of the 8 patients with stage II GAS showed any response (P < 0.01). Two inoperative tumors were GAS. With a median follow-up duration of 56 months, the 5-year progression-free and overall survival rates of GAS were significantly worse than those of UEA (38.5% vs 75.0% [P = 0.011] and 36.9% vs 90.0% [P < 0.001], respectively). CONCLUSIONS: These findings suggest that GAS should be distinguished from UEA by its chemoresistance, necessitating an alternative treatment strategy established for this distinct subtype of endocervical adenocarcinoma.

DOI： 10.1097/IGC.0000000000001145

Pelvic fractures after definitive and postoperative radiotherapy for cervical cancer: A retrospective analysis of risk factors. Reviewed International journal

Kasumi Yamamoto, Shoji Nagao, Kazuhiro Suzuki, Ai Kogiku, Tokihiro Senda, Hiroko Yano, Miho Kitai, Takaya Shiozaki, Kazuko Matsuoka, Satoshi Yamaguchi

Gynecologic oncology 147 ( 3 ) 585 - 588 2017.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: This study clarified the incidence of and identified the risk factors for post-radiation pelvic insufficiency fractures (PIFs) in women who received postoperative definitive or adjuvant radiotherapy (RT) for cervical cancer. PATIENTS AND METHODS: The medical records and data of imaging studies, including computed tomography scan and magnetic resonance imaging, of women with cervical cancer who received external-beam RT for the entire pelvic area between January 2003 and December 2012 at our institution were reviewed. RESULTS: A total of 533 patients with histologically diagnosed cervical cancer who received RT (298: definitive RT, 235: adjuvant RT) were included in this study. Eighty-four patients (15.8%) developed PIF in the irradiated field. Median age at onset of PIF was 72.5years (range: 54-95years), and 82 of them (98%) were postmenopausal women. Sixty-nine patients (80%) developed PIF within 3years from the completion of RT. The median time for the development of PIF was 14months (range: 1-81months). The most commonly involved fracture site was the sacral bone. Postmenopausal state, coexistence of rheumatoid arthritis, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) use were significant predisposing factors for the development of PIF, according to multivariate analysis. CONCLUSIONS: The incidence rate of PIF among patients who received RT for locally advanced cervical cancer was 15.8%. The principal predisposing factors for post-radiation PIF were postmenopausal state, rheumatoid arthritis, and HDR-ICBT use. Active interventions, including bone density screening followed by medication, should be considered during the early stage of RT for women with high-risk factors of PIF.

DOI： 10.1016/j.ygyno.2017.09.035

Cisplatin with dose-dense paclitaxel before and after radical hysterectomy for locally advanced cervical cancer: a prospective multicenter phase II trial with a dose-finding study. Reviewed International journal

Maki Tanioka, Satoshi Yamaguchi, Muneaki Shimada, Shoji Nagao, Kazuhiro Takehara, Masato Nishimura, Satoshi Morita, Shunichi Negoro, Kiyoshi Fujiwara, Junzo Kigawa

Medical oncology (Northwood, London, England) 34 ( 8 ) 134 - 134 2017.8

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

The aim of this study is to evaluate the outcome and safety of the multidisciplinary strategy using cisplatin plus dose-dense paclitaxel (dose-dense TP) before and after radical hysterectomy (RH) for stage IB2, IIA2, or IIB patients with cervical cancer. In the dose-finding phase, 12 patients received 3 cycles of cisplatin (75 mg/m2, day 1) with paclitaxel (70 or 80 mg/m2, days 1, 8, and 15) every 21 days as neoadjuvant chemotherapy (NAC). In the phase II study, 51 patients received 3 cycles of dose-dense TP at the recommended dose as NAC, and another 2 cycles of the same regimen after RH. The primary endpoint was 2-year progression-free survival (PFS). The secondary endpoints were 2-year overall survival (OS), adverse events (AEs), response rate (RR), and pathological complete response (pCR) rates. The recommended dose of paclitaxel at dose-finding phase was 80 mg/m2. In the phase II study, 34 patients (66.7%) had FIGO stage IIB disease. The RR and pCR rates were 94 and 28%. With a median follow-up duration of 58 months, each of the 2- and 5-year PFS rates was 88.2%, the 2- and 5-year OS rates were 94.1 and 88.2%, respectively. The incidence of grade 3/4 AEs was neutropenia (34%), nausea (12%), appetite loss (10%), fatigue (6%), and anemia (6%). Febrile neutropenia was uncommon (2%). Dose-dense TP before and after RH achieved a good long-term survival and was feasible for patients with locally advanced cervical cancer.

DOI： 10.1007/s12032-017-0992-4

子宮頸癌において治療開始前の白血球増加症並びに血小板増加症は予後予測因子となる

村田友香, 宮原義也, 鈴木嘉穂, 若橋宣, 市田耕太郎, 蝦名康彦, 山田秀人, 須藤保, 長尾昌二, 山口聡

日本婦人科腫瘍学会雑誌 35 ( 3 ) 663 - 663 2017.6

子宮頸癌における治療開始前の白血球増加症ならびに血小板増加症は予後予測因子となる

村田友香, 宮原義也, 鈴木嘉穂, 若橋宣, 市田耕太郎, 蝦名康彦, 山田秀人, 須藤保, 長尾昌二, 山口聡

産婦人科の進歩 69 ( 2 ) 234 - 234 2017.5

Correlation Between Tumor Mesothelin Expression and Serum Mesothelin in Patients with Epithelial Ovarian Carcinoma: A Potential Noninvasive Biomarker for Mesothelin-targeted Therapy. Reviewed International journal

Tatsuya Hanaoka, Kosei Hasegawa, Tomomi Kato, Sho Sato, Akira Kurosaki, Akiko Miyara, Shoji Nagao, Hiroyuki Seki, Masanori Yasuda, Keiichi Fujiwara

Molecular diagnosis & therapy 21 ( 2 ) 187 - 198 2017.4

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

BACKGROUND: The cell surface glycoprotein mesothelin is highly expressed in several malignant diseases. Normal mesothelin expression is limited to mesothelial cells lining the pleura, peritoneum, and pericardium, making it a biomarker and an attractive target for cancer therapy. METHODS: We investigated tumor mesothelin expression and serum mesothelin levels in patients with epithelial ovarian cancer or borderline tumors. In total, 161 patients selected from a previous prospective study were analyzed for tumor mesothelin expression using immunohistochemistry and serum mesothelin expression using enzyme-linked immunosorbent assay. RESULTS: Eighty-eight (68.8%) epithelial ovarian cancers and eight (24.2%) borderline tumors showed high mesothelin expression, which was associated with shorter progression-free and overall survival. The tumor mesothelin expression status was moderately correlated with serum mesothelin levels in epithelial ovarian cancer patients. Based on receiver operating characteristic analysis, a serum mesothelin level above 2.20 nM predicted high tumor mesothelin expression in epithelial ovarian cancer patients (area under the curve = 0.81). In 45 patients with recurrent epithelial ovarian cancer, we observed relatively lower levels of serum mesothelin, compared to the level at the primary diagnosis. We also tracked the change in the serum mesothelin level during the course of second-line chemotherapy and found a discrepancy between the clinical response and the serum mesothelin change in some patients, which suggested tumor heterogeneity among the tumor cells with or without mesothelin expression. CONCLUSION: Serum mesothelin may be a useful noninvasive biomarker surrogate for tumor mesothelin expression in future clinical trials for mesothelin-targeted therapy.

DOI： 10.1007/s40291-017-0255-2

Neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy for stage IB2, IIA2, and IIB patients with non-squamous cell carcinoma of the uterine cervix. Reviewed

Muneaki Shimada, Shoji Nagao, Keiichi Fujiwara, Nobuhiro Takeshima, Ken Takizawa, Tadahiro Shoji, Toru Sugiyama, Satoshi Yamaguchi, Ryuichiro Nishimura, Junzo Kigawa

International journal of clinical oncology 21 ( 6 ) 1128 - 1135 2016.12

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

BACKGROUND: We conducted a phase II study to evaluate the efficacy of neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy for patients with non-squamous cell carcinoma of the uterine cervix. METHODS: Sixty-one patients with International Federation of Gynecology and Obstetrics stage IB2, IIA2, or IIB non-squamous cell carcinoma of the uterine cervix were enrolled. The patients were administered docetaxel at a dose of 60 mg/m2, followed by carboplatin at a dose based on an area under the curve of 6. The treatments were repeated every 21 days for one to three cycles. Fifty-two patients were eligible to evaluate the efficacy of neoadjuvant chemotherapy followed by radical hysterectomy. Adverse events were evaluated in 59 patients. RESULTS: The response rate was 69 % (95 % CI, 57-82 %), with 5 patients achieving complete response, 31 partial response, 15 stable disease, and 1 progressive disease. Median follow-up duration was 1913 days with a range of 145-2632 days. Of 52 patients, 50 underwent radical hysterectomy after neoadjuvant chemotherapy. The 2-year overall survival rate was 81.8 % for stage IB2, 85.7 % for stage IIA2, and 92.6 % for stage IIB. The most frequent grade 3 and 4 hematological toxicity was neutropenia, with 43 patients experiencing grade 4 and 11 with grade 3. The nonhematological toxicities were mainly grade 1 or 2 in severity. CONCLUSION: Neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy may be a useful strategy for patients with non-squamous cell carcinoma of uterine cervix.

MPA療法が奏効せず腹腔鏡下子宮全摘出となった子宮体癌の1例治療中の子宮内膜組織診の変化の検討

若橋宣, 須藤保, 浮田真沙世, 市田耕太郎, 長尾昌二, 山口聡, 山田秀人

産婦人科の進歩 68 ( 3 ) 237 - 242 2016.8

Language：Japanese Publisher：「産婦人科の進歩」編集室

症例は39歳(1経妊0経産)で、近医で不妊治療中に子宮内膜細胞異常を指摘され紹介受診した。子宮内膜掻爬で類内膜腺癌G1と診断され、妊孕性温存希望のため高用量プロゲスチン(MPA)療法を開始した。6ヵ月後の内膜組織診で効果ありと判断し、2ヵ月間の追加治療後に経過観察としたが、初回治療終了6ヵ月後に類内膜腺癌G1の再発を認め、2回目のMPA療法を行った。8ヵ月後に腺癌は消失し、MPA療法を2ヵ月間追加して経過観察とした。2回目終了8ヵ月後に複雑型子宮内膜異型増殖症を認め、治療抵抗性の判断で子宮全摘術を勧めたが、妊孕性温存希望で3回目MPA療法となったが、4ヵ月後に増殖症の遺残を認め、患者・家族の了解のもと腹腔鏡下子宮全摘術、両側卵管切除術を行った。病理診断は複雑型子宮内膜異型増殖症を背景とした類内膜腺癌G1であった。術後1年経過で再発は認めていない。全経過を通じプロゲステロン受容体は陰性、エストロゲン受容体は陽性であった。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J00536&link_issn=&doc_id=20160815080004&doc_link_id=%2Fch5aioag%2F2016%2F006803%2F004%2F0237-0242%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fch5aioag%2F2016%2F006803%2F004%2F0237-0242%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Analysis of the effect of adjuvant radiotherapy on outcomes and complications after radical hysterectomy in FIGO stage IB1 cervical cancer patients with intermediate risk factors (GOTIC Study). Reviewed International journal

Kazuto Nakamura, Yoshikazu Kitahara, Toyomi Satoh, Yuji Takei, Masashi Takano, Shoji Nagao, Isao Sekiguchi, Mitsuaki Suzuki

World journal of surgical oncology 14 ( 1 ) 173 - 173 2016.6

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

BACKGROUND: There are no definitive criteria for identifying which patients with The International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer will benefit from adjuvant therapy after radical hysterectomy. The aims of this study were to clarify the efficacy of adjuvant therapy and assess complications after radical hysterectomy in patients with FIGO stage IB1 cervical cancer with intermediate risk factors. METHODS: Between January 2005 and December 2009, the medical records of 75 stage IB1 patients' intermediate risk factors (i.e., tumor size 2-4 cm, lymphovascular involvement, and/or deep stromal invasion >1/2) who underwent radical hysterectomy at six institutions were collected, and these patients were enrolled in this nonrandomized retrospective study. We simplified the criteria of intermediate risk factors as much as possible, as the criteria adopted in some clinical studies are complicated in practice. RESULTS: The patients were grouped according to the receipt of adjuvant therapy as follows: 46 patients, no further treatment; 19 patients, external beam radiation treatment, including 9 patients who received brachytherapy; 5 patients, concurrent chemoradiotherapy (CCRT); and 5 patients, chemotherapy (CT). The clinical outcomes and complications in each group were analyzed. After an average follow-up of 82.6 months (range, 24-135 months), only one patient with all three risk factors who received radiotherapy (RT) experienced recurrence. Excluding this patient, the remaining patients who received RT, CCRT, or CT had two or three risk factors. Lymphedema was significantly more common among patients who received RT or CCRT, whereas the incidence of ileus and ureteral obstruction was not different among the treatment groups. However, an unsutured peritoneum increased the risk of ileus. CONCLUSIONS: The findings of this study suggest that RT and CCRT after radical hysterectomy are not beneficial in patients with intermediate risk factors. In particular, RT and CCRT appeared to increase the incidence of lymphedema. A prospective randomized study is needed to verify the findings of this study.

DOI： 10.1186/s12957-016-0931-4

A preoperative low cancer antigen 125 level (≤25.8 mg/dl) is a useful criterion to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in epithelial ovarian cancer. Reviewed International journal

Akemi Morimoto, Shoji Nagao, Ai Kogiku, Kasumi Yamamoto, Maiko Miwa, Senn Wakahashi, Kotaro Ichida, Tamotsu Sudo, Satoshi Yamaguchi, Kiyoshi Fujiwara

Japanese journal of clinical oncology 46 ( 6 ) 517 - 21 2016.6

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The purpose of this study is to investigate the clinical characteristics to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer. METHODS: We reviewed the charts of women with advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer who underwent interval debulking surgery following neoadjuvant chemotherapy at our cancer center from April 2006 to April 2014. RESULTS: There were 139 patients, including 91 with ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) Stage IIIc in 56 and IV in 35], two with fallopian tube cancers (FIGO Stage IV, both) and 46 with primary peritoneal cancer (FIGO Stage IIIc in 27 and IV in 19). After 3-6 cycles (median, 4 cycles) of platinum-based chemotherapy, interval debulking surgery was performed. Sixty-seven patients (48.2%) achieved complete resection of all macroscopic disease, while 72 did not. More patients with cancer antigen 125 levels ≤25.8 mg/dl at pre-interval debulking surgery achieved complete resection than those with higher cancer antigen 125 levels (84.7 vs. 21.3%; P< 0.0001). Patients with no ascites at pre-interval debulking surgery also achieved a higher complete resection rate (63.5 vs. 34.1%; P< 0.0001). Moreover, most patients (86.7%) with cancer antigen 125 levels ≤25.8 mg/dl and no ascites at pre-interval debulking surgery achieved complete resection. CONCLUSIONS: A low cancer antigen 125 level of ≤25.8 mg/dl and the absence of ascites at pre-interval debulking surgery are major predictive factors for complete resection during interval debulking surgery and present useful criteria to determine the optimal timing of interval debulking surgery.

DOI： 10.1093/jjco/hyw029

子宮頸癌における治療開始前の白血球増加症は予後予測因子となる

宮原義也, 鈴木嘉穂, 若橋宣, 蝦名康彦, 森田宏紀, 須藤保, 長尾昌二, 山口聡, 山田秀人

日本婦人科腫瘍学会雑誌 34 ( 3 ) 491 - 491 2016.6

Diagnosis of desmoplastic small-round-cell tumor by cytogenetic analysis: a case report. Reviewed International journal

Senn Wakahashi, Tamotsu Sudo, Kotaro Ichida, Shintaro Sugita, Tadashi Hasegawa, Shoji Nagao, Satoshi Yamaguchi, Toshiko Sakuma, Hideto Yamada

Clinical case reports 4 ( 5 ) 520 - 3 2016.5

The Efficacy of Low-Dose Paclitaxel Added to Combination Chemotherapy of Carboplatin and Gemcitabine or Pegylated Liposomal Doxorubicin. Reviewed International journal

Shoji Nagao, Norihiro Iwasa, Akira Kurosaki, Tadaaki Nishikawa, Tatsuya Hanaoka, Kosei Hasegawa, Keiichi Fujiwara

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 26 ( 3 ) 443 - 8 2016.3

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Paclitaxel is known to produce the "platelet-sparing effect" that prevents the carboplatin-induced decrease in platelet count. We conducted a pilot study to assess whether the addition of low-dose paclitaxel to carboplatin-based combination chemotherapy prevents thrombocytopenia. METHODS: Patients with platinum-sensitive recurrent ovarian cancer received intravenous (IV) paclitaxel at 60 mg/m(2) followed by IV carboplatin at an area under the curve of 6 and IV pegylated liposomal doxorubicin at 30 mg/m(2) on day 1 in a 28-day cycle (DC-LOP) or IV gemcitabine at 1000 mg/m(2) on days 1 and 8 in a 21-day cycle (GC-LOP). RESULTS: During May 2011 to December 2011, 7 patients received 29 cycles of DC-LOP; during January 2012 to May 2013, 15 patients received 88 cycles of GC-LOP. Grade 3/4 thrombocytopenia occurred in 2 (33%) of 6 and 9 (56%) of 16 patients in the DC-LOP and GC-LOP groups, respectively. No grade 3/4 nonhematological toxicity was observed. Only one patient who received GC-LOP had grade 2 sensory and motor peripheral neuropathy. Paclitaxel-related toxicities, including muscle pain, arthralgia, and peripheral neuropathy, were consistently rare and mild. The response rates of DC-LOP and GC-LOP were 33% (0, complete response; 2, partial response; 3, stable disease; 1, progression disease) and 50% (2, complete response; 6, partial response; 7, stable disease; 1, progression disease), respectively. CONCLUSIONS: Although low-dose paclitaxel addition did not alleviate thrombocytopenia in the setting of this pilot study, the results do not deny the existence of the "platelet-sparing effect" by low-dose paclitaxel. Further investigation of the carboplatin-based combination chemotherapy including a drug with mild hematological toxicity is warranted.

DOI： 10.1097/IGC.0000000000000630

[The Near-Future of Intraperitoneal Chemotherapy in Epithelial Ovarian Cancer].

Shoji Nagao

Gan to kagaku ryoho. Cancer & chemotherapy 43 ( 2 ) 198 - 202 2016.2

子宮腺筋症の術前診断で腹腔鏡下子宮全摘出術を施行し子宮体癌と判明した1例

市田耕太郎, 若橋宣, 長尾昌二

日本産科婦人科内視鏡学会雑誌 31 ( 1 ) 244 - 248 2015.11

Language：Japanese Publisher：(一社)日本産科婦人科内視鏡学会

症例は45歳(3経妊3経産)で、過多月経と腹部腫瘍が指摘され、近医にて過多月経と貧血に対し子宮内膜全面掻爬とGnRHa投与が行われ、約半年後に不正性器出血を認め、内膜細胞診class IIIで紹介受診した。エコーで後壁が有意に肥厚した境界明瞭で内部不均一な腫瘤を認め、MRIで子宮体部後壁に35mmのT2で低信号を呈し、内部に点状の高信号を認め、子宮腺筋症を疑い腹腔鏡下子宮全摘出術を行った。摘出子宮を経腟的に回収し、腟断端を吸収糸で連続縫合し閉鎖した。病理所見では、子宮腺筋症は子宮筋層に限局し、子宮底層に淡赤色のごく一部で内膜側に連続する類内膜腺癌の病変を認め、類内膜腺癌G2と診断した。切除断端は陰性、左右付属器に浸潤・転移は認めなかったが、CT・PET-CTによる全身検索で傍大動脈リンパ節に腫大を認め、子宮体癌IIIC2期の診断で開腹による傍大動脈リンパ節、骨盤リンパ節郭清術を追加した。術後化学療法を行い、1年経過で再発は認めていない。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J02563&link_issn=&doc_id=20151228470027&doc_link_id=%2Fcj7sanai%2F2015%2F003101%2F027%2F0244-0248%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcj7sanai%2F2015%2F003101%2F027%2F0244-0248%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Clinical Features of Neuroendocrine Carcinoma of the Uterine Cervix: A Single-Institution Retrospective Review. Reviewed International journal

Shoji Nagao, Maiko Miwa, Naoko Maeda, Ai Kogiku, Kasumi Yamamoto, Akemi Morimoto, Senn Wakahashi, Kotaro Ichida, Tamotsu Sudo, Satoshi Yamaguchi, Toshiko Sakuma, Kiyoshi Fujiwara

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 25 ( 7 ) 1300 - 5 2015.9

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Neuroendocrine carcinoma of the cervix is a rare and aggressive subtype of cervical cancer and includes small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC). We conducted a single-institution retrospective review to explore the pattern of treatments and outcomes with the aim of defining an optimum treatment strategy for these carcinomas. METHODS: Twenty-three consecutive patients with SCNEC or LCNEC of the cervix diagnosed at the Hyogo Cancer Center between 1996 and 2013 were included in this study. Pertinent information, including clinical and pathological characteristics, and survival data were collected from clinical records and/or telephone surveys. The pathological review was conducted by a pathologist specializing in gynecologic cancer. RESULTS: Eleven patients had SCNEC and 12 had LCNEC. Eighteen patients with International Federation of Gynecology and Obstetrics (FIGO) stage I/II underwent type III radical hysterectomy with pelvic lymphadenectomy. After surgery, 9 received adjuvant chemotherapy (8, irinotecan plus cisplatin; 1, paclitaxel plus carboplatin), 7 received concurrent chemoradiation therapy (CCRT; 6, nedaplatin; 1, cisplatin), and 2 received radiation therapy (RT). Patients who received adjuvant chemotherapy had a better overall survival than did patients who received CCRT or RT (hazard ratio, 0.21; 95% confidence interval, 0.030-1.51; P = 0.12). Although the overall survival rates are not statistically significant, the 9 patients who underwent radical hysterectomy followed by adjuvant chemotherapy are all alive. Among the remaining 5 patients who did not undergo radical hysterectomy, 2 with FIGO stage III and 1 with stage IVa received CCRT, and 2 with stage IVb received palliative RT or chemotherapy. These 5 patients with FIGO stage III/IV died of disease within 36 months. CONCLUSIONS: Radical hysterectomy followed by platinum-based chemotherapy, especially the irinotecan plus cisplatin combination, is beneficial for long-term survival in patients with early-stage neuroendocrine carcinoma of the cervix.

DOI： 10.1097/IGC.0000000000000495

子宮子宮頸がんの放射線療法・化学療法子宮頸癌に対する放射線治療後の骨障害に関する後方視的検討

山本香澄, 長尾昌二, 小菊愛, 三輪真唯子, 森本明美, 松村聡子, 若橋宣, 市田耕太郎, 須藤保, 山口聡, 藤原潔

日本癌治療学会誌 50 ( 3 ) 1341 - 1341 2015.9

術前検査を用いた子宮体癌後腹膜リンパ節転移の予測

三輪真唯子, 長尾昌二, 小菊愛, 山本香澄, 森本明美, 松村聡子, 若橋宣, 市田耕太郎, 須藤保, 山口聡, 藤原潔

日本癌治療学会誌 50 ( 3 ) 1798 - 1798 2015.9

What is an appropriate second-line regimen for recurrent endometrial cancer? Ancillary analysis of the SGSG012/GOTIC004/Intergroup study. Reviewed International journal

Shoji Nagao, Shin Nishio, Satoshi Okada, Takeo Otsuki, Kiyoshi Fujiwara, Hiroshi Tanabe, Masashi Takano, Yoko Hasumi, Yuji Takei, Tetsuya Hasegawa, Takashi Matsumoto, Keiichi Fujiwara, Munetaka Takekuma, Kazuto Nakamura, Muneaki Shimada, Mitsuaki Suzuki, Junzo Kigawa

Cancer chemotherapy and pharmacology 76 ( 2 ) 335 - 42 2015.8

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: We previously reported that the concept of "platinum sensitivity" could be applied to recurrent endometrial cancer. We conducted an ancillary analysis to determine an appropriate second-line regimen for patients who received a platinum agent as first-line chemotherapy. METHODS: We extracted and reanalyzed data of patients treated with doxorubicin and cisplatin (AP), paclitaxel and carboplatin (TC), or docetaxel and carboplatin (DC) as first- and second-line chemotherapies from the SGSG012/GOTIC004/Intergroup study. RESULTS: We identified 216 patients: 38 received AP as first-line chemotherapy, of which 36 received TC or DC (Tax-C) as second-line chemotherapy; and 178 received Tax-C as first-line chemotherapy, of which 51 received AP and 127 received Tax-C as second-line chemotherapy. Median progression-free survival (PFS) and overall survival (OS) after second-line chemotherapy decreased in the order of Tax-C followed by Tax-C (10 and 48 months, respectively), AP followed by Tax-C (9 and 23 months, respectively), and Tax-C followed by AP (3 and 12 months, respectively). Median PFS and OS after second-line chemotherapy for platinum-resistant patients receiving Tax-C as first-line chemotherapy were longer in Tax-C than in AP (7 and 23 vs. 3 and 10 months, respectively) as second-line chemotherapy [hazard ratio (HR) 3.255, 95 % confidence interval (CI) 1.908-5.555, p < 0.0001; HR 3.179, 95 % CI 1.835-5.507, p < 0.0001, respectively]. Median PFS and OS after second-line chemotherapy for platinum-sensitive patients receiving Tax-C as first-line chemotherapy were almost equivalent to those receiving Tax-C or AP as second-line chemotherapy. CONCLUSIONS: For platinum-resistant recurrent endometrial cancer patients, Tax-C may be preferred over AP as second-line chemotherapy.

DOI： 10.1007/s00280-015-2793-9

MPAが奏功せず腹腔鏡下子宮全摘となった一例治療中の子宮内膜組織診の変化の検討

若橋宣, 浮田真沙世, 中江彩, 小菊愛, 山本香澄, 三輪真唯子, 森本明美, 松村聡子, 市田耕太郎, 須藤保, 長尾昌二, 山口聡, 佐久間淑子, 藤原潔

日本産科婦人科内視鏡学会雑誌 31 ( Suppl.I ) 267 - 267 2015.8

婦人科腫瘍の診断術前検査を用いた子宮体癌後腹膜リンパ節転移の予測

三輪真唯子, 長尾昌二, 小菊愛, 山本香澄, 森本明美, 若橋宣, 市田耕太郎, 須藤保, 山口聡, 藤原潔

日本婦人科腫瘍学会雑誌 33 ( 3 ) 529 - 529 2015.6

当院で経験した外陰癌29症例の臨床的検討

小菊愛, 山本香澄, 三輪真唯子, 森本明美, 若橋宣, 市田耕太郎, 須藤保, 長尾昌二, 山口聡, 藤原潔

日本婦人科腫瘍学会雑誌 33 ( 3 ) 625 - 625 2015.6

子宮頸癌に対する放射線治療後の骨障害に関する後方視的検討

山本香澄, 長尾昌二, 小菊愛, 三輪真唯子, 森本明美, 若橋宣, 市田耕太郎, 須藤保, 山口聡, 藤原潔

日本婦人科腫瘍学会雑誌 33 ( 3 ) 559 - 559 2015.6

当院で経験した外陰癌29症例の臨床的検討

小菊愛, 鈴木陽介, 山本香澄, 三輪真唯子, 森本明美, 若橋宣, 市田耕太郎, 須藤保, 長尾昌二, 山口聡, 藤原潔

産婦人科の進歩 67 ( 2 ) 226 - 226 2015.5

腹腔鏡下子宮全摘術に至ったMPA療法が奏功しなかった子宮内膜異型増殖症の1例

若橋宣, 鈴木陽介, 小菊愛, 山本香澄, 三輪真唯子, 森本明美, 市田耕太郎, 須藤保, 長尾昌二, 山口聡, 佐久間淑子, 藤原潔

産婦人科の進歩 67 ( 2 ) 226 - 226 2015.5

子宮頸部神経内分泌癌の治療戦略

長尾昌二, 小菊愛, 山本香澄, 三輪真唯子, 森本明美, 若橋宣, 市田耕太郎, 須藤保, 山口聡, 藤原潔

日本産科婦人科学会雑誌 67 ( 2 ) 825 - 825 2015.2

妊孕能温存希望のある子宮頸癌I期症例に対するRadical Trachelectomyの治療成績

山本香澄, 山口聡, 小菊愛, 三輪真唯子, 森本明美, 若橋宣, 市田耕太郎, 長尾昌二, 須藤保, 藤原潔

日本産科婦人科学会雑誌 67 ( 2 ) 832 - 832 2015.2

Gynecologic Cancer InterGroup (GCIG) consensus review for clear cell carcinoma of the uterine corpus and cervix. Reviewed International journal

Kosei Hasegawa, Shoji Nagao, Masanori Yasuda, David Millan, Akila N Viswanathan, Rosalind M Glasspool, Mojgan Devouassoux-Shisheboran, Alan Covens, Domenica Lorusso, Christian Kurzeder, Jae-Weon Kim, Laurence Gladieff, Jane Bryce, Michael Friedlander, Keiichi Fujiwara

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 24 ( 9 Suppl 3 ) S90-5 2014.11

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

Clear cell carcinomas of the uterine corpus and cervix are rare gynecological cancers with limited information regarding the pathogenesis and biology. At present, the approach to management is the same as for patients with the more common histological subtypes of endometrioid endometrial cancer and adenocarcinoma of the cervix. Surgical resection is the standard treatment for patients with early-stage disease, but there is no evidence-based approach to direct the management of patients with more advanced-stage disease at presentation or with recurrent disease. We review the epidemiology, pathology, and what is known about both uterine corpus and cervical clear cell cancers and make management recommendations.

DOI： 10.1097/IGC.0000000000000297

Feasibility study of combination chemotherapy with paclitaxel, doxorubicin and cisplatin without prophylactic granulocyte colony-stimulating factor injection for intermediate-to-high risk or recurrent endometrial cancer. Reviewed International journal

Shoji Nagao, Tadaaki Nishikawa, Tatsuya Hanaoka, Akira Kurosaki, Norihiro Iwasa, Kosei Hasegawa, Keiichi Fujiwara

Japanese journal of clinical oncology 44 ( 11 ) 1040 - 4 2014.11

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: We evaluated the feasibility of combination chemotherapy with paclitaxel, doxorubicin and cisplatin without prophylactic granulocyte colony-stimulating factor injection for intermediate-to-high-risk or recurrent endometrial cancer. METHODS: Women with histologically confirmed FIGO Stages I-II with >1/2 myometrial invasion, Stage III/IV or recurrent endometrial cancer were enrolled. Patients received intravenous doxorubicin (45 mg/m(2)), followed by cisplatin (50 mg/m(2)) on Day 1 and intravenous paclitaxel (160 mg/m(2)) on Day 2. Granisetron (75 µg) was administered depending on neutrophil counts on Days 3 and 8. Treatment was repeated every 21 days for six cycles or until disease progression or unacceptable toxicity. The primary endpoint was the completion rate of the scheduled chemotherapy; secondary endpoints were Grade 3/4 toxicity and response rate in patients with measurable lesions. RESULTS: From September 2010 to December 2012, 35 women, including 7 with FIGO Stage I, 4 with Stage II, 13 with Stage III, 10 with Stage IV and 1 with recurrent endometrial cancer, were enrolled. There were 26 endometrial carcinomas (Grade 1, 16; Grade 2, 6; Grade 3, 4), 4 carcinosarcomas, 2 serous adenocarcinomas, 1 neuroendocrine carcinoma, 1 poorly differentiated carcinoma and 1 mixed carcinoma. Twenty-five patients (71%) completed six chemotherapy cycles. Grade 3/4 hematological toxicities included neutrocytopenia (97%), thrombocytopenia (6%) and anemia (34%). Three patients (9%) experienced neutropenic fever. Grade 3/4 non-hematological toxicities were observed in 13 patients. In 15 patients with evaluable lesions, the response rate was 80%. CONCLUSIONS: Combination chemotherapy with paclitaxel, doxorubicin and cisplatin without prophylactic granulocyte colony-stimulating factor injection is feasible.

DOI： 10.1093/jjco/hyu124

術前化学療法を施行した進行卵巣癌における腫瘍減量手術の時期決定に有用な臨床的指標に関する検討

森本明美, 山本香澄, 三輪真唯子, 玉田将, 若橋宣, 市田耕太郎, 須藤保, 長尾昌二, 山口聡, 藤原潔

日本婦人科腫瘍学会雑誌 32 ( 3 ) 503 - 503 2014.6

[II. Future perspectives of intraperitoneal chemotherapy for ovarian cancer].

Keiichi Fujiwara, Shoji Nagao, Akira Kurosaki, Kosei Hasegawa

Gan to kagaku ryoho. Cancer & chemotherapy 41 ( 2 ) 184 - 7 2014.2

当院での卵巣癌肉腫20例の検討

山本香澄, 三輪真唯子, 森本明美, 浮田真沙世, 玉田将, 若橋宣, 市田耕太郎, 須藤保, 長尾昌二, 山口聡, 藤原潔

日本産科婦人科学会雑誌 66 ( 2 ) 628 - 628 2014.2

Applicability of the concept of "platinum sensitivity" to recurrent endometrial cancer: the SGSG-012/GOTIC-004/Intergroup study. Reviewed International journal

Shoji Nagao, Shin Nishio, Hirofumi Michimae, Hiroshi Tanabe, Satoshi Okada, Takeo Otsuki, Maki Tanioka, Keiichi Fujiwara, Mitsuaki Suzuki, Junzo Kigawa

Gynecologic oncology 131 ( 3 ) 567 - 73 2013.12

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The concept of "platinum sensitivity" has been widely applied in the management of recurrent ovarian cancer. This study aimed to evaluate the applicability of this concept to recurrent endometrial cancer. PATIENTS AND METHODS: In this multicenter retrospective cohort study, the clinical data of patients with recurrent endometrial cancer, who had a history of receiving first-line platinum-based chemotherapy and who received second-line platinum-based chemotherapy at the time of recurrence between January 2005 and December 2009 were reviewed. RESULTS: A total of 262 patients from 30 centers with initial FIGO stage classifications of I (29), II (23), III (122), and IV (88) were enrolled. In total, 153 endometrioid adenocarcinomas, 34 serous adenocarcinomas, 17 clear cell adenocarcinomas, 36 carcinosarcomas, and 22 "other" tumors were documented. The response rates for patients with platinum-free intervals of <6 months, 6-11 months, 12-23 months, and ≥24 months were 25%, 38%, 61%, and 65%, respectively. The median progression-free survival after second-line platinum-based chemotherapy for patients with platinum-free intervals of <12 months and ≥12 months was 4.4 (95% confidence interval (CI)=3.7-5.8) months and 10.3 (95% CI=8.2-12.6) months, respectively (log-rank P<0.0001), and the median overall survival was 13.8 (95% CI=10.6-18.1) months and 40.9 (95% CI=25.3-54.2) months, respectively (log-rank P<0.0001). CONCLUSION: Platinum-free interval is a predictor of response and survival after second-line platinum-based chemotherapy in patients with recurrent endometrial cancer. The concept of "platinum sensitivity" could be applicable to recurrent endometrial cancer.

DOI： 10.1016/j.ygyno.2013.09.021

子宮癌術後に尿道周囲に限局し再発した3症例

三輪真唯子, 山本香澄, 森本明美, 玉田将, 浮田真沙世, 若橋宣, 市田耕太郎, 須藤保, 長尾昌二, 山口聡, 藤原潔

日本癌治療学会誌 48 ( 3 ) 2434 - 2434 2013.9

[Intraperitoneal chemotherapy].

Shoji Nagao, Akira Kurosaki, Norihiro Iwasa, Keiichi Fujiwara

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 4 610 - 6 2012.6

Extrauterine low-grade endometrial stromal sarcomaの1例

堀祐子, 花岡立也, 西川忠曉, 黒崎亮, 大石理恵, 岩佐紀宏, 長谷川幸清, 長尾昌二, 藤原恵一

日本産科婦人科学会雑誌 64 ( 2 ) 648 - 648 2012.2

中腎管遺残過形成を背景に中腎性腺癌が発生し、脱分化を伴って癌肉腫へ移行した子宮頸部癌肉腫の1例

黒崎亮, 長尾昌二, 花岡立也, 西川忠曉, 大石理恵, 堀祐子, 岩佐紀宏, 長谷川幸清, 藤原恵一

日本産科婦人科学会雑誌 64 ( 2 ) 797 - 797 2012.2

子宮頸部明細胞腺癌の4例

西川忠曉, 長尾昌二, 花岡立也, 黒崎亮, 大石理恵, 岩佐紀宏, 長谷川幸清, 藤原恵一

日本産科婦人科学会雑誌 64 ( 2 ) 794 - 794 2012.2

First attempt of large phase III oncology trial using Japanese new trial evaluation system, the evaluation system of investigational medical care Reviewed

Eriko Aotani, Shinobu Kukino, Miwa Nonaka, Shoji Nagao, Keiichi Fujiwara

Japanese Pharmacology and Therapeutics 38 ( 1 ) S59 - S64 2010.7

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

Background: This is the first attempt to conduct a large-scale phaseIII oncology trial using the Evaluation System of Investigational Medical Care (ESIMeC). Methods: The study design is a randomized phase II / III trial comparing administration routes of carboplatin either intravenously (IV) or intraperitoneally (IP) in combination with weekly administration of paclitaxel for ovarian cancer patients. Target accrual is 746. Both IP carboplatin and weekly paclitaxel have not been approved for national insurance coverage in Japan. Results: Because of the expensive drug cost, it was first assumed impossible to conduct the trial if the study chair is responsible for purchasing the investigational drugs from the limited research grant or the patients have to pay for the investigational drugs without insurance coverage. Therefore, we negotiated with the pharmaceutical companies including generic makers to supply the investigational drugs with free of charge. The duration from initial consultation to the Ministry of Health, Labor, and Welfare to the finial approval to conduct the trial using ESIMeC was 8 months. Conclusion: The ESIMeC appears to be an efficient system as the official evaluation process of investigator-initiated, non-indication directed clinical trials, which manifestly require quality control of the trials. However, cost coverage for the investigational medicine or technique remains as an important issue to be resolved in the future, especially in large phase III oncology trials.

Evidence-based guidelines for treatment of cervical cancer in Japan: Japan Society of Gynecologic Oncology (JSGO) 2007 edition. Reviewed

Satoru Nagase, Yoshiki Inoue, Naohiko Umesaki, Daisuke Aoki, Masatsugu Ueda, Hideki Sakamoto, Shigemitsu Kobayashi, Ryo Kitagawa, Takafumi Toita, Shoji Nagao, Kiyoshi Hasegawa, Ichio Fukasawa, Keiichi Fujiwara, Yoh Watanabe, Kiyoshi Ito, Hitoshi Niikura, Tsuyoshi Iwasaka, Kazunori Ochiai, Hidetaka Katabuchi, Toshiharu Kamura, Ikuo Konishi, Noriaki Sakuragi, Tadao Tanaka, Yasuo Hirai, Yuji Hiramatsu, Makio Mukai, Hiroyuki Yoshikawa, Tadao Takano, Kosuke Yoshinaga, Takeo Otsuki, Michiko Sakuma, Noriyuki Inaba, Yasuhiro Udagawa, Nobuo Yaegashi

International journal of clinical oncology 15 ( 2 ) 117 - 24 2010.4

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

Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.

DOI： 10.1007/s10147-010-0061-x

Splenectomy during Secondary Cytoreductive Surgery for Epithelial Ovarian Cancer Reviewed International journal

Jitti Hanprasertpong, Rie Ohishi, Norihiro Iwasa, Shoji Nagao, Kojun Okamoto, Keiichi Fujiwara

ASIAN PACIFIC JOURNAL OF CANCER PREVENTION 11 ( 2 ) 413 - 416 2010

Language：English Publishing type：Research paper (scientific journal) Publisher：ASIAN PACIFIC ORGANIZATION CANCER PREVENTION

Splenic metastasis from ovarian cancer is unusual. Most splenic metastases are encountered in the setting of widespread visceral metastases. We present 6 cases of splenic metastasis of epithelial ovarian cancer. Three cases underwent a splenectomy as a part of interval debulking surgery, and the rest received a splenectomy as a surgery for recurrent disease. The splenectomies were well-tolerated in all patients and no serious morbidity or mortality resulted. Only one patient experienced a transient elevation in platelet count.

NCI issues clinical announcement for preferred method of treatment for advanced ovarian cancer Reviewed

S. Nagao, K. Fujiwara, R. Ohishi, Y. Nakanishi, N. Iwasa, M. Shimizu, T. Goto, K. Shimoya

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 18 ( 6 ) 1210 - 1214 2008.11

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Nagao S, Fujiwara K, Ohishi R, Nakanishi Y, Iwasa N, Shimizu M, Goto T, Shimoya K. Combination chemotherapy of intraperitoneal carboplatin and intravenous paclitaxel in suboptimally debulked epithelial ovarian cancer. Int J Gynecol Cancer 2008;18:1210-1214.
The objective of this study was to retrospectively assess the efficacy and safety of combination chemotherapy of intraperitoneal (IP) carboplatin and intravenous (IV) paclitaxel in suboptimally debulked ovarian cancer. Between March 1998 and March 2006, 44 patients with histologically confirmed epithelial ovarian carcinoma or peritoneal carcinoma with a residual mass greater than 1 cm received combination chemotherapy of IV paclitaxel and IP carboplatin. Administration of IV paclitaxel at 175 mg/m(2) immediately followed by IP carboplatin at an area under the curve of 6 was scheduled every 3 weeks for at least six cycles. The diagnosis and stage were ovarian carcinoma stage II in 8, III in 25, and IV in 6 cases, and peritoneal carcinoma stage III in 5 cases. Eighty-three percent of patients completed more than six cycles of chemotherapy. The incidences of grade 3/4 hematologic toxicities were 41 (93%) for neutrocytopenia, 10 (41%) for thrombocytopenia, and 18 (23%) for anemia. Observed grade 3/4 nonhematologic toxicities were 1 (2%) for allergy, 1 (2%) for fatigue, 1 (2%) for vomiting, 1 (2%) for liver dysfunction, and 4 (9%) for peripheral neuropathy. Two patients (5%) encountered catheter problems (one obstruction and one infection). Overall response rate was 80% (16 complete response, 19 partial response, 3 stable disease, and 6 progressive disease). Median progression-free survival and overall survival were 24 and 31 months, respectively. Combination chemotherapy of IP carboplatin and IV paclitaxel is effective and safe in suboptimally debulked ovarian cancer, and further evaluation is warranted.

DOI： 10.1111/j.1525-1438.2008.01192.x

[Paclitaxel and carboplatin with or without pirarubicin (THP-ADR) as first line chemotherapy in elderly patients].

Shoji Nagao, Naoki Okimoto, Atsushi Hongo, Yasushi Mizutani, Junichi Kodama, Mitsuo Yoshinouchi, Yuji Hiramatsu, Takafumi Kudo

Gan to kagaku ryoho. Cancer & chemotherapy 30 ( 2 ) 243 - 9 2003.2

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

To evaluate the validity of administration of paclitaxel and carboplatin with or without pirarubicin (THP-ADR) as first line chemotherapy in elderly patients with gynecologic cancer, we explored the efficacy and safety of these regimens. From October 1, 1998 to September 30, 2001, we administered paclitaxel and carboplatin with or without THP-ADR pursuant to the chart we prepared originally as first line chemotherapy in patients with gynecologic cancer. Eleven elderly patients (age > 70 years) and 62 younger patients (age < 70 years) were entered into the present study. Paclitaxel was administered as a 3-hour intravenous (i.v.) infusion at dosages of 135 to 180 mg/m2 immediately followed by carboplatin over 60 minutes at dosages of area under the curve (AUC) 3 to 5, administered intravenously or intraperitoneally. We observed grade 3/4 anemia more frequently in elderly patients receiving the regimen including paclitaxel and carboplatin without THP-ADR (9% v.s. 47%, p < 0.0001). Grade 3/4 anemia (10% v.s. 22%, p = 0.02) and grade 3/4 thrombocytopenia (7% v.s. 22%, p = 0.007), febrile neutropenia (14% v.s. 44%, p = 0.02) also occurred more frequently in elderly patients receiving the regimen including paclitaxel and carboplatin with THP-ADR. The overall response rates were equivalent among elderly and younger patients (69% and 78%), respectively. The regimen consisting of paclitaxel and carboplatin without THP-ADR was applied safely to elderly patients.

[The effect of L-Glutamine and Shakuyaku-Kanzo-to for paclitaxel-induced myalgia/arthralgia].

Kosei Hasegawa, Yasushi Mizutani, Hiroyuki Kuramoto, Shoji Nagao, Hisashi Masuyama, Atsuhi Hongo, Jyunichi Kodama, Mitsuo Yoshinouchi, Yuji Hiramatsu, Takafumi Kudo, Hiroyuki Okuda

Gan to kagaku ryoho. Cancer & chemotherapy 29 ( 4 ) 569 - 74 2002.4

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

Myalgia/arthralgia is a crucial side effect of paclitaxel, and may become the major dose-limiting side effect. However, this is a situation where there is little effective preventive treatment. L-Glutamine was reported as a neuroprotective agent for vincristine-induced neurotoxicity. In Japan, there have been reports on steroid and Shakuyaku-Kanzou-to (a herbal medicine) for paclitaxel-induced myalgia/arthralgia. This study aimed to compare the effect of L-Glutamine and Shakuyaku-Kanzou-to, and to discuss the validity of these agents for the paclitaxel-induced myalgia/arthralgia. Our results suggested that Shakuyaku-Kanzou-to showed no remarkable effects against paclitaxel-induced myalgia/arthralgia as had been reported before; however, both L-Glutamine and Shakuyaku-Kanzou-to decreased the duration of grade 2 toxicity (CALGB Expanded Common Toxicity Criteria) in comparison with those who were not treated. L-Glutamine and Shakuyaku-Kanzou-to might therefore a preventive effect against moderate or severer myalgia/arthralgia during paclitaxel-treated chemotherapy. Further trials are needed to confirm the value of these drugs.

Rapid and sensitive detection of physical status of human papillomavirus type 16 DNA by quantitative real-time PCR. Reviewed International journal

Shoji Nagao, Mitsuo Yoshinouchi, Yasunari Miyagi, Atsushi Hongo, Junichi Kodama, Sachio Itoh, Takafumi Kudo

Journal of clinical microbiology 40 ( 3 ) 863 - 7 2002.3

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

A rapid quantitative real-time PCR method was employed to quantify the copy number of E2 and E6 genes for analysis of the physical status of human papillomavirus type 16 (HPV-16) DNA. Significant differences with respect to both copy numbers were found when more than 40% of HPV-16 DNA was integrated with disruption of the E2 gene in an experimental model. The physical status of HPV-16 DNA in 50 clinical samples was exclusively episomal in 21 cases (42%), concomitant in 14 cases (28%), and integrated in 15 cases (30%). The prevalence of integrated and/or concomitant forms of HPV-16 DNA increased with progression of cervical disease. Four of 11 cervical intraepithelial neoplasia involved integrated forms of HPV-16 DNA partially or exclusively. This rapid, sensitive technique is useful in the analysis of the physical status of HPV DNA.

腹腔鏡補助下膣式子宮全摘術の難易度推定のための術前診断スコア (LAVH Score)

松本貴, 倉本博行, 矢野真理, 山本寄人, 長尾昌二, 兵頭慎治, 木花敏雅, 野田清史, 石井修平, 森巍

日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology 14 ( 1 ) 121 - 124 1998.12

当院における腹腔鏡補助下腟式子宮全摘術(LAVH)の検討(TVH施行例との比較とLAVHの意義について)

松本貴, 松岡亮平, 今井香里, 長尾昌二, 片山富博, 森巍

日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology 12 ( 1 ) 83 - 86 1996.12

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