Faculty Profiles - NAKAMURA Keiichiro

Papers - NAKAMURA Keiichiro

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CD63 as a potential biomarker for patients with ovarian cancer. International journal

Keiichiro Nakamura, Naoyuki Ida, Akira Hirasawa, Kazuhiro Okamoto, Thuy Ha Vu, Dao Thi Hai Ly, Hisashi Masuyama

European journal of obstetrics, gynecology, and reproductive biology 306 87 - 93 2025.1

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

INTRODUCTION: Exosomes play an important role in regulating physiological processes and mediating the systemic dissemination of various types of cancer. We investigated the association of exosomal tetraspanins CD9, CD63, and CD81 in patients with ovarian cancer (OC). MATERIAL AND METHODS: We measured the plasma tetraspanins CD9, CD63, and CD81 by enzyme-linked immunosorbent assay in 91 patients who underwent treatment for OC between April 2018 and March 2024. Additionally, we analyzed clinical pathologic factors, chemotherapy response, and prognosis. RESULTS: In terms of stages, CD63 expression was significantly higher in patients with stage IV compared to those with stage I OC (p = 0.003). In terms of histological type, CD63 expression was significantly higher in high-grade serous carcinoma (HGSC) than in clear cell carcinoma (CCC) with OC (p = 0.009). Furthermore, CD63 levels were significantly higher in advanced-stage, HGSC than in patients with early-stage, non-HGSC and early-stage, HGSC OC (p = 0.045 and p = 0.002, respectively). In the Neoadjuvant chemotherapy (NAC) of 12 patients with OC assessed as having either a partial response (PR) or complete response (CR), CD63 was significantly decreased (p = 0.043), whereas perforin was significantly increased (p = 0.001). In the NAC of 16 patients with OC, CD63 of the response rate to chemotherapy tended to differ between the progressive disease (PD) and PR/CR groups (p = 0.056). A moderate inverse correlation was observed between CD63 and perforin levels (R = 0.638, R2 = 0.428, p = 0.008). CONCLUSIONS: CD63 could be a potential biomarker for all types of OC patients.

DOI： 10.1016/j.ejogrb.2025.01.011

Declining Prevalence of Human Papillomavirus Co-Infections Among Young Japanese Women With Cervical Cancer and Its Precursors. Reviewed International journal

Eri Yoshiizumi, Mamiko Onuki, Iwao Kukimoto, Fumiaki Takahashi, Tomoya Matsui, Kyoko Hamasaki, Hiroyuki Kanao, Ai Nio, Hideaki Yahata, Mayuko Goda, Takanori Yokoyama, Tsuyoshi Hisa, Kazuto Tasaki, Yuri Tenjimbayashi, Haruya Saji, Wataru Kudaka, Yuji Takei, Shogo Shigeta, Takeshi Motohara, Hiroko Matsumiya, Keiichiro Nakamura, Hiroyuki Yoshida, Mitsuya Ishikawa, Junzo Hamanishi, Hidekatsu Nakai, Mayuyo Mori-Uchino, Yasuyuki Hirashima, Akihiko Sekizawa, Hiroyuki Yoshikawa, Nobuo Yaegashi, Koji Matsumoto

Journal of medical virology 96 ( 12 ) e70096 2024.12

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

Co-infections with human papillomavirus (HPV) of multiple genotypes mainly occur due to increased sexual activity. To address the prevalence and trend of HPV co-infections in Japan, HPV-type-specific data from Japanese women (n = 8128) aged < 40 years and newly diagnosed with cervical abnormalities at 24 hospitals between 2012 and 2023 were analyzed. These included cervical intraepithelial neoplasia grade 1/2 (CIN1/2, n = 2745), CIN3/adenocarcinoma in situ (AIS) (n = 3953), and invasive cervical cancer (ICC, n = 1430). For women enrolled in this study since 2019, information on sexual behaviors was collected via a self-administered questionnaire. Time-trend analyses by disease category showed significant declines in the prevalence of multiple HPV infections in CIN1/2 (49.1%-38.3%, ptrend = 0.0004), CIN3/AIS (44.7%-31.5%, ptrend = 0.0002), and ICC (26.7%-10.5%, ptrend < 0.0001) during the last decade. When these data were analyzed separately for women aged 20-29 and 30-39 years, similar declining trends were observed in each disease category. Using data from 2111 women for whom information on sexual history was available, the number of sexual partners was strongly associated with increased multiple HPV infections (p < 0.0001). In conclusion, the declining prevalence of HPV co-infections in cervical cancer and its precursors may reflect a decrease in sexual activity among Japanese women of reproductive age.

DOI： 10.1002/jmv.70096

ADAR1 could be a potential diagnostic target for intrauterine infection patients. International journal

Keiichiro Nakamura, Kunitoshi Shigeyasu, Thuy Ha Vu, Jota Maki, Kazuhiro Okamoto, Hisashi Masuyama

Scientific reports 14 ( 1 ) 29419 - 29419 2024.11

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

Intrauterine infection (IUI) is mainly an ascending infection in which vaginal and cervical pathogens ascend to the uterus and can affect the fetus. Until now, there is still no effective diagnostic biomarker for IUI, such as chorioamnionitis (CAM) and funisitis (FUN). Deoxyribonucleic acid (DNA)/Ribonucleic acid (RNA) editing molecules such as apolipoprotein-B mRNA-editing complex (APOBEC) 3 families and Adenosine deaminase family acting on RNA (ADAR)1 were examined in chorioamniotic membranes and umbilical cord of 83 patient samples. Furthermore, Ureaplasma parvum induced ADAR1 was investigated in human HTR-8/SVneo EVT cell line. ADAR1 had a significantly higher area under the curve (AUC) (0.721 and 0.745) than other APOBEC3s or cytokines in CAM and FUN patients. In vitro, ureaplasma parvum was demonstrated to activate ADAR1 (p = 0.025) and reduce RIG-I, IRF3, IFN-[Formula: see text], and IFN-β expression in EVT cell line (p = 0.005, p = 0.010, p < 0.001, and p = 0.018, respectively). High expression of ADAR1 was strongly associated with CAM and FUN patients (multivariate analyses; p = 0.035 and p = 0.002). ADAR1 could be a potential diagnostic target for IUI, such as CAM and FUN patients.

DOI： 10.1038/s41598-024-81097-4

Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan.

Yoshinori Tani, Keiichiro Nakamura, Masae Yorimitsu, Noriko Seki, Mie Nakanishi, Hironori Itou, Miyuki Shimizu, Dan Yamamoto, Etsuko Takahara, Hisashi Masuyama

International journal of clinical oncology 2024.11

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

BACKGROUND: In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification. METHODS: We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and univariate and multivariate analyses. RESULTS: The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p = 0.008 and OS: p = 0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p < 0.001 for both) than other treatments. Our findings suggest that lymphadenectomy and chemotherapy effectively reduced vaginal stump and lymph node metastases in FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.008, respectively). Furthermore, in the multivariate analysis, not undergoing lymphadenectomy or chemotherapy were independent predictors of recurrence and poor prognoses in patients with FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.031, respectively). CONCLUSION: Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC.

DOI： 10.1007/s10147-024-02647-4

Apolipoprotein-B mRNA-editing complex 3B could be a new potential therapeutic target in endometriosis. International journal

Thuy Ha Vu, Keiichiro Nakamura, Kunitoshi Shigeyasu, Chiaki Kashino, Kazuhiro Okamoto, Kotaro Kubo, Yasuhiko Kamada, Hisashi Masuyama

Scientific reports 14 ( 1 ) 24968 - 24968 2024.10

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

This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p < 0.001, p < 0.001, p = 0.029, p = 0.001). Knockdown of APOBEC3B increased apoptosis, which was 28.03% and 22.27% higher than in mock and control siRNA samples, respectively. APOBEC3B knockdown also decreased PIK3CA expression and increased Caspase 8 expression, suggesting a potential role in the regulation of apoptosis. Furthermore, knockdown of APOBEC3B significantly inhibited cell proliferation, invasion, and migration compared to mock and control siRNA. (Cell proliferation: mock: p < 0.001 and control siRNA: p = 0.049. Cell invasion: mock: p < 0.001 and control siRNA: p = 0.029. Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis.

DOI： 10.1038/s41598-024-76589-2

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

婦人科がん患者の医療機関への就労相談は,有効な職場復帰のカギとなる

中村圭一郎, 谷佳紀, 大石恵一, 三苫智裕, 依田尚之, 樫野千明, 牧尉太, 光井崇, 鎌田泰彦, 増山寿

日本女性医学学会雑誌 32 ( 1 ) 125 - 125 2024.10

帝王切開後の子宮創部菲薄化予防に対するBarbed suturesの効果多施設共同ランダム化比較試験

牧尉太, 三苫智裕, 大石恵一, 中村圭一郎, 鎌田泰彦, 山本暖, 山本梨沙, 玉田隆, 河西邦浩, 増山寿

日本女性医学学会雑誌 32 ( 1 ) 131 - 131 2024.10

婦人科がん患者の長期治療は職場復帰に影響を与える

谷佳紀, 中村圭一郎, 坂田周治郎, 大石恵一, 三苫智裕, 依田尚之, 樫野千明, 牧尉太, 光井崇, 鎌田泰彦, 増山寿

日本女性医学学会雑誌 32 ( 1 ) 109 - 109 2024.10

妊娠関連腰痛・骨盤痛を有する妊婦へ運動指導を行うと疼痛改善効果がみられる

大石恵一, 牧尉太, 三苫智裕, 坂田周治郎, 中村圭一郎, 増山寿

日本女性医学学会雑誌 32 ( 1 ) 152 - 152 2024.10

The adenosine deaminase family acting on RNA 1 can be a useful diagnostic biomarker in chorioamnionitis. International journal

Keiichiro Nakamura, Kunitoshi Shigeyasu, Jota Maki, Eriko Eto, Hisashi Masuyama

Placenta 153 53 - 58 2024.8

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

INTRODUCTION: Chorioamnionitis (CAM) involves infection and inflammation of the chorion and amniotic membrane, but there are still no effective diagnostic biomarkers for CAM. METHODS: We investigated the correlation between RNA editing enzyme Adenosine deaminase family acting on RNA 1 (ADAR1) and CAM in chorion and amniotic membrane specimens derived from premature rupture of the membrane (PROM), CAM (pathologically diagnosed), and clinical CAM (clinically diagnosed) patients using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: ADAR1 was upregulated in the chorion and amniotic membrane specimens of CAM and clinical CAM patients (p < 0.001 and p = 0.005). ADAR1 had a significantly higher area under the curve (AUC) (0.735 and 0.828) than markers of inflammation characteristics in diagnosing CAM and clinical CAM patients. ADAR1 also had significantly higher AUC (0.701 and 0.837) than clinical characteristics for CAM and clinical CAM patients. DISCUSSION: ADAR1 can be a useful diagnostic biomarker in CAM patients.

DOI： 10.1016/j.placenta.2024.05.133

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

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

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

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

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

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

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

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

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

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

DOI： 10.21873/invivo.13489

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

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

Japanese journal of clinical oncology 2023.11

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

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

DOI： 10.1093/jjco/hyad159

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

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

Cancer science 114 ( 11 ) 4426 - 4432 2023.11

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

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

DOI： 10.1111/cas.15943

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

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

Japanese journal of clinical oncology 2023.9

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

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

DOI： 10.1093/jjco/hyad125

子宮体癌卵巣転移が多彩な組織像を呈した1例

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

現代産婦人科 72 ( Suppl. ) S59 - S60 2023.9

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

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

Anticancer research 43 ( 8 ) 3653 - 3658 2023.8

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

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

DOI： 10.21873/anticanres.16546

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

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

Radiology case reports 18 ( 7 ) 2447 - 2451 2023.7

Language：English

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

DOI： 10.1016/j.radcr.2023.04.031

当院におけるMSI陽性者の遺伝外来受診に関する現状と課題

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

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

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

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

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

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

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

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

卵巣癌治療中に皮膚筋炎を発症し治療に難渋した一例

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

現代産婦人科 71 ( 2 ) 261 - 265 2023.6

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

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

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

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

Scientific reports 13 ( 1 ) 4720 - 4720 2023.3

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

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

DOI： 10.1038/s41598-023-30452-y

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

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

Scientific reports 13 ( 1 ) 2078 - 2078 2023.2

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

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

DOI： 10.1038/s41598-023-29397-z

初回進行卵巣癌に対するPARP阻害剤維持療法の施行状況と安全性の検討

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

日本産科婦人科学会雑誌 75 ( 臨増 ) S - 291 2023.2

子宮頸癌に対し放射線治療後骨盤骨折発生の多施設共同後ろ向きコホート研究

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

日本産科婦人科学会雑誌 75 ( 臨増 ) S - 450 2023.2

腹腔鏡下手術の適応への判断に超音波ガイド下針生検を施行した子宮腫瘤の検討

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

日本産科婦人科学会雑誌 75 ( 臨増 ) S - 427 2023.2

当科におけるマイクロサテライト不安定性検査とペムブロリズマブ投与の現況

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

現代産婦人科 71 ( 1 ) 117 - 121 2022.12

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

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

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J05038&link_issn=&doc_id=20221221480020&doc_link_id=%2Fcv0mtrob%2F2022%2F007101%2F020%2F0117-0121%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2022%2F007101%2F020%2F0117-0121%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

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

現代産婦人科 71 ( 1 ) 99 - 103 2022.12

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

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

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

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

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

日本女性医学学会雑誌 30 ( 1 ) 112 - 112 2022.10

産官学協働の地域モデルと高齢女性へのホルモン補充療法を用いた臨床研究がもたらす意義

三苫智裕, 牧尉太, 谷和祐, 樫野千明, 依田尚之, 光井崇, 鎌田泰彦, 中村圭一郎, 増山寿

日本女性医学学会雑誌 30 ( 1 ) 158 - 158 2022.10

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

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

日本女性医学学会雑誌 30 ( 1 ) 112 - 112 2022.10

産官学協働の地域モデルと高齢女性へのホルモン補充療法を用いた臨床研究がもたらす意義

三苫智裕, 牧尉太, 谷和祐, 樫野千明, 依田尚之, 光井崇, 鎌田泰彦, 中村圭一郎, 増山寿

日本女性医学学会雑誌 30 ( 1 ) 158 - 158 2022.10

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. 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 63 ( 5 ) 772 - 779 2022.9

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

Molecular Characteristics of Metastatic Lesions Have Superior Prognostic Impact on Endometrial Cancer. International journal

Kazuhiro Okamoto, Keiichiro Nakamura, Junko Haraga, Hisashi Masuyama

Anticancer research 42 ( 9 ) 4535 - 4543 2022.9

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

BACKGROUND/AIM: In endometrial cancer (EC), lymph node (LN) metastasis significantly impacts prognosis. Thus far, no studies have reported the molecular genetics of each metastatic lesion. This study aimed to investigate the molecular characteristics of primary and metastatic LNs and their association with clinical outcomes. PATIENTS AND METHODS: The clinicopathological and molecular characteristics of 33 patients with EC with regional LN metastasis (FIGO stage IIIC) were investigated; we evaluated the mutational status of p53 and DNA mismatch repair (MMR) proteins in the primary lesion, all the positive LNs (102 lesions), mutational variation between primary and paired metastatic lesions, inter-lesion heterogeneity, and their association with clinical outcomes. RESULTS: Immunohistochemically, 12 patients (36.4%) displayed aberrant p53 expression in metastatic lesions, and a concordant rate of 93.4% was observed between primary and metastatic lesions. Inter-lesion heterogeneity was observed in 20 cases (60.6%). In Kaplan-Meier analysis, patients with aberrant p53 expression in metastatic LNs exhibited worse progression-free survival (PFS) than those with wild-type p53 expression (p=0.008). Wild-type p53 expression in primary lesion with inter-lesion heterogeneity had a significantly worse PFS (p=0.049) than those without heterogeneity. In the Cox univariate analysis, p53 expression in metastatic LNs was significantly associated with recurrence (p=0.013). Genetic diversity between primary and metastatic lesions and among metastases was validated by evaluating the p53 and MMR proteins using immunohistochemistry analysis. CONCLUSION: The molecular characteristics of metastatic lesions in addition to those of primary lesions could provide beneficial prognostic information in patients with EC with regional LN metastasis.

DOI： 10.21873/anticanres.15956

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

Regional differences in human papillomavirus type 52 prevalence among Japanese women with cervical intraepithelial neoplasia†. International journal

Iwao Kukimoto, Mamiko Onuki, Kasumi Yamamoto, Hideaki Yahata, Yoichi Aoki, Harushige Yokota, Katsuyuki Konnai, Ai Nio, Kazuhiro Takehara, Shoji Kamiura, Naotake Tsuda, Yuji Takei, Muneaki Shimada, Hidekatsu Nakai, Hiroyuki Yoshida, Takeshi Motohara, Hiroyuki Yamazaki, Keiichiro Nakamura, Asuka Okunomiya, Nobutaka Tasaka, Mitsuya Ishikawa, Yasuyuki Hirashima, Yuko Shimoji, Mayuyo Mori, Takashi Iwata, Fumiaki Takahashi, Hiroyuki Yoshikawa, Nobuo Yaegashi, Koji Matsumoto

Japanese journal of clinical oncology 52 ( 10 ) 1242 - 1247 2022.8

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

Although geographical differences in the distribution of human papillomavirus genotypes have been observed worldwide, no studies have reported on national differences in the prevalence of human papillomavirus types in Japan. Here, we report a cross-sectional study to explore regional differences in the prevalence of human papillomavirus types among Japanese women with cervical intraepithelial neoplasia or invasive cervical cancer. Using human papillomavirus genotyping data from the nationwide prospective study on human papillomavirus vaccine effectiveness, we compared the frequency of detection of 15 high-risk and two low-risk human papillomavirus types in each disease category between the women who visited hospitals located in eastern Japan and those who visited hospitals located in western Japan. The risk of cervical intraepithelial neoplasia progression was assessed by calculating a prevalence ratio of each human papillomavirus type for cervical intraepithelial neoplasia grade 2/3 versus grade 1. Among the human papillomavirus types studied, human papillomavirus 52 was detected significantly more frequently in western hospitals than in eastern hospitals in cervical intraepithelial neoplasia grade 1 patients, but was less frequent in cervical intraepithelial neoplasia grade 2/3. The prevalence of particular human papillomavirus types was not significantly different between patients in hospitals in eastern Japan and those in hospitals in western Japan for invasive cervical cancer. In both eastern and western hospitals, a higher risk of cervical intraepithelial neoplasia progression was observed in patients infected with human papillomavirus 16, 31 or 58. In contrast, there was a significantly higher prevalence of human papillomavirus 52 infection in women with cervical intraepithelial neoplasia grade 2/3 than in those with cervical intraepithelial neoplasia grade 1 in eastern hospitals (prevalence ratio, 1.93; 95% confidence interval, 1.48-2.58), but not in western hospitals (prevalence ratio, 1.03; 95% confidence interval, 0.83-1.30). Regional differences of human papillomavirus 52 prevalence in cervical intraepithelial neoplasia lesions may exist and emphasize the importance of continuous monitoring of human papillomavirus type prevalence throughout the country in order to accurately assess the efficacy of human papillomavirus vaccines.

DOI： 10.1093/jjco/hyac127

Liquid Biopsy Revealed HBOC Pedigree and Led to Medical Management Among the Relatives.

Chikako Ogawa, Akira Hirasawa, Reimi Sogawa, Kayoko Hasuoka, Shuta Tomida, Mashu Futagawa, Yusaku Urakawa, Mariko Kochi, Hideki Yamamoto, Keiichiro Nakamura, Hisashi Masuyama

Acta medica Okayama 76 ( 4 ) 479 - 483 2022.8

Language：English

A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient's daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance.

DOI： 10.18926/AMO/63908

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

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

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

ADAR1 and AZIN1 RNA editing function as an oncogene and contributes to immortalization in endometrial cancer. International journal

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

Gynecologic oncology 166 ( 2 ) 326 - 333 2022.6

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

OBJECTIVE: Adenosine-to-inosine (A-to-I) RNA editing is a recently described epigenetic modification, which is believed to constitute a key oncogenic mechanism in human cancers. However, its functional role and clinical significance in endometrial cancer (EC) remain unclear. METHODS: Adenosine Deaminase family Acting on RNA1 (ADAR1) expression and Antizyme inhibitor 1 (AZIN1) RNA editing were examined to clarify the correlation with clinicopathological parameters and prognosis in EC patients. The biological functions and inhibitory effects of ADAR1 knockdown were investigated in JHUCS-1 and TU-ECS-1 EC cell lines. RESULTS: ADAR1 showed significant association with worse histology (P = 0.006), and lymph vascular space involvement (P = 0.049) in EC. The level of AZIN1 RNA editing was also significantly associated with worse histology (P = 0.012). ADAR1 expression was significantly correlated with AZIN1 RNA editing level (R = 0.729, R2 = 0.547, P < 0.001). Multivariate analysis indicated that higher ADAR1 expression along with AZIN1 RNA editing is an independent predictor of prognosis in EC patients (P = 0.015). Knockdown of ADAR1 led to increased MDA-5, RIG-I, PKR, and IRF-7 expression, which in turn resulted in increased levels of Bak and apoptosis in EC cells. CONCLUSIONS: High ADAR1 expression along with AZIN1 RNA editing could be a predictor of worse prognosis in EC. ADAR1 could be a potential therapeutic target in EC patients.

DOI： 10.1016/j.ygyno.2022.05.026

高齢者に発症した排尿障害を伴う陰唇癒着症の1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, 増山寿

現代産婦人科 70 ( 2 ) 273 - 276 2022.6

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

陰唇癒着症は左右の小陰唇または大陰唇が癒着している状態であり、低エストロゲン状態を背景に脆弱となった外陰部へ機械的刺激や炎症などが起こり、それらが誘因となり陰唇内面同士に癒着が生じるものである。今回、排尿障害を契機に診断された陰唇癒着症の一例を経験したので文献的考察を踏まえて報告する。症例は79歳、1妊1産、排尿障害を主訴に前医を受診され、陰唇癒着症の診断にて当院に紹介となった。外陰部は左右の陰唇が完全に癒着しており、会陰部に尿の流出路と思われるピンホール状の孔を認めた。骨盤造影MRI検査を施行し、泌尿生殖器の解剖学的な異常はなく、T2強調画像にて、外尿道口から外陰部正中に向かう尿の流出路と思われる線上の高信号域、また外陰部正中に尿の貯留と思われる嚢胞状の領域を認めた。排尿障害を伴う陰唇癒着症の診断にて外陰部癒着剥離術を行う方針となった。脊椎麻酔下に、ピンホール状の孔を基点として鋭的鈍的に孔を拡張し、腟、本来の尿道口を確認、陰唇の間を覆っている外陰部の皮膚様の組織を陰核付近まで切開し、癒着を剥離した。大陰唇の皮膚と小陰唇の内側の粘膜面を再癒着防止のために全周性に縫合し、手術を終了した。術後経過は良好で術後2日目に退院となった。退院2週間後の外来再診時に創部に異常なく全抜糸した。前医での週2回の創部洗浄、エストロゲン含有ゲルの塗布を指示し、経過観察とした。術後2ヵ月の外来再診時に再癒着なきことを確認し、終診とした。高齢者の陰唇癒着症は報告例も少なく、明確な治療指針は示されていない。陰唇癒着症の症状は様々であるが、排尿障害、尿失禁を主訴とする高齢女性を診察する際には陰唇癒着症も鑑別に挙げ、外陰部の診察を行い、陰唇癒着症の場合には適切な介入を行う必要がある。(著者抄録)

卵巣癌のSister Mary Joseph's noduleに対して臍切除を行った3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, 増山寿

現代産婦人科 70 ( 2 ) 409 - 415 2022.6

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

Sister Mary Joseph's nodule(SMJN)は腹腔内または骨盤の悪性腫瘍の臍転移であり、1-3%と稀である。SMJNの転移経路は腹膜播種からの転移が90%以上といわれているが、術中所見で腹膜播種を伴わない卵巣癌のSMJNの3例を経験したので報告する。症例1は75歳女性。卵巣癌IVB期(pT1cN0M1、類内膜癌)に対し単純子宮全摘出術(TAH)+両側付属器摘出術(BSO)+大網部分切除術(pOMT)+臍切除を施行しComplete surgeryが完遂できた。術後補助化学療法としてtri-weekly Paclitaxel+Carboplatin(tri-TC)+Bevacizmabを8サイクル施行後、Bevacizmabの維持療法を行い現在再発はない。症例2は74歳女性。卵巣癌IVB期(pT1aN0M1、類内膜癌)に対しTHA+BSO+pOMT+臍切除を施行した。後療法は本人の希望で施行せず、術後3ヵ月に死亡の転帰となった。症例3は50歳女性。初診時の画像所見から卵巣癌疑い、子宮体癌疑い、腹膜播種疑い、臍腫瘍を指摘された。子宮内膜組織診や臍生検から癌の同定はできなかったが、臨床的に卵巣癌または子宮体癌と診断し、weekly Paclitaxel+Carboplatin 14サイクルを術前化学療法として施行した。TAH+BSO+pOMT+臍切除を施行し、卵巣癌IVB期(ypT3bN0M1、類内膜癌)の診断であった。同抗癌剤を継続後、Niraparibにて維持療法中であるが再発所見を認めない。3症例共に臍切除を施行したが、術後合併症は生じなかった。症状や画像所見から臍転移を疑う卵巣癌症例では積極的に切除し、病期が変わることで治療方針の決定や予後に影響を及ぼす可能性がある。(著者抄録)

Hereditary gynecologic tumors and precision cancer medicine. International journal

Chikako Ogawa, Akira Hirasawa, Naoyuki Ida, Keiichiro Nakamura, Hisashi Masuyama

The journal of obstetrics and gynaecology research 48 ( 5 ) 1076 - 1090 2022.5

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

Gynecologic cancers are more often caused by genetic factors than other cancers. Genetic testing has become a promising avenue for the prevention, prognosis, and treatment of cancers. This review describes molecular features of gynecologic tumors linked to hereditary syndromes, gives an overview of the current state of clinical management, and clarifies the role of gynecology in the treatment of hereditary tumors. Typical hereditary gynecologic tumors include hereditary breast and ovarian cancer, Lynch syndrome, Peutz-Jeghers syndrome, and Cowden syndrome. Multigene panel testing, which analyzes a preselected subset of genes for genetic variants, has recently become the first-choice test because it can provide more accurate risk assessment than a single test. Furthermore, comprehensive genomic cancer profiling enables personalized cancer treatment and aids in germline findings.

DOI： 10.1111/jog.15197

The Combination of D-dimer and Glasgow Prognostic Score Can Be Useful in Predicting VTE in Patients with Stage IIIC and IVA Ovarian Cancer.

Kotaro Kubo, Keiichiro Nakamura, Kazuhiro Okamoto, Hirofumi Matsuoka, Naoyuki Ida, Tomoko Haruma, Chikako Ogawa, Hisashi Masuyama

Acta medica Okayama 76 ( 2 ) 129 - 135 2022.4

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

Cancer patients have increased risk of venous thromboembolism (VTE) that must be assessed before treatment. This study aimed to determine effective VTE biomarkers in gynecologic cancer (GC). We investigated the correlation between D-dimer levels, Khorana risk score (KRS), Glasgow prognostic score (GPS), and VTE in 1499 GC patients (583 cervical cancer (CC), 621 endometrial cancer (EC), and 295 ovarian cancer (OC) patients) treated at our institution between January 2008 and December 2019. χ2 and Mann-Whitney U-tests were used to determine statistical significance. We used receiver operating characteristic-curve analysis to evaluate the discriminatory ability of each parameter. D-dimer levels were significantly correlated with KRS and GPS in patients with GC. VTE was diagnosed in 11 CC (1.9%), 27 EC (4.3%), and 39 OC patients (13.2%). Optimal D-dimer cut-off values for VTE were 3.1, 3.2, and 3.9 μg/ml in CC, EC and OC patients, respectively. D-dimer could significantly predict VTE in all GC patients. Furthermore, D-dimer combined with GPS was more accurate in predicting VTE than other VTE biomarkers in stage IIIC and IVA OC (AUC: 0.846; p<0.001). This study demonstrates that combined D-dimer and GPS are useful in predicting VTE in patients with OC.

DOI： 10.18926/AMO/63406

Human papillomavirus vaccine effectiveness by age at first vaccination among Japanese women. International journal

Mamiko Onuki, Kasumi Yamamoto, Hideaki Yahata, Hiroyuki Kanao, Harushige Yokota, Hisamori Kato, Kumi Shimamoto, Kazuhiro Takehara, Shoji Kamiura, Naotake Tsuda, Yuji Takei, Shogo Shigeta, Noriomi Matsumura, Hiroyuki Yoshida, Takeshi Motohara, Hidemichi Watari, Keiichiro Nakamura, Akihiko Ueda, Nobutaka Tasaka, Mitsuya Ishikawa, Yasuyuki Hirashima, Wataru Kudaka, Ayumi Taguchi, Takashi Iwata, Fumiaki Takahashi, Iwao Kukimoto, Hiroyuki Yoshikawa, Nobuo Yaegashi, Koji Matsumoto

Cancer science 113 ( 4 ) 1428 - 1434 2022.4

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

In Japan, the National Immunization Program against human papillomavirus (HPV) targets girls aged 12-16 years, and catch-up vaccination is recommended for young women up to age 26 years. Because HPV infection rates increase soon after sexual debut, we evaluated HPV vaccine effectiveness by age at first vaccination. Along with vaccination history, HPV genotyping results from 5795 women younger than 40 years diagnosed with cervical intraepithelial neoplasia grade 2-3 (CIN2-3), adenocarcinoma in situ (AIS), or invasive cervical cancer were analyzed. The attribution of vaccine-targeted types HPV16 or HPV18 to CIN2-3/AIS was 47.0% for unvaccinated women (n = 4297), but 0.0%, 13.0%, 35.7%, and 39.6% for women vaccinated at ages 12-15 years (n = 36), 16-18 years (n = 23), 19-22 years (n = 14), and older than 22 years (n = 91), respectively, indicating the greater effectiveness of HPV vaccination among those initiating vaccination at age 18 years or younger (P < .001). This finding was supported by age at first sexual intercourse; among women with CIN2-3/AIS, only 9.2% were sexually active by age 14 years, but the percentage quickly increased to 47.2% by age 16 and 77.1% by age 18. Additionally, the HPV16/18 prevalence in CIN2-3/AIS was 0.0%, 12.5%, and 40.0% for women vaccinated before (n = 16), within 3 years (n = 8), and more than 3 years after (n = 15) first intercourse, respectively (P = .004). In conclusion, our data appear to support routine HPV vaccination for girls aged 12-14 years and catch-up vaccination for adolescents aged 18 years and younger in Japan.

DOI： 10.1111/cas.15270

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症例の検討

篠崎真里奈, 久保光太郎, 栗山千晶, 依田尚之, 岡本和浩, 松岡敬典, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 475 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

当院で免疫チェックポイント阻害剤を投与した6症例

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

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 301 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

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

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

当院で免疫チェックポイント阻害剤を投与した6症例

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

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 301 2022.2

Changes in HPV16/18 Prevalence among Unvaccinated Women with Cervical Intraepithelial Neoplasia in Japan: Assessment of Herd Effects following the HPV Vaccination Program Reviewed International journal

Mamiko Onuki, Kasumi Yamamoto, Hideaki Yahata, Hiroyuki Kanao, Koji Horie, Katsuyuki Konnai, Ai Nio, Kazuhiro Takehara, Shoji Kamiura, Naotake Tsuda, Yuji Takei, Shogo Shigeta, Hidekatsu Nakai, Hiroyuki Yoshida, Takeshi Motohara, Tatsuya Kato, Keiichiro Nakamura, Junzo Hamanishi, Nobutaka Tasaka, Mitsuya Ishikawa, Nobuhiro Kado, Yusuke Taira, Mayuyo Mori, Takashi Iwata, Fumiaki Takahashi, Iwao Kukimoto, Hiroyuki Yoshikawa, Nobuo Yaegashi, Koji Matsumoto

Vaccines 10 ( 2 ) 188 - 188 2022.1

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

Since the human papillomavirus (HPV) vaccination program for Japanese girls aged 12–16 years began in 2010, vaccination uptake has been low in women born before 1993 but high (approximately 70%) in those born during 1994–1999. We previously compared the prevalence of vaccine types HPV16 and HPV18 in cervical intraepithelial neoplasia grade 1–3 (CIN1–3) or adenocarcinoma in situ (AIS) between vaccinated and unvaccinated cohorts and found direct protection effects among vaccinated women in Japan. In this study, we focused on changes in HPV16/18 prevalence among “unvaccinated” cohorts with CIN/AIS. We analyzed HPV16/18 prevalence among 5051 unvaccinated women aged <40 years, newly diagnosed with CIN/AIS during 2012–2021 for time trends. Declining trends in HPV16/18 prevalence over 9 years were observed in CIN1 (36.0–10.0%, Ptrend = 0.03) and CIN2–3/AIS (62.5–36.4%, Ptrend = 0.07) among women aged <25 years. HPV16/18 prevalence in CIN1 and CIN2–3/AIS diagnosed at age 20–24 years was lower in 1994–1999 birth cohorts compared with 1988–1993 birth cohorts (4.5% vs. 25.7% for CIN1 and 40.0% vs. 58.1% for CIN2–3/AIS, both p = 0.04). Significant reduction in HPV16/18 prevalence among young unvaccinated women with CIN1 and CIN2–3/AIS suggests herd effects of HPV vaccination in Japan.

DOI： 10.3390/vaccines10020188

EG-VEGF Induces Invasion of a Human Trophoblast Cell Line via PROKR2.

Kazumasa Tani, Takashi Mitsui, Sakurako Mishima, Akiko Ohira, Jota Maki, Eriko Eto, Kei Hayata, Keiichiro Nakamura, Hisashi Masuyama

Acta medica Okayama 75 ( 6 ) 677 - 684 2021.12

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

Extravillous trophoblast (EVT) invasion is important for embryo implantation, placental development, and successful remodeling of the uterine spiral artery. Endocrine gland derived-vascular endothelial growth factor (EG-VEGF) and matrix metalloproteinases (MMPs) are implicated in EVT invasion; however, the high con-centrations found in pregnancy pathologies have not been investigated in non-tumor trophoblasts. The roles of EG-VEGF, prokineticin receptors (PROKR1/2), MMP-2, and MMP-9 in EVT invasion during spiral artery remodeling were evaluated using human EVT from HTR-8/SVneo cell lines. The expression of MMP-2, MMP-9, and mitogen-activated protein kinase (MAPK), and Akt pathways in HTR-8/SVneo cells treated with recom-binant EG-VEGF alongside anti-PROKR1 and/or anti-PROKR2 antibodies was evaluated using quantitative reverse transcription-PCR and western blotting. Wound-healing and cell invasion assays were performed to assess the migration and invasion of these treated cells. Interestingly, 20 nM EG-VEGF activated ERK1/2 sig-naling and upregulated MMP-2 and MMP-9. This effect was suppressed by anti-PROKR2 antibody via ERK1/2 downregulation. Anti-PROKR2 antibody inhibited the migration and invasion of EG-VEGF-stimulated HTR-8/SVneo cells. Elevated concentrations of EG-VEGF enhance EVT invasion in a human trophoblast cell line by upregulating MMP-2 and MMP-9 via PROKR2. These new insights into the regulation of epithelial cell invasion may help in developing therapeutic interventions for placental-related diseases during pregnancy.

DOI： 10.18926/AMO/62806

子宮頸癌終末期に癌性収縮性心膜炎をきたした一例

道満佳衣, 春間朋子, 岡本和浩, 松岡敬典, 依田尚之, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 70 ( 1 ) 49 - 52 2021.12

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

【緒言】癌性心膜炎は癌の心膜転移によって生じる病態であり、主に進行癌の末期に併発することが多い。初期は無症状であるが進行すると、呼吸苦や頻脈といった心タンポナーデ症状が出現する。今回子宮頸癌の終末期に急速な心不全を呈し、癌性収縮性心膜炎と診断された症例を経験したので報告する。【症例】52歳女性。47歳時に右水腎症を契機に子宮頸癌が疑われ、当科へ紹介となった。精査にて子宮頸癌IIIB期、T3bN0M0と診断され、同時化学放射線治療を施行した。1年3ヵ月後に肺転移と胸膜播種を認めたため、肺部分切除術と化学療法を施行した。その後も胸膜播種の再燃と化学療法を繰り返したが、画像上stable diseaseを保つことができ、患者のactivities of daily livingも保たれていた。しかし、子宮頸癌発症から5年4ヵ月後の定期受診時に呼吸困難感の訴えがあり、CTで心膜の不整肥厚を認め癌性心膜炎を疑われた。同時に新規病変である多発腹膜播種と肝転移も指摘された。化学療法の再開を予定したが、数日で安静時の呼吸困難感と全身浮腫が出現し緊急入院となった。入院時精査で心膜肥厚と右心不全の所見を認め、癌性収縮性心膜炎が強く疑われた。心膜肥厚による拡張障害のため心嚢液穿刺の適応はなく、開胸による心膜切除が治療選択となる。しかしながら、子宮頸癌終末期であることと高侵襲かつ対症療法にしかならないことを考慮すると、化学療法を行える全身状態にもっていくことは困難であると考えられた。入院後は、心不全による呼吸苦に対して主にモルヒネ製剤を用いて緩和治療に努めたが、急速に心不全が悪化し、入院13日目に永眠された。【結語】癌性心膜炎は稀かつ予後不良な病態であるが、本症例のように心嚢液貯留ではなく収縮性心膜炎による拡張障害をきたした場合、さらに予後不良な状態となり得ると考えられた。(著者抄録)

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卵巣がんの破裂を契機に腹部コンパートメント症候群をきたした1症例

谷佳紀, 依田尚之, 岡本和弘, 松岡敬典, 久保光太郎, 春間朋子, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 70 ( 1 ) 209 - 213 2021.12

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

【背景】腹部コンパートメント症候群(Abdominal compartment syndrome:ACS)とは腹腔内圧の上昇により臓器障害/臓器不全を生じる病態であるが、婦人科悪性腫瘍に関連したACSの報告は極めて稀である。今回、我々は卵巣がんの破裂を契機に発症したACSの1例を経験したため報告する。【症例】59歳女性、2妊2産。もやもや病の既往がありクロピドグレルとアスピリンを内服していた。2ヵ月前から腹部緊満感を自覚しており、突然の腹痛、嘔気を認め近医を受診した。腸閉塞の疑いで前医紹介となったが、CTで巨大卵巣腫瘍、血性腹水を指摘され緊急入院となり、血圧低下を伴ったためICU管理となった。外科的治療介入を要する可能性があり、集学的管理目的に当院ICUに転院となった。進行する腹部緊満感と多臓器不全からACSが疑われ、卵巣腫瘍の慢性経過による腹腔内圧の緩徐な上昇と腹腔内出血を契機とした急激な血性腹水の増加が病態と考えられた。保存的治療で管理が困難なため止血や減圧を目的に開腹両側付属器切除術を施行した。卵巣腫瘍は破綻し内容液と腹水は明らかに膿性であった。組織学的診断は類内膜癌、菌塊を認めた。多臓器不全は術後速やかに改善、ICUで全身管理を継続し術後57日目に退院となった。廃用症候群のため後療法は施行せず経過観察の方針とした。10ヵ月経過するが、再発なく自立生活が可能な全身状態である。【考察】本症例は内服歴や画像所見から、出血を契機としたACSを疑ったが、臨床経過から不顕性に腫瘍内感染していた卵巣がんが破綻することで急激に敗血症が発症、さらに輸液管理も腹腔内への急激な体液移動を助長し腹腔内圧が上昇した結果ASCを発症したと考えられた。また、CT画像で腹水の性状の鑑別が困難であることも診断に難渋した要因であった。【結語】卵巣腫瘍の破裂を契機にACSをきたした際には、腹腔内出血以外の原因も鑑別に挙げ、詳細な臨床所見の収集、腹水試験穿刺などの侵襲的精査も施行し、迅速な診断、治療を行うべきである。(著者抄録)

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hCGの下降が非順調型であった肺転移を伴う侵入奇胎の1例

兼森雅敏, 久保光太郎, 松岡敬典, 岡本和浩, 依田尚之, 春間朋子, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 70 ( 1 ) 81 - 85 2021.12

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

【緒言】侵入奇胎は胞状奇胎絨毛が子宮筋層内へ浸潤したものであり、全胞状奇胎の10-20%に続発し、約1/3の症例に肺転移を認める。侵入奇胎はヒト絨毛性ゴナドトロピン(human chorionic gonadotropin;hCG)が特異的マーカーであり化学療法が著効するが、hCGの下降が非順調型をたどる症例も存在する。治療に難渋した侵入奇胎の1例を報告する。【症例】43歳3妊1産。妊娠反応陽性で前医を受診したが、超音波検査で絨毛性疾患を疑われた。血中hCG 178,800mIU/mlであり、前医で子宮内容除去術施行し全胞状奇胎の診断であった。再掻爬施行するもhCGの下降が不良であり精査加療目的に当院紹介受診した。当院で測定した血中hCG値は6,822mIU/mlであり、CTにて左肺に多発する結節影を認めた。絨毛癌診断スコア3点でありStageIIIの侵入奇胎と診断し、MA療法(メトトレキサート+アクチノマイシンD)を開始した。9コース施行時点で肺病変は縮小を認めていたが、hCG値は0.7mIU/ml、β-hCG値は0.9mIU/mlと陰性化しきらない状態であった。下垂体性hCGの確認のため、下肢静脈血栓の既往があるのでGnRH agonist療法を施行したところ、hCGは陰性化し、その後MA12コースまで施行し、現在外来フォロー中である。【考案】今回の症例では多発肺転移を認めMA療法で治療を開始したが、hCGの下降は非順調型であり長期間の治療を要した。hCG値が陰性化しきらず下垂体性hCGを疑ったが、血栓症の既往がありエストロゲン製剤が使用できなかったため、GnRH agonist製剤の投与によりhCGが低下することを確認した。【結論】侵入奇胎は化学療法が奏効する疾患であるが、hCGの低下が不良であるなど治療抵抗性の症例も存在する。低単位のhCG分泌が持続する症例では、偽陽性など判断に難渋する場面も少なくなく、そのような場合にはホルモン治療(ホルモン補充やGnRH agonist療法)を用いてhCGの低下を図ることが重要である。(著者抄録)

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J05038&link_issn=&doc_id=20211220410015&doc_link_id=%2Fcv0mtrob%2F2021%2F007001%2F015%2F0081-0085%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2021%2F007001%2F015%2F0081-0085%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

トラベクテジン血管外漏出による皮膚壊死2例の治療経験

杉原悟, 池田賢太, 山崎修, 森実真, 下江敬生, 中村圭一郎

西日本皮膚科 83 ( 5 ) 417 - 422 2021.10

Language：Japanese Publisher：日本皮膚科学会-西部支部

症例1:72歳,女性。子宮平滑筋肉腫の多発肺転移に対して投与されたトラベクテジンの血管外漏出があり,右胸部CVポート刺入部を中心に広範囲の組織壊死を来した。適宜デブリドマンを施行し,4×8cmの範囲に全層植皮術を行い漏出後71日目に略治を得た。症例2:67歳,女性。子宮平滑筋肉腫の多発リンパ節転移,肺転移に対して投与されたトラベクテジンの血管外漏出があり,右胸部CVポート刺入部を中心に広範囲の組織壊死を来した。適宜デブリドマンを施行し,5×5cmの範囲に全層植皮術を行い漏出後96日目に略治を得た。紅斑部の病理所見では,いずれも表皮,真皮には炎症所見は目立たず,皮下組織の広範囲な壊死があった。表皮・真皮の温存ができると考え,皮下組織のみのデブリドマンによって植皮範囲を縮小できた。トラベクテジンの血管外漏出に遭遇した際は感染やさらなる壊死の拡大を防ぎ,創部の縮小を目指して加療することが必要である。また医原性の障害であり,自験例のように数回のデブリドマンと植皮術が必要で,傷閉鎖までは長期間を要することを慎重に説明していくことが重要である。(著者抄録)

診療進行再発卵巣癌に対するレジメン選択三海婦人科癌スタディグループ(SGSG)アンケート調査結果

澁谷剛志, 長尾昌二, 佐藤慎也, 竹原和宏, 宇佐美知香, 中村圭一郎, 古宇家正, 末岡幸太郎, 紀川純三

産婦人科の実際 70 ( 10 ) 1105 - 1108 2021.10

Language：Japanese Publisher：金原出版(株)

＜文献概要＞目的:進行卵巣癌に対するレジメン選択は,ベバシズマブ(BEV)の使用を含め施設間で異なっている可能性がある。われわれはわが国におけるレジメン選択の現状を把握することを目的とし,三海婦人科癌スタディグループ(SGSG)参加施設へアンケート調査を実施した。方法:2019年9月にSGSG参加施設35施設に対して,初回術後治療,術前化学療法(NAC),インターバル腫瘍減量手術(IDS)後,プラチナ感受性再発,のそれぞれのタイミングで第一選択として使用するレジメンをアンケート形式で調査した。成績:全35施設中20施設から回答があった。初回術後治療としてTC+BEV療法を第一選択としている施設は15施設(75%)であった。プラチナ感受性再発に対してBEV併用レジメンを第一選択としている施設は17施設(85%)であった。NACにおける第一選択のレジメンはTC療法が8施設(40%),dose-dense TC療法が6施設(30%),TC+BEV療法が6施設(30%)であった。IDS後にレジメンを変更している施設が8施設(40%)あった。結論:初回治療とプラチナ感受性再発に対してBEV併用レジメンを使用している施設が多く,NACの治療方針は多様であった。

高齢者に発症した排尿障害を伴う会陰癒着症の1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, 増山寿

現代産婦人科 69 ( Suppl. ) S83 - S83 2021.9

卵巣癌のSister Mary Joseph's nodule(SMJN)に対して臍切除を行った3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, 増山寿

現代産婦人科 69 ( Suppl. ) S90 - S90 2021.9

がんゲノム入門がんゲノムプロファイリング検査を行うために必要な知識と実例

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

現代産婦人科 69 ( Suppl. ) S29 - S29 2021.9

MSI-Highを有する再発子宮体癌に対してペムブロリズマブを使用し、髄膜脳炎を発症した一例

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

現代産婦人科 69 ( Suppl. ) S54 - S54 2021.9

直腸壁全層に及ぶ腸管子宮内膜症に対し、TaTME(経肛門的全直腸間膜切除術)を併用し腹腔鏡下に根治術を施行した一例

岡本和浩, 鎌田泰彦, 許春花, 樫野千明, 松岡敬典, 依田尚之, 光井崇, 久保光太郎, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科内視鏡学会雑誌 37 ( Suppl.I ) 281 - 281 2021.9

当院での遺伝性乳癌卵巣癌症候群(HBOC)に対するリスク低減卵管卵巣摘出術(RRSO)の現状

久保光太郎, 入江恭平, 岡本和浩, 松岡敬典, 依田尚之, 小川千加子, 鎌田泰彦, 中村圭一郎, 増山寿

日本産科婦人科内視鏡学会雑誌 37 ( Suppl.I ) 337 - 337 2021.9

当院の診断的腹腔鏡下手術の現状

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

日本産科婦人科内視鏡学会雑誌 37 ( Suppl.I ) 338 - 338 2021.9

The Spiral Trial: A multicenter, randomized, controlled trial of Spiral thread sutures versus conventional thread sutures to prevent thinning of uterine scars following elective cesarean section. International journal

Jota Maki, Hikari Nakatou, Kazumasa Tani, Eriko Eto, Kei Hayata, Dan Yamamoto, Kenji Kai, Takashi Tamada, Kazuyo Akamatsu, Kunihiro Kawanishi, Keiichiro Nakamura, Hisashi Masuyama

Contemporary clinical trials 107 106449 - 106449 2021.8

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

BACKGROUND: The aim of this randomized controlled trial (RCT) is to investigate whether Spiral-thread sutures are superior to conventional sutures (0-Vicryl) for preventing uterine scar thinning following elective cesarean section. METHODS: This multicenter, parallel-group RCT will be conducted in four hospitals across three medical regions in Japan to assess 200 women (≥20 years old) with singleton pregnancies who are scheduled to undergo cesarean sections. Eligible women will be randomly assigned (1:1 ratio) to receive either the conventional uterine suture continuous absorption thread, which is most commonly used in Japan, or the Spiral thread. The primary endpoint is the degree of scar thinning, measured by transvaginal ultrasonography 6-7 months postoperatively, to evaluate the position of the uterus (anterior or posterior tilt) and myometrial wound thickness. The degree of thinning will be compared between the groups, and four measurements (mm) of the thinning area, including caudal distance, depth of the depression, remaining thickness of the myometrium on the serous side of the most depressed area, and width of the depression, will be recorded in the sagittal view on transvaginal ultrasound. Secondary endpoints will include total operative time, suture application time (from birth to the end of uterine suturing), operative blood loss, number of additional Z-sutures or continuous sutures required to stop bleeding, maternal abnormality frequency (surgical complications and postoperative infections), surgeon's years of experience, and clinical interpretation of individual subscale scores. DISCUSSION: This study shall provide important evidence on the optimal suture for preventing hysterotomy wound thinning after the first cesarean section. TRIAL REGISTRATION: National Institute of Public Health, Japan: jRCT1062200001 (May 7, 2020; https://rctportal.niph.go.jp/en/detail?trial_id=jRCT1062200001) and Okayama University Certified Review Board: CRB6180001 (April 9, 2020, version 3.0).

DOI： 10.1016/j.cct.2021.106449

ヒト絨毛細胞の浸潤におけるPROKR2を介したEG-VEGFの役割(The role of EG-VEGF through PROKR2 in the invasion of human trophoblast cells)

Tani Kazumasa, Mitsui Takashi, Mishima Sakurako, Oohira Akiko, Maki Jota, Eto Eriko, Hayata Kei, Nakamura Keiichiro, Masuyama Hisashi

The Journal of Obstetrics and Gynaecology Research 47 ( 8 ) 2829 - 2829 2021.8

卵巣癌易罹患性に関する遺伝学的背景を持つ卵巣子宮内膜症性嚢胞から癌化をきたした2症例

小川千加子, 依田尚之, 松岡敬典, 入江恭平, 岡本和浩, 春間朋子, 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 63回 245 - 245 2021.7

当科における子宮頸癌に対するがんパネル検査の現況

松岡敬典, 小川千加子, 岡本和浩, 依田尚之, 久保光太郎, 春間朋子, 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 63回 337 - 337 2021.7

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

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

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

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) Publisher：SPRINGER JAPAN KK

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/m(2), 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

当院で施行した卵巣がんのがんゲノム医療の現況

依田尚之, 小川千加子, 岡本和浩, 松岡敬典, 久保光太郎, 春間朋子, 中村圭一郎, 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 63回 209 - 209 2021.7

当院における子宮体がんの遺伝子パネル検査の検討

岡本和浩, 小川千加子, 松岡敬典, 依田尚之, 久保光太郎, 春間朋子, 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 63回 214 - 214 2021.7

卵巣癌易罹患性に関する遺伝学的背景を持つ卵巣子宮内膜症性嚢胞から癌化をきたした2症例

小川千加子, 依田尚之, 松岡敬典, 入江恭平, 岡本和浩, 春間朋子, 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 63回 245 - 245 2021.7

当科における子宮頸癌に対するがんパネル検査の現況

松岡敬典, 小川千加子, 岡本和浩, 依田尚之, 久保光太郎, 春間朋子, 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 63回 337 - 337 2021.7

当院で施行した卵巣がんのがんゲノム医療の現況

依田尚之, 小川千加子, 岡本和浩, 松岡敬典, 久保光太郎, 春間朋子, 中村圭一郎, 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 63回 209 - 209 2021.7

当院における子宮体がんの遺伝子パネル検査の検討

岡本和浩, 小川千加子, 松岡敬典, 依田尚之, 久保光太郎, 春間朋子, 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 63回 214 - 214 2021.7

当院で施行したリスク低減卵管卵巣摘出術(RRSO)症例の検討

入江恭平, 小川千加子, 岡本和浩, 松岡敬典, 依田尚之, 久保光太郎, 春間朋子, 中村圭一郎, 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 63回 259 - 259 2021.7

高齢者婦人科癌患者のCharlson Comorbidity Indexは予後予測因子になる

中村圭一郎, 入江恭平, 岡本和浩, 松岡敬典, 依田尚之, 久保光太郎, 春間朋子, 小川千加子, 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 63回 350 - 350 2021.7

当科における卵巣明細胞癌の検討

春間朋子, 岡本和浩, 松岡敬典, 依田尚之, 久保光太郎, 小川千加子, 中村圭一郎, 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 63回 263 - 263 2021.7

Successful Treatment of Acute Promyelocytic Leukemia Complicated with Endometrial Cancer by Arsenic Trioxide.

Hiroyuki Sugiura, Hisakazu Nishimori, Hirofumi Matsuoka, Keiichiro Nakamura, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

Acta medica Okayama 75 ( 2 ) 219 - 224 2021.4

Language：English

Acute promyelocytic leukemia (APL) is a hematological emergency that requires urgent intervention because of the high incidence of early hemorrhagic death. When patients with APL experience a synchronous solid organ tumor, the tumor's treatment must also be done properly. Differentiation-inducing therapy using arsenic trioxide (ATO) has less hematological toxicity compared to cytotoxic chemotherapy and might be preferable for untreated APL patients with a synchronous solid organ tumor. Here we describe the first successful case of untreated APL and synchronous endometrial cancer (in an adult Japanese woman) treated with ATO consolidation therapy and the subsequent surgery and chemotherapy for endometrial cancer.

DOI： 10.18926/AMO/61904

Successful Treatment of Acute Promyelocytic Leukemia Complicated with Endometrial Cancer by Arsenic Trioxide

Hiroyuki Sugiuraa, Hisakazu Nishimori, Hirofumi Matsuoka, Keiichiro Nakamura, Keiko Fujii, Nobuharu Fujii, Ken-ichi Matsuoka, Yoshinobu Maeda

ACTA MEDICA OKAYAMA 75 ( 2 ) 219 - 224 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Acute promyelocytic leukemia (APL) is a hematological emergency that requires urgent intervention because of the high incidence of early hemorrhagic death. When patients with APL experience a synchronous solid organ tumor, the tumor's treatment must also be done properly. Differentiation-inducing therapy using arsenic trioxide (ATO) has less hematological toxicity compared to cytotoxic chemotherapy and might be preferable for untreated APL patients with a synchronous solid organ tumor. Here we describe the first successful case of untreated APL and synchronous endometrial cancer (in an adult Japanese woman) treated with ATO consolidation therapy and the subsequent surgery and chemotherapy for endometrial cancer.

DNA mismatch repair deficiency and p53 abnormality are age-related events in mixed endometrial carcinoma with a clear cell component. International journal

Naoyuki Ida, Keiichiro Nakamura, Masayuki Saijo, Atsuko Nasu, Tadashi Yoshino, Hisashi Masuyama, Hiroyuki Yanai

Pathology, research and practice 220 153383 - 153383 2021.4

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

Mixed endometrial carcinoma (MEC) is defined as a tumor composed of two or more spatially distinct subtypes, at least one of which is serous or clear cell carcinoma. In this study, the clinicopathological features of 15 MEC cases containing a clear cell component (MEC-C) were investigated. The ages of patients ranged from 32 to 83 years (median, 61 years). The combinations of carcinoma components observed were endometrioid and clear cell in ten patients; endometrioid, clear cell and serous in three; and clear cell and serous in two. Immunohistochemically, nine had DNA mismatch repair (MMR) protein deficiency (MMR-d), nine had loss of ARID1A and three cases had aberrant p53 expression. MMR-d and loss of ARID1A showed a strong correlation. Only one case showed both MMR-d and aberrant p53 expression. The patients with MMR-d were younger than those without MMR-d (median; 58 years vs. 71 years). Loss of ARID1A also showed significant predilection for younger women than ARID1A intact cases. In conclusion, MMR-d was observed in 60 % of MEC-C, showed predilection for young women, and was associated with ARID1A loss. In contrast, non- MMR-d MEC-C occurred in elder women and some tumors may associate with TP53 mutation. These findings suggest that MEC-C develop via two different molecular mechanisms and they are age-related events.

DOI： 10.1016/j.prp.2021.153383

TC療法を受ける婦人科癌患者におけるSF36を活用したQOL調査

春間朋子, 岡本和浩, 松岡敬典, 依田尚之, 久保光太郎, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 73 ( 臨増 ) S - 280 2021.3

卵巣がんの破裂を契機に腹部コンパートメント症候群をきたした1症例

谷佳紀, 依田尚之, 岡本和浩, 松岡敬典, 久保光太郎, 春間朋子, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 73 ( 臨増 ) S - 329 2021.3

Shear Wave Elastographyは子宮頸癌に対する放射線治療の効果予測に有用である

松岡敬典, 中村圭一郎, 岡本和浩, 依田尚之, 久保光太郎, 春間朋子, 小川千加子, 増山寿

日本産科婦人科学会雑誌 73 ( 臨増 ) S - 312 2021.3

当院の子宮体癌に対する低侵襲手術の検討

久保光太郎, 依田尚之, 岡本和浩, 松岡敬典, 春間朋子, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 73 ( 臨増 ) S - 401 2021.3

高エストロゲン血症を伴う卵巣偽粘液腫の一例

川口優里香, 小川千加子, 松岡敬典, 岡本和浩, 依田尚之, 春間朋子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 73 ( 臨増 ) S - 331 2021.3

当院の子宮頸癌IB2期の検討

依田尚之, 岡本和浩, 松岡敬典, 春間朋子, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 73 ( 臨増 ) S - 308 2021.3

ヒト絨毛細胞の浸潤におけるPROKR2を介したEG-VEGFの役割(The role of EG-VEGF through PROKR2 in the invasion of human trophoblast cells)

Tani Kazumasa, Mitsui Takashi, Mishima Sakurako, Oohira Akiko, Maki Jota, Eto Eriko, Hayata Kei, Nakamura Keiichiro, Masuyama Hisashi

日本産科婦人科学会雑誌 73 ( 臨増 ) S - 161 2021.3

子宮頸癌サバイバーにおける治療後筋肉・脂肪量変化の検討

坂井裕樹, 中村圭一郎, 松岡敬典, 依田尚之, 原賀順子, 久保光太郎, 春間朋子, 小川千加子, 鎌田泰彦, 増山寿

日本婦人科腫瘍学会雑誌 39 ( 1 ) 348 - 348 2021.1

Trabectedinの血管外漏出により重篤な皮膚障害を生じた1例

依田尚之, 中村圭一郎, 松岡敬典, 原賀順子, 春間朋子, 小川千加子, 増山寿

日本婦人科腫瘍学会雑誌 39 ( 1 ) 372 - 372 2021.1

放射線治療患者におけるShear Wave Elastography超音波を用いた腫瘍硬度の検討

松岡敬典, 中村圭一郎, 坂井裕樹, 依田尚之, 原賀順子, 久保光太郎, 春間朋子, 小川千加子, 鎌田泰彦, 増山寿

日本婦人科腫瘍学会雑誌 39 ( 1 ) 346 - 346 2021.1

子宮頸癌サバイバーにおける治療後筋肉・脂肪面積変化の検討

坂井裕樹, 中村圭一郎, 松岡敬典, 依田尚之, 原賀順子, 久保光太郎, 春間朋子, 小川千加子, 増山寿

現代産婦人科 69 ( 1 ) 11 - 17 2020.12

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

癌治療の発展によりがんサバイバーが増え、治療後の生活の質がますます重要になっている。そこで今回、子宮頸癌治療後における経時的な身体的変化を着目し、検討した。当科で広汎性子宮全摘術及び同時化学放射線治療(concurrent chemoradiotherapy:CCRT)を行った子宮頸癌患者27名を対象とし、治療前後(治療前、治療直後、治療後1年、治療後3年、治療後5年)のCT画像を用いて、第三腰椎レベルの骨格筋面積(skeletal muscle index:SMI)、腸腰筋面積(iliopsoas muscle index:IMI)、皮下脂肪面積(subcutaneous fat mass index:SFMI)、内臓脂肪面積(visceral fat mass index:VFMI)を計測し、経時的変化を検討した。治療前平均SMI、IMI、SFMI、VFMIは35.56±3.61、3.67±0.76、51.56±19.76、34.88±17.89cm2/m2であった。治療後、筋肉・脂肪面積が20%以上減少した症例は治療直後ではIMI 3例(11.1%)、SFMI 4例(14.8%)、VFMI 12例(44.4%)、治療後1年IMI 2例(7.4%)、SFMI 9例(33.3%)、VFMI 11例(40.7%)、治療後3年IMI 3例(11.1%)、SFMI 3例(11.1%)、VFMI 7例(25.9%)、治療後5年IMI 6例(22.2%)、SFMI 6例(22.2%)、VFMI 8例(29.6%)であった。治療後における筋肉・脂肪面積変化は下肢リンパ浮腫や消化管・排尿障害の有害事象と関連はなく、治療後生活向上に向け、さらなる身体・精神面の解明が必要である。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J05038&link_issn=&doc_id=20201214470003&doc_link_id=%2Fcv0mtrob%2F2020%2F006901%2F003%2F0011-0017%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2020%2F006901%2F003%2F0011-0017%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

当院の早期子宮体がんにおける低侵襲手術の現況

依田尚之, 久保光太郎, 岡本和浩, 松岡敬典, 春間朋子, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科内視鏡学会雑誌 36 ( Suppl.I ) [O - 464] 2020.11

当院における子宮体癌に対する低侵襲手術の変遷

久保光太郎, 楠元理恵, 依田尚之, 岡本和浩, 松岡敬典, 春間朋子, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科内視鏡学会雑誌 36 ( Suppl.I ) [O - 410] 2020.11

CVポート部より漏出したトラベクテジンによる広範囲壊死の2例

杉原悟, 池田賢太, 山崎修, 下江敬生, 中村圭一郎, 森実真

日本皮膚外科学会誌 24 ( 2 ) 58 - 58 2020.10

当院でのロボット支援下子宮体癌手術の現況

中村圭一郎, 久保光太郎, 原賀順子, 松原侑子, 松岡敬典, 小川千加子, 増山寿

産婦人科手術 ( 31 ) 196 - 196 2020.8

Molecular Characterization of Second Primary Endometrial Cancer. International journal

Junko Haraga, Keiichiro Nakamura, Tomoko Haruma, Akihiro Nyuya, Takeshi Nagasaka, Hisashi Masuyama

Anticancer research 40 ( 7 ) 3811 - 3818 2020.7

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

BACKGROUND/AIM: The objective of this study was to determine the molecular and clinicopathological features, as well as the prognosis of patients with endometrial cancer (EC) having prior malignancy (second primary EC: SPEC) compared with those without a history of prior malignancy (first primary EC: FPEC). MATERIALS AND METHODS: We enrolled 294 FPEC patients and 32 SPEC patients who had undergone surgical resection with curative intent. EC was divided into four groups according to Cancer Genome Atlas Research Network (TCGA) classification. RESULTS: SPEC patients having greater than a 10-year interval from prior malignancy had risk factors including type II histology, deeper myometrial invasion, cervical invasion, and copy number high (CNH) phenotype compared with patients having less than a 10-year interval (p=0.007, p=0.002, p=0.015 and p=0.001). CONCLUSION: SPEC patients having greater than a 10-year interval from prior malignancy possessed numerous high-risk factors for EC.

DOI： 10.21873/anticanres.14370

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

Mamiko Onuki, Koji Matsumoto, Takashi Iwata, Kasumi Yamamoto, Yoichi Aoki, Shoji Maenohara, Naotake Tsuda, Shoji Kamiura, Kazuhiro Takehara, Koji Horie, Nobutaka Tasaka, Hideaki Yahata, Yuji Takei, Hisamori Kato, Takeshi Motohara, Keiichiro Nakamura, Mitsuya Ishikawa, Tatsuya Kato, Hiroyuki Yoshida, Noriomi Matsumura, Hidekatsu Nakai, Shogo Shigeta, Fumiaki Takahashi, Kiichiro Noda, Nobuo Yaegashi, Hiroyuki Yoshikawa

CANCER SCIENCE 111 ( 7 ) 2546 - 2557 2020.7

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

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012-2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2-3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type-specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type-specific RCs between CIN1 and CIN2-3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type-specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2-3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2-3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01-4.98), followed by HPV31 (2.51, 1.54-5.24), HPV18 (2.43, 1.59-4.32), HPV35 (1.56, 0.43-8.36), HPV33 (1.01, 0.49-3.31), HPV52 (0.99, 0.76-1.33), and HPV58 (0.97, 0.75-1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71-2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14-0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9-valent vaccine contributed to 89.7% (95% CI, 88.7-90.7) of CIN2-3/AIS and 93.8% (95% CI, 92.4-95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9-valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.

DOI： 10.1111/cas.14445

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan. International journal

Mamiko Onuki, Koji Matsumoto, Takashi Iwata, Kasumi Yamamoto, Yoichi Aoki, Shoji Maenohara, Naotake Tsuda, Shoji Kamiura, Kazuhiro Takehara, Koji Horie, Nobutaka Tasaka, Hideaki Yahata, Yuji Takei, Yoichi Aoki, Hisamori Kato, Takeshi Motohara, Keiichiro Nakamura, Mitsuya Ishikawa, Tatsuya Kato, Hiroyuki Yoshida, Noriomi Matsumura, Hidekatsu Nakai, Shogo Shigeta, Fumiaki Takahashi, Kiichiro Noda, Nobuo Yaegashi, Hiroyuki Yoshikawa

Cancer science 111 ( 7 ) 2546 - 2557 2020.7

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

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012-2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2-3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type-specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type-specific RCs between CIN1 and CIN2-3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type-specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2-3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2-3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01-4.98), followed by HPV31 (2.51, 1.54-5.24), HPV18 (2.43, 1.59-4.32), HPV35 (1.56, 0.43-8.36), HPV33 (1.01, 0.49-3.31), HPV52 (0.99, 0.76-1.33), and HPV58 (0.97, 0.75-1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71-2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14-0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9-valent vaccine contributed to 89.7% (95% CI, 88.7-90.7) of CIN2-3/AIS and 93.8% (95% CI, 92.4-95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9-valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.

DOI： 10.1111/cas.14445

Age-dependent Alteration in Mitochondrial Dynamics and Autophagy in Hippocampal Neuron of Cannabinoid CB1 Receptor-deficient Mice. International journal

Kosuke Kataoka, Andras Bilkei-Gorzo, Chihiro Nozaki, Akinobu Togo, Keiichiro Nakamura, Keisuke Ohta, Andreas Zimmer, Toru Asahi

Brain research bulletin 160 40 - 49 2020.7

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

Endocannabinoid system activity contributes to the homeostatic defense against aging and thus may counteract the progression of brain aging. The cannabinoid type 1 (CB1) receptor activity declines with aging in the brain, which impairs neuronal network integrity and cognitive functions. However, the underlying mechanisms that link CB1 activity and memory decline remain unknown. Mitochondrial activity profoundly influences neuronal function, and age-dependent mitochondrial activity change is one of the known hallmarks of brain aging. As CB1 receptor is expressed on mitochondria and may regulate neuronal energy metabolism in hippocampus, we hypothesized that CB1 receptors might influence mitochondria in hippocampal neurons. Here, we found that CB1 receptor significantly affected mitochondrial autophagy (mitophagy) and morphology in an age-dependent manner. Serine 65-phosphorylated ubiquitin, a key marker for mitophagy, was reduced in adult CB1-deficient mice (CB1-KO) compared to those in wild type controls, particularly in CA1 pyramidal cell layer. Transmission electron microscopy (TEM) analysis showed reduced mitophagy-like events in hippocampus of adult CB1-KO. TEM analysis also showed that mitochondrial morphology in adult CB1-KO mice was altered shown by an increase in thin and elongated mitochondria in hippocampal neurons. 3D reconstruction of mitochondrial morphology after scanning electron microscopy additionally revealed an enhanced density of interconnected mitochondria. Altogether, these findings suggest that reduced CB1 signaling in CB1-KO mice leads to reduced mitophagy and abnormal mitochondrial morphology in hippocampal neurons during aging. These mitochondrial changes might be due to the impairments in mitochondrial quality control system, which links age-related decline in CB1 activity and impaired memory.

DOI： 10.1016/j.brainresbull.2020.03.014

Seromucinous borderline tumorにおける術前検査所見の後方視的検討

清水かれん, 原賀順子, 松原侑子, 松岡敬典, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 68 ( 2 ) 239 - 244 2020.6

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

2014年6月に女性生殖器腫瘍のWHO分類第4版が刊行され、新たにseromucinous tumorという分類が加えられた。改訂後5年が経過し、しばしば症例を経験するが、術前診断は容易ではない。そこで、我々はseromucinous borderline tumor(SMBT)の術前診断における画像検査や血液検査の特徴を示すことを目的とし、検討を行った。方法は、2006年3月から2019年4月までに当院で手術を行い、病理組織診断でSMBT、もしくは2014年改定によりSMBTに包括されたmullerian mixed-epitherial borderline tumor、endocervical-like mucinous borderline tumorと診断された21例を対象とし、診療録を参照し後方視的に検討した。対象年齢の年齢は中央値49歳、病期はI期20例(95.2%)、III期1例(4.8%)であった。血清中CA125は中央値63.2U/mLであり、35U/mL以上の異常高値を示した例は13例(61.9%)であった。腫瘍径は中央値6.0cmであった。MRI所見では15例(71.4%)において嚢胞内容液はT1強調画像で高信号を示し、子宮内膜症の存在を反映していた。T2強調画像では充実部分の低信号のコアとその周囲の高信号がSMBTの特徴とされるが、その所見を認めたのは8例(38.1%)であった。造影効果については既存の報告と同様に、様々な造影強度であった。今回SMBT21例の画像所見を中心に検討を行ったが、一定の特徴はあるものの非典型例も多数認めた。術前診断の精度向上にはさらなる症例の蓄積が望まれる。(著者抄録)

Risk of Gynecologic Cancer as Second versus First Primary Cancer in Japan

Chikako Ogawa, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Hisashi Masuyama

ACTA MEDICA OKAYAMA 74 ( 2 ) 109 - 114 2020.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The X-2 test and the Kaplan-Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31(10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients.

The presence of chronic diseases contributes to the occurrence risk factors for gynecological cancers in Japan

Kazuhiro Okamoto, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Chikako Ogawa, Hisashi Masuyama

MOLECULAR AND CLINICAL ONCOLOGY 12 ( 4 ) 336 - 342 2020.4

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The aim of the present study was to determine whether chronic diseases (CD), such as hypertension, diabetes mellitus, dyslipidemia, heart diseases and cerebrovascular diseases, are occurrence risk factors and affect the survival of patients with gynecological cancers (GC). The correlations between CD and the characteristics and survival of 1,590 GC patients [685 with cervical cancer (CC), 613 with endometrial cancer (EM) and 292 with ovarian cancer (OV)] were investigated in the present study. Of the CD patients, 189 had CC (27.6%), 265 had EM (43.2%) and 72 had OV (24.7%). The incidence of CD increased with age in GC patients. The number of CD patients aged >= 70 years, was 8.6-fold higher in the CC group, 3.0-fold higher in the EM group, and 9.6-fold higher in the OV group compared with those aged <50 years. CD and excess body weight were associated with GC regardless of patient age. However, there was no correlation between CD and survival at any age in GC patients. These findings indicate that CD contribute to >24% of the occurrence risk factors in GC patients in Japan.

DOI： 10.3892/mco.2020.1989

The presence of chronic diseases contributes to the occurrence risk factors for gynecological cancers in Japan. International journal

Kazuhiro Okamoto, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Chikako Ogawa, Hisashi Masuyama

Molecular and clinical oncology 12 ( 4 ) 336 - 342 2020.4

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

The aim of the present study was to determine whether chronic diseases (CD), such as hypertension, diabetes mellitus, dyslipidemia, heart diseases and cerebrovascular diseases, are occurrence risk factors and affect the survival of patients with gynecological cancers (GC). The correlations between CD and the characteristics and survival of 1,590 GC patients [685 with cervical cancer (CC), 613 with endometrial cancer (EM) and 292 with ovarian cancer (OV)] were investigated in the present study. Of the CD patients, 189 had CC (27.6%), 265 had EM (43.2%) and 72 had OV (24.7%). The incidence of CD increased with age in GC patients. The number of CD patients aged ≥70 years, was 8.6-fold higher in the CC group, 3.0-fold higher in the EM group, and 9.6-fold higher in the OV group compared with those aged <50 years. CD and excess body weight were associated with GC regardless of patient age. However, there was no correlation between CD and survival at any age in GC patients. These findings indicate that CD contribute to >24% of the occurrence risk factors in GC patients in Japan.

DOI： 10.3892/mco.2020.1989

Risk of Gynecologic Cancer as Second versus First Primary Cancer in Japan.

Chikako Ogawa, Keiichiro Nakamura, Hirofumi Matsuoka, Yuko Matsubara, Junko Haraga, Hisashi Masuyama

Acta medica Okayama 74 ( 2 ) 109 - 114 2020.4

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

This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The χ2 test and the Kaplan-Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31 (10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients.

DOI： 10.18926/AMO/58268

子宮頸癌治療後における筋肉量(骨格筋量・腸腰筋量)変化の検討

松岡敬典, 中村圭一郎, 松原侑子, 原賀順子, 小川千加子, 増山寿

日本産科婦人科学会雑誌 72 ( 臨増 ) S - 314 2020.3

hCGの下降が非順調型であった肺転移を伴う侵入奇胎の1例

兼森雅敏, 久保光太郎, 松原侑子, 松岡敬典, 原賀順子, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 72 ( 臨増 ) S - 452 2020.3

【やさしくわかる産科婦人科検査マスターブック】(第2章)婦人科腫瘍分野がん化学療法のQOL評価

中村圭一郎, 原賀順子, 増山寿

産科と婦人科 87 ( Suppl. ) 195 - 199 2020.3

Reduction in HPV16/18 prevalence among young women with high-grade cervical lesions following the Japanese HPV vaccination program. International journal

Koji Matsumoto, Nobuo Yaegashi, Takashi Iwata, Kasumi Yamamoto, Yoichi Aoki, Masao Okadome, Kimio Ushijima, Shoji Kamiura, Kazuhiro Takehara, Koji Horie, Nobutaka Tasaka, Kenzo Sonoda, Yuji Takei, Yoichi Aoki, Katsuyuki Konnai, Hidetaka Katabuchi, Keiichiro Nakamura, Mitsuya Ishikawa, Hidemichi Watari, Hiroyuki Yoshida, Noriomi Matsumura, Hidekatsu Nakai, Shogo Shigeta, Fumiaki Takahashi, Kiichiro Noda, Hiroyuki Yoshikawa

Cancer science 110 ( 12 ) 3811 - 3820 2019.12

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

The Japanese government began a human papillomavirus (HPV) vaccination program for girls aged 12-16 years in 2010 but withdrew its recommendation in 2013 because of potential adverse effects, leading to drastically reduced vaccination uptake. To evaluate population-level effects of HPV vaccination, women younger than 40 years of age newly diagnosed with cervical intraepithelial neoplasia grade 1-3 (CIN1-3), adenocarcinoma in situ (AIS), or invasive cervical cancer (ICC) have been registered at 21 participating institutes each year since 2012. A total of 7709 women were registered during 2012-2017, of which 5045 were HPV genotyped. Declining trends in prevalence of vaccine types HPV16 and HPV18 during a 6-year period were observed in CIN1 (50.0% to 0.0%, Ptrend < .0001) and CIN2-3/AIS (83.3% to 45.0%, Ptrend = .07) only among women younger than 25 years of age. Overall, HPV vaccination reduced the proportion of HPV16/18-attributable CIN2-3/AIS from 47.7% to 33.0% (P = .003): from 43.5% to 12.5% as routine vaccination (P = .08) and from 47.8% to 36.7% as catch-up vaccination (P = .04). The HPV16/18 prevalence in CIN2-3/AIS cases was significantly reduced among female individuals who received their first vaccination at age 20 years or younger (P = .02). We could not evaluate vaccination effects on ICC owing to low incidence of ICC among women aged less than 25 years. We found HPV vaccination to be effective in protecting against HPV16/18-positive CIN/AIS in Japan; however, our data did not support catch-up vaccination for women older than 20 years. Older adolescents who skipped routine vaccination due to the government's suspension of its vaccine recommendation could benefit from receiving catch-up vaccination before age 20 years.

DOI： 10.1111/cas.14212

Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma Impact on Prognosis and Insights Into Tumorigenesis

Masayuki Saijo, Keiichiro Nakamura, Naoyuki Ida, Atsuko Nasu, Tadashi Yoshino, Hisashi Masuyama, Hiroyuki Yanai

AMERICAN JOURNAL OF SURGICAL PATHOLOGY 43 ( 11 ) 1493 - 1500 2019.11

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

Endometrial carcinosarcoma (ECS) is a rare and aggressive mixed-type epithelial and mesenchymal tumor. This study focused on the histologic appearance, loss of DNA mismatch repair (MMR) protein expression, and aberrant p53 expression in the epithelial component, and overall prognosis of 57 cases with ECS. Histologically, 21 and 36 cases exhibited low-grade (endometrioid grade 1 and 2) and high-grade (others) epithelial components, respectively. In a Kaplan-Meier analysis, patients with a high-grade epithelial component exhibited worse progression-free survival (PFS), compared with those with a low-grade component. Although the former group also exhibited worse overall survival, the difference was not significant. Thirty-six cases exhibited aberrant p53 expression. Of these, 5 cases exhibited focally aberrant p53 expression in carcinomatous components with diffuse aberrant p53 expression in mesenchymal components. Aberrant expression of p53 did not show significant association with prognosis. Six patients with MMR deficiency exhibited relatively better PFS. In conclusion, a low-grade epithelial component is a superior predictor of the PFS of ECS, compared with MMR protein and p53 expression status. In some cases of ECS, TP53 mutation may be a late event associated with histogenesis of the sarcomatous component.

DOI： 10.1097/PAS.0000000000001353

Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma: Impact on Prognosis and Insights Into Tumorigenesis. International journal

Masayuki Saijo, Keiichiro Nakamura, Naoyuki Ida, Atsuko Nasu, Tadashi Yoshino, Hisashi Masuyama, Hiroyuki Yanai

The American journal of surgical pathology 43 ( 11 ) 1493 - 1500 2019.11

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

Endometrial carcinosarcoma (ECS) is a rare and aggressive mixed-type epithelial and mesenchymal tumor. This study focused on the histologic appearance, loss of DNA mismatch repair (MMR) protein expression, and aberrant p53 expression in the epithelial component, and overall prognosis of 57 cases with ECS. Histologically, 21 and 36 cases exhibited low-grade (endometrioid grade 1 and 2) and high-grade (others) epithelial components, respectively. In a Kaplan-Meier analysis, patients with a high-grade epithelial component exhibited worse progression-free survival (PFS), compared with those with a low-grade component. Although the former group also exhibited worse overall survival, the difference was not significant. Thirty-six cases exhibited aberrant p53 expression. Of these, 5 cases exhibited focally aberrant p53 expression in carcinomatous components with diffuse aberrant p53 expression in mesenchymal components. Aberrant expression of p53 did not show significant association with prognosis. Six patients with MMR deficiency exhibited relatively better PFS. In conclusion, a low-grade epithelial component is a superior predictor of the PFS of ECS, compared with MMR protein and p53 expression status. In some cases of ECS, TP53 mutation may be a late event associated with histogenesis of the sarcomatous component.

DOI： 10.1097/PAS.0000000000001353

Pre-treatment psoas major volume is a predictor of poor prognosis for patients with epithelial ovarian cancer. International journal

Yuko Matsubara, Keiichiro Nakamura, Hirofumi Matsuoka, Chikako Ogawa, Hisashi Masuyama

Molecular and clinical oncology 11 ( 4 ) 376 - 382 2019.10

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

Low skeletal muscle mass (sarcopenia) is an important prognostic risk factor for the outcome of a variety of cancer types. The current study investigated whether skeletal muscle area (SMA), psoas area (PA) and psoas major volume (PV) are associated with progression-free survival (PFS) and overall survival (OS) in patients with epithelial ovarian cancer (OC). A total of 92 OC patients were enrolled in the present study. Pre-treatment with SMA and PA was assessed using computed tomography (CT) and PV was calculated using a three-dimensional-CT (3D-CT). The clinical factors associated with sarcopenia and prognosis were retrospectively evaluated. For all patients, the median PFS and OS were 19 and 32 months, respectively. Patients exhibiting lower PV (<195.6 cm3) had significantly poorer PFS and OS compared with patients exhibiting higher PV (≥195.6 cm3; P=0.018 and P=0.006), while those with low SMA (<92.92 cm2) had significantly worse OS than patients with higher SMA (≥92.92 cm2; P=0.030). PV was also demonstrated to be superior to SMA and PA in prognosis prediction. PV by 3D-CT can serve as an indicator of poor prognosis in patients with OC.

DOI： 10.3892/mco.2019.1912

前置癒着胎盤のCesarean hysterectomyに総腸骨動脈バルーン閉塞術(CIABO)を併用し総腸骨動脈解離を発症した一例

築澤良亮, 衛藤英理子, 牧尉太, 玉田祥子, 光井崇, 早田桂, 中村圭一郎, 増山寿

現代産婦人科 68 ( Suppl. ) S46 - S46 2019.9

Assessment of glucose kinetics with real-time continuous glucose monitoring during labor. International journal

Jota Maki, Eriko Eto, Shoko Tamada, Takashi Mitsui, Kei Hayata, Keiichiro Nakamura, Yuji Hiramatsu, Hisashi Masuyama

The journal of obstetrics and gynaecology research 45 ( 9 ) 1851 - 1859 2019.9

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

AIM: Changes in glucose levels during labor have not been sufficiently investigated in pregnant women. Using real-time continuous glucose monitoring, we aimed to assess glucose kinetics during labor among pregnant women with gestational diabetes mellitus (PwGDM), and those with normal glucose tolerance (PwNGT). METHODS: Japanese PwGDM and PwNGT who had planned a transvaginal delivery at Okayama University Hospital were enrolled. The correlation between changes in glucose levels during labor among the PwGDM and PwNGT groups at four time periods was assessed: (i) active phase of 1st stage of labor; (ii) 2nd stage of labor; (iii) postpartum 0-12 h; and (iv) postpartum 12-48 h. RESULTS: In total, 18 and 22 PwGDM and PwNGT, respectively, were enrolled. During labor, both groups had similar changes in glucose levels over time, which peaked during period 3. The main effect of glucose level changes was the labor period (P < 0.001), not the presence of gestational diabetes mellitus. Furthermore, differences in glucose levels in the PwGDM group were observed between periods 1 and 2 (P = 0.037), 1 and 3 (P = 0.024), 3 and 4 (P = 0.005); differences in glucose levels in the PwNGT group were observed between periods 3 and 4 (P = 0.024). CONCLUSION: During labor, both PwGDM and PwNGT groups showed similar changes in glucose levels over time. During delivery, the PwGDM who regularly measured their own glucose levels could be managed using the same nutritional management methods as those for PwNGT.

DOI： 10.1111/jog.14058

Seromucinous borderline tumorにおける術前検査所見の後方視的検討

清水かれん, 原賀順子, 松原侑子, 松岡敬典, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 68 ( Suppl. ) S60 - S60 2019.9

Predictors for pathological parametrial invasion in clinical stage IIB cervical cancer. International journal

Koji Matsuo, Muneaki Shimada, Keiichiro Nakamura, Yuji Takei, Kimio Ushijima, Toshiyuki Sumi, Tatsuru Ohara, Hideaki Yahata, Mikio Mikami, Toru Sugiyama

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 45 ( 8 ) 1417 - 1424 2019.8

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

OBJECTIVE: To examine predictors of pathological parametrial invasion in clinical stage IIB cervical cancer, and to examine prognostic factors in pathological stage IIB disease. METHODS: This study is an ancillary analysis of a nation-wide retrospective cohort examining 6,003 clinical stage IB-IIB cervical cancers. Women with clinical stage IIB disease who underwent primary radical hysterectomy with lymphadenectomy were examined (n = 714). Multivariate analysis was performed to identify independent clinico-pathological factors for pathological parametrial invasion and to identify independent prognostic factors in pathological stage IIB disease. RESULTS: Parametrial invasion was identified on the surgical specimen in 400 cases (56.0%, 95% confidence interval 52.4-59.7). On multivariate analysis, deep stromal invasion (DSI, adjusted-OR 3.922), multiple pelvic nodal metastases (adjusted-OR 3.266), lympho-vascular space invasion (adjusted-OR 2.333), and uterine corpus invasion (adjusted-OR 1.656) remained independent tumor factors for pathological parametrial invasion. In classification-tree models, tumors with DSI and multiple pelvic nodal metastases had the highest incidence of pathological parametrial invasion (75.0-87.7%); contrary, tumors without DSI had the lowest incidence (21.9%). Among patients with pathological stage IIB disease, the absolute difference in 5-year disease-free survival rates was 57.2%, ranging between 80.9% in those with squamous histology with none/single pelvic nodal metastasis and 23.7% in those with non-squamous histology with multiple pelvic nodal metastases. CONCLUSION: In clinical stage IIB cervical cancer, accuracy for pathological parametrial invasion is low-modest. With absence of DSI, only one in five clinical stage IIB diseases has pathological stage IIB disease. Survival of pathological stage IIB varies widely and is largely dependent on nodal factors.

DOI： 10.1016/j.ejso.2019.02.019

ロボット支援下子宮悪性腫瘍手術における助手の重要性

久保光太郎, 松原侑子, 松岡敬典, 原賀順子, 小川千加子, 鎌田泰彦, 中村圭一郎, 増山寿

日本産科婦人科内視鏡学会雑誌 35 ( Suppl.I ) 123 - 123 2019.8

後腹膜に発生した巨大Lipoleiomyomaの一例

片山沙希, 久保光太郎, 松岡敬典, 依田尚之, 西田傑, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 67 ( 2 ) 341 - 345 2019.6

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

Lipoleiomyomaは稀な良性腫瘍であり、その多くは子宮体部発生であり後腹膜発生は稀である。今回我々は、術中に後腹膜由来と判明したLipoleiomyomaの1例を経験したので文献的考察を交えて報告する。症例は58歳女性、1ヵ月前より急速に進行する腹部膨満感を主訴に前医を受診した。MRI検査にて、腹腔内を占める30cm超の巨大腫瘤を指摘された。卵巣癌が疑われ、当院を紹介受診された。当院で画像を再読影し、画像所見から子宮筋腫変性が第一に疑われたが発生由来臓器は特定できなかった。治療と診断目的にて開腹手術の方針となった。腫瘍は柔らかく後腹膜腔に存在しており、子宮との連続性は認められなかった。腫瘍は内容液を含め10kgを超えていた。子宮と両側付属器は肉眼的に異常所見を認めなかったが、腫瘍が子宮由来である可能性も考慮し、子宮全摘出術と両側付属器切除を施行した。術中出血は1250mlと多く、輸血を必要とした。術後病理検査ではLipoleiomyomaであり、術後経過は良好であった。Lipoleiomyomaは閉経前後の女性に多く認められ、急速増大した症例報告も認められている。後腹膜発生の症例も報告されているが、画像診断のみでは発生由来の判別は困難な場合もある。脂肪組織を含有する巨大な骨盤内腫瘍を認めた場合には当疾患も念頭において、十分な準備の後に手術を選択する必要がある。(著者抄録)

当院で縮小手術を施行した75歳以上の子宮体癌患者の検討

依田尚之, 中村圭一郎, 松原侑子, 西條昌之, 松岡敬典, 西田傑, 小川千加子, 増山寿

日本婦人科腫瘍学会雑誌 37 ( 3 ) 503 - 503 2019.6

治療前サルコペニアは子宮頸癌の予後を反映しない

松岡敬典, 中村圭一郎, 松原侑子, 依田尚之, 西條昌之, 西田傑, 小川千加子, 増山寿

日本婦人科腫瘍学会雑誌 37 ( 3 ) 477 - 477 2019.6

当院の子宮頸癌症例におけるFIGO2018分類での検討

松原侑子, 中村圭一郎, 松岡敬典, 西條昌之, 依田尚之, 西田傑, 小川千加子, 増山寿

日本婦人科腫瘍学会雑誌 37 ( 3 ) 443 - 443 2019.6

子宮全摘子宮頸癌放射線治療後残存に対するSalvage Surgeryの8例

小川千加子, 松原侑子, 松岡敬典, 依田尚之, 西田傑, 中村圭一郎, 増山寿

日本婦人科腫瘍学会雑誌 37 ( 3 ) 475 - 475 2019.6

Sarcopenia Is Not a Prognostic Factor of Outcome in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy or Radiotherapy. International journal

Hirofumi Matsuoka, Keiichiro Nakamura, Yuko Matsubara, Naoyuki Ida, Takeshi Nishida, Chikako Ogawa, Kuniaki Katsi, Susumu Kanazawa, Hisashi Masuyama

Anticancer research 39 ( 2 ) 933 - 939 2019.2

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

BACKGROUND/AIM: The objective of this study was to determine if sarcopenia was a predictor of poor prognosis in patients with cervical cancer (CC) undergoing concurrent chemoradiation therapy (CCRT) or radiation therapy (RT). MATERIALS AND METHODS: A total of 236 patients with CC undergoing CCRT or RT were retrospectively examined. We determined if clinical characteristics and survival were correlated with pretreatment sarcopenia, measured as psoas muscle index (PI) or skeletal muscle index (SMI). RESULTS: Pretreatment PI and SMI were related to parametrial involvement with CC undergoing CCRT or RT (p=0.002, and, p=0.034, respectively). The median progression-free survival (PFS) and overall survival (OS) times in patients undergoing CCRT or RT were 29.0 and 34.5 months, respectively. Neither PI nor SMI were prognostic predictors in patients with CC undergoing CCRT or RT. CONCLUSION: Sarcopenia is not a predictive factor of outcome in patients with CC undergoing CCRT or RT.

DOI： 10.21873/anticanres.13196

上皮性卵巣癌患者の筋肉量と予後予測について

松原侑子, 中村圭一郎, 松岡敬典, 西條昌之, 依田尚之, 西田傑, 小川千加子, 増山寿

日本産科婦人科学会雑誌 71 ( 臨増 ) S - 604 2019.2

腹腔鏡下両側付属器切除後に判明した正常大卵巣の明細胞境界悪性腫瘍の一例

片山沙希, 久保光太郎, 松岡敬典, 依田尚之, 西田傑, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 71 ( 臨増 ) S - 625 2019.2

異なる転帰をたどった成熟嚢胞性奇形腫を伴う抗NMDA受容体抗体脳炎の2症例

西田傑, 松原侑子, 依田尚之, 松岡敬典, 西條昌之, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 71 ( 臨増 ) S - 527 2019.2

リアルタイムCGMを用いた陣痛発来後から産褥早期までの血糖動態の検討

牧尉太, 衛藤英理子, 中村圭一郎, 平松祐司, 増山寿

糖尿病と妊娠 18 ( 3 ) S - 92 2018.11

婦人科がんサバイバーは健康的な生活を心掛けている

中村圭一郎, 松岡敬典, 牧尉太, 西條昌之, 依田尚之, 増山寿

日本女性医学学会雑誌 26 ( Suppl. ) 237 - 237 2018.10

婦人科がんサバイバーは健康的な生活を心掛けているライフスタイル変化についてのアンケート調査結果より

中村圭一郎, 原賀順子, 西田傑, 依田尚之, 西條昌之, 小川千加子, 楠本知行, 増山寿

日本婦人科腫瘍学会雑誌 36 ( 4 ) 692 - 701 2018.10

Language：Japanese Publisher：(公社)日本婦人科腫瘍学会

婦人科癌は治療法の進歩によりがんサバイバーが増え、がんサバイバーにとって、再発や死亡を防ぐことが重要である。がん治療終了後生活は生活習慣(食事、喫煙、飲酒)、運動などに注意することが大切とされているが、未だ婦人科領域におけるがん治療終了後生活の現状は把握されていない。そこでがん治療を行った229名の婦人科癌患者を対象に16項目のアンケートを用い、がん治療後の生活実態を調査した。定期的な外来検診を行った健康的な婦人科癌患者に直接アンケートを配布し、ボックスにて回収を行った(99.9%回収)。その結果、がん治療後食事量が減少した患者は24.0%、脂肪摂取が減った患者は34.9%、塩分量が減少した患者は24.9%、緑黄色野菜が増えた患者は47.2%であり、禁煙や喫煙減少した患者は59.2%、禁酒や飲酒量減少した患者は46.8%を占めており、がん治療終了後健康的な生活を送ることに多くのがんサバイバーが心掛けていることを認識できた。(著者抄録)

The Influence of Chemotherapy-Induced Peripheral Neuropathy on Quality of Life of Gynecologic Cancer Survivors. International journal

Hirofumi Matsuoka, Keiichiro Nakamura, Yuko Matsubara, Naoyuki Ida, Masayuki Saijo, Chikako Ogawa, Hisashi Masuyama

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 28 ( 7 ) 1394 - 1402 2018.9

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

OBJECTIVE: The aim of this observational study was to investigate correlations between long-term chemotherapy-induced peripheral neurotoxicity (CIPN) and quality of life (physical well-being, social well-being, emotional well-being, and functional well-being [FWB]) among survivors of gynecologic cancer (GC). METHODS: We aimed to assess the correlation of quality of life and long-term CIPN with the temporal change in recurrence-free GC survival. Questionnaire responses and clinical data of 259 GC survivors were collected and assessed according to treatment received. The χ test was used to determine the significance of correlations. RESULTS: Of 165 evaluable patients treated by chemotherapy, 36 patients (21.8%) developed CIPN of Common Toxicity Criteria for Adverse Events grade 1 or higher during the study. Chemotherapy-induced peripheral neurotoxicity had significantly improved over time in the domain of FWB at 61 months or more after the end of chemotherapy (posttreatment 4) among GC survivors (P = 0.003). Furthermore, CIPN treated by more than 6 courses of the paclitaxel and carboplatin regimen among GC survivors showed significant improvement over time in the emotional well-being domain at 25 to 60 months and 61 months or more after the end of chemotherapy (posttreatments 3 and 4) (P = 0.037 and P = 0.023) and in FWB at posttreatment 4 (P < 0.001). CONCLUSIONS: Emotional and functional domains of CIPN improved over time among GC survivors treated by more than 6 courses of the paclitaxel and carboplatin regimen. Based on these results, further research is required to identify additional preventative or curative approaches.

DOI： 10.1097/IGC.0000000000001320

Lynch症候群子宮体癌におけるMMR statusとLynch症候群関連腫瘍家族歴との相関

原賀順子, 永坂岳司, 春間朋子, 西田傑, 入谷大洋, 母里淑子, 小川千加子, 中村圭一郎, 藤原俊義, 増山寿

日本外科系連合学会誌 43 ( 3 ) 401 - 401 2018.5

Clinical outcomes of women with ovarian metastases of colorectal cancer treated with oophorectomy with respect to their somatic mutation profiles. International journal

Yoshiko Mori, Akihiro Nyuya, Kazuya Yasui, Toshiaki Toshima, Takashi Kawai, Fumitaka Taniguchi, Keisuke Kimura, Ryo Inada, Masahiko Nishizaki, Junko Haraga, Keiichiro Nakamura, Yuzo Umeda, Hiroyuki Kishimoto, Toshiyoshi Fujiwara, Yosuke Katata, Yoshiyuki Yamaguchi, Takeshi Nagasaka

Oncotarget 9 ( 23 ) 16477 - 16488 2018.3

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

We clarified the clinical prevalence of ovarian metastases from colorectal cancers (CRCs) in 296 female patients with CRC and evaluated clinical outcomes with relation to their mutational profiles, such as BRAF/KRAS mutation and microsatellite instability (MSI) status. The female CRCs were categorised into three subsets: CRCs with ovarian metastases [6.4% (n = 19), 5-year overall survival (OS) = 24.7%], CRCs with extra-ovarian metastases only [32.4% (n = 96), 5-year OS = 34.5%] and CRCs without any recurrence or metastasis [61.2% (n = 181), 5-year OS = 91.3%]. All patients with ovarian metastases underwent oophorectomy; of these, 9 who received preoperative chemotherapy had measurable metastases to extra-ovarian sites and the ovaries. Although 5 of 9 (56%) achieved partial response or complete response at extra-ovarian sites, no patient archived objective response at ovarian sites. Regarding the mutation profiles, in CRCs with extra-ovarian metastases only, the median survival time (MST) after initial treatments to progression to stage IV or recurrence was 13 [95% confidence interval (CI): 7-16 months] in BRAF-mutant and 34 months (95% CI: 22-58 months) in BRAF wild-type (P = 0.0033). Although ovarian metastases demonstrated poor response to systemic chemotherapy in CRCs with ovarian metastases, the MST after initial treatments to progression to stage IV or recurrence was 22 (95% CI: 21-25 months) in BRAF-mutant and 38 months (95% CI: 24-42 months) in BRAF wild-type (P = 0.0398). The outcomes of patients with ovarian metastases could be improved by oophorectomy regardless of their mutation profiles.

DOI： 10.18632/oncotarget.24735

Prognostic nutritional index as a predictor of survival in patients with recurrent cervical cancer. International journal

Naoyuki Ida, Keiichiro Nakamura, Masayuki Saijo, Tomoyuki Kusumoto, Hisashi Masuyama

Molecular and clinical oncology 8 ( 2 ) 257 - 263 2018.2

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

Systemic inflammatory responses (SIRs) can help predict survival in various cancers. The present study investigated the accuracy of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI) in predicting survival for patients with recurrent cervical cancer. A retrospective review of prognoses examined the associations among NLR, PLR, and PNI, and clinical characteristics and survival in 79 patients with recurrent cervical cancer after undergoing concurrent chemoradiation therapy (CCRT) or radical hysterectomies with or without CCRT. The Mann-Whitney U-test was used for statistical analyses. In addition, 12-month, 24-month and overall survival were analyzed by the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses. Median survival was 15.0 months over follow-up periods of 2-93 months. At the last follow-up point, 54 had succumbed to disease and 25 were alive with disease. In univariate analysis, NLR, PLR and PNI were significantly associated with 12-month, 24 month and overall survival (12 months: P=0.021, P=0.001 and P<0.001; 24 months: P=0.020, P=0.008 and P<0.001; overall; P=0.032, P=0.032 and P<0.001, respectively). In multivariate analyses, PNI was an independent prognostic factor for 12-month, 24-month and overall survival (P=0.001, P=0.001 and P<0.001, respectively). PNI is a useful predictor of survival of recurrent cervical cancer.

DOI： 10.3892/mco.2017.1508

再発リスクを有する子宮体癌において,POLE変異/MSIは予後良好因子である

原賀順子, 永坂岳司, 春間朋子, 西田傑, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 70 ( 2 ) 646 - 646 2018.2

婦人科悪性腫瘍手術後患者における大建中湯の有用性

藤田志保, 関典子, 西條昌之, 依田尚之, 大道千晶, 原賀順子, 西田傑, 小川千加子, 楠本知行, 鎌田泰彦, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 70 ( 2 ) 968 - 968 2018.2

当院での悪性腫瘍手術における希釈式自己血輸血の現状

大平安希子, 原賀順子, 関典子, 依田尚之, 西條昌之, 大道千晶, 西田傑, 小川千加子, 楠本知行, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 70 ( 2 ) 776 - 776 2018.2

サルコペニアは同時化学放射線療法を施行した子宮頸癌患者の予後不良因子になる

清時毅典, 中村圭一郎, 依田尚之, 西條昌之, 大道千晶, 原賀順子, 西田傑, 小川千加子, 楠本知行, 増山寿

日本産科婦人科学会雑誌 70 ( 2 ) 948 - 948 2018.2

子宮体癌における遺伝子変異やメチル化変異の検討

西田傑, 中村圭一郎, 原賀順子, 西條昌之, 依田尚之, 小川千加子, 楠本知行, 増山寿

日本産科婦人科学会雑誌 70 ( 2 ) 655 - 655 2018.2

初期子宮体癌低侵襲手術における術式に関する検討

楠本知行, 依田尚之, 西條昌之, 西田傑, 原賀順子, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 70 ( 2 ) 764 - 764 2018.2

Sarcopenia Is an Important Prognostic Factor in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy. International journal

Takanori Kiyotoki, Keiichiro Nakamura, Junko Haraga, Chiaki Omichi, Naoyuki Ida, Masayuki Saijo, Takeshi Nishida, Tomoyuki Kusumoto, Hisashi Masuyama

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 28 ( 1 ) 168 - 175 2018.1

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

OBJECTIVE: This study aimed to investigate the correlation of sarcopenia findings with prognostic factors in patients with cervical cancer (CC) undergoing concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively collected data on body composition and clinicopathological features from the medical records of 60 patients with CC who underwent CCRT and analyzed correlations between prognosis and changes in body composition as measured by computed tomography (skeletal muscle and iliopsoas muscle [IM]). Statistical analyses were performed using the Mann-Whitney U test. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox proportional hazard regression was used for univariate and multivariate analyses. RESULTS: The median follow-up for all patients who were alive at the last follow-up was 33.5 months (range, 1-104 months). The PFS and OS rates were worse for patients with at least 15.0% than for those with less than 15.0% loss of skeletal muscle and IM from baseline (P < 0.001 for both). Furthermore, multivariate analyses showed that at least 15.0% loss of IM was an independent prognostic factor for PFS and OS (P = 0.002 for both). CONCLUSIONS: Sarcopenia (≥15.0% loss of IM from baseline) was revealed to be an important prognostic factor in patients with CC undergoing CCRT.

DOI： 10.1097/IGC.0000000000001127

Accuracy of four mononucleotide-repeat markers for the identification of DNA mismatch-repair deficiency in solid tumors

Yuko Takehara, Takeshi Nagasaka, Akihiro Nyuya, Tomoko Haruma, Junko Haraga, Yoshiko Mori, Keiichiro Nakamura, Toshiyoshi Fujiwara, C. Richard Boland, Ajay Goel

JOURNAL OF TRANSLATIONAL MEDICINE 16 2018.1

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

Background: To screen tumors with microsatellite instability (MSI) arising due to DNA mismatch repair deficiency (dMMR), a panel of five quasi-monomorphic mononucleotide-repeat markers amplified in a multiplex PCR (Pentaplex) are commonly used. In spite of its several strengths, the pentaplex assay is not robust at detecting the loss of MSH6-deficiency (dMSH6). In order to overcome this challenge, we designed this study to develop and optimize a panel of four quasi-monomorphic mononucleotide-repeat markers (Tetraplex) for identifying solid tumors with dMMR, especially dMSH6.Methods: To improve the sensitivity for tumors with dMMR, we established a quasi-monomorphic variant range (QMVR) of 3-4 bp for the four Tetraplex markers. Thereafter, to confirm the accuracy of this assay, we examined 317 colorectal cancer (CRC) specimens, comprising of 105 dMMR [45 MutL homolog (MLH) 1-deficient, 45 MutS protein homolog (MSH)2-deficient, and 15 MSH6-deficient tumors] and 212 MMR-proficient (pMMR) tumors as a test set. In addition, we analyzed a cohort of 138 endometrial cancers (EC) by immunohistochemistry to determine MMR protein expression and validation of our new MSI assay.Results: Using the criteria of >= 1 unstable markers as MSI-positive tumor, our assay resulted in a sensitivity of 97.1% [95% confidence interval (Cl) = 91.9-99.0%] for dMMR, and a specificity of 95.3% (95% Cl = 91.5-97.4%) for pMMR CRC specimens. Among the 138 EC specimens, 41 were dMMR according to immunohistochemistry. Herein, our Tetraplex assay detected dMMR tumors with a sensitivity of 92.7% (95% Cl = 80.6-97.5%) and a specificity of 97.9% (95% Cl = 92.8-99.4%) for pMMR tumors. With respect to tumors with dMSH6, in the CRC-validation set, Tetraplex detected | dMSH6 tumors with a sensitivity of 86.7% (13 of 15 dMSH6 CRCs), which was subsequently validated in the EC test set I as well (sensitivity, 75.0%; 6 of 8 dMSH6 ECs).Conclusions: Our newly optimized Tetraplex system will help offer a robust and highly sensitive assay for the identification of dMMR in solid tumors.

DOI： 10.1186/s12967-017-1376-4

Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability. International journal

Tomoko Haruma, Takeshi Nagasaka, Keiichiro Nakamura, Junko Haraga, Akihiro Nyuya, Takeshi Nishida, Ajay Goel, Hisashi Masuyama, Yuji Hiramatsu

PloS one 13 ( 4 ) e0195655 2018

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

BACKGROUND: The molecular characterization of endometrial cancer (EC) can facilitate identification of various tumor subtypes. Although EC patients with POLE mutations reproducibly demonstrate better prognosis, the outcome of patients with microsatellite instability (MSI) remains controversial. This study attempted to interrogate whether genetic stratification of EC can identify distinct subsets with prognostic significance. MATERIALS AND METHODS: A cohort of 138 EC patients who underwent surgical resection with curative intent was enrolled. Sanger sequencing was used to evaluate mutations in the POLE and KRAS genes. MSI analysis was performed using four mononucleotide repeat markers and methylation status of the MLH1 promoter was measured by a fluorescent bisulfite polymerase chain reaction (PCR). Protein expression for mismatch repair (MMR) proteins was evaluated by immunohistochemistry (IHC). RESULTS: Extensive hypermethylation of the MLH1 promoter was observed in 69.6% ECs with MLH1 deficiency and 3.5% with MMR proficiency, but in none of the ECs with loss of other MMR genes (P < .0001). MSI-positive and POLE mutations were found in 29.0% and 8.7% EC patients, respectively. Our MSI analysis showed a sensitivity of 92.7% for EC patients with MMR deficiency, and a specificity of 97.9% for EC patients with MMR proficiency. In univariate and multivariate analyses, POLE mutations and MSI status was significantly associated with progression-free survival (P = 0.0129 and 0.0064, respectively) but not with endometrial cancer-specific survival. CONCLUSIONS: This study provides significant evidence that analyses of proofreading POLE mutations and MSI status based on mononucleotide repeat markers are potentially useful biomarkers to identify EC patients with better prognosis.

DOI： 10.1371/journal.pone.0195655

骨盤腎と全身性強皮症を合併し治療方針の決定に難渋した子宮頸癌の1例

秋定幸, 春間朋子, 原賀順子, 依田尚之, 楠本知行, 中村圭一郎, 関典子, 増山寿, 平松祐司

現代産婦人科 66 ( 1 ) 109 - 115 2017.12

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

今回比較的稀な先天奇形である骨盤腎と、全身性強皮症を合併した子宮頸癌IIB期の1例を経験した。症例は65歳3経妊3経産。前医での子宮頸部組織診で扁平上皮癌の診断で、精査加療目的に当科紹介となった。当科受診時の内診で子宮頸部に浸潤癌様腫瘤と軽度の子宮傍組織浸潤を認めた。MRI検査では子宮頸部に長径5.2cmの不整形腫瘤と両側閉鎖リンパ節の腫大を指摘され、PET/CT検査で同部位へのFDGの高集積を認めた。子宮頸癌IIB期(T2bN1M0)と診断した。同時化学放射線治療(CCRT)を行った場合、放射線照射領域内に左骨盤腎が入り、左腎臓は無機能腎となることが予想され、さらに化学療法で白金製剤を使用することから腎機能の悪化が懸念された。しかし病期、肥満を考慮し、本人と相談の上、腎機能の推移を慎重にモニタリングしながらCCRTを行う方針とした。しかしCCRT治療開始後(全骨盤18Gy照射、weekly Cisplatin 40mg/m21コース)、皮膚への色素沈着と手指硬化を認め全身性強皮症と診断された。全身性強皮症患者に対する放射線治療はGrade 3以上の晩期障害がコントロール群と比較し約2.5倍になったとの報告もあり、放射線科治療医と相談しCCRTの継続は困難と判断した。手術療法を行う方針とし、単純子宮全摘、両側付属器切除術、骨盤リンパ節郭清を施行した。術後病理検査では腫瘍の縮小を認めており、左閉鎖リンパ節に腫瘍の瘢痕があるものの、その他明らかなリンパ節転移は認めなかった。術後は化学療法を施行し治療後3ヵ月現在再発兆候なく経過観察中である。(著者抄録)

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The Influence of Adverse Effects on Quality of Life of Survivors of Gynecologic Cancer

Chiaki Omichi, Keiichiro Nakamura, Junko Haraga, Naoyuki Ida, Masayuki Saijo, Takeshi Nishida, Tomoyuki Kusumoto, Hisashi Masuyama

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 27 ( 9 ) 2014 - 2019 2017.11

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

Objective: The objective of this observational study was to investigate correlations between adverse effects (lower-extremity lymphedema [LEL], dysuria, and severe gastrointestinal symptoms) and quality of life (QOL) (physicalwell-being [PWB], socialwell-being, emotional well-being [EWB], and functionalwell-being) before treatment, at least 6 weeks after treatment (posttreatment1), and 3 or 6 months after treatment (posttreatment2) of patientswith gynecologic cancer (GC).Methods: From August 2012 to October 2016, questionnaire responses and clinical data of 75 patients with GC were collected and assessed by treatment received. The chi(2) test was used to determine the significance of correlations.Results: Participants with LEL had significantly poorer QOL than did those without it in the domains of PWB at posttreatment1 (P = 0.026) and EWB at posttreatment2 (P = 0.020). Moreover, patients with 2 adverse effects (LEL plus dysuria or severe gastrointestinal symptoms) had significantly poorer QOL than did those with no or single adverse effect in the domains of PWB at posttreatment1 and posttreatment2 (posttreatment1: P = 0.049, P = 0.001; posttreatment2: P = 0.002, P = 0.028) and poorer QOL compared with those with no adverse effect in the domain of EWB at posttreatment1 (P = 0.017).Conclusions: Poorer QOL in emotional and physical domains is associated with adverse effects of treatment in patients with GC. It is important to consider the effects of radical therapy not only on survival but also on the QOL of survivors.

DOI： 10.1097/IGC.0000000000001125

Reply to "Letter to the Editor" by M. Saijo et al. "Glasgow prognostic score is predictive of prognosis for patients with endometrial cancer ". International journal

Masayuki Saijo, Keiichiro Nakamura, Hisashi Masuyama, Naoyuki Ida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

European journal of obstetrics, gynecology, and reproductive biology 216 260 - 260 2017.9

当院での悪性腫瘍手術における希釈式自己血輸血の現状

大平安希子, 原賀順子, 関典子, 依田尚之, 西條昌之, 大道千晶, 西田傑, 小川千加子, 楠本知行, 中村圭一郎, 増山寿

現代産婦人科 66 ( Suppl. ) S62 - S62 2017.9

腹腔鏡下子宮筋腫核出術後に生じた巨大parasitic myomaの一例

原賀順子, 玉田祥子, 田中梓菜, 楠本知行, 中村圭一郎, 増山寿, 平松祐司

日本産科婦人科内視鏡学会雑誌 33 ( Suppl.I ) 1164 - 1164 2017.8

腹腔鏡下子宮体がん手術単一施設同一術者での経験から

楠本知行, 依田尚之, 西條昌之, 原賀順子, 大道千晶, 西田傑, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科内視鏡学会雑誌 33 ( Suppl.I ) 352 - 352 2017.8

Gene expression profiles in BRAF V600E mutant colorectal cancer and association with SFRP2 methylation status

Kazuya Yasui, Takeshi Nagasaka, Toshiaki Toshima, Takashi Kawai, Kunitoshi Shigeyasu, Yoshiko Mori, Junko Haraga, Keiichiro Nakamura, Yuzo Umeda, Hiroshi Tazawa, Ajay Goel, Toshiyoshi Fujiwara

CANCER RESEARCH 77 2017.7

巨大parasitic myomaの一例

玉田祥子, 田中梓菜, 早田桂, 楠本知行, 鎌田泰彦, 中村圭一郎, 関典子, 増山寿, 平松祐司

産婦人科手術 ( 28 ) 157 - 157 2017.6

子宮内膜癌再発に対する妊孕性温存治療後、生殖補助医療で妊娠し生児を得た一例

矢野肇子, 酒本あい, 安藤まり, 樫野千明, 松岡敬典, 長谷川徹, 早田桂, 小谷早葉子, 楠本知行, 鎌田泰彦, 中村圭一郎, 関典子, 増山寿, 中塚幹也, 平松祐司

現代産婦人科 65 ( 2 ) 217 - 221 2017.5

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

近年40歳以下の若年子宮内膜癌患者は増加しており、その妊孕性温存が注目されている。我々は子宮内膜癌IA期発症後にmedroxyprogesterone acetate(MPA)による高用量黄体ホルモン療法後の再発に対し再度MPA療法を行い、生殖補助医療により生児を得た症例を経験したので報告する。症例は32歳女性既婚、未経妊。不正性器出血を主訴に前医を受診した。子宮内膜組織診でendometrioid adenocarcinoma、Grade 1と診断され、当科紹介となった。当院での精査で、子宮内膜癌IA期相当と診断、妊孕性温存希望のため、MPA療法を6ヵ月間行った。子宮内膜組織診で悪性所見の消失を確認後、妊娠を試みるも妊娠成立せず、初回治療から3年2ヵ月後に組織診断でendometrioid adenocarcinomaの再発が指摘された。依然挙児希望は強く、リスクを十分に説明した上で再度MPA療法を6ヵ月間行った。子宮内膜組織診で悪性所見の消失を確認し、不妊治療を再開した。生殖補助医療を選択し、GnRHアンタゴニスト法で14個の卵子を採取し体外受精した。受精後6日目に胚盤胞まで達した3AA胚1個を凍結した。子宮内膜組織診で陰性を確認後、ホルモン補充周期で凍結融解胚移植を行い、妊娠成立した。妊娠経過は順調で、妊娠40週4日に胎児機能不全の適応で帝王切開術を施行した。MPA療法は治療後1〜3年以内に再発する症例が多く、寛解後早期の不妊治療開始が推奨され、体外受精により妊娠する症例が多い。本症例のように子宮内膜癌再発後にMPA療法と生殖補助医療を行い、生児を得た症例の報告は散見されるが、本邦のガイドラインでは推奨されていないため、十分な説明と同意のもとに慎重に行われるべきである。(著者抄録)

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Glasgow prognostic score is a prognosis predictor for patients with endometrial cancer

Masayuki Saijo, Keiichiro Nakamura, Hisashi Masuyama, Naoyuki Ida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY 210 355 - 359 2017.3

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objective: This study investigated whether the inflammation-based Glasgow prognostic score (GPS) predicted the prognosis of patients with endometrial cancer (EC) in terms of progression-free survival (PFS) and overall survival (OS).Study design: Pretreatment GPS was examined to determine the correlations with recurrence and survival in 431 patients with EC. Statistical analyses were performed using the Mann-Whitney U test. PFS and OS were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses.Results: Median PFS and OS were 49.7 and 52.7 months, respectively. The follow-up range was I to 140 months. Kaplan-Meier analysis revealed that patients with EC cancer and high GPS (GPS 2) had a shorter PFS and OS than those with lower GPS (GPS 0 + 1) (PFS: P < 0.001; OS; P < 0.001). On multivariate analysis, GPS (GPS 2) was an independent predictor of both recurrence (P < 0.001) and survival (P < 0.001) for all cases of EC.Conclusion: GPS can be useful as an indicator of poor prognosis in patients with EC. (C) 2017 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ejogrb.2017.01.024

Radical Hysterectomy Plus Concurrent Chemoradiation/Radiation Therapy Is Negatively Associated With Return to Work in Patients With Cervical Cancer

Keiichiro Nakamura, Hisashi Masuyama, Naoyuki Ida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 27 ( 1 ) 117 - 122 2017.1

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

Objective: Cervical cancer is one of the most common malignant diseases in working-age women. This study investigated the influence of adverse effects of various treatment modalities on return to work in women with cervical cancer.Methods: Questionnaires and clinical data from medical records of 97 patients with early stage (stages I and II) cervical cancer were collected and assessed by treatment received. The following treatment groups were analyzed for correlations between time to return to work and various adverse effects: radical hysterectomy (RH) alone, RH group (n = 29); concurrent chemoradiation therapy (CCRT)/radiation therapy (RT) alone, CCRT/RT group (n = 21); and RH + CCRT/RT group (n = 47). The chi(2) test was used to determine the significance of the correlations.Results: The mean age at the time of diagnosis was 43.0 years and the average interval since treatment was 4.5 years. The RH + CCRT/RT group was the most strongly negatively associated with return towork in employed patients who had undergone CCRT/RT group of cervical cancer (P = 0.012). There was a significant association between failure to return to work and lower extremity lymphedema (P = 0.049). A more than-6-month interval between treatment and return towork and reduced personal income occurred in a significantly higher percentage of patients in the RH + CCRT group than in the CCRT/RT group (P = 0.034 and P = 0.034).Conclusions: Of the treatments assessed, RH + CCRT/RT has the greatest negative effect on return to work in women with cervical cancer.

DOI： 10.1097/IGC.0000000000000840

Pretreatment prognostic nutritional index is a significant predictor of prognosis in patients with cervical cancer treated with concurrent chemoradiotherapy. International journal

Junko Haraga, Keiichiro Nakamura, Chiaki Omichi, Takeshi Nishida, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Hisashi Masuyama, Norihisa Katayama, Susumu Kanazawa, Yuji Hiramatsu

Molecular and clinical oncology 5 ( 5 ) 567 - 574 2016.11

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

This study investigated whether pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index (PNI) are prognostic factors in patients with cervical cancer who undergo concurrent chemoradiotherapy (CCRT) and radiotherapy (RT). A total of 131 patients who underwent CCRT and RT for cervical cancer were retrospectively investigated and the correlations of NLR, PLR and PNI with clinical parameters and prognosis were assessed in CCRT and RT. The CCRT and RT groups had a median progression-free survival (PFS) of 41.82 and 24.72 months, respectively, and an overall survival of 49.70 and 29.56 months, respectively. At a cut-off value of NLR≥2.85, the PFS and OS in patients with higher NLR undergoing RT were significantly shorter compared with those in patients with lower NLR (P=0.029 and P=0.017, respectively). At a cut-off value for PNI of ≤48.55 in patients undergoing CCRT and ≤45.80 in patients undergoing RT, the PFS and OS in patients with lower PNI were significantly shorter compared with those in patients with higher PNI (PFS and OS with CCRT, P<0.001 and P<0.001, respectively; PFS and OS with RT, P=0.002 and P=0.008, respectively). Multivariate analyses also identified low PNI as an independent prognostic factor for PFS and OS in patients receiving CCRT. Therefore, low PNI was shown to predict poor prognosis in patients with cervical cancer.

Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells

Hisashi Masuyama, Keiichiro Nakamura, Etsuko Nobumoto, Yuji Hiramatsu

INTERNATIONAL JOURNAL OF ONCOLOGY 49 ( 3 ) 1211 - 1220 2016.9

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Epithelial ovarian cancer remains the most devastating gynecologic cancer with drug resistance and rapid recurrence. Pregnane X receptor (PXR) is a nuclear receptor that affects drug metabolism/efflux and drug-drug interaction through control of multiple drug resistance 1 (MDR1), which implies a major role in multidrug resistance, and other genes. We examined whether the inhibition of PXR-mediated pathway using siRNA interference and an antagonist for PXR could influence the paclitaxel and cisplatin cytotoxicity in ovarian cancer cells. PXR agonists, phthalate and pregnenolone had significant positive effects on cytochrome P450 (CYP) 3A4 expression and PXR-mediated transcription through the CYP3A4 promoter, whereas MDR1 expression and PXR-mediated transcription though the MDR1 promoter were significantly increased in the presence of paclitaxel or cisplatin. Downregulation of PXR suppressed the augmented MDR1 expression and PXR-mediated transcription by PXR ligands, and significantly enhanced cell growth inhibition and apoptosis in the presence of paclitaxel or cisplatin. Additionally, ketoconazole, a PXR antagonist, suppressed the augmented MDR1 expression and PXR-mediated transactivation by paclitaxel and cisplatin, and enhanced cell growth inhibition and apoptosis in their presence. In conclusion, inhibition of PXR-mediated pathways could be a novel means of augmenting sensitivity, or overcoming resistance to anticancer agents for ovarian cancer.

DOI： 10.3892/ijo.2016.3611

Dimethylesculetin ameliorates maternal glucose intolerance and fetal overgrowth in high-fat diet-fed pregnant mice via constitutive androstane receptor

Hisashi Masuyama, Takashi Mitsui, Jota Maki, Kazumasa Tani, Keiichiro Nakamura, Yuji Hiramatsu

MOLECULAR AND CELLULAR BIOCHEMISTRY 419 ( 1-2 ) 185 - 192 2016.8

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

The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance along with obesity. 6,7-dimethylesculetin (DE) is an active component of Yin Zhi Huang which is a traditional Asian medicine used to treat neonatal jaundice via CAR. In this study, we examined whether DE could affect the expression of gluconeogenic and lipogenic genes via human CAR pathway using human HepG2 cells in vitro. We also studied whether DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in high-fat diet (HFD)-induced obese pregnant mice. Dimethylesculetin suppressed the mRNA expression of gluconeogenic genes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, and lipogenic genes, sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1, and enhanced CAR-mediated transcription. Blocking the CAR-mediated pathway abolished the effect of DE in vitro. DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in HFD-induced obese pregnant mice in vivo. Our data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin resistance through CAR to prevent the perinatal outcomes such as preeclampsia, gestational diabetes, and macrosomia. Further analysis of possible complications and side effects using animal models is required.

DOI： 10.1007/s11010-016-2772-4

Return to work after cancer treatment of gynecologic cancer in Japan. International journal

Keiichiro Nakamura, Hisashi Masuyama, Takeshi Nishida, Junko Haraga, Naoyuki Ida, Masayuki Saijo, Tomoko Haruma, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

BMC cancer 16 558 - 558 2016.7

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

BACKGROUND: Gynecologic cancer is one of the most common malignant diseases in working-age women. This study investigated whether several characteristics influence return to work after treatment of gynecologic cancer. METHODS: We investigated the correlations between return to work and several other characteristics in 199 gynecologic cancer survivors. Questionnaires were distributed to patients with cancer (≥1 year after treatment and age of <65 years) who visited Okayama University. Logistic regression analysis and receiver operating characteristic curves were used to determine whether each characteristic influenced return to work (no return to work or job change) in these gynecologic cancer survivors. RESULTS: For all patients, the mean age at the time of diagnosis was 47.0 years, and the average number of years after treatment was 4.5. Forty-four patients (53.7 %) who were non-regular employees continued to be employed at the same workplace. Non-regular employment had a significantly higher area under the curve (AUC) (0.726) than other characteristics in terms of negatively affecting return to work. Additionally, non-regular employment tended to have a higher AUC (0.618) than other characteristics in terms of job changes. CONCLUSIONS: Non-regular employment was the variable most likely to negatively affect return to work and job changes in employed patients who underwent treatment for gynecologic cancer.

DOI： 10.1186/s12885-016-2627-0

Glasgow prognostic score is an independent marker for poor prognosis with all cases of epithelial ovarian cancer

Chiaki Omichi, Keiichiro Nakamura, Junko Haraga, Hisashi Masuyama, Yuji Hiramatsu

CANCER MEDICINE 5 ( 6 ) 1074 - 1080 2016.6

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

Inflammatory markers are important prognostic factors in various cancers. This study investigated whether inflammatory markers of the Glasgow prognostic score (GPS) predicted progression-free survival (PFS) and overall survival (OS) for patients with all cases of epithelial ovarian cancer (OC). Pretreatment GPS was examined for the correlations with PFS and OS in 216 patients in all stages of epithelial OC. Statistical analyses were performed using the Mann-Whitney U-test. PFS and OS were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses. For all patients, the median PFS was 35.1 months, and median OS was 46.7 months; follow-up range was 1-162 months. Kaplan-Meier analysis revealed that patients with high GPS (GPS 2) at pretreatment had a shorter PFS and OS than did patients with lower GPS (GPS 0 + 1) in for early, advanced, and all-stages of OC (PFS: P < 0.001 for early-, advanced- and all-stages; OS; P < 0.001 for early- and all-stage, P = 0.015 for advanced-stage). GPS (GPS 2) was also found to be an independent predictor of both recurrence (P = 0.002) and survival (P = 0.001) of all cases of epithelial OC by a multivariate analysis. GPS can serve as an indicator of poor prognosis in patients with all stages of epithelial OC, including early-stage disease and regardless of histology.

DOI： 10.1002/cam4.681

Neutrophil to lymphocyte ratio in the pre-treatment phase of final-line chemotherapy predicts the outcome of patients with recurrent ovarian cancer. International journal

Keiichiro Nakamura, Takeshi Nagasaka, Takeshi Nishida, Tomoko Haruma, Chikako Ogawa, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

Oncology letters 11 ( 6 ) 3975 - 3981 2016.6

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

Inflammation and tumor immunology are associated with prognosis in a variety of cancers. The aim of the present retrospective study was to identify associations between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), cancer antigen 125 (CA125) concentrations, tumor response, performance status (PS) and survival of patients that developed recurrent ovarian cancer subsequent to receiving chemotherapy. The NLR and PLR measured prior to fourth-line chemotherapy were significantly increased compared with those measured prior to second-line chemotherapy (P=0.029 and 0.049, respectively). By using receiver operating characteristic curves, the cut-off values were determined for the NLR, PLR and CA125 levels that were measured during the pre-treatment phase, which predicted the outcomes. According to univariate analyses, pre-treatment NLR >3.91, PLR >299.0 and PS 2 were each significantly associated with poor outcomes (P=0.001, 0.005 and 0.021, respectively). According to multivariate analyses, only pre-treatment NLR was associated with poor outcome (P=0.035). The present findings indicate that pre-treatment NLR is an important predictor of prognosis in patients with ovarian cancer that experience recurrence following chemotherapy.

Three histologically distinct cancers of the uterine corpus: A case report and review of the literature. International journal

Hisashi Masuyama, Junko Haraga, Takashi Nishida, Chikako Ogawa, Tomoyuki Kusumoto, Keiichiro Nakamura, Noriko Seki, Hiroyuki Yanai, Yuji Hiramatsu

Molecular and clinical oncology 4 ( 4 ) 563 - 566 2016.4

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

Collision tumors, which are characterized by the coexistence of two or more completely distinct and independent tumors in the uterine corpus, are very rare. A collision tumor is mainly composed of two distinct tumor types, epithelial and mesenchymal. To the best of our knowledge, there has only been a single case in which a choriocarcinoma with an endometrial carcinoma were coexistent but histologically distinct. We herein report the first case of a collision tumor in a 52-year-old woman, with a history of two pregnancies and two deliveries. The collision tumor was composed of three histologically distinct neoplasms in the uterine corpus, namely an endometrioid carcinoma, an undifferentiated carcinoma and a choriocarcinoma. The patient underwent hysterectomy, bilateral adnexectomy and pelvic lymph node dissection, followed by six cycles of adjuvant chemotherapy with paclitaxel/carboplatin due to the high risk of endometrial cancer, and an additional five cycles of chemotherapy with methotrexate, as the β-human chorionic gonadotropin level was beyond the normal range. Following adjuvant chemotherapy, the tumor markers were within normal limits and no relapses of the cancer have been observed during 1 year of follow-up. Diagnosing a collision tumor prior to surgery is difficult if the neoplasms are in close proximity, or if one of the tumors predominates. Careful pathological examination is crucial for accurately diagnosing the neoplasms in a collision tumor and ensuring appropriate management and a favorable prognosis.

Pregnancy complications and glucose intolerance in women with polycystic ovary syndrome

Mari Sawada, Hisashi Masuyama, Kei Hayata, Yasuhiko Kamada, Keiichiro Nakamura, Yuji Hiramatsu

ENDOCRINE JOURNAL 62 ( 11 ) 1017 - 1023 2015.11

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN ENDOCRINE SOC

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by insulin resistance and hyperandrogenism. The interaction of these factors might result in increased risks of miscarriage and pregnancy complications such as gestational diabetes mellitus (GDM). To examine the pregnancy risks in women with PCOS, we compared obstetrical outcomes between patients with and without PCOS. We also studied the differences in maternal characteristics, glucose intolerance and pregnancy complications between PCOS patients with and without GDM, with and without obesity, and between successful pregnancies and miscarriages. We observed a high incidence of GDM and prevalence of GDM diagnosis in the first trimester in PCOS. Patients with GDM had higher body mass index (BMI) and lower homeostasis model assessment of beta-cell function (HOMA-beta) at preconception than those without GDM. Obese pregnant women with PCOS demonstrated a high incidence of GDM with severe insulin resistance, including high fasting insulin, HOMA of insulin resistance (HOMA-IR), and HOMA-beta at preconception compared with normal-weight patients. BMI was significantly correlated with HOMA-IR or HOMA-beta, and both indices were lower in PCOS patients with than without GDM for the same BMI. There were no significant differences in maternal characteristics (excluding maternal age) between PCOS patients with successful pregnancy and PCOS patients with miscarriages. Our data suggest that pregnant women with PCOS have an increased risk of GDM, especially if they have obesity and/or poorer insulin secretion. Measure of beta-cell function, such as HOMA-beta, at preconception might be a useful predictor of the risk of GDM in pregnant PCOS patients.

DOI： 10.1507/endocrj.EJ15-0364

The Glasgow Prognostic Score Determined During Concurrent Chemoradiotherapy Is an Independent Predictor of Survival for Cervical Cancer

Takeshi Nishida, Keiichiro Nakamura, Junko Haraga, Chikako Ogawa, Tomoyuki Kusumoto, Noriko Seki, Hisashi Masuyama, Norihisa Katayama, Susumu Kanazawa, Yuji Hiramatsu

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 25 ( 7 ) 1306 - 1314 2015.9

Language：English Publishing type：Research paper (scientific journal) Publisher：BMJ PUBLISHING GROUP

Objective The Glasgow prognostic score (GPS) determined at pretreatment is important in the prediction of prognosis in various cancers. We investigated if the GPS used both at pretreatment and during concurrent chemoradiotherapy (CCRT) could predict the prognosis of patients with cervical cancer.Methods We collected GPS and clinicopathological data from the medical records of 91 patients who underwent CCRT for cervical cancer; their GPSs at pretreatment and during CCRT were retrospectively analyzed for correlations with recurrence and survival. Statistical analyses were performed using the Mann-Whitney U test. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses.Results The median follow-up for all patients who were alive at the time of last follow-up was 38.0 months (range, 1-108 months). The DFS and OS rates of patients with a high GPS during CCRT (GPS 1 + 2; 55 patients; 60.4%) were significantly shorter than those for patients with a low GPS (GPS 0; 36 patients; 39.6%) (DFS, P < 0.001; OS, P < 0.001). Furthermore, multivariate analyses showed that high GPS during CCRT was an independent prognostic factor of survival for OS (P = 0.008).Conclusions During CCRT, a high GPS was revealed to be an important predictor of survival for cervical cancer.

DOI： 10.1097/IGC.0000000000000485

Pretreatment platelet-lymphocyte ratio is an independent predictor of cervical cancer recurrence following concurrent chemoradiation therapy. International journal

Keiichiro Nakamura, Takeshi Nishida, Tomoko Haruma, Junko Haraga, Chiaki Omichi, Chikako Ogawa, Tomoyuki Kusumoto, Noriko Seki, Hisashi Masuyama, Yuji Hiramatsu

Molecular and clinical oncology 3 ( 5 ) 1001 - 1006 2015.9

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

The aim of the present study was to identify the correlations between inflammation markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and C-reactive protein (CRP) and the prognosis in patients with recurrent cervical cancer. The associations among NLR, PLR and CRP and clinical characteristics and prognosis were examined in 32 patients receiving chemotherapy with recurrent cervical cancer following concurrent chemoradiation therapy (CCRT). The patient median survival time was 198 days (range, 42-1,022 days). Pretreatment NLR and PLR were significantly correlated with the recurrence of cervical cancer following CCRT (R=-0.538, P=0.002; and R=-0.542, P=0.001, respectively). Pretreatment PLR >322.0 was significantly associated with a poor prognosis for recurrent cervical cancer following CCRT by univariate and multivariate analyses (P=0.015 and P=0.029). These findings indicate that pretreatment PLR is an important predictor of prognosis in patients with recurrent cervical cancer following CCRT.

子宮子宮体がんの病理と診断子宮体癌におけるMSIおよびMMR deficiencyの頻度・相関とその臨床像

春間朋子, 永坂岳司, 中村圭一郎, 原賀順子, 西田傑, 小川千加子, 楠本知行, 関典子, 平松祐司

日本癌治療学会誌 50 ( 3 ) 988 - 988 2015.9

妊娠17週にて子宮破裂を発症した既往帝王切開後妊娠の1例

光井崇, 西田傑, 中村圭一郎, 早田桂, 谷和祐, 河原義文, 衛藤英理子, 延本悦子, 瀬川友功, 増山寿, 平松祐司

日本産科婦人科学会雑誌 67 ( 2 ) 907 - 907 2015.2

Pre-treatment neutrophil to lymphocyte ratio is a predictor of prognosis in endometrial cancer

Tomoko Haruma, Keiichiro Nakamura, Takeshi Nishida, Chikako Ogawa, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

Anticancer Research 35 ( 1 ) 337 - 344 2015.1

Language：English Publishing type：Research paper (scientific journal) Publisher：International Institute of Anticancer Research

Background/Aim: Inflammation and tumor immunology are important in the prognosis of various cancers. We herein investigated whether pre-treatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and serum cancer antigen 125 (CA125) predict recurrence and survival in patients with endometrial cancer (EC).
Patients and Methods: We collected complete blood counts and clinicopathological data from medical records of 320 patients with EC
their pre-treatment NLR, PLR and CA125 were analyzed for correlations with recurrence and survival, retrospectively.
Results: Disease-free survival (DFS) and overall survival (OS) rates of patients with high NLR and CA125 were significantly shorter than those for patients with low NLR and CA125 (DFS: p=0.002 and p&lt
0.001
OS: p&lt
0.001 and p&lt
0.001, respectively). Furthermore, NLR was also an independent predictive factor for mortality in multivariate analysis (hazard ratio (HR)=3.318
95% confidence interval (CI)=1.154-9.538
p=0.026).
Conclusion: Pre-treatment NLR is a predictor of poor prognosis in EC.

Pure choriocarcinoma of the ovary in silver-russell syndrome

Tomoko Haruma, Chikako Ogawa, Takeshi Nishida, Tomoyuki Kusumoto, Keiichiro Nakamura, Noriko Seki, Takaaki Katayama, Yuji Hiramatsu

Acta Medica Okayama 69 ( 3 ) 183 - 188 2015

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

Pure ovarian choriocarcinoma is an extremely rare malignancy that can be gestational or non-gestational in origin. Silver-Russell syndrome (SRS) is a rare congenital developmental disorder characterized by pre- and postnatal growth failure, relative macrocephaly, a triangular face, hemihypotrophy, and fifth-finger clinodactyly. We report a rare case of pure ovarian choriocarcinoma occurring in a 19-year-old woman with SRS. Following surgery, multiple chemotherapy courses were effective and she was free of disease at the 10-month follow-up.

後腹膜desmoid型線維腫症の症例

西條昌之, 中村圭一郎, 安藤まり, 依田尚之, 岡本和浩, 樫野千明, 谷和祐, 松岡敬典, 春間朋子, 福島千加子, 楠本知行, 関典子, 平松祐司, 佃和憲

現代産婦人科 62 ( 2 ) 263 - 267 2014.4

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

Desmoid線維腫症は100万人あたり2.4〜4.3例の稀な疾患で、線維腫症の1つであるが、周囲に浸潤性増殖しやすく、根治術を行っても局所再発を繰り返す難治性疾患であることが知られている。症例は22歳、0経妊0経産。4月某日に下腹部痛、軽度の悪心・嘔吐を主訴に近医受診し、巨大骨盤内腫瘤を指摘、精査加療目的に当科を紹介された。MRIでは多房性で一部充実部分を伴った26×24cmの腫瘤を認め、悪性腫瘍も危惧されたため、5月某日に開腹術を施行した。子宮・卵巣は正常であり、腫瘍は後腹膜由来で、回盲部を含め、横行結腸や脾臓下極に浸潤しており、腫瘍摘出とともに横行結腸部分切除吻合、脾臓の部分切除を行った。摘出した腫瘍は2980gで、内容は血性混濁液が存在し、総重量は5kgに達した。病理組織検査にてDesmoid-type fibromatosisと診断され、術後経過は良好で手術後13日目に退院した。後腹膜desmoid線維腫症の1症例を経験したので、若干の文献的考察を加えて報告する。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J05038&link_issn=&doc_id=20140620430022&doc_link_id=%2Fcv0mtrob%2F2013%2F006202%2F022%2F0263-0267%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2013%2F006202%2F022%2F0263-0267%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Maximum standardized lymph node uptake value could be an important predictor of recurrence and survival in patients with cervical cancer. International journal

Keiichiro Nakamura, Ikuo Joja, Takeshi Nagasaka, Tomoko Haruma, Yuji Hiramatsu

European journal of obstetrics, gynecology, and reproductive biology 173 77 - 82 2014.2

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

OBJECTIVES: To investigate prognostic values of maximum standardized lymph node (LN) uptake (SUVmax), minimum apparent LN diffusion coefficient (ADCmin), and LN short-axis length in women with cervical cancer. STUDY DESIGN: Retrospective review of diffusion-weighted magnetic resonance imaging (DWI) and positron emission tomography/computed tomography (PET/CT) of LN confined to the pelvis in 80 cervical cancer patients before undergoing radiotherapy (RT) with or without concurrent chemotherapy. Optimal cut-off values for disease-free survival (DFS) and overall survival (OS) were determined by receiver operating characteristic (ROC) curve analysis. We used ROC curve analyses to evaluate whether LN SUVmax, LN ADCmin and LN short-axis length predicted risk of recurrence or survival. RESULTS: Median DFS and OS for all patients were 18.97 and 22.28 months, respectively. DFS and OS rates of patients with high LN SUVmax was significantly lower than those of patients exhibiting low LN SUVmax (P=0.003 and P=0.019). Patients with low LN ADCmin had poorer DFS and OS than those with high LN ADCmin (P=0.033 and P=0.005). DFS for patients exhibiting longer LN short-axis length was significantly lower than those of patients exhibiting shorter LN short-axis length (P=0.018). Multivariate analyses indicated that high LN SUVmax was an independent predictor for both DFS and OS (P=0.0231 and P=0.0146). CONCLUSIONS: LN SUVmax could be an important predictor of recurrence and survival in patients with cervical cancer confined to the pelvis.

DOI： 10.1016/j.ejogrb.2013.10.030

子宮頸癌心臓転移の一例

岡本和浩, 楠本知行, 安藤まり, 依田尚之, 樫野千明, 西條昌之, 谷和祐, 春間朋子, 福島千加子, 関典子, 中村圭一郎, 増山寿, 平松祐司

現代産婦人科 62 ( Suppl. ) S46 - S46 2013.9

婦人科癌大量胸腹水に対して利尿剤の大量投与が有効であった2症例

谷川真奈美, 関典子, 春間朋子, 福島千加子, 楠本知行, 中村圭一郎, 平松祐司, 市原英基, 松岡順治

現代産婦人科 62 ( Suppl. ) S54 - S55 2013.9

Three Cases of Struma Ovarii Underwent Laparoscopic Surgery with Definite Preoperative Diagnosis

Nurliza Binti Md Nor, Tomoyuki Kusumoto, Seiji Inoue, Keiichiro Nakamura, Noriko Seki, Atsushi Hongo, Junichi Kodama, Yuji Hiramatsu

ACTA MEDICA OKAYAMA 67 ( 3 ) 191 - 195 2013.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Struma ovarii is a rare neoplasm that accounts for approximately 0.3% of ovarian tumors. Due to its ultrasound morphology, which is quite similar to that of malignant ovarian carcinoma, most struma ovarii cases are open operated with laparotomy rather than laparoscopy. We present 3 cases of struma ovarii, which were diagnosed preoperatively by imaging studies and removed by laparoscopic surgery. All patients were premenopausal women between ages 31-50. The magnetic resonance imaging (MRI) findings were complex masses composed of multiple cysts and solid components with T2-hypointense regions as well as multiple T1-hyperintense cystic areas, findings that are typical for struma ovarii. A combination of plain computed tomography (CT), positron emission tomography (PET)-CT, and scintigraphy was useful for diagnosis. Laboratory examination revealed elevated serum thyroglobulin, which led to the diagnosis of struma ovarii. Laparoscopic surgeries were performed without rupturing the tumors. Although it has been difficult to differentiate between struma ovarii and malignant tumors by conventional methods, recently MRI techniques appear make it possible to diagnose struma ovarii preoperatively from the abovementioned imaging characteristic, together with laboratory data. As for treatment, we think laparoscopy could be successful for struma ovarii, but the surgeon must be careful not to rupture the tumor intra-abdominally in order to prevent dissemination, which could lead to malignancy.

The mean apparent diffusion coefficient value (ADCmean) on primary cervical cancer is a predictive marker for disease recurrence. International journal

Keiichiro Nakamura, Ikuo Joja, Takeshi Nagasaka, Chikako Fukushima, Tomoyuki Kusumoto, Noriko Seki, Atsushi Hongo, Junichi Kodama, Yuji Hiramatsu

Gynecologic oncology 127 ( 3 ) 478 - 83 2012.12

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

OBJECTIVE: The purpose of this study is to investigate the correlation of the max, mean and minimal apparent diffusion coefficient values (ADCmax, ADCmean, and ADCmin) on diffusion weighted imaging findings with prognostic factors in cervical cancer. METHODS: A cohort of 80 cervical cancer patients underwent pelvic magnetic resonance imaging (MRI) within the 2 to 4 weeks prior to radical hysterectomy. The optimal cutoff value for segregating disease free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. We used ROC curve analyses to evaluate whether preoperative ADCmax, ADCmean, ADCmin on MRI predicted the risk group of recurrence. RESULTS: Analyses of ROC curves identified an optimal The ROC curves identified an optimal ADCmax, ADCmean, and ADCmin cutoff values of 1.122 × 10(-3)mm(2)/s, 0.852 × 10(-3)mm(2)/s, 0.670 × 10(-3)mm(2)/s and for predicting the recurrence of cervical cancer. The patients categorized into the lower ADCmean or ADCmin groups showed the shorter disease free survivals compared with the higher ADCmean or ADCmin, respectively (P<0.0001 or P=0.0210). In particular, the ADCmean of primary cervical cancer was an independent predictive factor for disease recurrence by a multivariate analysis (P=0.0133). CONCLUSIONS: The ADCmean of primary cervical cancer calculated by MRI could be an important factor for identifying patients with a risk of disease recurrence.

DOI： 10.1016/j.ygyno.2012.07.123

Antitumor effects of novel shorter truncated insulin-like growth factor I receptors

Yojiro Ojima, Atsushi Hongo, Yixuan Liu, Lisha Zhu, Tomoyuki Kusumoto, Keiichiro Nakamura, Noriko Seki, Junichi Kodama, Yuji Hiramatsu

CANCER BIOLOGY & THERAPY 13 ( 7 ) 559 - 566 2012.5

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

We generated novel truncated insulin-like growth factor I receptors (IGF-IRs) designated as 126/STOP, 223/STOP and 325/STOP in order to establish shorter soluble IGF-IRs than previously reported 486/STOP without abrogating the same antitumor effects. Stable transfection of 223/STOP and 325/STOP, but not 126/STOP caused inhibition of anchorage-independent growth of CaOV-3 ovarian cancer cells in vitro. This antitumor effect was reproduced when we used recombinant proteins of these constructs, suggesting a bystander effect of these shorter truncated IGF-IRs. Tumorigenesis in vivo of CaOV-3 cells tranfected with 223/STOP or 325/STOP was strictly inhibited, and inoculation of these cells in nude mice caused massive apoptosis exclusively in vivo. Phosphorylations of IGF-IR and Akt, but not Erk were attenuated in 223/STOP- or 325/STOP-transfected CaOV-3 cells and downregulations of IGF-IR and Akt phosphorylation seemed to play at least a partial role in the antitumor effect of these novel truncated IGF-IRs. Since 223/STOP and 325/STOP are smaller in size than previously reported 486/STOP, and they retain the same antitumor effects, they could be good candidates for clinical application in the future.

DOI： 10.4161/cbt.19609

α-fetoprotein-producing endometrial adenocarcinoma without an obvious hepatoid component Reviewed

Junichi Kodama, Noriko Seki, Hiroyuki Yanai, Tomoyuki Kusumoto, Keiichiro Nakamura, Atsushi Hongo, Yuji Hiramatsu

Oncology Letters 1 ( 2 ) 243 - 245 2010.3

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

Endometrial carcinomas producing α-fetoprotein (AFP) are extremely rare. We report a case of AFP-producing, Grade 2 endometrioid adenocarcinoma without an obvious hepatoid component. A 59-year-old multiparous woman presented with abdominal swelling. The serum level of AFP was 1292.8 ng/ml. Magnetic resonance images of the pelvis showed a markedly enlarged uterus, with a tumor growing exophytically within the endometrial cavity. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The histopathological examination demonstrated a Stage IIA, Grade 2 endometrioid adenocarcinoma without an obvious hepatoid component. The endometrioid adenocarcinoma cells were partly positive for AFP immunoreactivity. The patient received adjuvant chemotherapy and was disease-free 60 months after the operation. This case confirms the existence of AFP-producing endometrioid adenocarcinomas without hepatoid features.

DOI： 10.3892/ol_00000043

Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are potential targets in uterine leiomyosarcoma

Keiichiro Nakamura, Fernando Abarzua, Atsushi Hongo, Junichi Kodama, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

International Journal of Oncology 37 ( 3 ) 605 - 614 2010

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

Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are Kunitz-type serine protease inhibitors that have a broad inhibitory spectrum against serine proteases. This study examined the role of HAI-1 and HAI-2 in uterine leiomyosarcoma (LMS) patients, and in vitro. HAI-1 and HAI-2 was examined in uterine normal smooth muscle, leiomyoma and LMS specimens using immunohistochemistry. We investigated biological functions and inhibitory effects of HAI-1 and HAI-2 using uterine LMS cell line SK-LMS-1 and SKN. The expression levels of HAI-1 and HAI-2 were significantly decreased in uterine LMS specimens relative to corresponding uterine normal smooth muscle and leiomyoma specimens. Furthermore, the low HAI-1 and HAI-2 expression was a significant predictor for poor prognosis when compared with high HAI-1 and HAI-2 expression (disease-free survival rate
p=0.024 and p=0.045, overall survival rate
p=0.043 and p=0.009). HAI-1 and HAI-2 showed potential inhibitory effects that mediated cell proliferation, migration and cellular invasion which led to apoptosis and necrosis through a reduction of HGFA, matriptase and hepsin expression. These findings indicate that HAI-1 and HAI-2 may be possible tumor suppressor genes for uterine LMS and thus, both could be considered therapeutic agents for the treatment of LMS.

DOI： 10.3892/ijo_00000709

Expression of Matriptase and Clinical Outcome of Human Endometrial Cancer Reviewed

Keiichiro Nakamura, Atsushi Hongo, Junichi Kodama, Fernando Abarzua, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

ANTICANCER RESEARCH 29 ( 5 ) 1685 - 1690 2009.5

Language：English Publishing type：Research paper (scientific journal) Publisher：INT INST ANTICANCER RESEARCH

Background: Matriptase, a type II transmembrane serine protease is involved in angiogenesis, degradation of extracellular matrix and in progression of some epithelial cancers. The purpose of the present study was to examine matriptase expression and evaluate its clinicopathological significance in endometrial cancer. Patients and Methods: Matriptase expression was examined in normal endometrium (n=20), endometrial hyperplasia (n=11) and endometrial cancer (n=65) samples. The distribution of cases that scored positive for each of the biological parameters examined was correlated with matriptase expression status obtained by immunohistochemistry. Results: Matriptase was found to be significantly overexpressed in endometrial cancer as compared with normal endometrium and endometrial hyperplasia. Interestingly, matriptase expression is associated with stage (p=0.010), grade (p=0.021), depth of myometrial invasion (p=0.004), cervical involvement (p=0.021), lymph node metastasis (p=0.009), LVS involvement (p=0.041) and peritoneal cytology (p=0.045). The high matriptase expression was a significant predictor for poor prognosis when compared with low matriptase expression (Disease-free survival rate; p=0.032, Overall survival rate; p=0.011). Conclusion: High matriptase expression in endometrial cancer may be associated with poor prognosis.

The role of hepatocyte growth factor activator inhibitor-1 (HAI-1) as a prognostic indicator in cervical cancer

Keiichiro Nakamura, Fernando Abarzua, Atsushi Hongo, Junichi Kodama, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

International Journal of Oncology 35 ( 2 ) 239 - 248 2009

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

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a Kunitz-type serine protease inhibitor that has a broad inhibitory spectrum against serine proteases. This is the first study to investigate the role of HAI-1 and its clinical importance in cervical cancer. We attempted to investigate the inhibitory effects of HAI-1 using cervical carcinoma cell lines SiHa with integrated human papillomavirus (HPV) 16 and HeLa with integrated HPV 18. HAI-1 expression in cervical cancer (n=91) were assessed by immunohistochemistry. HAI-1 was found to be a potential inhibitory effects mediated by reduction of hepsin, matriptase and prostasin expression. This led to apoptosis through a reduction in the levels of Bcl-2, Bcl-xL, MUPP-1 and MAGI-3 in cervical cancer cell lines. There were significant correlations between HAI-1 expression and stage (p=0.013), tumor size (p=0.002), stromal invasion (p&lt
0.001), vaginal invasion (p=0.031), parametrial invasion (p=0.012), lymph-node metastasis (p=0.019), and LVS involvement (p=0.002). The disease-free and overall survival rates of patients exhibiting high HAI-1 expression were significantly higher than those of patients exhibiting low HAI-1 expression (p=0.022 and p=0.011, respectively). The present study proposes that these findings may be considered HAI-1 as a therapeutic target for treatment and identify as a favorable prognostic marker for cancer patients of cervical cancer.

DOI： 10.3892/ijo_00000333

Hepsin inhibits the cell growth of endometrial cancer

Keiichiro Nakamura, Norio Takamoto, Fernando Abarzua, Atsushi Hongo, Junichi Kodama, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 22 ( 3 ) 389 - 397 2008.9

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the, family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3 sigma expression which leads to both cell cycle arrest at the G(2)/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.

DOI： 10.3892/ijmm_00000035

Secretory leukoprotease inhibitor inhibits cell growth through apoptotic pathway on ovarian cancer

Keiichiro Nakamura, Norio Takamoto, Atsushi Hongo, Junichi Kodama, Fernando Abrzua, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

ONCOLOGY REPORTS 19 ( 5 ) 1085 - 1091 2008.5

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

In light of the poor prognosis for ovarian cancer, research continues for innovative and efficacious treatment modalities. It is now widely accepted that new approaches for the treatment of ovarian cancers are pivotal in further improving prognosis of this disease. Secretory leukoprotease inhibitor (SLPI) is an 11.7-kDa non-glycosylated, serine protease inhibitor that has a broad inhibitory spectrum against serine protease. SLPI showed potential therapeutic inhibitory effects mediated by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), TNF-alpha, death receptor (DR)-4, DR-5 and TNF receptor (TNFR)-I expression which lead to an activation of apoptosis pathway through Caspase-2, Caspase-8 and Caspase-9. We examined whether levels of SLPI protein expression correlated with clinicopathological characteristics in 58 ovarian cancer samples, and investigated the role of SLPI and its biological functions. SLPI expression showed a significant correlation between low expression of SLPI and amount of ascites (p=0.021), lymph node metastasis (p=0.011). We propose that SLPI could be considered a therapeutic target for the treatment of ovarian cancer.

Expression of the serine protease hepsin and clinical outcome of human endometrial cancer

Tamaki Matsuo, Keiichiro Nakamura, Norio Takamoto, Junichi Kodama, Atsushi Hongo, Fernando Abrzua, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

Anticancer Research 28 ( 1 A ) 159 - 164 2008.1

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

Background: Hepsin is a type II transmembrane serine protease originally identified in the human liver as a cDNA clone. Hepsin was found to be significantly overexpressed in cancer samples compared to matched various tissues (e.g. prostate, renal, ovarian carcinoma). The purpose of the present study was to examine hepsin expression and to evaluate its clinicopathological significance in endometrial cancer. Patients and Methods: Hepsin expression was examined by immunohistochemisty in 34 cases with normal endometrium as a control, 11 cases with endometrial hyperplasia, and 128 cases with endometrioid adenocarcinoma. Results: Hepsin expression was found to be significantly higher in endometrial cancer compared to normal endometrium and endometrial hyperplasia. High levels of hepsin expression were associated with advanced stage (p&lt
0.001), high grade (p=0.002), depth of myometrial invasion (p&lt
0.001), cervical involvement (p=0.007), lymph node metastasis (p=0.001), lymph vascular space (LVS) involvement (p=0.006), ovarian metastasis (p=0.002), and peritoneal cytology (p=0.03) of endometrial cancer. Conclusion: These findings indicate that hepsin protein expression could be an important indication for high risk of endometrial cancer.

外陰Merkel Cell Carcinomaの一症例

豊嶋英理子, 関典子, 中村圭一郎, 本郷淳司, 児玉順一, 平松祐司, 柳井広之, 河本義之, 藤原道久, 高尾彰, 物部泰昌

日本臨床細胞学会岡山支部会誌 26 13 - 14 2007.12

単発性肝転移再発を来たした子宮頸部小細胞癌の2症例

豊嶋英理子, 本郷淳司, 関典子, 中村圭一郎, 児玉順一, 平松祐司

現代産婦人科 56 ( 2 ) 59 - 59 2007.9

Hepsin shows inhibitory effects through apoptotic pathway on ovarian cancer cell lines

Keiichiro Nakamura, Yasutomo Nasu, Atsushi Hongo, Tamaki Matsuo, Junichi Kodama, Shin Ebara, Atsushi Nagai, Fernando Abrzua, Hiromi Kumon, Yuji Hiramatsu

International Journal of Oncology 28 ( 2 ) 393 - 398 2006

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

In light of the poor prognosis for ovarian cancer patients, the research continues for innovative and efficacious treatment modalities. Along with surgical and chemotherapeutic regimens, gene therapy has emerged as one of the leading contenders in the treatment armamentarium. Hepsin is a type II transmembrane serine protease originally identified in the human liver as a cDNA clone. However, the biological function of Hepsin expression remains unclear. Apoptotic cell was increasingly common among higher proportions of Hepsin transfectants. We discovered that first-time stable transfectants of Hepsin significantly inhibited cell growth in the monolayer, anchorage-independent cell growth in the soft agar in vitro, and tumorigenicity in vivo in ovarian cancer cell lines. These results demonstrated that Hepsin has a potential therapeutic effect that inhibits through up-regulation of p53-dependent apoptosis and caspase-3, -6, and -7 activations. Our findings in this study identify Hepsin as a target for new approaches in ovarian cancer treatment.

DOI： 10.3892/ijo.28.2.393

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