Details of a Researcher - Yamagami, Wataru

Papers - Yamagami, Wataru

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Advancing Precision Oncology: Whole-Exome Sequencing in Endometrial Cancer Liquid-Based Cytology

Takamatsu R, Nakamura K, Chiyoda T, Tsuji K, Kawano R, Yoshimi N, Yamagami W, Nishihara H

Arch Pathol Lab Med 149 ( 6 ) 561 - 567 2025.06

Research paper (scientific journal), Joint Work

Prognostic impact of peritoneal cytology on treating endometrial cancer using data from the Japan Society of Obstetrics and Gynecology cancer registry

Sakai K, Yamagami W, Takahashi F, Tokunaga H, Yamamoto E, Yokoyama Y, Yoshino K, Kawana K, Nagase S

J Gynecol Oncol 36 ( 3 ) e41 - e41 2025.05

Research paper (scientific journal), Joint Work

CXCL9 and CXCL13 shape endometrial cancer immune-activated microenvironment via tertiary lymphoid structure formation

Nagase Y, Kodama M, Aimono E, Nakamura K, Takamatsu R, Abe K, Yoshimura T, Chiyoda T, Yamagami W, Nishihara H

Cancer Sci 116 ( 5 ) 1193 - 1202 2025.05

Research paper (scientific journal), Joint Work

mTOR-mediated p62/SQSTM1 stabilization confers a robust survival mechanism for ovarian cancer

Tamura T, Nagai S, Masuda K, Imaeda K, Sugihara E, Yamasaki J, Kawaida M, Otsuki Y, Suina K, Nobusue H, Akahane T, Chiyoda T, Kisu I, Kobayashi Y, Banno K, Sakurada K, Okita H, Yamaguchi R, Ahmed AA, Yamagami W, Saya H, Aoki D, Nagano O

Cancer Lett 616 217565 - 217565 2025.04

Research paper (scientific journal), Single Work

難治性のほてり・発汗に対して補腎剤が著効した3症例

横田めぐみ，椎名美季，大野あゆみ，谷本慧子，堀場裕子，山上亘

産婦人科漢方研究のあゆみ 40 58 - 62 2025.04

Research paper (scientific journal), Joint Work

めまいを訴える更年期女性への漢方処方と効果

椎名美季，横田めぐみ，大野あゆみ，谷本慧子，堀場裕子，山上亘

産婦人科漢方研究のあゆみ 40 26 - 30 2025.04

Research paper (scientific journal), Joint Work

横紋筋融解症を発症し早産に至った筋強直性ジストロフィー合併妊娠の1例

山田郁，大谷利光，緒方泰彦，石川直嗣，梶川かおる，秋田啓介，玉井順子，田中雄也，春日義史，池ノ上学，山上亘，田中守

東京産科婦人科学会会誌 74 ( 2 ) 367 - 370 2025.04

Joint Work, Accepted

Immunotherapy for endometrial cancer

Wada M, Yamagami W

Int J Clin Oncol 30 ( 3 ) 449 - 456 2025.03

Research paper (scientific journal)

子宮内膜異型増殖症に対する鏡視下子宮全摘出術前における、子宮内膜全面掻爬術の有用性に関する検討

坂巻智美，吉村拓馬，落合大輔，地阪光代，平田桃，高橋美央，坂井健良，和田美智子，千代田達幸，山上亘，田中守

東京産科婦人科学会会誌 74 ( 1 ) 8 - 12 2025.01

Research paper (scientific journal), Joint Work, Accepted

Delayed and immediate cutaneous adverse events during pembrolizumab combination chemotherapy against cervical cancer: Case series

Adachi T., Matsui T., Okata-Karigane U., Takahashi C., Tahara U., Hyodo M., Miyagawa A., Kobayashi K., Nakamura Y., Funakoshi T., Nishio H., Yamagami W., Takahashi H.

Journal of Dermatology 52 ( 1 ) 132 - 137 2025.01

Research paper (scientific journal), Joint Work, ISSN 03852407

Immune checkpoint inhibitors (ICIs), such as pembrolizumab (PEM), are widely recognized for their antitumor efficacy, but they can also lead to various cutaneous adverse events (CAEs). While most CAEs can be managed with topical corticosteroids, severe cases may necessitate halting immunotherapy. The incidence of severe CAEs is notably higher in combination therapies involving ICIs than in monotherapies, emphasizing the need for stringent, long-term management strategies. This includes potential modifications or discontinuations of the combination therapy. PEM, when added to the conventional paclitaxel + cisplatin (or carboplatin) ± bevacizumab regimen, has shown significant improvements in overall and progression-free survival for patients with Stage IVB metastatic or locally uncontrolled recurrent cervical cancer. This case series retrospectively examined the incidence and management of CAEs in 19 female patients treated with this combination therapy between October 2022 and May 2023. Four patients exhibiting CTCAE grade 3 were identified. The four cases of severe CAEs involved erythema multiforme after the initial course of PEM combination chemotherapy. Notably, three patients experienced immediate hypersensitivity reactions, including anaphylaxis, during subsequent treatments. This observation underscores the necessity for rigorous dermatological monitoring of patients undergoing PEM combination chemotherapy. Such vigilance is crucial for early detection of adverse reactions and timely adjustment of treatment regimens, thereby enhancing patient safety.

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Transcriptome Concordance Between Borderline Tumors and Endometrioid Carcinoma: An Integrative Genomic Analysis

Takahashi M, Nakamura K, Chiyoda T, Okada C, Nohara S, Takamatsu R, Yanazume S, Kobayashi H, Nishihara H, Yamagami W

Cancer Med 14 ( 2 ) e70601 - e70601 2025.01

Research paper (scientific journal), Joint Work

Prognostic impact of the number of resected pelvic nodes in endometrial cancer: Japanese Gynecologic Oncology Group Study JGOG2043 post hoc analysis

Konno Y, Mayama M, Takehara K, Yokoyama Y, Suzuki J, Susumu N, Harano K, Nakagawa S, Nakanishi T, Yamagami W, Yoshihara K, Nomura H, Okamoto A, Aoki D, Watari H

J Gynecol Oncol 36 ( 1 ) e3 - e3 2025.01

Research paper (scientific journal), Joint Work

Safe Implementation of Robotic Surgery for Gynecologic Diseases at a Tertiary Center: Retrospective Analysis of 149 Cases and Review of the Literature

Yoshimura T, Nishio H, Sakai K, Nogami Y, Hayashi S, Yamagami W

Gynecol Minim Invasive Ther 14 ( 1 ) 33 - 39 2024.12

Research paper (scientific journal)

The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine.

Hashimoto T, Nakamura Y, Fujisawa T, Imai M, Shibuki T, Iida N, Ozaki H, Nonomura N, Morizane C, Iwata H, Okano S, Yamagami W, Yamazaki N, Kadowaki S, Taniguchi H, Ueno M, Boku S, Oki E, Komatsu Y, Yuki S, Makiyama A, Otsuka T, Hara H, Okano N, Nishina T, Sakamoto Y, Miki I, Kobayashi S, Yuda J, Kageyama SI, Nagamine M, Sakashita S, Sakamoto N, Yamashita R, Koga Y, Bando H, Ishii G, Kuwata T, Park WY, Ohtsu A, Yoshino T

Cancer discovery 14 ( 11 ) 2243 - 2261 2024.11

ISSN 2159-8274

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術中迅速病理診断で類内膜癌G1/G2,筋層浸潤1/2未満の子宮体癌に対して骨盤リンパ節郭清は必要か?

吉村拓馬，坂井健良，落合大輔，坂巻智美，地阪光代，高橋美央，吉浜智子，千代田達幸，田中守，山上亘

関東連合産科婦人科学会誌 61 ( 4 ) 479 - 484 2024.11

Research paper (scientific journal), Joint Work

A phase II trial evaluating the efficacy and safety of repeated high dose medroxyprogesterone acetate (MPA) therapy for patients with recurrent early-stage endometrial cancer or atypical endometrial hyperplasia: Japanese. Gynecologic Oncology Group study (JGOG2051/KGOG2031, REMPA trial)

Sakai K, Yamagami W, Sato Y, Susumu N, Yokoyama Y, Takehara K, Mandai M, Okamoto A

J Gynecol Oncol 35 ( 6 ) e106 - e106 2024.11

Research paper (scientific journal), Joint Work

子宮体癌における術後補助化学中に壊死性筋膜炎が疑われた1例

真鍋悠歌，横田めぐみ，高畑海音子，和田美智子，山上亘，田中守

東京産科婦人科学会会誌 73 ( 4 ) 811 - 817 2024.10

Research paper (scientific journal), Joint Work, Accepted

子宮頸管妊娠に対しメトトレキサート（MTX）と子宮動脈塞栓症（UAE）を併用し保存的治療を行った2例

白石慧，上條慎太郎，佐久間萌子，大岡令奈，松沢優一，内田志穂，祝井麻希，内田明花，山田満稔，山上亘，田中守

東京産科婦人科学会会誌 73 ( 4 ) 848 - 853 2024.10

Research paper (scientific journal), Joint Work, Accepted

Cost-effectiveness analysis of hospital treatment volume and survival outcomes in endometrial cancer in Japan.

Machida H, Matsuo K, Higashi T, Aoki D, Enomoto T, Okamoto A, Katabuchi H, Nagase S, Mandai M, Yaegashi N, Yamagami W, Mikami M

Journal of gynecologic oncology 35 ( 5 ) e61 2024.09

Research paper (scientific journal), Joint Work, ISSN 2005-0380

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Schlafen 11 further sensitizes BRCA-deficient cells to PARP inhibitors through single-strand DNA gap accumulation behind replication forks

Onji H., Tate S., Sakaue T., Fujiwara K., Nakano S., Kawaida M., Onishi N., Matsumoto T., Yamagami W., Sugiyama T., Higashiyama S., Pommier Y., Kobayashi Y., Murai J.

Oncogene 43 ( 32 ) 2475 - 2489 2024.08

ISSN 09509232

The preferential response to PARP inhibitors (PARPis) in BRCA-deficient and Schlafen 11 (SLFN11)-expressing ovarian cancers has been documented, yet the underlying molecular mechanisms remain unclear. As the accumulation of single-strand DNA (ssDNA) gaps behind replication forks is key for the lethality effect of PARPis, we investigated the combined effects of SLFN11 expression and BRCA deficiency on PARPi sensitivity and ssDNA gap formation in human cancer cells. PARPis increased chromatin-bound RPA2 and ssDNA gaps in SLFN11-expressing cells and even more in cells with BRCA1 or BRCA2 deficiency. SLFN11 was co-localized with chromatin-bound RPA2 under PARPis treatment, with enhanced recruitment in BRCA2-deficient cells. Notably, the chromatin-bound SLFN11 under PARPis did not block replication, contrary to its function under replication stress. SLFN11 recruitment was attenuated by the inactivation of MRE11. Hence, under PARPi treatment, MRE11 expression and BRCA deficiency lead to ssDNA gaps behind replication forks, where SLFN11 binds and increases their accumulation. As ovarian cancer patients who responded (progression-free survival >2 years) to olaparib maintenance therapy had a significantly higher SLFN11-positivity than short-responders (<6 months), our findings provide a mechanistic understanding of the favorable responses to PARPis in SLFN11-expressing and BRCA-deficient tumors. It highlight the clinical implications of SLFN11. (Figure presented.)

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Case report of two long term ovarian cancer survivors with brain metastases following multimodal treatment including chemotherapy, radiotherapy and maintenance olaparib: An institutional case series and literature review

Tsuchino Y., Chiyoda T., Jisaka M., Sakamaki T., Hirata M., Takahashi M., Yoshimura T., Sakai K., Wada M., Yamagami W.

Gynecologic Oncology Reports (Gynecologic Oncology Reports) 54 101444 2024.08

ISSN 2352-5789

Brain metastasis from ovarian cancer is a very rare condition with a poor prognosis. However, due to its rarity, there is no established treatment strategy. We present a case series of brain metastasis with ovarian cancer, focusing on two long-term survivors treated with multimodal therapy. Among the nine cases, the median survival time after brain metastases was six months (range: 0–58 months). Eight patients had high-grade serous carcinoma (HGSC). Three of the four patients who underwent genetic testing tested positive for germline BRCA2 (gBRCA2) mutation. Two patients survived longer than 4 years after the diagnosis of brain metastases. Both of these patients received chemotherapy, radiation therapy, and olaparib, a molecularly targeted drug, as maintenance therapy. This case series suggests that patients with gBRCA2 mutation-positive HGSC may be at a high risk of developing brain metastases. A multidisciplinary approach, including PARP inhibitors, may improve the prognosis of patients with brain metastases from ovarian cancer.

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原発性卵巣癌が疑われたが審査腹腔鏡により転移性卵巣癌と診断された診断された2例

落合大輔，千代田達幸，西尾浩，地阪光代，坂巻智美，平田桃，吉村拓馬，高橋美央，坂井健良，和田美智子，山上亘，田中守

東京産科婦人科学会会誌 73 ( 3 ) 627 - 632 2024.07

Research paper (scientific journal), Joint Work, Accepted

Detailed report on the clinicopathological factors of patients with endometrial cancer in Japan: a JSOG gynecologic tumor registry-based study

Makabe T, Yamagami W, Takahashi F, Tokunaga H, Yamamoto E, Yokoyama Y, Yoshino K, Kawana K, Nagase S

J Gynecol Oncol 35 ( 4 ) e54 - e54 2024.07

Research paper (scientific journal), Joint Work

Gastric-type adenocarcinoma of the uterine cervix: clinical features and future directions

Nishio H., Matsuda R., Iwata T., Yamagami W.

Japanese Journal of Clinical Oncology (Japanese Journal of Clinical Oncology) 54 ( 5 ) 516 - 520 2024.05

ISSN 03682811

The concept of gastric-type mucinous carcinoma of the uterine cervix (GAS) has been accepted worldwide because of its aggressive clinical behaviour and the absence of high-risk human papilloma virus infection. The World Health Organization (WHO) 2020 classification divides cervical tumours into two categories: human papilloma virus-associated and human papilloma virus-independent. Hence, GAS is now classified as an human papilloma virus-independent gastric type. Because clinical studies have reported that GAS is refractory to conventional treatments such as chemotherapy and radiotherapy, especially at an advanced stage, and has aggressive features with widespread dissemination to unusual sites, such as the omentum, peritoneum and distant organs, it is urgent to establish new treatment strategies by comparing the molecular profiles of human papilloma virus-associated adenocarcinomas. A series of genetic mutations characteristic to GAS encourage the development of future treatment strategies such as targeted therapy and immunotherapy.

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Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma

Matoba Y, Zarrella DT, Pooladanda V, Azimi Mohammadabadi M, Kim E, Kumar S, Xu M, Qin X, Ray LJ, Devins KM, Kumar R, Kononenko A, Eisenhauer E, Veillard IE, Yamagami W, Hill SJ, Sarosiek KA, Yeku OO, Spriggs DR, Rueda BR

Br J Cancer (British Journal of Cancer) 130 ( 9 ) 1463 - 1476 2024.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 00070920

Background: Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3’s role in promoting USC pathology is lacking. Methods: We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3’s impact on cell function. Results: TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. Conclusion: These findings suggest inhibiting Gal3 may benefit USC patients.

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めまいを訴える更年期女性への漢方処方と効果

椎名美季，横田めぐみ，大野あゆみ，谷本慧子，堀場裕子，山上亘

産婦人科漢方のあゆみ 40 26 - 30 2024.04

Research paper (scientific journal), Joint Work, Last author

難治性のほてり・発汗に対して補腎剤が著効した3症例

横田めぐみ，椎名美季，大野あゆみ，谷本慧子，堀場裕子，山上亘

産婦人科漢方研究のあゆみ 40 58 - 62 2024.04

Research paper (scientific journal), Joint Work, Last author

血清hCG値の推移を観察した妊娠高血圧腎症合併間葉性異形成胎盤の1例

山本大貴，田中邦生，高橋まりな，梶川かおる，秋田啓介，福間優花，大谷利光，池ノ上学，春日義史，山上亘，田中守

東京産科婦人科学会会誌 73 ( 2 ) 402 - 406 2024.04

Research paper (scientific journal), Joint Work

Pretreatment systemic inflammatory markers predict survival in endometrial cancer: A Japanese Gynecologic Oncology Group 2043 exploratory data analysis

Nishio S, Murotani K, Yamagami W, Suzuki S, Nakai H, Kato K, Tokunaga H, Nomura H, Yokoyama Y, Takehara K, Okamoto A

Gynecol Oncol (Gynecologic Oncology) 181 46 - 53 2024.02

Research paper (scientific journal), Joint Work, ISSN 00908258

Objective: We investigated whether pretreatment systemic inflammatory markers are associated with survival outcomes in patients with endometrial cancer (EC). Methods: Data from the Japanese Gynecologic Oncology Group 2043 were analyzed. Patients who did not receive chemotherapy or were lost to follow-up were excluded. Associations of pretreatment systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, with progression-free survival (PFS) and overall survival (OS) were analyzed. The optimal NLR, PLR, and HALP score cutoff values for PFS and OS were determined. Survival estimates were calculated and compared using the Kaplan–Meier method and log-rank test. Results: We included 712 patients (median age: 55 [range, 28–74] years; body mass index [BMI]: 21.1 [15.2–38.6] kg/m2). For PFS, optimal NLR, PLR, and HALP score cutoff values were 1.48, 0.017, and 35.52, respectively, and for OS, the values were 1.88, 0.026, and 19.87, respectively. At optimal PFS-related cutoff values, NLR was associated with BMI; PLR with age, BMI, and clinical stage; and HALP score with BMI, clinical stage, and lymph node metastasis. At optimal OS-related cutoff values, NLR was associated with BMI, PLR, and BMI; the HALP score was associated with age and BMI. The HALP score was a prognostic factor for PFS (p = 0.025), while PLR and HALP scores were prognostic factors for OS (both p = 0.028). Conclusions: Pretreatment systemic inflammatory markers are associated with survival outcomes in patients with EC, with the HALP score being a prognostic factor for PFS and OS.

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BRCA1/2 reversion mutations in a pan-cancer cohort

Nakamura K, Hayashi H, Kawano R, Ishikawa M, Aimono E, Mizuno T, Kuroda H, Kojima Y, Niikura N, Kawanishi A, Takeshita K, Suzuki S, Ueno S, Okuwaki K, Sasaki J, Yamaguchi M, Masuda K, Chiyoda T, Yamagami W, Okada C, Nohara S, Tanishima S, Nishihara H

Cancer Sci 115 ( 2 ) 635 - 647 2024.02

Research paper (scientific journal), Joint Work, Accepted

Impact of COVID-19 on gynecological cancer incidence: a large cohort study in Japan

Komatsu H, Ikeda Y, Kawana K, Nagase S, Yoshino K, Yamagami W, Tokunaga H, Kato K, Kimura T, Aoki D, the Committee on Gynecologic Oncology of the Japan Society of Obstetrics Gynecology

Int J Clin Oncol (International Journal of Clinical Oncology) 29 ( 1 ) 72 - 77 2024.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 13419625

Background: The influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of newly diagnosed gynecological cancers has not been extensively investigated in Japan. This study determined the impact of COVID-19 on the incidence of gynecological cancer. Methods: Using the Japanese Society of Obstetricians and Gynecologic Oncology registry database, the distribution of the number of patients based on clinical staging or tumor-node-metastasis classifications before and during the COVID-19 pandemic was analyzed to compare the trends. The clinical staging classification of cervical cancer in Japan was based on the International Federation of Gynecology and Obstetrics (FIGO) 2008 from 2018 to 2020 and on the FIGO 2018 from 2021. Since FIGO-2018 classified N1 cases as stage IIIC, we focused on T classification without referencing the clinical staging (FIGO staging) of patients with cervical cancer in 2021. Results: The number of patients with endometrial cancer and malignant ovarian tumors of all clinical stages increased uniformly yearly, while that of those with stage III cervical cancer rapidly increased in 2021 owing to the adoption of the revised classification. On comparing cases of cervical cancer in 2020 and 2021, we found that T1 cases decreased and T2 and T3 cases increased in 2021 compared to those in 2020 (p = 0.006). Cervical intraepithelial neoplasia/adenocarcinoma in situ incidence decreased in 2020 compared to that in 2019 but increased again in 2021. The number of patients with cervical cancer decreased in most prefectures in 2020. Conclusion: The incidence of locally advanced cervical cancer increased during the COVID-19 pandemic.

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Japan Society of Gynecologic Oncology 2022 guidelines for uterine cervical neoplasm treatment

Seino M, Nagase S, Tokunaga H, Yamagami W, Kobayashi Y, Tabata T, Kaneuchi M, Hirashima Y, Niikura H, Yoshino K, Takehara K, Baba T, Katabuchi H, Mikami M

J Gynecol Oncol (Journal of Gynecologic Oncology) 35 ( 1 ) e15 - e15 2024.01

Research paper (scientific journal), Accepted, ISSN 20050380

The Japan Society of Gynecologic Oncology (JSGO) Guidelines 2022 for the Treatment of Uterine Cervical Cancer are revised from the 2017 guideline. This guideline aimed to provide standard care for cervical cancer, indicate appropriate current treatment methods for cervical cancer, minimize variances in treatment methods among institutions, improve disease prognosis and treatment safety, reduce the economic and psychosomatic burden of patients by promoting the performance of appropriate treatment, and enhance mutual understanding between patients and healthcare professionals. The guidelines were prepared through the consensus of the JSGO Guideline Committee, based on a careful review of evidence gathered through the literature searches and the medical health insurance system and actual clinical practice situations in Japan. The guidelines comprise seven chapters and 5 algorithms. The main features of the 2022 revision are as follows: 1) added discussed points at the final consensus meeting; 2) revised the treatment methods based on the International Federation of Gynecology and Obstetrics 2018 staging system; 3) examined minimally invasive surgery based on Laparoscopic Approach to Cervical Cancer trial; 4) added clinical question (CQ) for treatments of rare histological types, gastric type, and small-cell neuroendocrine carcinoma; 5) added CQ for intensity-modulated radiation therapy; 6) added CQ for cancer genomic profiling test; and 7) added CQ for cancer survivorship. Each recommendation is accompanied by a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSGO Guidelines 2022 for the Treatment of Uterine Cervical Cancer.

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Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

Kitazawa S, Chiyoda T, Nakamura K, Sakai K, Yoshihama T, Nishio H, Kobayashi Y, Iwata T, Banno K, Yamagami W, Nishihara H, Aoki D

Int J Clin Oncol (International Journal of Clinical Oncology) 28 ( 11 ) 1554 - 1562 2023.11

Research paper (scientific journal), Joint Work, Accepted, ISSN 13419625

Background: Japan’s health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. Methods: We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022. Results: Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with other). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. Conclusion: Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients’ prognosis and performance status should be considered before performing the test.

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Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2020 and Annual Treatment Report for 2015

Yoshino K, Kurita T, Takahashi F, Nagase S; Board members of the 2022 Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology

J Obstet Gynaecol Res 49 ( 11 ) 2584 - 2592 2023.11

Research paper (scientific journal), Joint Work

当院における卵巣癌初回化学療法後の維持療法としてのニラパリブ使用経験

鈴木渉，吉浜智子，平田桃，家谷佳那，北澤晶子，高橋美央，吉村拓馬，坂井健良，千代田達幸，山上亘，田中　守，青木大輔

東京産科婦人科学会会誌 72 ( 3 ) 420 - 424 2023.07

Research paper (scientific journal), Accepted

Trends and characteristics of fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer in Japan: a survey by the Gynecologic Oncology Committee of the Japan Society of Obstetrics and Gynecology

Ushijima K., Tsuda N., Yamagami W., Mitsuhashi A., Mikami M., Yaegashi N., Enomoto T.

Journal of Gynecologic Oncology (Journal of Gynecologic Oncology) 34 ( 3 ) e38 2023.05

ISSN 20050380

Objective: The objective of this study was to examine the current trends in fertility-sparing (FS) treatment for young atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) patients in Japan. Methods: This study was conducted by the Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology (JSOG) in the 2017–2018 fiscal year. A nationwide, retrospective questionnaire-style survey—as performed. We collected the data of 413 patients from 102 JSOG gynecological cancer registered institutions. Results: FS treatment was performed with medroxyprogesterone (MPA) (87.2%) or MPA + metformin (11.6%). Pathological complete remission (CR) after initial treatment was achieved in 78.2% of patients. The significant clinicopathological factors correlated to CR after initial treatment were histology (AEH vs. endometrioid carcinoma grade 1 [ECG1]), body mass index (BMI) (<25 vs. ≥25 kg/m2), and treatment period (<6 vs. ≥6 months). ECG1, time to complete remission (TTCR) ≥6 months, maintenance therapy (−), and pregnancy (−) were associated with a significantly higher risk of recurrence on multivariate analysis. The total pregnancy rate was 47%, and the live birth rate was 40.1%. Patients who received infertility treatments showed a higher live birth rate (50.6%) than those who did not (7.7%). Conclusion: In this survey, we confirmed that FS treatment in Japan is centered on MPA alone and in combination with metformin, and that the treatment efficacy is similar to that reported in previous reports. A multicenter survey study in Japan showed FS treatment for young AEH and EC patients in compliance with the indications is feasible.

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Obstetric outcomes after medroxyprogesterone acetate treatment for early stage endometrial cancer or atypical endometrial hyperplasia: a single hospital-based study

Oishi M., Kasuga Y., Fukuma Y., Hamuro A., Tamai J., Tanaka Y., Hasegawa K., Yoshimura T., Ikenoue S., Ochiai D., Yamagami W., Tanaka M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 28 ( 4 ) 587 - 591 2023.04

Research paper (scientific journal), ISSN 13419625

Background: To investigate perinatal outcomes in pregnancy after high-dose medroxyprogesterone acetate (MPA) therapy for early stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) and to determine whether pregnancy after MPA therapy is at a higher risk of placenta accreta. Methods: Data of 51 pregnancies in 46 women who received MPA therapy for EC or AEH and delivered after 22 weeks of gestation at Keio University Hospital were reviewed. A retrospective matched case–control study was performed to determine the risk of placenta accreta in pregnancy after MPA therapy compared with singleton pregnancies without any history of maternal malignancy treatments. Results: The incidence of placenta accreta was higher in the MPA group than in the control group (15.7 vs. 0%, p = 0.0058). However, no differences in other perinatal outcomes were observed between groups. While gestational weeks at delivery in the MPA group were later than those in the control group (p = 0.0058), no difference in the incidence of preterm delivery was recorded between groups. In the MPA therapy group, the number of patients who underwent ≥ 6 dilation and curettage (D&C) was higher in the placenta accreta group than in the non-placenta accreta group (50.0 vs. 14.0%, p = 0.018). Patients with ≥ 6 D&Cs demonstrated a 6.0-fold increased risk of placenta accreta (p = 0.043, 95% CI 1.05–34.1) than those receiving ≤ 3 D&Cs. Conclusion: Pregnancy after MPA therapy is associated with a high risk of placenta accreta. In cases in which the frequency of D&C is high, placenta accreta should be considered.

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更年期女性の精神症状に漢方薬を使用した10症例

谷本慧子，横田めぐみ，椎名美季，大野あゆみ，弟子丸亮太，岩田　卓，堀場裕子，青木大輔

産婦人科漢方研究のあゆみ 39 109 - 114 2023.04

Research paper (scientific journal)

月経前症候群・月経前不快気分障害に対する抑肝散・抑肝散加陳皮半夏の有用性

大野あゆみ，横田めぐみ，椎名美季，谷本慧子，弟子丸亮太，岩田　卓，青木大輔

産婦人科漢方研究のあゆみ 39 64 - 67 2023.04

Research paper (scientific journal)

更年期の動悸に苓桂朮甘湯を処方した12例の検討

横田めぐみ，椎名美季，大野あゆみ，谷本慧子，堀場裕子，弟子丸亮太，田中　守，青木大輔

産婦人科漢方研究のあゆみ 39 39 - 43 2023.04

Research paper (scientific journal)

子宮内膜異型増殖症の術前診断で腹腔鏡下手術を施行した症例の検討

平田桃, 坂井健良, 山上亘, 北澤晶子, 家谷佳那, 高橋美央, 吉村拓馬, 吉浜智子, 千代田達幸, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 72 ( 2 ) 177 - 182 2023.04

Research paper (scientific journal), Accepted

Evaluation of the role of intraoperative frozen section and magnetic resonance imaging in endometrial cancer

Ooka R., Nanki Y., Yamagami W., Kawaida M., Nagai S., Hirano T., Sakai K., Makabe T., Chiyoda T., Kobayashi Y., Kataoka F., Aoki D.

International Journal of Gynecology and Obstetrics (International Journal of Gynecology and Obstetrics) 160 ( 2 ) 554 - 562 2023.02

Research paper (scientific journal), Accepted, ISSN 00207292

Objective: To evaluate the accuracy of preoperative endometrial biopsy and magnetic resonance imaging (MRI) of endometrial cancer compared with that of intraoperative frozen section. Methods: This retrospective study included 264 patients who underwent surgery with intraoperative frozen section for endometrial cancer at our institution between 2014 and 2018. Diagnosis was determined by histologic type, grade, and myometrial invasion. Concordance rate, sensitivity, and specificity of preoperative diagnosis and intraoperative frozen diagnosis were calculated, in comparison to the final pathologic diagnosis. Results: Preoperative and intraoperative diagnoses showed no statistically significant difference in determining histologic type and grade (P = 0.152). Intraoperative diagnosis showed higher sensitivity for endometrioid carcinoma grade 3 and other types, and higher specificity for grade 1. For myometrial invasion, intraoperative diagnosis showed significantly higher concordance rate than preoperative MRI findings (P < 0.01). Intraoperative diagnosis showed higher sensitivity and specificity in patients with and without myometrial invasion, respectively. Conclusion: Higher agreement between intraoperative and final diagnoses, especially in myometrial invasion, suggests that intraoperative frozen section is a good indicator for appropriate surgical procedure decision making.

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Evaluation of the one-step nucleic acid amplification assay for detecting lymph node metastasis in patients with cervical and endometrial cancer: A multicenter prospective study.

Togami S, Tanimoto A, Yanazume S, Tokunaga H, Nagai T, Watanabe M, Yahata H, Asanoma K, Yamamoto H, Tanaka T, Ohmichi M, Yamada T, Todo Y, Yamada R, Kato H, Yamagami W, Masuda K, Kawaida M, Niikura H, Moriya T, Kobayashi H

Gynecologic oncology (Gynecologic Oncology) 170 70 - 76 2023.01

ISSN 0090-8258

Objective: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. Methods: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-μm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. Results: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961–0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819–0.973) and 0.989 (95% CI: 0.973–0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. Conclusions: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.

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Case Series of Mayer–Rokitansky–Küster–Hauser Syndrome: Analysis of 17 Cases

Miyake A., Kobayashi Y., Imaeda K., Yoshihama T., Nakamura K., Yokota M., Hayashi S., Yamagami W., Banno K., Aoki D.

Clinical and Experimental Obstetrics and Gynecology (Clinical and Experimental Obstetrics and Gynecology) 50 ( 1 ) 2023.01

ISSN 03906663

Background: The Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is a rare disorder characterized by congenital vaginal defects and uterine traces. Because of its rarity, standardized management for MRKH syndrome is unavailable. This study reviewed the management of the patients with MRKH syndrome in our institution. Methods: Using medical records, we retrospectively reviewed the surgical techniques, outcomes, postoperative management methods, and outpatient follow-up of 17 patients with MRKH syndrome in Keio University Hospital. Results: Of the 14 patients who requested vaginoplasty, 12 underwent surgery with Davydov’s modified procedure after the Frank method, and it took 17 months to 34 months (median two years) for the vaginal cavity to enlarge by 5–6 cm. The Frank method is a non-surgical dilation with instrumental stretching of the vaginal vestibular mucosa. Davydov’s procedure is a surgical vaginoplasty in which the vesicoureteral space is coated by the peritoneum. Although one patient lost 3800 mL of bleeding from the plexus vein and four needed to remove the prosthesis under anesthesia about one month after surgery, all patients achieved anatomic success with a vaginal cavity length of 6 cm or more and could have sexual intercourse with their sexual partners. However, two patients interrupted their preoperative hospital visits, and three were lost to follow-up postoperatively. Two of the three patients who did not accept vaginoplasty presented myoma at uterine trace and underwent myomectomy. Another one was scheduled for surgery through psychological support. Conclusions: Davydov’s modified procedure is effective, and dilating the vaginal cavity adequately using the Frank method before surgery is needed to ensure sufficient vaginal length with less perineum. During the operation, attention is required to care for the plexus vein. Comprehensive psychological support, providing appropriate information to the patient for mental maturity, and planning surgery according to their life stages are essential for successful treatment.

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Impact of adjuvant chemotherapy on the overall survival of patients with resectable bulky small cell neuroendocrine cervical cancer: a JSGO-JSOG joint study

Seino M., Nagase S., Ohta T., Yamagami W., Ebina Y., Kobayashi Y., Tabata T., Kaneuchi M., Enomoto T., Mikami M.

Journal of Gynecologic Oncology (Journal of Gynecologic Oncology) 34 ( 1 ) e4 - e4 2023.01

Research paper (scientific journal), ISSN 20050380

Objective: The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment. Methods: The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology between 2004 and 2015. All cases were modified and unified by International Federation of Gynecology and Obstetrics 2008 (Union for International Cancer Control 7th edition). Results: There were 822 registered patients diagnosed with SCNEC from 2004 to 2015 which comprised 1.1% (822/73,698) of all uterine cervical cancer cases. Rates of lymph-node and distant metastasis were significantly higher in T1b2 (38.9% and 13.7%, respectively) than T1b1 (14.2% and 4.4%, respectively) (p<0.01). In IB2 and T1bN1M0 SCNEC, the 5-year survival rate with surgery followed by chemotherapy was significantly higher than that with surgery followed by radiation therapy/concurrent chemoradiation therapy (p<0.01). Conclusion: SNCEC tumors >4 cm in size had greater rates of lymph-node and distant metastasis when compared with tumors ≤4 cm. Adjuvant chemotherapy, rather than radiotherapy, may improve prognosis after surgery in T1bN1M0 SCNEC.

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Impact of the COVID-19 pandemic on surgery for benign diseases in gynecology: A nationwide survey by the Japan Society of Obstetrics and Gynecology

Komatsu H, Nakagawa S, Yamagami W, Yamada H, Miyashita S, Yoshino K, Kawana K, Shibahara H, Hamatani T, Aoki D

J Obstet Gynaecol Res. (Journal of Obstetrics and Gynaecology Research) 49 ( 1 ) 314 - 320 2023.01

Research paper (scientific journal), Joint Work, Corresponding author, Accepted, ISSN 13418076

Aim: This study aimed to clarify the impact of coronavirus disease 2019 on gynecology practice in Japan, in particular, on surgeries for benign gynecological diseases. Methods: An online questionnaire was distributed to 966 facilities in Japan, including core facilities, facilities participating in perinatal and gynecologic oncology registries, and facilities certified for training by the Japanese Society of Obstetrics and Gynecology Endoscopy. The number of surgeries performed was compared between 2019 and 2020, when the novel coronavirus disease was prevalent. Results: Five hundred and eighty (58.2%) facilities responded. The total number of surgeries decreased from 129 648 in 2019 to 118 565 in 2020, by 8.5%, for all surgical procedures. However, there was a clear increase in the number of robotic surgeries performed in 2020 compared to that in 2019 for all populations. The number of total hysterectomies decreased markedly from 15 385 in 2019 to 12 531 in 2020, a fall of 10.1%. Conclusions: The number of surgeries for benign gynecological diseases decreased by 8.5% in 2020 compared to that in 2019. This value is among the lowest in the world.

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Adenocarcinoma in situ or early-stage cervical cancer is a risk factor for preterm delivery after cervical conization: a multicenter observational study

Kasuga Y., Ikenoue S., Nishio H., Yamagami W., Ochiai D., Tanabe K., Tashima Y., Hirao N., Miyakoshi K., Kasai K., Suda Y., Nemoto T., Shiraishi S., Yoshida H., Kurahashi T., Takamatsu K., Iwasaki S., Yamashita H., Akiba Y., Arase T., Hara S., Nakada S., Tanaka M., Aoki D.

Journal of Maternal-Fetal and Neonatal Medicine (Journal of Maternal-Fetal and Neonatal Medicine) 35 ( 25 ) 9837 - 9842 2022.12

ISSN 14767058

Objective: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. Methods: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). Results: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p =.014) was higher and a history of preterm delivery (p =.0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p =.0099 and.0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26–13.68, p =.019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88–46.42, p <.0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55–34.86, p =.012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24–20.73, p =.024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11–16.62, p =.035) increased the risk of preterm delivery in the multiple regression models in primiparous women. Conclusion: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGES Prior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization. The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

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Prognostication of early-onset endometrioid endometrial cancer based on genome-wide DNA methylation profiles

Hirano T., Arai E., Fujimoto M., Nakayama Y., Tian Y., Ito N., Makabe T., Yamagami W., Susumu N., Aoki D., Kanai Y.

Journal of Gynecologic Oncology (Journal of Gynecologic Oncology) 33 ( 6 ) e74 2022.11

ISSN 20050380

Objective: The aim of this study was to establish criteria that would indicate whether fertility preservation therapy would likely be safe for patients aged 40 years or less with endometrioid endometrial cancer based on their DNA methylation profile. Methods: Forty-nine fresh-frozen tissue samples from patients with endometrial cancer from an initial cohort and 31 formalin-fixed paraffin-embedded tissue samples from a second cohort were subjected to genome-wide DNA methylation analysis using the Infinium MethylationEPIC BeadChip. Results: Epigenomic clustering of early-onset endometrial cancer was correlated with the widely used recurrence risk classification. Genes showing differences in DNA methylation levels between the low-recurrence-risk category and intermediate-and high-risk categories were accumulated in pathways related to fibroblast growth factor and nuclear factor-κB signaling. DNA hypomethylation and overexpression of ZBTB38 were frequently observed in the low-risk category. Eight hundred thirty-one marker CpG probes showed area under the curve values of >0.7 on the receiver operating characteristic curve for discrimination of patients belonging to the low-risk category. By combining marker CpG sites, seven panels for placing patients into the low-risk category with 91.3% or more sensitivity and specificity in both the initial and second cohorts were established. Conclusions: DNA methylation diagnostics criteria using up to 6 of 8 CpG sites for LPP, FOXO1, RNF4, EXOC6B, CCPG1, RREB1 and ZBTB38 may be applicable to recurrence risk estimation for patients aged 40 years or less with endometrial cancer, regardless of tumor cell content, even if formalin-fixed paraffin-embedded biopsy or curettage materials are used.

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卵巣小細胞癌（高カルシウム血症型）の1例

吉村拓馬，西尾浩，家谷佳那，坂井健良，吉浜智子，千代田達幸，山上亘，青木大輔，川井田みほ

関東連合産科婦人科学会誌 59 ( 4 ) 499 - 504 2022.11

Joint Work

Lenvatinib plus pembrolizumab in Japanese patients with endometrial cancer: Results from Study 309/KEYNOTE-775

Yonemori K., Yunokawa M., Ushijima K., Sakata J., Shikama A., Minobe S., Usami T., Enomoto T., Takehara K., Hasegawa K., Yamagami W., Yamamoto K., Han S., Dutta L., Orlowski R., Miura T., Makker V., Fujiwara K.

Cancer Science (Cancer Science) 113 ( 10 ) 3489 - 3497 2022.10

ISSN 13479032

Study 309/KEYNOTE-775 is a phase 3 open-label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer with progression after platinum-based therapy. Primary endpoints of superiority for lenvatinib plus pembrolizumab were met for progression-free survival (PFS) and overall survival (OS) in all-comers (ie, regardless of mismatch repair [MMR] status) and patients with MMR proficiency (pMMR). We present results for the Japanese subset. Patients were randomized to oral lenvatinib 20 mg/day plus intravenous pembrolizumab 200 mg every 3 weeks (Q3W; up to 35 cycles of pembrolizumab) or TPC (intravenous doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 QW [3 weeks on/1 week off]). Primary endpoints were PFS by blinded independent central review per RECIST version 1.1 and OS. One hundred four patients were randomized in Japan (data cutoff, October 26, 2020; median follow-up, 11.8 [range, 1.1–26.9] months). Hazard ratios (HRs) for PFS with lenvatinib plus pembrolizumab versus TPC were 1.04 (95% CI, 0.63–1.73) in patients with pMMR and 0.81 (0.50–1.31) in all-comers. Hazard ratios for OS were 0.74 (0.41–1.34) with pMMR and 0.59 (0.33–1.04) for all-comers. Adverse events were manageable and led to discontinuation of one/both study drugs in 36.5% of patients in the lenvatinib plus pembrolizumab group versus 7.8% in the TPC group. Similar to the global Study 309/KEYNOTE-775 results, this analysis suggested favorable efficacy and manageable safety with lenvatinib plus pembrolizumab after platinum-based chemotherapy in Japanese patients with advanced endometrial cancer and supports this combination as a new standard of care in this population.

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Efficacy and safety of olaparib maintenance monotherapy for Japanese patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer

Yoshihama T., Kuroda Y., Chiyoda T., Takahashi M., Yoshimura T., Saotome K., Nanki Y., Sakai K., Kobayashi Y., Yamagami W., Aoki D.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 27 ( 10 ) 1644 - 1650 2022.10

ISSN 13419625

Background: Olaparib maintenance therapy for platinum-sensitive relapsed ovarian cancer has been approved in Japan since April 2018. Here, we report the experience administering this therapy in our hospital, with the aim of evaluating efficacy and safety in the Japanese population. Methods: The study included 52 patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer. All patients started olaparib at a dose of 300 mg twice daily. Information about treatment efficacy and adverse effects was collected retrospectively from medical records. Results: Median age was 58 years old (range: 33–80), and 82.7% of the patients were diagnosed with high-grade serous carcinoma. Sixteen patients (30.8%) possessed the BRCA1/2 pathogenic variant (15 germline and 1 tissue), 3 (5.8%) possessed variants of unknown significance (2 germline and 1 tissue), 16 (30.8%) possessed wild type, and 17 (32.7%) were not analyzed. Median progression-free survival was 15.3 months (95% CI 9.0–21.6). Patients with BRCA1/2 pathogenic variants showed significantly longer PFS than patients with wild-type BRCA1/2 (p = 0.007). Disease progression caused 34 cases to discontinue olaparib. Eighteen (34.6%) individuals exhibited ≥ grade 3 anemia, although they recovered in response to appropriate management. One patient discontinued olaparib because of prolonged renal dysfunction. Another patient presented with grade 3 fatigue, but recovered after 2 weeks of interruption and continued olaparib treatment. Conclusion: Olaparib maintenance therapy for platinum-sensitive recurrent ovarian cancer in the Japanese population is sufficiently safe and no less effective than reports from previous studies.

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当院におけるMayer-Rokitansky-Kuester-Hauser症候群17例の診療経験

三宅温子, 小林佑介, 今枝慶蓉, 吉浜智子, 横田めぐみ, 林茂徳, 山上亘, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 71 ( 3 ) 436 - 440 2022.07

Research paper (scientific journal), Joint Work, Accepted

TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

Akahane T., Masuda K., Hirasawa A., Kobayashi Y., Ueki A., Kawaida M., Misu K., Nakamura K., Nagai S., Chiyoda T., Yamagami W., Hayashi S., Kataoka F., Banno K., Sugano K., Okita H., Kosaki K., Nishihara H., Aoki D.

Journal of Gynecologic Oncology (Journal of Gynecologic Oncology) 33 ( 4 ) e50 2022.07

ISSN 20050380

Objective: Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer. Methods: We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease. Results: TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. Conclusion: The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.

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卵巣原発小細胞癌の2例

家谷佳那, 山上亘, 川井田みほ, 吉村拓馬, 北澤晶子, 高橋美央, 坂井健良, 吉浜智子, 辻浩介, 千代田達幸, 冨永英一郎, 青木大輔

日本婦人科病理学会誌 13 ( 1 ) 47 - 54 2022.06

Joint Work, Corresponding author, Accepted

類内膜癌を癌腫成分に有する卵巣癌肉腫の2例

吉村拓馬, 山上亘, 川井田みほ, 家谷佳那, 北澤晶子, 高橋美央, 坂井健良, 吉浜智子, 野上侑哉, 千代田達幸, 青木大輔

日本婦人科病理学会誌 13 ( 1 ) 33 - 40 2022.06

Research paper (scientific journal), Joint Work, Corresponding author, Accepted

Significance of histology and nodal status on the survival of women with early-stage cervical cancer: validation of the 2018 FIGO cervical cancer staging system

Machida H., Matsuo K., Kobayashi Y., Momomura M., Takahashi F., Tabata T., Kondo E., Yamagami W., Ebina Y., Kaneuchi M., Nagase S., Mikami M.

Journal of Gynecologic Oncology (Journal of Gynecologic Oncology) 33 ( 3 ) e26 2022.05

ISSN 20050380

Objective: To assess the efficacy of the FIGO 2018 classification system for nodal-specific classifications for early-stage cervical cancer; specifically, to examine the impact of nodal metastasis on survival and the effect of postoperative treatments, according to histological subtypes. Methods: This society-based retrospective observational study in Japan examined 16,539 women with the 2009 FIGO stage IB1 cervical cancer who underwent primary surgical treatment from 2004 to 2015. Associations of cause-specific survival (CSS) with nodal metastasis and postoperative adjuvant therapy were examined according to histology type (squamous cell carcinoma [SCC], n=10,315; and non-SCC, n=6,224). Results: The nodal metastasis rate for SCC was higher than that for non-SCC (10.7% vs. 8.3%, p<0.001). In multivariable analysis, the impact of nodal metastasis on CSS was greater for non-SCC tumors (adjusted-hazard ratio [HR], 3.11; 95% confidence interval [CI], 2.40– 4.02) than for SCC tumors (adjusted-HR, 2.20; 95% CI, 1.70–2.84; p<0.001). Propensity score matching analysis showed significantly lower CSS rates for women with pelvic nodal metastasis from non-SCC tumors than from SCC tumors (5-year CSS rate, 75.4% vs. 90.3%, p<0.001).The CSS rates for women with nodal metastasis in SCC histology were similar between the postoperative concurrent chemoradiotherapy/radiotherapy and chemotherapy groups (89.2% vs. 86.1%, p=0.42), whereas those in non-SCC histology who received postoperative chemotherapy improved the CSS (74.1% vs. 67.7%, p=0.043). Conclusion: The node-specific staging system in the 2018 FIGO cervical cancer classification is applicable to both non-SCC tumors and SCC tumors; however, the prognostic significance of nodal metastases and efficacy of postoperative therapies vary according to histology.

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子宮体癌に対して腹腔鏡下手術を施行し術後子宮頸部間質浸潤を認めた9例の検討

家谷佳那, 山上亘, 北澤晶子, 高橋美央, 吉村拓馬, 坂井健良, 吉浜智子, 千代田達幸, 林茂徳, 田中守, 青木大輔

東京産科婦人科学会会誌 71 ( 2 ) 172 - 177 2022.04

Research paper (scientific journal), Joint Work, Corresponding author, Accepted

咽喉頭異常感症を訴える更年期女性に対する半夏厚朴湯の効果と検討

大野あゆみ, 横田めぐみ, 谷本慧子, 堀場裕子, 千代田達幸, 山上亘, 弟子丸亮太, 岩田卓, 阪埜浩司, 青木大輔

産婦人科漢方研究のあゆみ 38 15 - 20 2022.04

Research paper (scientific journal), Joint Work, Accepted

A retrospective study for investigating the outcomes of endometrial cancer treated with radiotherapy

Sakai K., Yamagami W., Machida H., Ebina Y., Kobayashi Y., Tabata T., Kaneuchi M., Nagase S., Enomoto T., Aoki D., Mikami M.

International Journal of Gynecology and Obstetrics (International Journal of Gynecology and Obstetrics) 156 ( 2 ) 262 - 269 2022.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 00207292

Objective: To clarify the role of radiotherapy for endometrial cancer. Methods: Data were analyzed for 39 247 patients with endometrial cancer registered with the Gynecologic Cancer Registry of the Japan Society of Obstetrics and Gynecology from 2004 to 2011. Results: The rates of 5-year overall survival (5y-OS) in the radiotherapy and surgery groups were 53.6% and 94.5% in stage I or II, and 15.5% and 67.5% in stage III or IV, respectively. The prognosis in the radiotherapy group was significantly poorer than that in the surgery group. In multivariate analysis, age, advanced stage, histological type, risk of recurrence, and initial radiotherapy were independent prognostic factors. The rates of 5y-OS with no adjuvant therapy, adjuvant chemotherapy, and adjuvant radiotherapy were 95.3%, 92.9%, and 87.1% for stage I or II, respectively, with significant differences among all groups (P < 0.001), and 60.0%, 70.4%, and 55.5% for stage III or IV, respectively, with significant differences of adjuvant chemotherapy with no adjuvant therapy (P < 0.001) and with adjuvant radiotherapy (P < 0.001). In multivariate analysis, age, advanced stage, histological type, lymphadenectomy, and adjuvant radiotherapy were independent prognostic factors. Conclusion: Patients treated with radiotherapy had a significantly poorer prognosis and the appropriate indication of radiotherapy for endometrial cancer requires further study.

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Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2018 and Annual Treatment Report for 2013

Nagase S, Ohta T, Takahashi F, Yamagami W, Yaegashi N; Board Members of the 2020 Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology. Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology

J Obstet Gynaecol Res (Journal of Obstetrics and Gynaecology Research) 48 ( 3 ) 541 - 552 2022.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 13418076

To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2018 and the Annual Treatment Report for 2013, on the outcomes of patients who started treatment in 2013. The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2018 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2013 was analyzed by using the Kaplan–Meier, log-rank, and Wilcoxson tests. Treatment was initiated in 2018 for 7304 patients with cervical cancer; 11 230 with endometrial cancer; 7031 with ovarian, tubal, and peritoneal cancer; 2072 with ovarian borderline tumors; and with the others (222 vulvar cancer, 159 vaginal cancer, 413 uterine sarcoma, 54 uterine adenosarcoma, and 135 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5-year survival rates of the patients with cervical cancer were 93.1%, 75.9%, 59.1%, and 31.2% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 94.1%, 89.2%, 73.6%, and 25.8% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 89.7%, 76.8%, 49.1%, and 32.4% for Stages I, II, III, and IV, respectively. The annual report is important to provide knowledge on gynecological malignancy trends in Japan.

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Association between hospital treatment volume and survival of women with gynecologic malignancy in Japan: a JSOG tumor registry-based data extraction study.

Machida H, Matsuo K, Oba K, Aoki D, Enomoto T, Okamoto A, Katabuchi H, Nagase S, Mandai M, Yaegashi N, Yamagami W, Mikami M

Journal of gynecologic oncology (Journal of Gynecologic Oncology) 33 ( 1 ) e3 2022.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 2005-0380

Objective: Associations between hospital treatment volume and survival outcomes for women with 3 types of gynecologic malignancies, and the trends and contributing factors for high-volume centers were examined. Methods: The Japan Society of Obstetrics and Gynecology tumor registry databased retrospective study examined 206,845 women with 80,741, 73,647, and 52,457 of endometrial, cervical, and ovarian tumor, respectively, who underwent primary treatment in Japan between 2004 and 2015. Associations between the annual treatment volume and overall survival (OS) for each tumor type were examined using a multivariable Cox proportional hazards model with restricted cubic splines. Institutions were categorized into 3 groups (low-, moderate-, and high-volume centers) based on hazard risks. Results: Hazard ratio (HR) for OS each the 3 tumors decreased with hospital treatment volume. The cut-off points of treatment volume were defined for high-(≥50, ≥51, and ≥27), moderate-(20–49, 20–50, and 17–26), and low-volume centers (≤19, ≤19, and ≤16) by cases/ year for endometrial, cervical, and ovarian tumors, respectively. Multivariate analysis revealed younger age, rare tumor histology, and initial surgical management as contributing factors for women at high-volume centers (all, p<0.001). The proportion of high-volume center treatments decreased, whereas low-volume center treatments increased (all p<0.001). Treatment at high-volume centers improved OS than that at other centers (adjusted HR [aHR]=0.83, 95% confidence interval [CI]=0.78–0.88; aHR=0.78, 95% CI=0.75–0.83; and aHR=0.90, 95% CI=0.86–0.95 for endometrial, cervical, and ovarian tumors). Conclusion: Hospital treatment volume impacted survival outcomes. Treatments at high-volume centers conferred survival benefits for women with gynecologic malignancies. The proportion of treatments at high-volume centers have been decreasing recently.

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Characteristics and clinicopathological features of patients with ovarian metastasis of endometrial cancer: a retrospective study

Matoba Y., Yamagami W., Chiyoda T., Kobayashi Y., Tominaga E., Banno K., Aoki D.

Journal of Obstetrics and Gynaecology (Journal of Obstetrics and Gynaecology) 42 ( 6 ) 2456 - 2462 2022

ISSN 01443615

There are no criteria for patient selection for ovarian-preserving surgery for endometrial cancer (EC). In this study, intraoperative findings of ovarian swelling (OvS) and the clinicopathological features of patients with EC with or without ovarian metastasis were analysed to identify risk factors for ovarian metastasis. Patients who underwent surgery for EC between 2012 and 2019 at our hospital were enrolled. In univariate analysis, all features were significantly higher in metastasis(+) cases. In multivariate analysis, lymphatic space invasion (LSI), cervical stromal involvement (CSI), peritoneal dissemination, and OvS were significant risk factors. In univariate analysis in stage I and II cases classified without adnexal pathological factors, type 2 histologic type, LSI, CSI, and OvS were significantly higher in metastasis(+) cases. LSI, CSI, and OvS were significant risk factors in multivariate analysis. Patients with type 1 histologic type EC without myometrial invasion ≥1/2, CSI and extrauterine lesions are appropriate for ovarian preservation. IMPACT STATEMENTWhat is already known on this subject? The number of premenopausal patients with endometrial cancer (EC) is increasing. Bilateral oophorectomy for EC results in surgical primary ovarian insufficiency, and thus, surgery with ovarian preservation has been examined. However, there are few reports on risk factors for ovarian metastasis of EC and no established criteria for patient background or pathological factors to determine suitability for ovarian preservation surgery. What do the results of this study add? In univariate analysis, all pathological findings suggestive of disease progression were more frequent in cases with ovarian metastases. In multivariate analysis, lymphatic space invasion (LSI), cervical stromal involvement (CSI), peritoneal dissemination, and ovarian swelling (OvS) were identified as significant risk factors for ovarian metastasis. In an analysis of stage I and II cases classified without adnexal pathological factors, type 2 histologic type, LSI, CSI, and OvS were significantly more common in cases with ovarian metastasis, and LSI, CSI, and OvS emerged as significant risk factors for ovarian metastasis in multivariate analysis. What are the implications of these findings for clinical practice and/or further research? Patients with type 1 histologic type EC without depth of myometrial invasion ≥1/2, CSI, or extrauterine lesions may be appropriate cases for ovarian preservation.

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Clinical Usefulness of Endometrial Cytology in Determining the Therapeutic Effect of Fertility Preserving Therapy

Yoshimura T., Yamagami W., Takahashi M., Hirano T., Sakai K., Makabe T., Chiyoda T., Banno K., Aoki D.

Acta Cytologica (Acta Cytologica) 66 ( 2 ) 1 - 8 2021.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 00015547

Introduction: The significance of endometrial cytology in determining the therapeutic efficacy of medroxyprogesterone acetate (MPA) therapy is unclear. This study aimed to evaluate the clinical usefulness of endometrial cytology during MPA therapy. Methods: Overall, 77 patients who underwent dilatation and curettage (D&C) to evaluate the therapeutic efficacy of MPA therapy at our hospital between January 2018 and December 2019 were retrospectively analyzed. The results of D&C, cytological evaluation, and other clinicopathological factors were analyzed based on the patients' medical records. Results: The sensitivity and specificity of cytology were 61% and 92%, respectively, with D&C being the gold standard for diagnosis in 142 D&C/cytological examinations. Among patients with no residual disease on D&C, 5 (4%) had suspicious or positive cytology. Although MPA therapy was terminated in 3 of these patients, only 1 patient had early recurrence, and the frequency of recurrence was similar to that of patients who showed negative results in both D&C and cytology. Discussion/Conclusion: The sensitivity of endometrial cytology in determining the therapeutic effect of MPA therapy is low, and we confirmed that the omission of D&C is unacceptable. Our findings also suggested that the addition of cytological evaluation to D&C during MPA therapy had a low clinical significance.

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Comparison of treatment outcomes of surgery and radiotherapy, including concurrent chemoradiotherapy for stage Ib2-IIb cervical adenocarcinoma patients: a retrospective study

Kondo E, Yoshida K, Tabata T, Kobayashi Y, Yamagami W, Ebina Y, Kaneuchi M, Nagase S, Machida H, Mikami M

J Gynecol Oncol (Journal of Gynecologic Oncology) 33 ( 2 ) e14 2021.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 20050380

Objective: The study compared the treatment outcomes of surgery versus radiotherapy, including concurrent chemoradiotherapy, in stage Ib2–IIb cervical adenocarcinoma patients in Japan. Methods: Of 57,470 patients diagnosed with stage I–IV cervical cancer from January 2001– December 2011, 1,932 patients with stage Ib2–IIb cervical adenocarcinoma were initially treated by surgery or radiotherapy. The primary endpoint was 5-year overall survival (OS) in all and 614 propensity score-matched (PSM) patients (307 per group). We compared OS and prognosis factors based on age, primary stage, and treatment arm. Results: In Japan, >80% (n=1,573) of stage Ib2–IIb cervical adenocarcinoma patients underwent surgery. The 5-year OS of surgery vs. radiotherapy groups were 82.1% (n=704) vs. 79.7% (n=59) (hazard ratio [HR]=1.494; 95% confidence interval [CI]=0.826–2.702; p=0.181) for stage Ib2, 76.6% (n=239) vs. 66.7% (n=54) (HR=1.679; 95% CI=0.986–2.858; p=0.053) for stage IIa, and 71.1% (n=630) vs. 58.9% (n=246) (HR=1.711; 95% CI=1.341–2.184; p<0.001) for stage IIb. In 614 PSM patients balanced for age and carcinoma stage Ib2–IIb, the 5-year OS of surgery vs. radiation groups was 73.0% (n=307) vs. 65.5% (n=307) (HR=1.394; 95% CI=1.044–1.860; p=0.023). In multivariable analysis, age (HR=1.293; 95% CI=1.045–1.601; p=0.018), treatment arm, radiotherapy (HR=1.556; 95% CI=1.253–1.933; p<0.001), and stage IIb (HR=1.783; 95% CI=1.443–2.203; p=0.018) were independent prognosis factors for 5-year OS in stage Ib2–IIb adenocarcinoma patients. Conclusion: Age (>65 years), treatment arm (radiotherapy), and stage IIb significantly affect OS in cervical adenocarcinoma patients. Surgery may be considered for <65-year-old patients with stage IIb adenocarcinoma.

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Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan

Ohta T., Nagase S., Okui Y., Enomoto T., Yamagami W., Mikami M., Tokunaga H., Ino K., Ushijima K., Shozu M., Tashiro H., Mandai M., Miyamoto S., Morishige K.I., Yoshida Y., Yoshino K., Saito T., Kobayashi E., Kobayashi H., Takekuma M., Terai Y., Fujii T., Kanao H., Aoki D., Katabuchi H., Yaegashi N.

International Journal of Clinical Oncology 26 ( 12 ) 2318 - 2330 2021.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 13419625

Objective: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. Methods: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients’ characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. Results: The median patient age was 44 (20–80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49–51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. Conclusion: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

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Hysteroscopic treatment assisted by photodynamic diagnosis for atypical polypoid adenomyoma: A report of two cases

Matoba Y., Banno K., Kobayashi Y., Yamagami W., Nakamura M., Kisu I., Aoki D.

Photodiagnosis and Photodynamic Therapy 36 102583 2021.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 15721000

Atypical polypoid adenomyoma (APA) is an intrauterine tumor for which hysteroscopic tumor resection allows for fertility preservation. Complete resection is important because of the high recurrence rate of APA, but is difficult due to the lack of characteristic hysteroscopic findings. We previously reported a case in which photodynamic diagnosis (PDD) was useful for detection of APA. Here, we report two additional cases of APA treated by hysteroscopic resection with PDD. The procedure was approved by the ethical committee. Case 1: A 35-year-old female who underwent hysteroscopic surgery for a submucosal tumor suspected to be APA with hypermenorrhea. Case 2: A 37-year-old female in whom hysteroscopic surgery was performed for a residual APA lesion after hormone therapy. In Case 1, PDD identified the tumor borders and this enabled as complete resection as possible. In Case 2, lesions could not be identified clearly under white light, but some areas were PDD-positive and were excised. Among 19 specimens from these two cases and the previously reported case, all PDD-positive specimens were pathologically diagnosed as APA. The sensitivity and specificity of PDD for APA were 76.9% and 100%, respectively. These results suggest that PDD can contribute to identification of APA.

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Clinicopathological characteristics and prognostic factors of ovarian granulosa cell tumors: A JSGO-JSOG joint study

Ebina Y., Yamagami W., Kobayashi Y., Tabata T., Kaneuchi M., Nagase S., Enomoto T., Mikami M.

Gynecologic Oncology 163 ( 2 ) 269 - 273 2021.11

Research paper (scientific journal), Joint Work, Accepted, ISSN 00908258

Objectives: The aim of this study was to elucidate the clinicopathological features of ovarian granulosa cell tumors (GCTs) and to identify the prognostic factors. Methods: The Japanese Society of Gynecologic Oncology (JSGO) conducted an observational retrospective cohort study of women with GCTs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology (JSOG) between 2002 and 2015. Clinicopathological features, including lymph node metastasis, were evaluated. In addition, we performed a prognostic analysis of patients between 2002 and 2011 for whom survival data were available. Kaplan–Meier and multivariate Cox proportional hazards analyses were performed. Results: We identified 1426 patients with GCTs. Of the 222 patients who underwent lymph node dissection, 10 (4.5%) had lymph node metastasis. The incidence of lymph node metastasis in patients with pT1, pT2, and pT3 was 2.1%, 13.3%, and 26.7%, respectively (p < 0.001). Prognostic analysis was performed on 674 patients. In the multivariate Cox regression analysis, residual disease after initial surgery (hazard ratio (HR) = 10.39, 95% confidence interval (CI) = 3.15–34.29) and lymph node metastasis (HR = 5.58, 95% CI = 1.62–19.19) were independent risk factors for cancer-specific survival. Conclusions: In the initial surgery for GCTs, lymph node dissection can be omitted if the operative finding is pT1. In cases of pT2 or higher, lymph node dissection should be considered. Debulking is critical for achieving no gross residual tumor at the end of the surgery.

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Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger

Makabe T., Yamagami W., Hirasawa A., Miyabe I., Wakatsuki T., Kikuchi M., Takahashi A., Noda J., Yamamoto G., Aoki D., Akagi K.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 26 ( 9 ) 1767 - 1774 2021.10

Research paper (scientific journal), Joint Work, Accepted, ISSN 13419625

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients. [Methods] Sixty-five patients aged 40 years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells. [Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3’ untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35. [Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40 years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.

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Prospective feasibility study of neoadjuvant dose-dense paclitaxel plus carboplatin with bevacizumab therapy followed by interval debulking surgery for advanced ovarian, fallopian tube, and primary peritoneal cancer patients

Iwasa-Inoue N., Nomura H., Kataoka F., Chiyoda T., Yoshihama T., Nanki Y., Sakai K., Kobayashi Y., Yamagami W., Morisada T., Hirasawa A., Aoki D.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 27 ( 2 ) 441 - 447 2021.10

Research paper (scientific journal), Joint Work, Accepted, ISSN 13419625

Background: This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian, fallopian tube, and primary peritoneal cancer patients in the neoadjuvant setting. Methods: Ovarian, fallopian tube or primary peritoneal cancer patients with stage III–IV disease received neoadjuvant chemotherapy (NAC) every 3 weeks consisting of paclitaxel (80 mg/m2) on days 1, 8, and 15; carboplatin (AUC 6.0 mg/mL × min.) on day 1; and bevacizumab (15 mg/kg) on day 1. Interval debulking surgery (IDS) was performed after 3 cycles of dose-dense TC-bevacizumab therapy. The primary endpoint was the rate of complete resection by IDS. Secondary endpoints were treatment completion rate, treatment exposure, response rate to NAC, adverse events, and perioperative complications. Results: Twenty-four patients were included in this study. The median age was 55.5 years (37–80 years), and most patients had high-grade serous carcinoma accounted (n = 18). IDS was performed in all patients with complete resection achieved in 75% (95% confidence interval: 57.7–92.3%). The lower limit exceeded the preset threshold rate of 55%. The response rate to NAC was 79%, and serum CA125 levels were in the normal range after NAC in 57% of patients. Grade 4 hematological toxicities and grade 3/4 non-hematological toxicities occurred in 29% and 17% of patients during NAC, respectively. Grade 3/4 perioperative complications were seen in 29% of patients, but no gastrointestinal perforations or treatment-related deaths occurred. Conclusions: Neoadjuvant dose-dense TC-bevacizumab therapy was well tolerated, and a satisfactory rate of complete resection by IDS was achieved.

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ARID1A mutation/ARID1A loss is associated with a high immunogenic profile in clear cell ovarian cancer

Kuroda Y., Chiyoda T., Kawaida M., Nakamura K., Aimono E., Yoshimura T., Takahashi M., Saotome K., Yoshihama T., Iwasa N., Sakai K., Yamagami W., Nishihara H., Aoki D.

Gynecologic Oncology 162 ( 3 ) 679 - 685 2021.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 00908258

Objectives: ARID1A mutation is frequently found in clear cell ovarian cancer (CCC) and endometrioid ovarian cancer (EC). Anti-PD-1 monotherapy has been found to have limited efficacy in epithelial ovarian cancer; however, anti-PD-1 therapy showed significant clinical benefit in some CCC. We sought to define the relationship of ARID1A mutation/ARID1A expression to the immunogenic profile of different histologic subtypes of ovarian cancer. Methods: We performed next-generation sequencing of 160 cancer-related genes. Also, we analyzed the immunohistochemical status of ARID1A, PD-L1, and CD8 with survival in different histologic subtypes of ovarian cancer in a total of 103 cases. Results: ARID1A mutation was found in 0% of the high-grade serous ovarian cancer (HGSC) (n = 36), 41.5% of the CCC (n = 41), 45.0% of the EC (n = 20), and 33.3% of the mucinous ovarian cancer (MC) (n = 6) cases. ARID1A loss was found in 19.4% of the HGSC, 75.6% of the CCC, 60.0% of the EC and 0% of the MC cases. ARID1A mutation was found to be associated with high PD-L1 (p < 0.001) or CD8 levels (p < 0.001) in CCC but not in other histologic subtypes. Meanwhile, ARID1A loss was associated with high PD-L1 or CD8 levels in CCC (p < 0.001) and HGSC (p < 0.001) but not in EC and MC. In addition, ARID1A mutation was associated with high tumor mutation burden in CCC (p = 0.006). Conclusions: ARID1A mutation/ARID1A expression is associated with immune microenvironmental factors in CCC but not in EC. ARID1A status can be a biomarker for selecting candidates for immune checkpoint blockade in CCC.

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当院で経験した子宮体部大細胞神経内分泌癌(LCNEC)の3例

平松真生子, 山上亘, 平野卓朗, 吉村拓馬, 千代田達幸, 西尾浩, 仲村勝, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 70 ( 3 ) 493 - 497 2021.07

Research paper (scientific journal), Joint Work, Accepted

Evaluating the importance of routine drainage following laparoscopic pelvic lymph node dissection for gynecological malignancies

Sakai K, Nakamura M, Yamagami W, Chiyoda T, Kobayashi Y, Nishio H, Hayashi S, Nomura H, Kataoka F, Tominaga E, Banno K, Aoki D

Int J Gynaecol Obstet 153 ( 3 ) 438 - 442 2021.06

Research paper (scientific journal), Joint Work, Accepted

Survey of the clinical practice pattern of using sentinel lymph node biopsy in patients with gynecological cancers in Japan: the Japan Society of Gynecologic Oncology study

Togami S., Kobayashi H., Niikura H., Shimada M., Susumu N., Tanaka T., Terai Y., Nagai T., Baba T., Yahata H., Yamagami W., Yamaguchi K., Yamashita T., Yaegashi N., Katabuchi H., Aoki D.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 26 ( 5 ) 971 - 979 2021.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 13419625

Background: Sentinel lymph node (SN) biopsy is essential for evaluating survival and minimal treatment-related morbidity associated with cervical, endometrial, and vulvar cancer in Japan. As such, our aim in this study was to evaluate the current practice pattern of using SN biopsy for cervical, endometrial, and vulvar cancer in Japan. Methods: We deployed a 47-question survey on the use of SN biopsy for gynecological cancers to 216 gynecological oncology training facilities. The survey included information on the use of SN biopsy for uterine (cervical and endometrial) and vulvar cancers; details on the type, timing, and concentration of tracers used; surgical approach used for SN biopsy; method of biopsy and pathological examination; and facilities’ experience with clinical research on SN biopsy. Results: The response rate was 84% (181/216), with 40 facilities (22%) having experience in SN biopsy for gynecological cancers, 34 (85%) for uterine cancers, and 15 (37%) for vulvar cancers. Radioisotope, indocyanine green (ICG), and blue dyes were available for the detection of uterine cancers in 21 (52%), 25 (62%), and 19 (48%) facilities and for vulvar cancers in 9 (22%), 3 (7%), and 11 (27%) facilities, respectively. Thirty-four facilities (85%) used intraoperative frozen section procedure for diagnosis when possible, with 24 (71%) of these facilities using 2-mm specimen cuts. Diagnosis included pathological examination (85%), immunostaining (57%), and one-step nucleic acid amplification (5%). Conclusion: Increasing research evidence, providing insurance coverage for radioisotope tracers, and increasing the availability of training are expected to increase the use of SN biopsy in Japan.

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Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2017 and annual treatment report for 2012

Nagase S., Ohta T., Takahashi F., Yaegashi N., Enomoto T., Katabuchi H., Kawana K., Kobayashi H., Kobayashi Y., Shozu M., Baba T., Morishige K., Yoshida Y., Yoshino K., Yamagami W., Tokunaga H.

Journal of Obstetrics and Gynaecology Research 47 ( 5 ) 1631 - 1642 2021.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 13418076

Aim: To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2017 and the Annual Treatment Report for 2012, on the outcomes of patients who started treatment in 2012. Methods: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2017 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial and ovarian cancer in 2012 was analyzed by using the Kaplan-Meier, log-rank and Wilcoxon tests. Results: Treatment was initiated in 2017 for 7710 patients with cervical cancer; 11 120 with endometrial cancer; 7029 with ovarian, tubal and peritoneal cancer; 2164 with ovarian borderline tumors; and with the others (213 vulvar cancer, 139 vaginal cancer, 366 uterine sarcoma, 41 uterine adenosarcoma and 131 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5-year survival rates of the patients with cervical cancer were 92.9, 75.5, 58.2 and 26.7% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 93.6, 85.6, 72.6 and 27.3% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 92.5, 83.5, 49.5 and 30.8% for stages I, II, III and IV, respectively. Conclusion: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

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The trend and outcome of postsurgical therapy for high-risk early-stage cervical cancer with lymph node metastasis in Japan: a report from the Japan Society of Gynecologic Oncology (JSGO) guidelines evaluation committee

Ikeda M, Shida M, Shigeta S, Nagase S, Takahashi F, Yamagami W, Katabuchi H, Yaegashi N, Aoki D, Mikami M

J Gynecol Oncol. (Journal of Gynecologic Oncology) 32 ( 3 ) e44 2021.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 20050380

Objective: The Japan Society of Gynecologic Oncology published the first guidelines for the treatment of cervical cancer in 2007. The aim of this research was to evaluate the influence of the introduction of the first guideline on clinical trends and outcomes of patients with early-stage cervical cancer who underwent surgery. Methods: This analysis included 9,756 patients who were diagnosed based on the pathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b and pN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Data of these patients were retrospectively reviewed, and clinicopathological trends were assessed. The influence of the introduction of the guideline on survival was determined by using a competing risk model. Results: For surgery cases, the estimated subdistribution hazard ratio (HR) by the competing risk model for the influence of the guideline adjusted for age, year of registration, pT classification, pN classification, histological type, and treatment methods was 1.024 (p=0.864). Following the introduction of the first guideline in 2007, for patients with lymph node metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereas that of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). For pN1 cases, the estimated subdistribution HR by the competing risk model for the influence of the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapy between CT and CCRT/RT (p=0.078). Conclusions: Survival of surgical cases was not improved by the introduction of the guidelines. It is necessary to consider more effective postsurgical therapy for high-risk early-stage cervical cancer.

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Atypical vessels in hysteroscopy: Usefulness in prediction of malignant diseases in patients treated with tamoxifen.

Oka E, Sakai K, Yamagami W, Hirano T, Makabe T, Yoshihama T, Chiyoda T, Kataoka F, Banno K, Aoki D

The journal of obstetrics and gynaecology research (Journal of Obstetrics and Gynaecology Research) 47 ( 4 ) 1510 - 1515 2021.04

Research paper (scientific journal), Accepted, ISSN 1341-8076

Aim: Tamoxifen (TAM) is widely used in adjuvant endocrine therapy for invasive breast cancer as a selective estrogen modulator, but this treatment has a risk of developing endometrial malignancy. However, hysteroscopic findings during or after TAM treatment are unclear. The aim of this study is to examine the association between hysteroscopic patterns and malignant histological findings during or after treatment with TAM. Methods: The subjects were patients who received TAM after surgery for breast cancer and underwent hysteroscopy at our institution from January 2016 to December 2019. Clinicopathological factors and hysteroscopic findings were collected from medical records and investigated retrospectively. Histologically, atypical endometrial hyperplasia, endometrial cancer, and carcinosarcoma were classified as malignant diseases. Results: A total of 26 patients were eligible for the study. Hysteroscopic findings included an irregular surface of the endometrium (n = 3, 11.5%), atypical vessels (n = 10, 38.5%), papillary structure (n = 3, 11.5%), and polypoid structure (n = 18, 69.2%). Histological examination revealed malignancy in six patients (23.0%). The percentage of atypical vessels in patients with malignancies was significantly higher than that in patients with a normal endometrium or benign lesion (100% vs. 20%, p = 0.0009). The sensitivity and specificity of atypical vessels in hysteroscopy for diagnosis of malignant diseases were 100% and 80%, respectively. Conclusions: Hysteroscopic findings of atypical vessels may be useful for prediction of malignant diseases in patients treated with TAM.

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術前診断は子宮体癌であったが、子宮摘出検体で絨毛癌の確定診断に至った1例

吉村拓馬, 山上亘, 川井田みほ, 平野卓朗, 坂井健良, 真壁健, 千代田達幸, 小林佑介, 片岡史夫, 阪埜浩司, 亀山香織, 青木大輔

日本婦人科病理学会誌 11 ( 1 ) 39 - 44 2021.03

Research paper (scientific journal), Joint Work, Accepted

Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome.

Yoshihama T, Hirasawa A, Sugano K, Yoshida T, Ushiama M, Ueki A, Akahane T, Nanki Y, Sakai K, Makabe T, Yamagami W, Susumu N, Kameyama K, Kosaki K, Aoki D

International cancer conference journal 10 ( 1 ) 6 - 10 2021.01

Research paper (scientific journal), Joint Work, Accepted

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A prospective cohort study on the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer

Nanki Y., Nomura H., Iwasa N., Saotome K., Dozen A., Yoshihama T., Hirano T., Hashimoto S., Chiyoda T., Yamagami W., Kataoka F., Aoki D.

Japanese journal of clinical oncology (Japanese Journal of Clinical Oncology) 51 ( 1 ) 54 - 59 2021.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 0368-2811

Objective: this prospective cohort study aimed to assess the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer. Methods: in this study, 40 Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer selected to receive bevacizumab with chemotherapy were enrolled. Patients in poor general condition were excluded. Each patient was monitored prospectively for adverse events, administration status, disease status and survival. Treatment was continued until intolerable adverse events or disease progression. The primary endpoint was safety. Results: bevacizumab plus platinum-based chemotherapy was performed for 30 patients (median cycle; 16.5), while bevacizumab plus non-platinum chemotherapy was performed for 10 patients (median cycle; 5.5). Among bevacizumab-related adverse events, hypertension occurred in 80% of patients, proteinuria in 83%, mucositis in 25%, bleeding in 20%, thromboembolic events in 5.0% and fistula in 2.5%. Gastrointestinal perforation or other life-threatening lethal adverse events were not observed. Response rate and median progression-free survival were 73% and 19.3 months for patients with bevacizumab plus platinum-based chemotherapy, and 30% and 3.9 months for patients with bevacizumab plus non-platinum chemotherapy, respectively. There was no correlation between response rate and occurrence of adverse events such as hypertension or proteinuria. Conclusion: bevacizumab combined with chemotherapy was tolerable and effective for Japanese patients with relapsed ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Hypertension and proteinuria are frequently occurred and managed properly for continuing treatment.

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Impact of lymphadenectomy on the treatment of endometrial cancer using data from the JSOG cancer registry.

Saotome K, Yamagami W, Machida H, Ebina Y, Kobayashi Y, Tabata T, Kaneuchi M, Nagase S, Enomoto T, Aoki D, Mikami M

Obstet Gynecol Sci. (Obstetrics and Gynecology Science) 64 ( 1 ) 80 - 89 2021.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 2287-8572

Objective Regional lymph node (LN) dissection is a standard surgical procedure for endometrial cancer, but there is currently no clear consensus on its therapeutic significance. We aimed to determine the impact of regional LN dissection on the outcome of endometrial cancer. Methods Study subjects comprised 36,813 patients who were registered in the gynecological tumor registry of the Japan Society of Obstetrics and Gynecology, had undergone initial surgery for endometrial cancer between 2004 and 2011, and whose clinicopathological factors and prognosis were appropriate for our investigation. The following clinicopathological factors were obtained from the registry: age, surgical stage classification, Union for International Cancer Control tumor, node, metastasis classification, histological type, histological differentiation, presence or absence of LN dissection, and postoperative treatment. We retrospectively analyzed the clinicopathological factors and therapeutic outcomes for patients with endometrial cancer. Results Analysis of all subjects showed that the group that underwent LN dissection had a significantly better overall survival than the group that did not undergo dissection. Analysis based on stage showed similar results across groups, except for stage Ia. Analysis based on stage and histological type showed similar results across groups, except for stage Ia endometrial carcinoma G1 or Ia G2. Multivariate analysis of prognostic factors indicated that LN dissection is an independent prognostic factor and that it has a greater impact on prognosis than adjuvant chemotherapy. Conclusion Despite the limitations of a retrospective study with some biases, the results suggest that LN dissection in endometrial cancer has a prognostic effect.

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子宮体癌への妊孕性温存療法後の帝王切開分娩後に発生したretained products of conceptionに対し子宮鏡下手術を施行した1例

真壁健, 山上亘, 平野卓朗, 坂井健良, 千代田達幸, 片岡史夫, 青木大輔

日本産科婦人科内視鏡学会雑誌 ((一社)日本産科婦人科内視鏡学会) 36 ( 2 ) 317 - 321 2020.12

ISSN 1884-9938

Epidemiological guideline influence on the therapeutic trend and patient outcome of uterine cervical cancer in Japan: Japan society of gynecologic oncology guideline evaluation committee project

Shigeta S., Shida M., Nagase S., Ikeda M., Takahashi F., Shibata T., Yamagami W., Katabuchi H., Yaegashi N., Aoki D., Mikami M.

Gynecologic Oncology 159 ( 1 ) 248 - 255 2020.10

Research paper (scientific journal), Joint Work, Accepted, ISSN 00908258

© 2020 Elsevier Inc. Objective: The Japan Society of Gynecologic Oncology published its first clinical guidelines for uterine cervical cancer in 2007 which has been revised twice in 2011 and 2017. The aim of this study was to investigate the influence of the first guideline publication on the therapeutic trend and patient outcome by analyzing uterine cervical cancer cases registered to the cancer registry organized by the Japan Society of Obstetrics and Gynecology. Methods: Data of uterine cervical cancer cases registered to the cancer registry from 2000 to 2012 were provided. Epidemiological and clinical trend were analyzed by the Chi-squared test with subsequent standardized residual analysis. Overall survival among the patients registered between 2004 and 2009 was analyzed using the Fine and Gray competing risk model. Results: 68,707 cases were registered during the study period. A trend analysis revealed that the guideline publication may have led to a decrease in neoadjuvant chemotherapy in parallel with an increase in radiation therapy mainly in stage II and III patients undergoing primary treatment. A survival analysis indicated that the introduction of the guideline may have improved overall survival among stage III uterine cervical cancer patients, even though a significant difference was not observed in all of the cases. Conclusions: This study demonstrated the potential influence of the guideline publication on the clinical trend and patient outcome. As this is the first assessment of the guideline for uterine cervical cancer in Japan, continuous evaluation is necessary to further comprehend the significance of this guideline.

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Evaluation of safety and diagnostic performance for flexible hysteroscopy in 1591 outpatient cases

Kobayashi Y., Tsuji K., Nakamura K., Nagai S., Takahashi T., Kobayashi A., Anko M., Hirano T., Watanabe K., Matoba Y., Kunitomi H., Adachi M., Yamagami W., Tominaga E., Banno K., Aoki D.

Japanese journal of clinical oncology 50 ( 10 ) 1157 - 1161 2020.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 03682811

© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com. BACKGROUND: To date, only few large studies are available concerning the safety and diagnostic concordance rates of outpatient flexible hysteroscopy. In our institution, outpatient hysteroscopy has been routinely and educationally applied Kosuke Tsuji to intrauterine lesions; thus, we retrospectively investigated the institution's outpatient flexible hysteroscopy cases. METHODS: A total of 1591 cases of outpatient flexible hysteroscopy conducted at our institution in 2012-2016 were retrospectively analyzed in terms of their clinical background, complications and diagnostic concordance rates. RESULTS: A total of 1591 cases included 546 cases of benign tumors (317 endometrial polyps, 168 myomas and 61 endometrial hyperplasia), 361 cases of atypical endometrial hyperplasia, 571 cases of endometrial cancers and 113 cases of other diagnoses. No major complications, including uterine perforation, occurred. However, one patient (0.06%) was diagnosed with septic shock caused by intrauterine infection that required prolonged immunosuppressive drug administration. Meanwhile, 335 patients diagnosed with benign tumors through outpatient flexible hysteroscopy underwent operation, and the diagnostic concordance rate was 74.6% (250 cases). However, this rate included 14 cases (4.2%) diagnosed with malignant tumors postoperatively. In preoperative endometrial cancer cases, the sensitivity and specificity for cervical invasion diagnosis were 39.4 and 90.8%, respectively. In addition, only one patient manifested positive ascites cytology intraoperatively, possibly caused by outpatient hysteroscopy. CONCLUSIONS: Outpatient flexible hysteroscopy is highly safe, with a slight negligible effect on ascites cytology. However, the diagnosis should be determined by multidisciplinary approaches, as hysteroscopy alone can miss malignancy.

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Uterine cervical cancer associated with obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome: A case report and review of the literature

Oka E., Chiyoda T., Iwata T., Yamagami W., Aoki D.

Gynecologic Oncology Reports 34 100645 2020.09

Research paper (scientific journal), Joint Work, Accepted

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Impact of the COVID-19 epidemic at a high-volume facility in gynecological oncology in Tokyo, Japan: A single-center experience

Nogami Y., Kobayashi Y., Tsuji K., Yokota M., Nishio H., Nakamura M., Yamagami W., Morisada T., Tominaga E., Banno K., Aoki D.

Journal of Ovarian Research 13 ( 1 ) 105 2020.09

Research paper (scientific journal), Joint Work, Accepted

© 2020 The Author(s). Background: The number of cases of novel coronavirus disease 2019 (COVID-19) in Japan have risen since the first case was reported on January 24, 2020, and 6225 infections have been reported as of June 30, 2020. On April 8, 2020, our hospital began screening patients via pre-admission reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and chest computed tomography (CT). Although no patients exhibited apparent pneumonia, treatment delay or changes in treatment plans were required for a few patients based on the results of screening tests. During an emerging infectious disease pandemic, the likelihood of being infected, as well as the disease itself, affects clinical decision making in several ways. We summarized and presented our experience. Case presentation: After the introduction of pre-admission screening, RT-PCR and CT were performed in 200 and 76 patients, respectively, as of June 30, 2020. The treatment of five patients, including two patients with cervical cancer, two patients with ovarian tumors, and one patient with ovarian cancer, was affected by the results. Two asymptomatic RT-PCR-positive patients did not develop COVID-19, but their treatment was delayed until the confirmation of negative results. The other three patients were RT-PCR-negative, but abnormal CT findings suggested the possibility of COVID-19, which delayed treatment. The patients receiving first-line preoperative chemotherapy for ovarian cancer had clinically evident exacerbations because of the treatment delay. Conclusion: During the epidemic phase of an emerging infectious disease, we found that COVID-19 has several other effects besides its incidence. The postponing treatment was the most common, therefore, treatment of ovarian tumors and ovarian cancer was considered to be the most likely to be affected among gynecological diseases. Protocols that allow for easy over-diagnosis can be disadvantageous, mainly because of treatment delays, and therefore, the protocols must be developed in light of the local infection situation.

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Clinical implications of next-generation sequencing-based panel tests for malignant ovarian tumors

Saotome K., Chiyoda T., Aimono E., Nakamura K., Tanishima S., Nohara S., Okada C., Hayashi H., Kuroda Y., Nomura H., Susumu N., Iwata T., Yamagami W., Kataoka F., Nishihara H., Aoki D.

Cancer Medicine 9 ( 20 ) 7407 - 7417 2020.08

Research paper (scientific journal), Joint Work, Accepted

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Precision medicine based on cancer genomics is being applied in clinical practice. However, patients do not always derive benefits from genomic testing. Here, we performed targeted amplicon exome sequencing-based panel tests, including 160 cancer-related genes (PleSSision-160), on 88 malignant ovarian tumors (high-grade serous carcinoma, 27; endometrioid carcinoma, 15; clear cell carcinoma, 30; mucinous carcinoma, 6; undifferentiated carcinoma, 4; and others, 6 (immature teratoma, 1; carcinosarcoma, 3; squamous cell carcinoma, 1; and mixed, 1)), to assess treatment strategies and useful biomarkers for malignant ovarian tumors. Overall, actionable gene variants were found in 90.9%, and druggable gene variants were found in 40.9% of the cases. Actionable BRCA1 and BRCA2 variants were found in 4.5% of each of the cases. ERBB2 amplification was found in 33.3% of mucinous carcinoma cases. Druggable hypermutation/ultramutation (tumor mutation burden ≥ 10 SNVs/Mbp) was found in 7.4% of high-grade serous carcinoma, 46.7% of endometrioid carcinoma, 10% of clear cell carcinoma, 0% of mucinous carcinoma, 25% of undifferentiated carcinoma, and 33.3% of the other cancer cases. Copy number alterations were significantly higher in high-grade serous carcinoma (P <.005) than in other histologic subtypes; some clear cell carcinoma showed high copy number alterations that were correlated with advanced stage (P <.05) and worse survival (P <.01). A high count of copy number alteration was associated with worse survival in all malignant ovarian tumors (P <.05). Our study shows that targeted agents can be detected in approximately 40% of malignant ovarian tumors via multigene panel testing, and copy number alteration count can be a useful marker to help assess risks in malignant ovarian tumor patients.

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A retrospective study for investigating the relationship between old and new staging systems with prognosis in ovarian cancer using gynecologic cancer registry of Japan Society of Obstetrics and Gynecology (JSOG): disparity between serous carcinoma and clear cell carcinoma

Yamagami W., Nagase S., Takahashi F., Ino K., Hachisuga T., Mikami M., Enomoto T., Katabuchi H., Aoki D.

Journal of gynecologic oncology 31 ( 4 ) e45 2020.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 20050380

Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology. OBJECTIVE: International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and peritoneal cancers was revised in 2014. The aim of this study is to clarify whether the revised FIGO2014 staging reflects the prognosis of patients with ovarian cancer by histological type in Japan. METHODS: We extracted 9,747 patients who were diagnosed with ovarian cancer since 2004 until 2008 and who could be classified into appropriate stages from the Gynecologic Cancer Registry of Japan Society of Obstetrics and Gynecology. These cases were analyzed after revision to FIGO2014 based on the pTNM classification. RESULTS: Among stage I, the 5-year overall survival rate (5y-OS) in FIGO2014 was 94.9% in stage IA, 92.3% in stage IC1, 86.1% in IC2, and 84.9% in IC3 with significant differences between stages IA and IC1 (p=0.012), IC1 and IC2 (p<0.001). There was a significant difference between stages IA and IC1 in clear cell and mucinous carcinoma but not in serous and endometrioid carcinoma. Among stage III, the 5y-OS was 75.6% in stage IIIA1, 68.9% in IIIA2, 58.6% in IIIB, and 44.4% in IIIC, with significant differences between stages IIIA2 and IIIB (p=0.009), IIIB and IIIC (p<0.001). Among stage IV, the 5y-OS was 43.1% in stage IVA* and 32.1% in IVB with a significant difference (p=0.002). CONCLUSION: The results suggest that changes in classification for stage III and stage IV are appropriate, but the subclassification for stage IC might be too detailed. There was a discrepancy of prognosis by histological type between stage IA and IC1.

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更年期症状を契機に診断された甲状腺機能異常の2例

平田桃, 横田めぐみ, 谷本慧子, 仲村勝, 山上亘, 森定徹, 片岡史夫, 岩田卓, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 69 ( 3 ) 575 - 580 2020.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 2186-0599

更年期障害を疑われ受診したが、甲状腺疾患を認めた2症例につき報告する。症例1:52歳、0妊0産。子宮頸部腺癌IB1期に対し広汎子宮全摘出術および両側付属器摘出術後である。冷え、関節痛を主訴に受診し、採血でTSH高値を認め精査にて潜在性甲状腺機能低下症の診断となった。症例2:65歳。1妊1産。ほてり、動悸を主訴に受診した。変動するTSHを認め、精査の結果、橋本病に合併した無痛性甲状腺炎の診断となった。甲状腺機能異常は亢進症/低下症ともに症状が更年期障害と類似していることから鑑別疾患の一つとして念頭に置くことが重要である。(著者抄録)

Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing

Nanki Y., Chiyoda T., Hirasawa A., Ookubo A., Itoh M., Ueno M., Akahane T., Kameyama K., Yamagami W., Kataoka F., Aoki D.

Scientific Reports 10 ( 1 ) 12581 2020.06

Research paper (scientific journal), Joint Work, Accepted

© 2020, The Author(s). The use of primary patient-derived organoids for drug sensitivity and resistance testing could play an important role in precision cancer medicine. We developed expandable ovarian cancer organoids in < 3 weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumours. Seven pairs of organoids (3 high-grade serous, 1 clear cell, 3 endometrioid) and original tumours shared 59.5% (36.1–73.1%) of the variants identified. Copy number variations were also similar among organoids and primary tumours. The organoid that harboured the BRCA1 pathogenic variant (p.L63*) showed a higher sensitivity to PARP inhibitor, olaparib, as well as to platinum drugs compared to the other organoids, whereas an organoid derived from clear cell ovarian cancer was resistant to conventional drugs for ovarian cancer, namely platinum drugs, paclitaxel, and olaparib. The overall success rate of primary organoid culture, including those of various histological subtypes, was 80% (28/35). Our data show that patient-derived organoids are suitable physiological ex vivo cancer models that can be used to screen effective personalised ovarian cancer drugs.

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Proposal of a two-tier system in grouping adenocarcinoma of the uterine cervix

Machida H., Matsuo K., Matsuzaki S., Yamagami W., Ebina Y., Kobayashi Y., Tabata T., Kaneuchi M., Nagase S., Enomoto T., Mikami M.

Cancers 12 ( 5 ) 1251 2020.05

Research paper (scientific journal), Joint Work, Accepted

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. (1) Background: This study examined the use of a two-tier system in grouping cervical adenocarcinoma for survival discrimination. (2) Methods: A nationwide retrospective observational cohort study was conducted using the Japan Society of Gynecologic Oncology tumor registry database from 2001 to 2015 (n = 86,754). Adenocarcinoma subtypes were grouped as type 1 (endocervical usual type and endometrioid) or type 2 (serous, clear, mucinous, and not otherwise specified), based on their relative survival compared with that of squamous tumors. (3) Results: The majority of the adenocarcinoma cases were type 1 (n = 10,121) versus type 2 tumors (n = 5157). Type 2 tumors were more likely to be old and have stage IV disease than those with squamous tumors. The number of type 2 tumors increased from 2001 to 2014 (106.1% relative increase, p < 0.001). Type 2 tumors had disproportionally poorer survival compared to other types (5-year survival rates: 68.9% for type 2, 75.4% for type 1, and 78.0% for squamous; p < 0.001). On multivariate analysis, type 2 tumors remained an independent prognostic factor associated with decreased survival compared with squamous (adjusted hazard ratio 2.00, 95% CI 1.84–2.15, p < 0.001). (4) Conclusion: The survival of cervical adenocarcinoma varies largely across the histological subtypes, and the proposed two-tier grouping may be useful for survival discrimination.

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骨転移を伴う再発子宮体癌に対して、ホルモン療法とデノスマブの併用療法が効果を示した1例

佐竹恵, 山上亘, 吉村拓馬, 平野卓朗, 真壁健, 坂井健良, 辻浩介, 小林佑介, 片岡史夫, 阪埜浩司, 青木大輔, 進伸幸

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 69 ( 2 ) 341 - 345 2020.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 2186-0599

再発子宮体癌の化学療法無奏効例では治療法の選択に苦慮することが多い。われわれは、酢酸メドロキシプロゲステロン(MPA)を用いたホルモン療法とデノスマブを併用することで、長期の病勢コントロールが可能だった症例を経験した。症例は46歳で、子宮体癌IIIA期の類内膜癌G1に対して、広汎子宮全摘出術、両側付属器摘出術、傍大動脈リンパ節郭清、大網部分切除術を施行後、術後療法にてパクリタキセル、カルボプラチン療法(TC療法)を施行した。その後、骨盤腹膜および腟断端への再発が出現し、ドセタキセル、シスプラチン療法(DP療法)を施行するも奏効せず、その後症状を伴って出現した骨転移に対して緩和的放射線照射を施行した。しかし、照射野内再発により疼痛が増悪したことから、MPAとデノスマブを併用した治療を開始したところ、20ヵ月間にわたり病変縮小、疼痛軽快が維持された。骨転移を伴う婦人科癌では、デノスマブによる良好な病勢コントロールが得られる可能性が示唆された。(著者抄録)

Identification of a novel uterine leiomyoma GWAS locus in a Japanese population.

Sakai K, Tanikawa C, Hirasawa A, Chiyoda T, Yamagami W, Kataoka F, Susumu N, Terao C, Kamatani Y, Takahashi A, Momozawa Y, Hirata M, Kubo M, Fuse N, Takai-Igarashi T, Shimizu A, Fukushima A, Kadota A, Arisawa K, Ikezaki H, Wakai K, Yamaji T, Sawada N, Iwasaki M, Tsugane S, Aoki D, Matsuda K.

Sci Rep 10 ( 1 ) 1197 2020.01

Research paper (scientific journal), Joint Work, Accepted

Japan Society of Gynecologic Oncology 2018 guidelines for treatment of uterine body neoplasms

Yamagami W., Mikami M., Nagase S., Tabata T., Kobayashi Y., Kaneuchi M., Kobayashi H., Yamada H., Hasegawa K., Fujiwara H., Katabuchi H., Aoki D.

Journal of gynecologic oncology 31 ( 1 ) e18 2020.01

Research paper (scientific journal), Joint Work, Accepted

The Fourth Edition of the Guidelines for Treatment of Uterine Body Neoplasm was published in 2018. These guidelines include 9 chapters: 1. Overview of the guidelines, 2. Initial treatment for endometrial cancer, 3. Postoperative adjuvant therapy for endometrial cancer, 4. Post-treatment surveillance for endometrial cancer, 5. Treatment for advanced or recurrent endometrial cancer, 6. Fertility-sparing therapy, 7. Treatment of uterine carcinosarcoma and uterine sarcoma, 8. Treatment of trophoblastic disease, 9. Document collection; and nine algorithms: 1-3. Initial treatment of endometrial cancer, 4. Postoperative adjuvant treatment for endometrial cancer, 5. Treatment of recurrent endometrial cancer, 6. Fertility-sparing therapy, 7. Treatment for uterine carcinosarcoma, 8. Treatment for uterine sarcoma, 9. Treatment for choriocarcinoma. Each chapter includes overviews and clinical questions, and recommendations, objectives, explanation, and references are provided for each clinical question. This revision has no major changes compared to the 3rd edition, but does have some differences: 1) an explanation of the recommendation decision process and conflict of interest considerations have been added in the overview, 2) nurses, pharmacists and patients participated in creation of the guidelines, in addition to physicians, 3) the approach to evidence collection is listed at the end of the guidelines, and 4) for clinical questions that lack evidence or clinical validation, the opinion of the Guidelines Committee is given as a "Recommendations for tomorrow".

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Evaluating the importance of routine drainage following laparoscopic pelvic lymph node dissection for gynecological malignancies

Sakai K., Nakamura M., Yamagami W., Chiyoda T., Kobayashi Y., Nishio H., Hayashi S., Nomura H., Kataoka F., Tominaga E., Banno K., Aoki D.

International Journal of Gynecology and Obstetrics (International Journal of Gynecology and Obstetrics) 2020

Research paper (scientific journal), Joint Work, ISSN 00207292

© 2020 International Federation of Gynecology and Obstetrics Objective: To determine the efficacy of drainage following pelvic lymph node (PLN) dissection, especially for cases involving laparoscopic surgery. Methods: In this retrospective study, 368 patients with malignant gynecological tumors who underwent systemic PLN dissection at Keio University Hospital between January 2012 and October 2018 were enrolled. Drainage tubes were placed in the retroperitoneal fossa in all patients. Medical records were used for data collection. Results: Laparoscopy was performed on 81 patients, and laparotomy was performed on 287 patients. In the laparoscopy group, tubes were removed 1 day post surgery. In the laparotomy group, tubes were removed 1 day post surgery in 167 patients and 4 days post surgery in 120 patients. Compared with the laparotomy group, we determined the laparoscopy group to have a significantly lower prevalence of lymphocyst (6.2% vs 20.2%, p = 0.002) but a similar prevalence of lymphedema (4.9% vs 5.2%), and symptomatic lymphocyst (2.5% vs 4.5%). The two laparotomy groups did not differ significantly with respect to the prevalence of lymphedema (4.8% vs 5.8%), lymphocyst (20.4% vs 20.0%), or symptomatic lymphocyst (4.2% vs 5.0%). Conclusion: Our results suggest that routine drainage should be omitted, especially in cases involving laparoscopic surgery.

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肥満が腹腔鏡下子宮体癌手術に及ぼす影響の検討

平野卓朗, 片岡史夫, 南木佳子, 吉浜智子, 真壁健, 坂井健良, 山上亘, 林茂徳, 野村弘行, 青木大輔

日本産科婦人科内視鏡学会雑誌 ((一社)日本産科婦人科内視鏡学会) 35 ( 2 ) 238 - 243 2019.12

ISSN 1884-9938

子宮体癌IA期に対し腹腔鏡下子宮体癌手術を行った150例を対象に、骨盤リンパ節郭清を施行した75例(A群)と未施行75例(B群)に分類した。検討項目は肥満症例(BMIが25以上)と非肥満症例における患者背景(年齢、未産婦数、糖尿病の頻度、高血圧の頻度、病理組織型、手術進行期、治療成績(手術時間、推定出血量、術後入院期間、リンパ節郭清群の摘出リンパ節個数)、術中・術後合併症、術後治療の有無、無増悪生存割合、全生存割合で、2群間で比較した。また、過去の開腹下子宮体癌手術49例の摘出リンパ節数を肥満症例と非肥満症例で比較した。その結果、A群において肥満症例が非肥満手術例に比べ手術時間、摘出リンパ節個数が有意に多かった。しかし、その他の項目に有意差はなく、肥満は腹腔鏡下子宮体癌手術に影響を及ぼさないと考えられた。

頸管浸潤を有する子宮体癌と鑑別困難な異型ポリープ状腺筋腫に対し子宮鏡下手術で妊孕性を温存し得た2例

早乙女啓子，平野卓朗，山上亘

日本子宮鏡研究会雑誌 1 ( 1 ) 15 - 17 2019.11

Research paper (scientific journal), Joint Work, Accepted

若年子宮体癌/子宮内膜異型増殖症に対する高用量黄体ホルモン療法の再発例の検討

北澤晶子, 山上亘, 真壁健, 平野卓朗, 坂井健良, 千代田達幸, 小林佑介, 野村弘行, 片岡史夫, 阪埜浩司, 進伸幸, 田中守, 青木大輔

関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会) 56 ( 4 ) 591 - 596 2019.11

Research paper (scientific journal), Joint Work, Accepted, ISSN 2186-0610

背景:若年の子宮体癌,子宮内膜異型増殖症(AEH)に対する妊孕性温存療法として,medroxyprogesterone acetate(MPA)を用いた高用量黄体ホルモン療法があるがその再発率の高さが問題となる.本研究ではMPA療法後の再発例の特徴を明らかにすることを目的とした.方法:1998〜2015年,当科で初回治療としてMPA療法を施行した182名を対象とし,倫理委員会の承認のもと,臨床病理学的因子や予後について後方視的に解析した.初回治療前の組織型はAEHで再発時AEHであった34例をA群,初回治療時EMG1で再発時AEHであった37例をB群,初回治療時EMG1で再発時EMG1であった27例をC群とした.結果:病変消失率はいずれも100%で,A群はB+C群に比較し再々発率が低く,再々発までの期間が長かった.妊娠例と非妊娠例では再々発率,再々発までの期間に有意差を認めなかった.結論:G1症例では再発時に進行する可能性もあり慎重な管理が求められる.治療後妊娠例は再発が少ないことから病変消失後の積極的な不妊治療がすすめられるが,分娩後も再発する可能性があり継続した管理が求められる.(著者抄録)

Intraoperative Capsule Rupture, Postoperative Chemotherapy, and Survival of Women With Stage I Epithelial Ovarian Cancer.

Matsuo K, Machida H, Yamagami W, Ebina Y, Kobayashi Y, Tabata T, Kaneuchi M, Nagase S, Enomoto T, Mikami M

Obstet Gynecol 134 ( 5 ) 1017 - 1026 2019.10

Research paper (scientific journal), Joint Work, Accepted, ISSN 00297844

© 2019 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. OBJECTIVE:To examine the incidence and prognostic effects of intraoperative capsule rupture and to assess the effectiveness of postoperative chemotherapy for intraoperative tumor rupture in apparent stage I epithelial ovarian cancer.METHODS:This is a society-based retrospective observational study in Japan that examined 15,163 women with stage IA-IC1 epithelial ovarian cancer who underwent primary surgical treatment between 2002 and 2015. Associations between intraoperative capsule rupture and cause-specific survival, and between postoperative chemotherapy and cause-specific survival among intraoperatively ruptured cases were examined by histology type (clear cell n=6,107, endometrioid n=3,910, mucinous n=3,382, and serous n=1,764).RESULTS:Clear cell histology had the highest risk of intraoperative capsule rupture (57.3%), followed by endometrioid (48.8%), serous (41.8%), and mucinous (32.0%) histologies (P<.001). On multivariable analysis, clear cell type exhibited the largest effect of intraoperative capsule rupture on cause-specific survival (adjusted hazard ratio [HR] 1.99, 95% CI 1.45-2.75), followed by serous (adjusted HR, 1.61, 95% CI 0.84-3.11), mucinous (adjusted HR 1.28, 95% CI 0.79-2.09), and endometrioid (adjusted HR, 1.14, 95% CI 0.64-2.01) tumors. Postoperative chemotherapy for intraoperatively ruptured cases did not improve cause-specific survival in any histologic types in multivariable analysis: clear cell, adjusted HR 0.86, 95% CI 0.56-1.31; serous, adjusted HR 1.08, 95% CI 0.42-2.74; mucinous, adjusted HR 1.11, 95% CI 0.55-2.27; and endometrioid, adjusted HR 2.81, 95% CI 0.85-9.30 (all, P>.05). In the cohort-level analysis of ruptured cases (n=7,227), postoperative chemotherapy use has significantly decreased in mucinous (16.3% relative decrease), endometrioid (13.1% relative decrease), and clear cell (9.3% relative decrease) (all, P<.05); but, the cohort-level 5-year cause-specific survival rate did not change over time (all, P>.05).CONCLUSION:Among apparent stage I epithelial ovarian cancer, the clear cell type possesses a disproportionally high risk of capsule rupture during adnexectomy and is associated with the most adverse effect on survival. A decrease in the use of postoperative chemotherapy for intraoperatively ruptured cases in Japan is likely the result of increasing awareness of the absence of survival benefits.

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子宮体癌の術前子宮鏡検査と腹腔細胞診

平野卓朗, 山上亘, 真壁健, 坂井健良, 二宮委美, 野村弘行, 片岡史夫, 平沢晃, 進伸幸, 青木大輔

日本臨床細胞学会雑誌 ((公社)日本臨床細胞学会) 58 ( 5 ) 196 - 201 2019.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 0387-1193

目的:子宮体癌の腹腔細胞診陽性の背景因子を明らかにし、子宮鏡検査が腹腔細胞診陽性に与える影響を検討することを目的とした。方法:当院にて子宮鏡検査を施行した後に、開腹もしくは腹腔鏡下に手術療法を施行した414例に関して、腹腔細胞診の結果と臨床病理学的因子との関連を後方視的に検討した。成績:414例中13例(3%)で腹腔細胞診陽性であった。腹腔細胞診陽性の有意なリスク因子として、単変量解析では類内膜癌Grade 3+特殊組織型、付属器転移、大網転移、腹膜播種が挙げられ(p<0.001)、多変量解析では類内膜癌Grade 3+特殊組織型(p=0.01)と大網転移が挙げられた(p<0.001)。またリスク因子別では大網転移陽性例で腹腔細胞診陽性例が最も多かった(7/10例、70%)。12例で腹腔細胞診陽性のリスク因子である類内膜癌Grade 3+特殊組織型もしくは大網転移を認めた。1例のみリスク因子を有さず腹腔細胞診が陽性となった症例を認め、多発子宮筋腫や子宮腺筋症によって、子宮鏡の検査時間や還流圧を通常より要したことが原因と推定されたが、術後再発を認めず経過している。結論:術前に子宮鏡検査を施行したにもかかわらず腹腔細胞診陽性となった例は少なく、そのほとんどが腹腔細胞診陽性のリスク因子を有する症例であったため、術前子宮鏡検査による腹腔細胞診への影響は軽微であろうと考えられた。(著者抄録)

Hysteroscopic Photodynamic Diagnosis Using 5-Aminolevulinic Acid: A High-Sensitivity Diagnostic Method for Uterine Endometrial Malignant Diseases.

Matoba Y, Banno K, Kisu I, Kobayashi Y, Tsuji K, Nagai S, Yamagami W, Nakamura M, Tominaga E, Kawaida M, Aoki D

J Minim Invasive Gynecol 27 ( 5 ) 1087 - 1094 2019.08

Research paper (scientific journal), Joint Work, Accepted

Genome-wide DNA methylation profile of early-onset endometrial cancer: Its correlation with genetic aberrations and comparison with late-onset endometrial cancer

Makabe T., Arai E., Hirano T., Ito N., Fukamachi Y., Takahashi Y., Hirasawa A., Yamagami W., Susumu N., Aoki D., Kanai Y.

Carcinogenesis 40 ( 5 ) 611 - 623 2019.07

Research paper (scientific journal), Accepted, ISSN 01433334

© 2019 The Author(s) 2019. Published by Oxford University Press. The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among 'transcriptional factors'. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.

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Trends and characteristics of epithelial ovarian cancer in Japan between 2002 and 2015: A JSGO–JSOG joint study

Machida H., Matsuo K., Yamagami W., Ebina Y., Kobayashi Y., Tabata T., Kanauchi M., Nagase S., Enomoto T., Mikami M.

Gynecologic Oncology 153 ( 3 ) 589 - 596 2019.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 00908258

© 2019 Elsevier Inc. Objective: To examine the trends of epithelial ovarian cancer histologic subtypes in Japan. Methods: A nationwide retrospective registry study was performed between 2002 and 2015 (Japan cohort, n = 48,640). Trends were also examined in The Surveillance, Epidemiology, and End Results Program (US cohort, n = 49,936). Time-specific proportional changes of four major histological subtypes (serous, clear cell, endometrioid, and mucinous) were examined. Results: The Japan cohort had more stage I disease (44.1% versus 24.9%) and less stage IV disease (10.0% versus 23.1%) than the US cohort (P < 0.001). The Japan cohort had more non-serous histology, particularly clear cell carcinoma (26.9% versus 8.4%), than the US cohort (P < 0.001). In the Japan cohort, proportion of clear cell carcinoma increased significantly from 23.4% to 29.1% between 2002 and 2010 (P < 0.001). Among stage I disease, clear cell carcinoma increased significantly in the Japan cohort from 32.9% to 40.3% between 2002 and 2015 (P < 0.001), whereas mucinous carcinoma increased significantly in the US cohort from 15.0% to 24.8% (P = 0.01). In 2015, clear cell carcinoma was most common among women aged <50 years from the Japan cohort (30.2%) versus serous carcinoma in the US cohort (50.8%). In the Japan cohort, the peak age was 75 years for serous, 57 for clear cell, and 45 for endometrioid carcinoma (P < 0.001). Mucinous carcinoma decreased until 43 years and increased again after age 73 years (P < 0.001). Conclusion: Characteristics of epithelial ovarian cancer in Japan are largely different compared to the US. In Japan, clear cell carcinoma has increased significantly in recent years to account for nearly 30% of epithelial ovarian cancer.

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術中に回収したフィルム破片が術後にトロッカーのソフトバルブであると判明した1例

小林佑介, 野村弘行, 仲村勝, 山上亘, 林茂徳, 森定徹, 片岡史夫, 冨永英一郎, 阪埜浩司, 青木大輔

東京産科婦人科学会会誌 68 ( 1 ) 69 - 72 2019.01

Research paper (scientific journal), Joint Work, Accepted

当院における静脈内平滑筋腫症(IVL)3症例の治療経験

桑名温子, 辻浩介, 小林佑介, 高橋孝幸, 安康真由香, 竹田貴, 國富晴子, 山上亘, 冨永英一郎, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 68 ( 1 ) 107 - 114 2019.01

Research paper (scientific journal), Joint Work, Accepted

Hysteroscopic Photodynamic Diagnosis Using 5-Aminolevulinic Acid: A High-Sensitivity Diagnostic Method for Uterine Endometrial Malignant Diseases

Matoba Y., Banno K., Kisu I., Kobayashi Y., Tsuji K., Nagai S., Yamagami W., Nakamura M., Tominaga E., Kawaida M., Aoki D.

Journal of Minimally Invasive Gynecology (Journal of Minimally Invasive Gynecology) 2019

ISSN 15534650

© 2019 AAGL Study Objective: To examine the diagnostic accuracy of hysteroscopic photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5ALA) in patients with endometrial cancer and premalignant atypical endometrial hyperplasia. Design: A single-center, open-label, exploratory intervention study. Setting: University Hospital in Japan. Patients: Thirty-four patients who underwent hysteroscopic resection in the Department of Obstetrics and Gynecology at Keio University Hospital. Interventions: Patients were given 5ALA orally approximately 3 hours before surgery and underwent observation of the uterine cavity and endometrial biopsy using 5ALA-PDD during hysteroscopic resection. Specimens were diagnosed histopathologically and the diagnostic sensitivity and specificity of hysteroscopic 5ALA-PDD for malignancy in the uterine cavity was determined. Red (R), blue (B), and green (G) intensity values were determined from PDD images, and the relationships of histopathological diagnosis with these values were used to develop a model for objective diagnosis of uterine malignancy. Measurements and Main Results: Three patients were excluded from the study because of failure of the endoscope system. A total of 113 specimens were collected endoscopically. The sensitivity and specificity of 5ALA-PDD for diagnosis of malignancy in the uterine cavity were 93.8% and 51.9%, respectively. The R/B ratio in imaging analysis was highest in malignant lesions, followed by benign lesions and normal uterine tissue, with significant differences among these groups (p <.05). The R/B and G/B ratios were used in a formula for prediction of malignancy based on logistic regression and the area under the receiver operating characteristic curve for this formula was 0.838. At a formula cutoff value of 0.220, the sensitivity and specificity for diagnosis of malignant disease were 90.6% and 65.4%, respectively. Conclusion: To our knowledge, this is the first study of the diagnostic accuracy of 5ALA-PDD for malignancies in the uterine cavity. Hysteroscopic 5ALA-PDD had higher sensitivity and identifiability of lesions. These findings suggest that hysteroscopic 5ALA-PDD may be useful for diagnosis of minute lesions.

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難治性骨盤内炎症性疾患を呈した好酸球性胃腸炎の1例

玉川真澄, 仙波宏史, 山上亘, 高柳裕子, 春日義史, 小林佑介, 冨永英一郎, 田中守, 青木大輔

関東連合産科婦人科学会誌 55 ( 4 ) 453 - 458 2018.11

Research paper (scientific journal), Joint Work

The contribution of pathogenic variants of cancer susceptibility genes for primary ovarian, fallopian tube, and peritoneal cancers in Japanese.

Hirasawa, Akira, Imoto, Issei, Takuya, Naruto, Akahane, Tomoko, Yamagami, Wataru, Nomura, Hiroyuki, Masuda, Kiyoshi, Susumu, Nobuyuki, Tsuda, Hitoshi, Aoki, Daisuke

CLINICAL CANCER RESEARCH 24 ( 15 ) 40 - 40 2018.08

Research paper (scientific journal), Joint Work, ISSN 1078-0432

GSTP1 rs1695 is associated with both hematological toxicity and prognosis of ovarian cancer treated with paclitaxel plus carboplatin combination chemotherapy: a comprehensive analysis using targeted resequencing of 100 pharmacogenes

Yoshihama T, Fukunaga K, Hirasawa A, Nomura H, Akahane T, Kataoka F, Yamagami W, Aoki D, Mushiroda T.

Oncotarget (Oncotarget) 9 ( 51 ) 29789 - 29800 2018.07

Research paper (scientific journal), Joint Work

© Yoshihama et al. Purpose: To find genetic variants that predicted toxicity and/or efficacy of paclitaxel plus carboplatin combination therapy (TC therapy). Patients and methods: In a retrospective case-control study, we analyzed 320 patients who had received TC therapy for gynecological cancers (ovarian, fallopian tube, peritoneal, uterine, and cervical cancers) and collected their germline DNA. We performed a comprehensive pharmacogenomic analysis using a targeted resequencing panel of 100 pharmacogenes. For 1,013 variants passing QC, case-control association studies and survival analyses were conducted. Results: GSTP1 rs1695 showed the smallest p value for hematotoxicity association, and the 105Ile wild type allele had a significantly higher risk of severe hematotoxicity (neutropenia G4, thrombocytopenia ≥ G3 and anemia ≥ G3) than the 105Val allele (p=0.00034, odds ratio=5.71 (95% confidence interval:1.77-18.44)). Next, we assessed 5-year progression-free survival (PFS) and overall survival (OS) in 56 advanced ovarian cancer patients who received tri-weekly TC as a first-line chemotherapy. Patients with the 105Ile/105Ile genotype showed significantly better PFS (p=0.00070) and OS (p=0.0012) than those with the 105Ile/105Val or 105Val/105Val genotype. Conclusion: Our study indicates that the GSTP1 rs1695 105Ile/105Ile genotype is associated with both severe hematotoxicity and high efficacy of TC therapy, identifying a possible prognostic indicator for patients with TC therapy.

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有害事象によりベバシズマブ投与を中止した婦人科がん症例の検討

大野あゆみ, 千代田達幸, 野村弘行, 同前愛, 早乙女啓子, 冨永英一郎, 岩田卓, 山上亘, 片岡史夫, 平沢晃, 田中守, 青木大輔

東京産科婦人科学会会誌 67 ( 3 ) 396 - 400 2018.07

Research paper (scientific journal), Joint Work, Accepted

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer

Saito, Toshiaki, Tabata, Tsutomu, Ikushima, Hitoshi, Yanai, Hiroyuki, Tashiro, Hironori, Niikura, Hitoshi, Minaguchi, Takeo, Muramatsu, Toshinari, Baba, Tsukasa, Yamagami, Wataru, Ariyoshi, Kazuya, Ushijima, Kimio, Mikami, Mikio, Nagase, Satoru, Kaneuchi, Masanori, Yaegashi, Nobuo, Udagawa, Yasuhiro, Katabuchi, Hidetaka

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY (International Journal of Clinical Oncology) 23 ( 2 ) 201 - 234 2018.04

Research paper (scientific journal), ISSN 1341-9625

© 2017, The Author(s). Background: Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese. Objective: The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan. Methods: The guideline was created according to the basic principles in creating the guidelines of JSGO. Results: The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget’s disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions. Conclusion: Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.

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Is repeated high-dose medroxyprogesterone acetate (MPA) therapy permissible for patients with early stage endometrial cancer or atypical endometrial hyperplasia who desire preserving fertility?

Yamagami, Wataru, Susumu, Nobuyuki, Makabe, Takeshi, Sakai, Kensuke, Nomura, Hiroyuki, Kataoka, Fumio, Hirasawa, Akira, Banno, Kouji, Aoki, Daisuke

JOURNAL OF GYNECOLOGIC ONCOLOGY (Journal of Gynecologic Oncology) 29 ( 2 ) 2018.03

Research paper (scientific journal), Joint Work, ISSN 2005-0380

© 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology. Objective: Reports on the repeated administration of medroxyprogesterone acetate (MPA) for intrauterine recurrence after fertility-preserving therapy for atypical endometrial hyperplasia (AEH) and early grade 1 endometrioid carcinoma (G1) are lacking. We aimed to clarify the outcomes of repeated MPA therapy in cases of intrauterine recurrence after fertility-preserving therapy with MPA against AEH/early G1. Methods: Patients with AEH or stage IA well-differentiated endometrioid carcinoma without myometrial invasion who underwent first-line MPA therapy for primary lesions or intrauterine recurrence were divided into initial treatment and repeated treatment groups (162 and 82 patients, respectively). Oral MPA administration (400−600 mg/day) was continued until pathological tumor disappearance. Data regarding clinicopathological factors, adverse events, and outcomes following the initial and repeated hormonal treatments were extracted from medical records and analyzed. Results: Complete response rates in the initial and repeated treatment groups were 98.5% and 96.4%, respectively, among patients with AEH, and were 90.7% and 98.1%, respectively, among patients with G1. In the initial treatment group, 5-year recurrence-free survival (RFS) rates were 53.7% and 33.2% among patients with AEH and G1, respectively. In the repeated treatment group, RFS rates were 14.0% and 11.2% among patients with AEH and G1, respectively. Among patients with AEH, the pregnancy rate tended to be lower in the repeated treatment group than in the initial treatment group (11.1% vs. 29.2%; p=0.107), while no significant group difference was observed among patients with G1 (20.8% vs. 22.7%). Conclusion: Repeated treatment is sufficiently effective for intrauterine recurrence after hormonal therapy for AEH/early G1.

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Quality indicators for cervical cancer care in Japan

Watanabe T., Mikami M., Katabuchi H., Kato S., Kaneuchi M., Takahashi M., Nakai H., Nagase S., Niikura H., Mandai M., Hirashima Y., Yanai H., Yamagami W., Kamitani S., Higashi T.

Journal of Gynecologic Oncology (Journal of Gynecologic Oncology) 29 ( 6 ) 2018

ISSN 20050380

© 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology. Objective: We aimed to propose a set of quality indicators (QIs) based on the clinical guidelines for cervical cancer treatment published by The Japan Society of Gynecologic Oncology, and to assess adherence to standard-of-care as an index of the quality of care for cervical cancer in Japan. Methods: A panel of clinical experts devised the QIs using a modified Delphi method. Adherence to each QI was evaluated using data from a hospital-based cancer registry of patients diagnosed in 2013, and linked with insurance claims data, between October 1, 2012, and December 31, 2014. All patients who received first-line treatment at the participating facility were included. The QI scores were communicated to participating hospitals, and additional data about the reasons for non-adherence were collected. Results: In total, 297 hospitals participated, and the care provided to 15,163 cervical cancer patients was examined using 10 measurable QIs. The adherence rate ranged from 50.0% for ‘cystoscope or proctoscope for stage IVA’ to 98.8% for ‘chemotherapy using platinum for stage IVB’. Despite the variation in care, hospitals reported clinically valid reasons for more than half of the non-adherent cases. Clinically valid reasons accounted for 75%, 90.9%, 73.4%, 44.5%, and 88.1% of presented non-adherent cases respectively. Conclusion: Our study revealed variations in pattern of care as well as an adherence to standards-of-care across Japan. Further assessment of the causes of variation and non-adherence can help identify areas where improvements are needed in patient care.

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Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

Hirasawa, Akira, Imoto, Issei, Naruto, Takuya, Akahane, Tomoko, Yamagami, Wataru, Nomura, Hiroyuki, Masuda, Kiyoshi, Susumu, Nobuyuki, Tsuda, Hitoshi, Aoki, Daisuke

ONCOTARGET 8 ( 68 ) 112258 - 112267 2017.12

Research paper (scientific journal), Joint Work, ISSN 1949-2553

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Assessing the effect of guideline introduction on clinical practice and outcome in patients with endometrial cancer in Japan: a project of the Japan Society of Gynecologic Oncology (JSGO) guideline evaluation committee

Shigeta, Shogo, Nagase, Satoru, Mikami, Mikio, Ikeda, Masae, Shida, Masako, Sakaguchi, Isao, Ushioda, Norichika, Takahashi, Fumiaki, Yamagami, Wataru, Yaegashi, Nobuo, Udagawa, Yasuhiro, Katabuchi, Hidetaka

JOURNAL OF GYNECOLOGIC ONCOLOGY 28 ( 6 ) 1019 - 1023 2017.11

Research paper (scientific journal), Joint Work, ISSN 2005-0380

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Efficacy and safety of dose-dense paclitaxel plus carboplatin as neoadjuvant chemotherapy for advanced ovarian, fallopian tube or peritoneal cancer

Yoshihama, Tomoko, Nomura, Hiroyuki, Iwasa, Naomi, Kataoka, Fumio, Hashimoto, Shiho, Nanki, Yoshiko, Hirano, Takuro, Makabe, Takeshi, Sakai, Kensuke, Yamagami, Wataru, Hirasawa, Akira, Aoki, Daisuke

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 47 ( 11 ) 1019 - 1023 2017.11

Research paper (scientific journal), Joint Work, ISSN 0368-2811

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A Comparison of Dye Versus Fluorescence Methods for Sentinel Lymph Node Mapping in Endometrial Cancer

Yamagami, Wataru, Susumu, Nobuyuki, Kataoka, Fumio, Makabe, Takeshi, Sakai, Kensuke, Ninomiya, Tomomi, Wada, Michiko, Nomura, Hiroyuki, Hirasawa, Akira, Banno, Kouji, Nakahara, Tadaki, Kameyama, Kaori, Aoki, Daisuke

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 27 ( 7 ) 1517 - 1524 2017.09

Research paper (scientific journal), ISSN 1048-891X

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Opportunistic bilateral salpingectomy during benign gynecological surgery for ovarian cancer prevention: a survey of Gynecologic Oncology Committee of Japan Society of Obstetrics and Gynecology

Mikami, Mikio, Nagase, Satoru, Yamagami, Wataru, Ushijma, Kimio, Tashiro, Hironori, Katabuchi, Hidetaka

JOURNAL OF GYNECOLOGIC ONCOLOGY 28 ( 4 ) 902 - 911 2017.07

Research paper (scientific journal), ISSN 2005-0380

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Clinical utility of a self-administered questionnaire for assessment of hereditary gynecologic cancer

Masuda, Kenta, Hirasawa, Akira, Irie-Kunitomi, Haruko, Akahane, Tomoko, Ueki, Arisa, Kobayashi, Yusuke, Yamagami, Wataru, Nomura, Hiroyuki, Kataoka, Fumio, Tominaga, Eiichiro, Banno, Kouji, Susumu, Nobuyuki, Aoki, Daisuke

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 47 ( 5 ) 401 - 406 2017.05

Research paper (scientific journal), ISSN 0368-2811

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UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan

Yoshihama, Tomoko, Hirasawa, Akira, Nomura, Hiroyuki, Akahane, Tomoko, Nanki, Yoshiko, Yamagami, Wataru, Kataoka, Fumio, Tominaga, Eiichiro, Susumu, Nobuyuki, Mushiroda, Taisei, Aoki, Daisuke

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 47 ( 2 ) 170 - 174 2017.03

Research paper (scientific journal), ISSN 0368-2811

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Carcinoma of the lower uterine segment diagnosed with Lynch syndrome based on MSH6 germline mutation: A case report

Adachi, Masataka, Banno, Kouji, Masuda, Kenta, Yanokura, Megumi, Iijima, Moito, Takeda, Takashi, Kunitomi, Haruko, Kobayashi, Yusuke, Yamagami, Wataru, Hirasawa, Akira, Kameyama, Kaori, Sugano, Kokichi, Aoki, Daisuke

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 ( 2 ) 416 - 420 2017.03

Research paper (scientific journal), ISSN 1341-8076

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Clinical statistics of gynecologic cancers in Japan

Yamagami, Wataru, Nagase, Satoru, Takahashi, Fumiaki, Ino, Kazuhiko, Hachisuga, Toru, Aoki, Daisuke, Katabuchi, Hidetaka

JOURNAL OF GYNECOLOGIC ONCOLOGY 28 ( 2 ) 1517 - 1524 2017.03

Research paper (scientific journal), Joint Work, ISSN 2005-0380

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Carcinoma of the lower uterine segment diagnosed with Lynch syndrome based on MSH6 germline mutation: A case report.

Adachi M, Banno K, Masuda K, Yanokura M, Iijima M, Takeda T, Kunitomi H, Kobayashi Y, Yamagami W, Hirasawa A, Kameyama K, Sugano K, Aoki D.

J Obstet Gynaecol Res 43 ( 2 ) 416 - 420 2017.02

Research paper (scientific journal)

Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis

Takeda, Takashi, Banno, Kouji, Yanokura, Megumi, Adachi, Masataka, Iijima, Moito, Kunitomi, Haruko, Nakamura, Kanako, Iida, Miho, Nogami, Yuya, Umene, Kiyoko, Masuda, Kenta, Kobayashi, Yusuke, Yamagami, Wataru, Hirasawa, Akira, Tominaga, Eiichiro, Susumu, Nobuyuki, Aoki, Daisuke

GENES 7 ( 10 ) 1751 - 1758 2016.10

Research paper (scientific journal), ISSN 2073-4425

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Retrospective Analysis on the Feasibility and Efficacy of Docetaxel-Cisplatin Therapy for Recurrent Endometrial Cancer

Ninomiya, Tomomi, Yamagami, Wataru, Susumu, Nobuyuki, Makabe, Takeshi, Sakai, Kensuke, Wada, Michiko, Takigawa, Aya, Chiyoda, Tatsuyuki, Nomura, Hiroyuki, Kataoka, Fumio, Hirasawa, Akira, Banno, Kouji, Aoki, Daisuke

ANTICANCER RESEARCH 36 ( 4 ) 1751 - 1758 2016.05

Research paper (scientific journal), ISSN 0250-7005

Practice patterns of adjuvant therapy for intermediate/high recurrence risk cervical cancer patients in Japan

Ikeda, Yuji, Furusawa, Akiko, Kitagawa, Ryo, Tokinaga, Aya, Ito, Fuminori, Ukita, Masayo, Nomura, Hidetaka, Yamagami, Wataru, Tanabe, Hiroshi, Mikami, Mikio, Takeshima, Nobuhiro, Yaegashi, Nobuo

JOURNAL OF GYNECOLOGIC ONCOLOGY 27 ( 3 ) 400 - 404 2016.05

Research paper (scientific journal), ISSN 2005-0380

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The importance of para-aortic lymph nodes in sentinel lymph node mapping for endometrial cancer by using hysteroscopic radio-isotope tracer injection combined with subserosal dye injection: Prospective study

Kataoka, Fumio, Susumu, Nobuyuki, Yamagami, Wataru, Kuwahata, Michiko, Takigawa, Aya, Nomura, Hiroyuki, Takeuchi, Hiroya, Nakahara, Tadaki, Kameyama, Kaori, Aoki, Daisuke

GYNECOLOGIC ONCOLOGY 140 ( 3 ) 400 - 404 2016.03

Research paper (scientific journal), ISSN 0090-8258

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Intravenous low-grade endometrial stromal sarcoma with intracardiac extension: A CASE OF inaccurate tumor location on contrast-enhanced computed tomography.

Nogami Y, Yamagami W, Maki J, Banno K, Susumu N, Tomita K, Matsubara K, Obara H, Kitagawa Y, Aoki D.

Mol Clin Oncol 4 ( 2 ) 179 - 182 2016.02

Research paper (scientific journal), Joint Work

Factors affecting pregnancy outcomes in young women treated with fertility-preserving therapy for well-differentiated endometrial cancer or atypical endometrial hyperplasia

Inoue, Osamu, Hamatani, Toshio, Susumu, Nobuyuki, Yamagami, Wataru, Ogawa, Seiji, Takemoto, Takashi, Hirasawa, Akira, Banno, Kouji, Kuji, Naoaki, Tanaka, Mamoru, Aoki, Daisuke

REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY 14 1861 - 1869 2016.01

Research paper (scientific journal), ISSN 1477-7827

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婦人科悪性腫瘍に脳梗塞を合併したTrousseau症候群5例の検討

沖山愛，山上亘，坂井健良，真壁健，二宮委美，野村弘行，片岡史夫，平沢晃，阪埜浩司，進伸幸，青木大輔

日本婦人科腫瘍学会雑誌 34 ( 4 ) 620 - 625 2016

Research paper (scientific journal)

子宮体部・卵巣同時発生重複癌40症例の臨床病理学的検討

小笠原淳, 小林佑介, 野村弘行, 山上亘, 片岡史夫, 平沢晃, 冨永英一郎, 鈴木淳, 阪埜浩司, 進伸幸, 田中守, 青木大輔

東京産科婦人科学会会誌 65 ( 3 ) 436 - 439 2016

Research paper (scientific journal), Joint Work

卵巣明細胞腺癌合併妊娠に対して待機的治療を行った2例

高橋孝幸, 野村弘行, 二宮委美, 岩佐尚美, 中平直希, 松本直, 山上亘, 片岡史夫, 宮越敬, 田中守, 青木大輔

関東連合産科婦人科学会誌 53 ( 4 ) 633 - 639 2016

Research paper (scientific journal), Joint Work

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology

Yamagami, Wataru, Aoki, Daisuke

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 41 ( 12 ) 1861 - 1869 2015.12

Research paper (scientific journal), ISSN 1341-8076

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Intratumoral CD8(+) Lymphocyte Infiltration as a Prognostic Factor and Its Relationship With Cyclooxygenase 2 Expression and Microsatellite Instability in Endometrial Cancer

Suemori, Tomohiro, Susumu, Nobuyuki, Iwata, Takashi, Banno, Kouji, Yamagami, Wataru, Hirasawa, Akira, Sugano, Kokichi, Matsumoto, Eri, Aoki, Daisuke

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 25 ( 7 ) 1165 - 1172 2015.10

Research paper (scientific journal), ISSN 1048-891X

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Polymorphisms of estrogen metabolism-related genes ESR1, UGT2B17, and UGT1A1 are not associated with osteoporosis in surgically menopausal Japanese women

Yokota M, Hirasawa A, Makita K, Akahane T, Sakai K, Makabe T, Horiba Y, Yamagami W, Ogawa M, Iwata T, Yanamoto S, Deshimaru R, Banno K, Susumu N, Aoki D

Prz Menopauzalny 14 ( 3 ) 161 - 167 2015.09

Joint Work

Hysteroscopic transcervical resection is useful to diagnose myometrial invasion in atypical polypoid adenomyoma coexisting with atypical endometrial hyperplasia or endometrial cancer with suspicious myometrial invasion

Yamagami, Wataru, Susumu, Nobuyuki, Ninomiya, Tomomi, Nakadaira, Naoki, Iwasa, Naomi, Kuwahata, Michiko, Nomura, Hiroyuki, Kataoka, Fumio, Banno, Kouji, Aoki, Daisuke

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 41 ( 5 ) 768 - 775 2015.05

Research paper (scientific journal), ISSN 1341-8076

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Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers

Kobayashi Y, Nakamura K, Nomura H, Banno K, Irie H, Adachi M, Iida M, Umene K, Nogami Y, Masuda K, Kisu I, Ueki A, Yamagami W, Kataoka F, Hirasawa A, Tominaga E, Susumu N, Aoki D

Int J Gynecol Cancer 25 ( 3 ) 440 - 446 2015.03

Research paper (scientific journal), Joint Work

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology

Yamagami, Wataru, Aoki, Daisuke

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 41 ( 2 ) 167 - 177 2015.03

Research paper (scientific journal), ISSN 1341-8076

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Osteoporosis is less frequent in endometrial cancer survivors with hypertriglyceridemia

Hirasawa, Akira, Makita, Kazuya, Akahane, Tomoko, Yamagami, Wataru, Makabe, Takeshi, Yokota, Megumi, Horiba, Yuko, Ogawa, Mariko, Yanamoto, Shigehisa, Deshimaru, Rhota, Tominaga, Eiichiro, Banno, Kouji, Susumu, Nobuyuki, Aoki, Daisuke

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 45 ( 1 ) 127 - 131 2015.01

Research paper (scientific journal), Joint Work, ISSN 0368-2811

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Effectiveness of third-line chemotherapy in recurrent ovarian cancer patients.

Yoshihama T, Chiyoda T, Kataoka F, Nomura H, Iguchi Y, Hashimoto S, Yamagami W, Tominaga E, Susumu N, Tsuda H, Aoki D

Eur J Gynaecol Oncol 36 ( 4 ) 424 - 427 2015

Research paper (scientific journal), Joint Work

Pathological factors associated with omental metastases in endometrial cancer.

Sakai K, Yamagami W, Susumu N, Nomura H, Kataoka F, Banno K, Tsuda H, Aoki D

Eur J Gynaecol Oncol 36 ( 4 ) 397 - 401 2015

Joint Work

血栓予防の目的で抗凝固療法を施行した婦人科手術症例の術後出血に関する検討

小林新, 冨永英一郎, 宮内安澄, 山上亘, 片岡史夫, 鈴木淳, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 64 ( 1 ) 11 - 15 2015

Research paper (scientific journal), Joint Work

Simultaneous Analysis of the Gene Expression Profiles of Cancer and Stromal Cells in Endometrial Cancer

Iguchi, Yoko, Ito, Yoichi M., Kataoka, Fumio, Nomura, Hiroyuki, Tanaka, Hideo, Chiyoda, Tatsuyuki, Hashimoto, Shiho, Nishimura, Sadako, Takano, Masashi, Yamagami, Wataru, Susumu, Nobuyuki, Aoki, Daisuke, Tsuda, Hiroshi

GENES CHROMOSOMES & CANCER 53 ( 9 ) 725 - 737 2014.09

Research paper (scientific journal), Joint Work, ISSN 1045-2257

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Clinicopathological study on para-aortic lymph node metastasis without pelvic lymph node metastasis in endometrial cancer

Tomisato, Shoko, Yamagami, Wataru, Susumu, Nobuyuki, Kuwahata, Michiko, Takigawa, Aya, Nomura, Hiroyuki, Kataoka, Fumio, Hirasawa, Akira, Banno, Kouji, Aoki, Daisuke

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 40 ( 6 ) 1733 - 1739 2014.06

Research paper (scientific journal), ISSN 1341-8076

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Hypertriglyceridemia is Frequent in Endometrial Cancer Survivors

Hirasawa, Akira, Makita, Kazuya, Akahane, Tomoko, Yokota, Megumi, Yamagami, Wataru, Banno, Kouji, Susumu, Nobuyuki, Aoki, Daisuke

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 43 ( 11 ) 1087 - 1092 2013.11

Research paper (scientific journal), Joint Work, ISSN 0368-2811

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Candidate Biomarkers for Genetic and Clinicopathological Diagnosis of Endometrial Cancer

Banno, Kouji, Nogami, Yuya, Kisu, Iori, Yanokura, Megumi, Umene, Kiyoko, Masuda, Kenta, Kobayashi, Yusuke, Yamagami, Wataru, Susumu, Nobuyuki, Aoki, Daisuke

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 14 ( 6 ) 12123 - 12137 2013.06

Research paper (scientific journal), Joint Work, ISSN 1422-0067

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Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer: comparison of magnetic resonance imaging and frozen sections

Kisu, Iori, Banno, Kouji, Lin, Li-Yu, Ueno, Akihisa, Abe, Takayuki, Kouyama, Keisuke, Okuda, Shigeo, Masugi, Yohei, Umene, Kiyoko, Nogami, Yuya, Tsuji, Kosuke, Masuda, Kenta, Ueki, Arisa, Kobayashi, Yusuke, Yamagami, Wataru, Susumu, Nobuyuki, Aoki, Daisuke

ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA 92 ( 5 ) 525 - 535 2013.05

Research paper (scientific journal), Joint Work, ISSN 0001-6349

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Gene scoring model to predict recurrence in low- and intermediate-risk uterine endometrial cancer: Establishment of uterine print

Chiyoda, Tatsuyuki, Ito, Yoichi M., Kataoka, Fumio, Yamagami, Wataru, Nomura, Hiroyuki, Tsuda, Hiroshi, Tanaka, Hideo, Takano, Masashi, Nishimura, Sadako, Iguchi, Yoko, Hashimoto, Shiho, Yoshihama, Tomoko, Susumu, Nobuyuki, Aoki, Daisuke

JOURNAL OF CLINICAL ONCOLOGY 31 ( 15 ) 1733 - 1739 2013.05

Research paper (scientific journal), ISSN 0732-183X

MicroRNAs in endometrial cancer

Banno, Kouji, Yanokura, Megumi, Kisu, Iori, Yamagami, Wataru, Susumu, Nobuyuki, Aoki, Daisuke

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 18 ( 2 ) 186 - 192 2013.04

Research paper (scientific journal), Joint Work, ISSN 1341-9625

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The Origin of Stroma Surrounding Epithelial Ovarian Cancer Cells

Akahane, Tomoko, Hirasawa, Akira, Tsuda, Hiroshi, Kataoka, Fumio, Nishimura, Sadako, Tanaka, Hideo, Tominaga, Eiichiro, Nomura, Hiroyuki, Chiyoda, Tatsuyuki, Iguchi, Yoko, Yamagami, Wataru, Susumu, Nobuyuki, Aoki, Daisuke

INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY 32 ( 1 ) 26 - 30 2013.01

Research paper (scientific journal), Joint Work, ISSN 0277-1691

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経腟Hybrid NOTESにより婦人科・外科2領域同時手術を施行した1例

片岡史夫, 野村弘行, 有馬宏和, 野上侑哉, 西尾浩, 山上亘, 藤井多久磨, 青木大輔

東京産科婦人科学会会誌 62 ( 1 ) 144 - 148 2013

Research paper (scientific journal), Joint Work

転移性脳腫瘍による動眼神経麻痺が契機となって発見された子宮体癌の1例

大谷利光，冨永英一郎, 辻浩介, 山上亘, 鈴木淳, 阪埜浩司, 進伸幸, 青木大輔, 吉村泰典

東京産科婦人科学会会誌 62 ( 1 ) 91 - 95 2013

Research paper (scientific journal), Joint Work

Osler-Weber-Rendu病を合併した子宮体癌の1例

竹田貴, 山上亘, 井口蓉子, 岩田卓, 冨永英一郎, 阪埜浩司, 進伸幸, 青木大輔, 吉村泰典

東京産科婦人科学会会誌 62 ( 3 ) 372 - 376 2013

Research paper (scientific journal), Joint Work

Association of epigenetic inactivation of the WRN gene with anticancer drug sensitivity in cervical cancer cells.

Masuda K, Banno K, Yanokura M, Tsuji K, Kobayashi Y, Kisu I, Ueki A, Yamagami W, Nomura H, Tominaga E, Susumu N, Aoki D

Oncol Rep 28 ( 4 ) 1146 - 1152 2012.10

Research paper (scientific journal), Joint Work

Association of epigenetic inactivation of the WRN gene with anticancer drug sensitivity in cervical cancer cells

Masuda, Kenta, Banno, Kouji, Yanokura, Megumi, Tsuji, Kosuke, Kobayashi, Yusuke, Kisu, Iori, Ueki, Arisa, Yamagami, Wataru, Nomura, Hiroyuki, Tominaga, Eiichiro, Susumu, Nobuyuki, Aoki, Daisuke

ONCOLOGY REPORTS 28 ( 4 ) 1146 - 1152 2012.10

Research paper (scientific journal), Joint Work, ISSN 1021-335X

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[A treatment strategy for endometrial cancer].

Susumu N, Yamagami W, Nomura H, Banno K, Aoki D.

日本臨床 70 ( Suppl 4 ) 381 - 387 2012.06

Research paper (scientific journal), Joint Work

Retrospective study comparing irinotecan and pegylated liposomal doxorubicin in treatment of recurrent platinum-refractory/resistant epithelial ovarian cancer.

Nomura H, Tsuda H, Kataoka F, Chiyoda T, Yamagami W, Tominaga E, Susumu N, Aoki D.

Eur J Gynaecol Oncol 33 ( 1 ) 86 - 89 2012

Research paper (scientific journal), Joint Work

Effective multidisciplinary treatment for ovarian granulosa cell tumor with multiple metastases--a case report.

Yamagami W, Ooki S, Semba H, Ninomiya T, Hayashi S, Yamashita H, Arai H

Eur J Gynaecol Oncol. 33 ( 4 ) 370 - 375 2012

Research paper (scientific journal)

子宮体癌に対する高用量黄体ホルモン療法後の経過観察中に血栓塞栓症を発症した2例

日原華子, 山上亘, 進伸幸, 小林佑介, 田中京子, 阪埜浩司, 藤井多久磨, 青木大輔, 吉村泰典

東京産科婦人科学会会誌 61 ( 2 ) 260 - 264 2012

Research paper (scientific journal), Joint Work

Immunofluorescence-Detected Infiltration of CD4(+)FOXP3(+) Regulatory T Cells is Relevant to the Prognosis of Patients With Endometrial Cancer

Yamagami, Wataru, Susumu, Nobuyuki, Tanaka, Hideo, Hirasawa, Akira, Banno, Kouji, Suzuki, Nao, Tsuda, Hiroshi, Tsukazaki, Katsumi, Aoki, Daisuke

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 21 ( 9 ) 1628 - 1634 2011.12

Research paper (scientific journal), ISSN 1048-891X

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卵巣腫瘍との鑑別が困難であった小腸原発消化管間葉系腫瘍(GIST)の1例

二宮委美, 山上亘, 大木慎也, 佐藤真美, 仙波宏史, 福武麻里絵, 近藤亜未, 林茂徳, 上野和典, 山下博, 高橋純, 新井宏治

東京産科婦人科学会会誌 60 ( 2 ) 369 - 372 2011

Research paper (scientific journal), Joint Work

Antitumor effects of human monoclonal antibody HMMC-1 on lymph node metastasis of endometrial cancer in a mouse model

Suzuki, Atsushi, Susumu, Nobuyoshi, Suzuki, Nao, Nomura, Hiroyuki, Kataoka, Fumio, Yamagami, Wataru, Kataoka, Shiro, Ishida, Isao, Aoki, Daisuke

GYNECOLOGIC ONCOLOGY 104 ( 3 ) S28 - S28 2007.03

Research paper (scientific journal), ISSN 0090-8258

FOXP3(+) regulatory T cells affect the development and progression of hepatocarcinogenesis

Kobayashi, Noritoshi, Hiraoka, Nobuyoshi, Yamagami, Wataru, Ojima, Hidenori, Kanai, Yae, Kosuge, Tomoo, Nakajima, Atsushi, Hirohashi, Setsuo

CLINICAL CANCER RESEARCH 13 ( 3 ) 902 - 911 2007.02

Research paper (scientific journal), ISSN 1078-0432

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Use of the collagen gel droplet embedded drug sensitivity test to determine drug sensitivity against ovarian mature cystic teratoma with malignant transformation to adenocarcinoma: A case report

Yamagami, Wataru, Banno, Kouji, Kawaguchi, Makiko, Yanokura, Megumi, Kuwabara, Yoshiko, Hirao, Nobumaru, Susumu, Nobuyuki, Tsukazaki, Katsumi, Aoki, Daisuke

CHEMOTHERAPY 53 ( 2 ) 137 - 141 2007

Research paper (scientific journal), ISSN 0009-3157

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Clinical characteristics of prognostic factors in poorly differentiated (G3) endometrioid adenocarcinoma in Japan

Kuwabara Y, Susumu N, Banno K, Hirao T, Kawaguchi M, Yamagami W, Suzuki N, Aoki D, Nozawa S.

Jpn J Clin Oncol. 35 ( 1 ) 23 - 27 2005.01

Research paper (scientific journal), Accepted

Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predisposition to cancer

Yamagami, W, Susumu, N, Banno, K, Hirao, T, Kataoka, F, Hirasawa, A, Suzuki, N, Aoki, D, Nozawa, S

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 31 ( 5 ) 444 - 451 2005

Research paper (scientific journal), Joint Work, ISSN 1341-8076

診断に苦慮した胎児水頭症の一例

渡邊広是，　西村　修，　荒瀬　透，　杉本　到，　菊地正晃，　長谷川壽彦，　山上　亘，　北岡芳久

栃木県産婦人科医報 30 ( 1 ) 24-25 2003.10

Research paper (scientific journal), Joint Work

新生児神経皮膚黒色症の一例

Yamagami Wataru, Tamada Yutaka, Sugihara Kazuhiro, Tanaka Jun, Ooshiba Youko, Itakura Kouichi, Arai Hiroharu, Iwata Satoshi

日本産科婦人科学会東京地方部会会誌 51 ( 1 ) 9-12 2002.03

Research paper (scientific journal), Joint Work

Romano-Ward 症候群合併妊娠の一例

Yamagami Wataru，Yasuoka Akiko，Ozawa Nobuaki，Sueoka Kou，Yoshimura Yasunori，Nozawa Shirou

日本産科婦人科学会東京地方部会会誌 50 ( 2 ) 204-208 2001.06

Research paper (scientific journal), Joint Work

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