Papers - Yamagami, Wataru

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

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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

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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

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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

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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

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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

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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

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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

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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

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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)