Details of a Researcher - Chiyoda, Tatsuyuki

Papers - Chiyoda, Tatsuyuki

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Current status and future of liquid biopsy in gynecologic cancers

千代田達幸, 青木大輔

月刊Precision Medicine 4 ( 12 ) 2021

ISSN 2434-3625

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

Kensuke Sakai, Chizu Tanikawa, Akira Hirasawa, Tatsuyuki Chiyoda, Wataru Yamagami, Fumio Kataoka, Nobuyuki Susumu, Chikashi Terao, Yoichiro Kamatani, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Michiaki Kubo, Nobuo Fuse, Takako Takai-Igarashi, Atsushi Shimizu, Akimune Fukushima, Aya Kadota, Kokichi Arisawa, Hiroaki Ikezaki, Kenji Wakai, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Daisuke Aoki, Koichi Matsuda

SCIENTIFIC REPORTS (NATURE PUBLISHING GROUP) 10 ( 1 ) 1197 2020.12

Research paper (scientific journal), Joint Work, ISSN 2045-2322

Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P=6.12x10(-25) with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma.

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

Yoshiko Nanki, Tatsuyuki Chiyoda, Akira Hirasawa, Aki Ookubo, Manabu Itoh, Masaru Ueno, Tomoko Akahane, Kaori Kameyama, Wataru Yamagami, Fumio Kataoka, Daisuke Aoki

SCIENTIFIC REPORTS (NATURE PUBLISHING GROUP) 10 ( 1 ) 12581 2020.12

Research paper (scientific journal), Joint Work, ISSN 2045-2322

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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PROSPECTIVE FEASIBILITY STUDY OF NEOADJUVANT DOSE-DENSE PACLITAXEL PLUS CARBOPLATIN WITH BEVACIZUMAB THERAPY FOR ADVANCED OVARIAN, FALLOPIAN TUBE AND PRIMARY PERITONEAL CANCER PATIENTS

Nomura H., Iwasa N., Kataoka F., Chiyoda T., Yamagami W., Fujii T., Aoki D.

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 30 A150 - A150 2020.11

ISSN 1048-891X

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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 (Gynecologic Oncology Reports) 34 100645 2020.11

ISSN 2352-5789

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

Keiko Saotome, Tatsuyuki Chiyoda, Eriko Aimono, Kohei Nakamura, Shigeki Tanishima, Sachio Nohara, Chihiro Okada, Hideyuki Hayashi, Yuka Kuroda, Hiroyuki Nomura, Nobuyuki Susumu, Takashi Iwata, Wataru Yamagami, Fumio Kataoka, Hiroshi Nishihara, Daisuke Aoki

CANCER MEDICINE (WILEY) 9 ( 20 ) 7407 - 7417 2020.10

Research paper (scientific journal), Joint Work, ISSN 2045-7634

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. ActionableBRCA1andBRCA2variants were found in 4.5% of each of the cases.ERBB2amplification 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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Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis

Tatsuyuki Chiyoda, Manabu Sakurai, Toyomi Satoh, Satoru Nagase, Mikio Mikami, Hidetaka Katabuchi, Daisuke Aoki

Journal of Gynecologic Oncology (Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology and Colposcopy) 31 ( 5 ) 1 - 13 2020.09

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

© 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology. Objective: To assess the effectiveness of lymphadenectomy at primary debulking surgery (PDS) on the survival of patients with epithelial ovarian cancer (EOC). Methods: We searched PubMed, Ichushi, and the Cochrane Library. Randomized controlled trials (RCTs) and retrospective cohort studies comparing survival of women with EOC undergoing lymphadenectomy at PDS with that of women without lymphadenectomy were included. We performed a meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse events. Results: For advanced-stage EOC, 2 RCTs including 1,074 women and 7 cohort studies comprising 3,161 women were evaluated. Meta-analysis revealed that lymphadenectomy was associated with improved OS (hazard ratio [HR]=0.80; 95% confidence interval [CI]=0.70– 0.90). However, meta-analysis of 2 RCTs revealed no significant difference in OS between the lymphadenectomy and no-lymphadenectomy groups (OS: HR=1.02; 95% CI=0.85–1.22). For early-stage EOC, 1 RCT comprising 268 women and 4 cohort studies comprising 14,228 women were evaluated. Meta-analysis showed that lymphadenectomy was associated with improved OS (HR=0.75; 95% CI=0.68–0.82). A RCT of early-stage EOC reported that lymphadenectomy was not associated with improved OS (HR=0.85; 95% CI=0.49–1.47). Surgery-related deaths were similar in both groups (risk ratio [RR]=1.00; 95% CI=0.99–1.01); however, blood transfusion was required less frequently in the no-lymphadenectomy group (RR=0.74; 95% CI=0.63–0.86). Conclusions: Meta-analysis of RCTs and observational studies suggest that lymphadenectomy was associated with improved OS in advanced-and early-stage EOC. However, results from RCTs demonstrate that lymphadenectomy was not associated with improved OS in advanced-and early-stage EOC.

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腹腔鏡下子宮筋腫核出術における超音波凝固切開装置と電気メス・クーパーの手術成績の比較検討

松沢優一, 林茂徳, 長谷川慶太, 吉村拓馬, 永井晋平, 平野卓朗, 千代田達幸, 仲村勝, 片岡史夫, 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 ( 2 ) 147 - 152 2020.04

ISSN 2186-0599

腹腔鏡下子宮筋腫核出術(laparoscopic myomectomy:LM)の際のデバイスとして、ランダム化比較試験で超音波凝固切開装置は電気メスと比較して出血量の減少、手術時間の短縮を有意に認めたとの報告がある。今回当院にてLMを施行した183例を、超音波凝固切開装置使用(A群:80例)、モノポーラ・クーパー使用(B群:103例)にわけ比較検討した。手術時間、出血量に関して2群間の平均値において統計学的有意差は認められず、デバイスの違いによる差は認められなかった。そこで我々は手術時間、出血量に及ぼす影響の強さについて年齢、BMI、摘出筋腫重量、摘出筋腫個数、筋腫最大径、デバイス(A群、B群)、術者の各種因子を用いて重回帰分析を行い、手術時間、出血量に影響を及ぼす因子について検討を行った。手術時間に関しては摘出筋腫個数が、出血量に関しては筋腫最大径が最も影響を与える因子となった。(著者抄録)

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) 153 ( 3 ) 438 - 442 2020

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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A case of "retained products of conception" treated with hysteroscopic surgery occurring after cesarean delivery in a patient who underwent fertility-preserving therapy for endometrial cancer

Makabe Takeshi, Yamagami Wataru, Hirano Takuro, Sakai Kensuke, Chiyoda Tatsuyuki, Kataoka Fumio, Aoki Daisuke

JAPANESE JOURNAL OF GYNECOLOGIC AND OBSTETRIC ENDOSCOPY (JAPAN SOCIETY OF GYNECOLOGIC AND OBSTETRIC ENDOSCOPY AND MINIMALLY INVASIVE THERAPY) 36 ( 2 ) 317 - 321 2020

ISSN 1884-9938

<p>　A 37-year old woman was diagnosed as early-stage endometrial cancer (G1 endometrioid carcinoma) during infertility treatment. The patient desired fertility preservation, and underwent fertility-preserving hormonal therapy. She became pregnant after successful cancer treatment and underwent cesarean section for breech presentation. During the surgery, it was observed that the placenta had adhered to the uterine wall, and it was removed manually. A postoperative examination revealed an intrauterine mass, which was diagnosed as retained products of conception (RPOC). Because active bleeding was not observed, conservative management was initiated. However, the lesion did not resolve. Therefore, we performed hysteroscopic surgery and endometrial curettage to evaluate the recurrence of endometrial cancer. A 2-cm white polypoid lesion was discovered in the uterus, and it was excised using a loop electrode. The resected margin was ischemic with little bleeding. The resected polypoid lesions were pathologically diagnosed as necrotic hyaline tissue, whereas that of the endometrial curettage lesion was endometrial hyperplasia. To determine the method and timing of treatment for RPOC, it is necessary to consider the presence or absence of active bleeding and individual characteristics of patients such as a history of endometrial cancer.</p><p></p>

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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

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)

CLINICAL IMPACT OF LYMPHADENECTOMY FOR ENDOMETRIAL CANCER IN JAPAN

Yamagami W., Saotome K., Hirano T., Nanki Y., Sakai K., Makabe T., Chiyoda T., Kobayashi Y., Kataoka F., Banno K., Aoki D.

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 29 A110 - A110 2019.11

ISSN 1048-891X

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EFFECTIVENESS OF DRAINAGE FOLLOWING LAPAROSCOPIC PELVIC LYMPH NODE DISSECTION

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 GYNECOLOGICAL CANCER 29 A580 - A580 2019.11

ISSN 1048-891X

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Plasma circulating tumor DNA as a genomic biomarker for ovarian cancer

Nanki Y., George A. M., Chen Y., Brueffer C., Hirasawa A., Chiyoda T., Akahane T., Aoki D., Saal L. H.

EUROPEAN JOURNAL OF HUMAN GENETICS 27 1670 - 1671 2019.10

ISSN 1018-4813

特集卵巣がん征圧へのマイルストーン 7.「PleSSision検査」の実際

千代田達幸, 四十物絵理子, 早乙女啓子, 西原広史, 青木大輔

産婦人科の実際 (金原出版) 68 ( 3 ) 283 - 288 2019.03

ISSN 0558-4728

連載 FOCUS 卵巣癌実地臨床に導入されたPARP阻害薬

千代田達幸, 同前愛, 早乙女啓子, 青木大輔

臨床婦人科産科 (株式会社医学書院) 73 ( 1 ) 152 - 162 2019.01

ISSN 0386-9865

卵巣癌実地臨床に導入されたPARP阻害薬

AOKI DAISUKE

臨床婦人科産科 73 ( 1 ) 152 - 162 2019.01

Joint Work

SPHK1 is a novel target of metformin in ovarian cancer

Hart P, Chiyoda T, Liu X, Weigert M, Curtis M, Chiang C, Loth R, Lastra R, McGregor S, Locasale J, Lengyel E, Romero I

Molecular Cancer Research (Molecular Cancer Research) 17 ( 4 ) 870 - 881 2019

Joint Work, ISSN 15417786

© 2019 American Association for Cancer Research Inc. All rights reserved. The role of phospholipid signaling in ovarian cancer is poorly understood. Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingosine that has been associated with tumor progression through enhanced cell proliferation and motility. Similarly, sphingosine kinases (SPHK), which catalyze the formation of S1P and thus regulate the sphingolipid rheostat, have been reported to promote tumor growth in a variety of cancers. The findings reported here show that exogenous S1P or overexpression of SPHK1 increased proliferation, migration, invasion, and stem-like phenotypes in ovarian cancer cell lines. Likewise, overexpression of SPHK1 markedly enhanced tumor growth in a xenograft model of ovarian cancer, which was associated with elevation of key markers of proliferation and stemness. The diabetes drug, metformin, has been shown to have anticancer effects. Here, we found that ovarian cancer patients taking metformin had significantly reduced serum S1P levels, a finding that was recapitulated when ovarian cancer cells were treated with metformin and analyzed by lipidomics. These findings suggested that in c

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Biomarkers of Gynecological Cancers.

Chiyoda Tatsuyuki, Dozen Ai, Saotome Keiko, Nanki Yoshiko, Aoki Daisuke

Biomarkers in Cancer Therapy-Liquid Biopsy Comes of Age- Springer Nature 133 - 150 2019

Joint Work, Accepted

Sentinel Node Navigation Surgery for Endometrial Cancer

Susumu Nobuyuki, Yamagami Wataru, Kataoka Fumio, Hirano Takuro, Makabe Takeshi, Sakai Kensuke, Chiyoda Tatsuyuki, Nomura Hiroyuki, Hirasawa Akira, Aoki Daisuke

SURGERY FOR GYNECOLOGIC CANCER 295 - 312 2019

ISSN 978-981-13-1518-3

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