論文 - 山上　亘

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年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0387-1193

　概要を見る

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年08月

研究論文（学術雑誌）, 共著, 査読有り

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年07月

研究論文（学術雑誌）, 査読有り,  ISSN  01433334

　概要を見る

© 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.

• Access to Document (DOI)

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年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00908258

　概要を見る

© 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.

• Access to Document (DOI)

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年01月

研究論文（学術雑誌）, 共著, 査読有り

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年01月

研究論文（学術雑誌）, 共著, 査読有り

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年

ISSN  15534650

　概要を見る

© 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.

• Access to Document (DOI)

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年11月

研究論文（学術雑誌）, 共著

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年08月

研究論文（学術雑誌）, 共著,  ISSN  1078-0432

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年07月

研究論文（学術雑誌）, 共著, 査読有り

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年07月

研究論文（学術雑誌）, 共著

　概要を見る

© 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.

• Access to Document (DOI)

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

Saito T., Tabata T., Ikushima H., Yanai H., Tashiro H., Niikura H., Minaguchi T., Muramatsu T., Baba T., Yamagami W., Ariyoshi K., Ushijima K., Mikami M., Nagase S., Kaneuchi M., Yaegashi N., Udagawa Y., Katabuchi H.

International Journal of Clinical Oncology （International Journal of Clinical Oncology）  23 （ 2 ） 201 - 234 2018年04月

研究論文（学術雑誌）,  ISSN  1341-9625

　概要を見る

© 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.

• Access to Document (DOI)

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 W., Susumu N., Makabe T., Sakai K., Nomura H., Kataoka F., Hirasawa A., Banno K., Aoki D.

Journal of Gynecologic Oncology （Journal of Gynecologic Oncology）  29 （ 2 ）  2018年03月

研究論文（学術雑誌）, 共著,  ISSN  2005-0380

　概要を見る

© 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.

• Access to Document (DOI)

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年

ISSN  20050380

　概要を見る

© 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.

• Access to Document (DOI)

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年12月

研究論文（学術雑誌）, 共著,  ISSN  1949-2553

• Access to Document (DOI)

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年11月

研究論文（学術雑誌）, 共著,  ISSN  2005-0380

• Access to Document (DOI)

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年11月

研究論文（学術雑誌）, 共著,  ISSN  0368-2811

• Access to Document (DOI)

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年09月

研究論文（学術雑誌）,  ISSN  1048-891X

• Access to Document (DOI)

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

山上 亘

JOURNAL OF GYNECOLOGIC ONCOLOGY 28 （ 4 ） 902 - 911 2017年07月

研究論文（学術雑誌）,  ISSN  2005-0380

• Access to Document (DOI)

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

山上 亘

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 47 （ 5 ） 401 - 406 2017年05月

研究論文（学術雑誌）,  ISSN  0368-2811

• Access to Document (DOI)