論文 - 青木　大輔

女性性器形成手術を振り返って得られた鏡視下手術併用の有用性についての検討

今枝慶蓉，小林佑介，中村加奈子，林 茂徳，野村弘行，森定 徹，片岡史夫，宮越 敬，冨永英一郎，阪埜浩司，田中 守，青木大輔

関東連合産科婦人科学会誌 55 （ 4 ） 573 - 578 2018年11月

研究論文（学術雑誌）, 共著

新生児皮膚所見および家族歴から色素失調症と診断された不育症の一例

内田志穂，的場優介，宮越 敬，佐藤 卓，丸山哲夫，田中 守，青木大輔

関東連合産科婦人科学会誌 55 （ 4 ） 529 - 533 2018年11月

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遺伝性乳癌卵巣癌に対するリスク低減卵管卵巣摘出後のQOLに関する検討

谷本慧子，平沢 晃，牧田和也，岩田 卓，堀場裕子，横田めぐみ，小川真里子，弟子丸亮太，柳本茂久，高松 潔，青木大輔

日本女性医学学会雑誌 26 （ 1 ） 45 - 47 2018年11月

研究論文（学術雑誌）, 共著

Emerging problems in uterus transplantation

Kisu, I., Kato, Y., Obara, H., Matsubara, K., Matoba, Y., Banno, K. and Aoki, D.

Bjog 125 （ 11 ） 1352 - 1356 2018年10月

研究論文（学術雑誌）,  ISSN  1470-0328

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Basic research on uterus transplantation in nonhuman primates in Japan

Kisu, I., Banno, K., Matoba, Y., Adachi, M. and Aoki, D.

J Obstet Gynaecol Res 44 （ 10 ） 1871 - 1881 2018年10月

ISSN  1341-8076

　概要を見る

Uterus transplantation (UTx) is now a potential option for women with uterine factor infertility to have a child. However, UTx is still in an experimental stage and basic animal studies including in nonhuman primates are needed for accumulation of data that will provide important information for establishment of UTx in humans. Herein, we summarized our experiences using cynomolgus macaques, with the goal of promoting further development of UTx studies in nonhuman primates. Our basic studies using cynomolgus macaques were summarized, including the results of other teams in nonhuman primates. Our team in Japan launched UTx research in 2009 using cynomolgus macaques and has accumulated a large archive of results in the UTx research field, including examination of uterine blood flow, surgical procedures of autologous and allogeneic UTx, organ perfusion methods in deceased donor models, immunological response and rejection and ischemia/reperfusion injury. We achieved the first delivery after autologous UTx in primates and the first periodic recovery of menstruation after allogeneic UTx in nonhuman primate models. Results from animal studies, including those in nonhuman primates, provide the basis for clinical application of UTx. Therefore, our accumulated data since 2009 and our basic experience in cynomolgus macaque are meaningful for future UTx trials in Japan. In addition, more validation in nonhuman primate models is needed for resolution of medical issues and further development of UTx in humans, despite clinical application of UTx in several countries.

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Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer

Aoki, Y., Ochiai, K., Lim, S., Aoki, D., Kamiura, S., Lin, H., Katsumata, N., Cha, S. D., Kim, J. H., Kim, B. G., Hirashima, Y., Fujiwara, K., Kim, Y. T., Kim, S. M., Chung, H. H., Chang, T. C., Kamura, T., Takizawa, K., Takeuchi, M. and Kang, S. B.

Br J Cancer 119 （ 5 ） 530 - 537 2018年08月

ISSN  0007-0920

　概要を見る

BACKGROUND: This open-label phase III trial evaluated efficacy and safety of S-1 plus cisplatin vs. cisplatin alone as first-line chemotherapy in patients with stage IVB, recurrent, or persistent cervical cancer. METHODS: Patients were randomised (1:1) to S-1 plus cisplatin (study group) or cisplatin alone (control group). In each cycle, cisplatin 50 mg/m(2) was administered on Day 1 in both groups. S-1 was administered orally at 80-120 mg daily on Days 1-14 of a 21-day cycle in the study group. The primary endpoint was overall survival (OS). RESULTS: A total of 375 patients were enrolled, of whom 364 (188, study group; 176, control group) received treatment. Median OS was 21.9 and 19.5 months in the study and control groups, respectively (log-rank P = 0.125; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.67-1.05). Median progression-free survival (PFS) was 7.3 and 4.9 months in the study and control groups, respectively (HR 0.62, 95% CI 0.48-0.80, P < 0.001). The adverse event (AE) rate increased in the study group despite the absence of any unexpected AEs. CONCLUSIONS: S-1 plus cisplatin did not show superiority over cisplatin alone in OS but significantly increased PFS in patients with stage IVB, recurrent, or persistent cervical cancer. Since the standard therapy has changed in the course of this study, further studies are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population.

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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. and Mushiroda, T.

Oncotarget 9 （ 51 ） 29789 - 29800 2018年07月

研究論文（学術雑誌）, 共著,  ISSN  1949-2553

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腫瘍内出血により重症貧血をきたし、早期新生児死亡に至った胎児リンパ管腫の1例

菊森のぞみ，正木 繭，日原華子，渡邊広是，岸川 剛，檜垣敬二，荘 隆一郎，宮越 敬，秋葉洋平，田中 守，青木大輔

東京産科婦人科学会会誌 67 （ 3 ） 463 - 466 2018年07月

研究論文（学術雑誌）, 共著

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

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Clinical management of epithelial ovarian cancer

Kobayashi Y., Nomura H., Kataoka F., Tominaga E., Banno K., Aoki D.

Cell Biology of the Ovary: Stem Cells, Development, Cancer, and Clinical Aspects （Cell Biology of the Ovary: Stem Cells, Development, Cancer, and Clinical Aspects）     135 - 151 2018年06月

　概要を見る

© Springer Nature Singapore Pte Ltd 2018. Ovarian cancer has high morbidity and mortality worldwide, and its mortality is the highest among female genital cancers. Improvement in clinical outcome is an urgent issue for ovarian cancer, and clinical management including treatment has been repeatedly studied. Tumor markers such as CA125, CA19-9, and HE4 and image diagnosis using MRI, CT, PET, etc. are indispensable diagnostic aid tools. In the initial treatment, primary debulking surgery (PDS) is basically effective, but fertility preservation can be considered depending on the case. For advanced cancers, interval debulking surgery (IDS) is considered after several cycles of neoadjuvant chemotherapy (NAC). Although the combination of paclitaxel and carboplatin (TC) regimen was originally established as the standard chemotherapy for ovarian cancer regardless of tissue type, new treatments in clinical trials, including molecular-targeted therapeutic agents, are being investigated. The main treatment for recurrent cancer is chemotherapy, and sensitivity to chemotherapy based on the disease-free interval has been considered in the choice of treatment. Furthermore, in recent years, risk-reducing bilateral salpingo-oophorectomy has been undertaken to prevent the onset of hereditary breast and ovarian cancer. It is also being studied how to manage the follow-up after treatment and hormone replacement.

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Liquid-based cytology versus conventional cytology for detection of uterine cervical lesions: a prospective observational study

Nishio, H., Iwata, T., Nomura, H., Morisada, T., Takeshima, N., Takano, H., Sasaki, H., Nakatani, E., Teramukai, S. and Aoki, D.

Jpn J Clin Oncol 48 （ 6 ） 522 - 528 2018年06月

ISSN  0368-2811

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Postoperative chemotherapy for node-positive cervical cancer: Results of a multicenter phase II trial (JGOG1067)

Matoda, M., Takeshima, N., Michimae, H., Iwata, T., Yokota, H., Torii, Y., Yamamoto, Y., Takehara, K., Nishio, S., Takano, H., Mizuno, M., Takahashi, Y., Takei, Y., Hasegawa, T., Mikami, M., Enomoto, T., Aoki, D. and Sugiyama, T.

Gynecol Oncol 149 （ 3 ） 513 - 519 2018年06月

ISSN  0090-8258

　概要を見る

OBJECTIVE: This multicenter phase II Japanese Gynecologic Oncology Group study (JGOG1067) was designed to evaluate the efficacy and safety of postoperative chemotherapy in patients with node-positive cervical cancer. METHODS: Patients with stage IB-IIA squamous cervical cancer who underwent radical hysterectomy and were confirmed to have pelvic lymph node metastasis were eligible for this study. The patients postoperatively received irinotecan (CPT-11; 60mg/m(2) intravenously on days 1 and 8) and nedaplatin (NDP; 80mg/m(2) intravenously on day 1). Chemotherapy administration commenced within 6weeks after surgery and was repeated every 28days for up to 5cycles. The primary endpoint of this study was the 2-year recurrence-free survival (RFS) rate. The secondary endpoints were the 5-year overall survival (OS) rate, 5-year RFS rate, and adverse events such as complications of chemotherapy and lower-limb edema. RESULTS: Sixty-two patients were analyzed according to our protocol, among whom 55 (88.7%) completed 5cycles of scheduled treatment. The median follow-up period was 66.1months (range, 16.8-96.6months). The 2-year and 5-year RFS rates were 87.1% (95% confidence interval [CI]: 75.9-99.3) and 77.2% (95% CI: 64.5-85.8), respectively. Fourteen patients (22.5%) experienced recurrence during the follow-up period, 8 of whom died of the disease. The 5-year OS rate in this study was 86.5% (95% CI: 74.8-93.0). Only 9.7% of the patients experienced lymphedema in their legs. CONCLUSION: Postoperative chemotherapy without radiotherapy was found to be very effective in high-risk patients with node-positive cervical cancer.

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Population-based cohort study assessing the efficacy of cervical cytology (Pap smear) and human papillomavirus (HPV) testing as modalities for cervical cancer screening

Morisada, T., Saika, K., Saito, E., Kono, K., Saito, H. and Aoki, D.

Jpn J Clin Oncol 48 （ 5 ） 495 - 498 2018年05月

ISSN  0368-2811

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Isolation techniqueを用いた腹腔鏡下卵巣腫瘍摘出における回収袋の工夫

的場優介，林 茂徳，中川 亮，飯島茂異人，中村加奈子，木須伊織，阪埜浩司，田中　守，青木大輔

東京産科婦人科学会会誌 67 （ 2 ） 341 - 348 2018年05月

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Multicenter Clinicopathological Study of High-Grade Serous Carcinoma Presenting as Primary Peritoneal Carcinoma

Komiyama, S., Nishijima, Y., Kondo, H., Nomura, H., Yamaguchi, S., Futagami, M., Arai, H., Yokoyama, Y., Suzuki, N., Mikami, M., Kubushiro, K., Aoki, D., Udagawa, Y. and Nishimura, R.

Int J Gynecol Cancer 28 （ 4 ） 657 - 665 2018年05月

ISSN  1048-891X

　概要を見る

OBJECTIVE: We conducted a multicenter clinicopathological study to characterize patients with high-grade serous carcinoma presenting as primary peritoneal carcinoma (clinical PPC). METHODS: At 9 sites in Japan, patients with clinical PPC diagnosed according to Gynecologic Oncology Group criteria were enrolled retrospectively. The Gynecologic Oncology Group criteria allow for minor ovarian involvement by high-grade serous carcinoma. There was no systematic detailed histopathological review of the fallopian tubes to determine whether they were involved by serous carcinoma. RESULTS: There were 139 patients and 64% were aged 60 years or older. Median pretreatment serum CA-125 was 1653.5 IU/mL. Pretreatment performance status was poor in more than 50%, endometrial cytology was positive in 40.3%, and the preoperative clinical diagnosis was correct in 72.7%. Primary debulking surgery was performed in 36% of patients, whereas 64% underwent neoadjuvant chemotherapy (NAC) with interval debulking surgery (IDS). The main tumor sites were the upper abdomen (greater omentum), extrapelvic peritoneum, mesentery, and diaphragm. Lymph node metastasis was found in 46.8% of patients undergoing systematic retroperitoneal node dissection. The optimal surgery rate was 32.0% with primary debulking surgery versus 53.9% with NAC and IDS (P = 0.0139). The response rate was 82.0% with NAC and 80.6% with postoperative chemotherapy. Median progression-free survival was 19.0 months and median overall survival was 41.0 months. Multivariate analysis showed that prognostic factors for progression-free survival were NAC and residual tumor diameter after debulking surgery, whereas the only prognostic factor for overall survival was the residual tumor diameter. CONCLUSIONS: This study identified various characteristics of clinical PPC. Neoadjuvant chemotherapy with IDS is a reasonable treatment strategy, and complete debulking surgery is optimum.

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Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer

Takeda, T., Tsuji, K., Banno, K., Yanokura, M., Kobayashi, Y., Tominaga, E. and Aoki, D.

J Gynecol Oncol 29 （ 3 ） e29 2018年05月

ISSN  2005-0380

　概要を見る

OBJECTIVE: Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. METHODS: The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM(5) were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. RESULTS: Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM(5), but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. CONCLUSION: This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.

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妊娠糖尿病管理中の低カリウム性四肢麻痺を契機に検出されたCushing症候群合併妊娠の1例

高橋美央，秋葉洋平，宮越　敬，安康真由香，今枝慶蓉，落合大吾，松本 直，田中　守，青木大輔

東京産科婦人科学会会誌 67 （ 2 ） 280 - 283 2018年05月

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第59回日本婦人科腫瘍学会学術講演会記録 婦人科腫瘍医のためのがん薬物療法総論

野村弘行，岩佐尚美，早乙女啓子，同前 愛，青木大輔

日本婦人科腫瘍学会雑誌 36 （ 2 ） 197 - 205 2018年04月

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腹腔鏡下子宮筋腫核出術におけるDouglas窩より筋腫摘出法の検討

田中雄也，林 茂徳，竹田 貴，飯島茂異人，冨永英一郎，田中　守，青木大輔

東京産科婦人科学会会誌 67 （ 2 ） 149 - 153 2018年04月

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各論：遺伝性婦人科腫瘍

植木有紗，阪埜浩司，青木大輔

最新醫學 73 （ 3 ） 374 - 379 2018年03月