論文 - 青木　大輔

Involvement of the MDR1 gene and glycolipids in anticancer drug-resistance of human ovarian carcinoma-derived cells.

Tanaka K, Kiguchi K, Mikami M, Aoki D, Iwamori M

Human cell 32 （ 4 ） 447 - 452 2019年10月

ISSN  0914-7470

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Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques

Kisu I, Ishigaki H, Emoto K, Kato Y, Yamada Y, Matsubara K, Obara H, Masugi Y, Matoba Y, Adachi M, Banno K, Saiki Y, Itagaki I, Kawamoto I, Iwatani C, Nakagawa T, Tsuchiya H, Sasamura T, Urano H, Ema M, Ogasawara K, Aoki D, Nakagawa K, Shiina T

J Clin Med 8 （ 10 ） 1572 2019年10月

研究論文（学術雑誌）, 共著, 査読有り

子宮悪性腫瘍手術直後の排尿障害に対する超音波断層法を用いた残尿量推定の有用性の検討：看護師による導尿前スクリーニングとして

飯島美穂，阪埜浩司，堀川未来，渡部景都，野上侑哉，青木大輔

日本婦人科腫瘍学会雑誌 37 （ 8 ） 714 - 722 2019年10月

研究論文（学術雑誌）, 共著, 査読有り

子宮鏡検査が子宮角部妊娠の診断に有用であった1例

岡 愛実子，山田満稔，佐藤健二，升田博隆，上條慎太郎，浜谷敏生，田中 守，青木大輔

東京産科婦人科学会会誌 68 （ 4 ） 710 - 713 2019年10月

研究論文（学術雑誌）, 共著

A Clinical Trial to Verify the Efficiency of the LC-1000 Exfoliative Cell Analyzer as a New Method of Cervical Cancer Screening

Nakamura M., Ueda M., Iwata T., Kiguchi K., Mikami Y., Kakuma T., Aoki D.

Acta Cytologica 63 （ 5 ） 1 - 10 2019年09月

研究論文（学術雑誌）, 査読有り,  ISSN  00015547

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Atypical polypoid adenomyoma treated by hysteroscopy with photodynamic diagnosis using 5-aminolevulinic acid: A case report

Matoba Y., Banno K., Kobayashi Y., Kisu I., Aoki D.

Photodiagnosis and Photodynamic Therapy （Photodiagnosis and Photodynamic Therapy）  27   295 - 297 2019年09月

ISSN  15721000

　概要を見る

© 2019 The Authors Surgical resection for atypical polypoid adenomyoma (APA) is an option for fertility preservation. Due to the high recurrence rate of APA, studies have been conducted to improve total resection of tumors. Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) improves tumor resection, but this has not been applied for APA. The patient was 35-year-old. After initial treatment, the APA lesion did not disappear. We performed hysteroscopic tumor resection using 5-ALA-PDD. Only one PDD-positive lesion was found and histopathologically diagnosed as APA. Other areas were PDD-negative and showed no histopathologic APA or malignant findings. This is the first report of hysteroscopic 5-ALA-PDD for APA. This method makes it easy to identify morbid lesions, and may lead to improved total resection and decreased recurrence.

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Safety and efficacy of mucosal immunotherapy using human papillomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine for the treatment of high-grade squamous intraepithelial lesion (HSIL): the study protocol of a randomized placebo-controlled clinical trial (MILACLE study)

Ikeda Y, Uemura Y, Asai-Sato M, Nakao T, Nakajima T, Iwata T, Akiyama A, Satoh T, Yahata H, Kato K, Maeda D, Aoki D, Kawana K

Jpn J Clin Oncol 49 （ 9 ） 877 - 880 2019年09月

研究論文（学術雑誌）, 査読有り

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 58 （ 5 ） 196 - 201 2019年09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

ISSN  0143-3334

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The first Japanese nationwide multicenter study of <i>BRCA</i> mutation testing in ovarian cancer: CHARacterizing the cross-sectionaL approach to Ovarian cancer geneTic TEsting of <i>BRCA</i> (CHARLOTTE).

Enomoto T, Aoki D, Hattori K, Jinushi M, Kigawa J, Takeshima N, Tsuda H, Watanabe Y, Yoshihara K, Sugiyama T

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 29 （ 6 ） 1043 - 1049 2019年07月

ISSN  1048-891X

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腫瘍の肉眼所見、画像所見と病理組織学所見との乖離から術前の原発巣確定に苦慮した2症例の経験

木村寛子，仲村 勝，佐伯直彦，冨永英一郎，田中 守，青木大輔

東京産科婦人科学会会誌 68 （ 3 ） 454 - 458 2019年07月

研究論文（学術雑誌）, 共著, 査読有り

Atypical endometrial hyperplasia diagnosed by hysteroscopic photodynamic diagnosis using 5-aminolevulinic acid

Matoba Y., Banno K., Kisu I., Tsuji K., Aoki D.

Photodiagnosis and Photodynamic Therapy （Photodiagnosis and Photodynamic Therapy）  26   45 - 47 2019年06月

ISSN  15721000

　概要を見る

© 2019 The Authors Endometrial cancer is diagnosed by endometrial biopsy, imaging and hysteroscopy, but it is sometimes difficult to find small lesions. 5-aminolevulinic acid (5ALA) forms protoporphyrin IX, which accumulates in tumors and fluoresces upon light irradiation. 5ALA is used for photodynamic diagnosis (PDD) for detecting malignant diseases. A 60-year-old female was suspected to have endometrial cancer by magnetic resonance imaging. Endometrial biopsy was performed repeatedly, but no malignant lesion was detected. We performed hysteroscopic 5ALA-PDD and could detect a small lesion. The lesion was excised and diagnosed as atypical endometrial hyperplasia histopathologically. This is the first report that showed hysteroscopic 5ALA-PDD can contribute to diagnosis of early-stage neoplastic lesion in the uterine cavity.

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Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial

Nomura H., Aoki D., Michimae H., Mizuno M., Nakai H., Arai M., Sasagawa M., Ushijima K., Sugiyama T., Saito M., Tokunaga H., Matoda M., Nakanishi T., Watanabe Y., Takahashi F., Saito T., Yaegashi N.

JAMA Oncology （JAMA Oncology）  5 （ 6 ） 833 - 840 2019年06月

ISSN  23742437

　概要を見る

© 2019 American Medical Association. All rights reserved. Importance: The efficacy of taxane plus platinum regimens has been demonstrated for advanced or recurrent endometrial cancer; however, it has not been assessed in postoperative adjuvant chemotherapy for endometrial cancer. Objective: To evaluate the clinical benefit of taxane plus platinum compared with standard doxorubicin plus cisplatin as postoperative adjuvant chemotherapy in endometrial cancer. Design, Setting, and Participants: In this multicenter, open-label, phase 3 randomized clinical trial, patients with endometrial cancer at high-risk stage I or II or stage III or IV that did not extend beyond the abdominal cavity and had 2 cm or greater residual tumor were included from 118 institutions in Japan from November 24, 2006, to January 7, 2011. Data was analyzed from March 15, 2017, to June 30, 2017. Interventions: Eligible patients were randomly assigned (1:1:1) to receive 6 cycles of doxorubicin, 60 mg/m2, plus cisplatin, 50 mg/m2, on day 1; docetaxel, 70 mg/m2, plus cisplatin, 60 mg/m2, on day 1; or paclitaxel, 180 mg/m2, plus carboplatin (area under the curve, 6.0 mg/mL × min) on day 1 every 3 weeks. Main Outcomes and Measures: The primary end point was progression-free survival. Secondary end points were overall survival, occurrence of adverse events, tolerability, and status of lymph node dissection. Results: Among 788 eligible patients, the median (SD) age was 59 (22-74) years; 263 patients were assigned to doxorubicin plus cisplatin treatment, 263 patients to docetaxel plus cisplatin treatment, and 262 patients to paclitaxel plus carboplatin treatment. The number of patients who did not complete 6 cycles was 53 (20.1%) for the doxorubicin plus cisplatin group, 45 (17.1%) for the docetaxel plus cisplatin group, and 63 (24.0%) for the paclitaxel plus carboplatin group. Tolerability of these regimens were not statistically different. After a median follow-up period of 7 years, there was no statistical difference of progression-free survival (doxorubicin plus cisplatin, 191; docetaxel plus cisplatin, 208; paclitaxel plus carboplatin, 187; P =.12) or overall survival (doxorubicin plus cisplatin, 217; docetaxel plus cisplatin, 223; paclitaxel plus carboplatin, 215; P =.67) among the 3 groups. The 5-year progression-free survival rate was 73.3% for the doxorubicin plus cisplatin group, 79.0% for the docetaxel plus cisplatin group, and 73.9% for the paclitaxel plus carboplatin group, while the 5-year overall survival rates were 82.7%, 88.1%, and 86.1%, respectively. Conclusions and Relevance: There was no significant difference of survival among patients receiving doxorubicin plus cisplatin, docetaxel plus cisplatin, or paclitaxel plus carboplatin as postoperative adjuvant chemotherapy for endometrial cancer. Because each regimen showed adequate tolerability but different toxic effects, taxane plus platinum regimens may be a reasonable alternative to treatment with doxorubicin plus cisplatin. Trial Registration: UMIN-CTR identifier: UMIN000000522.

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Characterization of a novel glycolipid with a difucosylated H-antigen in human blood group O erythrocytes with monoclonal antibody HMMC-1 and its detection in human uterine cervical carcinoma tissues.

Tanaka K, Suzuki A, Aoki D, Iwamori M

Glycoconjugate journal 36 （ 3 ） 219 - 226 2019年06月

ISSN  0282-0080

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Uterus transplantation: advantages and disadvantages of a deceased donor

Kisu I, Banno K, Matoba Y, Aoki D

Arch Gynecol Obstet 299 （ 5 ） 1213 - 1214 2019年05月

研究論文（学術雑誌）

Local anatomy around terminal ureter related to the anterior leaf of the vesicouterine ligament in radical hysterectomy

Nakamura M., Tanaka K., Hayashi S., Morisada T., Iwata T., Imanishi N., Aoki D.

European Journal of Obstetrics and Gynecology and Reproductive Biology （European Journal of Obstetrics and Gynecology and Reproductive Biology）  235   66 - 70 2019年04月

研究論文（学術雑誌）, 査読有り,  ISSN  03012115

　概要を見る

© 2019 Elsevier B.V. Objectives: Radical hysterectomy is performed for invasive cervical cancer. In this surgery, separation of the anterior leaf and posterior leaves of the vesicouterine ligament (VUL) is important. We studied the local anatomy of the anterior leaf of the VUL, especially the branches of the umbilical artery from the view point of surgery and cadaver dissection. Study Design: We observed the cervicovesical blood vessels and the connective tissue layer continued from umbilical artery and searched for the origin of the cervicovesical blood vessels in radical hysterectomy. We also dissected a formalin-fixed female cadaver, and observed the same points. Results: After separation of the connective tissue of urinary bladder from the cervical fascia, we could discern the outline of the distal ureter near the ureterovesical junction. We separate the connective tissue of the so-called anterior leaf of the VUL enwrapping the ureter gently, and then the ureter with the connective tissue is completely rolled out laterally. We identified a cervicovesical vessel crossing over the ureter. We looked for the central side of the cervicovesical vessel and found that cervicovesical vessel was a branch of the superior vesical artery. And, during cadaver dissection, we found that the connective tissue and the branches of the superior vesical artery were similarly observed. Conclusions: We found the precise anatomy of the connective tissue layer from umbilical artery to urinary bladder and the superior vesical artery. Our procedure based on the precise anatomy obtained in this study is reasonable anatomically as a method for separation of the vesicouterine ligament during radical hysterectomy.

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分娩後に急性腎不全を発症し非典型溶血性尿毒症症候群(aHUS)と診断した1例

竹田 将人, 池ノ上 学, 坂井 健良, 遠藤 豊英, 大石 真希, 落合 大吾, 宮越 敬, 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）  68 （ 2 ） 339 - 343 2019年04月

研究論文（学術雑誌）, 査読有り,  ISSN  2186-0599

　概要を見る

血栓性微小血管症(TMA)は溶血性貧血、血小板減少、臓器機能障害を三徴とする病態であり、非典型溶血性尿毒症症候群(atypical hemolytic uremic syndrome:aHUS)はその一つである。今回、分娩後経過から早期にaHUSを診断し、良好な予後を得た症例を経験したため報告する。症例は33歳、1妊1産。妊娠経過は良好で、妊娠38週に自然経腟分娩となった。分娩後、弛緩出血に対して輸血および子宮内バルーンタンポナーデを行い止血を得たが、産後2日目より腎機能障害、肝機能障害を認め当院へ搬送となった。TMAの三徴を認め、ADAMTS-13活性は正常値でありaHUSと診断した。血液透析と血漿補充により腎機能は改善し、産後22日目に退院となった。溶血性貧血と血小板減少を伴う急激な腎機能障害を認めた場合、早期からaHUSを鑑別疾患に挙げることが肝要である。(著者抄録)

Laparoscopic Surgery for Ovarian Cyst Infection with Avoidance of Ureteral Injury and Uterine Perforation following Intrauterine Insemination after Abdominal Modified Radical Trachelectomy.

Iijima M, Hayashi S, Kobayashi Y, Tsuji K, Tominaga E, Banno K, Aoki D

Case Rep Obstet Gynecol 2019   8607417 2019年04月

研究論文（学術雑誌）,  ISSN  2090-6684

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Warburg effect in Gynecologic cancers

Kobayashi Y., Banno K., Kunitomi H., Takahashi T., Takeda T., Nakamura K., Tsuji K., Tominaga E., Aoki D.

Journal of Obstetrics and Gynaecology Research （Journal of Obstetrics and Gynaecology Research）  45 （ 3 ） 542 - 548 2019年03月

研究論文（学術雑誌）,  ISSN  13418076

　概要を見る

© 2018 Japan Society of Obstetrics and Gynecology Mammalian cells produce energy by oxidative phosphorylation under aerobic conditions. However, in the 1920s, Otto Warburg reported the so-called “Warburg effect” in which cancer cells produce ATP that is biased toward glycolysis rather than mitochondrial oxidative phosphorylation not only in anaerobic environment but also in aerobic environment. Glucose is converted into lactate without going into mitochondria after being metabolized in glycolysis. Compared with oxidative phosphorylation, the glycolysis has a faster ATP production rate but it is very inefficient, resulting in cancer cells consuming a large amount of glucose. Increased glucose metabolism has become a biomarker for cancer cells and has led to the development of positron emission tomography with fluorodeoxyglucose. Till date, the Warburg effect has been an inefficient system for cancer cells with regard to efficient energy production, but since the consumption of oxygen can be suppressed as the tumor grows in mass, it is thought that the Warburg effect is advantageous in this situation wherein the tumor can increase despite the lack of vessels. In addition, an increased lactate by the glycolysis causes acidosis in the microenvironment of tissues, which is thought to damage the surrounding normal tissues and favor the invasion and metastasis of cancer. Thus, Warburg effect is one of the key mechanisms for cancer development and will be the next promising target. In this review, we introduce key players that can be targeted in the Warburg effect and outline the prospects of treatment, targeting the Warburg effect in gynecological cancer.

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腹腔内へ迷入した異物(ミレーナ)を腹腔鏡下手術により回収し得た1例

中村 加奈子, 林 茂徳, 安康 真由香, 清河 駿樹, 水口 雄貴, 冨永 英一郎, 阪埜 浩司, 青木 大輔

栃木県産婦人科医報 （栃木県産科婦人科学会）  45   25 - 29 2019年03月

　概要を見る

子宮内避妊器具や子宮内黄体ホルモン放出システム(ミレーナ)は避妊や月経困難症の治療のために使用されるが子宮穿孔や腹腔内への迷入などの合併症を来たすことがある。今回我々は、腹腔内に迷入したミレーナを腹腔鏡下手術により回収した症例を経験した。術中、ミレーナは鏡視下の観察のみで容易に発見できたが大網に強固に癒着していたため、大網とともに部分切除することで合併症を来たすことなく回収した。腹腔内異物を腹腔鏡下手術により摘出を試みる場合、異物の発見が鏡視下の観察のみで困難な場合を想定した外科用X線撮影装置の準備や強固な癒着を想定した術式を計画することが安全に手術による摘出を成功させる上で重要である。(著者抄録)