2022/04/12 更新

写真a

タマウチ サトシ
玉内 学志
TAMAUCHI Satoshi
所属
医学部附属病院 産科婦人科 助教
大学院担当
大学院医学系研究科
職名
助教

学位 1

  1. 医学博士 ( 2019年3月   名古屋大学 ) 

研究分野 1

  1. ライフサイエンス / 産婦人科学

現在の研究課題とSDGs 2

  1. 婦人科癌患者の妊孕性温存治療

  2. 卵巣癌の新規治療法の開発

 

論文 55

  1. Peritoneal Restoration by Repurposing Vitamin D Inhibits Ovarian Cancer Dissemination via Blockade of the TGF-β1/Thrombospondin-1 Axis.

    Kitami K, Yoshihara M, Tamauchi S, Sugiyama M, Koya Y, Yamakita Y, Fujimoto H, Iyoshi S, Uno K, Mogi K, Ikeda Y, Yokoi A, Yoshikawa N, Nishino K, Niimi K, Nawa A, Enomoto A, Kajiyama H

    Matrix biology : journal of the International Society for Matrix Biology     2022年3月

     詳細を見る

    記述言語:英語  

    DOI: 10.1016/j.matbio.2022.03.003

    PubMed

  2. Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis.

    Ikeda Y, Yoshihara M, Yoshikawa N, Yokoi A, Tamauchi S, Nishino K, Niimi K, Kajiyama H

    BMC women's health   22 巻 ( 1 ) 頁: 80   2022年3月

     詳細を見る

    記述言語:英語  

    DOI: 10.1186/s12905-022-01642-z

    PubMed

  3. Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy

    Uno Kaname, Yoshikawa Nobuhisa, Tazaki Akira, Ohnuma Shoko, Kitami Kazuhisa, Iyoshi Shohei, Mogi Kazumasa, Yoshihara Masato, Koya Yoshihiro, Sugiyama Mai, Tamauchi Satoshi, Ikeda Yoshiki, Yokoi Akira, Kikkawa Fumitaka, Kato Masashi, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   12 巻 ( 1 ) 頁: 4513   2022年3月

     詳細を見る

    記述言語:日本語   出版者・発行元:Scientific Reports  

    Most patients with ovarian cancer experience recurrence and develop resistance to platinum-based agents. The diagnosis of platinum resistance based on the platinum-free interval is not always accurate and timely in clinical settings. Herein, we used laser ablation inductively coupled plasma mass spectrometry to visualize the platinum distribution in the ovarian cancer tissues at the time of interval debulking surgery after neoadjuvant chemotherapy in 27patients with advanced high-grade serous ovarian cancer. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum throughout the tumor and adjacent stroma. The type A patients treated post-surgery with platinum-based adjuvant chemotherapy showed significantly shorter periods of recurrence after the last platinum-based chemotherapy session (p = 0.020) and were diagnosed with “platinum-resistant recurrence”. Moreover, type A was significantly correlated with worse prognosis (p = 0.031). Post-surgery treatment with non-platinum-based chemotherapy could be effective for the patients classified as type A. Our findings indicate that the platinum resistance can be predicted prior to recurrence, based on the platinum distribution; this could contribute to the selection of more appropriate adjuvant chemotherapy, which may lead to improves prognoses.

    DOI: 10.1038/s41598-022-08503-7

    Web of Science

    Scopus

    PubMed

  4. Survival benefits of retroperitoneal lymphadenectomy for optimally-resected advanced ovarian high-grade serous carcinoma: a multi-institutional retrospective study.

    Ikeda Y, Yoshihara M, Tamauchi S, Yokoi A, Yoshikawa N, Kajiyama H

    Journal of gynecologic oncology     2022年2月

     詳細を見る

    記述言語:英語  

    DOI: 10.3802/jgo.2022.33.e40

    PubMed

  5. Clinical effects of cervical conization with positive margins in cervical cancer

    Nagao Yukari, Yokoi Akira, Yoshida Kosuke, Sumi Masanori, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   11 巻 ( 1 ) 頁: 23288   2021年12月

     詳細を見る

    記述言語:日本語   出版者・発行元:Scientific Reports  

    Radical surgery after cervical conization is a common approach for the treatment of cervical cancer. In some cases, disease progression is observed after positive margins at conization, but the effect of conization on disease progression remains unclear. Thus, the aim of this study was to investigate the clinical outcomes of positive margins at conization in cervical cancer. A total of 101 patients who underwent cervical conization before radical hysterectomy and pelvic lymph node dissection were considered eligible by reviewing medical records. The association between the positive margins and patient outcomes, including subsequent lymph node metastasis, was evaluated. The rate of lymphovascular space invasion (LVSI) positivity at radical surgery was significantly higher in patients with positive margins (p = 0.017) than in those with negative margins, although there was no significant difference in the rate of pelvic lymph node metastasis (p = 0.155). Moreover, there was no significant difference in the overall survival or progression-free survival between the two groups (p = 0.332 and 0.200, respectively). A positive margin at conization presented no significant prognostic disadvantage; thus, diagnostic conization is one of the most suitable treatment options for early-stage cervical cancer that is difficult to accurately assess.

    DOI: 10.1038/s41598-021-02635-y

    Web of Science

    Scopus

    PubMed

  6. 特集 図解 分子メカニズムから理解する婦人科がんの薬物療法 【各論】 Ⅰ 卵巣悪性腫瘍 2.胚細胞腫瘍

    玉内 学志, 梶山 広明

    産婦人科の実際   70 巻 ( 12 ) 頁: 1472 - 1478   2021年11月

     詳細を見る

    出版者・発行元:金原出版  

    DOI: 10.18888/sp.0000001964

    CiNii Research

  7. Achievement of live birth after overcoming two gynecological malignancies treated with radical trachelectomy and medroxyprogesterone acetate therapy

    Tamauchi Satoshi, Moriyama Yoshinori, Suzuki Shiro, Ikeda Yoshiki, Yoshikawa Nobuhisa, Kajiyama Hiroaki

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   47 巻 ( 11 ) 頁: 4101 - 4105   2021年11月

     詳細を見る

    記述言語:日本語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Cervical cancer is a human papilloma virus-related disease, whereas endometrial cancer and atypical endometrial hyperplasia (AEH) are hormone-related diseases, so co-occurrence of the two is possible. However, scientific studies about such cases are rare. We encountered a case of cervical adenocarcinoma and AEH in a 33-year-old nulliparous woman. Two fertility-sparing treatments were performed, a radical trachelectomy for the cervical cancer and high-dose medroxyprogesterone acetate treatment for the AEH. After remission of the diseases, the patient became pregnant by in vitro fertilization and delivered a baby at 36 weeks' gestation by cesarean section. Although the patient had two uterine malignancies, proper evaluation of the diseases, consultation with the patient and her husband, and appropriate management led to fertility preservation, and live birth was achieved.

    DOI: 10.1111/jog.15001

    Web of Science

    Scopus

    PubMed

  8. Impact of incomplete surgery and adjuvant chemotherapy for the intraoperative rupture of capsulated stage I epithelial ovarian cancer: a multi-institutional study with an in-depth subgroup analysis

    Yoshihara Masato, Tamauchi Satoshi, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Mogi Kazumasa, Kajiyama Hiroaki

    JOURNAL OF GYNECOLOGIC ONCOLOGY   32 巻 ( 5 ) 頁: e66   2021年9月

     詳細を見る

    記述言語:日本語   出版者・発行元:Journal of gynecologic oncology  

    OBJECTIVE: The aim of the present study was to examine the effects of incomplete surgery and adjuvant chemotherapy on the prognosis of patients with intraoperative rupture of capsulated stage I epithelial ovarian cancer (OvCa). METHODS: A regional retrospective study was conducted between 1986 and 2019. Among 4,730 patients with malignant ovarian tumors, 534 women with International Federation of Gynecology and Obstetrics stage IA and IC1 epithelial OvCa were eligible. Differences in survival outcomes were examined between patients with stage IA and IC1 tumors and the effects of uterine preservation, complete-staging lymphadenectomy, and adjuvant chemotherapy were investigated by an in-depth subgroup analysis. To analyze therapeutic effects, baseline imbalances were adjusted using propensity score (PS). RESULTS: The prognosis of patients with stage IC1 tumors was worse than those with stage IA. Surgical spill did not affect the site of recurrence. In the PS-adjusted subgroup analysis, uterine preservation (hazard ratio [HR]=1.669; 95% confidence interval [CI]=1.052-2.744), incomplete-staging lymphadenectomy (HR=1.689; 95% CI=1.211-2.355), and the omission of adjuvant chemotherapy (HR=3.729; 95% CI=2.090-6.653) significantly increased the HR of recurrence for patients with stage IC1 tumors compared to those with stage IA tumors. Adjuvant chemotherapy decreased the impact of rupture with uterine preservation (HR=0.159; 95% CI=0.230-1.168) or incomplete-staging lymphadenectomy (HR=0.987; 95% CI=0.638-1.527). CONCLUSION: The present results suggest intraoperative rupture of capsulated stage I epithelial OvCa is associated with a poor prognosis. When chemotherapy is given for patients receiving incomplete surgery, there is no longer an increased risk of recurrence observed with the rupture.

    DOI: 10.3802/jgo.2021.32.e66

    Web of Science

    Scopus

    PubMed

  9. Is cystectomy an option as conservative surgery for young patients with borderline ovarian tumor? A multi-institutional retrospective study

    Ikeda Yoshiki, Yoshihara Masato, Yoshikawa Nobuhisa, Tamauchi Satoshi, Yokoi Akira, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS     2021年8月

     詳細を見る

    記述言語:日本語   出版者・発行元:International Journal of Gynecology and Obstetrics  

    Objective: To investigate the impact of cystectomy for borderline ovarian tumor (BOT) on tumor recurrence compared with salpingo-oophorectomy using inverse probability of treatment weighting (IPTW). Methods: A central pathologic review and a search of the medical records from 14 collaborating institutions from 1986 to 2017 identified 4708 women with a malignant ovarian neoplasm. Data for young women with Stage I BOT were extracted. To compare recurrence-free survival between the surgery groups, Cox regression analyses and the IPTW-adjusted Kaplan-Meier method were employed. Results: During a median follow-up of 62.0 (1.2–270.4) months, 10 of the 285 patients identified (3.5%) developed recurrence. In multivariate analysis, the practice of cystectomy was not a significant prognostic indicator of recurrence-free survival (hazard ratio [95% confidence interval] 1.276 [0.150–10.864]; P = 0.823). In the IPTW-adjusted cohort, the 5-year recurrence-free survival rates were 95.8% and 96.0% in patients receiving cystectomy and salpingo-oophorectomy, respectively (P = 0.378). Conclusion: If patients are selected appropriately, cystectomy in itself may not increase tumor recurrence in young women with early-stage BOT. A large-scale prospective clinical study is necessary to validate this finding.

    DOI: 10.1002/ijgo.13844

    Web of Science

    Scopus

    PubMed

  10. Metabolome analysis reveals a diversity of cancer tissues in advanced epithelial ovarian cancer

    Yoshida Kosuke, Yoshikawa Nobuhisa, Kitami Kazuhisa, Tamauchi Satoshi, Ikeda Yoshiki, Yokoi Akira, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    CANCER CELL INTERNATIONAL   21 巻 ( 1 ) 頁: 314   2021年6月

     詳細を見る

    記述言語:日本語   出版者・発行元:Cancer Cell International  

    Background: Epithelial ovarian cancer remains one of the leading causes of cancer deaths among women worldwide, and advanced epithelial ovarian cancer frequently metastasizes to the omentum. The characteristics of metastatic cancer may differ from those of primary ovarian cancer and reflect the unique omental microenvironment. This study investigated metabolomic differences in epithelial ovarian cancers. Methods: Patients with advanced epithelial ovarian cancer were eligible for this study. Five patients underwent surgery and resection of paired primary ovarian and omental metastatic cancer at Nagoya University. Metabolome analysis was performed in these paired cancer and metastatic cancer tissues through a facility service (C-SCOPE) at Human Metabolome Technologies, Inc. The concentrations of 116 compounds were measured by CE-TOFMS and CE-QqQMS, and 30 metabolic parameters were calculated. For statistical analyses, Welch’s t-test was used for comparisons between two independent groups. Results: Metabolite profiles were all different, which reflects diversity among these cancer tissues. Of the measured compounds, urea was the only metabolite that was significantly decreased in omental metastatic cancers compared with the primary cancers (p = 0.031). Moreover, in omental metastatic cancers, the pentose phosphate pathway was more dominant than glycolysis. Furthermore, in some cases, lactic acids in omental metastatic cancers were markedly decreased compared with primary cancers. With regard to histological subtype, the total levels of amino acids, especially the percentage of glutamine, were significantly enriched in serous carcinomas compared with nonserous carcinomas (p = 0.004 and p = 0.001). Moreover, the reduced forms of glutathione and polyamines were also more abundant in serous carcinomas than in nonserous carcinomas (p = 0.025 and 0.048). Conclusions: The metabolite profiles differed depending on tumor location and histological subtype. Metabolome analysis may be a useful tool for identifying cancer diagnostic and prognostic markers.

    DOI: 10.1186/s12935-021-02014-7

    Web of Science

    Scopus

    PubMed

  11. Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer

    Hattori Satomi, Yoshikawa Nobuhisa, Mogi Kazumasa, Yoshida Kosuke, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yokoi Akira, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kajiyama Hiroaki

    CURRENT ONCOLOGY   28 巻 ( 3 ) 頁: 1663 - 1672   2021年6月

     詳細を見る

    記述言語:日本語   出版者・発行元:Current Oncology  

    (1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor >6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028); the corresponding five-year OS rates in patients with a tumor ≤6.9 and >6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

    DOI: 10.3390/curroncol28030155

    Web of Science

    Scopus

    PubMed

  12. Does complete-staging lymphadenectomy improve survival outcomes in stage I endometrioid epithelial ovarian carcinoma? A multi-institutional retrospective study with propensity score-weighted analysis

    Yoshihara Masato, Tamauchi Satoshi, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Tano Sho, Matsui Shigeyuki, Kajiyama Hiroaki

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   51 巻 ( 3 ) 頁: 387 - 392   2021年3月

     詳細を見る

    記述言語:日本語   出版者・発行元:Japanese Journal of Clinical Oncology  

    Background: We investigated the prognostic impact of complete-staging lymphadenectomy on patients with clinically apparent Stage I endometrioid epithelial ovarian carcinoma. Methods: We conducted a regional multi-institutional retrospective study between 1986 and 2018. Amongst 4897 patients with malignant ovarian tumours diagnosed under central pathological review, 259 women with Stage I endometrioid epithelial ovarian carcinoma were eligible. We evaluated differences in survival of patients with both pelvic and para-aortic lymphadenectomy (Group A) and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation (Group B). To analyse the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. Results: In total, 145 patients (56.0%) received both pelvic and para-aortic lymphadenectomy. With propensity score-based adjustment, estimated survival was better in Group A compared with that in Group B but not significant. Pelvic and para-aortic lymphadenectomy also led to no significant improvement of overall survival in most of the subgroups. However, point estimations of the hazard ratio for lymphadenectomy in patients with an age of 45 or younger (hazard ratio, 0.304; 95% confidence interval, 0.094-0.982), a Grade 1-2 (hazard ratio, 0.441; 95% confidence interval, 0.204-0.954) and T1c2-3 tumour (hazard ratio, 0.449; 95% confidence interval, 0.164-1.231) were better compared with those with the opposite characteristics. Conclusions: Complete-staging lymphadenectomy was not a significant prognostic factor in patients with Stage I endometrioid epithelial ovarian carcinoma, where we still need to explore appropriate candidate for the procedure.

    DOI: 10.1093/jjco/hyaa206

    Web of Science

    Scopus

    PubMed

  13. The role of chrXq27.3 miRNA cluster in advanced ovarian clear cell carcinoma

    Yoshida Kosuke, Yokoi Akira, Yoshihara Masato, Tamauchi Satoshi, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Kikkawa Fumitaka, Kajiyama Hiroaki

    CANCER SCIENCE   112 巻   頁: 291 - 291   2021年2月

     詳細を見る

    記述言語:日本語  

    Web of Science

  14. Visualization of platinum resistance through mapping trace elements

    Uno Kaname, Yoshikawa Nobuhisa, Yoshihara Masato, Tazaki Kei, Kato Masashi, Kitami Kazuhisa, Iyoshi Shohei, Tamauchi Satoshi, Sugiyama Mai, Koya Yoshihiro, Kajiyama Hiroaki

    CANCER SCIENCE   112 巻   頁: 906 - 906   2021年2月

     詳細を見る

    記述言語:日本語  

    Web of Science

  15. Active vitamin D inhibits mesothelial-mesenchymal-transition accelerating peritoneal dissemination in ovarian cancer

    Kitami Kazuhisa, Yoshihara Masato, Sugiyama Mai, Koya Yoshihiro, Iyoshi Shohei, Uno Kaname, Mogi Kazumasa, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   112 巻   頁: 351 - 351   2021年2月

     詳細を見る

    記述言語:日本語  

    Web of Science

  16. Luteolin suppresses Ovarian Cancer progression via decrease the expression of VRK1

    Chang Xuboya, Kajiyama Hiroaki, Yoshikawa Nobuhisa, Yokoi Akira, Tamauchi Satoshi, Yoshihara Masato

    CANCER SCIENCE   112 巻   頁: 770 - 770   2021年2月

     詳細を見る

    記述言語:日本語  

    Web of Science

  17. Intra-tumoral polarity induced by Notch signaling can be a novel therapeutic target for advanced ovarian cancer

    Yoshihara Masato, Sugiyama Mai, Koya Yoshihiro, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Mogi Kazumasa, Tano Sho, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   112 巻   頁: 363 - 363   2021年2月

     詳細を見る

    記述言語:日本語  

    Web of Science

  18. How do peritoneal mesothelial cells on adipose tissue attract ovarian cancer cells?

    Mogi Kazumasa, Yoshihara Masato, Kitami Kazuhisa, Iyoshi Shohei, Uno Kaname, Tano Sho, Sugiyama Mai, Koya Yoshihiro, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   112 巻   頁: 341 - 341   2021年2月

     詳細を見る

    記述言語:日本語  

    Web of Science

  19. 特集 サインから読み解く婦人科画像診断 9. 婦人科超音波のサイン 2. Dermoid cone,acoustic shadow,hair ball

    玉内 学志, 梶山 広明

    画像診断   37 巻 ( 9 ) 頁: 959 - 959   2017年7月

     詳細を見る

    出版者・発行元:学研メディカル秀潤社  

    DOI: 10.15105/gz.0000000065

    CiNii Research

  20. Reduced response to controlled ovarian stimulation after radical trachelectomy: A pitfall of fertility-sparing surgery for cervical cancer

    Tamauchi Satoshi, Kajiyama Hiroaki, Osuka Satoko, Moriyama Yoshinori, Yoshihara Masato, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS   154 巻 ( 1 ) 頁: 162 - 168   2021年7月

     詳細を見る

    記述言語:日本語   出版者・発行元:International Journal of Gynecology and Obstetrics  

    Objective: To clarify the decrease in response to controlled ovarian stimulation in patients who receive in vitro fertilization treatment after radical trachelectomy. Methods: The outcomes of ovarian stimulation were retrospectively evaluated and compared between patients who have undergone radical trachelectomy and control patients who had male factor infertility or unexplained infertility. Results: A total of 30 ovarian stimulation cycles in 14 radical trachelectomy patients and 54 cycles in 30 control patients were reviewed. The median age at ovarian stimulation was 34.8 years in the radical trachelectomy group and 36.5 years in the control group. Compared with the control group, the radical trachelectomy group had significantly lower mean estradiol concentration (1461.7 pg/ml, SD 775.0 vs. 1950.9 pg/ml, SD 1057.3, P = 0.029) during controlled ovarian stimulation cycle and smaller median number of retrieved oocytes (5, range 1–14 vs. 8, range 1–19, P = 0.007), despite the higher use of gonadotropin (3527.5 IU, SD 1313.4 vs. 2670.8 IU, SD 905.1, P = 0.001). Conclusion: The response to controlled ovarian stimulation decreased after radical trachelectomy.

    DOI: 10.1002/ijgo.13529

    Web of Science

    Scopus

    PubMed

  21. Expression of the chrXq27.3 miRNA cluster in recurrent ovarian clear cell carcinoma and its impact on cisplatin resistance 国際誌

    Yoshida Kosuke, Yokoi Akira, Sugiyama Mai, Oda Shingo, Kitami Kazuhisa, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka, Yokoi Tsuyoshi, Kajiyama Hiroaki

    ONCOGENE   40 巻 ( 7 ) 頁: 1255 - 1268   2021年2月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oncogene  

    Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer and exhibits dismal prognosis due to chemoresistance. Moreover, only few effective therapeutic options exist for patients with recurrent OCCC, and an understanding of its molecular characteristics is essential for the development of novel therapeutic approaches. In the present study, we investigated unique MicroRNAs (miRNA) profiles in recurrent/metastatic OCCC and the role of miRNAs in cisplatin resistance. Comprehensive miRNA sequencing revealed that expression of several miRNAs, including miR-508-3p, miR-509-3p, miR-509-3-5p, and miR-514a-3p was remarkably less in recurrent cancer tissues when compared with that in paired primary cancer tissues. These miRNAs are located in the chrXq27.3 region on the genome. Moreover, its expression was negative in omental metastases in two patients with advanced OCCC. In vitro analyses revealed that overexpression of miR-509-3p and miR-509-3-5p reversed cisplatin resistance and yes-associated protein 1 (YAP1) was partially responsible for the resistance. Immunohistochemistry revealed that YAP1 expression was inversely correlated with the chrXq27.3 miRNA cluster expression. In conclusion, these findings suggest that alteration of the chrXq27.3 miRNA cluster could play a critical role in chemoresistance and miRNAs in the cluster and their target genes can be potential therapeutic targets.

    DOI: 10.1038/s41388-020-01595-3

    Web of Science

    Scopus

    PubMed

  22. Establishment of a patient-derived xenograft model and cell line of malignant transformation of mature cystic teratoma of the ovary 国際誌

    Tamauchi Satoshi, Suzuki Shiro, Xuboya Chang, Yoshihara Masato, Yoshida Kosuke, Ikeda Yoshiki, Yoshikawa Nobuhisa, Kajiyama Hiroaki, Kikkawa Fumitaka

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   47 巻 ( 2 ) 頁: 713 - 719   2021年2月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aim: Malignant transformation of mature cystic teratoma (MTMCT) of the ovary is a rare gynecological malignancy and commonly arises in women older than 50 years of age. The most common histological type of MTMCT is squamous cell carcinoma (SCC), and the prognosis is extremely poor. Patient-derived xenograft (PDX) models are promising animal models for preclinical drug screening. Here, we report the generation of a new PDX model of MTMCT, and a new cell line established from the tumors of PDX model animals. Methods: Tumor tissue was obtained from a 32-year-old patient with MTMCT. To generate PDX, NSG (NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ) mice, a strain of super-immunodeficient mice, were used. Tumor-bearing mice were sacrificed, followed by the collection of these tumors and re-transplantation into new NSG mice (in vivo passage). Tumor samples were also cultured in vitro. Adherent cells were continuously cultured and passaged, a cell line was established. Results: In the primary PDX mouse, tumor engraftment was confirmed 30 days after tumor implantation. After three times in vivo passage, we confirmed that the cryopreserved tumors could be engrafted even when transplanted into BALB/c nude mice. Using the tumor tissue at the time of the first in vivo passage, a new cell line NOSCC1 was established. PDX tumors and cell-line derived xenograft tumors exhibited similar morphology of SCC. Conclusion: We established a new PDX model of MTMCT and a new cell line of it, which may be important tools for the development of new therapies and the elucidation of the carcinogenic mechanisms of MTMCT.

    DOI: 10.1111/jog.14596

    Web of Science

    Scopus

    PubMed

  23. A uterine pseudotumor of immunoglobulinG4-related disease

    Senda Yasutaka, Ikeda Yoshiki, Tamauchi Satoshi, Yoshikawa Nobuhisa, Kikkawa Fumitaka, Kajiyama Hiroaki

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   47 巻 ( 1 ) 頁: 430 - 435   2021年1月

     詳細を見る

    記述言語:日本語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Immunoglobulin G4-related disease (IgG4-RD) is characterized by systemic lesions presenting as swellings, nodules and wall thickenings. The first-line therapy is glucocorticoids. This disease is common among middle-aged and elderly men, and its uterine mass formation is uncommon. We encountered a 39-year-old nulliparous woman with an IgG4-related uterine mass and enlarged pelvic lymph nodes. Complete remission was achieved by fertility-sparing resection of the uterine mass without glucocorticoids. This case showed that IgG4-RD can present as a uterine mass and we need to be careful of its diagnostic and therapeutic strategies because an IgG4-related uterine mass is difficult to distinguish from sarcoma or malignant lymphoma. Our case also demonstrated that IgG4-related lymphadenopathy could regress spontaneously without complete lymphadenectomy or glucocorticoids when IgG4-RD does not affect vital organs. A pelvic mass with hyperproteinemia may be a hint to remind us of IgG4-RD and may trigger a preoperative immunoglobulin test.

    DOI: 10.1111/jog.14531

    Web of Science

    Scopus

    PubMed

  24. Sarcopenia as a Predictor of Survival Among Patients With Organ Metastatic Cervical Cancer 国際誌

    Yoshikawa Nobuhisa, Shirakawa Akira, Yoshida Kosuke, Tamauchi Satoshi, Suzuki Shiro, Kikkawa Fumitaka, Kajiyama Hiroaki

    NUTRITION IN CLINICAL PRACTICE   35 巻 ( 6 ) 頁: 1041 - 1046   2020年12月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nutrition in Clinical Practice  

    Background: This study was conducted to investigate the prognostic significance of sarcopenia in patients with organ metastatic cervical cancer. Methods: Accordingly, the data of 40 patients with organ metastatic cervical cancer treated at our institute from December 2004 to December 2017 were retrospectively analyzed. The correlation between clinicopathological characteristics and survival was then evaluated using univariate and multivariate analyses. Psoas muscle index (PMI), calculated from the psoas muscle area at the L3 vertebral-body level using computed tomography images obtained for pretreatment evaluation, was adopted as an index of sarcopenia. Results: The median follow-up period was 14 months (range, 1–91 months). Kaplan-Meier analysis showed a 3- and 5-year overall survival (OS) rate of 46.1% and 35.8% for all patients, respectively. Receiver operating characteristic curve maximizing the area under the curve showed that the optimal PMI for predicting 1-year survival was 3.72 cm2/m2. Patients with a PMI > 3.72 cm2/m2 had significantly better OS than those with a PMI ≤ 3.72 cm2/m2 (P =.046). Multivariate analysis revealed that only PMI was significantly associated with OS in patients with organ metastatic cervical cancer. Furthermore, patients with a PMI > 3.72 cm2/m2 who underwent concurrent chemoradiotherapy (CCRT) had a longer OS than those receiving other therapies (P <.001). Conclusions: High PMI was determined to be a favorable prognostic factor for patients with organ metastatic cervical cancer. Moreover, patients with organ metastatic cervical cancer who have a PMI > 3.72 cm2/m2 may benefit from CCRT as an initial treatment.

    DOI: 10.1002/ncp.10482

    Web of Science

    Scopus

    PubMed

  25. Does uterine preservation affect survival outcomes of patients with stage I ovarian sex cord-stromal cell tumours? A multi-institutional study

    Yoshihara Masato, Tamauchi Satoshi, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Yoshikawa Nobuhisa, Ikeda Yoshiki, Kawai Michiyasu, Nagasaka Tetsuro, Kajiyama Hiroaki

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY   254 巻   頁: 52 - 56   2020年11月

     詳細を見る

    記述言語:日本語   出版者・発行元:European Journal of Obstetrics and Gynecology and Reproductive Biology  

    Objective: Sex cord-stromal tumours of the ovary are relatively uncommon neoplasms that account for 3 % of all ovarian cancers. Uterine preservation with careful staging is achievable; however, conservative surgery remains controversial. This study examined the prognostic effects of uterine preservation in patients with stage I sex cord-stromal tumours. Study design: This retrospective cohort study was undertaken between January 1986 and February 2019, and the clinicopathological data of 4897 women with malignant ovarian tumours were collected. Seventy-seven patients with stage I sex cord-stromal tumours were eligible for inclusion. The characteristics and survival outcomes of these patients were examined. To investigate the prognostic effects of uterine-preserving surgery, baseline imbalances between patients with and without uterine-preserving surgery were adjusted using an inverse probability of treatment weighting with propensity scores composed of independent clinical variables. Results: The mean ages of patients in the uterine-preserving surgery and non-uterine-preserving surgery groups were 39.8 and 57.8 years, respectively. After inverse probability of treatment weighting adjustments, no significant differences in overall survival (p = 0.205) or recurrence-free survival (p=0.071) were observed between the uterine-preserving surgery and non-uterine-preserving surgery groups. Estimated 10-year overall survival rates were 98.7 % in the uterine-preserving surgery group and 95.9 % in the non-uterine-preserving surgery group, and 10-year recurrence-free survival rates were 87.2 % in the uterine-preserving surgery group and 78.2 % in the non-uterine-preserving surgery group. Uterine-preserving surgery did not significantly affect the site of tumour recurrence. Conclusion: Uterine-preserving surgery may be a feasible surgical option for patients with stage I sex cord-stromal tumours. Further research is needed to guarantee prognostic accuracy and develop effective therapeutic approaches for sex cord-stromal tumours.

    DOI: 10.1016/j.ejogrb.2020.09.009

    Web of Science

    Scopus

    PubMed

  26. Follicular dendritic cell sarcoma of the uterine cervix: a case report

    Nakamura Takuto, Yoshihara Masato, Tamauchi Satoshi, Kajiyama Hiroaki, Kikkawa Fumitaka

    BMC WOMENS HEALTH   20 巻 ( 1 ) 頁: 182   2020年8月

     詳細を見る

    記述言語:日本語   出版者・発行元:BMC Women's Health  

    Background: Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal tumor that mostly occurs in systemic lymph nodes. FDCS in the uterine cervix has not yet been reported. Case presentation: A 49-year-old woman was referred to our department with a cervical tumor, which was histologically suspected to be undifferentiated carcinoma. She underwent hysterectomy, salpingo-oophorectomy, and pelvic lymphadenectomy after neoadjuvant chemotherapy with paclitaxel and carboplatin. The resected specimen contained high numbers of spindle cells and was immunohistochemically confirmed to be FDCS. The tumor was completely resected and recurrence was not detected at a 16-month follow-up. Conclusion: FDCS is an extremely rare malignant tumor in the uterine cervix, and an accurate diagnosis and complete resection are essential for a good prognosis.

    DOI: 10.1186/s12905-020-01045-y

    Web of Science

    Scopus

    PubMed

  27. Impact of uterus-preserving surgery on Stage I primary mucinous epithelial ovarian carcinoma: A multi-institutional study with propensity score-weighted analysis

    Yoshihara Masato, Kajiyama Hiroaki, Tamauchi Satoshi, Iyoshi Shohei, Yokoi Akira, Suzuki Shiro, Kawai Michiyasu, Nagasaka Tetsuro, Takahashi Kunihiko, Matsui Shigeyuki, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS   150 巻 ( 2 ) 頁: 177 - 183   2020年8月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Gynecology and Obstetrics  

    Objective: To investigate the clinical characteristics of women with Stage I primary mucinous epithelial ovarian carcinoma (mEOC) and evaluate the impact of uterus-preserving surgery (UPS) in terms of survival prognosis. Methods: A regional multi-institutional retrospective study conducted between January 1986 and March 2017 by reviewing records of the Tokai Ovarian Tumor Study Group. Clinical and pathologic data and survival outcomes were assessed for women with Stage I primary mEOC. The baseline imbalance between women with and those without UPS was adjusted by an inverse probability of treatment weighting method using the propensity score (PS) of independent clinical variables. Results: Among 4730 women with malignant ovarian tumors, 185 had Stage I primary mEOC and were included in the study. The mean age was 47.6 years (range 12–87 years), and 56 (30.3%) women underwent UPS. After PS-based adjustment, women in the UPS group did not have a poorer prognosis regarding overall survival (P=0.776) or recurrence-free survival (P=0.683). Even after age stratification, there was no statistical difference in survival outcomes between the UPS and non-UPS groups. Conclusion: UPS was not associated with decreased survival and may be a treatment option for women with Stage I primary mEOC irrespective of age.

    DOI: 10.1002/ijgo.13244

    Web of Science

    Scopus

    PubMed

  28. The impact of systematic retroperitoneal lymphadenectomy on long-term oncologic outcome of women with advanced ovarian clear-cell carcinoma

    Kajiyama Hiroaki, Suzuki Shiro, Yoshikawa Nobuhisa, Tamauchi Satoshi, Shibata Kiyosumi, Kikkawa Fumitaka

    JOURNAL OF GYNECOLOGIC ONCOLOGY   31 巻 ( 4 ) 頁: e47 - 11   2020年7月

     詳細を見る

    記述言語:日本語   出版者・発行元:Journal of Gynecologic Oncology  

    Objective: The impact of systematic retroperitoneal lymphadenectomy (SRL) remains controversial in patients with advanced ovarian clear-cell carcinoma (CCC) who are optimally debulked. Methods: Between 1986 and 2017, a total of 3,227 women with epithelial ovarian carcinoma were analyzed in a multi-institutional study. Among them, 166 optimally debulked women with stage IIB–IV CCC were collected (residual tumor of <1 cm). All patients were divided into 2 groups: 1) Group I (n=112): underwent standard radical surgery with SRL, 2) Group II (n=54): underwent non-staging limited surgery. The pathological slides were assessed based on central pathological review. Oncologic outcomes were compared between the two groups using a propensity score (PS)-matching technique to adjust for various clinicopathologic factors. Results: The median follow-up duration of all surviving women was 52.8 (1.6–184.2) months. Overall, 88 patients (53.0%) experienced recurrence and 68 patients (41.0%) died of the disease. In the original cohort, the 5-year overall survival (OS) rates of groups I and II were 57.9 and 64.9%, respectively (log-rank p=0.415). In the PS-adjusted cohort, the 5-year OS rates were 64.9 and 58.8% in women in groups I and II, respectively (p=0.453). Furthermore, in the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in OS between the 2 groups (group I vs. group II; hazard ratio=1.170; 95% confidence interval=0.633–2.187; p=0.615). Conclusions: This study suggests that the performance of SRL including radical surgery may not lead to a significant improvement in the oncologic outcome of advanced CCC patients with optimal cytoreduction.

    DOI: 10.3802/jgo.2020.31.e47

    Web of Science

    Scopus

    PubMed

  29. The Preoperative Prognostic Nutritional Index for the Prediction of Outcomes in Patients with Early-Stage Ovarian Clear Cell Carcinoma 国際誌

    Yoshikawa Nobuhisa, Yoshida Kosuke, Tamauchi Satoshi, Ikeda Yoshiki, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   10 巻 ( 1 ) 頁: 7135 - 7135   2020年4月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    The prognostic nutritional index (PNI), which reflects preoperative malnutrition, is useful for predicting the incidence of postoperative complications and has been reported in recent years to predict the long-term prognosis of various malignancies. The purpose of this study was to clarify the significance of PNI as a prognostic factor for early-stage clear cell ovarian carcinoma. A total of 82 patients with stage I–II (FIGO 2014) ovarian clear cell carcinoma undergoing primary surgery at our hospital from January 2005 to December 2017 were enrolled. PNI was calculated using the formula: 10 × serum albumin (g/ dL) + 0.005 × peripheral blood lymphocyte count (/mm3). Preoperative PNI exhibited relatively high area under the curve value (0.709) for 5 year survival, and the optimal cutoff value was 46.5. The overall survival was significantly shorter in the PNI-low group than in the PNI-high group. Multivariate analysis showed that high PNI was a significant independent prognostic factor for favorable prognosis (hazard ratio = 0.102, p = 0.010). There was no significant difference in recurrence-free survival between the two groups (p = 0.220), but the postrecurrence survival was significantly longer in the PNI-high group than in the PNI-low group (p = 0.0383). The preoperative PNI was a useful predictor of prognosis, even in early-stage ovarian clear cell carcinoma.

    DOI: 10.1038/s41598-020-64171-5

    Web of Science

    Scopus

    PubMed

  30. The Therapeutic Effects of Goreisan, a Traditional Japanese Herbal Medicine, on Lower-Limb Lymphedema after Lymphadenectomy in Gynecologic Malignancies: A Case Series Study

    Yoshikawa Nobuhisa, Kajiyama Hiroaki, Otsuka Naoki, Tamauchi Satoshi, Ikeda Yoshiki, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Utsumi Fumi, Shibata Kiyosumi, Kikkawa Fumitaka

    EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE   2020 巻   頁: 6298293   2020年4月

     詳細を見る

    記述言語:日本語   出版者・発行元:Evidence-based Complementary and Alternative Medicine  

    Background. Lower-limb lymphedema (LLL) is a chronic and progressive complication of gynecologic cancer treatment, including pelvic lymphadenectomy. This study aims to investigate the therapeutic effect of goreisan, a traditional Japanese medicine, which has been used for hydrostatic modulation on patients with LLL. Methods. Patients diagnosed with LLL in our hospital in 2018 were included and principally treated with complex decongestive therapy (CDT), including elastic clothing and lymph drainage. The patients who received a combination therapy of CDT and goreisan (CDT-G group) were prescribed goreisan extract granules, with a dose of 7.5 g per os daily in three doses. Patients who were not prescribed goreisan received CDT alone (CDT group). The severity of lymphedema was evaluated by the estimated limb volume calculated by limb circumferences and the ratio of extracellular water (ECW) to total body water (TBW). Results. Nineteen women with LLL after pelvic lymphadenectomy were included in the study. The number of patients in the CDT and CDT-G groups was 8 and 11, respectively. There were no statistically significant differences between the CDT and CDT-G groups in terms of patient characteristics and severity of LLL before treatment. Reduction in ECW/TBW in the CDT-G group (in the whole body and the affected lower limb) after the intervention was significantly more remarkable than that in the CDT group. Conclusions. Goreisan-based Japanese herbal therapy may be effective in patients with LLL after retroperitoneal lymphadenectomy.

    DOI: 10.1155/2020/6298293

    Web of Science

    Scopus

    PubMed

  31. Is standard radical surgery necessary for elderly patients with early-stage epithelial ovarian carcinoma? similar to Propensity score matched analysis similar to

    Kajiyama Hiroaki, Yoshihara Masato, Tamauchi Satoshi, Yoshikawa Nobuhisa, Niimi Kaoru, Suzuki Shiro, Shibata Kiyosumi, Kikkawa Fumitaka

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   50 巻 ( 4 ) 頁: 411 - 418   2020年4月

     詳細を見る

    記述言語:日本語   出版者・発行元:Japanese Journal of Clinical Oncology  

    Objective: The impact of 'standard full-staged radical surgery (SRS)' on overall survival (OS) in elderly patients with early-stage epithelial ovarian cancer (EOC) remains unclear. In the current study, we investigated the impact of SRS on OS in elderly patients with early-stage EOC in a multicentric analysis using a propensity score (PS)-matching technique. Methods: Between 1986 and 2017, 3227 patients with EOC were registered and accumulated by the Tokai Ovarian Tumor Study Group, consisting of 14 collaborating institutions, after a central pathological review. Among them, 204 elderly patients aged older than or equal to 65 years who had a stage I EOC were analyzed, including 72 patients who had received SRS (Group I) and 132 who had undergone non-SRS limited surgery (Group II). Oncologic outcomes were compared between the two groups using a PS-matching technique to adjust for various clinicopathologic risk factors. Results: The median follow-up duration of all surviving patients was 55.9 months. Consequently, 54 patients (26.5%) developed recurrence. In addition, 33 patients (16.2%) died of the disease. In the original cohort, the 5-year OS rates of Groups I and II were 95.8 and 82.3%, respectively. We identified a marginally significant difference between the two groups (Log-rank: P = 0.086). In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in OS between the two groups [OS (Group I vs. II), HR: 0.766 (95% CI: 0.271-2.165), P = 0.615]. Conclusions: After adjustment for clinicopathologic factors, non-SRS limited surgery may not worsen the oncologic outcome in elderly women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.

    DOI: 10.1093/jjco/hyz194

    Web of Science

    Scopus

    PubMed

  32. CCL2 secreted from cancer-associated mesothelial cells promotes peritoneal metastasis of ovarian cancer cells through the P38-MAPK pathway

    Yasui Hiroaki, Kajiyama Hiroaki, Tamauchi Satoshi, Suzuki Shiro, Peng Yang, Yoshikawa Nobuhisa, Sugiyama Mai, Nakamura Kae, Kikkawa Fumitaka

    CLINICAL & EXPERIMENTAL METASTASIS   37 巻 ( 1 ) 頁: 145 - 158   2020年2月

     詳細を見る

    記述言語:日本語   出版者・発行元:Clinical and Experimental Metastasis  

    Epithelial ovarian cancer (EOC) is considered to secrete various factors in order to promote peritoneal dissemination through cell-to-cell interaction between cancer and mesothelial cells. We previously revealed that TGF-β secreted from EOC induces normal human peritoneal mesothelial cells (HPMCs) to differentiate into cancer-associated mesothelial cells (CAMCs). However, the relationship between tumor cells and CAMCs in EOC is still unclear. We hypothesized that CAMCs also secrete chemokines that attract cancer cells and induce peritoneal dissemination of EOC. We examined chemokines secreted from HPMCs and CAMCs by human chemokine array, and revealed that conditioned medium of CAMCs (CAMCs-CM) included many types of chemokines. The signals of CCL2 were the highest compared with other chemokines. The secretion and relative expression of CCL2 were significantly higher in CAMCs. Recombinant CCL2 promoted trans-mesothelial migration of HPMCs and the migration and invasion by EOC cells. In addition, CCL2 secreted from CAMCs promoted invasion of EOC cells. Furthermore, the neutralizing antibody of CCL2 reduced invasion by EOC. Clinical outcomes of patients whose tissue expressed higher CCR2 were significantly poorer than in patients whose tissue expression was lower. CCL2 activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK). In addition, CAMCs-CM activated the p38 MAPK pathway. Phosphorylation of p38 MAPK reduced with the presence of neutralizing antibody of CCL2. In conclusion, these data indicate CCL2 in CAMCs-CM promoted the malignant potential of EOC. CCL2 plays a crucial role in the tumor microenvironment of EOC.

    DOI: 10.1007/s10585-019-09993-y

    Web of Science

    Scopus

    PubMed

  33. Prognostic impact of pelvic and para-aortic lymphadenectomy on clinically-apparent stage I primary mucinous epithelial ovarian carcinoma: a multi-institutional study with propensity score-weighted analysis

    Yoshihara Masato, Kajiyama Hiroaki, Tamauchi Satoshi, Iyoshi Shohei, Yokoi Akira, Suzuki Shiro, Kawai Michiyasu, Nagasaka Tetsuro, Takahashi Kunihiko, Matsui Shigeyuki, Kikkawa Fumitaka

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   50 巻 ( 2 ) 頁: 145 - 151   2020年2月

     詳細を見る

    記述言語:日本語   出版者・発行元:Japanese Journal of Clinical Oncology  

    Background: The exact impact of full-staging lymphadenectomy on patients with primary mucinous epithelial ovarian carcinoma confined to the ovary is still unclear. In this study, we investigated the prognostic impact of lymphadenectomy covering both pelvic and para-aortic lymph nodes in patients with clinically-apparent stage I mucinous epithelial ovarian carcinoma, using data from multi-institutions under a central pathological review system and analyses with a propensity score-based method. Methods: We conducted a regional multi-institutional retrospective study between 1986 and 2017. Among 4730 patients with malignant ovarian tumors, a total of 186 women with mucinous epithelial ovarian carcinoma were eligible. We evaluated differences in survival outcomes between patients with both pelvic and para-aortic lymphadenectomy and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation. To analyze the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. Results: Fifty-five patients received both pelvic and para-aortic lymphadenectomy. With PS-based adjustment, both pelvic and para-aortic lymphadenectomy did not have additive effects regarding overall survival (P = 0.696) and recurrence-free survival (P = 0.978). Multivariate analysis similarly showed no significant impact of both pelvic and para-aortic lymphadenectomy on their prognosis. Conclusions: The effect of pelvic and para-aortic lymphadenectomy is limited for clinically-apparent stage I primary mucinous epithelial ovarian carcinoma as long as full peritoneal and clinical lymph node evaluations are conducted. The results of this study should be used as the basis for additional studies, including prospective trials.

    DOI: 10.1093/jjco/hyz163

    Web of Science

    Scopus

    PubMed

  34. The role of additional hysterectomy after concurrent chemoradiation for patients with locally advanced cervical cancer

    Yoshida Kosuke, Kajiyama Hiroaki, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   25 巻 ( 2 ) 頁: 384 - 390   2020年2月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Clinical Oncology  

    Background: The standard treatment for cervical cancer is chemoradiation although some patients showed treatment resistance. The purpose of this study was to investigate the clinical efficacy of surgery after chemoradiation for cervical cancer. Methods: Patients with FIGO stage IB2 to IIB cervical cancer were included in the study between 2005 and 2015. A total of 50 patients who underwent surgery after neoadjuvant chemoradiation and 76 patients who received only chemoradiation were compared. Baseline differences between the two groups were adjusted with inverse probability of treatment weighting method using propensity scores composed of the following independent variables: age, stage, tumor size, lymph node metastasis, and histological subtypes. Results: Median follow-up was 64.8 (range 4.8–143.9) months. After adjustment with inverse probability of treatment weighting, Kaplan–Meier curves showing adjusted progression-free survival and overall survival were significantly longer in the neoadjuvant chemoradiation compared with the chemoradiation-only group (p = 0.027 and p = 0.017, respectively). Moreover, in patients with squamous cell carcinoma, recurrence in previously irradiated field and recurrence both in and out of previously irradiated field were significantly decreased in the neoadjuvant chemoradiation compared with the chemoradiation-only group (3.1% and 18.4%, respectively; OR 0.142, p = 0.001]. Adverse events of surgery after chemoradiation were acceptable, although temporary hydronephrosis was frequently observed (23.1%). Conclusions: Surgery after chemoradiation reduced pelvic recurrence, and as a result, patients who underwent neoadjuvant chemoradiation showed more favorable survival outcomes compared with those who only underwent chemoradiation.

    DOI: 10.1007/s10147-019-01551-6

    Web of Science

    Scopus

    PubMed

  35. Impact of age on clinicopathological features and survival of epithelial ovarian neoplasms in reproductive age

    Hanatani Maya, Yoshikawa Nobuhisa, Yoshida Kosuke, Tamauchi Satoshi, Ikeda Yoshiki, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kawai Michiyasu, Kajiyama Hiroaki, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   25 巻 ( 1 ) 頁: 187 - 194   2020年1月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Clinical Oncology  

    Background: Little is known about the effect of age on the prognosis of epithelial ovarian neoplasms. In the reproductive age, fertility-sparing surgery had been widely implemented. This study aimed to elucidate impact of age on the clinicopathologic characteristics and survival of epithelial ovarian neoplasms in the reproductive age. Methods: The clinical records of patients diagnosed as epithelial ovarian cancer or epithelial borderline ovarian tumor at the age of 40 years or younger at multiple institutions in the Tokai Ovarian Tumor Study Group were reviewed retrospectively. All patients were stratified into two age groups: group A (≤ 30 years) and group B (31–40 years). Univariate and multivariate analyses were performed to evaluate overall survival and disease-free survival. Results: A total of 583 patients (325 patients: cancer, 258 patients: borderline) were included. The median follow-up time was 62.0 months (range 1–270 months). Compared with group B, group A had a significantly higher rate of borderline tumor (66.7% vs. 32.7%, p < 0.001); stage I disease (85.9% vs. 70.4%, p < 0.001); mucinous type (69.2% vs. 35.6%, p < 0.001); conservative surgery (83.8% vs. 41.6%, p < 0.001); no adjuvant chemotherapy (67.2% vs. 44.7%, p < 0.001); and CA125 ≤ 35 U/mL (39.4% vs. 28.8%, p < 0.05). There was a significant difference in the overall survival (p = 0.0051) and the disease-free survival (p = 0.0039) between the two groups. Multivariate analysis revealed that the independent prognostic factors for the overall survival were age, stage, histology, and ascitic fluid cytology. Conclusion: In epithelial ovarian neoplasms, younger patients had a survival advantage over older patients.

    DOI: 10.1007/s10147-019-01550-7

    Web of Science

    Scopus

    PubMed

  36. Complete Response of Recurrent Small Cell Carcinoma of the Uterine Cervix to Paclitaxel, Carboplatin, and Bevacizumab Combination Therapy

    Nakao Yuri, Tamauchi Satoshi, Yoshikawa Nobuhisa, Suzuki Shiro, Kajiyama Hiroaki, Kikkawa Fumitaka

    CASE REPORTS IN ONCOLOGY   13 巻 ( 1 ) 頁: 373 - 378   2020年

     詳細を見る

    記述言語:日本語   出版者・発行元:Case Reports in Oncology  

    We report a case of recurrent small cell carcinoma of the uterine cervix that showed a complete response to paclitaxel, carboplatin, and bevacizumab (TC + Bev) combination therapy. Small cell carcinoma of the uterine cervix is extremely rare, with an incidence of only 1.3% in Japan, and a poor outcome. The patient was a 62-year-old woman with a chief complaint of irregular vaginal bleeding. Magnetic resonance imaging showed a 10-cm irregular mass from the uterine corpus's posterior wall to the cervix. Abdominal total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling were performed for suspected uterine sarcoma. Histopathological findings revealed small cell carcinoma with lymph node metastasis. Although 6 cycles of etoposide + cisplatin were performed, para-aortic lymph node recurrence was found 3 months after chemotherapy. Subsequently, the patient received 8 cycles of TC + Bev, which eliminated the metastases. The patient is currently alive at 24 months.

    DOI: 10.1159/000506446

    Web of Science

    Scopus

    PubMed

  37. Clinical Significance of Ubiquitin-associated Protein 2-like in Patients With Uterine Cervical Cancer

    Yoshida Kosuke, Kajiyama Hiroaki, Inami Eri, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Shibata Kiyosumi, Nawa Akihiro, Kikkawa Fumitaka

    IN VIVO   34 巻 ( 1 ) 頁: 109 - 116   2020年

     詳細を見る

    記述言語:日本語   出版者・発行元:In Vivo  

    Background: Ubiquitin-associated protein 2-like (UBAP2L) has been demonstrated to be associated with the progression of multiple types of cancer. However, the function of UBAP2L in uterine cervical cancer remains unclear. Materials and Methods: Between 2005 and 2015, 84 patients who underwent surgery were included in this study. The patients were stratified into two groups on the basis of immunohistochemical staining for UBAP2L, and survival analysis was performed. Moreover, loss-of-function analysis was performed using the cervical cancer cell lines CaSki and SiHa. Results: Based on immunohistochemistry, the overall survival in patients with low UBAP2L expression was significantly longer than that of those with high UBAP2L expression (p=0.045). The in vitro experiment revealed that knockdown of UBAP2L remarkably inhibited cell proliferation in both live cell imaging and the MTS assay. Conclusion: Patients with high UBAP2L expression had unfavorable prognosis and UBAP2L appears to play an important role in proliferation.

    DOI: 10.21873/invivo.11751

    Web of Science

    Scopus

    PubMed

  38. Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma

    Shimbo Akiko, Kajiyama Hiroaki, Tamauchi Satoshi, Yoshikawa Nobuhisa, Ikeda Yoshiki, Nishino Kimihiro, Suzuki Shiro, Niimi Kaoru, Sakata Jun, Kikkawa Fumitaka

    ONCOLOGY REPORTS   42 巻 ( 6 ) 頁: 2323 - 2332   2019年12月

     詳細を見る

    記述言語:日本語   出版者・発行元:Oncology Reports  

    Recently, connective tissue growth factor (CTGF) was demonstrated to be associated with aggressive characteristics, including proliferation, invasion and metastasis, in a number of malignancies. Here, we investigated the expression and function of CTGF in epithelial ovarian carcinoma (EOC) to clarify its molecular mechanism and clinical significance. Paraffin sections from clinical samples of EOC (N=104) were immunostained with the CTGF antibody, and then the staining positivity was semiquantitatively examined. Moreover, we explored the role of CTGF expression in the migration-promoting effect on and chemoresistance of EOC cells. The results revealed that of the 104 EOC patients, the low and high CTGF staining expression rates were 65 (62.5%) and 39 (37.5%), respectively. Patients belonging to the higher-level CTGF group showed poorer progression-free (PFS) and overall survival (OS) rates than those in the lower-level group [PFS (log-rank: P=0.0076) and OS (log-rank: P=0.0078), respectively]. Multivariable analysis showed that CTGF expression was a significant predictor of poorer PFS and OS [PFS: HR (high vs. low): 1.837, 95% CI: 1.023-3.289 (P=0.0418); OS: HR: 2.141, 95% CI: 1.077-4.296 (P=0.0300)]. In in vitro studies, in acquired paclitaxel (PTX)-resistant EOC cells, the silencing of CTGF expression led to the restoration of PTX sensitivity. Furthermore, we confirmed that the TGF‑β‑dependent migration‑promoting effect on these CTGF‑depleted cells was completely inhibited. In conclusion, the results of the present study suggest the possible involvement of CTGF in the migration‑promoting effect and chemoresistance of EOC, suggesting that it may be a target for overcoming the malignant properties of EOC.

    DOI: 10.3892/or.2019.7352

    Web of Science

    Scopus

    PubMed

  39. Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background 国際誌

    Yoshida Kosuke, Yokoi Akira, Kagawa Takumi, Oda Shingo, Hattori Satomi, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Shibata Kiyosumi, Kajiyama Hiroaki, Yokoi Tsuyoshi, Kikkawa Fumitaka

    CARCINOGENESIS   40 巻 ( 12 ) 頁: 1435 - 1444   2019年12月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Carcinogenesis  

    Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma remain unclear. This study aims to elucidate the molecular background of malignant transformation from the aspects of microRNA (miRNA) profiling. We examined 7 patients with squamous cell carcinoma and 20 patients with mature teratoma and extracted their total RNA from formalin-fixed paraffin-embedded tissues. Then we prepared small RNA libraries and performed comprehensive miRNA sequencing. Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and mature teratoma tissues. Then we narrowed down cancer-related miRNAs, comparing paired-cancer and normal ovaries. Comparisons of cancer and mature teratoma identified two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p). In addition, these findings were validated in fresh cancer tissues of patient-derived xenograft (PDX) models. Moreover, several miRNAs, including miR-151a-3p and miR-378a-3p, were elevated in the murine plasma when tumor tissues were enlarged although miR-26a-5p and miR-99a-5p were not elucidated in the murine plasma. Finally, we performed target prediction and functional annotation analysis in silico and indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including 'pathway in cancer' and 'cell cycle'. In conclusion, this is the first study on miRNA sequencing for squamous cell carcinoma arising from mature teratoma. The study identified four cancer-related miRNAs that were considered to be related to the feature of malignant transformation. Moreover, miRNAs circulating in the murine plasma of the PDX model could be novel diagnostic biomarkers.

    DOI: 10.1093/carcin/bgz135

    Web of Science

    Scopus

    PubMed

  40. The usefulness of bevacizumab for relief from symptomatic malignant ascites in patients with heavily treated recurrent ovarian cancer 国際誌

    Shimizu Yusuke, Kajiyama Hiroaki, Yoshida Kosuke, Tamauchi Satoshi, Nakanishi Toru, Kikkawa Fumitaka

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   45 巻 ( 12 ) 頁: 2435 - 2439   2019年12月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aim: Accumulation of ascites fluid is a major obstacle in the late phase of epithelial ovarian cancer. However, there is no consensus on a specific treatment for malignant ascites. The present study evaluated the clinical benefit of half-dose bevacizumab therapy (7.5 mg/kg every 3–4 weeks). Methods: This was a single-arm interventional study performed at Aichi Cancer Center Hospital. Four patients with platinum-resistant epithelial ovarian cancer and symptomatic malignant ascites were no longer considered candidates for standard chemotherapy. As a palliative approach, half-dose bevacizumab therapy (7.5 mg/kg every 3–4 weeks) was used with informed consent. The clinical data of these patients were retrospectively reviewed. Results: All patients had been heavily pretreated and showed progressive disease. Thus, standard chemotherapy was no longer feasible, and palliative paracentesis for malignant ascites was clinically needed. Among the four patients, three did not require additional paracentesis after bevacizumab therapy, and there were no adverse events. One patient needed paracentesis owing to lymphorrhea. Conclusion: The use of bevacizumab therapy as a palliative approach for malignant ascites might be an option in patients with terminal-stage ovarian cancer. However, further evaluation is needed with regard to the possibility of severe side effects and medical expenses.

    DOI: 10.1111/jog.14112

    Web of Science

    Scopus

    PubMed

  41. COMPREHENSIVE MIRNA SEQUENCING OF SQUAMOUS CELL CARCINOMA ARISING FROM OVARIAN MATURE TERATOMA

    Yoshida K., Yokoi A., Tamauchi S., Ikeda Y., Yoshikawa N., Nishino K., Niimi K., Suzuki S., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   29 巻   頁: A544 - A545   2019年11月

     詳細を見る

    記述言語:日本語  

    DOI: 10.1136/ijgc-2019-ESGO.1079

    Web of Science

  42. Prognostic factors and effects of fertility-sparing surgery in women of reproductive age with ovarian clear-cell carcinoma: a propensity score analysis

    Yoshihara Masato, Kajiyama Hiroaki, Tamauchi Satoshi, Suzuki Shiro, Takahashi Kunihiko, Matsui Shigeyuki, Kikkawa Fumitaka

    JOURNAL OF GYNECOLOGIC ONCOLOGY   30 巻 ( 6 ) 頁: e102   2019年11月

     詳細を見る

    記述言語:日本語   出版者・発行元:Journal of Gynecologic Oncology  

    Objective: The aim of this study was to investigate the clinical characteristics of young patients with stage I clear-cell carcinoma (CCC) and evaluate the prognostic factors and effects of fertility-sparing surgery (FSS) using propensity score (PS) adjustment. Methods: We conducted a regional multi-institutional study between 1986 and 2017. Among 4,277 patients with ovarian tumor, clinical and pathological data of 103 fertile women with stage I unilateral CCC were collected. We evaluated survival and reproductive outcomes in these patients. Additionally, to analyze the effects of FSS, baseline imbalance between patients with and those without FSS was adjusted with an inverse probability of treatment weighting using PSs involving independent clinical variables. Results: The mean patient age was 39.4 years, and the median follow-up period for surviving patients was 55.6 months. In multivariate analysis, stage IC2/IC3 (vs. IA/IC1) was the only independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS). FSS was not associated with poorer prognosis when compared to the prognosis with non-preserving surgery with regard to both RFS and OS. No statistical difference in survival outcomes between FSS and other approaches was confirmed after PS adjustment. Among patients who underwent FSS, four deliveries with healthy neonates were noted without any gestational complications. Conclusion: FSS can be considered in stage I CCC, specifically in stage IA and IC1 patients who strongly desire to have children in the future. Further clinical research is needed to clarify the optimal application of FSS for CCC.

    DOI: 10.3802/jgo.2019.30.e102

    Web of Science

    Scopus

    PubMed

  43. REDUCED RESPONSE TO CONTROLLED OVARIAN STIMULATION AFTER RADICAL TRACHELECTOMY

    Tamauchi S., Kajiyama H., Osuka S., Moriyama Y., Yoshihara M., Iyoshi S., Yoshida K., Ikeda Y., Yoshikawa N., Nishino K., Niimi K., Suzuki S., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   29 巻   頁: A269 - A270   2019年11月

     詳細を見る

    記述言語:日本語  

    DOI: 10.1136/ijgc-2019-ESGO.469

    Web of Science

  44. Fertility-Sparing surgery for young women with ovarian endometrioid carcinoma: a multicenteric comparative study using inverse probability of treatment weighting.

    Kajiyama H, Yoshihara M, Tamauchi S, Yoshikawa N, Suzuki S, Kikkawa F

    European journal of obstetrics & gynecology and reproductive biology: X   4 巻   頁: 100071   2019年10月

     詳細を見る

    記述言語:英語   出版者・発行元:European Journal of Obstetrics and Gynecology and Reproductive Biology: X  

    Introduction: The aim of this study was to evaluate the oncologic outcome of women with stage I ovarian endometrioid carcinoma (EC) who underwent fertility-sparing surgery (FSS). Materials and nethods: Between 1986 and 2017, a total of 3227 patients with epithelial ovarian carcinoma were retrospectively evaluated based on a central pathological review and search of the medical records from multiple institutions. We identified 24 and 54 patients with stage I EC who underwent FSS and conventional radical surgery (CRS), respectively. Inverse probability of treatment weighting (IPTW)–adjusted Kaplan-Meier and Cox regression analyses were employed to compare OS between the two groups. Results: With follow-up of a total of 78 patients, 9 patients (11.5%) developed recurrence. In addition, 5 patients (6.4%) died of the disease. Recurrence was noted in 3 (10.7%) patients in the FSS group and 6 (11.1%) patients in the CRS group. Death was noted in 2 (8.3%) patients in the FSS group and 3 (5.6%) patients in the CRS group. In the original cohort, there was no significant difference in overall survival (OS) or recurrence-free survival (RFS) between the FSS and RS groups {Log-rank: OS (P = 0.630), RFS (P = 0.757)}. In the IPTW-adjusted cohort, the 5-year OS rates were 96.6 and 92.4% in patients with FSS and CRS, respectively (P = 0.319). Furthermore, the 5-year RFS rate was 88.6% for the FSS group and 88.1% for the CRS group (Log-rank: P = 0.556). Conclusions: Young women with stage I EC undergoing FSS showed a relatively satisfactory prognosis, equal to those receiving CRC.

    DOI: 10.1016/j.eurox.2019.100071

    Scopus

    PubMed

  45. Relationship between preexisting mental disorders and prognosis of gynecologic cancers: A case-control study

    Tamauchi Satoshi, Kajiyama Hiroaki, Moriyama Yoshinori, Yoshihara Masato, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   45 巻 ( 10 ) 頁: 2082 - 2087   2019年10月

     詳細を見る

    記述言語:日本語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aim: Cancer treatment involves long-term therapy and follow-up, with mental disorders (MD) often affecting the treatment process. Hence, in this study, we retrospectively analyze cases involving gynecologic cancer with MD and clarify the relationship between psychosis and cancer prognosis. Methods: Patients with both gynecologic cancer and MD from January 2003 to August 2016 were recruited in this study. Cases were limited to those whose MD had been diagnosed before their cancer. Control patients without MD were also analyzed. Both cases and controls were adjusted for age, cancer type, and cancer stage. Results: A total of 54 patients with gynecologic cancer and MD, as well as 108 controls without MD, were included. The median age of the patients was 52 years. Details regarding cancer type were as follows: 11 ovarian cancers, 26 uterine corpus cancers and 17 cervical cancers. Among these, 25 schizophrenia cases, 15 depressive disorders, 4 bipolar disorders and 10 other MD were recorded. No significant differences in the 5-year survival rate were found between patients and controls. In advanced-stage cervical cancer, however, the prognosis was significantly poor given the low rate of initial treatment completion. Moreover, patients with advanced-stage cervical cancer had significantly lower chemotherapy completion rates compared to those with other gynecologic malignancies. Conclusion: Mental disorders do not affect the prognosis of gynecologic cancers, except for advanced cervical cancer. Accordingly, improving the low rate of initial treatment completion seems to be a focal point for better prognosis in advanced cervical cancer.

    DOI: 10.1111/jog.14053

    Web of Science

    Scopus

    PubMed

  46. Oncologic and reproductive outcomes of cystectomy as a fertility-sparing treatment for early-stage epithelial ovarian cancer

    Kajiyama Hiroaki, Suzuki Shiro, Niimi Kaoru, Tamauchi Satoshi, Kawai Michiyasu, Nagasaka Tetsuro, Shibata Kiyosumi, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   24 巻 ( 7 ) 頁: 857 - 862   2019年7月

     詳細を見る

    記述言語:日本語   出版者・発行元:International Journal of Clinical Oncology  

    Background: Fertility-sparing surgery (FSS) has mainly been chosen for young women with ovarian-confined/well-differentiated epithelial ovarian cancer (EOC). In general, FSS consists of at least conservation of contralateral ovary and the uterus with a staging surgery. However, information on the clinical outcome in women who underwent cystectomy as a fertility-preserving option is lacking. Methods: After a central pathological review and search of the medical records from multiple institutions between 1987 and 2015, a total of eight early-stage EOC patients treated with cystectomy as FSS were retrospectively evaluated. Diagnosis and staging were based on International Federation of Gynecology and Obstetrics criteria (2014). Surgery consisted of uni- or bilateral cystectomy. The oncologic and reproductive outcomes were assessed. Results: The median age was 29 years (range 26–38 years). The median follow-up time was 103.6 months (range 42.2–218.3 months). The stage was IA in 3, IC1 in 4, and IC3 in one patient. Five patients received adjuvant chemotherapy. After cystectomy, two patients experienced recurrence in the pelvic cavity and bilateral ovaries, respectively. The former patient died of the disease 42 months after cystectomy, and conversely, the latter one was rescued by subsequent radical surgery. Four full-term childbirths were observed in three patients. Conclusions: Although oophorectomy is considered as an appropriate fertility-preserving operation, cystectomy may be an unavoidable option when it is the only surgical procedure available. It is desirable to verify the utility by accumulating larger numbers of patients through a future registry system.

    DOI: 10.1007/s10147-019-01416-y

    Web of Science

    Scopus

    PubMed

  47. Endometriosis and cancer

    Kajiyama Hiroaki, Suzuki Shiro, Yoshihara Masato, Tamauchi Satoshi, Yoshikawa Nobuhisa, Niimi Kaoru, Shibata Kiyosumi, Kikkawa Fumitaka

    FREE RADICAL BIOLOGY AND MEDICINE   133 巻   頁: 186 - 192   2019年3月

     詳細を見る

    記述言語:日本語   出版者・発行元:Free Radical Biology and Medicine  

    Endometriosis, characterized by the presence of extra-uterine endometrium, is a common gynecologic disorder in reproductive-age women. Although the detailed molecular mechanism of etiology remains unelucidated, recent studies have gradually revealed both genetic and epigenetic backgrounds of the development of endometriosis. In clinical practice, endometriosis has been recognized as a precursor lesion of several types of malignancies and endometriosis-associated carcinoma. An imbalance between reactive oxygen species and local antioxidants has been reported to contribute to the development of endometriosis-associated carcinoma as well as the pathophysiology of this disease through a systemic inflammatory response in the peritoneal cavity. This review mainly presents an epidemiology, possible etiology of endometriosis, precursor lesions, molecular features, and the association between the microenvironmental accumulations of oxidative stress in endometriosis-associated ovarian cancer progression.

    DOI: 10.1016/j.freeradbiomed.2018.12.015

    Web of Science

    Scopus

    PubMed

  48. Reproductive outcomes of 105 malignant ovarian germ cell tumor survivors: a multicenter study

    Tamauchi Satoshi, Kajiyama Hiroaki, Yoshihara Masato, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY   219 巻 ( 4 ) 頁: 385.e1 - 385.e7   2018年10月

     詳細を見る

    記述言語:日本語   出版者・発行元:American Journal of Obstetrics and Gynecology  

    Background: Malignant ovarian germ cell tumors usually occur in young women. Until the 1970s, before establishment of systemic chemotherapy, malignant ovarian germ cell tumors had a very poor prognosis. Recently, prognosis has improved, and fertility-sparing treatment is being adopted in patients who desire to become pregnant. However, the number of malignant ovarian germ cell tumor survivors who actually became pregnant remains unknown. Objective: The present study aimed to clarify the reproductive outcomes in malignant ovarian germ cell tumor survivors by using data from a multicenter database and an additional survey on reproductive outcomes. Study Design: The study used the Tokai Ovarian Tumor Study Group database on ovarian cancer patients. We assessed the database from 1986 through 2016 and selected malignant ovarian germ cell tumor patients <40 years of age who received fertility-sparing treatment. Questionnaires on reproductive outcomes were sent to the registered facilities. The following data were collected and used in this study: age, date of onset, surgical procedure, chemotherapy regimen, tumor type, International Federation of Gynecology and Obstetrics stage, survival outcome and period, number of pregnancies and childbirths, marital status, childbearing desire, method of pregnancy, gestational weeks at delivery, birthweight of the baby, obstetric complications, and menstrual status after fertility-sparing treatment. Results: A total of 110 malignant ovarian germ cell tumor patients who received fertility-sparing treatment were identified. The median follow-up period was 10.4 years. Five patients were excluded because of death or loss of fertility after treatment for recurrence. Thus, 105 patients were finally included. The additional survey revealed that 42 of 45 patients who desired childbirth became pregnant. The total number of pregnancies was 65, and 56 babies were born to 40 malignant ovarian germ cell tumor survivors. Conclusion: The reproductive outcomes of malignant ovarian germ cell tumor survivor are promising with fertility-sparing treatment. Malignant ovarian germ cell tumor survivors can become pregnant and give birth if they desire.

    DOI: 10.1016/j.ajog.2018.07.021

    Web of Science

    Scopus

    PubMed

  49. Efficacy of medroxyprogesterone acetate treatment and retreatment for atypical endometrial hyperplasia and endometrial cancer

    Tamauchi Satoshi, Kajiyama Hiroaki, Utsumi Fumi, Suzuki Shiro, Niimi Kaoru, Sakata Jun, Mizuno Mika, Shibata Kiyosumi, Kikkawa Fumitaka

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   44 巻 ( 1 ) 頁: 151 - 156   2018年1月

     詳細を見る

    記述言語:日本語   出版者・発行元:Journal of Obstetrics and Gynaecology Research  

    Aim: Medroxyprogesterone acetate (MPA) is used to preserve fertility in patients with Grade 1 endometrial cancer without myometrial invasion (G1EA) and those with atypical endometrial hyperplasia (AEH). However, the efficacy of retreatment with MPA has not been sufficiently established for patients who experience recurrence but wish to retain their fertility. This study aimed to show the effectiveness of MPA treatment and retreatment for AEH and G1EA. Methods: A total of 39 patients received MPA treatment between 2005 and 2015, including nine with G1EA and 30 with AEH. The patients received high-dose (600 mg/day) MPA for 26 weeks. If a complete response was not achieved, MPA treatment was continued. After complete remission, if there was a recurrence, the patient was offered a choice of a hysterectomy or retreatment with MPA. The gynecologic and obstetric outcomes were retrospectively analyzed. Results: The median age was 34 years, and the median body mass index was 23.3 kg/m2. The median follow-up period was 52 months. Complete response rates for the initial treatment were 89% for G1EA and 93% for AEH. Recurrence occurred in 88% of patients with G1EA (7/8) and 50% of those with AEH (14/28). Seven patients with G1EA and 11 with AEH received MPA retreatment, and 100% and 92% of these achieved a complete response. During the study period, a total of 14 pregnancies were recorded with 10 live births. Conclusion: MPA can be effective for G1EA and AEH treatment even when they recur.

    DOI: 10.1111/jog.13473

    Web of Science

    Scopus

    PubMed

  50. ESTABLISHMENT AND CHARACTERISATION OF PATIENT-DERIVED XENOGRAFT MODELS FOR MALIGNANT GYNECOLOGIC TUMORS

    Suzuki S., Tamauchi S., Shimizu Y., Yoshihara M., Nakamura K., Yoshikawa N., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   27 巻   頁: 494 - 494   2017年11月

     詳細を見る

  51. ESTABLISHMENT AND CHARACTERISATION OF PATIENT-DERIVED XENOGRAFT MODELS FOR MALIGNANT GYNECOLOGIC TUMORS

    Suzuki S., Tamauchi S., Shimizu Y., Yoshihara M., Nakamura K., Yoshikawa N., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   27 巻   頁: 1382 - 1382   2017年11月

     詳細を見る

  52. EVALUATING THE LONG TERM PROGNOSTIC FACTOR AND THE ROLE OF CYTOREDUCTION IN THE OVERALL POPULATION OF PATIENTS WITH CLINICAL AND SURGICAL STAGE IV ENDOMETRIAL CARCINOMA

    Shimizu Y., Kajiyama H., Suzuki S., Yoshikawa N., Nakamura K., Yoshihara M., Tamauchi S., Yoshida K., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   27 巻   頁: 1213 - 1213   2017年11月

     詳細を見る

  53. ESTABLISHMENT AND CHARACTERISATION OF PATIENT-DERIVED XENOGRAFT MODELS FOR MALIGNANT GYNECOLOGIC TUMORS

    Suzuki S, Tamauchi S, Shimizu Y, Yoshihara M, Nakamura K, Yoshikawa N, Kajiyama H, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   27 巻   頁: 1382 - 1382   2017年11月

  54. EVALUATING THE LONG TERM PROGNOSTIC FACTOR AND THE ROLE OF CYTOREDUCTION IN THE OVERALL POPULATION OF PATIENTS WITH CLINICAL AND SURGICAL STAGE IV ENDOMETRIAL CARCINOMA

    Shimizu Y, Kajiyama H, Suzuki S, Yoshikawa N, Nakamura K, Yoshihara M, Tamauchi S, Yoshida K, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   27 巻   頁: 1213 - 1213   2017年11月

  55. ESTABLISHMENT AND CHARACTERISATION OF PATIENT-DERIVED XENOGRAFT MODELS FOR MALIGNANT GYNECOLOGIC TUMORS

    Suzuki S, Tamauchi S, Shimizu Y, Yoshihara M, Nakamura K, Yoshikawa N, Kajiyama H, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   27 巻   頁: 494 - 494   2017年11月

▼全件表示

科研費 2

  1. 細胞分裂期キナーゼ阻害との合成致死性に基づいた新しい卵巣癌治療法の開発

    研究課題/研究課題番号:20K18162  2020年4月 - 2022年3月

    科学研究費助成事業  若手研究

    玉内 学志

      詳細を見る

    担当区分:研究代表者 

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    卵巣癌は婦人科領域において最も予後不良な癌種の一つであり、抗癌剤への容易な耐性獲得がその主因である。BRCA遺伝子変異との合成致死性に基づき開発されたPARP阻害剤オラパリブが使用可能になったが、より広く適応可能且つ治療効果の高い分子標的薬の開発が望まれている。VRK1は卵巣癌細胞株における網羅的ノックダウンスクリーニングによって見いだされた新規治療のターゲット遺伝子であり、本研究では、VRK1を高発現する卵巣癌PDXモデルを用いて、VRK1阻害剤による腫瘍増殖抑制効果や、卵巣癌におけるVRK1阻害の合成致死性への関与と、それを引き起こす分子メカニズムを解明することを目的とする。
    【目的】ルテオリンは緑黄色野菜などに含まれるフラボノイドの一種であり、消化器癌における抗腫瘍効果や膀胱癌の発癌予防効果が部分的に解明されつつある。本研究では、上皮性卵巣癌に対するルテオリンの効能を、細胞株や患者腫瘍由来モデル (PDX) を用いて検証した。
    【方法】卵巣癌細胞株A2780とES2を用いて細胞増殖、細胞周期、細胞死、リン酸化アレイを行った。当科で樹立したPDXモデルであるTIL15を用いて、担癌マウスにおけるルテオリンの抗腫瘍効果を検証し、摘出腫瘍の組織学的評価を行った。
    【成績】ルテオリンの投与によって、卵巣癌細胞株の増殖が濃度依存性に抑制された。ルテオリン投与によってアポトーシスは亢進せず、有糸分裂の阻害によって細胞増殖を抑制することがわかった。ルテオリンの投与によってERK1/2のリン酸化が低下し、MAPK経路の抑制を介して有糸分裂抑制効果を示すことが示唆された。PDXにおいては、ルテオリン投与群ではコントロール群に比して有意な腫瘍径の縮小が認められ、シスプラチンとの併用によって相加効果が認められた。摘出腫瘍の免疫染色では細胞周期M期のマーカーであるリン酸化ヒストンH3 (Ser10) が、著明に抑制されていた。
    【結論】ルテオリンは上皮性卵巣癌に対しても増殖抑制効果や抗腫瘍効果を示し、初回治療や維持療法において活用できる可能性が示唆された。
    予定していた動物実験を完了した。
    ルテオリンによるVRK1阻害作用と、VRK1阻害による卵巣癌腫瘍増殖抑制のメカニズムの解明をさらに進める。
    また、ルテオリンによるVRK1阻害作用は特異的ではないため、特異的にVRK1の活性を阻害する物質のスクリーニングを行い、同阻害物質を用いた検討も行っていく予定である。

  2. 難治性卵巣癌の微小環境が誘導する抗癌剤ホルミシスとその克服へ向けての新展開

    研究課題/研究課題番号:19K23884  2019年8月 - 2021年3月

    科学研究費助成事業  研究活動スタート支援

    玉内 学志

      詳細を見る

    担当区分:研究代表者 

    配分額:2860000円 ( 直接経費:2200000円 、 間接経費:660000円 )

    卵巣癌は婦人科領域において最も予後不良な癌種の一つであり、抗癌剤への容易な耐性獲得がその主因である。再発卵巣癌は多発的な病変を形成するが、抗癌剤治療によって縮小する病変と増大する病変とがしばしば混在し、この病態は近年では腫瘍内の遺伝子多様性(heterogeneity)の観点で論じられてきたが、腫瘍周辺の微小環境の違いがエピジェネティックに誘導する悪性形質である可能性がある。本研究では、これら微小環境が関与する抗癌剤耐性メカニズムを解明し、再発卵巣癌に対する新規治療戦略への布石を作ることを目的とする。
    【目的】多発的な病変を形成する再発卵巣癌では、抗癌剤によって縮小する病変と増大する病変とがしばしば混在し、これは微小環境の違いによって腫瘍にデリバリーされる酸素量と抗癌剤量に偏りが生じると、かえって癌の増殖を促進させてしまうという仮説に基づき検証を行った。
    【成績】NOS3は、IC50量の1/10~1/100量のCDDPを投与することで細胞増殖が有意に亢進した。この濃度帯の細胞増殖亢進は20%酸素培養に比して1%酸素培養で顕著だった。メタボローム解析では、抗癌剤からの保護作用を持つとされる還元型グルタチオン及びグルタチオン総量が、IC501/100量の細胞で増加していた。
    低濃度の抗癌剤投与は、かえって癌細胞の増殖を亢進させ (抗癌剤ホルミシス)、低酸素状態によってこの作用が増強することが判明した。卵巣癌の腹膜微小環境においては、酸素や抗癌剤のデリバリーに不均衡が生じることは十分あり得、抗癌剤ホルミシスを念頭において治療に当たる必要があると考えられる。