2022/10/19 更新

写真a

イケダ ヨシキ
池田 芳紀
IKEDA Yoshiki
所属
医学部附属病院 産科婦人科 病院講師
職名
病院講師
外部リンク

学位 2

  1. 博士(医学) ( 2022年4月   名古屋大学 ) 

  2. 修士(工学) ( 2001年3月   東京大学 ) 

研究キーワード 4

  1. 卵巣腫瘍

  2. 人工知能

  3. 婦人科腫瘍

  4. 低侵襲手術

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 1

  1. 医療技能のデジタル化で実現する卵巣腫瘍の革新的診断システムの開発

経歴 4

  1. 名古屋大学   医学部附属病院 産科婦人科   病院講師

    2022年4月 - 現在

  2. 名古屋大学   医学部附属病院 産科婦人科   助教

    2021年4月 - 2022年3月

  3. 名古屋大学   医学部附属病院 産科婦人科   病院助教

    2020年4月 - 2021年3月

  4. 名古屋大学   大学院医学系研究科 産婦人科学   特任助教

    2018年2月 - 2020年3月

学歴 3

  1. 福井大学   医学部   医学科

    2004年10月 - 2009年3月

  2. 東京大学   大学院工学系研究科   応用化学専攻

    1999年4月 - 2001年3月

  3. 東京大学   工学部   応用化学科

    1995年4月 - 1999年3月

所属学協会 8

  1. 日本産科婦人科学会

  2. 日本婦人科腫瘍学会

  3. 日本産科婦人科内視鏡学会

  4. 日本婦人科ロボット手術学会

  5. 日本内視鏡外科学会

  6. 日本ロボット外科学会

  7. 日本遺伝性腫瘍学会

  8. 日本女性医学学会

▼全件表示

委員歴 4

  1. Nature Publishing Group   Editorial Board Member, Scientific Reports  

    2022年8月 - 現在   

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    団体区分:その他

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  2. 日本産科婦人科内視鏡学会   ガイドライン委員  

    2022年4月 - 現在   

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    団体区分:学協会

  3. 日本婦人科腫瘍学会   代議員・査読委員  

    2022年1月 - 現在   

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    団体区分:学協会

  4. 日本産科婦人科学会   産科婦人科用語集・用語解説集委員会 編集委員  

    2021年6月 - 現在   

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    団体区分:学協会

 

論文 47

  1. Survival benefits of retroperitoneal lymphadenectomy for optimally-resected advanced ovarian high-grade serous carcinoma: a multi-institutional retrospective study 査読有り 国際誌

    Ikeda Yoshiki, Yoshihara Masato, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Kajiyama Hiroaki

    JOURNAL OF GYNECOLOGIC ONCOLOGY   33 巻 ( 4 ) 頁: e40   2022年7月

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    担当区分:筆頭著者   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 Gynecologic Oncology  

    Objective: The survival benefits of retroperitoneal lymphadenectomy (RLNA) for epithelial ovarian cancer (EOC) remain controversial because clinical behaviors differ among subtypes. The purpose of the present study was to clarify whether RLNA increases the survival rate of advanced high-grade serous carcinoma (HGSC). Methods: This was a retrospective cohort analysis of 3,227 patients with EOC treated between 1986 and 2017 at 14 institutions. Among them, 335 patients with stage IIB-IV HGSC who underwent optimal cytoreduction (residual tumor of <1 cm) were included. Patients were divided into the RLNA group (n=170) and non-RLNA group (n=165). All pathological slides were assessed based on a central pathological review. Oncologic outcomes were compared between the two groups in the original and weighted cohorts adjusted with the inverse probability of treatment weighting. Results: The median observation period was 49.8 (0.5–241.5) months. Overall, 219 (65%) out of 335 patients had recurrence or progression, while 146 (44%) died of the disease. In the original cohort, RLNA was a significant prognostic factor for longer progression-free survival (PFS) (hazard ratio [HR]=0.741; 95% confidence interval [CI]=0.558–0.985) and overall survival (OS) (HR=0.652; 95% CI=0.459–0.927). In the weighted cohort in which all variables were well balanced as standardized differences decreased, RLNA was also a significant prognostic factor for more favorable oncologic outcomes (PFS, adjusted HR=0.742; 95% CI=0.613–0.899) and OS, adjusted HR=0.620; 95% CI=0.488–0.787). Conclusion: The present study demonstrated that RLNA for stage III-IV HGSC with no residual tumor after primary debulking surgery contributed to better oncologic outcomes.

    DOI: 10.3802/jgo.2022.33.e40

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  2. Peritoneal restoration by repurposing vitamin D inhibits ovarian cancer dissemination via blockade of the TGF-beta 1/thrombospondin-1 axis 査読有り 国際誌

    Kitami Kazuhisa, Yoshihara Masato, Tamauchi Satoshi, Sugiyama Mai, Koya Yoshihiro, Yamakita Yoshihiko, Fujimoto Hiroki, Iyoshi Shohei, Uno Kaname, Mogi Kazumasa, Ikeda Yoshiki, Yokoi Akira, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Nawa Akihiro, Enomoto Atsushi, Kajiyama Hiroaki

    MATRIX BIOLOGY   109 巻   頁: 70 - 90   2022年5月

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    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:Matrix Biology  

    Ovarian cancer (OvCa), a lethal gynecological malignancy, disseminates to the peritoneum. Mesothelial cells (MCs) act as barriers in the abdominal cavity, preventing the adhesion of cancer cells. However, in patients with OvCa, they are transformed into cancer-associated mesothelial cells (CAMs) via mesenchymal transition and form a favorable microenvironment for tumors to promote metastasis. However, attempts for restoring CAMs to their original state have been limited. Here, we investigated whether inhibition of mesenchymal transition and restoration of MCs by vitamin D suppressed the OvCa dissemination in vitro and in vivo. The effect of vitamin D on the mutual association of MCs and OvCa cells was evaluated using in vitro coculture models and in vivo using a xenograft model. Vitamin D restored the CAMs, and thrombospondin-1 (component of the extracellular matrix that is clinically associated with poor prognosis and is highly expressed in peritoneally metastasized OvCa) was found to promote OvCa cell adhesion and proliferation. Mechanistically, TGF-β1 secreted from OvCa cells enhanced thrombospondin-1 expression in CAMs via Smad-dependent TGF-β signaling. Vitamin D inhibited mesenchymal transition in MCs and suppressed thrombospondin-1 expression via vitamin D receptor/Smad3 competition, contributing to the marked reduction in peritoneal dissemination in vivo. Importantly, vitamin D restored CAMs from a stabilized mesenchymal state to the epithelial state and normalized thrombospondin-1 expression in preclinical models that mimic cancerous peritonitis in vivo. MCs are key players in OvCa dissemination and peritoneal restoration and normalization of thrombospondin-1 expression by vitamin D may be a novel strategy for preventing OvCa dissemination.

    DOI: 10.1016/j.matbio.2022.03.003

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  3. Is cystectomy an option as conservative surgery for young patients with borderline ovarian tumor? A multi-institutional retrospective study 査読有り 国際誌

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

    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS   157 巻 ( 2 ) 頁: 437 - 443   2022年5月

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    担当区分:筆頭著者   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 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

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  4. Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis 査読有り 国際誌

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

    BMC WOMENS HEALTH   22 巻 ( 1 ) 頁: 80 - 80   2022年3月

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    担当区分:筆頭著者   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:BMC Women's Health  

    Objective: In young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients’ survival. Methods: Between 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts. Results: During 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234–1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330–2.669), P = 0.905}. Conclusions: Even after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS.

    DOI: 10.1186/s12905-022-01642-z

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  5. Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy 査読有り 国際誌

    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 - 4513   2022年3月

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    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  

    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

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  6. Laparoscopic pelvic surgery after reconstructive surgery with vertical rectus abdominis muscle flap: A case report. 査読有り

    Nishino K, Ikeda Y, Kitami K, Niimi K, Kajiyama H

    International journal of surgery case reports   90 巻   頁: 106706   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Surgery Case Reports  

    Introduction: Patients who have experienced vertical rectus abdominis muscle (VRAM) flap reconstruction are under risk of the abdominal incisional hernia (donor site hernia), and laparotomy increases the risk. Presentation of the case: We present the case of a 71-year-old nulliparous woman who experienced radical vulvectomy against extramammary Paget disease and reconstructive surgery with VRAM flap 7 years ago and developed right ovarian tumor. In this case, right ovarian tumor was removed with laparoscopic surgery, instead of laparotomy, and the risk of incisional hernia was successfully minimized. Discussion: Incisional (donor site) hernia after reconstructive surgery using VRAM flap has been reported in between 2 and 10%. While VRAM flap can fill larger amount of skin and subcutaneous tissue to recipient site, the risk of postoperative incisional hernia of abdominal wall is substantial. Conclusion: Reconstructive surgery of with VRAM flap is required for extramammary vulvar Paget disease expanding wide range, and develops the risk of incisional hernia. Laparoscopic surgery should be applied in patients who have experienced VRAM flap reconstruction and developed pelvic tumor for avoiding the risk of incisional hernia as long as it can be allowed on oncologic aspects such as recurrence.

    DOI: 10.1016/j.ijscr.2021.106706

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  7. Hypoalbuminemia for the prediction of survival in patients with stage IVB cervical cancer.

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

    PloS one   17 巻 ( 9 ) 頁: e0273876   2022年

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    記述言語:英語   出版者・発行元:PLoS ONE  

    We evaluated the prognostic significance of malnutrition in patients with metastatic cervical cancer. In this study, we retrospectively analyzed the cases of 43 patients with stage IVB (FIGO2018) cervical cancer treated at our institute from December 2004 to December 2017. We determined the correlation between clinicopathological characteristics and survival by performing univariate and multivariate analyses. The serum albumin value at diagnosis was used as an index of malnutrition. The median follow-up period was 16.4 months (range, 0.9–91.4 months). On Kaplan-Meier analysis, the 1- and 2-year overall survival (OS) rates for all patients were 61.6% and 48.6%, respectively. The optimal serum albumin for predicting 1-year survival was 3.3 g/dL, as determined by the receiver operating characteristic curve to maximize the area under the curve. The OS of the patients with albumin >3.3 g/ dL (n = 28) was significantly better than that of the patients with albumin ≤3.3 g/dL (n = 15) (p = 0.004). The univariate and multivariate analyses revealed that pretreatment serum albumin and mode of primary treatment were significantly associated with survival in patients with stage IVB cervical cancer. Hypoalbuminemia was an unfavorable prognostic factor for patients with metastatic cervical cancer.

    DOI: 10.1371/journal.pone.0273876

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  8. Clinical effects of cervical conization with positive margins in cervical cancer 査読有り 国際誌

    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 - 23288   2021年12月

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    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  

    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

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  9. Achievement of live birth after overcoming two gynecological malignancies treated with radical trachelectomy and medroxyprogesterone acetate therapy 査読有り

    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

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    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  

    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

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  10. Core 2 beta 1,6-N-acetylglucosaminyltransferases accelerate the escape of choriocarcinoma from natural killer cell immunity 査読有り

    Nakamura Kenichi, Niimi Kaoru, Yamamoto Eiko, Ikeda Yoshiki, Nishino Kimihiro, Suzuki Shiro, Kajiyama Hiroaki, Kikkawa Fumitaka

    BIOCHEMISTRY AND BIOPHYSICS REPORTS   26 巻   頁: 100951   2021年7月

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    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:Biochemistry and Biophysics Reports  

    Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted from choriocarcinoma and contains a core2 O-glycan formed by core2 β1,6-N-acetylglucosaminyl transferase (C2GnT). Choriocarcinoma is considered immunogenic as it is gestational and contains paternal chromosomal components. Here we examined the function of C2GnT in the evasion of choriocarcinoma cells from natural killer (NK) cell-mediating killing. We determined that C2GnT is highly expressed in malignant gestational trophoblastic neoplasms. C2GnT KO downregulates core2 O-glycan expression in choriocarcinoma cells, which are more efficiently killed by NK cells than control cells. C2GnT KO cell containing tumor necrosis factor-related apoptosis inducing ligand have lower viability than control cells. Additionally, poly-N-acetyllactosamine in core2 branched oligosaccharides on MHC class I-related chain A (MICA) and mucin1 (MUC1) is significantly reduced in C2GnT KO cells. Meanwhile, the cumulative survival rate of nude mice inoculated with C2GnT KO tumors was higher than that of the control group. These findings suggest that choriocarcinoma cells may escape NK cell-mediated killing via glycosylation of MICA and MUC1.

    DOI: 10.1016/j.bbrep.2021.100951

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  11. Metabolome analysis reveals a diversity of cancer tissues in advanced epithelial ovarian cancer 査読有り

    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

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    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: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

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  12. Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer 査読有り

    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

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    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: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

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  13. A poor prognostic metastatic nongestational choriocarcinoma of the ovary: a case report and the literature review 査読有り

    Nishino Kimihiro, Yamamoto Eiko, Ikeda Yoshiki, Niimi Kaoru, Yamamoto Toshimichi, Kajiyama Hiroaki

    JOURNAL OF OVARIAN RESEARCH   14 巻 ( 1 ) 頁: 56   2021年4月

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    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 Ovarian Research  

    Background: Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis. Case presentation: A nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma. Conclusion: Metastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome.

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  14. Expression of the chrXq27.3 miRNA cluster in recurrent ovarian clear cell carcinoma and its impact on cisplatin resistance 査読有り

    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

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    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.

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  15. Establishment of a patient-derived xenograft model and cell line of malignant transformation of mature cystic teratoma of the ovary 査読有り

    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

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    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.

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  16. A uterine pseudotumor of immunoglobulinG4-related disease 査読有り

    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

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    担当区分:責任著者   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  

    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.

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  17. Does uterine preservation affect survival outcomes of patients with stage I ovarian sex cord-stromal cell tumours? A multi-institutional study 査読有り 国際誌

    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

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    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: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.

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  18. Adjusted multiple gases in the plasma flow induce differential antitumor potentials of plasma-activated solutions 査読有り

    Nakamura Kae, Yoshikawa Nobuhisa, Yoshihara Masato, Ikeda Yoshiki, Higashida Akihiro, Niwa Akihiro, Jindo Takahiro, Tanaka Hiromasa, Ishikawa Kenji, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka, Kajiyama Hiroaki

    PLASMA PROCESSES AND POLYMERS   17 巻 ( 10 )   2020年10月

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    記述言語:日本語   出版者・発行元:Plasma Processes and Polymers  

    We present a novel plasma system that can generate a plasma-activated medium by changing the proportion of reactive gases such as oxygen, nitrogen, and hydrogen in the plasma flow. The correlation between the biological activity of plasma-activated solutions prepared under multiple plasma gas-flow conditions was evaluated. Mixed nitrogen, in addition to oxygen, in the gas flow is most powerful for producing plasma-activated Ringer's lactate solution against antitumor effects on ovarian cancer cells as compared with oxygen or nitrogen alone. The antitumor effect of plasma-activated solutions is controllable by the modification of the proportion of reactive gases (especially nitrogen and oxygen gases) in the plasma flow. These results suggest that the plasma flow conditions may be one of the candidates for the specifications of the plasma-activated solutions to the therapeutic effect.

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  19. The Preoperative Prognostic Nutritional Index for the Prediction of Outcomes in Patients with Early-Stage Ovarian Clear Cell Carcinoma 査読有り

    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   2020年4月

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    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.

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

    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

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    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: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.

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  21. The role of additional hysterectomy after concurrent chemoradiation for patients with locally advanced cervical cancer 査読有り

    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

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    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.

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  22. Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway 査読有り

    Yoshikawa Nobuhisa, Liu Wenting, Nakamura Kae, Yoshida Kosuke, Ikeda Yoshiki, Tanaka Hiromasa, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   10 巻 ( 1 ) 頁: 1614   2020年1月

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    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 biological function of non-thermal atmospheric pressure plasma has been widely accepted in several types of cancer. We previously developed plasma-activated medium (PAM) for clinical use, and demonstrated that PAM exhibits a metastasis-inhibitory effect on ovarian cancer through reduced MMP-9 secretion. However, the anti-tumor effects of PAM on endometrial cancer remain unknown. In this study, we investigated the inhibitory effect of PAM on endometrial cancer cell viability in vitro. Our results demonstrated that AMEC and HEC50 cell viabilities were reduced by PAM at a certain PAM ratio, and PAM treatment effectively increased autophagic cell death in a concentration dependent manner. In addition, we evaluated the molecular mechanism of PAM activity and found that the mTOR pathway was inactivated by PAM. Moreover, our results demonstrated that the autophagy inhibitor MHY1485 partially inhibited the autophagic cell death induced by PAM treatment. These findings indicate that PAM decreases the viability of endometrial cancer cells along with alteration of the mTOR pathway, which is critical for cancer cell viability. Collectively, our data suggest that PAM inhibits cell viability while inducing autophagic cell death in endometrial cancer cells, representing a potential novel treatment for endometrial cancer.

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  23. Impact of age on clinicopathological features and survival of epithelial ovarian neoplasms in reproductive age 査読有り

    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

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    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.

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  24. Clinical Significance of Ubiquitin-associated Protein 2-like in Patients With Uterine Cervical Cancer 査読有り

    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

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    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: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.

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

    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

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    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: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.

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  26. Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background 査読有り

    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

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    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.

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  27. COMPREHENSIVE MIRNA SEQUENCING OF SQUAMOUS CELL CARCINOMA ARISING FROM OVARIAN MATURE TERATOMA 査読有り

    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

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  28. REDUCED RESPONSE TO CONTROLLED OVARIAN STIMULATION AFTER RADICAL TRACHELECTOMY 査読有り

    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

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/ijgc-2019-ESGO.469

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  29. Relationship between preexisting mental disorders and prognosis of gynecologic cancers: A case-control study 査読有り

    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

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    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: 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.

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  30. Comparison of long-term oncologic outcomes between metastatic ovarian carcinoma originating from gastrointestinal organs and advanced mucinous ovarian carcinoma 査読有り

    Kajiyama Hiroaki, Suzuki Shiro, Utsumi Fumi, Yoshikawa Nobuhisa, Nishino Kimihiro, Ikeda Yoshiki, Niimi Kaoru, Yamamoto Eiko, Kawai Michiyasu, Shibata Kiyosumi, Nagasaka Tetsuro, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   24 巻 ( 8 ) 頁: 950 - 956   2019年8月

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    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: Occasionally, ovarian tumors are found to have originated from non-ovarian organs as metastatic lesions since the ovary is a common site of metastasis from many cancers. The aim of the current study was to estimate the long-term oncologic outcome of patients with metastatic mucinous ovarian carcinoma (MmOC) in comparison with those with primary mucinous ovarian carcinoma (PmOC) at an advanced stage. Materials and methods: The data of one hundred and sixty-seven patients with mucinous ovarian cancer, including 91 patients with MmOC from the digestive organs and 76 patients with stage III–IV PmOC, were retrospectively analyzed. The prognostic significances of clinicopathologic factors were evaluated employing both uni- and multivariable analyses. Pathological slides were evaluated based on centralized pathological review. Results: The median age of patients with PmOC and MmOC was 55 (18–81) and 51 years (30–82), respectively. With follow-up of a total of 167 patients, 145 patients (86.8%) developed recurrence. In addition, 122 patients (73.0%) died of the disease. Regardless of the residual tumor status, patients with PmOC did not a show a significantly poorer OS than those with MmOC. Furthermore, in a Cox multivariable hazard model, after adjustment for various clinicopathologic confounders, a gastric cancer (GC)-originated tumor and larger residual tumor were significant predictors of poorer OS [GC (vs. PmOC): HR (95% CI) 2.205 (1.303–3.654), P = 0.0036]. Conclusion: The oncologic outcome of patients with MmOC was extremely poor; however, it was almost the same as that of those with PmOC. We should recognize MmOC derived from gastric carcinoma as a highly aggressive malignancy.

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  31. Does postoperative prophylactic irradiation of para-aortic lymph nodes reduce the risk of recurrence in uterine cervical cancer with positive pelvic lymph nodes? 査読有り

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

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   24 巻 ( 5 ) 頁: 567 - 574   2019年5月

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    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: In cervical cancer, para-aortic lymph nodes are common sites of metastasis. The purpose of the study was to evaluate the clinical benefits of prophylactic irradiation as postoperative therapy. Methods: A retrospective cohort study was conducted during 2001–2015 at a single institution. Patients with a high risk of para-aortic lymph nodes recurrence were eligible for this study, and we identified patients who had pelvic lymph node metastasis and underwent radical surgery and concurrent chemo-radiotherapy. As a result, 33 and 46 patients were included in the treatment (prophylactic irradiation) and non-treatment groups, respectively. Baseline differences between the two groups were adjusted with the inverse probability of treatment weighting using propensity scores composed of the independent variables including age, stage, tumor size, pathological findings, lymph node status, and pathological subtypes. Results: In the 68-month median follow-up period (range 6–178 months), 25 patients experienced recurrence, and 17 patients were dead. After adjustment with the inverse probability of treatment weighting, the recurrence rates tended to decrease in the treatment group, but there was no significant difference between the two groups [treatment vs. non-treatment, 29.4% and 44.3%, respectively; hazard ratio, 0.593 (95% CI 0.320–1.099); P = 0.097]. However, adjusted para-aortic lymph nodes recurrence rates were not significantly different [treatment vs. non-treatment, 7.8% and 11.4%, respectively; odds ratio, 0.660 (95% CI 0.187–2.322); P = 0.558]. Moreover, Kaplan–Meier curves showing post-recurrence survival revealed no significant difference between the two groups (P = 0.141). Conclusions: Prophylactic para-aortic lymph nodes irradiation did not reduce the risk of recurrence.

    DOI: 10.1007/s10147-018-1376-2

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  32. Reproductive outcomes of 105 malignant ovarian germ cell tumor survivors: a multicenter study 査読有り 国際誌

    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

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    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: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

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  33. ROLE OF CORE 2 beta 1, 6-N ACETYLGLCOSAMINYL TRANSFERASE IN EVASION MECHANISM THROUGH NK CELL IMMUNITY 査読有り

    NIimi Kaoru, Ikeda Yoshinori, Nishino Kimihiro, Yamamoto Eiko, Kikkawa Fumitaka

    PLACENTA   69 巻   頁: E29-E29   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  34. GENETIC STUDY ON ORIGINS OF CHORIOCARCINOMAS BY SHORT TANDEM REPEAT ANALYSIS 査読有り

    Nishino Kimihiro, Nakamura Kenichi, Ikeda Yoshiki, Niimi Kaoru, Yamamoto Eiko, Yamamoto Toshimichi, Kikkawa Fumitaka

    PLACENTA   69 巻   頁: E88-E89   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  35. CLINICAL CHARACTERISTICS OF PSTT AND ETT IN JAPAN 査読有り

    Niimi K., Yamamoto E., Nishino K., Nakamura K., Ikeda Y., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 919 - 919   2018年9月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  36. SHORT TANDEM REPEAT ANALYSIS DISTINGUISHING THE GENOTYPE OF CHORIOARCINOMA 査読有り

    Nishino K., Yamamoto E., Watanabe E., Nakamura K., Ikeda Y., Niimi K., Yamamoto T., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 920 - 920   2018年9月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  37. ROLE OF CORE 2 beta 1, 6-N ACETYLGLCOSAMINYL TRANSFERASE IN EVASION MECHANISM THROUGH NK CELL IMMUNITY 査読有り

    Nakamura K., Kaoru N., Ikeda Y., Nishino K., Yamamoto E., KIkkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 195 - 195   2018年9月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  38. PROPENSITY SCORE ADJUSTED ANALYSIS OF PROPHYLACTIC IRRADIATION TO PARA-AORTIC LYMPH NODE AFTER RADICAL HYSTERECTOMY FOR UTERINE CERVICAL CANCER. 査読有り

    Yoshida K., Yoshihara M., Ikeda Y., Yoshikawa N., Nishino K., Utumi F., Niimi K., Suzuki S., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 447 - 447   2018年9月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  39. EFFECT OF CONCURRENT CHEMO-RADIOTHERAPY ON CLINICAL OUTCOMES IN SMALL CELL CARCINOMA OF THE UTERINE CERVIX 査読有り

    Ikeda Y., Kajiyama H., Yoshida K., Yoshikawa N., Nishino K., Utsumi F., Niimi K., Suzuki S., Kawai M., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 294 - 294   2018年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  40. CLINICAL CHARACTERISTICS OF PSTT AND ETT IN JAPAN 査読有り

    Niimi K, Yamamoto E, Nishino K, Nakamura K, Ikeda Y, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 919 - 919   2018年9月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  41. SHORT TANDEM REPEAT ANALYSIS DISTINGUISHING THE GENOTYPE OF CHORIOARCINOMA 査読有り

    Nishino K, Yamamoto E, Watanabe E, Nakamura K, Ikeda Y, Niimi K, Yamamoto T, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 920 - 920   2018年9月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  42. ROLE OF CORE 2 beta 1, 6-N ACETYLGLCOSAMINYL TRANSFERASE IN EVASION MECHANISM THROUGH NK CELL IMMUNITY 査読有り

    Nakamura K, Kaoru N, Ikeda Y, Nishino K, Yamamoto E, KIkkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 195 - 195   2018年9月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  43. ROLE OF CORE 2 beta 1, 6-N ACETYLGLCOSAMINYL TRANSFERASE IN EVASION MECHANISM THROUGH NK CELL IMMUNITY 査読有り

    NIimi Kaoru, Ikeda Yoshinori, Nishino Kimihiro, Yamamoto Eiko, Kikkawa Fumitaka

    PLACENTA   69 巻   頁: E29-E29   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  44. PROPENSITY SCORE ADJUSTED ANALYSIS OF PROPHYLACTIC IRRADIATION TO PARA-AORTIC LYMPH NODE AFTER RADICAL HYSTERECTOMY FOR UTERINE CERVICAL CANCER. 査読有り

    Yoshida K, Yoshihara M, Ikeda Y, Yoshikawa N, Nishino K, Utumi F, Niimi K, Suzuki S, Kajiyama H, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 447 - 447   2018年9月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  45. GENETIC STUDY ON ORIGINS OF CHORIOCARCINOMAS BY SHORT TANDEM REPEAT ANALYSIS 査読有り

    Nishino Kimihiro, Nakamura Kenichi, Ikeda Yoshiki, Niimi Kaoru, Yamamoto Eiko, Yamamoto Toshimichi, Kikkawa Fumitaka

    PLACENTA   69 巻   頁: E88-E89   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  46. EFFECT OF CONCURRENT CHEMO-RADIOTHERAPY ON CLINICAL OUTCOMES IN SMALL CELL CARCINOMA OF THE UTERINE CERVIX 査読有り

    Ikeda Y, Kajiyama H, Yoshida K, Yoshikawa N, Nishino K, Utsumi F, Niimi K, Suzuki S, Kawai M, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   28 巻   頁: 294 - 294   2018年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  47. Fertility-sparing surgery of malignant transformation arising from mature cystic teratoma of the ovary. 査読有り

    Yoshikawa N, Teshigawara T, Ikeda Y, Nishino K, Sakata J, Utsumi F, Niimi K, Sekiya R, Suzuki S, Kawai M, Shibata K, Kikkawa F, Kajiyama H

    Oncotarget   9 巻 ( 44 ) 頁: 27564 - 27573   2018年6月

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

    Background: The purpose of this study was to evaluate the long-term clinical outcome of young women with malignant transformation arising from mature cystic teratoma of the ovary (MT-MCT) by comparing radical surgery and fertility-sparing surgery (FSS). Patients and methods: All patients treated with radical surgery or FSS for MT-MCT in multiple institutions were registered in this analysis. Univariate and multivariate analyses were performed to evaluate clinical outcome, including overall survival (OS) and disease-free survival (DFS). Results: From 1986 to 2016, 62 patients with MT-MCT were treated in our group. The median follow-up period was 38.0 (2.0-227.9) months, and the median age was 54 (17-82) years old. Multivariate analysis revealed that only advanced stage was significantly correlated with poorer prognosis of patients [hazard ratio (HR) for death: 6.58, 95% confidence interval (CI): 1.82-24.78, P = 0.0048; HR for recurrence: 5.59, 95% CI: 1.52-21.83, P = 0.01]. Of a total of 13 women with stage I-II disease at less than 45 years old, 7 were treated with FSS, and there was no recurrence except for in one woman with stage II MT-MCT. There was no significant difference in long-term oncological outcome between radical surgery and FSS. Conclusion: FSS may be indicated for patients with stage I MT-MCT, who hope to preserve fertility, as no relapse was found after FSS.

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▼全件表示

書籍等出版物 1

  1. FUSE資格者が教える電気メス

    渡邊 祐介( 範囲: エネルギーデバイス用語集 フェーズ2 エディター)

    メジカルビュー社  2022年4月  ( ISBN:978-4-7583-0468-9

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    記述言語:日本語 著書種別:学術書

科研費 2

  1. 医療技能のデジタル化で実現する卵巣腫瘍の革新的診断システムの開発

    研究課題/研究課題番号:20K09667  2020年4月 - 2023年3月

    科学研究費助成事業  基盤研究(C)

    池田 芳紀, 小泉 憲裕

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    担当区分:研究代表者 

    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    本研究の目的は、医療技能のデジタル化(医デジ化)により卵巣腫瘍の革新的診断システムを開発することである。卵巣腫瘍の確定診断は手術以外には困難である。病歴、腫瘍マーカー、超音波検査、MRI、CT等の情報から、手術前に卵巣腫瘍の良・悪性や病理組織型を医師が勘や経験に基づき推定している。本研究で提案するのは、人工知能(AI)技術を用いてこの医師の技能をデジタルに再現し、術後に確定した病理組織型の情報から学習を積むことによって、人間を超える高い精度で卵巣腫瘍の良・悪性、病理組織型を術前に診断するシステムである。卵巣悪性腫瘍の早期発見手法として研究を発展させ、最終的には卵巣悪性腫瘍の死亡率低下を目指す。
    本研究の目的は、医療技能のデジタル化により、卵巣腫瘍の革新的診断システムを開発することである。卵巣腫瘍の術前診断は、既往歴、家族歴、腫瘍マーカー、超音波検査、MRI、CTなどから得られる情報を参考に、医師が良・悪性を推定している。エキスパートの画像診断医は自らカルテ上の診療情報を紐解き、卵巣腫瘍の病理組織型の推定を画像読影時に行っている。人工知能技術を用いてこの医師の技能をデジタル化し機能としてシステムに実装し、学習を積むことで、人間を超える高い診断精度を実現する。卵巣悪性腫瘍の早期発見手法として研究を発展・確立し、最終的には卵巣悪性腫瘍の死亡率減少を目指す。本研究は下記の4つのステップで卵巣腫瘍の診断システムの開発を行う。本研究期間においては1~2のステップを繰り返してシステムの性能を高め、その有効性を検証する予定である。当該年度は1の段階で最初の目標である約200症例分の診療情報、検査データの抽出を終え、画像検査データの抽出作業の途中段階である。
    1.名古屋大学産婦人科で治療した卵巣腫瘍症例の診療情報、検査データの抽出・解析;名古屋大学産婦人科で治療した卵巣腫瘍症例の患者臨床情報、血液・画像検査データ、摘出物の最終病理組織型の情報を抽出する。共同研究者のグループに集積して解析し、システムの枠組みを構築する。
    2.システムの性能の評価;上記で使用していない卵巣腫瘍症例のデータをシステムに入力し、出力された良性・境界悪性・悪性の診断と病理組織型の正診率を評価する。
    3.症例数を拡大し診断精度の向上を図る;名古屋大学産婦人科と複数の関連病院で組織する東海卵巣腫瘍研究会の登録症例へとデータの集積を拡大する。
    4.卵巣悪性腫瘍の早期発見に向けてシステムの発展・確立;一般的な検診で収集可能な臨床情報・血液検査データと経腟超音波データのみで診断を可能にし、早期発見手法として実用化を検討する。
    進捗状況としては大幅に遅れている。COVID-19の流行により当該年度のスタート時点からすでに研究活動に制限がかかっていたことが最大の原因である。当該年度は、名古屋大学産婦人科で治療した卵巣腫瘍症例の患者臨床情報、血液・画像検査データ、摘出物の最終病理組織型の情報を抽出し、共同研究者のグループに集積して解析し、システムの枠組みを構築する予定であった。まず初めに必要な作業としては、多数例の臨床情報、検査データ、画像データを匿名化して収集することである。データ収集のためには研究補助員が電子カルテシステムを参照する必要があり、施設に出勤しての作業がどうしても必要なため、テレワーク下では作業困難であった。データ収集作業が予定通りスタートできず計画より大幅に遅れを生じた。研究補助員を雇用しデータ収集作業を本格的に開始できたのが10月以降となったため、当初の計画より約半年間の遅れを生じている。当該年度は、最初の目標であった約200症例分の診療情報、検査データの抽出を終えてはいるが、画像検査データの抽出作業の途中段階であり、十分なデータ解析が行えていない。共同研究者のグループでのデータ解析・システムの枠組みの構築は次年度に繰り越して行わざるを得なくなった。
    研究計画に遅れが生じており、最初の目標であった約200症例分の診療情報、検査データの抽出を終えてはいるが、現在のところ画像検査データの匿名化・抽出作業の途中の段階である。画像検査データの抽出が終わり次第、共同研究者のグループでのデータ解析およびシステムの枠組みの構築を行う。遅れを取り戻すために、画像検査データの抽出作業のスピードを上げることも検討している。データ収集作業に携わる研究補佐員を増員すればスピードを上げることは可能であるが、人件費の増加につながる。研究計画の遅れに伴い、医用画像処理用のハードウェア・システム購入を見合わせている状況であり、この分の予算をデータ収集作業に携わる研究補佐員を増員するための費用に回すかどうか、本研究期間全体の計画を考慮しつつ今後の研究の進捗をみながら検討していく。

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  2. 難治性腹膜播種の完全除去を目指す大気圧プラズマを応用した革新的腹腔内治療の開発

    研究課題/研究課題番号:19K21346  2019年4月 - 2020年3月

    科学研究費助成事業  研究活動スタート支援

    池田 芳紀

      詳細を見る

    担当区分:研究代表者 

    配分額:2990000円 ( 直接経費:2300000円 、 間接経費:690000円 )

    婦人科悪性腫瘍における腹膜播種は難治性で予後不良な進展様式の一つである。様々な分子標的薬、免疫療法等の研究が進められているが、効果は十分とは言い難い。研究代表者が所属するグループは大気圧プラズマによる癌治療の実用化に向け、実験室で使用可能な簡易プラズマ発生装置を開発し、卵巣癌腹膜播種に対してin vitroおよびin vivoで劇的な抗腫瘍効果を証明したが、そのメカニズムには未知の部分が多い。本研究では大気圧プラズマによる腹膜微小環境の変化を様々な角度から検証し、抗腫瘍効果のメカニズムを解明する。
    プラズマ活性溶液の子宮体癌に対する効果に関してはこれまでに報告がなく、我々はプラズマ活性溶液が子宮体癌細胞に対して抗腫瘍効果を有し、その作用機序はオートファジー(細胞の自食作用)細胞死が関与することを初めて示した。複数の子宮体癌細胞に対しプラズマ活性溶液を投与したところ、子宮体癌細胞の増殖を抑制し、細胞死を誘導することがわかった。プラズマ活性溶液の作用機序としてオートファジー細胞死の活性化(オートファジーに関連するタンパクLC3Bの発現増加)が関与することを突き止めた。
    子宮体癌はわが国では毎年約15,000人が罹患、約2,100人が死亡し、罹患数、死亡数ともに年々増加している。早期に診断された場合の予後は良好であるが、進行した状態で診断された場合や再発した場合の予後は不良で、化学療法に抵抗性をもつ難治性腹膜播種であるケースも多い。また、わが国の保険診療の下で子宮体癌に対して投与可能な薬剤は限られており、腹膜播種を伴う進行・再発子宮体癌に対する新規治療法の開発への需要が高まっている。本研究成果により、子宮体癌に対する新規治療法としてプラズマ活性溶液の臨床応用の可能性が拓かれた。

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担当経験のある科目 (本学) 3

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    2022

  2. 産婦人科学

    2021

  3. 現代医療と生命科学

    2021