Publications by authors named "Satoru Nagase"

131 Publications

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2018 and Annual Treatment Report for 2013.

J Obstet Gynaecol Res 2022 Jan 13. Epub 2022 Jan 13.

Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Japan.

To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2018 and the Annual Treatment Report for 2013, on the outcomes of patients who started treatment in 2013. The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2018 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2013 was analyzed by using the Kaplan-Meier, log-rank, and Wilcoxson tests. Treatment was initiated in 2018 for 7304 patients with cervical cancer; 11 230 with endometrial cancer; 7031 with ovarian, tubal, and peritoneal cancer; 2072 with ovarian borderline tumors; and with the others (222 vulvar cancer, 159 vaginal cancer, 413 uterine sarcoma, 54 uterine adenosarcoma, and 135 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5-year survival rates of the patients with cervical cancer were 93.1%, 75.9%, 59.1%, and 31.2% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 94.1%, 89.2%, 73.6%, and 25.8% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 89.7%, 76.8%, 49.1%, and 32.4% for Stages I, II, III, and IV, respectively. The annual report is important to provide knowledge on gynecological malignancy trends in Japan.
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http://dx.doi.org/10.1111/jog.15134DOI Listing
January 2022

Comparison of treatment outcomes of surgery and radiotherapy, including concurrent chemoradiotherapy for stage Ib2-IIb cervical adenocarcinoma patients: a retrospective study.

J Gynecol Oncol 2021 Dec 6. Epub 2021 Dec 6.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.

Objective: The study compared the treatment outcomes of surgery versus radiotherapy, including concurrent chemoradiotherapy, in stage Ib2-IIb cervical adenocarcinoma patients in Japan.

Methods: Of 57,470 patients diagnosed with stage I-IV cervical cancer from January 2001-December 2011, 1,932 patients with stage Ib2-IIb cervical adenocarcinoma were initially treated by surgery or radiotherapy. The primary endpoint was 5-year overall survival (OS) in all and 614 propensity score-matched (PSM) patients (307 per group). We compared OS and prognosis factors based on age, primary stage, and treatment arm.

Results: In Japan, >80% (n=1,573) of stage Ib2-IIb cervical adenocarcinoma patients underwent surgery. The 5-year OS of surgery vs. radiotherapy groups were 82.1% (n=704) vs. 79.7% (n=59) (hazard ratio [HR]=1.494; 95% confidence interval [CI]=0.826-2.702; p=0.181) for stage Ib2, 76.6% (n=239) vs. 66.7% (n=54) (HR=1.679; 95% CI=0.986-2.858; p=0.053) for stage IIa, and 71.1% (n=630) vs. 58.9% (n=246) (HR=1.711; 95% CI=1.341-2.184; p<0.001) for stage IIb. In 614 PSM patients balanced for age and carcinoma stage Ib2-IIb, the 5-year OS of surgery vs. radiation groups was 73.0% (n=307) vs. 65.5% (n=307) (HR=1.394; 95% CI=1.044-1.860; p=0.023). In multivariable analysis, age (HR=1.293; 95% CI=1.045-1.601; p=0.018), treatment arm, radiotherapy (HR=1.556; 95% CI=1.253-1.933; p<0.001), and stage IIb (HR=1.783; 95% CI=1.443-2.203; p=0.018) were independent prognosis factors for 5-year OS in stage Ib2-IIb adenocarcinoma patients.

Conclusion: Age (>65 years), treatment arm (radiotherapy), and stage IIb significantly affect OS in cervical adenocarcinoma patients. Surgery may be considered for <65-year-old patients with stage IIb adenocarcinoma.
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http://dx.doi.org/10.3802/jgo.2022.33.e14DOI Listing
December 2021

Correction: Metabolomic analysis of uterine serous carcinoma with acquired resistance to paclitaxel.

Oncotarget 2021 Nov 9;12(23):2321-2322. Epub 2021 Nov 9.

Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Iidanishi, Yamagata 990-9585, Japan.

[This corrects the article DOI: 10.18632/oncotarget.25868.].
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http://dx.doi.org/10.18632/oncotarget.27474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590814PMC
November 2021

Association between hospital treatment volume and survival of women with gynecologic malignancy in Japan: a JSOG tumor registry-based data extraction study.

J Gynecol Oncol 2022 Jan 1;33(1):e3. Epub 2021 Nov 1.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.

Objective: Associations between hospital treatment volume and survival outcomes for women with 3 types of gynecologic malignancies, and the trends and contributing factors for high-volume centers were examined.

Methods: The Japan Society of Obstetrics and Gynecology tumor registry databased retrospective study examined 206,845 women with 80,741, 73,647, and 52,457 of endometrial, cervical, and ovarian tumor, respectively, who underwent primary treatment in Japan between 2004 and 2015. Associations between the annual treatment volume and overall survival (OS) for each tumor type were examined using a multivariable Cox proportional hazards model with restricted cubic splines. Institutions were categorized into 3 groups (low-, moderate-, and high-volume centers) based on hazard risks.

Results: Hazard ratio (HR) for OS each the 3 tumors decreased with hospital treatment volume. The cut-off points of treatment volume were defined for high- (≥50, ≥51, and ≥27), moderate- (20-49, 20-50, and 17-26), and low-volume centers (≤19, ≤19, and ≤16) by cases/year for endometrial, cervical, and ovarian tumors, respectively. Multivariate analysis revealed younger age, rare tumor histology, and initial surgical management as contributing factors for women at high-volume centers (all, p<0.001). The proportion of high-volume center treatments decreased, whereas low-volume center treatments increased (all p<0.001). Treatment at high-volume centers improved OS than that at other centers (adjusted HR [aHR]=0.83, 95% confidence interval [CI]=0.78-0.88; aHR=0.78, 95% CI=0.75-0.83; and aHR=0.90, 95% CI=0.86-0.95 for endometrial, cervical, and ovarian tumors).

Conclusion: Hospital treatment volume impacted survival outcomes. Treatments at high-volume centers conferred survival benefits for women with gynecologic malignancies. The proportion of treatments at high-volume centers have been decreasing recently.
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http://dx.doi.org/10.3802/jgo.2022.33.e3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728670PMC
January 2022

Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023.

Cancer Sci 2022 Jan 18;113(1):240-250. Epub 2021 Nov 18.

Department of Obstetrics and Gynecology, St. Mary's Hospital, Fukuoka, Japan.

We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m administered intravenously], topotecan [1.25 mg/m intravenously], paclitaxel [80 mg/m intravenously], or gemcitabine [1000 mg/m intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m intravenously). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator-assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32-0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38-1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment-related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification.
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http://dx.doi.org/10.1111/cas.15185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748228PMC
January 2022

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA).

J Clin Oncol 2021 11 2;39(33):3671-3681. Epub 2021 Sep 2.

Department of Obstetrics and Gynecology, University of the Ryukyus Hospital, Okinawa, Japan.

Purpose: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer.

Materials And Methods: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety.

Results: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; .002). There was no statistical difference in overall response rate between groups (7.6% 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% 98.1%), with no additional or new safety risks.

Conclusion: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.
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http://dx.doi.org/10.1200/JCO.21.00334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601279PMC
November 2021

Clinicopathological characteristics and prognostic factors of ovarian granulosa cell tumors: A JSGO-JSOG joint study.

Gynecol Oncol 2021 11 26;163(2):269-273. Epub 2021 Aug 26.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.

Objectives: The aim of this study was to elucidate the clinicopathological features of ovarian granulosa cell tumors (GCTs) and to identify the prognostic factors.

Methods: The Japanese Society of Gynecologic Oncology (JSGO) conducted an observational retrospective cohort study of women with GCTs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology (JSOG) between 2002 and 2015. Clinicopathological features, including lymph node metastasis, were evaluated. In addition, we performed a prognostic analysis of patients between 2002 and 2011 for whom survival data were available. Kaplan-Meier and multivariate Cox proportional hazards analyses were performed.

Results: We identified 1426 patients with GCTs. Of the 222 patients who underwent lymph node dissection, 10 (4.5%) had lymph node metastasis. The incidence of lymph node metastasis in patients with pT1, pT2, and pT3 was 2.1%, 13.3%, and 26.7%, respectively (p < 0.001). Prognostic analysis was performed on 674 patients. In the multivariate Cox regression analysis, residual disease after initial surgery (hazard ratio (HR) = 10.39, 95% confidence interval (CI) = 3.15-34.29) and lymph node metastasis (HR = 5.58, 95% CI = 1.62-19.19) were independent risk factors for cancer-specific survival.

Conclusions: In the initial surgery for GCTs, lymph node dissection can be omitted if the operative finding is pT1. In cases of pT2 or higher, lymph node dissection should be considered. Debulking is critical for achieving no gross residual tumor at the end of the surgery.
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http://dx.doi.org/10.1016/j.ygyno.2021.08.012DOI Listing
November 2021

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan.

Int J Clin Oncol 2021 Dec 25;26(12):2318-2330. Epub 2021 Aug 25.

Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Japan.

Objective: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy.

Methods: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival.

Results: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS.

Conclusion: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.
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http://dx.doi.org/10.1007/s10147-021-02017-4DOI Listing
December 2021

A report on the 73th Annual Congress of the Japan Society of Obstetrics and Gynecology International Workshop for Junior Fellows: Risk-reducing surgery for hereditary breast and ovarian cancer.

J Obstet Gynaecol Res 2021 Nov 1;47(11):3761-3766. Epub 2021 Aug 1.

Board of education, Japan Society of Obstetrics and Gynecology, Tokyo, Japan.

At the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, young doctors from Japan and South Korea made presentations on the present condition of risk-reducing surgery for hereditary breast and ovarian cancer (RRSO) in their respective country. RRSO was insured in Japan in April 2020, whereas in South Korea, it was insured 7 years earlier in 2013. In Japan, certification criteria have been set for facilities that perform RRSO, and the number of facilities is increasing, but regional disparities still exist in its distribution. The number of gBRCA1/2 testing facilities is larger, and the cost is more affordable in South Korea than in Japan. Additionally, South Korea provides genetic counseling to a wider range of relatives compared to Japan. In the future, as the indications for the gBRCA1/2 test have expanded as a companion diagnostic for the use of PARP inhibitors, it is expected that the number of candidates for the gBRCA1/2 mutation test and RRSO will increase in Japan. It is important to increase the number of BRCA tests while maintaining the quality of genetic counseling in order to provide adequate information on BRCA mutations and RRSO for patients to support their decision. For the development of hereditary breast and ovarian cancer (HBOC) medical care, it is necessary to publish a nationwide database in Japan and continue to analyze and discuss the data based on the results.
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http://dx.doi.org/10.1111/jog.14952DOI Listing
November 2021

Association of menopause, aging and treatment procedures with positive margins after therapeutic cervical conization for CIN 3: a retrospective study of 8,856 patients by the Japan Society of Obstetrics and Gynecology.

J Gynecol Oncol 2021 09 10;32(5):e68. Epub 2021 May 10.

Department of Obstetrics and Gynecology, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan.

Objective: The Japan Society of Obstetrics and Gynecology conducted a retrospective multi-institutional survey of patients who underwent cervical conization in Japan. This study aimed to determine the predictive factors for positive surgical margins in cervical intraepithelial neoplasia grade 3 (CIN 3) patients after therapeutic cervical conization and those for positive margins in patients who did not experience recurrence and did not undergo additional treatment.

Methods: In 2009 and 2013, 14,832 patients underwent cervical conization at 205 institutions in Japan. Of these, 8856 patients who underwent therapeutic conization fulfilled the inclusion criteria. Their histologic findings and clinical outcomes were evaluated based on standard statistical procedures and clinical and demographic characteristics.

Results: Negative and positive margins were observed in 7,585 and 1,271 (14.4%) patients, respectively. The predictors of positive margins were menopausal status (p<0.001), loop electrosurgical excision procedure (p<0.001), and Shimodaira-Taniguchi (S-T) conization (p<0.001). Of 1,271 patients with positive margins, 1,060 underwent no additional treatment; among those 1,060 patients, 129 (12.2%) experienced recurrence. The predictors of positive margins in patients who did not undergo additional treatment and did not experience recurrence were age, parity, gravidity, S-T conization, and laser scalpel conization.

Conclusion: Menopausal status and treatment procedures were associated with positive margins after therapeutic conization of CIN 3. It is important to understand the characteristics of treatment procedures and select an appropriate procedure for each case. For elderly or menopausal patients with positive margins, immediate additional treatment is recommended.
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http://dx.doi.org/10.3802/jgo.2021.32.e68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362807PMC
September 2021

A retrospective study for investigating the outcomes of endometrial cancer treated with radiotherapy.

Int J Gynaecol Obstet 2022 Feb 10;156(2):262-269. Epub 2021 Jun 10.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.

Objective: To clarify the role of radiotherapy for endometrial cancer.

Methods: Data were analyzed for 39 247 patients with endometrial cancer registered with the Gynecologic Cancer Registry of the Japan Society of Obstetrics and Gynecology from 2004 to 2011.

Results: The rates of 5-year overall survival (5y-OS) in the radiotherapy and surgery groups were 53.6% and 94.5% in stage I or II, and 15.5% and 67.5% in stage III or IV, respectively. The prognosis in the radiotherapy group was significantly poorer than that in the surgery group. In multivariate analysis, age, advanced stage, histological type, risk of recurrence, and initial radiotherapy were independent prognostic factors. The rates of 5y-OS with no adjuvant therapy, adjuvant chemotherapy, and adjuvant radiotherapy were 95.3%, 92.9%, and 87.1% for stage I or II, respectively, with significant differences among all groups (P < 0.001), and 60.0%, 70.4%, and 55.5% for stage III or IV, respectively, with significant differences of adjuvant chemotherapy with no adjuvant therapy (P < 0.001) and with adjuvant radiotherapy (P < 0.001). In multivariate analysis, age, advanced stage, histological type, lymphadenectomy, and adjuvant radiotherapy were independent prognostic factors.

Conclusion: Patients treated with radiotherapy had a significantly poorer prognosis and the appropriate indication of radiotherapy for endometrial cancer requires further study.
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http://dx.doi.org/10.1002/ijgo.13725DOI Listing
February 2022

The trend and outcome of postsurgical therapy for high-risk early-stage cervical cancer with lymph node metastasis in Japan: a report from the Japan Society of Gynecologic Oncology (JSGO) guidelines evaluation committee.

J Gynecol Oncol 2021 05;32(3):e44

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Japan.

Objective: The Japan Society of Gynecologic Oncology published the first guidelines for the treatment of cervical cancer in 2007. The aim of this research was to evaluate the influence of the introduction of the first guideline on clinical trends and outcomes of patients with early-stage cervical cancer who underwent surgery.

Methods: This analysis included 9,756 patients who were diagnosed based on the pathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b and pN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Data of these patients were retrospectively reviewed, and clinicopathological trends were assessed. The influence of the introduction of the guideline on survival was determined by using a competing risk model.

Results: For surgery cases, the estimated subdistribution hazard ratio (HR) by the competing risk model for the influence of the guideline adjusted for age, year of registration, pT classification, pN classification, histological type, and treatment methods was 1.024 (p=0.864). Following the introduction of the first guideline in 2007, for patients with lymph node metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereas that of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). For pN1 cases, the estimated subdistribution HR by the competing risk model for the influence of the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapy between CT and CCRT/RT (p=0.078).

Conclusions: Survival of surgical cases was not improved by the introduction of the guidelines. It is necessary to consider more effective postsurgical therapy for high-risk early-stage cervical cancer.
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http://dx.doi.org/10.3802/jgo.2021.32.e44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039172PMC
May 2021

The 2020 Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.

J Gynecol Oncol 2021 03;32(2):e49

Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

The fifth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was published in 2020. The guidelines contain 6 chapters-namely, (1) overview of the guidelines; (2) epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (3) recurrent epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (4) borderline epithelial tumors of the ovary; (5) malignant germ cell tumors of the ovary; and (6) malignant sex cord-stromal tumors. Furthermore, the guidelines comprise 5 algorithms-namely, (1) initial treatment for ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (2) treatment for recurrent ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (3) initial treatment for borderline epithelial ovarian tumor; (4) treatment for malignant germ cell tumor; and (5) treatment for sex cord-stromal tumor. Major changes in the new edition include the following: (1) revision of the title to "guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer"; (2) involvement of patients and general (male/female) participants in addition to physicians, pharmacists, and nurses; (3) clinical questions (CQs) in the PICO format; (4) change in the expression of grades of recommendation and level of evidence in accordance with the GRADE system; (5) introduction of the idea of a body of evidence; (6) categorization of references according to research design; (7) performance of systematic reviews and meta-analysis for three CQs; and (8) voting for each CQ/recommendation and description of the consensus.
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http://dx.doi.org/10.3802/jgo.2021.32.e49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930451PMC
March 2021

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2017 and annual treatment report for 2012.

J Obstet Gynaecol Res 2021 May 25;47(5):1631-1642. Epub 2021 Feb 25.

Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Japan.

Aim: To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2017 and the Annual Treatment Report for 2012, on the outcomes of patients who started treatment in 2012.

Methods: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2017 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial and ovarian cancer in 2012 was analyzed by using the Kaplan-Meier, log-rank and Wilcoxon tests.

Results: Treatment was initiated in 2017 for 7710 patients with cervical cancer; 11 120 with endometrial cancer; 7029 with ovarian, tubal and peritoneal cancer; 2164 with ovarian borderline tumors; and with the others (213 vulvar cancer, 139 vaginal cancer, 366 uterine sarcoma, 41 uterine adenosarcoma and 131 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5-year survival rates of the patients with cervical cancer were 92.9, 75.5, 58.2 and 26.7% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 93.6, 85.6, 72.6 and 27.3% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 92.5, 83.5, 49.5 and 30.8% for stages I, II, III and IV, respectively.

Conclusion: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.
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http://dx.doi.org/10.1111/jog.14724DOI Listing
May 2021

High Parity Is an Independent Risk Factor for Tooth Loss in Women: A Community-Based Takahata Study in Japan.

Tohoku J Exp Med 2021 01;253(1):77-84

Department of Dentistry, Oral and Maxillofacial Plastic and Reconstructive Surgery, Faculty of Medicine, Yamagata University.

Risk factors for tooth loss have been widely examined previously. However, no previous study has comprehensively investigated the risk factors, including lifestyle-related specific factors (parity, oral health habits, and socioeconomic status), for fewer than 20 teeth among women in the general population in Japan. This cross-sectional study explored the association of these risk factors, especially parity, with having fewer than 20 teeth among Japanese women. A self-reported questionnaire including items on lifestyle-related risk factors (parity, oral health, diet [e.g., alcohol and sucrose consumption]) and socioeconomic status was sent by post to female residents (age ≥ 40 years) of Takahata town, Yamagata Prefecture, in 2005. Multivariate logistic regression analysis including 3,854 eligible participants was performed to investigate the association between various factors (including parity) and having fewer than 20 teeth. The results indicated that, compared with nulliparous women, women with two, three, and four completed pregnancies had 2.485-, 2.844-, and 4.305-fold increased risk of having fewer than 20 teeth, respectively. Our study is the largest-scale study of the general female population in Japan and the first study to comprehensively investigate risk factors (parity, oral health status, and socioeconomic status) for fewer than 20 teeth. We thus found that higher parity, especially, two or more, was independent risk factors for having less than 20 teeth among Japanese women. In conclusion, the present study emphasizes the importance of good oral health habits in women, especially, during pregnancy and in the postpartum period, to maintain 20 or more teeth.
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http://dx.doi.org/10.1620/tjem.253.77DOI Listing
January 2021

Impact of lymphadenectomy on the treatment of endometrial cancer using data from the JSOG cancer registry.

Obstet Gynecol Sci 2021 Jan 27;64(1):80-89. Epub 2020 Nov 27.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.

Objective: Regional lymph node (LN) dissection is a standard surgical procedure for endometrial cancer, but there is currently no clear consensus on its therapeutic significance. We aimed to determine the impact of regional LN dissection on the outcome of endometrial cancer.

Methods: Study subjects comprised 36,813 patients who were registered in the gynecological tumor registry of the Japan Society of Obstetrics and Gynecology, had undergone initial surgery for endometrial cancer between 2004 and 2011, and whose clinicopathological factors and prognosis were appropriate for our investigation. The following clinicopathological factors were obtained from the registry: age, surgical stage classification, Union for International Cancer Control tumor, node, metastasis classification, histological type, histological differentiation, presence or absence of LN dissection, and postoperative treatment. We retrospectively analyzed the clinicopathological factors and therapeutic outcomes for patients with endometrial cancer.

Results: Analysis of all subjects showed that the group that underwent LN dissection had a significantly better overall survival than the group that did not undergo dissection. Analysis based on stage showed similar results across groups, except for stage Ia. Analysis based on stage and histological type showed similar results across groups, except for stage Ia endometrial carcinoma G1 or Ia G2. Multivariate analysis of prognostic factors indicated that LN dissection is an independent prognostic factor and that it has a greater impact on prognosis than adjuvant chemotherapy.

Conclusion: Despite the limitations of a retrospective study with some biases, the results suggest that LN dissection in endometrial cancer has a prognostic effect.
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http://dx.doi.org/10.5468/ogs.20186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834758PMC
January 2021

Analysis of pathological and clinical characteristics of cervical conization according to age group in Japan.

Heliyon 2020 Oct 8;6(10):e05193. Epub 2020 Oct 8.

Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, Japan.

Objective: With increased screening, more patients with precancerous or early cervical cancer are now being identified. Age at pregnancy, and thus number of patients requiring fertility preservation, have also increased, resulting in more diagnostic and therapeutic cervical conization (conization) procedures. We here investigated the pathological and clinical characteristics of patients undergoing conization, with a focus on age. The objectives of our study were to identify the risk factors potentially involved in cervical intraepithelial neoplasia (CIN) recurrence or persistence, additional treatment after conization, the effects of conization on pregnancy, and the actual status of conization in Japan.

Study Design: A "Subcommittee for Investigation of Cervical Conization" within the Gynecologic Oncology Committee in the Japan Society of Obstetrics and Gynecology investigated pathological and clinical characteristics of conization at 205 institutions in Japan. We analyzed pathological and clinical characteristics according to age ≤50 and >50 years.

Results: Patients aged 20-40 years accounted for 12904 (87%) of the 14,832 study patients (median: 37 years, range: 16-88 years). However, 1838 (12.4%) were aged >50 years. The commonest post-operative diagnosis was CIN grade 3 in all age groups. Rates of invasive cancer, post-operative detection of more advanced lesions, positive surgical margins, additional treatment, and recurrence were significantly higher in patients aged ≥50 years than those aged <50 years (all p < 0.01), whereas rates of post-operative complications did not differ significantly between age groups. The relationship between cerclage and the incidence of amniorrhexis or premature birth did not differ significantly in any age group.

Conclusion: Post-conization management of patients aged ≥50 years requires considering the high rates of detection of more advanced lesions post-operatively, positive surgical margins, and recurrence. Cerclage should not be performed post-conization without careful consideration.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560578PMC
October 2020

Squamous cell carcinoma arising from a mature cystic teratoma of the ovary: Successful treatment with carboplatin, paclitaxel, and bevacizumab.

Gynecol Oncol Rep 2020 Nov 26;34:100632. Epub 2020 Aug 26.

Department of Obstetrics Gynecology, Faculty of Medicine, Yamagata University, Iida-nishi, 2-2-2, Yamagata 990-9585, Japan.

Ovarian mature cystic teratomas (MCT) are usually benign. However, squamous cell carcinoma (SCC) develops in 0.17-2% of MCT. Because of its low frequency, the optimal treatment for this disease is unclear. We present a case of SCC arising from MCT. Our patient was a 30-year-old nulliparous woman complaining of right lower abdominal pain, who was referred to our hospital for a pelvic solid mass with suspected malignant ovarian tumor. A diagnosis of SCC arising from MCT was suspected based on the elevation in SCC antigen and the imaging. After surgery to remove the tumor, the diagnosis was confirmed based on the pathology. Although the surgery by radical cytoreduction was optimal, the tumor showed early recurrence. Therefore, we administrated combination chemotherapy, consisting of carboplatin, paclitaxel, and bevacizumab, followed by maintenance therapy with bevacizumab. Response to the chemotherapy regimen was complete and the patient was alive with no evidence of recurrence for 45 months after starting the initial surgery. We discuss the clinical characteristics of the malignant transformation of MCT and the treatment of SCC arising from MCT.
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http://dx.doi.org/10.1016/j.gore.2020.100632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490979PMC
November 2020

Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis.

J Gynecol Oncol 2020 Sep;31(5):e67

Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.

Objective: To assess the effectiveness of lymphadenectomy at primary debulking surgery (PDS) on the survival of patients with epithelial ovarian cancer (EOC).

Methods: We searched PubMed, Ichushi, and the Cochrane Library. Randomized controlled trials (RCTs) and retrospective cohort studies comparing survival of women with EOC undergoing lymphadenectomy at PDS with that of women without lymphadenectomy were included. We performed a meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse events.

Results: For advanced-stage EOC, 2 RCTs including 1,074 women and 7 cohort studies comprising 3,161 women were evaluated. Meta-analysis revealed that lymphadenectomy was associated with improved OS (hazard ratio [HR]=0.80; 95% confidence interval [CI]=0.70-0.90). However, meta-analysis of 2 RCTs revealed no significant difference in OS between the lymphadenectomy and no-lymphadenectomy groups (OS: HR=1.02; 95% CI=0.85-1.22). For early-stage EOC, 1 RCT comprising 268 women and 4 cohort studies comprising 14,228 women were evaluated. Meta-analysis showed that lymphadenectomy was associated with improved OS (HR=0.75; 95% CI=0.68-0.82). A RCT of early-stage EOC reported that lymphadenectomy was not associated with improved OS (HR=0.85; 95% CI=0.49-1.47). Surgery-related deaths were similar in both groups (risk ratio [RR]=1.00; 95% CI=0.99-1.01); however, blood transfusion was required less frequently in the no-lymphadenectomy group (RR=0.74; 95% CI=0.63-0.86).

Conclusions: Meta-analysis of RCTs and observational studies suggest that lymphadenectomy was associated with improved OS in advanced- and early-stage EOC. However, results from RCTs demonstrate that lymphadenectomy was not associated with improved OS in advanced- and early-stage EOC.
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http://dx.doi.org/10.3802/jgo.2020.31.e67DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440977PMC
September 2020

xCT inhibitor sulfasalazine depletes paclitaxel-resistant tumor cells through ferroptosis in uterine serous carcinoma.

Oncol Lett 2020 Sep 6;20(3):2689-2700. Epub 2020 Jul 6.

Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.

Glutathione (GSH) is a primary antioxidant that protects cells against reactive oxygen species (ROS), and high levels of GSH promote cancer cell survival and resistance to chemotherapy. The glutamine transporter xCT is essential for the intracellular synthesis of GSH, whereby xCT determines the intracellular redox balance. However, whether xCT inhibition can overcome GSH-mediated resistance to chemotherapeutic agents in uterine serous carcinoma (USC) remains unclear. Thus, the present study investigated the effect of the xCT inhibitor, sulfasalazine (SAS) on cytotoxicity in paclitaxel-sensitive and -resistant USC cell lines. The molecular mechanism by which SAS induces ferroptotic cell death in paclitaxel-resistant cells was assessed. The results of the cytotoxicity assay demonstrated that SAS was more cytotoxic in paclitaxel-resistant cells compared with in -sensitive cells; however, paclitaxel cytotoxicity was not enhanced in either of the USC cell lines. Immunoblotting analysis and the cell death assays performed using ferroptosis inhibitors indicated that SAS-mediated cell death was induced through ferroptosis, and not apoptosis, in paclitaxel-resistant cells. Furthermore, ROS production was increased in paclitaxel-resistant but not in -sensitive cells, even at low SAS concentration, and JNK was activated, which is a downstream target in the Ras signaling pathway. Knockdown of JNK reversed the inhibitory effect of SAS on cell proliferation and cell death. The synthetic lethal interaction between ROS accumulation and Ras effector JNK activation may be critical for enhancing the sensitivity to ferroptotic cell death mediated by xCT inhibitor, SAS. Taken together, the results of the present study suggest that xCT inhibition may be an effective treatment for patients with recurrent paclitaxel-resistant USC.
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http://dx.doi.org/10.3892/ol.2020.11813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400102PMC
September 2020

MicroRNA Let-7c Contributes to Paclitaxel Resistance via Aurora-B in Endometrial Serous Carcinoma.

Tohoku J Exp Med 2020 08;251(4):263-272

Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine.

The incidence of endometrial cancer has rapidly risen over recent years. Paclitaxel, a key drug for endometrial cancer treatment, inhibits microtubule depolymerization and induces apoptosis in cancer cells. Endometrial serous carcinoma (ESC) accounts for < 10% of all endometrial carcinomas, but its aggressive nature makes it responsible for close to 40% of cancer deaths. Thus, novel therapeutic targets are required for ESC. To identify microRNAs that promote paclitaxel resistance, we established two paclitaxel-resistant cell lines from USPC1 human ESC cells by exposing paclitaxel to parental cells for 12 weeks. Paclitaxel concentrations were increased every 2 weeks, and after 12 weeks of paclitaxel exposure, two replicate paclitaxel-resistant cell lines were established (USPC1-PTSR1 and USPC1-PTXR2). The microarray analysis was performed using USPC1 cells and USPC1-PTXR1 cells, and eight candidate microRNAs were thus selected as potential mediators of paclitaxel sensitivity. Among these candidate microRNAs, let-7c precursor treatment of paclitaxel-resistant USPC1-PTXR1 cells caused the greatest increase in paclitaxel-mediated cytotoxicity. Let-7c inhibition conversely decreased paclitaxel-induced apoptosis. It is known that let-7a microRNA, a member of the let-7 family, inhibits growth of endometrial carcinoma cells targeting Aurora-B that controls progression through each phase of mitosis. We thus studied whether let-7c mediates Aurora-B expression in ESC cells. The expression levels of Aurora-B mRNA and protein were higher in USPC-PTXR1 cells compared with USPC1 cells. Let-7c inhibition increased Aurora-B expression in USPC1 cells but decreased Aurora-B expression in USPC1-PTXR1 cells. These results indicate that let-7c mediates paclitaxel resistance via inhibition of Aurora-B expression in ESC cells.
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http://dx.doi.org/10.1620/tjem.251.263DOI Listing
August 2020

Epidemiological guideline influence on the therapeutic trend and patient outcome of uterine cervical cancer in Japan: Japan society of gynecologic oncology guideline evaluation committee project.

Gynecol Oncol 2020 10 25;159(1):248-255. Epub 2020 Jul 25.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Japan.

Objective: The Japan Society of Gynecologic Oncology published its first clinical guidelines for uterine cervical cancer in 2007 which has been revised twice in 2011 and 2017. The aim of this study was to investigate the influence of the first guideline publication on the therapeutic trend and patient outcome by analyzing uterine cervical cancer cases registered to the cancer registry organized by the Japan Society of Obstetrics and Gynecology.

Methods: Data of uterine cervical cancer cases registered to the cancer registry from 2000 to 2012 were provided. Epidemiological and clinical trend were analyzed by the Chi-squared test with subsequent standardized residual analysis. Overall survival among the patients registered between 2004 and 2009 was analyzed using the Fine and Gray competing risk model.

Results: 68,707 cases were registered during the study period. A trend analysis revealed that the guideline publication may have led to a decrease in neoadjuvant chemotherapy in parallel with an increase in radiation therapy mainly in stage II and III patients undergoing primary treatment. A survival analysis indicated that the introduction of the guideline may have improved overall survival among stage III uterine cervical cancer patients, even though a significant difference was not observed in all of the cases.

Conclusions: This study demonstrated the potential influence of the guideline publication on the clinical trend and patient outcome. As this is the first assessment of the guideline for uterine cervical cancer in Japan, continuous evaluation is necessary to further comprehend the significance of this guideline.
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http://dx.doi.org/10.1016/j.ygyno.2020.07.023DOI Listing
October 2020

Clinical and image features: large-vessel vasculitis after granulocyte colony stimulating factor administration.

Acta Radiol 2020 Jun 14:284185120931685. Epub 2020 Jun 14.

Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata, Japan.

Background: Granulocyte colony stimulating factor (G-CSF) is known to cause vasculitis, mainly in the small vessels. Several cases of large-vessel vasculitis (LVV) caused by G-CSF have recently been reported in the literature; we retrospectively suspect that some cases of LVV in our institution were associated with administration of G-CSF.

Purpose: To evaluate the clinical and radiological findings in our cases and to compare them with those in previous reports.

Material And Methods: We retrospectively evaluated clinical and radiological findings in four cases of LVV that occurred after administration of G-CSF in our institution. We also reviewed papers on G-CSF-related LVV and compared their findings to ours.

Results: G-CSF-related LVV occurred in patients aged > 50 years and more frequently in women. Most patients developed vasculitis within 15 days after the last administration. While 14/16 patients were symptomatic, the remaining two patients were asymptomatic and diagnosed incidentally. In all cases, laboratory inflammatory markers increased, but there were no autoantibodies that clearly indicated other autoimmune vasculitis. Computed tomography revealed elevated soft tissue density around the affected vessels.

Conclusion: LVV is among the potential adverse events of G-CSF administration. We should keep this outcome in mind when we interpret medical images of patients with previous G-CSF treatment history even if they are asymptomatic.
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http://dx.doi.org/10.1177/0284185120931685DOI Listing
June 2020

Impact of endoplasmic reticulum stress on oocyte aging mechanisms.

Mol Hum Reprod 2020 08;26(8):567-575

Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan.

Endoplasmic reticulum (ER) stress is associated with several aging-related diseases; however, the mechanism underlying age-related deterioration of oocyte quality is unclear. Here, we used post-ovulatory, in vivo aged mouse oocytes as a model. Super-ovulated oocytes harvested from the oviduct at 14 h and 20 h post-hCG injection were designated as 'fresh' and 'aged', respectively. Embryo development following IVF was compared between fresh, aged and ER stress-induced oocytes. Expression of the ER stress marker GRP78 was examined at each stage. To evaluate the effect of salubrinal, an ER stress suppressor, on embryo development following IVF, expression levels of GRP78 and phospho-eukaryotic initiation factor 2 alpha were compared between aged and salubrinal-treated aged oocytes. Embryo transfer of salubrinal-treated aged oocytes was performed to examine the safety of salubrinal. Similar to aged oocytes, ER stress-induced oocytes showed lower fertilization rates and poor embryo development. Following IVF, expression of GRP78 decreased with embryo development. GRP78 expression was significantly higher in aged oocytes than in fresh oocytes. Salubrinal lowered GRP78 levels and improved embryo development. No adverse effect of salubrinal treatment was found on the birth weight of pups or on organogenesis in mice. The limitation of this study was that protein kinase-like ER kinase was the only ER stress pathway examined; the role of IRE1 and ATF6 pathways was not considered. Nevertheless, salubrinal can significantly improve embryo development in in vivo aged oocytes undergoing ER stress. Hence, regulation of ER stress might represent a promising therapeutic strategy to overcome poor oocyte quality.
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http://dx.doi.org/10.1093/molehr/gaaa040DOI Listing
August 2020

Proposal of a Two-Tier System in Grouping Adenocarcinoma of the Uterine Cervix.

Cancers (Basel) 2020 May 15;12(5). Epub 2020 May 15.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 259-1193, Japan.

(1) : This study examined the use of a two-tier system in grouping cervical adenocarcinoma for survival discrimination. (2) : A nationwide retrospective observational cohort study was conducted using the Japan Society of Gynecologic Oncology tumor registry database from 2001 to 2015 ( = 86,754). Adenocarcinoma subtypes were grouped as type 1 (endocervical usual type and endometrioid) or type 2 (serous, clear, mucinous, and not otherwise specified), based on their relative survival compared with that of squamous tumors. (3) : The majority of the adenocarcinoma cases were type 1 ( = 10,121) versus type 2 tumors ( = 5157). Type 2 tumors were more likely to be old and have stage IV disease than those with squamous tumors. The number of type 2 tumors increased from 2001 to 2014 (106.1% relative increase, < 0.001). Type 2 tumors had disproportionally poorer survival compared to other types (5-year survival rates: 68.9% for type 2, 75.4% for type 1, and 78.0% for squamous; < 0.001). On multivariate analysis, type 2 tumors remained an independent prognostic factor associated with decreased survival compared with squamous (adjusted hazard ratio 2.00, 95% CI 1.84-2.15, < 0.001). (4) : The survival of cervical adenocarcinoma varies largely across the histological subtypes, and the proposed two-tier grouping may be useful for survival discrimination.
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http://dx.doi.org/10.3390/cancers12051251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281760PMC
May 2020

A retrospective study for investigating the relationship between old and new staging systems with prognosis in ovarian cancer using gynecologic cancer registry of Japan Society of Obstetrics and Gynecology (JSOG): disparity between serous carcinoma and clear cell carcinoma.

J Gynecol Oncol 2020 Jul 13;31(4):e45. Epub 2020 Jan 13.

Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.

Objective: International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and peritoneal cancers was revised in 2014. The aim of this study is to clarify whether the revised FIGO2014 staging reflects the prognosis of patients with ovarian cancer by histological type in Japan.

Methods: We extracted 9,747 patients who were diagnosed with ovarian cancer since 2004 until 2008 and who could be classified into appropriate stages from the Gynecologic Cancer Registry of Japan Society of Obstetrics and Gynecology. These cases were analyzed after revision to FIGO2014 based on the pTNM classification.

Results: Among stage I, the 5-year overall survival rate (5y-OS) in FIGO2014 was 94.9% in stage IA, 92.3% in stage IC1, 86.1% in IC2, and 84.9% in IC3 with significant differences between stages IA and IC1 (p=0.012), IC1 and IC2 (p<0.001). There was a significant difference between stages IA and IC1 in clear cell and mucinous carcinoma but not in serous and endometrioid carcinoma. Among stage III, the 5y-OS was 75.6% in stage IIIA1, 68.9% in IIIA2, 58.6% in IIIB, and 44.4% in IIIC, with significant differences between stages IIIA2 and IIIB (p=0.009), IIIB and IIIC (p<0.001). Among stage IV, the 5y-OS was 43.1% in stage IVA* and 32.1% in IVB with a significant difference (p=0.002).

Conclusion: The results suggest that changes in classification for stage III and stage IV are appropriate, but the subclassification for stage IC might be too detailed. There was a discrepancy of prognosis by histological type between stage IA and IC1.
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http://dx.doi.org/10.3802/jgo.2020.31.e45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286757PMC
July 2020

Clinical and reproductive outcomes of fertility-sparing surgery in stage I epithelial ovarian cancer.

Mol Clin Oncol 2020 Jan 22;12(1):44-50. Epub 2019 Nov 22.

Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.

The aim of the present study was to evaluate the oncologic safety and reproductive outcome in patients with stage I epithelial ovarian cancer (EOC) treated with fertility-sparing surgery (FSS). Women aged ≤40 years with stage I EOC who had undergone FSS between 2000 and 2010 were retrospectively reviewed. Survival was examined using the Kaplan-Meier method and statistical significance was analyzed using the log-rank test. A total of 29 EOC patients (stage IA, n=14; stage IC1 n=6; stage IC3, n=9) from seven participating institutions belonging to the Tohoku Gynecologic Cancer Unit were enrolled. After a median follow-up duration of 60.6 months (range, 6-135 months), five patients (17.2%) experienced tumor recurrence. The respective five-year relapse-free survival (RFS) and overall survival (OS) rates were 90.9 and 100% for stage IA/IC1, and 43.8 and 87.5% for stage IC3. Significant differences in RFS were observed between stage IA/IC1 and IC3 patients (P=0.026). However, there was no significant difference in OS between patients with 1A/1C1 and those with 1C3 (P=0.712). After FSS, seven pregnancies occurred in five patients, which resulted in the birth of six healthy children. The results of the present study confirmed that FSS may be an acceptable treatment method for stage IA and IC1 EOC, exhibiting a favorable reproductive outcome. However, the safety of FSS for treating stage IC3 EOC is uncertain and warrants further investigation.
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http://dx.doi.org/10.3892/mco.2019.1954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904870PMC
January 2020

Successful laparoscopic resection of virilizing ovarian steroid cell tumor, not otherwise specified, in a 22-year-old woman: a case report and evaluation of the steroidogenic pathway.

Fukushima J Med Sci 2020 Jan 11;65(3):133-139. Epub 2019 Dec 11.

Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine.

Objective: Ovarian steroid cell tumor (SCT) is a rare tumor with steroid-producing ability. We report a 22-year-old woman with secondary amenorrhea and hirsutism caused by an ovarian SCT-not otherwise specified (NOS), who underwent successfully laparoscopic resection of the tumor.

Case Report: A 22-year-old null gravida woman presented to a hospital, having amenorrhea for 18 months and increasing facial hair. Physical examination revealed obesity (body mass index, 37.3 kg/m) with evident facial and trunk hair. Total and free serum testosterone, and dehydroepiandrosterone sulfate levels were found to be elevated. Levels of serum adrenocorticotropic hormone, gonadotropins, cortisol, aldosterone, and ovarian steroids were observed to be within reference intervals. Although polycystic ovaries were not found, a hyperechogenic solid tumor (3 cm) was detected on transvaginal ultrasonography. Laparoscopic resection of the tumor was performed. One month post-surgery, total and free testosterone levels were observed to have decreased, and menstruation resumed two months thereafter. The patient was histologically diagnosed with ovarian SCT-NOS. Expression of ovarian steroidogenic enzymes, which are related to hyperandrogenism, was observed. No disease recurrence has been reported for more than 5 years post-surgery.
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http://dx.doi.org/10.5387/fms.2019-25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012592PMC
January 2020

Survival outcome and perioperative complication related to neoadjuvant chemotherapy with carboplatin and paclitaxel for advanced ovarian cancer: A systematic review and meta-analysis.

Eur J Surg Oncol 2020 05 4;46(5):868-875. Epub 2019 Dec 4.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Japan; Department of Obstetrics and Gynecology, Niigata University School of Medicine, Niigata, Japan. Electronic address:

Objective: To compare the effectiveness and safety of neoadjuvant chemotherapy with carboplatin/paclitaxel followed by interval debulking surgery (NACT-IDS) to primary debulking surgery plus postoperative chemotherapy (PDS) for advanced ovarian cancer.

Methods: A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Ovarian Cancer Committee. Multiple public search engines including PubMed/MEDLINE and the Cochrane Database, were searched in March 2019 using the entry keywords "ovarian cancer [all fields]" AND "interval debulking surgery [all fields]", AND "neoadjuvant chemotherapy [all fields]". Key inclusion criteria were prospective clinical trials examining platinum-based NACT for stage II-IV epithelial ovarian cancer. The primary outcome of interest was survival, and the secondary outcome was adverse events with each intervention.

Results: After screening 333 studies, four phase III randomized clinical trials were identified that met the inclusion criteria. These trials included 1692 women (847 receiving NACT-IDS and 845 receiving PDS). It was found that NACT-IDS and PDS had similar overall survival (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.87-1.07, P = 0.53) and progression-free survival (HR: 0.98, 95%CI: 0.90-1.08, P = 0.74). In contrast, NACT-IDS was associated with significantly lower rates of perioperative complications (odds ratio [OR] 0.27, 95%CI: 0.20-0.36, P < 0.001) and perioperative mortality (OR: 0.17, 95%CI: 0.06-0.50, P < 0.001) compared to PDS.

Conclusion: This systematic review and meta-analysis suggests that NACT-IDS with carboplatin and paclitaxel does not negatively impact the survival of women with advanced ovarian cancer compared to PDS, while perioperative complications and mortality are significantly reduced by 70-80%.
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http://dx.doi.org/10.1016/j.ejso.2019.11.520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535131PMC
May 2020
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