Publications by authors named "Aikou Okamoto"

170 Publications

Prevalence of common aneuploidy in twin pregnancies.

J Hum Genet 2022 Jan 1. Epub 2022 Jan 1.

Department of Obstetrics & Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.
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http://dx.doi.org/10.1038/s10038-021-01001-0DOI Listing
January 2022

Scoring Systems of Peritoneal Dissemination for the Prediction of Operative Completeness in Advanced Ovarian Cancer.

Anticancer Res 2022 Jan;42(1):115-124

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

Background/aim: We investigated the predictive value of scoring systems of peritoneal disseminations for complete surgery (CS) at primary debulking surgery (PDS) in advanced ovarian cancer.

Patients And Methods: We retrospectively enrolled eligible patients with clinical stages III or IVA selected for PDS from January 2015 to December 2019. Concern variables were predictive index value (PIV) and peritoneal cancer index (PCI) from operative and pathological reports. Primary endpoints were cutoffs to predict operative completeness using the receiver operating characteristic curve.

Results: Among 111 patients, PIV ≥8 and PCI ≥13 were the best predictors of incomplete PDS, including optimal and suboptimal surgeries (AUC=0.821 and 0.855, respectively). CS rates in PIV ≤6 and PCI ≤12 were significantly higher than in PIV ≥8 (89.3% vs. 47.2%; p<0.05) and PCI ≥13 (90.9% vs. 41.2%: p<0.05).

Conclusion: PIV and PCI are potential predictors for CS at PDS.
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http://dx.doi.org/10.21873/anticanres.15465DOI Listing
January 2022

Impact of COVID-19 on cervical cancer screening in Japan: A survey of population-based screening in urban Japan by the Japan Society of Gynecologic Oncology.

J Obstet Gynaecol Res 2021 Dec 22. Epub 2021 Dec 22.

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

Aim: To assess the impact of COVID-19 on cervical cancer screening.

Method: The Japanese Society of Gynecologic Oncology launched COVID-19 Task Force surveyed the municipalities in urban areas of Japan. Questionnaires were sent to 20 ordinance-designated cities and 23 wards of Tokyo metropolitan area in Japan via telephone and mail in January 2021. An additional survey was conducted in March and April 2021, counted the monthly checkups in 2020 and, as a control data, the number of monthly checkups in 2019. "The State of Emergency" between April 7 and May 25, 2020, included 13 prefectures. The data collected in this research involved the number of screenings only. The chi-square test was performed for statistical analysis.

Results: The number of cancer screenings from March to August, with May being the month with the lowest number of screenings, was less than 50% of that in the previous year. In particular, the drop in the number of cancer screenings in the "Prefectures operating under special safety precautions" was remarkable and significantly lower than that in other Prefectures. However, after August, the number recovered to the usual level, despite the second wave of the pandemic occurring nationwide. The initial "the State of Emergency" caused a significant decrease in the number of people receiving population-based screenings, but the recovery has been remarkable, and the total number is expected to be the same as in previous years.

Conclusion: The initial "the State of Emergency" caused a significant decrease in the number of people receiving population-based screenings.
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http://dx.doi.org/10.1111/jog.15130DOI Listing
December 2021

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial.

Gynecol Oncol 2021 Dec 17. Epub 2021 Dec 17.

US Oncology Research, The Woodlands, TX, USA.

Objective: In the Phase 3 VELIA trial (NCT02470585), veliparib added to carboplatin plus paclitaxel concomitantly and as maintenance for women with newly-diagnosed advanced ovarian cancer significantly improved progression-free survival (PFS) versus chemotherapy alone. Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (gBRCA) status.

Methods: Women with untreated ovarian carcinoma were randomized (1:1:1) to: veliparib during chemotherapy and maintenance (veliparib-throughout), veliparib during chemotherapy followed by placebo maintenance (veliparib-combination only), or placebo during chemotherapy and maintenance (control). Chemotherapy included carboplatin plus dose-dense (DD; weekly) or every-3-week (Q3W) paclitaxel (a stratification factor at randomization), selected at the investigator's discretion pre-randomization. PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and gBRCA status.

Results: 1132 patients were analyzed by paclitaxel schedule. Pooled treatment arms demonstrated longer median PFS with DD (n = 586) versus Q3W (n = 546) paclitaxel (ITT: 20.5 vs 15.7 months, hazard ratio [HR] 0.77; homologous recombination proficient cancer: 15.1 vs 11.8 months, HR 0.64; BRCAwt: 18.0 vs 12.9 months, HR 0.70). Comparison between arms favored veliparib-throughout versus control in both DD (PFS, 24.2 vs 18.3 months, hazard ratio 0.67) and Q3W (19.3 vs 14.6, hazard ratio 0.69) subgroups. DD paclitaxel was associated with higher incidence of Grade 3/4 neutropenia, fatigue, and anemia versus Q3W. There were no differences in toxicity between gBRCAm (n = 211) and gBRCAwt (n = 902) subgroups.

Conclusions: DD paclitaxel was tolerable and associated with longer PFS in the HR proficient and gBRCAwt groups, versus Q3W. gBRCA status did not impact safety.
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http://dx.doi.org/10.1016/j.ygyno.2021.12.012DOI Listing
December 2021

A case of relapsing aseptic meningitis under excellent tumor response to pembrolizumab in microsatellite instability-high recurrent endometrial cancer.

Gynecol Oncol Rep 2021 Nov 23;38:100885. Epub 2021 Oct 23.

Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.

•This is the first report of aseptic meningitis due to immune checkpoint inhibitor treatment in endometrial cancer.•The meningitis was severe and relapsed multiple times unlike in other reported cases.•Oncologic outcome was excellent after overcoming this severe adverse event.
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http://dx.doi.org/10.1016/j.gore.2021.100885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651784PMC
November 2021

Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study.

Gynecol Oncol 2021 Dec 11. Epub 2021 Dec 11.

US Oncology Research, 9180 Pinecroft, The Woodlands, TX 77380, USA.

Objective: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy.

Methods: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, CA-125 levels were measured at baseline and each cycle; radiographic responses were assessed every 9 weeks.

Results: Of 1140 patients randomized, 742 had BRCA wild type (BRCAwt) tumors (HRP, n = 373; HRD/BRCAwt, n = 329). PFS hazard ratios between veliparib-throughout versus control were similar in both BRCAwt populations (HRD/BRCAwt: 22.9 vs 19.8 months; hazard ratio 0.76; 95% confidence interval [CI] 0.53-1.09; HRP: 15.0 vs 11.5 months; hazard ratio 0.765; 95% CI 0.56-1.04). By Cycle 3, the proportion with ≥90% CA-125 reduction from baseline was higher in those receiving veliparib (pooled arms) versus control (34% vs 23%; P = 0.0004); particularly in BRCAwt and HRP subgroups. Complete response rates among patients with measurable disease after surgery were 24% with veliparib (pooled arms) and 18% with control.

Conclusions: These results potentially broaden opportunities for PARPi utilization among patients who would not qualify for frontline PARPi maintenance based on other trials.
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http://dx.doi.org/10.1016/j.ygyno.2021.12.003DOI Listing
December 2021

Clinical Study of Sentinel Lymph Node Detection Using Photodynamic Eye for Abdominal Radical Trachelectomy.

Curr Oncol 2021 Nov 15;28(6):4709-4720. Epub 2021 Nov 15.

Department of Gynecology, Sasaki Foundation Kyoundo Hospital, 1-8 Kanda Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.

This study aimed to assess the accuracy of predicting pelvic lymph node status using sentinel lymph node (SLN) biopsy with indocyanine green (ICG) and to examine the outcomes of SLN biopsy-guided abdominal radical trachelectomy (ART). Patients with stage IA2-IB2 cervical cancer from January 2009 to January 2021 were included. ICG was injected before ART and SLNs were identified, excised, and assessed intraoperatively using fast-frozen sections. Systemic pelvic lymphadenectomy was subsequently performed. The SLN detection rate, sensitivity, and false-negative rate were determined. Thirty patients desiring fertility preservation were enrolled, of whom 26 successfully completed ART and four underwent radical hysterectomies because of metastatic primary SLNs. Bilateral SLNs were identified in all patients. The sensitivity, false-negative rate, and negative predictive value were 100%, 7.7%, and 92.3%, respectively. Three (12%) patients were lost to follow-up: two relapsed and one died of tumor progression. Of the nine patients who tried to conceive after surgery, four achieved pregnancy and three delivered healthy live infants. In women with early-stage cervical cancer who desired to conserve fertility, SLN mapping with ICG had a very high detection rate, sensitivity, and low false-negative rate. SLN biopsy-guided ART is a feasible and accurate method for assessing pelvic node status.
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http://dx.doi.org/10.3390/curroncol28060397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628807PMC
November 2021

Altered cervicovaginal microbiota in premenopausal ovarian cancer patients.

Gene 2022 Feb 29;811:146083. Epub 2021 Nov 29.

Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Electronic address:

Nearly three hundred thousand female patients are diagnosed with ovarian cancer in the world annually, and this number shows an increasing trend. However, characteristic symptoms caused by ovarian cancer are so few that early diagnosis remains challenging, and an effective screening method has not yet been established. Here, we conducted a case-control study in Japan to analyze the association between cervicovaginal microbiome and ovarian cancer, using 16S rRNA amplicon sequencing. Analysis of DNA extracted from cervical smear samples revealed Lactobacillus-dominant and Lactobacillus-deficient, highly-diversified bacterial communities in premenopausal and postmenopausal healthy controls, respectively, as reported for vaginal microbiota previously. We found that cervicovaginal microbiota in ovarian cancer patients, regardless of their menopausal status, were frequently a diversified community and similar to those in healthy subjects at postmenopausal ages. The diverse microbiota was associated with the major histotypes of epithelial ovarian cancer, including serous ovarian cancer and ovarian clear cell cancer. The present study implies the potential of a cervicovaginal microbiome biomarker in screening ovarian cancer in premenopausal women.
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http://dx.doi.org/10.1016/j.gene.2021.146083DOI Listing
February 2022

Smartphone application improves fertility treatment-related literacy in a large-scale virtual randomized controlled trial in Japan.

NPJ Digit Med 2021 Nov 30;4(1):163. Epub 2021 Nov 30.

Center for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.

People of reproductive age have unmet needs related to deficiencies in fertility literacy. Here, we aimed to investigate whether providing fertility-related information via a smartphone application could improve fertility treatment-related literacy in participants. We performed a randomized control-group pretest posttest study and recruited participants between June 18 and 25, 2020. Participants' fertility treatment-related literacy was assessed with a pretest that comprised of 28 questions and participants were allocated with stratified randomization to either intervention group or control group. The intervention comprised a one-week smartphone application-based provision of information on fertility-related information and the control group received general information about women's healthcare. Effectiveness of intervention was assessed using a posttest. A total of 4137 participants were administered the questionnaire and pretest, among which 3765 participants (91.0 %) responded and were randomly allocated into either the intervention group (N = 1883) or the control group (N = 1882). A significantly higher posttest mean score was observed for the intervention group compared to the control group (P = 0.0017). We also observed that posttest scores were significantly improved compared to pretest scores in both the intervention and control group (P < 0.001). When examining by specific test question, the proportion answering correctly increased at posttest compared to pretest for both intervention and control groups (P < 0.001). Furthermore, the intervention group showed a greater mean difference between posttest and pretest scores than the control group (P < 0.001). In conclusion, educational intervention using a smartphone application contributed to enhancing fertility treatment-related literacy.
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http://dx.doi.org/10.1038/s41746-021-00530-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632894PMC
November 2021

A case of laparoscopically treated broad ligament ectopic pregnancy followed by spontaneous gestation.

J Obstet Gynaecol Res 2021 Nov 18. Epub 2021 Nov 18.

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

We present a case of spontaneous pregnancy after laparoscopic surgery for a broad ligament pregnancy. A 34-year-old nulliparous woman presented with 6 weeks of amenorrhea. Due to the presence of an empty uterus with a 10 mm right adnexal mass on transvaginal ultrasonography and elevated serum human chorionic gonadotropin (hCG), ectopic pregnancy was suspected. Upon diagnostic laparoscopy, the presence of a 2 cm broad ligament ectopic pregnancy was confirmed. Laparoscopic removal of the gestational tissues was performed. Six months after surgery, a spontaneous pregnancy was established. At the 40th week of gestation, a cesarean section was performed due to arrested labor, resulting in live birth. To the best of our knowledge, there have been no reports of a spontaneous pregnancy occurring after laparoscopic surgery for broad ligament pregnancy. Laparoscopic surgery as a treatment option for broad ligament pregnancy may be useful in early gestational age because it can be completed without complications.
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http://dx.doi.org/10.1111/jog.15099DOI Listing
November 2021

Impact of COVID-19 on gynecologic cancer treatment in Japan: a nationwide survey by the Japan Society of Gynecologic Oncology (JSGO).

J Gynecol Oncol 2022 01 2;33(1):e8. Epub 2021 Nov 2.

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

Objective: As coronavirus disease 2019 (COVID-19) rages on, it is a challenging task to balance resources for treatment of COVID-19 and malignancy-based treatment. For the development of optimal strategies, assessing the conditions and constrains in treatment during the COVID-19 pandemic is pertinent. This study reported about a nationwide survey conducted by the Japan Society of Gynecologic Oncology.

Methods: We interviewed 265 designated training facilities about the state of their clinical practice from the time period between March and December 2020. We asked the facility doctors in charge to fill a web-based questionnaire.

Results: A total of 232 facilities (87.5%) responded. A decrease in the number of outpatient visits was reported, and the major reason attributed was reluctance of patients to visit hospitals rather than facility restrictions. The actual number of surgeries decreased by 3.9%, compared to 2019. There was a significant difference when the variable of "Prefectures operating under special safety precautions" or not was introduced. There was no increase in the rate of advanced stages in the three cancer types studied. However, 34.1% participants perceived COVID-19 affected management and prognosis.

Conclusion: Refraining from visiting hospitals based on the patient's judgment may be expected to be an issue in the future. No significant decrease in surgeries was observed, and it would seem that there were few forced changes in treatment plans, but "the State of Emergency" had an impact. There was no increase in the rate of advanced cancers, but this will need to be monitored.
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http://dx.doi.org/10.3802/jgo.2022.33.e8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728672PMC
January 2022

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

Clinical Availability of Tumour Biopsy Using Diagnostic Laparoscopy for Advanced Ovarian Cancer.

In Vivo 2021 Nov-Dec;35(6):3325-3331

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

Background/aim: Tumour biopsy using laparoscopy before neoadjuvant chemotherapy for advanced ovarian cancer has been widely accepted. However, there are few reports about its operative outcome compared to biopsy with laparotomy. We investigated the advantage of laparoscopic biopsy for advanced ovarian cancer.

Patients And Methods: We included 23 patients who underwent laparoscopy and 27 who underwent exploratory laparotomy before neoadjuvant chemotherapy between January 2012 and August 2020. We reviewed their medical records and evaluated their operative outcomes.

Results: Blood loss was significantly lower in the laparoscopy group (5 ml vs. 320 ml, p<0.05). The period until the initiation of neoadjuvant chemotherapy was significantly shorter in the laparoscopy group (12 days vs. 16 days, p<0.05). Overall survival did not differ significantly between the two groups (25.4 months vs. 24.7 months, p=0.53).

Conclusion: Laparoscopic tumour biopsy is useful and safe for histological diagnosis, thereby allowing for early introduction to neoadjuvant chemotherapy.
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http://dx.doi.org/10.21873/invivo.12629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627755PMC
October 2021

Improved library preparation protocols for amplicon sequencing-based noninvasive fetal genotyping for RHD-positive D antigen-negative alleles.

BMC Res Notes 2021 Sep 26;14(1):380. Epub 2021 Sep 26.

Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.

Objective: We aimed to simplify our fetal RHD genotyping protocol by changing the method to attach Illumina's sequencing adaptors to PCR products from the ligation-based method to a PCR-based method, and to improve its reliability and robustness by introducing unique molecular indexes, which allow us to count the numbers of DNA fragments used as PCR templates and to minimize the effects of PCR and sequencing errors.

Results: Both of the newly established protocols reduced time and cost compared with our conventional protocol. Removal of PCR duplicates using UMIs reduced the frequencies of erroneously mapped sequences reads likely generated by PCR and sequencing errors. The modified protocols will help us facilitate implementing fetal RHD genotyping for East Asian populations into clinical practice.
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http://dx.doi.org/10.1186/s13104-021-05793-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474863PMC
September 2021

FIGO staging for carcinoma of the vulva: 2021 revision.

Int J Gynaecol Obstet 2021 Oct;155(1):43-47

Oxford Gynecological Cancer Center, Churchill Hospital, Oxford, UK.

To revise the FIGO staging for carcinoma of the vulva using a new approach that involves analyses of prospectively collected data. The FIGO Committee for Gynecologic Oncology reviewed the recent literature to gain an insight into the impact of the 2009 vulvar cancer staging revision. The Committee resolved to revise the staging with a goal of simplification and actively collaborated with the United States National Cancer Database to analyze prospectively collected data on carcinoma of the vulva. Many tumor characteristics were collected for all stages of vulvar cancer treated between 2010 and 2017. Statistical analysis was performed with SAS software. Overall survival was estimated based on tumor characteristics. Log-rank and Wilcoxon tests were used to analyze overall survival similarities between and within groups of tumor characteristics. Characteristics with similar survivals were then grouped into the same stages and substages. Kaplan-Meier overall survival curves were generated for the resulting stages and substages. There were 12 063 cases with available data. The resulting new staging for carcinoma of the vulva has two substages in Stage I, no substage in Stage II, three substages in Stage III, and two substages in Stage IV. The Kaplan-Meier overall survival curves showed clear separation between stages and substages. The 2021 vulvar cancer staging is the first from the FIGO Committee for Gynecologic Oncology to be derived from data analyses. This revision has a new definition for depth of invasion, uses the same definition for lymph node metastases utilized in cervical cancer, and allows findings from cross-sectional imaging to be incorporated into vulvar cancer staging. The 2021 FIGO staging for carcinoma of the vulva is data-derived, validated, and much simpler than earlier revisions.
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http://dx.doi.org/10.1002/ijgo.13880DOI Listing
October 2021

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

Restoration of keratinocytic phenotypes in autonomous trisomy-rescued cells.

Stem Cell Res Ther 2021 08 25;12(1):476. Epub 2021 Aug 25.

Center for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.

Background: An extra copy of chromosome 21 in humans can alter cellular phenotypes as well as immune and metabolic systems. Down syndrome is associated with many health-related problems and age-related disorders including dermatological abnormalities. However, few studies have focused on the impact of trisomy 21 (T21) on epidermal stem cells and progenitor cell dysfunction. Here, we investigated the differences in keratinocytic characteristics between Down syndrome and euploid cells by differentiating cells from trisomy 21-induced pluripotent stem cells (T21-iPSCs) and autonomous rescued disomy 21-iPSCs (D21-iPSCs).

Methods: Our protocol for keratinocytic differentiation of T21-iPSCs and D21-iPSCs was employed. For propagation of T21- and D21-iPSC-derived keratinocytes and cell sheet formation, the culture medium supplemented with Rho kinase inhibitor on mouse feeder cells was introduced as growth rate decreased. Before passaging, selection of a keratinocytic population with differential dispase reactivity was performed. Three-dimensional (3D) air-liquid interface was performed in order to evaluate the ability of iPSC-derived keratinocytes to differentiate and form stratified squamous epithelium.

Results: Trisomy-rescued disomy 21-iPSCs were capable of epidermal differentiation and expressed keratinocytic markers such as KRT14 and TP63 upon differentiation compared to trisomy 21-iPSCs. The lifespan of iPSC-derived keratinocytes could successfully be extended on mouse feeder cells in media containing Rho kinase inhibitor, to more than 34 population doublings over a period of 160 days. Dispase-based purification of disomy iPSC-derived keratinocytes contributed epidermal sheet formation. The trisomy-rescued disomy 21-iPSC-derived keratinocytes with an expanded lifespan generated 3D skin in combination with a dermal fibroblast component.

Conclusions: Keratinocytes derived from autonomous trisomy-rescued iPSC have the ability of stratification for manufacturing 3D skin with restoration of keratinocytic functions.
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http://dx.doi.org/10.1186/s13287-021-02448-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390253PMC
August 2021

A multi-ethnic analysis of immune-related gene expression signatures in patients with ovarian clear cell carcinoma.

J Pathol 2021 11 1;255(3):285-295. Epub 2021 Sep 1.

School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Little is known about the immune environment of ovarian clear cell carcinoma (OCCC) and its impact on various ethnic backgrounds. The aim of this OCCC immune-related gene expression signatures (irGES) study was to address the interaction between tumour and immune environment of ethnically-diverse Asian and Caucasian populations and to identify relevant molecular subsets of biological and clinical importance. Our study included 264 women from three different countries (Singapore, Japan, and the UK) and identified four novel immune subtypes (PD1-high, CTLA4-high, antigen-presentation, and pro-angiogenic subtype) with differentially expressed pathways, and gene ontologies using the NanoString nCounter PanCancer Immune Profiling Panel. The PD1-high and CTLA4-high subtypes demonstrated significantly higher PD1, PDL1, and CTLA4 expression, and were associated with poorer clinical outcomes. Mismatch repair (MMR) protein expression, assessed by immunohistochemistry, revealed that about 5% of OCCCs had deficient MMR expression. The prevalence was similar across the three countries and appeared to cluster in the CTLA4-high subtype. Our results suggest that OCCC from women of Asian and Caucasian descent shares significant clinical and molecular similarities. To our knowledge, our study is the first study to include both Asian and Caucasian women with OCCC and helps to shine light on the impact of ethnic differences on the immune microenvironment of OCCC. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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http://dx.doi.org/10.1002/path.5769DOI Listing
November 2021

Prenatal enzyme replacement therapy for mice with lethal hypophosphatasia.

Regen Ther 2021 Dec 5;18:168-175. Epub 2021 Jul 5.

Center for Regenerative Medicine, National Center for Child Health and Development Research Institute, Tokyo, Japan.

Hypophosphatasia (HPP) is a congenital skeletal disease. Impairment of bone mineralization and seizures are due to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP). Enzyme replacement therapy (ERT) is available as a highly successful treatment for pediatric-onset HPP. However, the potential for prenatal ERT has not been fully investigated to date. In this study, we assessed outcomes and maternal safety using a combinational approach with prenatal and postnatal administration of recombinant TNAP in mice as a model of infantile HPP. For the prenatal ERT, we administered subcutaneous injections of recombinant TNAP to pregnant mice from embryonic day 11.5-14.5 until delivery, and then sequentially to pups from birth to day 18. For the postnatal ERT, we injected pups from birth until day 18. Prenatal ERT did not cause any ectopic mineralization in heterozygous maternal mice. Both prenatal and postnatal ERT preserved growth, survival rate and improved bone calcification in mice. However, the effects of additional prenatal treatment to newborn mice appeared to be minimal, and the difference between prenatal and postnatal ERT was subtle. Further improvement of the prenatal ERT schedule and long-term observation will be required. The present paper sets a standard for such future studies.
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http://dx.doi.org/10.1016/j.reth.2021.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267436PMC
December 2021

Isolation and characterization of fetal nucleated red blood cells from maternal blood as a target for single cell sequencing-based non-invasive genetic testing.

Reprod Med Biol 2021 Jul 14;20(3):352-360. Epub 2021 Jun 14.

Department of Maternal-Fetal Biology National Center for Child Health and Development Tokyo Japan.

Purpose: Although non-invasive prenatal testing (NIPT) based on cell-free DNA (cfDNA) in maternal plasma has been prevailing worldwide, low levels of fetal DNA fraction may lead to false-negative results. Since fetal cells in maternal blood provide a pure source of fetal genomic DNA, we aimed to establish a workflow to isolate and sequence fetal nucleated red blood cells (fNRBCs) individually as a target for NIPT.

Methods: Using male-bearing pregnancy cases, we isolated fNRBCs individually from maternal blood by FACS, and obtained their genomic sequence data through PCR screening with a Y-chromosome marker and whole-genome amplification (WGA)-based whole-genome sequencing.

Results: The PCR and WGA efficiencies of fNRBC candidates were consistently lower than those of control cells. Sequencing data analyses revealed that although the majority of the fNRBC candidates were confirmed to be of fetal origin, many of the WGA-based genomic libraries from fNRBCs were considered to have been amplified from a portion of genomic DNA.

Conclusions: We established a workflow to isolate and sequence fNRBCs individually. However, our results demonstrated that, to make cell-based NIPT targeting fNRBCs feasible, cell isolation procedures need to be further refined such that the nuclei of fNRBCs are kept intact.
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http://dx.doi.org/10.1002/rmb2.12392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254165PMC
July 2021

A rare case of heterotopic pregnancy after a single embryo transfer: A case report and literature review.

J Obstet Gynaecol Res 2021 Oct 12;47(10):3707-3711. Epub 2021 Jul 12.

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

Heterotopic pregnancy (HP) is a rare but life-threatening disease. We report a rare case of HP that occurred after single embryo transfer (SET) with spontaneous natural pregnancy possibly due to sexual intercourse (SI) during assisted reproductive technology treatment and reviewed previous reports. A 39-year-old woman at 7 weeks 5 days' gestation with anti-sperm antibody who underwent a single frozen-thawed embryo transfer in her natural cycle presented with lower abdominal pain and vaginal bleeding. She had several SIs before the day of SET. A viable intrauterine fetus and an extrauterine mass at the right adnexa were detected on transvaginal ultrasonography. An emergent laparoscopic surgery showed a swollen right fallopian tube, and right salpingectomy was performed. Unfortunately, intrauterine fetal death was diagnosed at 19 weeks' gestation. In conclusion, the possibility of HP should be considered in patients with SIs around the day of SET.
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http://dx.doi.org/10.1111/jog.14923DOI Listing
October 2021

Alteration of circulating cell-free DNA level by external cephalic version: A potential biomarker for direct evaluation of placental damage.

J Obstet Gynaecol Res 2021 Sep 29;47(9):3144-3150. Epub 2021 Jun 29.

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

Aim: To confirm that variations in cell-free fetal DNA (cffDNA) are indicators of external placental damage, we quantitatively investigated cffDNA alterations in maternal peripheral blood during external cephalic version (ECV).

Methods: We recruited 48 singleton pregnant women who underwent ECV in our hospital. Before and immediately after ECV, we harvested 10 ml of maternal peripheral blood samples for cffDNA analysis. cffDNA alterations were assessed based on the fetal fraction (FF) rate. We performed ECV without epidural anesthesia but administered epidural anesthesia if ECV was disrupted due to severe pain.

Results: The FF increased from 22.9% ± 5.7% to 27.0% ± 5.7% (p < 0.05) after ECV. The FF increased in both successful (before, 24.4% ± 5.9%; after, 28.1% ± 5.9%; p < 0.05) and unsuccessful (before, 21.8% ± 3.8%; after, 27.3% ± 4.2%; p < 0.05) cases, as well as in patients who received epidural anesthesia (before, 23.9% ± 4.7%; after, 28.5% ± 4.4%; p < 0.05) or underwent ECV more than once (before, 23.5% ± 6.1%; after, 28.4% ± 5.3%; p < 0.05).

Conclusions: FF alterations increased due to external stresses during ECV; the alterations were markedly greater when the strength and duration of external stress increased. These FF alterations may serve as potential biomarkers for the direct assessment of placental damage.
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http://dx.doi.org/10.1111/jog.14853DOI Listing
September 2021

Total parietal peritonectomy in primary debulking surgery for advanced ovarian cancer.

Gynecol Oncol Rep 2021 Aug 11;37:100805. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-19-18 Nishishinbashi, Minato-ku, Tokyo, Japan.

The object of this study is to evaluate the clinical safety and efficacy of total parietal peritonectomy (TPP) in primary debulking surgery (PDS) for advanced ovarian cancer. This retrospective single-center study analyzed 16 patients with FIGO stages IIIC-IVB epithelial ovarian cancer who underwent TPP in PDS and achieved macroscopically complete resection between April 2015 and June 2016. The median age of 16 patients was 52.5 years old. 12 were in stage IIIC and 4 were in stage IV. Regarding intraoperative complications, unintended diaphragm perforation was observed in two patients. Regarding postoperative complications (Clavien-Dindo classification grade 3-5) before the adjuvant chemotherapy, lymph cysts occured in 3 patients, intra-abdominal abscess in 3, ileus in 2, pancreatic fistula in 1 and temporary kidney failure in 1. Regarding postoperative complications (grade 3-5) after the initiation of adjuvant chemotherapy, diaphragmatic hernia occured in 1 patient, ileus in 2 and intra-abdominal abscess in 2. Except 1 patient who relapsed approximately one month from surgery and died, the other 15 patients overcamed complications and recovered without problems in daily life. This analysis was conducted 3 years after all patients underwent PDS, with the 3-year progression-free and overall survival of 62.5% (95% confidence interval [CI], 34.9-81.1) and 87.5% (95 %CI, 58.6-96.7), respectively. Based on the above results, TPP in PDS may improve the prognosis compared to previous reports such as LION trial. On the other hand, complications may increase. Therefore, further studies are necessary on its safety and efficacy.
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http://dx.doi.org/10.1016/j.gore.2021.100805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202340PMC
August 2021

Progression-free survival by investigator versus blinded independent central review in newly diagnosed patients with high-grade serous ovarian cancer: Analysis of the VELIA/GOG-3005 trial.

Gynecol Oncol 2021 08 8;162(2):375-381. Epub 2021 Jun 8.

US Oncology Research, The Woodlands, Houston, TX, USA. Electronic address:

Objective: In the phase 3 VELIA/GOG-3005 trial, veliparib added to carboplatin-paclitaxel and continued as maintenance improved progression-free survival (PFS) compared to carboplatin-paclitaxel alone in patients with newly diagnosed ovarian carcinoma. Primary analysis of PFS was by investigator (INV) assessment, with a supplemental analysis of PFS by blinded independent central review (BICR).

Methods: Patients received veliparib or placebo with carboplatin-paclitaxel (6 cycles) and as maintenance (30 additional cycles). The primary analysis compared PFS in the veliparib-throughout arm to the carboplatin-paclitaxel only arm in the BRCA mutation (BRCAm), homologous recombination deficiency (HRD), and intention-to-treat (ITT) populations. Exploratory analyses of PFS in BRCA wildtype (BRCAwt), homologous recombination proficient (HRP), and HRD + BRCAwt populations were also performed. PFS per BICR and overall concordance rates between INV and BICR assessments were analyzed.

Results: Hazard ratios for PFS by INV and BICR were consistent in each of the primary analysis and exploratory populations. In the ITT population, median PFS per INV was 23.5 months in the veliparib-throughout arm versus 17.3 months in the control arm (hazard ratio [HR] 0.683, 95% confidence interval [CI] 0.562-0.831; P < 0.001). Median PFS by BICR was 29.3 months versus 19.2 months (HR 0.687, 95% CI 0.504-0.806). In the ITT population, the overall concordance rates between INV and BICR were 78% and 75% for the veliparib-throughout and control arms, respectively.

Conclusions: Hazard ratios for PFS per BICR and per INV were consistent, with no suggestion of investigator bias. These findings support the reliability of PFS by INV in ovarian cancer trials.
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http://dx.doi.org/10.1016/j.ygyno.2021.05.031DOI Listing
August 2021

Analysis of Surgical Procedure of Four Cases of Ovarian Pregnancies Treated with Laparoscopic Surgery.

Gynecol Minim Invasive Ther 2021 Apr-Jun;10(2):117-120. Epub 2021 Apr 30.

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

Ovarian pregnancy is a rare disease, accounting for 0.5%-3% of ectopic pregnancies. Ovarian pregnancy risk factors and preoperative diagnosis have been extensively reported. However, its histopathology and surgical findings have been poorly studied. To examine appropriate surgical procedures, we investigated the clinical features, surgical findings, and histopathological examinations of four ovarian pregnancy cases treated in our hospital. In histopathological examination, most specimens did not contain ovarian tissues; in some cases, villous tissues were buried in a clot. Therefore, evaluating the appropriateness of surgical resection range from histopathological images was difficult. However, the postoperative course was favorable; no cases manifested complications. Considering all these facts, we regarded the surgical procedures of the four cases in this study as appropriate. For the treatment of ovarian pregnancies, especially for the outward development type, a sufficient therapeutic effect may be achieved even without extensive excision of the ovarian tissues by laparoscopic surgery.
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http://dx.doi.org/10.4103/GMIT.GMIT_120_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140542PMC
April 2021

Initiatives and achievements of the Japanese Society of Obstetrics and Gynecology, Obstetrics and Gynecology MIRAI Committee 2020.

J Obstet Gynaecol Res 2021 Jun 1;47(6):1973-1977. Epub 2021 May 1.

Division of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.

Backgrounds: In 2013, the total number of obstetrician-gynecologists decreased. The Japanese Society of Obstetrics and Gynecology established the Obstetrics and Gynecology MIRAI Committee in 2015. Within the MIRAI Committee, Japanese Trainees in Obstetrics and Gynecology (JTOG) was established; it was comprised of 20 promising young obstetrician-gynecologists recommended from regions across Japan. The office term is 2 years.

Objective: The purpose of this report is to learn and inform about the results of MIRAI's activities.

Methods: We surveyed the trends in new obstetrician-gynecologists and also matched each seminar participant with them.

Result: The number of new memberships has been increasing since the nadir in 2016. In particular, there are over 100 more new physicians specializing in the field in 2020 than there were at the nadir in 2016. It was revealed that approximately 50% of the participants in the summer school specialized in obstetrics and gynecology. Furthermore, approximately 70% of POP2 participants specialized in obstetrics and gynecology, which shows that these two recruitment seminars are extraordinarily effective events that result in an increase in the number of new obstetricians and gynecologists.

Conclusion: We conclude that the activities of this MIRAI Committee and JTOG have been effective. With the spread of COVID-19 and the inability of obstetrician-gynecologists and students/clinical trainees to perform social distancing, it is currently difficult to hold hands-on seminars. However, we hope that new JTOG members will be able to create a new seminar format.
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http://dx.doi.org/10.1111/jog.14734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251879PMC
June 2021

Treatment Strategies for ARID1A-Deficient Ovarian Clear Cell Carcinoma.

Cancers (Basel) 2021 Apr 7;13(8). Epub 2021 Apr 7.

Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.

Ovarian clear cell carcinoma (OCCC) is a histological subtype of ovarian cancer that is more frequent in Asian countries (~25% of ovarian cancers) than in US/European countries (less than 10%). OCCC is refractory to conventional platinum-based chemotherapy, which is effective against high-grade serous carcinoma (HGSC), a major histological subtype of ovarian cancer. Notably, deleterious mutations in SWI/SNF chromatin remodeling genes, such as , are common in OCCC but rare in HGSC. Because this complex regulates multiple cellular processes, including transcription and DNA repair, molecularly targeted therapies that exploit the consequences of SWI/SNF deficiency may have clinical efficacy against OCCC. Three such strategies have been proposed to date: prioritizing a gemcitabine-based chemotherapeutic regimen, synthetic lethal therapy targeting vulnerabilities conferred by SWI/SNF deficiency, and immune checkpoint blockade therapy that exploits the high mutational burden of -deficient tumor. Thus, ARID1A deficiency has potential as a biomarker for precision medicine of ovarian cancer.
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http://dx.doi.org/10.3390/cancers13081769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068058PMC
April 2021

Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39).

J Clin Oncol 2021 06 23;39(17):1842-1855. Epub 2021 Apr 23.

Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO) and Istituto Nazionale Tumori IRCCS Fondazione G Pascale, Napoli, Italy.

Purpose: To evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC).

Methods: This multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1-positive populations.

Results: Between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank = .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99; = .038), in the PD-L1-positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab 21% with placebo), hypertension (18% 20%, respectively), and anemia (12% 12%).

Conclusion: Current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.
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http://dx.doi.org/10.1200/JCO.21.00306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189598PMC
June 2021

Follicular development during hormone replacement therapy in patients with premature ovarian insufficiency.

Reprod Med Biol 2021 Apr 19;20(2):234-240. Epub 2021 Mar 19.

Department of Obstetrics and Gynecology Jikei University School of Medicine Tokyo Japan.

Purpose: To provide information about the relationship between follow-up period and follicular development in patients with infertility due to premature ovarian insufficiency (POI) who are undergoing hormone replacement therapy (HRT). It is necessary to detect follicle development for artificial insemination or in vitro fertilization.

Methods: This retrospective cohort study was conducted at a university hospital in Tokyo, Japan, from April 2014 to February 2019 in 20 patients [follicular development group, 11 women (55%); non-follicular development group, 9 women (45%)] with POI; their follicular development was followed up weekly. Background characteristics, including age, follicle-stimulating hormone (FSH) and anti-Mullerian hormone levels (AMH), the period from the last spontaneous menstruation to hormone replacement therapy initiation, and follow-up period during HRT were investigated. The period without follicular development was tabulated, and the subsequent cumulative follicular development detection rate was calculated.

Results: At least 1-year follow-up, the cumulative follicular development rate was 70%; follicular development was observed with a probability of 49.1% at 3 months, 33.4% at 6 months, and 8.3% at 12 months in the follow-up period.

Conclusions: The results show that the longer the non-follicle development period, the lower the probability of subsequent follicular development in patients with POI during HRT.
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http://dx.doi.org/10.1002/rmb2.12375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022089PMC
April 2021
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