Publications by authors named "Wataru Yamagami"

83 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jog.15134DOI Listing
January 2022

Clinical Usefulness of Endometrial Cytology in Determining the Therapeutic Effect of Fertility Preserving Therapy.

Acta Cytol 2021 Dec 15:1-8. Epub 2021 Dec 15.

Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinjuku-ku, Japan.

Introduction: The significance of endometrial cytology in determining the therapeutic efficacy of medroxyprogesterone acetate (MPA) therapy is unclear. This study aimed to evaluate the clinical usefulness of endometrial cytology during MPA therapy.

Methods: Overall, 77 patients who underwent dilatation and curettage (D&C) to evaluate the therapeutic efficacy of MPA therapy at our hospital between January 2018 and December 2019 were retrospectively analyzed. The results of D&C, cytological evaluation, and other clinicopathological factors were analyzed based on the patients' medical records.

Results: The sensitivity and specificity of cytology were 61% and 92%, respectively, with D&C being the gold standard for diagnosis in 142 D&C/cytological examinations. Among patients with no residual disease on D&C, 5 (4%) had suspicious or positive cytology. Although MPA therapy was terminated in 3 of these patients, only 1 patient had early recurrence, and the frequency of recurrence was similar to that of patients who showed negative results in both D&C and cytology.

Discussion/conclusion: The sensitivity of endometrial cytology in determining the therapeutic effect of MPA therapy is low, and we confirmed that the omission of D&C is unacceptable. Our findings also suggested that the addition of cytological evaluation to D&C during MPA therapy had a low clinical significance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000520701DOI Listing
December 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3802/jgo.2022.33.e14DOI Listing
December 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3802/jgo.2022.33.e3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728670PMC
January 2022

Hysteroscopic treatment assisted by photodynamic diagnosis for atypical polypoid adenomyoma: A report of two cases.

Photodiagnosis Photodyn Ther 2021 Dec 18;36:102583. Epub 2021 Oct 18.

Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan.

Atypical polypoid adenomyoma (APA) is an intrauterine tumor for which hysteroscopic tumor resection allows for fertility preservation. Complete resection is important because of the high recurrence rate of APA, but is difficult due to the lack of characteristic hysteroscopic findings. We previously reported a case in which photodynamic diagnosis (PDD) was useful for detection of APA. Here, we report two additional cases of APA treated by hysteroscopic resection with PDD. The procedure was approved by the ethical committee. Case 1: A 35-year-old female who underwent hysteroscopic surgery for a submucosal tumor suspected to be APA with hypermenorrhea. Case 2: A 37-year-old female in whom hysteroscopic surgery was performed for a residual APA lesion after hormone therapy. In Case 1, PDD identified the tumor borders and this enabled as complete resection as possible. In Case 2, lesions could not be identified clearly under white light, but some areas were PDD-positive and were excised. Among 19 specimens from these two cases and the previously reported case, all PDD-positive specimens were pathologically diagnosed as APA. The sensitivity and specificity of PDD for APA were 76.9% and 100%, respectively. These results suggest that PDD can contribute to identification of APA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pdpdt.2021.102583DOI Listing
December 2021

Prospective feasibility study of neoadjuvant dose-dense paclitaxel plus carboplatin with bevacizumab therapy followed by interval debulking surgery for advanced ovarian, fallopian tube, and primary peritoneal cancer patients.

Int J Clin Oncol 2021 Oct 14. Epub 2021 Oct 14.

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

Background: This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian, fallopian tube, and primary peritoneal cancer patients in the neoadjuvant setting.

Methods: Ovarian, fallopian tube or primary peritoneal cancer patients with stage III-IV disease received neoadjuvant chemotherapy (NAC) every 3 weeks consisting of paclitaxel (80 mg/m) on days 1, 8, and 15; carboplatin (AUC 6.0 mg/mL × min.) on day 1; and bevacizumab (15 mg/kg) on day 1. Interval debulking surgery (IDS) was performed after 3 cycles of dose-dense TC-bevacizumab therapy. The primary endpoint was the rate of complete resection by IDS. Secondary endpoints were treatment completion rate, treatment exposure, response rate to NAC, adverse events, and perioperative complications.

Results: Twenty-four patients were included in this study. The median age was 55.5 years (37-80 years), and most patients had high-grade serous carcinoma accounted (n = 18). IDS was performed in all patients with complete resection achieved in 75% (95% confidence interval: 57.7-92.3%). The lower limit exceeded the preset threshold rate of 55%. The response rate to NAC was 79%, and serum CA125 levels were in the normal range after NAC in 57% of patients. Grade 4 hematological toxicities and grade 3/4 non-hematological toxicities occurred in 29% and 17% of patients during NAC, respectively. Grade 3/4 perioperative complications were seen in 29% of patients, but no gastrointestinal perforations or treatment-related deaths occurred.

Conclusions: Neoadjuvant dose-dense TC-bevacizumab therapy was well tolerated, and a satisfactory rate of complete resection by IDS was achieved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-02050-3DOI Listing
October 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-02017-4DOI Listing
December 2021

ARID1A mutation/ARID1A loss is associated with a high immunogenic profile in clear cell ovarian cancer.

Gynecol Oncol 2021 09 14;162(3):679-685. Epub 2021 Jul 14.

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

Objectives: ARID1A mutation is frequently found in clear cell ovarian cancer (CCC) and endometrioid ovarian cancer (EC). Anti-PD-1 monotherapy has been found to have limited efficacy in epithelial ovarian cancer; however, anti-PD-1 therapy showed significant clinical benefit in some CCC. We sought to define the relationship of ARID1A mutation/ARID1A expression to the immunogenic profile of different histologic subtypes of ovarian cancer.

Methods: We performed next-generation sequencing of 160 cancer-related genes. Also, we analyzed the immunohistochemical status of ARID1A, PD-L1, and CD8 with survival in different histologic subtypes of ovarian cancer in a total of 103 cases.

Results: ARID1A mutation was found in 0% of the high-grade serous ovarian cancer (HGSC) (n = 36), 41.5% of the CCC (n = 41), 45.0% of the EC (n = 20), and 33.3% of the mucinous ovarian cancer (MC) (n = 6) cases. ARID1A loss was found in 19.4% of the HGSC, 75.6% of the CCC, 60.0% of the EC and 0% of the MC cases. ARID1A mutation was found to be associated with high PD-L1 (p < 0.001) or CD8 levels (p < 0.001) in CCC but not in other histologic subtypes. Meanwhile, ARID1A loss was associated with high PD-L1 or CD8 levels in CCC (p < 0.001) and HGSC (p < 0.001) but not in EC and MC. In addition, ARID1A mutation was associated with high tumor mutation burden in CCC (p = 0.006).

Conclusions: ARID1A mutation/ARID1A expression is associated with immune microenvironmental factors in CCC but not in EC. ARID1A status can be a biomarker for selecting candidates for immune checkpoint blockade in CCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2021.07.005DOI Listing
September 2021

Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger.

Int J Clin Oncol 2021 Sep 11;26(9):1767-1774. Epub 2021 Jun 11.

Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, 362-0806, Japan.

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients.[Methods] Sixty-five patients aged 40 years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells.[Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3' untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35.[Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40 years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-01953-5DOI Listing
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3802/jgo.2021.32.e44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039172PMC
May 2021

Survey of the clinical practice pattern of using sentinel lymph node biopsy in patients with gynecological cancers in Japan: the Japan Society of Gynecologic Oncology study.

Int J Clin Oncol 2021 May 25;26(5):971-979. Epub 2021 Mar 25.

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

Background: Sentinel lymph node (SN) biopsy is essential for evaluating survival and minimal treatment-related morbidity associated with cervical, endometrial, and vulvar cancer in Japan. As such, our aim in this study was to evaluate the current practice pattern of using SN biopsy for cervical, endometrial, and vulvar cancer in Japan.

Methods: We deployed a 47-question survey on the use of SN biopsy for gynecological cancers to 216 gynecological oncology training facilities. The survey included information on the use of SN biopsy for uterine (cervical and endometrial) and vulvar cancers; details on the type, timing, and concentration of tracers used; surgical approach used for SN biopsy; method of biopsy and pathological examination; and facilities' experience with clinical research on SN biopsy.

Results: The response rate was 84% (181/216), with 40 facilities (22%) having experience in SN biopsy for gynecological cancers, 34 (85%) for uterine cancers, and 15 (37%) for vulvar cancers. Radioisotope, indocyanine green (ICG), and blue dyes were available for the detection of uterine cancers in 21 (52%), 25 (62%), and 19 (48%) facilities and for vulvar cancers in 9 (22%), 3 (7%), and 11 (27%) facilities, respectively. Thirty-four facilities (85%) used intraoperative frozen section procedure for diagnosis when possible, with 24 (71%) of these facilities using 2-mm specimen cuts. Diagnosis included pathological examination (85%), immunostaining (57%), and one-step nucleic acid amplification (5%).

Conclusion: Increasing research evidence, providing insurance coverage for radioisotope tracers, and increasing the availability of training are expected to increase the use of SN biopsy in Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-01862-7DOI Listing
May 2021

Atypical vessels in hysteroscopy: Usefulness in prediction of malignant diseases in patients treated with tamoxifen.

J Obstet Gynaecol Res 2021 Apr 31;47(4):1510-1515. Epub 2021 Jan 31.

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

Aim: Tamoxifen (TAM) is widely used in adjuvant endocrine therapy for invasive breast cancer as a selective estrogen modulator, but this treatment has a risk of developing endometrial malignancy. However, hysteroscopic findings during or after TAM treatment are unclear. The aim of this study is to examine the association between hysteroscopic patterns and malignant histological findings during or after treatment with TAM.

Methods: The subjects were patients who received TAM after surgery for breast cancer and underwent hysteroscopy at our institution from January 2016 to December 2019. Clinicopathological factors and hysteroscopic findings were collected from medical records and investigated retrospectively. Histologically, atypical endometrial hyperplasia, endometrial cancer, and carcinosarcoma were classified as malignant diseases.

Results: A total of 26 patients were eligible for the study. Hysteroscopic findings included an irregular surface of the endometrium (n = 3, 11.5%), atypical vessels (n = 10, 38.5%), papillary structure (n = 3, 11.5%), and polypoid structure (n = 18, 69.2%). Histological examination revealed malignancy in six patients (23.0%). The percentage of atypical vessels in patients with malignancies was significantly higher than that in patients with a normal endometrium or benign lesion (100% vs. 20%, p = 0.0009). The sensitivity and specificity of atypical vessels in hysteroscopy for diagnosis of malignant diseases were 100% and 80%, respectively.

Conclusions: Hysteroscopic findings of atypical vessels may be useful for prediction of malignant diseases in patients treated with TAM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jog.14690DOI Listing
April 2021

Germline multigene panel testing revealed a pathogenic variant in a patient with suspected Lynch syndrome.

Int Cancer Conf J 2021 Jan 9;10(1):6-10. Epub 2020 Oct 9.

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

There has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as a pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39 years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, Lynch syndrome was suspected. However, germline multigene panel testing revealed a pathogenic variant rather than pathogenic variants in mismatch repair genes. In this case, with conventional genetic risk assessment, we were unable to determine whether the patient had a high risk of hereditary breast and ovarian cancer; thus, germline multigene panel testing may provide valuable information to improve disease management strategies for patients in clinical settings. Particularly, germline multigene panel testing may be useful for detecting hereditary tumor syndromes if a patient does not present with a typical family history of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13691-020-00449-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797406PMC
January 2021

Evaluating the importance of routine drainage following laparoscopic pelvic lymph node dissection for gynecological malignancies.

Int J Gynaecol Obstet 2021 Jun 21;153(3):438-442. Epub 2020 Dec 21.

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

Objective: To determine the efficacy of drainage following pelvic lymph node (PLN) dissection, especially for cases involving laparoscopic surgery.

Methods: In this retrospective study, 368 patients with malignant gynecological tumors who underwent systemic PLN dissection at Keio University Hospital between January 2012 and October 2018 were enrolled. Drainage tubes were placed in the retroperitoneal fossa in all patients. Medical records were used for data collection.

Results: Laparoscopy was performed on 81 patients, and laparotomy was performed on 287 patients. In the laparoscopy group, tubes were removed 1 day post surgery. In the laparotomy group, tubes were removed 1 day post surgery in 167 patients and 4 days post surgery in 120 patients. Compared with the laparotomy group, we determined the laparoscopy group to have a significantly lower prevalence of lymphocyst (6.2% vs 20.2%, p = 0.002) but a similar prevalence of lymphedema (4.9% vs 5.2%), and symptomatic lymphocyst (2.5% vs 4.5%). The two laparotomy groups did not differ significantly with respect to the prevalence of lymphedema (4.8% vs 5.8%), lymphocyst (20.4% vs 20.0%), or symptomatic lymphocyst (4.2% vs 5.0%).

Conclusion: Our results suggest that routine drainage should be omitted, especially in cases involving laparoscopic surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijgo.13507DOI Listing
June 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5468/ogs.20186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834758PMC
January 2021

Uterine cervical cancer associated with obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome: A case report and review of the literature.

Gynecol Oncol Rep 2020 Nov 13;34:100645. Epub 2020 Sep 13.

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

•Cervical cancer occurring in patients with OHVIRA syndrome is very rare.•This case reports on HPV-negative adenocarcinoma located in the nonvisible cervix.•Colposcopy and imaging are essential for cervical cancer with uterine malformation.•In OHVIRA syndrome, cervical malignancies may be overlooked.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gore.2020.100645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502329PMC
November 2020

Impact of the COVID-19 epidemic at a high-volume facility in gynecological oncology in Tokyo, Japan: a single-center experience.

J Ovarian Res 2020 Sep 11;13(1):105. Epub 2020 Sep 11.

Department of Obstetrics & Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan.

Background: The number of cases of novel coronavirus disease 2019 (COVID-19) in Japan have risen since the first case was reported on January 24, 2020, and 6225 infections have been reported as of June 30, 2020. On April 8, 2020, our hospital began screening patients via pre-admission reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and chest computed tomography (CT). Although no patients exhibited apparent pneumonia, treatment delay or changes in treatment plans were required for a few patients based on the results of screening tests. During an emerging infectious disease pandemic, the likelihood of being infected, as well as the disease itself, affects clinical decision making in several ways. We summarized and presented our experience.

Case Presentation: After the introduction of pre-admission screening, RT-PCR and CT were performed in 200 and 76 patients, respectively, as of June 30, 2020. The treatment of five patients, including two patients with cervical cancer, two patients with ovarian tumors, and one patient with ovarian cancer, was affected by the results. Two asymptomatic RT-PCR-positive patients did not develop COVID-19, but their treatment was delayed until the confirmation of negative results. The other three patients were RT-PCR-negative, but abnormal CT findings suggested the possibility of COVID-19, which delayed treatment. The patients receiving first-line preoperative chemotherapy for ovarian cancer had clinically evident exacerbations because of the treatment delay.

Conclusion: During the epidemic phase of an emerging infectious disease, we found that COVID-19 has several other effects besides its incidence. The postponing treatment was the most common, therefore, treatment of ovarian tumors and ovarian cancer was considered to be the most likely to be affected among gynecological diseases. Protocols that allow for easy over-diagnosis can be disadvantageous, mainly because of treatment delays, and therefore, the protocols must be developed in light of the local infection situation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-020-00711-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485922PMC
September 2020

Clinical implications of next-generation sequencing-based panel tests for malignant ovarian tumors.

Cancer Med 2020 10 19;9(20):7407-7417. Epub 2020 Aug 19.

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

Precision medicine based on cancer genomics is being applied in clinical practice. However, patients do not always derive benefits from genomic testing. Here, we performed targeted amplicon exome sequencing-based panel tests, including 160 cancer-related genes (PleSSision-160), on 88 malignant ovarian tumors (high-grade serous carcinoma, 27; endometrioid carcinoma, 15; clear cell carcinoma, 30; mucinous carcinoma, 6; undifferentiated carcinoma, 4; and others, 6 (immature teratoma, 1; carcinosarcoma, 3; squamous cell carcinoma, 1; and mixed, 1)), to assess treatment strategies and useful biomarkers for malignant ovarian tumors. Overall, actionable gene variants were found in 90.9%, and druggable gene variants were found in 40.9% of the cases. Actionable BRCA1 and BRCA2 variants were found in 4.5% of each of the cases. ERBB2 amplification was found in 33.3% of mucinous carcinoma cases. Druggable hypermutation/ultramutation (tumor mutation burden ≥ 10 SNVs/Mbp) was found in 7.4% of high-grade serous carcinoma, 46.7% of endometrioid carcinoma, 10% of clear cell carcinoma, 0% of mucinous carcinoma, 25% of undifferentiated carcinoma, and 33.3% of the other cancer cases. Copy number alterations were significantly higher in high-grade serous carcinoma (P < .005) than in other histologic subtypes; some clear cell carcinoma showed high copy number alterations that were correlated with advanced stage (P < .05) and worse survival (P < .01). A high count of copy number alteration was associated with worse survival in all malignant ovarian tumors (P < .05). Our study shows that targeted agents can be detected in approximately 40% of malignant ovarian tumors via multigene panel testing, and copy number alteration count can be a useful marker to help assess risks in malignant ovarian tumor patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571820PMC
October 2020

A prospective cohort study on the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer.

Jpn J Clin Oncol 2021 Jan;51(1):54-59

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

Objective: this prospective cohort study aimed to assess the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer.

Methods: in this study, 40 Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer selected to receive bevacizumab with chemotherapy were enrolled. Patients in poor general condition were excluded. Each patient was monitored prospectively for adverse events, administration status, disease status and survival. Treatment was continued until intolerable adverse events or disease progression. The primary endpoint was safety.

Results: bevacizumab plus platinum-based chemotherapy was performed for 30 patients (median cycle; 16.5), while bevacizumab plus non-platinum chemotherapy was performed for 10 patients (median cycle; 5.5). Among bevacizumab-related adverse events, hypertension occurred in 80% of patients, proteinuria in 83%, mucositis in 25%, bleeding in 20%, thromboembolic events in 5.0% and fistula in 2.5%. Gastrointestinal perforation or other life-threatening lethal adverse events were not observed. Response rate and median progression-free survival were 73% and 19.3 months for patients with bevacizumab plus platinum-based chemotherapy, and 30% and 3.9 months for patients with bevacizumab plus non-platinum chemotherapy, respectively. There was no correlation between response rate and occurrence of adverse events such as hypertension or proteinuria.

Conclusion: bevacizumab combined with chemotherapy was tolerable and effective for Japanese patients with relapsed ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Hypertension and proteinuria are frequently occurred and managed properly for continuing treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyaa140DOI Listing
January 2021

Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing.

Sci Rep 2020 07 28;10(1):12581. Epub 2020 Jul 28.

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

The use of primary patient-derived organoids for drug sensitivity and resistance testing could play an important role in precision cancer medicine. We developed expandable ovarian cancer organoids in < 3 weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumours. Seven pairs of organoids (3 high-grade serous, 1 clear cell, 3 endometrioid) and original tumours shared 59.5% (36.1-73.1%) of the variants identified. Copy number variations were also similar among organoids and primary tumours. The organoid that harboured the BRCA1 pathogenic variant (p.L63*) showed a higher sensitivity to PARP inhibitor, olaparib, as well as to platinum drugs compared to the other organoids, whereas an organoid derived from clear cell ovarian cancer was resistant to conventional drugs for ovarian cancer, namely platinum drugs, paclitaxel, and olaparib. The overall success rate of primary organoid culture, including those of various histological subtypes, was 80% (28/35). Our data show that patient-derived organoids are suitable physiological ex vivo cancer models that can be used to screen effective personalised ovarian cancer drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-69488-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387538PMC
July 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2020.07.023DOI Listing
October 2020

Evaluation of safety and diagnostic performance for flexible hysteroscopy in 1591 outpatient cases.

Jpn J Clin Oncol 2020 Sep;50(10):1157-1161

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

Background: To date, only few large studies are available concerning the safety and diagnostic concordance rates of outpatient flexible hysteroscopy. In our institution, outpatient hysteroscopy has been routinely and educationally applied Kosuke Tsuji to intrauterine lesions; thus, we retrospectively investigated the institution's outpatient flexible hysteroscopy cases.

Methods: A total of 1591 cases of outpatient flexible hysteroscopy conducted at our institution in 2012-2016 were retrospectively analyzed in terms of their clinical background, complications and diagnostic concordance rates.

Results: A total of 1591 cases included 546 cases of benign tumors (317 endometrial polyps, 168 myomas and 61 endometrial hyperplasia), 361 cases of atypical endometrial hyperplasia, 571 cases of endometrial cancers and 113 cases of other diagnoses. No major complications, including uterine perforation, occurred. However, one patient (0.06%) was diagnosed with septic shock caused by intrauterine infection that required prolonged immunosuppressive drug administration. Meanwhile, 335 patients diagnosed with benign tumors through outpatient flexible hysteroscopy underwent operation, and the diagnostic concordance rate was 74.6% (250 cases). However, this rate included 14 cases (4.2%) diagnosed with malignant tumors postoperatively. In preoperative endometrial cancer cases, the sensitivity and specificity for cervical invasion diagnosis were 39.4 and 90.8%, respectively. In addition, only one patient manifested positive ascites cytology intraoperatively, possibly caused by outpatient hysteroscopy.

Conclusions: Outpatient flexible hysteroscopy is highly safe, with a slight negligible effect on ascites cytology. However, the diagnosis should be determined by multidisciplinary approaches, as hysteroscopy alone can miss malignancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyaa098DOI Listing
September 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3802/jgo.2020.31.e45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286757PMC
July 2020

Identification of a novel uterine leiomyoma GWAS locus in a Japanese population.

Sci Rep 2020 Jan 27;10(1):1197. Epub 2020 Jan 27.

Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.

Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P = 6.12 × 10 with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-58066-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985131PMC
January 2020

Japan Society of Gynecologic Oncology 2018 guidelines for treatment of uterine body neoplasms.

J Gynecol Oncol 2020 Jan 17;31(1):e18. Epub 2019 Oct 17.

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

The Fourth Edition of the Guidelines for Treatment of Uterine Body Neoplasm was published in 2018. These guidelines include 9 chapters: 1. Overview of the guidelines, 2. Initial treatment for endometrial cancer, 3. Postoperative adjuvant therapy for endometrial cancer, 4. Post-treatment surveillance for endometrial cancer, 5. Treatment for advanced or recurrent endometrial cancer, 6. Fertility-sparing therapy, 7. Treatment of uterine carcinosarcoma and uterine sarcoma, 8. Treatment of trophoblastic disease, 9. Document collection; and nine algorithms: 1-3. Initial treatment of endometrial cancer, 4. Postoperative adjuvant treatment for endometrial cancer, 5. Treatment of recurrent endometrial cancer, 6. Fertility-sparing therapy, 7. Treatment for uterine carcinosarcoma, 8. Treatment for uterine sarcoma, 9. Treatment for choriocarcinoma. Each chapter includes overviews and clinical questions, and recommendations, objectives, explanation, and references are provided for each clinical question. This revision has no major changes compared to the 3rd edition, but does have some differences: 1) an explanation of the recommendation decision process and conflict of interest considerations have been added in the overview, 2) nurses, pharmacists and patients participated in creation of the guidelines, in addition to physicians, 3) the approach to evidence collection is listed at the end of the guidelines, and 4) for clinical questions that lack evidence or clinical validation, the opinion of the Guidelines Committee is given as a "Recommendations for tomorrow".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3802/jgo.2020.31.e18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918887PMC
January 2020

Intraoperative Capsule Rupture, Postoperative Chemotherapy, and Survival of Women With Stage I Epithelial Ovarian Cancer.

Obstet Gynecol 2019 11;134(5):1017-1026

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and the Norris Comprehensive Cancer Center, University of Southern California, University of Southern California, Los Angeles, California; and the Departments of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Keio University School of Medicine, Tokyo, Kobe University Graduate School of Medicine, Kobe, Kyorin University School of Medicine, Tokyo, Tokyo Women's Medical University, Tokyo, Otaru General Hospital, Sapporo, Yamagata University School of Medicine, Yamagata, and Niigata University School of Medicine, Niigata, Japan.

Objective: To examine the incidence and prognostic effects of intraoperative capsule rupture and to assess the effectiveness of postoperative chemotherapy for intraoperative tumor rupture in apparent stage I epithelial ovarian cancer.

Methods: This is a society-based retrospective observational study in Japan that examined 15,163 women with stage IA-IC1 epithelial ovarian cancer who underwent primary surgical treatment between 2002 and 2015. Associations between intraoperative capsule rupture and cause-specific survival, and between postoperative chemotherapy and cause-specific survival among intraoperatively ruptured cases were examined by histology type (clear cell n=6,107, endometrioid n=3,910, mucinous n=3,382, and serous n=1,764).

Results: Clear cell histology had the highest risk of intraoperative capsule rupture (57.3%), followed by endometrioid (48.8%), serous (41.8%), and mucinous (32.0%) histologies (P<.001). On multivariable analysis, clear cell type exhibited the largest effect of intraoperative capsule rupture on cause-specific survival (adjusted hazard ratio [HR] 1.99, 95% CI 1.45-2.75), followed by serous (adjusted HR, 1.61, 95% CI 0.84-3.11), mucinous (adjusted HR 1.28, 95% CI 0.79-2.09), and endometrioid (adjusted HR, 1.14, 95% CI 0.64-2.01) tumors. Postoperative chemotherapy for intraoperatively ruptured cases did not improve cause-specific survival in any histologic types in multivariable analysis: clear cell, adjusted HR 0.86, 95% CI 0.56-1.31; serous, adjusted HR 1.08, 95% CI 0.42-2.74; mucinous, adjusted HR 1.11, 95% CI 0.55-2.27; and endometrioid, adjusted HR 2.81, 95% CI 0.85-9.30 (all, P>.05). In the cohort-level analysis of ruptured cases (n=7,227), postoperative chemotherapy use has significantly decreased in mucinous (16.3% relative decrease), endometrioid (13.1% relative decrease), and clear cell (9.3% relative decrease) (all, P<.05); but, the cohort-level 5-year cause-specific survival rate did not change over time (all, P>.05).

Conclusion: Among apparent stage I epithelial ovarian cancer, the clear cell type possesses a disproportionally high risk of capsule rupture during adnexectomy and is associated with the most adverse effect on survival. A decrease in the use of postoperative chemotherapy for intraoperatively ruptured cases in Japan is likely the result of increasing awareness of the absence of survival benefits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/AOG.0000000000003507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818978PMC
November 2019
-->