Tissue factor pathway inhibitor 2 as a serum biomarker for endometrial cancer: a single-center retrospective study.

BACKGROUND: Endometrial cancer is the most common gynecological malignancy; however, there is no useful blood diagnostic biomarker. This study aimed to determine the utility of tissue factor pathway inhibitor 2 (TFPI2), a biomarker of ovarian cancer, as a diagnostic marker for endometrial cancer. METHODS: We examined serum TFPI2 levels in patients with endometrial cancer (n = 328) compared to those in healthy controls (n = 65) and evaluated the performance of serum TFPI2 levels as a diagnostic marker. We investigated the clinicopathological characteristics of patients with TFPI2-negative and TFPI2-positive endometrial cancer. Using immunohistochemistry (IHC), we examined TFPI2 expression in tumor tissues of 105 patients with type II endometrial carcinoma and evaluated the correlation between serum and tissue TFPI2 positivity. RESULTS: Patients with endometrial cancer had significantly higher serum TFPI2 levels than controls (196.7 pg/mL vs. 83.3 pg/mL; p < 0.001). The sensitivity and specificity were 54.3% and 95.4%, respectively (cutoff value, 191 pg/mL). Serum TFPI2 levels were significantly elevated along with the stage progression (stage I, 189.6 pg/mL; stage III, 230.9 pg/mL; stage IV, 312.5 pg/mL; p < 0.001). Patients with high-risk histology showed significantly elevated serum TFPI2 levels than those with low-risk histology (220.8 pg/mL vs. 187.7 pg/mL; p < 0.001). The positivity rate for TFPI2 was the highest among tumor markers, including CA125, CA19-9, and CEA. Serum TFPI2 and CA125 levels were almost independent (r = 0.203, p < 0.001), and the combined sensitivity increased to 58.8%. The 5-year survival rate was significantly worse in TFPI2-positive patients (≥ 191 pg/mL, n = 178) than in TFPI2-negative patients (< 191 pg/mL, n = 150) (hazard ratio, 8.22; 95% confidence interval, 2.49-27.1; p < 0.001). TFPI2 immunostaining revealed that 37.1% (39/105) of the samples were positive for TFPI2, with an IHC score of > 0. There was no significant difference in the immunostaining score according to histological type. Serum TFPI2 levels and immunostaining score showed poor agreement (kappa coefficient, -0.039). CONCLUSIONS: The serum TFPI2 level is a promising marker for diagnosing and predicting the prognosis of endometrial cancer. No correlation exists between serum and tissue TFPI2 levels. Further multicenter clinical trials are needed to test the utility of TFPI2 as a diagnostic marker.

Estrogen replacement therapy and non-hormonal medication use among patients with uterine cancer.

OBJECTIVE: As the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery. METHODS: The MarketScan Database was used to identify patients 18-49 years who underwent hysterectomy plus oophorectomy and those aged 50-75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests. RESULTS: A total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was -37.1% (95% CI, -40.5 to -33.6%) for patients 18-49 years of age and - 10.4% (95% CI, -10.9 to -9.9%) for those 50-75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50-75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18-49 years of age (P = .02) and those 50-75 years of age (P < .001). CONCLUSIONS: The use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer.

Weight-loss therapy in patients with obesity with endometrial intraepithelial neoplasia and uterine cancer.

OBJECTIVE: Although obesity is an important risk factor for endometrial intraepithelial neoplasia (EIN) and uterine cancer, little is known about the trends in use of weight-loss therapy for patients with obesity with EIN and uterine cancer. We examined the use of weight-loss therapy among patients with obesity with EIN and uterine cancer. METHODS: The Merative MarketScan Database was used to identify patients aged 18-70 years who were obese and diagnosed with EIN or uterine cancer. The primary treatment for EIN or uterine cancer was categorized as either primary hysterectomy or hormonal therapy. Nutrition counseling, bariatric surgeries, and weight-management medications were identified as weight-loss therapy. We analyzed trends in the use of any weight-loss therapies with Cochran-Armitage tests. A multivariable logistic regression model was developed to examine factors associated with weight-loss therapy use. RESULTS: Overall, 15,374 patients were identified, including 5561 (36.2%) patients with EIN and obesity, and 9813 (63.8%) patients with uterine cancer and obesity. Weight-loss therapy was utilized within 1 year after diagnosis in 480 (8.6%) patients with EIN and in 802 (8.2%) patients with uterine cancer. Use of any weight-loss therapy after diagnosis of EIN increased from 4.1% in 2009 to 12.6% in 2020 (P < .001), and the use of any weight-loss therapy after diagnosis of uterine cancer increased from 4.9% in 2009 to 11.4% in 2020 (P < .001). In a multivariable regression model, younger age and patients with high comorbidity score were associated with a higher likelihood of using any weight-loss therapy. CONCLUSIONS: Use of weight-loss therapy has increased, however there is still a significant underuse of this adjunctive therapy in patients with obesity with EIN or uterine cancer.

Fertility-preserving treatment for stage IA endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: The increasing use of fertility-preserving treatments in reproductive-aged patients with early-stage endometrial cancer necessitates robust evidence on the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device. We conducted a systematic review and meta-analysis to examine the outcomes following these 2 primary progestin-based therapies in reproductive-aged patients with early-stage endometrial cancer. DATA SOURCES: We conducted a systematic review of observational studies and randomized controlled trials following the Cochrane Handbook guidance. We conducted a literature search of 5 databases and 1 trial registry from inception of the study to April 16, 2024. STUDY ELIGIBILITY CRITERIA: Studies reporting complete response within 1 year in reproductive-aged patients with clinical stage IA endometrioid cancer undergoing progestin therapy treatment were included. We used data from both observational and randomized controlled studies. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary exposure assessed was the type of progestational treatment (oral progestins or LNG-IUD). The primary outcome was the pooled proportion of the best complete response (CR) within 1 year of primary progestational treatment. We performed a proportional meta-analysis to estimate the treatment response. Sensitivity analyses were performed by removing studies with extreme effect sizes or removing grade 2 tumors. The risk of bias was assessed in each study using the Joanna Briggs Institute critical appraisal checklist. RESULTS: Our analysis involved 754 reproductive-aged patients diagnosed with endometrial cancer, with 490 receiving oral progestin and 264 receiving levonorgestrel-releasing intrauterine device as their primary progestational treatment. The pooled proportion of the best complete response within 12 months of oral progestin and levonorgestrel-releasing intrauterine device treatment were 66% (95% CI, 55-76) and 86% (95% CI, 69-95), respectively. After removing outlier studies, the pooled proportion was 66% (95% CI, 57-73) for the oral progestin group and 89% (95% CI, 75-96) for the levonorgestrel-releasing intrauterine device group, showing reduced heterogeneity. Specifically, among studies including grade 1 tumors, the pooled proportions were 66% (95% CI, 54-77) for the oral progestin group and 83% (95% CI, 50-96) for the levonorgestrel-releasing intrauterine device group. The pooled pregnancy rate was 58% (95% CI, 37-76) after oral progestin treatment and 44% (95% CI, 6-90) after levonorgestrel-releasing intrauterine device treatment. CONCLUSION: This meta-analysis provides valuable insights into the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device treatment within a 12-month timeframe for patients with early-stage endometrial cancer who desire to preserve fertility. These findings have the potential to assist in personalized treatment decision-making for patients.

Excess morbidity and mortality associated with underuse of estrogen replacement therapy in premenopausal women who undergo surgical menopause.

BACKGROUND: Contrary to clinical guidelines, there has been a decrease over time in estrogen therapy use in premenopausal women undergoing bilateral oophorectomy for benign indications. OBJECTIVE: This study aimed to estimate the excess morbidity and mortality associated with current patterns of estrogen therapy use in women who undergo bilateral oophorectomy with hysterectomy for benign indications. STUDY DESIGN: We developed 2 Bayesian sampling Markov state-transition models to estimate the excess disease incidence (incidence model) and mortality (mortality model). The starting cohort for both models were women who had undergone bilateral oophorectomy with hysterectomy for benign indications at the age of 45 to 49 years. The models tracked outcomes in 5-year intervals for 25 years. The incidence model estimated excess incidence of breast cancer, lung cancer, colorectal cancer, coronary heart disease, and stroke, whereas the mortality model estimated excess mortality due to breast cancer, lung cancer, coronary heart disease, and all-other-cause mortality. The models compared current rates of estrogen therapy use with optimal (100%) use and calculated the mean difference in each simulated outcome to determine excess disease incidence and death. RESULTS: By 25 years after bilateral oophorectomy with hysterectomy, there were an estimated 94 (95% confidence interval, -158 to -23) fewer colorectal cancer cases, 658 (95% confidence interval, 339-1025) more coronary heart disease cases, and 881 (95% confidence interval, 402-1483) more stroke cases. By 25 years after bilateral oophorectomy with hysterectomy, there were an estimated 189 (95% confidence interval, 59-387) more breast cancer deaths, 380 (95% confidence interval, 114-792) more coronary heart disease deaths, and 759 (95% confidence interval, 307-1527) more all-other-cause deaths. In sensitivity analyses where we defined estrogen therapy use as a duration of >2 years of use, these differences increased >2-fold. CONCLUSION: Underuse of estrogen therapy in premenopausal women who undergo oophorectomy is associated with substantial excess morbidity and mortality.

Sarcopenia shortens overall survival of patients with platinum-resistant recurrent ovarian cancer: inverse probability of treatment-weighting analysis.

OBJECTIVE: The association between sarcopenia and prognosis in patients with platinum-resistant recurrent ovarian cancer remains unclear. This study investigated whether sarcopenia is a prognostic factor in patients with platinum-resistant recurrent ovarian cancer. METHODS: A total of 52 patients diagnosed with platinum-resistant recurrent ovarian cancer who had undergone non-platinum chemotherapy at our institution formed our study population. Body composition and clinicopathological data of these patients were collected retrospectively. Abdominal computed tomography (CT) scans obtained at the time of platinum-resistant recurrent ovarian cancer diagnosis were used to measure the cross-sectional area of skeletal muscles at L3 level. These values were corrected for height to calculate the skeletal muscle index, and accordingly sarcopenia was defined. Overall survival was defined as the primary outcome of the study. The impact of sarcopenia on overall survival was assessed using Cox proportional hazards regression models with inverse probability weighting of treatment based on propensity scores and log-rank tests. RESULTS: The median patient age was 63 years (IQR: 53-71). The most common International Federation of Gynecology and Obstetrics (FIGO) 2018 stage was stage III (50%) and the most common histology was serous or adenocarcinoma (67.3%). The optimal cut-off value of skeletal muscle index was 35.6 cm2/m2, which was calculated using the data of 21 patients with sarcopenia and 31 without sarcopenia. Sarcopenia was significantly associated with shorter overall survival (HR 1.93; 95% CI 1.06-3.49; p=0.03). Subgroup analysis based on patient attributes and prognostic factors suggested a consistent prognostic impact of sarcopenia. Sarcopenia was identified as a significant risk factor, particularly in patients who had higher CA125 levels (HR, 2.47; 95% CI, 1.07 to 5.69; p=0.034) and a higher neutrophil-to-lymphocyte ratio (HR, 2.92; 95% CI, 1.02 to 8.31; p=0.045). CONCLUSION: Sarcopenia significantly shortened the overall survival of patients with platinum-resistant recurrent ovarian cancer.

Three-year questionnaire study on human papillomavirus vaccination targeting new female college school students: Follow-up to a 2021 report to reveal the impact of a policy change in Japan.

AIM: The purpose of this study was to examine the trend in human papillomavirus (HPV) vaccination rates in Japan before and after a policy change in 2022, involving resumption of active recommendation and start of catch-up vaccination. METHODS: From 2021 to 2023, a web-based questionnaire survey was administered to newly enrolled female college students in Yokohama, Japan. The questionnaire included items such as age, HPV vaccination status, HPV vaccine awareness, and awareness of catch-up vaccination. We compared knowledge about the HPV vaccine and cervical cancer in 2021 and 2023, before and after resumption of the national vaccination program. RESULTS: The HPV vaccination rates were 5.4% in 2021, 7.5% in 2022, and 35.3% in 2023, with a significant upward trend (p < 0.001). A similar upward trend was observed for HPV vaccine awareness (p < 0.001). Comparing 2022 and 2023 after the start of catch-up vaccination, there was no significant difference in awareness of catch-up vaccination (p = 0.669), but there was a significant increase in awareness of free vaccination tickets (p < 0.001). After resumption of the national vaccination program with adoption of the catch-up vaccination program, there was no difference in knowledge of cervical cancer, but there was a difference in knowledge of the HPV vaccine. CONCLUSIONS: Although the HPV vaccination rate has increased after the policy change, it has not recovered to the level before the suspension of active recommendation. It is important for healthcare providers and school educators to actively communicate the safety and effectiveness of the HPV vaccine.

Prescription of hormone replacement therapy among cervical cancer patients with treatment-induced premature menopause.

OBJECTIVE: To examine the utilization of hormone replacement therapy (HRT) among newly diagnosed cervical cancer patients who experienced premature menopause due to primary treatment. METHODS: The MarketScan Databases were used to identify newly diagnosed cervical cancer patients <50 years of age with premature menopause after hysterectomy with bilateral salpingo-oophorectomy (primary surgery) or primary external beam pelvic radiation (primary radiotherapy). We examined the cumulative utilization of HRT until 24 months after the loss of ovarian function. Fine-Gray subdistribution hazard models were developed to examine the factors associated with cumulative HRT use. The duration of HRT use was analyzed by Kaplan-Meier curves. RESULTS: A total of 1826 patients, including 352 (19.3%) who underwent primary surgery and 1474 (80.7%) who received primary radiotherapy, were identified. Overall, 39.0% of patients received HRT within 24 months of primary treatment. HRT was used in 49.4% of those who underwent primary surgery and in 36.6% of those who received primary radiotherapy (p<0.0001). The median duration of HRT use was 60 days among the entire cohort and was significantly shorter for the primary radiotherapy group than the primary surgery group (35 vs 90 days, p<0.0001). Primary radiotherapy, older age, residency in the Northeastern USA, and Black race were associated with a lower likelihood of HRT use. CONCLUSIONS: HRT was prescribed to less than half of patients with newly diagnosed cervical cancer under the age of 50 who experienced premature menopause due to primary treatment. Among those who used HRT the duration of use was short.

Challenges facing workstyle reform for Japanese obstetricians and gynecologists revealed from time studies.

AIM: We aimed to grasp the actual working hours of Japanese obstetricians and gynecologists (OB/GYN doctors) as accurately as possible, using the same method of the Ministry of Health, Labour, and Welfare (MHLW). METHODS: The time study targeted OB/GYN doctors working at 10 universities nationwide including Niigata University and 21 institutions which take a role of perinatal care in Niigata prefecture. Working hours per week were calculated based on the following categories: regular and overtime work inside the hospital, work outside the hospital, self-improvement, education, research, and others. Data on weekly working hours were converted to yearly data for analyses. RESULTS: A time study of 10 universities nationwide revealed that 30% of doctors work overtime for more than 1860 h even if they do not include on-call shifts in their working hours. In 21 institutions in Niigata, physicians in Niigata University worked more overtime than other hospitals. It became clear that community health care was supported by dispatching physicians working at university. Furthermore, the results of simulations predicted the pessimistic situation of perinatal medical care in Niigata. CONCLUSIONS: Our study showed the possibility to exist much more OB/GYN doctors who work more than 1860 h of overtime work per year than the data presented by the MHLW based on nation-wide survey in 2019. The fact that the working hours at the side jobs had a great influence on the increase in overtime work of physicians in University was the same result as the report of MHLW published in 2021.

Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model.

The development of molecular targeted therapy has improved clinical outcomes in patients with life-threatening advanced lung cancers with driver oncogenes. However, selective treatment for KRAS-mutant lung cancer remains underdeveloped. We have successfully characterised specific molecular and pathological features of KRAS-mutant lung cancer utilising newly developed cell line models that can elucidate the differences in driver oncogenes among tissues with identical genetic backgrounds. Among these KRAS-mutation-associated specific features, we focused on the IGF2-IGF1R pathway, which has been implicated in the drug resistance mechanisms to AMG 510, a recently developed selective inhibitor of KRAS G12C lung cancer. Experimental data derived from our cell line model can be used as a tool for clinical treatment strategy development through understanding of the biology of lung cancer. The model developed in this paper may help understand the mechanism of anticancer drug resistance in KRAS-mutated lung cancer and help develop new targeted therapies to treat patients with this disease.

Internet-based behavioural activation to improve depressive symptoms and prevent child abuse in postnatal women (SmartMama): a protocol for a pragmatic randomized controlled trial.

BACKGROUND: Child abuse and postnatal depression are two public health problems that often co-occur, with rates of childhood maltreatment highest during the first year of life. Internet-based behavioural activation (iBA) therapy has demonstrated its efficacy for improving postnatal depression. No study has examined whether the iBA program is also effective at preventing child abuse. This study aims to investigate whether iBA improves depressive symptoms among mothers and prevents abusive behaviours towards children in postpartum mothers in a randomized controlled trial, stratifying on depressive mood status. The study also evaluates the implementation aspects of the program, including how users, medical providers, and managers perceive the program in terms of acceptability, appropriateness, feasibility, and harm done. METHODS: The study is a non-blinded, stratified randomized controlled trial. Based on cut-off scores validated on Japanese mothers, participants will be stratified to either a low Edinburgh Postnatal Depression Scale (EPDS) group, (EPDS 0-8 points) or a high EPDS group (EPDS ≥9 points). A total of 390 postnatal women, 20 years or older, who have given birth within 10 weeks and have regular internet-access will be recruited at two hospitals. Participants will be randomly assigned to either treatment, with treatment as usual (TAU) or through intervention groups. The TAU group receives 12 weekly iBA sessions with online assignments and feedback from trained therapists. Co-primary outcomes are maternal depressive symptoms (EPDS) and psychological aggression toward children (Conflict Tactic Scale 1) at the 24-week follow-up survey. Secondary outcomes include maternal depressive symptoms, parental stress, bonding relationship, quality of life, maternal health care use, and paediatric outcomes such as physical development, preventive care attendance, and health care use. The study will also investigate the implementation outcomes of the program. DISCUSSION: The study investigates the effectiveness of the iBA program for maternal depressive symptoms and psychological aggression toward children, as well as implementation outcomes, in a randomized-controlled trial. The iBA may be a potential strategy for improving maternal postnatal depression and preventing child abuse. TRIAL REGISTRATION: The study protocol (issue date: 2019-Mar-01, original version 2019005NI-00) was registered at the UMIN Clinical Trial Registry (UMIN-CTR: ID UMIN 000036864 ).

Effect of a Brief Web-Based Educational Intervention on Willingness to Consider Human Papillomavirus Vaccination for Children in Japan: Randomized Controlled Trial.

BACKGROUND: The human papillomavirus (HPV) vaccination rate in Japan has fallen to nearly zero since the suspension of governmental proactive recommendations in 2013, owing to the development of purported adverse events. OBJECTIVE: This study aimed to evaluate the effects of a brief web-based educational intervention using the theory of behavioral insights on the willingness of adults to consider the HPV vaccine for their daughters and sons. METHODS: We recruited 1660 participants aged 20 years or older in March 2018 via a webpage and provided them with a 10-item questionnaire related to the following aspects: awareness regarding HPV infection and vaccination, willingness for immunization, and actions for prevention. We randomly stratified participants based on sex and age with or without a brief educational intervention involving scientific information presented in an easy-to-read format. RESULTS: Only 484 (29.2%) of the respondents were aware of the benefits of HPV vaccination. Although only 352 (21.2%) of the respondents displayed a willingness for immunization of their daughters, there were 40 (4.8%) more respondents in the intervention group with this willingness (adjusted odds ratio [aOR] 1.32, 95% CI 1.04-1.69). In a subanalysis, the willingness toward vaccination for daughters in men was significantly higher in the intervention group (aOR 1.46, 95% CI 1.05-2.02). However, such a difference was not observed among women (aOR 1.20, 95% CI 0.83-1.73). CONCLUSIONS: This study suggests that a brief web-based educational intervention increases the willingness of adults to consider the HPV vaccine for their children, especially among men. Thus, providing adequate information to men may be a useful strategy to improve the currently low rates of HPV vaccination. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000049745 (UMIN-CTR); https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049745.

Ten-year questionnaire study on human papillomavirus vaccination targeting new female medical school students: Follow-up to the 2015 report.

AIM: We aimed to conduct a fixed-point observation questionnaire survey of changes in young women's human papillomavirus (HPV) vaccination status over the course of 10 years. We also investigated the influence of suspension of governmental recommendation for HPV vaccination since June 2013. METHODS: During 2011-2020, we conducted a self-completed questionnaire survey among newly enrolled female medical school students in Yokohama, Japan. The questionnaire featured items regarding HPV vaccination status, age, previous sex education, and knowledge about cervical cancer and HPV vaccination. RESULTS: HPV vaccine uptake rates in 2011 (5.4%) and 2012 (13.5%), when vaccination was self-funded, increased after 2013 (48.7%), when vaccination fees were subsidized. The rate dropped drastically in 2019 (14.3%) and 2020 (5.1%), after suspension of recommendation by the government. Comparisons between new students in 2015/2016, who had high vaccination rates (65.2%), and new students in 2019/2020, who had low vaccination rates (9.8%), showed decreased levels of HPV vaccination awareness, with fewer students having covered cervical cancer prevention in sex education and with respondents having less knowledge about the details of HPV vaccination. CONCLUSIONS: After the suspension of proactive HPV vaccine recommendation, markedly fewer students have been vaccinated against HPV, even those at the vaccination target age. This situation has substantially influenced the lower awareness about cervical cancer prevention, even among medical school students. To protect young women from cervical cancer in Japan, it is crucial for the government to resume proactive recommendation of HPV vaccines as soon as possible.

Inspection for micrometastasis is essential for predicting the prognosis of serous endometrial intraepithelial carcinoma: Case report and literature review.

Serous endometrial intraepithelial carcinoma is the precursor of invasive uterine serous carcinoma. Here, we present two cases of serous endometrial intraepithelial carcinoma with omental micrometastasis and discuss their clinical significance. Two menopausal patients with abnormal endometrial biopsy findings underwent hysterectomy and comprehensive surgical staging (bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy). Although gross examination failed to detect tumors, the pathological diagnosis was serous endometrial intraepithelial carcinoma. Both patients had omental micrometastasis; they were diagnosed with International Federation of Gynecology and Obstetrics stage IVB disease and received postoperative chemotherapy. One patient died of the carcinoma 9 months after the hysterectomy, and the other had a recurrence of carcinoma 17 months after the end of the initial therapy. The present cases and literature review highlight the importance of meticulous inspection for micrometastasis in the abdominal cavity, including the omentum and peritoneum, for predicting prognosis.

The physical and mental burden on obstetricians and gynecologists during the COVID-19 pandemic: A September 2020 questionnaire study.

AIM: The aim of this study was to clarify the physical and mental burden of the COIVD-19 pandemic on obstetricians and gynecologists in Japan and to identify factors that increase the burden of their psychological stress. METHODS: A web-based questionnaire was sent to obstetricians and gynecologists in Japan via email and social media to collect voluntary responses. This survey was conducted from September 1 to 30, 2020. RESULTS: A total of 852 valid responses were included in the analysis; 76% (644) of the physicians felt that the COVID-19 pandemic caused them physical and mental stress equal to or greater than the most severe disaster they had ever experienced. Physicians who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients (odds ratio (OR) 1.571, p = 0.012). Physicians experienced great stress to the point of wearing heavy personal protective equipment during routine vaginal deliveries by mothers with no COVID-19 symptoms. This trend was markedly pronounced for physicians working in regions with fewer cases of COVID-19 infection. CONCLUSIONS: Obstetricians and gynecologists who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients. One potential reason for this may be that they were required to wear more personal protective equipment than necessary. Infection control methods that ensure the safety of obstetricians and gynecologists while not causing unnecessary physical or psychological stress are needed.

Psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 pandemic.

AIM: To evaluate psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this cross-sectional study, we recruited pregnant women and puerperal women who delivered between January and September 2020 in Japan, using an online questionnaire. Participants were divided into low, middle, and high groups according to the degree of the epidemic in their region of residence. Related factors were analyzed using the chi-squared test. The relationship between COVID-19 epidemic regions and depression risks and anxiety using the Edinburgh Postnatal Depression Scale (EPDS) and Kessler 6 scale (K6) was evaluated using a univariate and multivariable logistic regression model. RESULTS: Overall, 7775 cases, including 4798 pregnant and 2977 puerperal women, were analyzed. The prevalence of high EPDS and K6 scores was significantly increased in pregnant women in the high than those in the low epidemic regions (EPDS: adjusted odds ratio [aOR] 1.453, 95% confidence interval [CI] 1.205-1.753; K6: aOR 1.601, 95% CI 1.338-1.918). There was no difference in EPDS score, but the prevalence of high K6 scores was significantly increased in puerperal women in the high than those in the low epidemic regions (aOR 1.342, 95% CI 1.066-1.690). Further, restriction on going to their hometown for delivery increased the prevalence of high EPDS scores among pregnant (aOR 1.663, 95% CI 1.296-2.133) and puerperal women (aOR 1.604, 95% CI 1.006-2.557). CONCLUSIONS: Decreased support due to the COVID-19 pandemic affected the psychological status of pregnant and puerperal women; hence, investing medical resources in their healthcare essential.

Attitudes toward overtime work and self-training: A survey on obstetricians and gynecologists in Japan.

AIM: The Ministry of Health, Labour, and Welfare of Japan proposed a regulation of overtime work as a reform in work style. However, the regulation may deteriorate the quality of medical services due to the reduction in training time. Thus, the study aimed to reveal perceptions in terms of generation gaps in views on self-training and overtime work, among members of the Japan Society of Obstetrics and Gynecology (JSOG). METHODS: A web-based, self-administered questionnaire survey was conducted among members of the JSOG. In total, 1256 respondents were included in the analysis. Data were collected on age, sex, experience as a medical doctor, location of workplace, work style, the type of main workplace, and number of full-time doctors in the main workplace. The study examined the attitudes of the respondents toward overtime work and self-training. The respondents were categorized based on experience as a medical doctor. RESULTS: According to years of experience, 112 (8.9%), 226 (18.0%), 383 (30.5%), 535 (42.6%) doctors have been working for ≤5, 6-10, 11-19, and ≥ 20 years, respectively. Although 54.5% of doctors with ≤5 years of experience expected the regulation on working hours to improve the quality of medical services, those with ≥20 years of experience expressed potential deterioration. After adjusting for covariates, more years of experience were significantly related with the expectation of deterioration in the quality of medical services. CONCLUSIONS: The study revealed a generation gap in the views about self-training and overtime work among obstetricians and gynecologists in Japan.

Current knowledge of and attitudes toward human papillomavirus-related disease prevention among Japanese: A large-scale questionnaire study.

AIM: The human papillomavirus (HPV) vaccination rate in Japan fell to nearly 0% following widespread coverage of possible adverse events. Developing a next approach to promote the effective prevention of HPV-related diseases including cervical cancer (CC) in Japan requires comprehensive understanding of knowledge and attitudes regarding CC prevention, HPV infection and HPV vaccination among the population including laypersons and medical professions in Japan. METHODS: A questionnaire survey was administered in a wide variety of settings in Japan. The questionnaire contained items on knowledge about CC, HPV infection and HPV vaccination; awareness of the HPV vaccine's effectiveness and associated adverse events; and attitudes toward the HPV vaccination for their daughters and for men/boys. RESULTS: Of 3033 targeted people, complete survey responses were received from 1182 men and 1602 women (total: 2784). The male laypersons' group had significantly lower knowledge than did the female laypersons' group (adjusted odds ratio, aOR = 3.86, P < 0.001). Compared with the male laypersons' group, the female laypersons' group tended to have less positive attitudes toward HPV vaccination for their daughters (aOR = 0.78, P = 0.006), but the female laypersons' group showed more positive attitudes toward vaccinating men/boys (aOR = 1.93, P < 0.001). CONCLUSION: The survey results indicated that men in Japan generally lacked knowledge and awareness of HPV-related diseases and their prevention. However, women had more negative attitudes toward HPV vaccination for their daughters than did men. Increasing male involvement in HPV prevention and changing women's perceptions of the HPV vaccine are essential steps to increase the HPV vaccination rate.

Normalization of abnormal plasma amino acid profile-based indexes in patients with gynecological malignant tumors after curative treatment.

BACKGROUND: We developed a novel plasma amino acid profile-based index (API) to detect ovarian, uterine, cervical, and endometrial cancers. In this study, we aimed to evaluate whether abnormal API values could be normalized after curative treatment in patients with gynecological malignant tumors. METHODS: Patients with gynecological cancer with abnormal API values were included in this study. Pre-operative absolute API values were compared with those after curative treatment. The normalization rates of API values in patients negative for the expression of three well-known tumor markers (SCC, CA125, and CA19-9) were also evaluated. In addition, related amino acid profiles in healthy controls and patients under pre- and post-treatment conditions were analyzed. RESULTS: Among 94 patients with abnormal pre-operative API values, the median API value was decreased from 9.52 to 2.17 after treatment (normalization rate: 88.3%). The decreased ranges were similar in patients with adenocarcinoma (6.28; 95% confidence interval [CI]: 5.43-6.95) and squamous carcinoma (7.44; 95% CI: 3.04-8.46). In 93.5% (43/46) of patients negative for tumor markers prior to operation, API values were normalized after the successful treatment. In addition, some pre-operative abnormal amino acid profiles, including Ile, Trp, and His, were reversibly normalized after treatment. CONCLUSION: The API is a promising tumor marker in gynecological malignancies for the diagnosis of remission, particularly in patients negative for general tumor markers. Further studies are needed to explore the mechanisms related to the normalization of abnormal amino acid profiles.

Magnetic Resonance Imaging Grading System for Preoperative Diagnosis of Leiomyomas and Uterine Smooth Muscle Tumors.

STUDY OBJECTIVE: To evaluate a new magnetic resonance imaging (MRI) grading system for preoperative differentiation between benign and variant-type uterine leiomyomas including smooth muscle tumors of uncertain malignant potential (STUMPs). DESIGN: Retrospective analysis (Canadian Task Force classification III). SETTING: Teaching hospital (Teine Keijinkai Hospital). PATIENTS: Three-hundred thirteen patient medical records were retrospectively reviewed if treated for uterine myomas and diagnosed with variant type leiomyomas or STUMPs (n = 27) or benign, typical leiomyomas (n = 286) and treated between January 2012 and December 2014. INTERVENTION: Uterine myoma classifications using MRI findings according to a 5-grade system (grades I-V) based on 3 elements. MEASUREMENTS AND MAIN RESULTS: Uterine myoma MRI classifications were based on 3 elements: T2-weighted imaging (high or low), diffusion-weighted imaging (high or low), and apparent diffusion coefficient values (high or low; apparent diffusion coefficient < 1.5 × 10-3 mm2/sec was considered low). Grades I to II were designated as typical or benign leiomyomas, grade III as degenerated leiomyomas, and grades IV to V as variant type leiomyomas or STUMPs. Accuracy levels were 98.9%, 100%, 94.3%, 58.8%, and 41.9% for grades I through V lesions, respectively. The grades were divided into 2 groups to discriminate benign leiomyomas and STUMPs (grades I-III were considered negative and grades IV-V positive). Grades IV to V scored 85.2% for sensitivity, 91.3% for specificity, 47.9% positive predictive value, 98.5% negative predictive value, a 9.745 positive likelihood ratio, and a .162 negative likelihood ratio. CONCLUSION: This novel MRI grading system for uterine myomas may be beneficial in differentiating benign leiomyomas from STUMPs or variant type leiomyomas and could be a future effective presurgical assessment tool.