Postoperative Pregnancy Outcomes Following Laparoscopic Surgical Management in Women with Stage III/IV Endometriosis: A Single-Center Follow-Up Study.

Objectives: The effects of laparoscopic surgical management in women with stage III/IV endometriosis remain controversial. The standard extent of resection for stage III/IV endometriosis with deep endometriosis to treat endometriosis-associated infertility is debatable. This study aimed to assess the postoperative pregnancy outcomes following a routine surgical intervention for stage III/IV endometriosis patients. Materials and Methods: Patients with stage III/IV endometriosis who underwent conservative laparoscopic surgery at our hospital between January 2010 and December 2018 were retrospectively analyzed. Statistical analyses were performed to determine the correlations between endometriosis features and postoperative pregnancy outcomes. Results: Of 256 patients enrolled, 94 wished to conceive. Exclusion criteria: ≥40 years, adenomyosis, partners with infertility issues. Finally, 71 women were included. The overall postoperative pregnancy rate was 76.1% (n = 54): 49 and five from non-assisted reproductive technology (ART) and ART, respectively. The postoperative pregnancy rate in patients diagnosed with infertility presurgery (40/71) was 70.0% (n = 28): 24 (non-ART) and four (ART). The endometriosis fertility index (EFI) score was higher in the pregnant than in the nonpregnant group (P = 0.03). The EFI score and surgical score of EFI were higher in the non-ART than in the ART group (P = 0.04; P = 0.02); in the infertile group, they were higher in the pregnant than in the nonpregnant group (P = 0.018; P = 0.027). Conclusion: Our postoperative pregnancy rate after conservative laparoscopic surgery for patients with stage III/IV endometriosis compared favorably with previous reports. EFI was a significant predictor of postoperative pregnancy. Our surgical approach to maintain a high surgical score of EFI might help treat endometriosis-associated infertility.

Decrease in activated regulatory T cell populations in the endometrium during ovulation in endometriosis.

Endometriosis is a serious disorder that can lead to infertility. The immune system, particularly regulatory T cells (Tregs), is involved in endometriosis and infertility; however, endometriosis-associated infertility is poorly understood. Tregs, which have an immunosuppressive function, fluctuate during the menstrual cycle. They are functionally heterogeneous and can be divided into subsets, with only activated Tregs (aTregs) having a true immunosuppressive function. The purpose of this study is to investigate the role of aTregs in endometriosis and how they contribute to endometriosis-associated infertility. We enrolled 72 women with (n = 39) and without (n = 33) endometriosis. Subpopulations of Tregs were examined in normal endometrium (NE), eutopic endometrium from women with endometriosis (EE), normal peritoneal fluid (N-PF), and peritoneal fluid from women with endometriosis (E-PF) via flow cytometry. The proportion of aTregs during the ovulatory phase was higher in NE than in EE (P < 0.05), and that during ovulatory and secretory phases was significantly higher in NE than in N-PF (P < 0.01 and 0.05, respectively). aTreg populations did not significantly differ between EE and E-PF. During the ovulatory phase, the proportion of resting Treg (rTreg) in the N-PF was significantly higher than during the proliferative phase (P < 0.05). The E-PF of rTreg populations did not differ significantly throughout the menstrual cycle. We found that Treg subsets were altered in the endometrium and PF of patients with endometriosis during the menstrual cycle. Our findings, particularly the reduction of aTregs in the EE, may provide an insight into the mechanism of endometriosis-associated infertility.

Low-Nutrient Environment-Induced Changes in Inflammation, Cell Proliferation, and PGC-1α Expression in Stromal Cells with Ovarian Endometriosis.

Although nutrient status plays an important role in cell metabolism, its significance in endometriosis is obscure. Herein, we investigated the effects of a low-nutrient microenvironment on endometriosis. Stromal cells (SCs) from ovarian endometrioma (OESCs) or normal endometrium without endometriosis (NESCs) were isolated and cultured. A low-nutrient microenvironment was replicated by replacing the culture medium with Hank's balanced salt solution. OESC and NESC proliferation under the low-nutrient condition was measured. The expression of exacerbating factors in endometriosis under the low-nutrient condition was examined at the mRNA and protein levels. OESCs showed higher proliferation than NESCs under the low-nutrient condition. In OESCs, the low-nutrient condition upregulated the mRNA expression of vascular endothelial growth factor (VEGF), interleukin-6 and -8, aromatase, Bcl-2, and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and downregulated that of BAX and induced transcription of PI.3, PII, and exon II. Western blotting revealed elevated VEGF and PGC-1α expression under the low-nutrient condition in OESCs. These changes coincided with the elevated expression of PGC-1α, which was reduced at the mRNA level upon nutrient status rescue. Endometriosis is exacerbated by altered angiogenesis, inflammation, anti-apoptosis, and local estrogen production while trying to survive under a low-nutrient microenvironment; it may be attributed to PGC-1α-mediated metabolic mechanisms.

Abstaining from annual health check-ups is a predictor of advanced cancer diagnosis: a retrospective cohort study.

BACKGROUND: Cancer prevention is a crucial challenge in preventive medicine. Several studies have suggested that voluntary health check-ups and recommendations from health professionals are associated with increased participation in cancer screening. In Japan, it is recommended that individuals aged 40-74 years should undergo annual health check-ups; however, the compliance to this recommendation is approximately <50%. According to the national survey, individuals who do not undergo annual health check-ups are at a higher risk for cancer. However, to the best of our knowledge, no previous study has investigated the association between the use of health check-ups and the incidence rate of cancer. We hypothesised that not undergoing periodic health check-ups and/or less use of outpatient medical services are predictors for advanced cancer. METHODS: To explore the relationship between health check-up or outpatient service utilisation and cancer incidence, this retrospective cohort study used data at two time points-baseline in 2014 and endpoint in 2017-from the National Health Insurance (NHI) claims and cancer registry. A multivariable logistic regression analysis was performed to investigate whether cancer diagnosis was associated with health check-up or outpatient service utilisation. RESULTS: A total of 72,171 participants were included in the analysis. The results of the multivariable logistic regression showed that individuals who skipped health check-ups had a higher risk of cancer diagnosis (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.04-1.40). Moreover, not undergoing health check-ups increased the risk of advanced-stage cancer (OR, 1.78; 95% CI, 1.29-2.44). Furthermore, increased rate of outpatient service utilisation was negatively associated with advanced cancer diagnosis. CONCLUSIONS: This is the first study reporting that not undergoing health check-ups is a predictor of cancer diagnosis and advanced cancer stage. Primary prevention strategies for NHI members who do not undergo health check-ups must be reassessed. Moreover, future research should examine secondary prevention strategies, such as health education and recommendations from health professionals to facilitate adequate utilisation of preventive health services.

Reduced innate lymphoid cells in the endometrium of women with endometriosis.

PROBLEM: Innate lymphoid cells (ILCs), a recently discovered family of innate immune cells, are responsible for the early immune response, and control both innate and adapted immune system via cytokine secretion. The role of ILCs in endometriosis has not been investigated; therefore, here, we aimed to investigate how the proportion of ILCs changes in endometriosis. METHOD OF STUDY: The percentage of each ILC group in CD45+ cells was examined in the peripheral blood, peritoneal fluid, endometrium, and ovarian endometrioma obtained from women with and without endometriosis (ERB-C-1216) using flow cytometry. RESULTS: Specimens were obtained from 19 women with endometriosis and 15 without endometriosis. In the endometrium, patients with endometriosis had lower proportion of ILC2 and 3 compared to control specimens (ILC2: .02±.01% vs .07±.03%; P < .05, ILC3: .31±.14% vs 1.10±.93%; P < .05). There was no significant change in the peripheral blood or the peritoneal fluid between the two groups. Additionally, ovarian endometrioma increased the proportion of ILCs (ILC1: .92±1.12%, ILC2: .08±.08%, ILC3: .70±.39%) compared to the endometrium samples of patients with endometriosis each with P < .05. Immunohistochemistry of IL-1ß and IL-23, which are ILC3-inducing factors, showed no significant change in the H-score of the epithelium of the two groups, but a significant increase was found in ovarian endometrioma. CONCLUSION: The proportion of ILC2 and 3 was reduced in the endometrium of patients with endometriosis, and ILCs were increased in ovarian endometrioma. Our findings may indicate a new immunological approach to understand the pathophysiology of endometriosis.

Trends in the co-use of alcohol and tobacco among Japanese adolescents: periodical nationwide cross-sectional surveys 1996-2017.

OBJECTIVES: This study aimed to assess trends in the prevalence of alcohol use depending on smoking behaviours and that of smoking depending on drinking behaviours among Japanese adolescents. DESIGN: This was a retrospective study using Japanese school-based nationwide surveys conducted between 1996 and 2017. SETTING: Surveyed schools, both junior and senior high schools, considered representative of the entire Japanese population, were sampled randomly. PARTICIPANTS: We enrolled 11 584-64 152 students from 179 to 103 schools yearly. They completed a self-reported and anonymous questionnaire on smoking and drinking behaviour. RESULTS: Since 1996, the prevalence of alcohol use and smoking among adolescents decreased in each survey (p<0.01). The prevalence of alcohol use in the non-smokers group was 29.0% in 1996 and 4.0% in 2017, and in the smokers group, it was 73.3% in 1996 and 57.4% in 2017. The reduction rate (the difference in prevalence between 1996 and 2017 divided by the prevalence in 1996) was 0.86 in the non-smokers group and 0.22 in the smokers group. The prevalence of smoking in the non-drinkers group was 6.7% in 1996 and 0.7% in 2017, while that in the drinkers group was 32.5% in 1996 and 18.9% in 2017. The reduction rate was 0.90 in the non-drinkers group and 0.42 in the drinkers group. Therefore, downward trends differed among the groups. In a subanalysis of senior high school students, we divided students into three groups according to their intention to pursue further education. Between 1996 and 2017, there was a consistent difference in the prevalence of alcohol use and smoking among these groups. CONCLUSIONS: Alcohol use and smoking among Japanese adolescents seem to have reduced. However, certain groups showed poor improvements, and health risk behaviour disparity exists, which may widen further. We need to focus on high-risk groups and implement appropriate measures or interventions accordingly.

Why Are COVID-19 Mortality Rates by Country or Region So Different?: An Ecologic Study of Factors Associated with Mortality from Novel Coronavirus Infections by Country.

BACKGROUND: In order to find out the factors associated with the large disparities in COVID-19 mortality rates by country, we conducted an ecological study by linking existing statistics. In Japan, a large variation was observed in between geographical areas when assessing mortality. We performed a regional correlation analysis to find factors related to regional mortality. METHODS: This study design was an ecologic study. A multiple regression analysis was performed with COVID-19 mortality rates of different countries as the dependent variable together with various health care and economic factors. We calculated the cumulative mortality rate as of June 30, 2020. For the regional correlation analysis of Japan, 47 prefectures were divided into nine regions. The factors examined were health care and tourism. Data for 33 Organization for Economic Co-operation and Development (OECD) countries were analyzed. In Japan's regional analysis, the whole country was classified into nine regions. RESULTS: Factors related to mortality were the incidence of Kawasaki disease (KD), number of computed tomographies (CTs), and alcohol consumption. Mortality was low in countries with high incidence of KD and high number of CTs, as well as in countries with high alcohol consumption. In European countries, high smoking prevalence and a high Gini coefficient were positively related to high mortality. According to a regional analysis in Japan, mortality was related to proportion of population in the densely inhabited districts, the number of foreign visitors per capita, and the number of Chinese visitors per capita. CONCLUSION: Low mortality in East Asia was associated with specific disease morbidity (KD), alcohol consumption, and CT numbers. It was suggested that the mortality gap in Japan was related to the number of foreign tourists and the proportion of population in the densely inhabited districts.

Heat-not-burn tobacco, electronic cigarettes, and combustible cigarette use among Japanese adolescents: a nationwide population survey 2017.

BACKGROUND: From among the global public health concerns, smoking remains one of the most crucial challenges. Especially for adolescents, the increase in the use of electronic cigarettes is controversial, as its use may lead to established smoking. In Japan, where a unique tobacco regulation system exists, the heat-not-burn tobacco market has been growing. However, the prevalence and association of combustible cigarettes and new tobacco-related products have not yet been closely investigated among Japanese adolescents. This study aimed to clarify the prevalence of smoking among adolescents, including new types of tobacco-related products, and to compare the characteristics of their users. METHODS: The 2017 Lifestyle Survey of Adolescents is a nationally-representative survey collected in Japan. From the national school directory, 98 junior high schools and 86 high schools were randomly sampled throughout Japan. The students completed an anonymous questionnaire at school. We calculated the prevalence of use for each type of tobacco product. Then, the use of a combination of products and the characteristics of different types of products were examined. RESULTS: In total, 64,152 students from 48 junior high schools and 55 high schools were included the analysis (school response rate = 56%, Mage = 15.7 years, 53.9% boys). The age-adjusted rate of ever (current) use of electronic cigarettes was 2.1% (0.7%) in junior high school and 3.5% (1.0%) in high school; that of combustible cigarettes was 2.6% (0.6%) in junior high school and 5.1% (1.5%) in high school. The rate of heat-not-burn tobacco use was lower relative to other products: 1.1% (0.5%) in junior high school and 2.2% (0.9%) in high school. An examination of the combined use of the three products identified a high number of dual users. Comparisons between different types of users indicated different backgrounds for combustible cigarette users and new product users. CONCLUSIONS: The prevalence of new tobacco-alternative products is growing in popularity among Japanese adolescents. Dual use is common, and many adolescents use new products only. Moreover, e-cigarettes might attract a broader range of groups to smoking. Continuous monitoring and research are needed to investigate their influence as a possible gateway to tobacco smoking.

Comparing Factors Related to Any Conventional Cigarette Smokers, Exclusive New Alternative Product Users, and Non-Users among Japanese Youth: A Nationwide Survey.

The impact of heated-tobacco-products (HTPs) and electronic cigarettes (e-cigarettes) on youth is a controversial public health issue, as it is unknown whether alternative products result in more youth using such products or smoking. In Japan, e-cigarettes with nicotine are prohibited, but e-cigarettes without nicotine are available. HTPs are marketed as tobacco products. Within this unique context, we aimed to compare any conventional cigarette smokers (including those who also used alternative products) with exclusive users of alternative products and examine factors relating to their use in Japan. In 2017, 22,275 students in grades 7-9 (age 12-15) and 42,142 in grades 10-12 (age 15-18) nationwide were surveyed. Overall, 1.8% were current users of any of the three products over the last month. Multivariable analysis revealed that risk factors for alternative product use were the same as those for cigarette use. Among all users, exclusive new product users were more likely to participate in club activities and intend to continue to higher education; any conventional cigarette users (including those who also used alternative products) were more likely to be exposed to secondhand smoke at home and to drink alcohol. Reducing adult smoking and disseminating health education remain relevant as strategies for preventing adolescents' future tobacco use.

Heated Tobacco Product Smokers in Japan Identified by a Population-Based Survey.

BACKGROUND: In this study, we aim to estimate the prevalence of heated tobacco product (HTP) smokers 3 years after the launch of HTPs in Japan. METHODS: Our study, performed in February 2018 in Japan, had a cross-sectional population-based design. A total of 4,628 adult participants (2,121 men and 2,507 women) were randomly sampled from all regions of Japan. The response rate was 57.9%. Interviews were conducted by trained investigators who visited participants' homes. A survey on current (past 30 days) and lifetime tobacco use (including e-cigarettes and HTPs), as well as numerous sociodemographic factors, was conducted. RESULTS: The age-adjusted rates and estimated number of lifetime-HTP smokers were 14.1% (95% confidence interval [CI], 12.5-15.6%; 7.11 million men) and 3.7% (95% CI, 2.9-4.4%; 1.99 million women). The age-adjusted rates for current HTP smokers were 8.3% (95% CI, 7.1-9.6%; 4.21 million men) and 1.9% (95% CI, 1.3-2.4%; 1.02 million women). Multiple variables were found to be associated with a higher prevalence of current HTP use, including being male, aged 20-39 years, a current Internet user, a risky drinker, or a heavy episodic drinker. HTP use was also higher among men with 10 years or more of education, women with 15 years or less of education, and men with middle- or high-level household incomes. CONCLUSION: We concluded that HTP use has increased substantially in Japan. However, regulations for HTPs are weaker than those for combustible cigarettes in Japan. Thus, HTPs should be subjected to the same regulations as combustible tobacco products.