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Alcohol consumption is internationally recognized as one of the compelling risk factors for breast cancer, but it does not necessarily correlate with the prognosis of breast cancer patients. Alcohol consumption in breast cancer patients was addressed in the 2022 Breast Cancer Clinical Practice Guidelines. A systematic review and meta-analysis of epidemiological studies on alcohol consumption and breast cancer recurrence, breast cancer-related mortality, all-cause mortality, and cardiovascular disease mortality in breast cancer patients was performed. The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant publications reporting cohort or case–control studies published until March 2021. A total of 33 studies (32 cohort studies and 1 case–control study) met the eligibility criteria; 4638 cases of recurrence, 12,209 cases of breast cancer-specific mortality, and 21,945 cases of all-cause mortality were observed. With regard to breast cancer recurrence, 7 studies assessed pre-diagnosis alcohol consumption (relative risk (RR) 1.02, 95% confidence interval (95% CI) 0.77–1.37, p = 0.88) and 3 studies assessed post-diagnosis alcohol consumption (RR 0.96, 95% CI 0.85–1.10, p = 0.57), and no significant increase or decrease in risk was observed. With regard to breast cancer-related mortality, 19 studies assessed pre-diagnosis alcohol consumption (RR 1.02, 95% CI 0.93–1.11, p = 0.69), 9 studies assessed post-diagnosis alcohol consumption (RR 0.96, 95% CI 0.77–1.19, p = 0.70), and no significant increase or decrease in risk was observed. With regard to all-cause mortality, 18 studies assessed pre-diagnosis alcohol consumption (RR 0.90, 95% CI 0.82–0.99, p = 0.02), 8 studies assessed post-diagnosis alcohol consumption (RR 0.88, 95% CI 0.74–1.02, p = 0.08), and pre-diagnosis alcohol consumption was associated with a significantly decreased risk. With regard to cardiovascular disease mortality and alcohol consumption, 2 studies assessed it, and the RRwas 0.47 (95% CI 0.28–0.79, p = 0.005), showing that alcohol consumption was associated with a significantly decreased risk. The limitations of this study are that drinking status was mainly based on a questionnaire survey, which is somewhat inaccurate and has many confounding factors, and the cut-off value for the maximum alcohol intake in many studies was low, and it is possible that the actual intake was only an appropriate amount. In many countries, a standard drinking amount is set, and wise decisions are required.

Takumi Kurabayashi,1 Yuki Ideno,2 Kazue Nagai,3 Naho Maruoka,3 Kiyoshi Takamatsu,4 Toshiyuki Yasui,5 Kunihiko Hayashi3 1Department of Obstetrics and Gynecology, Niigata City General Hospital, Niigata, Japan; 2Gunma University Center for Mathematics and Data Science, Maebashi, Gunma, Japan; 3Department of International/Community Health Laboratory Sciences, Graduate School of Health Sciences, Gunma University, Maebashi, Gunma, Japan; 4Department of Obstetrics and Gynecology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan; 5Department of Reproductive and Menopausal Medicine, Institute of Biomedical Science, Tokushima University Graduate School, Tokushima, JapanCorrespondence: Takumi KurabayashiDepartment of Obstetrics & Gynecology, Niigata City General Hospital, 463-7, Shumoku, Chuo-ku, Niigata City, Niigata Prefecture, 950-1197, JapanTel +81-25-281-5151Fax +81-25-281-5169Email takumi@hosp.niigata.niigata.jpPurpose: Although the validity of self-reported osteoporosis is often questioned, validation studies are lacking. This study was performed to investigate how well self-reported diagnoses of osteoporosis agreed with validated clinical information in young and middle-aged women in the Japan Nurses’ Health Study (JNHS), a nationwide prospective cohort study of nursing professionals.Patients and Methods: Data were reviewed for 15,717 subjects from the combined cohorts of the JNHS and a preceding pilot study (Gunma Nurses’ Health Study). The subjects’ mean age at the baseline (BL) survey was 41.6 ± 8.3 years, and the mean follow-up period was 11.5 ± 4.4 years. Participating nurses were mailed a follow-up questionnaire every 2 years. Respondents who self-reported a positive osteoporosis diagnosis during the study period were sent an additional confirmation questionnaire to corroborate the details.Results: The number (proportion) of women with osteoporosis was 884 (5.6%) [primary osteoporosis, 812 (5.2%); secondary osteoporosis, 72 (0.5%)]. The cumulative incidence of osteoporosis at the age of 40, 50, 60, 70, and 80 years was estimated to be 0.1% (95% confidence interval, 0.1– 0.2), 1.1% (0.9– 1.3), 7.7% (7.0– 8.4), 23.6% (21.6– 25.7), and 54.2% (40.2– 68.1), respectively. For BL and regular follow-up + expert review versus BL and regular follow-up + confirmation questionnaire + expert review, the positive predictive value (PPV) was 61.3% versus 85.6% and the negative predictive value (NPV) was 98.9% versus 98.2%, respectively.Conclusion: Self-reporting was associated with a high NPV for the incidence of osteoporosis. Although the PPV was slightly lower, additional corroborations by confirmation questionnaire might improve the PPV.Keywords: validation, self-reported diagnosis, osteoporosis, prospective cohort study, Japan Nurses’ Health Study

Objective: The aim of this study was to find out whether ThinPrep Integrated Imager (Hologic Inc.) screening is non-inferior to manual screening in the detection of cervical lesion. Study Design: For a total of 4,011 ThinPrep Pap test specimens stained by ThinPrep staining, manual screening (Manual arm) and ThinPrep Integrated Imager screening (Imager arm) were performed so as not to be screened by the same cytotechnologist, and the sensitivity and specificity in the detection of cervical lesion were compared using McNemar’s test. Results: The sensitivity to detect CIN1 or more squamous cell abnormalities or glandular abnormalities was 91.67% (= 374/408, 95% confidence interval [CI]: 88.44–94.08%) for the Manual arm and 92.40% (= 377/408, 95% CI: 89.28–94.70%) for the Imager arm, and the specificity was 88.87% (= 3,113/3,503, 95% CI: 87.77–89.88%) for the Manual arm and 89.55% (= 3,137/3,503, 95% CI: 88.48–90.54%) for the Imager arm. The differences in sensitivity and in specificity, respectively, were 0.74% (95% CI: −3.14–4.61%, McNemar’s test, p = 0.8041) and 0.69% (95% CI: −0.13–1.50%, McNemar’s test, p = 0.1125). About the equality of sensitivity and specificity between the 2 methods, 95% CIs of the difference between sensitivity and specificity are in the clinical equivalence range of ±5%, so the Imager arm is non-inferior to the Manual arm. Conclusion: The Imager arm was confirmed to have an equivalent and non-inferior capacity in the detection of cervical lesions compared with the Manual arm, suggesting that its practical application in cervical cytology tests is highly possible.

Laparoscopic myomectomy may become a cause to increase intraoperative hemorrhage. The purpose of this investigation was to study the relationship between clinical features, MR imaging findings and intraoperative hemorrhage during laparoscopic myomectomy. This study included 126 patients clinically and pathologically diagnosed as uterine leiomyoma between 2010 and 2015. These findings were statistically compared between significant intraoperative hemorrhage group (greater than 300 ml) and nonsignificant intraoperative hemorrhage group (less than 300 ml). Correlation between the maximum diameter of resected leiomyomas and the maximum diameter leiomyomas on MR imaging were also evaluated. Significant hemorrhage group showed larger maximum diameter of resected leiomyoma (p = 0.01), larger maximum diameter of leiomyoma on MR imaging (p = 0.01) and have cellular leiomyomas on MR imaging more frequently (p = 0.03) than nonsignificant intraoperative hemorrhage group. The maximum diameter of resected leiomyomas significantly correlated with that of leiomyomas on MR imaging (Spearman’s rho = 0.797, p

Prognostic clinicopathological factors for type 1 endometrial cancer are unknown and the purpose of the current study was to determine the independent prognostic variables for type 1 endometrial cancer. We performed a retrospective study of 168 patients with type 1 endometrial cancer primarily treated with comprehensive staging surgery. The median follow-up time was 68 (12–100) months. Independent risk factors for disease-free survival (DFS) and overall survival (OS) were determined using multivariate Cox regression models. Sub-group analysis of stage I was also performed. We also assessed the patterns of failure among patients with recurrences and investigated the associations with the prognostic variables determined by multivariate analysis. Twenty patients (11.9%) had recurrence and 13 patients (7.7%) died of the disease overall. Multivariate analysis revealed that grade 2 (G2) histology (p = 0.008) and positive peritoneal cytology (p = 0.001) predicted the recurrent event in type 1 endometrial cancer. G2 histology (p = 0.007) and positive peritoneal cytology (p = 0.003) were also found to be independent risk factors for tumor-related deaths. Among stage I patients, G2 histology and positive peritoneal cytology were also independent prognostic variables for DFS and OS. Patients with G2 histology and/or positive peritoneal cytology were more likely to have recurrence at distant sites. G2 histology and positive peritoneal cytology were independent prognostic factors for DFS and OS in type 1 endometrial cancer.

The third version of the Japan Society of Gynecologic Oncology guidelines for the treatment of uterine body neoplasms was published in 2013. The guidelines comprise nine chapters and nine algorithms. Each chapter includes a clinical question, recommendations, background, objectives, explanations, and references. This revision was intended to collect up-to-date international evidence. The highlights of this revision are to (1) newly specify costs and conflicts of interest; (2) describe the clinical significance of pelvic lymph node dissection and para-aortic lymphadenectomy, including variant histologic types; (3) describe more clearly the indications for laparoscopic surgery as the standard treatment; (4) provide guidelines for post-treatment hormone replacement therapy; (5) clearly differentiate treatment of advanced or recurrent cancer between the initial treatment and the treatment carried out after the primary operation; (6) collectively describe fertility-sparing therapy for both atypical endometrial hyperplasia and endometrioid adenocarcinoma (corresponding to G1) and newly describe relapse therapy after fertility-preserving treatment; and (7) newly describe the treatment of trophoblastic disease. Overall, the objective of these guidelines is to clearly delineate the standard of care for uterine body neoplasms in Japan with the goal of ensuring a high standard of care for all Japanese women diagnosed with uterine body neoplasms.

Hormone replacement therapy (HRT) plays a large part in maintaining and improving the quality of life (QOL) of postmenopausal women. Despite this obvious role, the use of HRT has stagnated in Japan as well as the United States, since the interim report of the HRT trial of Women's Health Initiative study was published in 2002. The Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and Women's Health formulated the Guidelines for Hormone Replacement Therapy in 2009, which was subsequently revised in 2012, with the aim of organizing perceptions about HRT and allowing people to provide or receive HRT with a sense of security. Later on, in light of changes in indications for HRT and attitudes toward its impact on cancer risks, amendments were made again in 2017. With the establishment of the 2017 guidelines, practitioners in Japan are able to address various issues related to HRT with more appropriate judgment. Moreover, the practice of reliable, safe and effective HRT is expected to promote further efforts toward improvement or maintenance of QOL in patients.

This survey sought to determine Japanese gynecologists' attitudes concerning administering hormone replacement therapy (HRT) for patients after surgery for endometrial cancer (EC).Eight hundred and eighty-eight members of the Japanese Gynecologic Oncology Group (JGOG) were asked to respond to an anonymous questionnaire on the JGOG website. The survey asked whether or not HRT was to be administered when surgery was performed (including a hysterectomy and bilateral oophorectomy) to treat EC before or after menopause. If HRT was not to be administered, respondents were asked the reason why. Respondents were presented with the same hypothetical patients that were featured in a previous survey in Germany, and differences in the mindsets of Japanese and German physicians were compared.Responses from 363 individuals (response rate 40.9 %) were analyzed. Seventy-eight percent of physicians considered HRT for patients undergoing surgery before menopause. The most prevalent reason of refusal to prescribe HRT was the risk of EC recurrence. Forty-eight percent of physicians considered HRT for patients undergoing surgery after menopause. The most prevalent reasons of refusal of HRT were its limited benefit and the availability of alternative therapies. Sixty-five percent of Japanese physicians responded that they would administer HRT to patients with low risk of recurrence vs. 46 % of physicians in Germany (P0.0002). Forty-nine percent of Japanese physicians approved of prescribing HRT for patients with high risk of recurrence vs. 25 % of physicians in Germany (P0.0001).Many Japanese gynecologists have a favorable attitude toward prescribing HRT after treatment of EC.

Hereditary breast and ovarian cancer syndrome (HBOC) is a hereditary tumor that can be definitively diagnosed by detection of germline mutation of the BRCA1 or BRCA2 gene. The HBOC Public Awareness and Management Sub-committee of the Tumor Committee, Japan Society of Obstetrics and Gynecology carried out a fact-finding survey on the status of treatment of HBOC in Japan. The directors of medical specialty teaching facilities were notified of the questionnaire by post, with the request for one respondent per facility. The response period was from 8 July 2014 to 31 March 2015. Of the 678 facilities that were asked to compete the questionnaire, 341 (50.3%) responded. The responses are shown in the respective tables. For questions with free responses, similar answers have been grouped together, and the written answers have been freely translated. Based on these results, the Japan Society of Obstetrics and Gynecology considers that the 14 conditions, including consultations by specialist staff, must be met before risk-reducing salpingo-oophorectomy is carried out.

The new non-reversed transcriptase inhibitor (NRTI) drugs for treatment of acquired immunodeficiency syndrome (AIDS) are reported. An improvement in the sensitivity and selectivity of high-performance liquid chromatography was obtained by diamond electrode-electrochemical detector and fluorescence detector owing to different structural information. The four anti-retroviral NRTI drugs (abacavir, didanosine, lamivudine and zidovudine) were separated on a CapcellPak C18 UG120 column (250 mm x 4.6 mm I.D., 5 microm) with an acetonitrile-25 mM potassium dihydrogenphosphate buffer (pH 8.0; 1:9, v/v) as the mobile phase. We applied dual detection (electrochemical detection and florescence detection) for improving the peak identification and also for improved selectivity, which assisted monitoring by trace-volume samples (e.g., plasma). The electrochemical detector, equipped with a diamond electrode, was set at 2000 mV (applied voltage) and the fluorescence detector was set at excitation wavelength 275 nm and emission wavelength 315 nm. The detection limits of the four NRTIs in spiked plasma were 1-100 ng/ml by electrochemical detection and 5-10 pg/ml by fluorescence detection. The calibration graphs were linear up to 20 microg/ml by electrochemical detection and 10 microg/ml by fluorescence detection. This is the first report of LC analysis of NRTIs by electrochemical detection, also combined with fluorescence detection. The detection limits of didanosine, lamivudine and zidovudine were improved 20-fold by electrochemical detection and 500-fold by fluorescence detection compared to previous reports on UV detection. The selectivity was also improved by dual detection. The proposed method was applied to the preliminary monitoring of NRTIs in plasma.

Background Patients with malignancy (n = 130) participated in the sperm cryopreservation program.

OBJECTIVE To gain insight into the characteristics and current status of climacteric symptoms reported by middle-aged and older women in Japan, we surveyed women presenting at our menopause clinic. DESIGN The participants included 1,069 women, ranging in age from 40 to less than 60 years (mean age, 50.2 y). Climacteric (indefinite) symptoms were objectively assessed with the use of the Keio questionnaire, which grades the severity of 40 types of symptoms classified into 20 subgroups. The total scores obtained for the 40 symptoms were used to calculate symptom prevalence and severity. To evaluate ovarian function, concentrations of estradiol and follicle-stimulating hormone (FSH) in sera were measured. RESULTS The most frequent symptom was general fatigue, reported by 88.2% of the women. Shoulder stiffness was the symptom rated to be severe by the highest percentage of women (38.1%). The prevalence and severity of hot flushes (and sweats) were slightly higher in perimenopausal and early postmenopausal women than in premenopausal and late postmenopausal women. The prevalence and severity of hot flushes and sweats were higher in women with estradiol 40 mIU/mL than in those with estradiol > or = 25 pg/mL and FSH < or = 40 mIU/mL. CONCLUSION General fatigue and shoulder stiffness, symptoms with low hormone dependence, are the two most frequent climacteric symptoms in our clinic. Hot flushes and sweats, symptoms with high hormone dependence, are also common symptoms.

Aim: Psychosocial elements are often found in the background of patients with menopausal disorders, and counseling based on these elements is essential for effective treatment. In the study presented here an attempt was made to extract psychosocial factors from Japanese cases of menopausal disorders in which the patients exhibited the impact of psychiatric elements and required counseling. Methods: A total of 97 cases in which the patients received counseling for the treatment of undefined complaints at our menopause clinic were analyzed. During counseling the patients were interviewed in regard to psychosocial factors and underwent psychological tests. Results: About half of them were found to have experienced various interpersonal problems as well as health-related problems. The frequency of problems such as empty nest syndrome and loss of relatives or friends was relatively low. Work-related anxiety or hardships of life were frequent among the premenopausal patients, while concern about aging was often noted in their postmenopausal counterparts. The incidence of empty nest syndrome was high among the ovariectomized women, but worry about aging was frequently reported by those undergoing natural menopause. Conclusion: This preliminary study revealed that problems related to families and the patient's health account for a large part of the psychosocial factors affecting the development of menopausal disorders in Japan. Incorporating these findings into counseling will make outpatient clinics services more acceptable to such patients.

Delirium is a common psychiatric illness among medically compromised patients. There is an increasing opportunity to use atypical antipsychotics to treat delirium. The effects of these drugs on delirium, however, the most appropriate way to use them, and the associated adverse effects remain unclear. To clarify these points, a prospective open trial on risperidone was carried out in 10 patients with delirium. At a low dose of 1.7 mg/d, on average, risperidone was effective in 80% of patients, and the effect appeared within a few days. There were no serious adverse effects. However, sleepiness (30%) and mild drug-induced parkinsonism (10%) were observed; the symptom of sleepiness was a reason for not increasing the dose. One patient responded to a dose as low as 0.5 mg/d, so it is recommended that treatment start at a low dose, which may then be increased gradually. This trial is a preliminary open study with a small sample size, and further controlled studies will be necessary.

Objectives This study was designed to investigate the current status of vaginal symptoms in Japanese postmenopausal women, and to clarify the significance of vaginal symptoms by analyzing their relationship to other climacteric symptoms. Methods The complaints of 613 women attending a menopause clinic (mean age ± standard deviation 53.5 ± 7.2 years; time since menopause or bilateral oophorectomy 6.4 ± 6.5 years) were evaluated according to the Keio modified menopause index. Results In total, 56.4% of subjects had at least one vaginal symptom. The most frequent vaginal symptom was dyspareunia, followed by vaginal dryness, discharge and itching, and the mean prevalence of the four symptoms was 31.7%. The peak intensity of vaginal symptoms occurred in the sixth decade, or 3–5 years after menopause or oophorectomy. Vaginal symptoms were usually associated with other climacteric symptoms, but some occurred independently. Conclusions A moderate proportion of Japanese postmenopausal women experience vaginal symp...

Background Because the primary aim of infertility treatment is to achieve pregnancy, mental health care during this treatment is often neglected. However, the inability to conceive children is stressful for couples throughout the world. Thus, the purpose of this study was to investigate factors related to the anxiety and depression of female infertility patients. Methods Participants included 83 Japanese women who initially visited the Reproduction Center of the Tokyo Dental College Ichikawa General Hospital to undergo testing and receive infertility treatment between February and April 2008. We administered two psychological tests, the Self-rating Depression Scale (SDS) test and the Hospital Anxiety and Depression Scale (HADS) test. We then examined the association of the test results with age, pregnancy and delivery history, employment status, duration of infertility, infertility treatment history, and male infertility. Results As patient age increased, total HADS and depression scores also increased. No correlation was observed between duration of infertility and SDS or HADS scores. Results were similar when the presence and absence of delivery history was compared. Patients who underwent infertility treatment were more likely to have high HADS depression scores compared to patients who had not undergone treatment. Additionally, patients whose husbands were infertile had significantly lower total HADS and anxiety scores than those whose husbands were not infertile. Conclusions Age and male infertility are factors that influence the presence of anxiety and depression in female infertility patients.

Background Granulosa cell tumours (GCTs) are frequently seen in menopausal women and are relatively indolent. Although the physiological properties of normal granulosa cells have been studied extensively, little is known about the molecular mechanism of GCT progression. Here, we characterise the unique behavioural properties of a granulosa tumour cell line, KGN cells, for the molecular analysis of GCT progression. Methods Population doubling was carried out to examine the proliferation capacity of KGN cells. Moreover, the invasive capacity of these cells was determined using the in vitro invasion assay. The expression level of tumour markers in KGN cells at different passages was then determined by Western blot analysis. Finally, the growth and metastasis of KGN cells injected subcutaneously (s.c.) into nude mice was observed 3 months after injection. Results During in vitro culture, the advanced passage KGN cells grew 2-fold faster than the early passage cells, as determined by the population doubling assay. Moreover, we found that the advanced passage cells were 2-fold more invasive than the early passage cells. The expression pattern of tumour markers, such as p53, osteopontin, BAX and BAG-1, supported the notion that with passage, KGN cells became more aggressive. Strikingly, KGN cells at both early and advanced passages metastasized to the bowel when injected s.c. into nude mice. In addition, more tumour nodules were formed when the advanced passage cells were implanted. Conclusion KGN cells cultured in vitro acquire an aggressive phenotype, which was confirmed by the analysis of cellular activities and the expression of biomarkers. Interestingly, KGN cells injected s.c. are metastatic with nodule formation occurring mostly in the bowel. Thus, this cell line is a good model for analysing GCT progression and the mechanism of metastasis in vivo.