Climacteric symptoms in postoperative patients among endometrial cancer, cervical cancer, and ovarian cancer: a cross-sectional study.

PURPOSE: To date, no studies have assessed climacteric symptoms after hystero-adnexectomy for endometrial, cervical, or ovarian cancer. Thus, this study aimed to compare climacteric symptoms among patients who underwent surgery for these three cancer types. METHODS: In this cross-sectional study, we interviewed patients who were registered at a menopausal outpatient clinic between January 1999 and July 2016 after undergoing total hysterectomy, intrapelvic only or intrapelvic plus para-aortic lymph node dissection, and bilateral adnexectomy performed via laparotomy as a cancer treatment. Climacteric symptoms were assessed using a patient-reported questionnaire covering core domains with five symptoms only at the initial consultation. Each symptom was graded from 0 (no symptoms) to 3 (severe symptoms). We evaluated the frequency of symptom severity according to the time elapsed since surgery and the cancer type. RESULTS: The numbers of patients with endometrial, ovarian, and cervical cancer were 328, 90, and 107, respectively. Overall, climacteric symptoms were more severe in patients with cervical cancer than in those with endometrial or ovarian cancer; symptom severity decreased with increasing time since surgery. However, symptom severity did not decrease significantly over time in patients with cervical cancer even after > 5 years had elapsed since surgery. CONCLUSION: The climacteric symptoms were less severe in patients with endometrial or ovarian cancer with longer time elapsed since surgery but not in those with cervical cancer. Patients with cervical cancer may require more prompt interventions, including symptomatic treatment and longer follow-up period, than those with endometrial or ovarian cancer.

Fertility awareness and subclinical infertility among women trying to get pregnant at home.

BACKGROUND: Recent studies on fertility awareness among the reproductive population have reported the lack of accurate knowledge about fertility and assisted reproductive technologies. However, there has been little information regarding women trying to get pregnant at home. The aim of this study was to explore the prevalence of subclinical infertility among women trying to get pregnant at home, and to evaluate awareness regarding infertility and reasons for not visiting infertility clinics among women who use pregnancy-assist mobile applications to help them conceive. METHODS: A total of 2084 Japanese women responded to this online survey. We selected 1541 women according to the study criteria. Based on the results of 61 questions, we evaluated knowledge regarding fertility, prevalence of subclinical infertility, and reasons for not visiting the clinic among the participants. RESULTS: Despite the desire to conceive, the participants had an apparent tendency to overestimate the age limit for childbearing. A total of 338 (21.9%) women answered that in general women aged > 45 years could get pregnant. Approximately 40% of the women had possible subclinical infertility and were unaware of the fact. Additionally, about 70% of the women considered themselves to have infertility problems. Women who were aware of the possibility of infertility hesitated to visit the clinic due to unfamiliarity with a gynecologist or clinic, and apprehensions about the gynecologic examination. CONCLUSIONS: In our study, some women required treatment for infertility. Nonetheless, they hesitated to visit an infertility clinic. Sexual health education, together with proper accessibility to gynecology clinics, are necessary to reduce involuntary childlessness.

A semen-based stimulation method to analyze cytokine production by uterine CD56bright natural killer cells in women with recurrent pregnancy loss.

Cytokine secretion by NK cells is abnormal in some women with recurrent pregnancy loss (RPL). Cytokine production is usually evaluated after stimulation with PMA and ionomycin. However, stimulation of uterine NK cells with semen corresponds more closely to physiological conditions at the time of conception. As seminal plasma has immunomodulatory properties, we aimed to elucidate compatibility between uterine NK cells and semen. Endometrial samples were stimulated with PMA/ionomycin, semen, seminal plasma, or spermatozoa. Thereafter, cytokine production by NK (CD56bright) cells was evaluated using flow cytometry and compared between women with and without a history of RPL associated with abnormal NK cell distribution in the endometrium or unexplained RPL. The ratios (%) of NK cells producing IFN-γ and TNF-α (NK1 phenotype), IL-4 (NK1/NK2 phenotype), and IL-10 (NK1/NKr1 phenotype) were significantly lower after stimulation with semen than with PMA/ionomycin (P < 0.01). After exposure to semen, ratios (%) of NK cells producing IL-4 and IL-10 in patients with unexplained RPL were significantly lower (P < 0.05), whereas those of NK1/NK2 and NK1/NKr1 were significantly higher (P < 0.01) than those in controls. The shift of endometrial NK cells to the NK2 phenotype was more pronounced when stimulated by semen than by PMA/ionomycin. However, a semen-induced shift to NK1 in women with unexplained RPL could induce miscarriage. Couple-specific immunological compatibility tests through semen stimulation in vitro might provide important information to avoid RPL.

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

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.

Streptococcal Toxic Shock Syndrome: Life Saving Role of Peritoneal Lavage and Drainage.

PURPOSE: We encountered a case where an infection with group A streptococcus (GAS; ie, Streptococcus pyogenes) initially caused primary peritonitis and then subsequently caused streptococcal toxic shock syndrome. The patient's life was likely saved by an emergency laparotomy followed by extensive peritoneal lavage and drainage. CASE PRESENTATION: A 40-year-old woman was admitted to the Emergency Department for lower abdominal pain and numbness in the extremities. She presented with systemic inflammatory response syndrome. An emergency laparotomy was performed, and ascites that resembled pus and general peritonitis were noted. Peritoneal lavage and drainage were performed, and GAS was isolated from peritoneal fluid. Gram staining of cervical polyp specimens revealed Gram-positive bacteria. CONCLUSIONS: The patient was diagnosed with streptococcal toxic shock syndrome due to an ascending GAS infection originating from vagina.

Symptoms and effects of physical factors in Japanese middle-aged women.

OBJECTIVE: The aim of the study was to clarify the prevalence and severity rates of symptoms and investigate whether symptoms varied in relation to body mass index (BMI). METHODS: The study group composed of 1,969 women, aged 40 to 60 years, who presented at our department from 1993 through 2014. The participation rate was 98%. The presence or absence of symptoms was evaluated by having the participants complete the Keio Questionnaire, a self-administered questionnaire. To allow the results to be compared according to ovarian function, serum levels of follicle-stimulating hormone and estradiol were measured. Participants were classified into three groups according to BMI: underweight, normal weight, and overweight. Symptoms were also compared among these subgroups. RESULTS: The most common symptom was general fatigue. Vasomotor symptoms differed significantly between pre- and postmenopause status. When symptoms were analyzed according to BMI, the severity rates of the following symptoms were significantly higher in the overweight group than in the normal weight and underweight groups: hot flushes, sweats, joint pain, numbness, and incontinence. On the contrary, the underweight group had significantly higher severities of cold constitution, nervousness, and wrinkled skin than did the other groups. In addition, an increase in BMI was associated with an increased severity of vasomotor symptoms. CONCLUSIONS: The prevalence and severities of shoulder stiffness, considered a characteristic symptom in Japanese women, were high. Increased BMI was shown to be associated with a higher severity of vasomotor symptoms, joint pain, nervousness, and urinary symptoms.

Polymorphisms of estrogen metabolism-related genes ESR1, UGT2B17, and UGT1A1 are not associated with osteoporosis in surgically menopausal Japanese women.

INTRODUCTION: Bilateral salpingo-oophorectomy (BSO) is a risk factor for osteoporosis. Previous studies have reported an association between genetic polymorphisms and the risk of developing osteoporosis. However, the relationship between osteoporosis and genetic polymorphisms in Japanese women treated with BSO is not well understood. To improve the quality of life for post-BSO patients, it is important to determine the genetic factors that influence their risk for osteoporosis. The aim of this study was to investigate the association between gene variations of estrogen metabolism-related genes and osteoporosis in surgically menopausal patients, which may improve their quality of life. MATERIAL AND METHODS: This study included 203 menopausal women treated with BSO because of gynecologic disorders. One hundred and twenty-six women with artificial (surgical) menopause, who had undergone BSO in the premenopausal period, were compared with 77 women with natural menopause, who had undergone BSO in the postmenopausal period. The women were tested for bone mineral density to diagnose osteoporosis. Polymorphisms of estrogen receptor 1 (ESR1) and UDP-glucuronosyl transferase (UGT) genes UGT2B17 and UGT1A1 were analyzed, and their association with bone mass and osteoporosis was statistically evaluated. RESULTS: No significant association was found between osteoporosis and polymorphisms in ESR1, UGT2B17, or UGT1A1 in both groups, suggesting that BSO might be a more significant physiological factor in influencing bone mass density compared to genetic variations. CONCLUSIONS: These results suggest that the ESR1, UGT2B17, and UGT1A1 polymorphisms are not genetic factors affecting osteoporosis in postmenopausal Japanese women.

NK22 Cells in the Uterine Mid-Secretory Endometrium and Peripheral Blood of Women with Recurrent Pregnancy Loss and Unexplained Infertility.

PROBLEM: We aimed to investigate natural killer 22 (NK22) cells in the peripheral blood and the uterine endometrium of women with unexplained recurrent pregnancy loss (URPL) and unexplained infertility (UI). METHOD OF STUDY: Peripheral blood and endometrial samples were collected from women with URPL (n = 43) and UI (n = 38). Intracellular cytokine production, such as IL-22, IFN-γ and TNF-α, and the expression of NKp46 on NK cells were analyzed by three-color flow cytometry. RESULTS: The percentages of endometrial CD56(+) /IL-22(+) and CD56(dim) /IL-22(+) cells in women with URPL were significantly higher than those of UI (P < 0.05, respectively). In addition, the percentage of CD56(bright) /IL-22(+) cells in women with RPL was negatively correlated with those of CD56(bright) /IFN-γ(+) and CD56(bright) /TNF-α(+) in both peripheral blood and endometrial NK cells. This was not seen in women with UI. The percentage of CD56(bright) /IL-22(+) cells was negatively correlated with CD56(bright) /NKp46 expressing NK cells in peripheral blood. CONCLUSION: Endometrial NK22 cells are differently regulated in women with URPL and UI. Women with URPL have higher level of NK22 cells with a potential to induce NK2 shift than women with UI.

NK cell abnormality and its treatment in women with reproductive failures such as recurrent pregnancy loss, implantation failures, preeclampsia, and pelvic endometriosis.

The regulation of uterine and peripheral blood natural killer (NK) cells has been associated with problems related to reproductive immunology such as recurrent pregnancy loss (RPL), implantation failure or preeclampsia. NKp46, one of the natural cytotoxicity receptors (NCRs), is a unique marker that functions in NK cell cytotoxicity and cytokine production. Expression of NKp46 on NK cells is lower in women with recurrent pregnancy loss and pregnancy-induced hypertension. Moreover, expression of NKp46 on peritoneal fluid NK cells is lower in women with pelvic endometriosis. Therefore, evaluation of NKp46 on peripheral blood NK cells may provide a means of screening for reproductive abnormalities. Recently, a new type of NK cell, the NK22 cell, has been reported. This cell may be a regulator not only of the mucosal barrier but also of reproduction. For women with RPL showing abnormal uterine and/or peripheral blood NK cells, both intravenous immunoglobulin treatment and intralipid treatment have been reported. The effects of these treatments are still controversial, and further studies are needed in order to clarify their true impact. The present review examines variations in the expression of NCRs on NK cells, the participation of NK22 cells in reproduction, and the possible use of intravenous immunoglobulin or intralipid treatment for women with recurrent pregnancy loss and NK cell abnormality.

Osteoporosis is less frequent in endometrial cancer survivors with hypertriglyceridemia.

We previously reported an association between dyslipidemia and endometrial cancers. Osteoporosis is also reported to relate with some cancers. A common etiologic event has been proposed between dyslipidemia and osteoporosis. However, the pattern of interrelationships among dyslipidemia, osteoporosis and endometrial cancer is not well understood. To improve the quality of life of endometrial cancer survivors, these relationships should be determined. This study included 179 Japanese menopausal women who underwent bilateral salpingo-oophorectomy, including 114 women with incident endometrial cancer and 65 without endometrial cancer. The women were categorized according to dyslipidemia status. Bone mineral density was measured and compared between groups. Osteoporosis was statistically more frequent in women with hypertriglyceridemia who did not have endometrial cancer. In contrast, osteoporosis was statistically less frequent in women with hypertriglyceridemia who had endometrial cancer. In this cross-sectional study in a Japanese population, osteoporosis was associated with hypertriglyceridemia in post-menopausal women without endometrial cancer, but was less frequent in endometrial cancer survivors with hypertriglyceridemia.

Expression of natural cytotoxicity receptors on peritoneal fluid natural killer cell and cytokine production by peritoneal fluid natural killer cell in women with endometriosis.

PROBLEM: To investigate the relationship between the expression of natural cytotoxicity receptors (NCRs) on peritoneal fluid (PF) natural killer (NK) (pfNK) cells and cytokine production by pfNK cells in women with endometriosis. METHOD OF STUDY: Peritoneal fluid was collected from women with endometriosis undergoing laparoscopic surgery (n = 21) and controls without endometriosis (n = 28). The expression of NK cell surface antigens such as CD16 and NCRs (NKp46, NKp44 and NKp30) on pfNK cells, and cytokines production by pfNK cells [tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, GM-CSF and transforming growth factor (TGF)-ß1] were measured using multicolor flow cytometry. RESULTS: The percentages of CD56(+)/NKp46(+) cells and CD56(dim) /NKp46(+) cells in severe endometriosis group were significantly lower than that in controls. TNF-α and IFN-γ production by pfNK cells in severe endometriosis group was significantly higher than those in controls. CONCLUSION: The differential expression of NKp46, TNF-α, and IFN-γ on pfNK cells in women with severe endometriosis may allow the proliferation and angiogenesis of endometriotic cells.

Family history and BRCA1/BRCA2 status among Japanese ovarian cancer patients and occult cancer in a BRCA1 mutant case.

BACKGROUND: This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer. METHODS: One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross-sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser-capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer. RESULTS: Nine of 102 (8.8%) families were regarded as having hereditary breast-ovarian cancer syndrome, two families (2.0%) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingo-oophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case. CONCLUSIONS: Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations.

Hypertriglyceridemia is frequent in endometrial cancer survivors.

OBJECTIVE: Previous studies have reported an association between endometrial cancer and the risk of metabolic syndrome; however, the pattern of endometrial cancer-associated dyslipidemia is not well understood. The standard therapy for endometrial cancer is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Premenopausal bilateral salpingo-oophorectomy may cause adverse events, including dyslipidemia. Gynecologists have to care dyslipidemia in endometrial cancer survivors at cancer follow-up clinic. METHODS: This study included 693 patients who had undergone bilateral salpingo-oophorectomy, and included 412 women with incident endometrial cancer and 281 controls. We divided the patients into two categories according to whether they had a premenopausal or postmenopausal bilateral oophorectomy. Serum lipid levels were measured and statistically analyzed. RESULTS: Hypertriglyceridemia was statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy both before and after menopause than in the corresponding non-endometrial cancer controls. High levels of low-density lipoprotein cholesterol and a high low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy before menopause than in non-endometrial cancer controls. CONCLUSIONS: Our report highlights the importance of the relationship between endometrial cancer and lipid metabolism, which may aid in preventing cerebrovascular or cardiovascular diseases due to dyslipidemia and improving the quality of life in endometrial cancer survivors.

Role of NKp46 expression in cytokine production by CD56-positive NK cells in the peripheral blood and the uterine endometrium.

PROBLEM: To investigate the role of natural cytotoxicity receptor, NKp46 expression in cytokine-producing NK cells. METHOD OF STUDY: CD56(+) /NKp46(+) NK cells from the peripheral blood and the uterine endometrium were magnetically separated. IFN-γ, TNF-α, IL-4, IL-10, and TGF-ß(1) expressions on NK cells were investigated using multicolor flow cytometry. RESULTS: Peripheral blood and uterine endometrial NK cells were grouped into 4 subpopulations based upon the degree of CD56 and NKp46 expressions. NKp46 expression was associated with higher frequency of cytokine-producing NK cells, including CD56(dim) NK cells. The percentage of TNF-α(+) and IL-10(+) NK cells per total CD56(+) /NKp46(+) NK cells in the uterine endometrium showed a significant correlation with those of the peripheral blood in all subpopulations, but that of IFN-γ(+) , IL-4(+,) and TGF-ß(1) (+) NK cells showed partial correlation. CONCLUSION: Expression of NKp46 is involved in cytokine production of CD56(+) NK cells in the peripheral blood and the uterine endometrium.

Carcinosarcoma of the fallopian tube: report of four cases and review of literature.

AIM: Carcinosarcoma of the fallopian tube is extremely rare and the therapeutic prognosis of this disease is unknown. METHODS: We report on four new cases of this disease and have reviewed 59 carcinosarcomas of the fallopian tube and analyzed the prognosis with respect to the chosen therapeutic method in order to explore the most appropriate therapy. RESULTS: Out of the 59 patients reviewed, the prognosis was examined in 51 patients that allowed it to be tracked. The 3-year survival rates were 63% for the 27 stage I/II patients and 40% for the 24 stage III/IV patients. The 3-year survival rates were 36% for the 14 surgery-alone patients, 59% for the 13 radiation therapy following surgery patients, 54% for the 27 chemotherapy following surgery patients (the chemotherapy group) and 100% in for the four chemoradiotherapy following surgery patients. A significant difference was observed between the surgery-alone and the chemotherapy groups (Wilcoxon test, P < 0.05), the chemoradiotherapy group demonstrating a better tendency as to survival rate than the surgery-alone group (Wilcoxon test, P = 0.06). Stage III/IV patients accounted for a two-thirds of the chemotherapy group. The 3-year survival rate for all the stage I-IV patients was 63% when a platinum drug was used and 21% when it was not used, suggesting the possibility of extending life through the use of a platinum drug. CONCLUSION: Chemotherapy using a platinum drug after surgery seems to be most effective treatment in this disease.

Changes of NK cells in preeclampsia.

The regulation of uterine and circulating peripheral blood natural killer (NK) cells has been associated with reproductive immunology such as recurrent pregnancy losses, implantation failures, or preeclampsia. Preeclampsia is a hypertensive disorder of pregnancy characterized by increased blood pressure accompanied by proteinuria and is a major cause of maternal and fetal mortality. Natural cytotoxicity receptors (NCRs) are unique markers, which regulate NK cell cytotoxicity and cytokine production. The relation of NCRs to reproduction is not fully characterized yet. The different profile of NCRs expression may suggest presence of abnormal regulation of NK cell in women with reproductive failures. Pregnant women with preeclampsia carry immunological abnormalities of NCRs on peripheral blood NK cells during pregnancy. The lower expression of NKp46(+) NK cells in women with preeclampsia may account for the higher production of NK1 cytokine that is known as NK1 shift in pregnant women with preeclampsia. Evaluation of NKp46 on peripheral blood NK cells may be applicable to find the onset of preeclampsia. In this review, various expressions of NK cell surface markers including NCRs on NK cells, NK cell cytotoxicity, and production of cytokines and angiogenic factors by NK cells were reviewed in relation to preeclampsia.

Uterine and circulating natural killer cells and their roles in women with recurrent pregnancy loss, implantation failure and preeclampsia.

The regulation of uterine and circulating peripheral blood natural killer (NK) cells has been associated with reproductive conditions including recurrent pregnancy loss (RPL), implantation failure and preeclampsia. Natural cytotoxicity receptors (NCRs) are unique markers that regulate NK cell cytotoxicity and cytokine production. The role of NCRs in reproductive events has not yet been fully characterized. There is an NK1 (Type 1) shift in peripheral blood NK cells in non-pregnant women prone to RPL and implantation failure. The different profile of NCR expression in endometrial or aborted decidual NK cells suggests the presence of abnormal regulation of NK cells in women with reproductive failure. Women with a history of RPL and preeclampsia carry immunological abnormalities of NCRs on peripheral blood NK cells during pregnancy. Evaluation of NKp46 on peripheral blood NK cells may be applicable for the prediction of preeclampsia. The lower expression of NKp46(+) NK cells in women with preeclampsia may account for the higher production of NK1 cytokines - known as the NK1 shift - in pregnant women with preeclampsia. In this review, the expression of NCRs in peripheral blood NK cells and endometrial or decidual NK cells is discussed in relation to reproductive failure.

Fibroma of the omentum resembling an ovarian tumor in the pelvis.

We would like to report the case of a patient with fibroma of the omentum that resembled an ovarian tumor in the pelvis. Since primary tumours of the omentum are rare, there is a paucity of information about the biology of such tumors in the basic texts and literature. An ultrasound examination of the patient revealed a mass, likely of ovarian origin, which consisted of liquid and solid components. It was suspected to be a malignant ovarian tumor. However, laparotomy demonstrated it was an omental tumor. This case shows that it can be difficult to pre-operatively diagnose omental fibromas because of their close resemblance to ovarian tumors.