Association Between Endometriosis and Mental Disorders Including Psychiatric Disorders, Suicide, and All-Cause Mortality -A Nationwide Population-Based Cohort Study in Taiwan.

Objective: A multitude of previous studies has substantiated that endometriosis correlated highly with psychiatric health. This study aims to investigate the association between endometriosis and psychiatric health. Methods: Utilizing the National Health Insurance Research Database of Taiwan, 100,770 enrolled participants, including 20,154 patients with endometriosis and 80,616 in the control group (1:4), matched for age, and index date from Taiwan's Longitudinal Health Insurance Database between January 1, 2000, and December 31, 2015. The Cox proportional regression model was used to compare the risk of mental disorders during the 16 years of follow-up after adjusting for confounding factors. Results: Of the study patients, 4083 (20.26%) developed mental disorders; 9225 of the 80,616 controls (11.44%) developed mental disorders. The Cox regression demonstrated that, after adjusting for age, monthly income, urbanization level, etc., people with endometriosis are more likely to suffer from mental disorders compared to those without endometriosis (hazard ratio [HR]=2.131; 95% confidence interval [CI]= 1.531-2.788; p<0.001). The result illustrated that women over 40 years old had a more significant risk. Conclusion: Compared to people without endometriosis, this study provides evidence that patients with endometriosis are at a 2.131-fold higher risk of developing mental disorders, especially in elder women. Regular psychiatric follow-up might be needed for those patients.

Clinical Characteristics of Hyperandrogenism Include Hirsutism, Polycystic Ovary Syndrome, and Acne: Association with Psychiatric Disease in Women -A Nationwide Population-Based Cohort Study in Taiwan.

Objective: Previous studies have shown an increased in psychiatric disorders in women with disorders associated with hyperandrogenism, but few nationwide cohorts have studied this phenomenon. Therefore, this study is aimed to examine the association between the clinical manifestations of hyperandrogenism and subsequent psychiatric disorders. Methods: Based on the National Health Insurance Research Database, 49,770 enrolled participants were matched for age and index date between January 1, 2000, and December 31, 2015. Hirsutism, polycystic ovary syndrome, and acne are characterized by hyperandrogenism. After adjusting for confounding factors, we used Cox proportional analysis to compare the risk of psychiatric disorders during the 16 years of follow-up. Results: Of all the participants, 1319 (13.25%) had psychiatric disorders in the study group, whereas only 3900(9.80%) had psychiatric disorders in the control group. After adjusting for age, and monthly income, the Cox regression analysis showed that the study patients were more likely to develop psychiatric disorders (hazard ratio [HR]: 2.004, 95% confidence interval [CI] = 1.327-2.724, P < 0.001). The results demonstrated that women aged 20-29 years had a more significant risk. Conclusion: Women with clinical characteristics of hyperandrogenism have a higher risk of developing psychiatric disorders, especially those aged 20-29 years.

Association of Postpartum Depression with Maternal Suicide: A Nationwide Population-Based Study.

BACKGROUND: To examine the association of postpartum depression (PPD) with maternal suicide in the Taiwanese population. METHODS: We examined the medical records of women aged 18-50 years who experienced childbirth and had PPD (the study cohort, n = 2882), who experienced childbirth but did not have PPD (comparison cohort 1, n = 5764), and who neither experienced childbirth nor had PPD (comparison cohort 2, n = 5764) between 2000 and 2015. The patients were followed up until suicide, withdrawal from the National Health Insurance program, or 31 December 2015. RESULTS: The rates of anxiety and depression symptoms, as well as the cumulative risk of suicide, were significantly higher in the study cohort. PPD was significantly correlated with an increased risk of maternal suicide and was associated with a greater risk of developing comorbidities such as hypertension, diabetes mellitus, hyperlipidemia, and stroke. The comparison cohorts did not differ significantly in terms of suicide risk. CONCLUSION: PPD was associated with a significantly higher rate of suicide and a shorter time to suicide after childbirth. Younger age, winter, and subclinical depression and anxiety positively predicted suicide in the study cohort. To prevent maternal suicide, clinicians should be observant of subclinical depression and anxiety symptoms among patients.

An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer.

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy owing to its high chemoresistance and late diagnosis, which lead to a poor prognosis. Hence, developing new therapeutic modalities is important for OvCa patient treatment. Our previous results indicated that a novel aptamer, Tx-01, can specifically recognize serous carcinoma cells and tissues. Here, we aim to clarify the clinical role and possible molecular mechanisms of Tx-01 in OvCa. Immunostaining and statistical analysis were performed to detect the interaction of Tx-01 and heat shock protein 70/Notch1 intracellular domain (HSP70/NICD) in OvCa. The in vitro and in vivo experiments were carried out to demonstrate the potential mechanisms of Tx-01. Results show that Tx-01 reduced serous OvCa OVCAR3 cell migration and invasion and inhibited HSP70 nuclear translocation by interrupting the intracellular HSP70/NICD interaction. Furthermore, Tx-01 suppressed serous-type OVCAR3 cell tumor growth in vivo. Tx-01 acts as a prognostic factor through its interaction with membrane-bound HSP70 (mHSP70 that locates on the cell surface without direct interaction to NICD) on ascitic circulating tumor cells (CTCs) and is reported to be involved in natural killer (NK) cell recognition and activation. Our data demonstrated that Tx-01 interacted with HSP70 and showed therapeutic and prognostic effects in serous OvCa. Tx-01 might be a potential inhibitor for use in serous OvCa treatment.

Downregulated Salt-inducible Kinase 3 Expression Promotes Chemoresistance in Serous Ovarian Cancer via the ATP-binding Cassette Protein ABCG2.

Background: Epithelial ovarian cancer (EOC) has a high tumor-associated mortality rate among gynecological cancers. Although CA125 is a well-studied biomarker for ovarian cancer, it is also elevated under numerous conditions, resulting in decreased specificity. Recently, we identified a novel tumor-associated antigen, salt-inducible kinase 3 (SIK3), during tumorigenesis in ovarian cancer. However, the association between SIK3 expression and patient outcomes in ovarian cancer remains unclear. Materials and Methods: We collected EOC samples from 204 patients and examined tumor SIK3 expression by immunohistochemistry (IHC) and CA125 expression in tumors and serum. The expression levels of SIK3 and CA125 were correlated with patient survival. SIK3 expression was silenced with SIK3-specific shRNAs to investigate the possible mechanisms related to chemoresistance in serous-type ovarian cancer cell lines OVCAR4 and SKOV3. Results: In advanced-stage serous ovarian cancer, patients with low SIK3 expression have poorer overall survival (OS) and progression-free survival (PFS) than patients with high SIK3 expression. Ovarian cancer cells with SIK3 knockdown display increased chemoresistance to Taxol plus cisplatin treatment, which is associated with the upregulation of the ABCG2 transporter. In addition, in serous ovarian cancer, SIK3 expression is inversely correlated to ABCG2 expression, and patients with low SIK3 and high ABCG2 expression have worse prognosis than patients with high SIK3 and low ABCG2 expression. Conclusion: Our results demonstrated that serous EOC patients with low SIK3 expression have poor prognosis, which is associated with chemoresistance mediated by ABCG2 upregulation. SIK3 and ABCG2 expression levels may be potential prognostic markers to predict the outcome in serous EOC patients.

Treatment outcomes of patients with stage II pure endometrioid-type endometrial cancer: a Taiwanese Gynecologic Oncology Group (TGOG-2006) retrospective cohort study.

OBJECTIVE: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. METHODS: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. RESULTS: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p<0.001), recurrent urinary tract infections (p=0.013), and leg lymphedema (p=0.038). Age over 50-year (HR=9.2; 95% confidence interval [CI]=1.2-70.9) and grade 3 histology (HR=7.28; 95% CI=1.45-36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR=5.13; 95% CI=1.38-19.1) and DSS (HR=5.97; 95% CI=1.06-58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p=0.046), but no impact on survival. CONCLUSION: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.

Acute abdomen in early pregnancy due to ovarian torsion following successful in vitro fertilization treatment.

OBJECTIVE: Ovarian torsion is an acute abdomen requiring prompt intervention. Ovarian torsion seldom occurs during pregnancy. However, with in vitro fertilization (IVF) treatments, ovarian hyperstimulation may increase the size of the ovaries and result in the occurrence of adnexal torsion. Here, we report two cases of ovarian torsion after IVF and discuss the optimal management of this emergency medical condition. CASE REPORT: The first case was a 23-year-old woman who received IVF-embryo transfer due to tubal factor infertility. Sudden-onset, lower abdominal pain developed at the 6th week of pregnancy. Conservative treatment with antibiotics was the initial approach, but a right oophorectomy had to be performed due to right ovarian torsion with hemorrhagic and gangrenous changes. The second case was a 38-year-old woman diagnosed with bilateral ovarian torsion at 8 weeks' gestation due to the sudden onset of low abdominal pain. Laparoscopy was arranged immediately after the diagnosis was confirmed. The left ovary was successfully preserved due to prompt intervention. Both pregnancies continued without problems after surgery. CONCLUSION: Ovarian hyperstimulation during IVF-embryo transfer treatment is a risk factor for developing adnexal torsion. Early diagnosis and prompt surgical intervention is the only way to protect the ovary and preserve the pregnancy. Laparoscopic surgery in early pregnancy causes no harm to the fetus and should be encouraged once the diagnosis is confirmed. Delaying surgery may induce serious infection and jeopardize the lives of both the fetus and mother.

Outcome of 3-day bleomycin, etoposide and cisplatin chemotherapeutic regimen for patients with malignant ovarian germ cell tumours: a Taiwanese Gynecologic Oncology Group study.

BACKGROUND: The combination of bleomycin, etoposide and cisplatin (BEP) is currently the most widely used treatment for malignant ovarian germ cell tumours (MOGCTs). The aim of this study was to evaluate the efficacy and adverse effects of the 3-day BEP regimen in Taiwan. The prognostic factors of the MOGCT patients were also analysed. PATIENTS AND METHODS: Two hundred and thirty-nine cases of MOGCTs were identified from the Taiwanese Gynecologic Oncology Group database, and 204 of those who received postoperative BEP chemotherapy were then analysed. RESULTS: The estimated rate of no evidence of disease was 94.0% for 204 patients with adjuvant BEP regimen. Seven grade 3/4 haematological adverse effects including four subjects with neutropenia, one with pancytopenia and two with neutropenic fever were recorded in the 853 total courses of chemotherapeutic cycles. The rates of haematological and non-haematological adverse effects were 0.82% and 2.3%, respectively. No treatment-related mortality was noted. In the analysis of prognostic factors, only tumour stage had a significant impact on disease recurrence (95% confidence interval (CI), 4.2­94.4, p < 0.001) and disease-related mortality (95% CI, 2.2­163.9, p = 0.007). CONCLUSIONS: The current 3-day adjuvant BEP regimen was effective and safe for patients with MOGCTs.

A potential for granulocyte-colony stimulating factor for use as a prophylactic agent for heatstroke in rats.

Heatstroke is a form of excessive hyperthermia associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system disorders predominate. Herein we determined to ascertain whether heat-induced multi-organ dysfunction in rats could be attenuated by granulocyte-colony stimulating factor (G-CSF) preconditioning. Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline, 0.3 ml, subcutaneously) or G-CSF (50-200 µg/kg body weight in 0.3 ml normal saline, subcutaneously) daily and consecutively for 5 days before the start of thermal experiments. They were exposed to an ambient temperature of 43°C for 68 min to induce heatstroke. G-CSF preconditioning significantly prolonged the survival time in heatstroke rats in a dose-related way (82-98 min vs 127-243 min). The non-preconditioning heatstroke animals showed hyperthermia, arterial hypotension, increased serum levels of systemic inflammatory response molecules, increased hypothalamic apoptotic cell numbers as well as neuronal damage scores, and increased serum levels of renal and hepatic dysfunction indicators. These heatstroke syndromes could be significantly reduced by G-CSF preconditioning. Thus our results revealed a potential for G-CSF used as a prophylactic agent for heatstroke in rats.

Premarin improves outcomes of spinal cord injury in male rats through stimulating both angiogenesis and neurogenesis.

OBJECTIVE: To ascertain whether Premarin improves spinal cord injury outcomes in male rats by stimulating both angiogenesis and neurogenesis. DESIGN: Chi Mei Medical Center research laboratory. SUBJECTS: Male Sprague-Dawley rats 240-258 g. INTERVENTIONS: Anesthetized rats, after the onset of spinal cord injury, were divided into two groups and given the vehicle solution (1 mL/kg of body weight) or Premarin (1 mg/kg of body weight). Saline or Premarin solutions were administered intravenously and immediately after spinal cord injury. MEASUREMENTS AND MAIN RESULTS: Premarin (an estrogen sulfate) causes attenuation of spinal cord injury-induced spinal cord infarction and hind limb locomotor dysfunction. Spinal cord injury-induced apoptosis as well as activated inflammation was also significantly Premarin-reduced. In injured spinal cord, angiogenesis, neurogenesis, and production of an antiinflammatory cytokine were all Premarin therapy-promoted. CONCLUSIONS: Our results indicate that Premarin therapy may protect against spinal cord apoptosis after spinal cord injury through mechanisms stimulating both angiogenesis and neurogenesis in male rats.

Chromosomal gain of 3q and loss of 11q often associated with nodal metastasis in early stage cervical squamous cell carcinoma.

BACKGROUND/PURPOSE: Cervical cancer remains a health problem among women worldwide. Delineation of genetic changes is critical to understanding the molecular basis of tumor progression, as well as for identifying genetic markers for early identification of patients at high risk for a poor outcome. METHODS: To provide comparative genomic hybridization data for cervical squamous cell carcinoma in Taiwan, and to gain further insight into genetic markers associated with lymph node metastasis of this disease, we performed comparative genomic hybridization analysis of 30 consecutive cases of cervical squamous cell carcinoma (24 stage IB and 6 stage IIB). RESULTS: The results disclosed that higher staged tumors or those with lymph node metastasis had more chromosomal imbalances. The commonly recurrent chromosomal imbalances were gains of 3q (46.7%), 1q (36.7%) and 8q (20.0%) and losses of 11q (36.7%), 3p (33.3%), 6q (23.3%), and 2q (20.0%). The frequencies of these chromosomal imbalances in stage IB and IIB tumors did not differ significantly. However, when compared with tumors without lymph node metastasis, the loss of 11q14-q22 (5/9 vs. 3/21, p = 0.019) and gains of 3q11-q22 and 3q26-qter (6/9 vs. 5/21, p = 0.026) were significantly more prevalent in tumors with lymph node metastasis. CONCLUSION: The results suggest that certain tumor-associated genes residing on 3q and 11q warrant further investigation to elucidate their role in the progression of this disease.

Simultaneous cesarean section and radical nephrectomy for angiomyolipoma with spontaneous bleeding during pregnancy: a case report.

BACKGROUND: Renal angiomyolipoma with spontaneous bleeding during pregnancy is an extremely rare condition and may jeopardize both the mother and fetus. The ethics of reproductive medicine, method of diagnosis, option for management and optimal time for surgical intervention can be arguable in this situation. CASE: A 31-year-old woman presented with dull right flank pain at 12 weeks' gestation. Abdominal sonography and renal magnetic resonance imaging revealed a hypervascular and fat-containing mass with mother and fetus bleeding at the right kidney. Due to stable hemodynamic status, the patient was treated conservatively and underwent elective, simultaneous cesarean section and radical nephrectomy safely at 38 weeks' gestation. Angiomyolipoma of the right kidney was diagnosed on pathologic examination. CONCLUSION: Renal angiomyolipoma with spontaneous bleeding during pregnancy is a dangerous condition that may cause mortality in the mother and fetus, but elective, simultaneous cesarean section and radical nephrectomy can be performed safely if the hemodynamic status is stable.

Comparing the clinical outcomes of intrauterine insemination by two different density gradient preparation methods.

BACKGROUND: Sperm preparation has play an integral part in the success of in-vitro fertilization. The aim of this study was to compare 2 different density gradient preparations for sperm separation in respect to sperm recovery, motility, motion parameters and clinical outcome after intrauterine insemination. METHODS: One-hundred and 21 women who received intrauterine insemination due to ovulation dysfunction were randomly allocated into 2 groups, using either the Percoll (Amersham, Pharmacia Biotech AB, Sweden) or the PureSperm (Nidacon, Göteborg, Sweden) density gradient method for sperm preparation. The characteristics of sperm before and after separation and the clinical outcome of intrauterine insemination were compared between the 2 groups. RESULTS: PureSperm and Percoll demonstrated comparable ability to recover the sperms with progressive motility. There was no difference in motion parameters and the number of sperm recovered with progressive motility between the Percoll and the PureSperm density gradient preparations. The clinical pregnancy rate was also comparable between the 2 groups, 12.5% (7/56) in the PureSperm group compared to 13.8% (9/65) in the Percoll group, (p > 0.05). CONCLUSIONS: Despite using different density composition and volume, PureSperm demonstrated clinical effect comparable to that of Percoll in preparing sperm for intrauterine insemination.