Risk of placenta accreta spectrum following myomectomy: a nationwide cohort study.

BACKGROUND: Whether myomectomy increases the risk of placenta accreta spectrum in the following pregnancies remains controversial. OBJECTIVE: This study aimed to investigate the effect of myomectomy on the risk of placenta accreta spectrum in the following pregnancies. Moreover, different methods of myomectomy on the risk of placenta accreta spectrum were explored. STUDY DESIGN: A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database, including all pregnant patients in Taiwan who gave birth between January 2008 and December 2017. A 1:1 propensity score estimation matching was performed for the analysis of myomectomy on the risk of placenta accreta spectrum. Among pregnant patients who received myomectomy, different methods of myomectomy on the risk of placenta accreta spectrum were compared with the control group. RESULTS: Among the 1,371,458 pregnant patients in this study, 11,255 pregnant patients had a history of myomectomy. The risk of placenta accreta spectrum was higher in pregnant patients with a history of myomectomy than in pregnant patients without a history of myomectomy (incidence: 0.96% vs 0.20%; adjusted odds ratio, 2.28; 95% confidence interval, 1.85-2.81; P<.01). Among pregnant patients with a history of myomectomy, 5045 (46.87%) received laparotomic myomectomy, 3973 (36.93%) received laparoscopic myomectomy, and 1742 (16.20%) received hysteroscopic myomectomy. The incidence of placenta accreta spectrum was higher in the hysteroscopic group than in the laparotomic group or the laparoscopic group (1.89% [hysteroscopic group] vs 0.71% [laparotomic group] and 0.81% [laparoscopic group]; P<.05). Compared with patients without a history of myomectomy, the adjusted odds ratio for placenta accreta spectrum was 3.88 (95% confidence interval, 2.68-5.63; P<.05) in the hysteroscopic group. CONCLUSION: Myomectomy, especially hysteroscopic myomectomy, is associated with an increased risk of placenta accreta spectrum in the subsequent pregnancy.

Association between Wakeup Frequency at Night and Atherogenic Dyslipidemia: Evidence for Sex Differences.

AIM: This study aimed to determine whether sleep disturbance, defined as the wakeup frequency at night, is associated with atherogenic dyslipidemia and to explore possible sex differences. METHODS: A total of 1,368 adults aged 19-70 years were included in the study of lifestyles and atherogenic dyslipidemia at the National Taiwan University Hospital in the period of 2008-2012. They completed a questionnaire regarding lifestyle information and sleep quality, including sleep hour duration, use of sleeping pills, and wakeup frequency during nighttime sleep. The measured lipid profiles included total cholesterol, triglycerides, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), non-HDL-C, and small dense LDL-C (sdLDL-C). Multivariate logistic regression was performed to determine habitual interrupted sleep and the odds ratio of atherogenic dyslipidemia following adjustment for conventional risk factors and for sex-based subgroup analysis. RESULTS: A wakeup frequency ≥ 3 times per night was independently associated with an increased risk [odds ratio (95% confidence interval)] of dyslipidemia was 1.96 (1.17-3.28), and non-HDL-C ≥ 160 mg/dL was 1.78 (1.09-2.89). A higher wakeup frequency was associated with increased atherogenic dyslipidemia in women than in men. The multivariate adjusted relative risks for non-HDL ≥ 160 mg/dL and cholesterol ≥ 200 mg/dL were 3.05 (1.27-7.34) and 4.01(1.29-12.45) for female individuals with insomnia and those with a wakeup frequency ≥ 2 times per night, respectively. CONCLUSION: A higher wakeup frequency was associated with atherogenic dyslipidemia in Taiwanese adults, particularly in women. This study also provided another evidence of increasing cardiovascular diseases in subjects with habitual interrupted sleep.

Vaginal birth after cesarean section: Experience from a regional hospital.

OBJECTIVE: Trial of labor after cesarean section (TOLAC) is an option for women with previous cesarean section. However, few women choose this option because of safety concerns. We evaluate the safety and risks associated with TOLAC and the success rate of vaginal birth after cesarean delivery (VBAC). MATERIAL AND METHODS: We reviewed all patients with a history of previous cesarean section that underwent elective repeat cesarean section (ERCS) or TOLAC in a regional teaching hospital from Nov, 2013 to May, 2018. Maternal basic clinical information, intrapartum management, postpartum complications, and neonatal outcomes were analyzed. RESULTS: 199 pregnant women with a history of at least one previous cesarean section were enrolled. 156 women received ERCS and 43 women (21.6%) underwent TOLAC, with 37 (86.0%) who underwent successful VBAC. The VBAC rate was 18.6%. Higher success rate was found in women with previous vaginal birth than in women without vaginal birth (100% vs. 81.8%). One case (2.3%) in the VBAC group was complicated with uterine rupture and inevitable neonatal death during second stage of labor. The uterus was repaired without maternal complications. In another case, the newborn's condition was complicated with low APGAR score (<7) at birth due to maternal chorioamnionitis. Among indications for previous cesarean section, cephalo-pelvic disproportion (CPD) was associated with TOLAC failure and uterine rupture after VBAC. CONCLUSION: VBAC is a feasible and safe option. Modes of delivery should be thoroughly discussed when considering TOLAC for women with history of previous cesarean section due to CPD, considering its association with TOLAC failure in second stage of labor.

Experience in different modes of delivery in twin pregnancy.

BACKGROUND/PURPOSE: Vaginal delivery, compared with Cesarean delivery, remains a less chosen mode of delivery for twin pregnancy. We studied the maternal and perinatal outcomes of twin pregnancy with different modes of delivery. METHODS: A retrospective study with data collected from a regional hospital, including vital twin pregnancies delivered at gestational age of 32 weeks and above. Medical charts were reviewed for prenatal conditions and postpartum outcomes. RESULTS: Ninety-eight pairs of twins were included and 44.9% were delivered via vaginal delivery. Women in the vaginal delivery group were significantly younger (32.5 ±4.3 years versus 34.8 ±4.6 years, p < 0.01), multiparous (34.1% versus 18.5%) and with more twins in vertex-vertex presentation (70.5% versus 33.3%) compared with women in the Cesarean delivery group. There were no differences between maternal postpartum complications and neonatal outcomes in both groups. The outcomes showed longer inter-twin delivery time interval (5.7 ± 5.6 versus 1.5 ± 0.9 min, p < 0.01), less estimated blood loss (198.7 ± 144.1 versus 763.2 ± 332.3 mL, p < 0.01), and shorter maternal hospital stay (3.0 ± 0.5 versus 5.7 ± 0.5 days, p< 0.01) in the vaginal delivery group. Twenty newborns had Apgar score below seven at birth. Logistic regression analysis revealed that low Apgar score was independently related to younger maternal age, maternal obstetric diseases and fetal non-vertex presentation. Gestational weeks and mode of delivery were not related to low Apgar score. CONCLUSION: With careful case selection, vaginal delivery could be safely performed in twin pregnancies with less estimated blood loss and better recovery than Cesarean delivery.

Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer.

Ovarian cancer is the most lethal gynecological cancer, and it is frequently diagnosed at advanced stages, with recurrences after treatments. Treatment failure and resistance are due to hypoxia-inducible factors (HIFs) activated by cancer cells adapt to hypoxia. IGFBP3, which was previously identified as a growth/invasion/metastasis suppressor of ovarian cancer, plays a key role in inhibiting tumor angiogenesis. Although IGFBP3 can effectively downregulate tumor proliferation and vasculogenesis, its effects are only transient. Tumors enter a hypoxic state when they grow large and without blood vessels; then, the tumor cells activate HIFs to regulate cell metabolism, proliferation, and induce vasculogenesis to adapt to hypoxic stress. After IGFBP3 was transiently expressed in highly invasive ovarian cancer cell line and heterotransplant on mice, the xenograft tumors demonstrated a transient growth arrest with de-vascularization, causing tumor cell hypoxia. Tumor re-proliferation was associated with early HIF-1α and later HIF-2α activations. Both HIF-1α and HIF-2α were related to IGFBP3 expressions. In the down-expression of IGFBP3 in xenograft tumors and transfectants, HIF-2α was the major activated protein. This study suggests that HIF-2α presentation is crucial in the switching of epithelial ovarian cancer from dormancy to proliferation states. In highly invasive cells, the cancer hallmarks associated with aggressiveness could be activated to escape from the growth restriction state.

Diagnosis of Peritoneal Tuberculosis from Primary Peritoneal Cancer.

Peritoneal tuberculosis (PTB) is an uncommon extrapulmonary infection mimickng primary peritoneal cancer (PPC). We retrospectively included 23 women with PTB and 47 women with PPC treated in a medical center to study the clinical and radiological features that differentiate PTB from PPC. Body temperature above 38 °C was a unique feature of PTB (34.7% versus 0%, p < 0.001). Body Mass Index (BMI) was lower (21.9 ± 3.7 versus 25.2 ± 4.1, p = 0.003), white blood cell (WBC) count was lower (5179.6 ± 1502.2 versus 7716.2 ± 2741.8, p < 0.001), and CA-125 level was lower (508.0 ± 266.1 versus 2130.1 ± 2367.2 U/mL, p < 0.001) in PTB compared with PPC. Imaging detected more pulmonary infiltration and consolidation (52.2% versus 6.4%, p < 0.001), and less omental/mesentery changes (52% versus 83%, p < 0.001) in PTB compared with PPC. The operated patients received earlier treatment compared to patients without operation (7.9 ± 5.3 days versus 17.2 ± 11.0 days, p = 0.010). In conclusion, fever above 38 °C, lower BMI, lower WBC count, less elevated CA-125 level, and imaging of less omental involvement were features of PTB differentiated from PPC.

IGFBP3 inhibits angiogenesis through intracellular regulation of THBS1 expression.

Insulin-like growth factor binding protein-3 (IGFBP3) has been postulated to be a mediator of growth suppression signaling. It was shown to function as a suppressor of invasion in epithelial ovarian cancer (EOC). In this study, we identified an angiogenesis inhibitor, thrombospondin-1 (THBS1), which correlated with IGFBP3 expression in EOC cells. After restoring IGFBP3 expression in an EOC cell line using an inducible plasmid, the transfectants showed an increase in IGFBP3 associated with a parallel increase in THBS1. IGFBP3 decreased cell capillary tube formation in HUVECs, which was reversed after anti-THBS1 treatment. IGFBP3 also decreased blood vessel development in chick embryo chorioallantoic membrane (CAM) assay, which was reversed after THBS1 silencing using THBS1 siRNA. Heterotransplantation of IGFBP3 transfectants significantly decreased tumor growth and vascular formation. Luciferase promoter assay illustrated that THBS1 promoter was activated in the presence of both intracellular and extracellular IGFBP3. The signal was stronger in intracellular IGFBP3 expression than that in extracellular IGFBP3 neutralization. In conclusion, we have identified a novel association between IGFBP3 expression and THBS1 elevation, which consequently results in a decrease in angiogenesis. IGFBP3 could activate THBS1 through promoter regulation mainly via an intracellular signaling pathway. Such angiogenesis-regulating ability could be associated with tumor progression and may represent a major function of IGFBP3 as an onco-suppressor in the pathogenesis of ovarian cancer.

Single-port laparoscopic hysterectomy for uteri greater than 500 grams.

OBJECTIVES: To study the operative outcomes of single-port laparoscopic hysterectomy in uteri greater than 500 g, using either laparoscopic assisted vaginal hysterectomy (LAVH) or laparoscopic supracervical hysterectomy (LSH). MATERIALS AND METHODS: 78 patients were included in a single institute by a single surgeon from March, 2013 to January, 2018. RESULTS: The median uterine weight was 686.5 g. Larger uterine weight was correlated with longer operative time and greater estimated blood loss. Two types of operations were performed: LAVH (n = 55) or LSH (n = 23). There were no differences in operative time (150.2 ± 45.1 vs. 158.6 ± 82.1, P = 0.66) and estimated blood loss (365.8 ± 298.5 vs. 356.5 ± 46.6, ml, P = 0.94) between LAVH and LSH. However, patients in LAVH had more excess blood loss (>500 mL) compared with LSH (32.7% vs. 21.7%, P = 0.42). In the later study period, the operative time was shorter and complication rates were lower. Such differences were especially significant in the LAVH group. By multiple regression analysis, operative time was independently correlated with age, body mass index, estimated blood loss and uterine weight in LAVH. The correlation between operative time and uterine weight in LSH was attenuated by estimated blood loss. Estimated blood loss was the dominant factor correlated with longer operative time in LSH. CONCLUSIONS: Both LAVH and LSH could be feasible in uteri greater than 500 g. LSH appeared to have less complication and less blood loss than LAVH. Operative time was correlated significantly with bleeding amount. Therefore, better bleeding control and surgical experience were warrants for single-port laparoscopic hysterectomy in uteri greater than 500 g.

SRPX and HMCN1 regulate cancer­associated fibroblasts to promote the invasiveness of ovarian carcinoma.

Cancer­associated fibroblasts (CAFs) are known to be essential in cancer initiation and development. However, the role of CAFs in promoting ovarian cancer (OC) invasion remains to be fully elucidated. To address this in the present study, 49 clinical OC specimens were used to evaluate the roles of CAFs in promoting ovarian tumor migration and invasion and disease progression. It was found that the sushi repeat­containing protein, X­linked (SRPX) and hemicentin 1 (HMCN1) genes were significantly upregulated in CAFs from high­grade serous carcinoma (HGSC) and clear cell carcinoma (CCC) samples, the two major histological types of OC with frequently poor patient survival rates. The short hairpin (sh)RNA­mediated silencing of SRPX and HMCN1 in fibroblasts significantly suppressed the Transwell invasive activities of OC cells. Further experiments showed that SRPX and HMCN1 regulated the invasiveness of OC via the Ras homology family member A (RhoA) signaling pathway in fibroblasts. Therefore, the findings of the present study suggest that targeting the CAF genes, SRPX and HMCN1, can inhibit OC migration and invasion. These data highlight the importance of CAF­OC crosstalk signaling in cancer invasion and demonstrate the potential for improved efficacy of OC treatment by targeting CAF­SRPX/HMCN1.

GnRHa Before Single-Port Laparoscopic Hysterectomy in a Large Barrel-Shaped Uterus.

BACKGROUND AND OBJECTIVES: Laparoscopic hysterectomy for a large barrel-shaped uterus is difficult. We assessed the feasibility of single-port laparoscopic hysterectomy in a large barrel-shaped uterus after gonadotropin-releasing hormone agonist (GnRHa). METHODS: We retrospectively reviewed 39 patients with a large barrel-shaped uterus who were treated with GnRHa (leuprolide acetate) before single-port laparoscopic hysterectomy. During the same period, 134 patients without GnRHa pretreatment were included as control subjects. RESULTS: Patients with GnRHa treatment had an average increase in hemoglobin of 3.0 mg/dL and a decrease in uterine weight of 330.9 g (40.1%). Ancillary ports were required in 2 patients in the treatment group and none in the control group. There were no differences in uterine weights, operative time, and estimated blood loss in the 2 groups of patients. The estimated average operative time was shortened by 34 min after GnRHa treatment. However, bladder and ureter injuries were marginally higher (10.3% versus 2.2%) and days of hospital stay (3.7 versus 3.1) were significantly longer in the treatment group compared with controls. Complication rates were correlated with previous operative history, pelvic adhesion, and larger uterine weight but not with GnRHa treatment and operative sequence. CONCLUSIONS: GnRHa pretreatment in patients with a large barrel-shaped uterus during SPH is feasible with shortened operative time. However, the higher complication rates in these patients suggest that a weight-reduced barrel-shaped uterus that is achieved with GnRHa treatment could still be difficult and should be handled in cautious.

Phthalate exposure increases subclinical atherosclerosis in young population.

The link between phthalate exposure and the risk of subclinical atherosclerosis in young population remains unclear. This study investigated the association between phthalate exposure and subclinical atherosclerosis, in terms of carotid intima-media thickness (CIMT), in young population. From a nationwide mass urine screening for renal health, conducted in 1992-2000 among school children 6-18 years of age in Taiwan, we recruited 789 subjects to participate in the cardiovascular health examination in 2006-2008. Among them, 787 received measurements of 7 urinary phthalate metabolites and CIMT. Results showed both mean and maximal values of CIMT at all segments of carotid arteries significantly increased with the urinary mono-2-ethylhexyl phthalate (MEHP), ∑ di-(2-ethylhexyl) phthalate (DEHP), and mono-n-butyl phthalate (MnBP) in a dose-response relationship after adjustment for multiple linear regression models. Multivariate logistic regression analysis showed that higher quartiles of urinary concentrations of MEHP, ∑DEHP, and MnBP were associated with a higher risk of thicker CIMT. Compared to subjects with the lowest quartile (Q1) of urinary MEHP, the adjusted odds ratios (95% confidence interval) for thicker CIMT among subjects with higher urinary MEHP were 2.13 (1.18-3.84) at Q2, 4.02 (2.26-7.15) at Q3 and 7.39 (4.16-13.12) at the highest Q4. In conclusion, urinary phthalate metabolites of MEHP, ∑DEHP, and MnBP are strongly associated with CIMT in adolescents and young adults in Taiwan.

Clinical studies investigating the use of leuprorelin in Asian women with endometriosis: a review.

We aimed to examine how leuprorelin has been studied for the treatment of women with endometriosis in Asia. We conducted a literature search of PubMed, the Cochrane Library and ClinicalTrials.gov. This review includes randomised trials of women with endometriosis treated with leuprorelin in Asia. Phase I-IV clinical trials published between January 1 2000 and December 31 2016 and written in English were included. Four studies were identified, showing that leuprorelin significantly improves pain and quality of life. The oestrone and oestradiol levels are decreased by leuprorelin but can be increased using an 'add-back' therapy with conjugated equine oestrogen and methoxyprogesterone. Menopause is more common in women treated with leuprorelin. The bone mineral density is reduced in women treated with leuprorelin. There are limited studies investigating the use of leuprorelin for the treatment of endometriosis in Asian populations. However, the research that has been conducted supports the use of leuprorelin in an Asian population.

Positive Association Between Small Dense Low-Density Lipoprotein Cholesterol Concentration and Biomarkers of Inflammation, Thrombosis, and Prediabetes in Non-Diabetic Adults.

AIMS: Recent studies suggest elevated levels of small dense low-density lipoprotein cholesterol (sdLDL-C) can predict the risk of incident coronary heart disease (CHD), even in individuals considered to be at low risk for cardiovascular disease(CVD) based on their LDL-C levels. This study aims to prospectively investigate the association between sdLDL-C concentration and traditional and nontraditional CHD risk markers to explore the underlying roles of sdLDL-C in atherogenic processes. METHODS: Between 2009 and 2011, 594 healthy volunteers aged 35-65 years were recruited as control subjects in a study of work-related risk factors and acute CHD. All participants fasted for 12-14 h, and venous blood samples were collected in the morning to measure serum lipid profiles and other CHD-related markers. A standard oral glucose tolerance test was performed on all participants to assess their subclinical diabetes and prediabetes status. RESULTS: There were significantly positive associations between sdLDL-C concentration and traditional (age, smoking and alcohol drinking habit, blood pressure, body mass index (BMI), serum lipid profiles, and diabetes status) and nontraditional risk factors (complete blood counts, (CBC), fibrinogen, high-sensitivity C-reactive protein, and subclinical diabetes status) for CVD. After adjusting for confounding variables which include age, gender, BMI, hypertension, household income, and smoking and alcohol drinking habits, all atherosclerotic risk markers except D-dimer were significantly and positively associated with sdLDL-C. CONCLUSIONS: Our data indicated sdLDL-C is strongly associated with atherosclerotic risk markers, such as inflammation, thrombosis, hematological markers, and prediabetes. This study supports the hypothesis that sdLDL-C is a promising CVD risk biomarker.

Robotic myomectomy for large uterine myomas.

OBJECTIVE: To evaluate surgical outcomes and feasibility of robotic myomectomy in large uterine myomas. MATERIALS AND METHODS: This is a retrospective study for robotic myomectomies performed from October 2012 to August 2017 by a single surgeon in a tertiary care referral hospital. Demographics, diagnosis, perioperative variables, operative outcomes and complications were recorded. Large uterine myoma was defined as the estimated diameter of dominant myoma equal to or larger than 10 cm by sonography. RESULTS: Seventy-four patients were included and 32 (43.2%) patients had large uterine myoma. Patients with myoma larger than 10 cm showed significantly heavier myoma weight (446.5 ± 206.2 mg vs. 288.1 ± 147.5, p < 0.001), similar blood loss (309.4 ± 190.3 mL vs. 200.9 ± 285.9 mL, p = 0.06), and longer operative time (263.4 ± 83.7 min vs. 219.1 ± 75.7 min, p = 0.02) compared with patients with myoma <10 cm. The largest myoma removed was 20 cm in diameter. Perioperative complications were rare. CONCLUSION: Robotic myomectomy is feasible for managing large uterine myomas. It is a safe procedure with acceptable longer operative time.

Double collecting system with ectopic ureterocele masquerading as an ovarian torsion.

OBJECTIVE: Ureterocele in a duplex system is rare and commonly presented with urinary tract infection at neonatal age, infant or childhood. Symptomatic ureterocele in reproductive-age is a diagnostic challenge and should be highly awarded to avoid miss-diagnosis. CASE REPORT: An adolescent girl with right ectopic ureterocele presented as acute abdomen that mimicked ovarian torsion received emergent laparoscopic surgery. Right ureterocele was identified and excised. Computed tomography later showed bilateral renal duplications with visible renal parenchyma and upper ureters. Recurrent abdominal pain with pelvic abscess occurred 10 days after surgery. Laparoscopic right partial nephrectomy of the upper moiety and resection of the residual ureterocele was performed. Cystoscopy showed absence of intravesical ureterocele and her symptoms were completely resolved after surgery. CONCLUSION: Infected ureterocele in a duplex system is a rare condition and should be kept in mind as differential diagnosis.

Learning curve in concurrent application of laparoscopic and robotic-assisted hysterectomy with lymphadenectomy in endometrial cancer.

OBJECTIVE: To evaluate the concurrent interaction of laparoscopic and robotic-assisted surgery in the initial learning period of endometrial cancer staging. MATERIALS AND METHODS: A retrospective cohort study was performed for the first 44 consecutive patients with endometrial cancer underwent laparoscopic (LSS) or robotic-assisted staging surgery (RSS) from February 2012 to October 2015 by a single surgeon in a tertiary care referral hospital. Demographics, diagnosis, perioperative variables, and complications were recorded. Quality of surgery was determined by the number of lymph nodes dissected and learning curve was estimated by operative time with respect to chronologic order of operation. RESULTS: Twenty-four patients received LSS and 20 patients received RSS. RSS required longer operative time, but obtained more total number of lymph nodes compared with LSS (286.9 vs. 201.9 min (p < 0.001); 26.2 vs. 20.7 (p < 0.05), respectively. There were no difference in blood loss, number of para-aortic nodes removed, complications and hospital stay between the two types of surgery. An additive model based on tumor grade, body mass index, estimated blood loss and chronological order of operation was constructed to fit operative time of these two types of surgery. Proficiency of achievement was not observed for LSS and was 6 for RSS. CONCLUSIONS: Operative time was longer but Lymph node dissection was easier in RSS. Learning curve for LSS to maintain similar surgical quality as RSS was not observed. The concurrent use of robotic platform in the initial practice of minimally invasive staging surgery could optimize surgical technique for LSS.

Clinical implication for endometriosis associated with ovarian cancer.

We reviewed current literature regarding the association of endometriosis and epithelial ovarian cancer based on epidemiology studies, molecular researches and clinical observations. Our methods include a review of literature research of MEDLINE, PubMed, Cochrane Library of Systematic Reviews and reference search in selected papers. The life time risk of epithelial ovarian cancer in women with endometriosis is low, yet there might be a cluster of individuals who have higher risk of developing epithelial ovarian cancer from endometriosis. Endometriosis associated ovarian cancer (EAOC) is predominant in particular histological subtypes of epithelial ovarian carcinoma and are related to some specific molecular aberrations. Clinical observations showed age as an important variable to the development of EAOC. Rapid growth of tumor and solid components in sonography are key features to detect malignant transformation of endometriosis. Evidence is not clear about prophylactic oophorectomy in preventing EAOC in patients with endometriosis. This review provided rationale data for identifying, monitoring, counseling and management of women with endometriosis who are potentially high risk for malignant transformation.