Vascular endothelial growth factor gene polymorphisms and endometriosis risk: a meta-analysis

Purpose

The vascular endothelial growth factor (VEGF) gene polymorphism has been reported to be associated with endometriosis risk. The purpose of the present study was to perform a comprehensive meta-analysis to explore whether VEGF gene polymorphisms confer risk to endometriosis.

Methods

By searching PubMed and EMBASE databases, a total of 11 studies were identified. Crude odds ratio (OR) and their corresponding 95% confidence intervals (CI) for VEGF gene polymorphisms and endometriosis risk were calculated.

Result

An association of VEGF gene +936TC polymorphism with endometriosis was found (Fixed-effect model: TT?+?TC vs. CC: OR 1.184, 95% CI 1.027?C1.366, P?=?0.020; TC vs. CC: OR 1.187, 95% CI 1.024?C1.375, P?=?0.023. Random-effcet model: TT?+?TC vs. CC: OR 1.203, 95% CI 1.003?C1.443, P?=?0.046; TC vs. CC: OR 1.188, 95% CI 1.021?C1.382, P?=?0.026). No association between VEGF genes ?460CT, +405CG, ?2578AC, ?1154GA polymorphisms and endometriosis was observed.

Conclusion

Our results indicate that VEGF +936TC gene polymorphism is a risk factor for endometriosis, and not ?460CT, +405CG, ?2578AC, ?1154GA.     

Visual pain mapping in endometriosis

Purpose

To construct pain maps in order to describe the distribution of pelvic pain in a group of endometriosis patients and endometriosis-free patients, to assess the feasibility of this method.

Methods

A total of 159 patients with pelvic pain who were scheduled for diagnostic laparoscopy.

Results

A total of 117 patients with and 42 patients without endometriosis were included. The pain distribution between these two patient groups appeared to differ in some peripheral anatomical structures. In the endometriosis patients, the pain was most frequently located in the rectouterine pouch.

Conclusions

In endometriosis patients, pain mapping to assess preoperative pain sensations relative to the anatomic location of endometriotic lesions is feasible. The pain provoked by vaginal examination is frequently perceived as median relative to the actual anatomic location of the endometriotic lesions. Several anatomic and neurophysiological factors may explain this phenomenon.     

Atorvastatin exerts anti-nociceptive activity and decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in a rat endometriosis model

Purpose

The purpose of this study was to examine the effects of atorvastatin in the treatment of experimental endometriosis.

Methods

Endometriosis was induced in 24 female rats. 4 weeks after the procedure dimensions of the foci were recorded. Rats were divided into three groups: in Group 1 (n = 8), a daily dose of 10 mg/kg atorvastatin was given for 14 days. In the second group (n = 8), a single dose of 1 mg/kg leuprolide acetate was injected intraperitoneally. The rats in Group 3 (n = 8) were received 1 mg/kg i.p. 0.9 % NaCl. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriotic foci were recorded. Biochemical, histopathological and immunohistochemical studies were performed and nociception was compared in groups.

Results

Atorvastatin treatment exhibited significant analgesic activity in hot plate model (P = 0.022). The serum hs-CRP and tumor necrosis TNF-α levels were similar between the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant decrease in both serum markers. The histological and immunohistochemical scores were also found to be markedly lower in Group 1 and Group 2 (P < 0.05).

Conclusion

Atorvastatin treatment may have a therapeutic potential in the treatment of endometriosis through its anti-inflammatory and anti-nociceptive properties.     

Effect of lesion location on endometriotic adhesion and angiogenesis in SCID mice

Objective

To evaluate the effects of lesion location on adhesion and angiogenesis of transplanted endometriotic lesions in SCID mice.

Methods

Three groups of female SCID mice included intraperitoneal (i.p.) (n = 12), subcutaneous (s.c.) (n = 12), and mock surgery (control) (n = 12). At 2 weeks after ovariectomy, the mice were transplanted with eutopic endometrium from endometriosis patients either subcutaneously or sutured within the peritoneal, or underwent mock surgery. After 4 weeks, the mice were sacrificed to evaluate the adhesion and volume changes of the implanted lesions. Furthermore, semiquantitative immunohistochemical staining was performed to analyze expression of MMP-2 and TIMP-2 as adhesion makers, and vWF, VEGF, and HIF-1α as angiogenesis markers.

Results

Adhesion occurred in 9 of 12 mice in the i.p. group, 3 of 12 mice in the s.c. group, and 3 of 12 mice in the control group. Fisher’s exact test showed that the difference of adhesion occurrence between i.p. and s.c. groups was statistically significant (p < 0.05). Graft volume changes were higher in the s.c. group than those in the i.p. group. MMP-2 expression was higher in the s.c. group than that in the i.p. group (p < 0.01). There was no significant difference of TIMP-2 expression between s.c. and i.p. groups. vWF, VEGF, and HIF-1α expression was significantly higher in the s.c. group than that in the i.p. group (p < 0.01).

Conclusions

Lesion location might be involved in the pathological changes of endometriosis. The intraperitoneal location is related to endometriotic adhesion, whereas the subcutaneous location is related to the infiltration of endometriotic lesions.     

Endometriosis in menopause: a single institution experience

Purpose

This study aims to present the clinical characteristics of a series of postmenopausal women with endometriosis and to evaluate the preferential location, extension and histopathological features of the lesions.

Methods

We retrospectively examined the clinical records of 72 postmenopausal women with endometriosis who underwent surgery between January 1998 and December 2010.

Results

The median age of patients at the time of surgery was 58.5?years. Eleven patients (15.3?%) had previous history of endometriosis and five patients had previously undergone surgery for this reason. Only two patients included in the study were using hormone replacement therapy at the time of surgery. The most frequent location of endometriotic lesions was the ovary and among patients with endometriomas, 35?% (20/57) had different grades of metaplasia, hyperplasia, atypia and endometrioid carcinoma arising in endometriosis. The proportions of epithelium, stroma and hemorrhage in endometriotic lesions were higher in patients with concomitant endometrial or ovarian cancer.

Conclusions

Endometriosis should be considered in the differential diagnosis of postmenopausal cystic lesions of the ovary. The administration of exogenous estrogen is not a prerequisite for the presence of endometriosis in postmenopausal women, and histological signs of functionally active lesions were also observed in the absence of exogenous hormone intake.     

Prophylactic adnexectomy along with vaginal hysterectomy for benign pathology

Objective

This study was designed to evaluate the safety and feasibility of prophylactic adnexectomy during vaginal hysterectomy for benign pathology.

Methods

We retrospectively reviewed medical records of all patients who underwent vaginal hysterectomy (VH) between 2008 and 2010. Clinical comparison of patients who underwent VH with adnexectomy (n?=?92) and VH only (n?=?686) was performed. Clinical characteristics (age, parity, body mass index, and previous pelvic surgery), surgical outcomes (uterine weight, operative time, estimated blood loss, pelvic adhesion, hemoglobin change and hospital stay) and intra- and postoperative complications (transfusion, bladder injury and fever) were evaluated.

Results

Clinical characteristics except for age (45.44?years for VH only vs. 47.15?years for VH with adnexectomy, P?=?0.007) were not different between the two groups. Similarly, surgical outcomes and complication rates were not different between the two groups.

Conclusion

Prophylactic bilateral adnexectomy can be performed safely during VH.     

Surgical outcomes of laparoscopic hysterectomy with concomitant endometriosis without bowel or bladder dissection: a cohort analysis to define a case-mix variable

Background

Pelvic endometriosis is often mentioned as one of the variables influencing surgical outcomes of laparoscopic hysterectomy (LH). However, its additional surgical risks have not been well established. The aim of this study was to analyze to what extent concomitant endometriosis influences surgical outcomes of LH and to determine if it should be considered as case-mix variable.

Results

A total of 2655 LH’s were analyzed, of which 397 (15.0%) with concomitant endometriosis. For blood loss and operative time, no measurable association was found for stages I (n?=?106) and II (n?=?103) endometriosis compared to LH without endometriosis. LH with stages III (n?=?93) and IV (n?=?95) endometriosis were associated with more intra-operative blood loss (p =?<?.001) and a prolonged operative time (p =?<?.001) compared to LH without endometriosis. No significant association was found between endometriosis (all stages) and complications (p?=?.62).

Conclusions

The findings of our study have provided numeric support for the influence of concomitant endometriosis on surgical outcomes of LH, without bowel or bladder dissection. Only stages III and IV were associated with a longer operative time and more blood loss and should thus be considered as case-mix variables in future quality measurement tools.

     

Expression and localization of CXCL16 and CXCR6 in ovarian endometriotic tissues

Purpose

Inflammatory mediators, including chemokines, may play crucial roles in the development of endometriosis. Therefore, we investigated the expression and localization of CXCL16 and its receptor, CXCR6, in ovarian endometriotic tissues. We also examined whether CXCL16 induces IL-8 production in endometriotic stromal cells.

Methods

We performed immunohistochemical and Western blotting analyses of in vivo and in vitro samples. IL-8 production was assayed using an ELISA.

Results

Both CXCL16 and CXCR6 were expressed by endometriotic epithelial cells and stromal cells, but not normal ovarian stroma. A Western blotting analysis using primary cultured endometriotic stromal cells showed a constant expression of CXCL16 and CXCR6 in the proliferative phase, secretory phase and during gonadotropin-releasing hormone agonist therapy. CXCL16 induced IL-8 production in several endometriotic stromal cells in vitro.

Conclusions

CXCL16 and CXCR6 might be involved in the pathophysiology of endometriosis through regulation of the inflammatory response.     

Efficacy of low-dose hCG in late follicular phase in controlled ovarian stimulation using GnRH agonist protocol

Objective

Safe, simple and cost-effective protocol is an important goal in ART cycles. The aim of this prospective study was whether administration of low-dose hCG in late follicular phase can be used clinically to replace gonadotropin administration in GnRH long protocol.

Materials and methods

122 patients who were candidates for ART enrolled the study and randomly divided into two groups. The control group (n?=?62) received standard long protocol and gonadotropin administration continued until the day of hCG injection (10,000?IU) for final follicular maturation. The study group (n?=?60) received GnRH long protocol and when at least ??6 follicles with mean diameter ??12?mm were observed in both ovaries, hMG was displaced by 200?IU per day of hCG until final follicular maturation.

Results

There were no significant differences in age, basal FSH, infertility duration and infertility etiology between two groups. There were no statistically significant differences between two groups regarding chemical pregnancy, clinical pregnancy, ongoing pregnancy, and abortion per cycle (50, 40, 40, and 20?% in study group vs. 45.2, 35.5, 35.5, and 21.4?% in control group, respectively). Mean dose of used gonadotropins was significantly higher in control group than that in the study group (2,524?±?893?IU in control group and 1,439?±?433?IU in study group) (p?=?0.000).

Conclusion

According to our data, we recommend the use of low-dose hCG in GnRH long protocol because of lower doses of used gonadotropins.     

Estimating the impact of pelvic immaturity and young maternal age on fetal malposition

Objective

Fetal malposition, specifically occiput posterior and transverse (OP/OT), is associated with higher intra-partum morbidity. We tested the hypothesis that young maternal age and pelvic immaturity are risk factors for fetal malposition.

Methods

In a cohort study of all nulliparous teen (??18?years) deliveries over a 4-year period at one institution, fetal head position at time of delivery was collected and correlated with maternal characteristics and outcome data. Using Risser staging observations, pelvic maturity age was set at 16, and accordingly, the women were divided into two groups (younger vs. older teens). Analysis was performed using Fisher??s exact, student t test, and logistic regression modeling.

Results

Older teen mothers (16?C18?years, n?=?609) had higher rates of malposition (22 vs. 12?%, p?=?0.02) when compared with younger teens (??15?years, n?=?98). Among all women with a malpositioned fetus, older teens had a higher body mass index (BMI: 32.6?±?6.7 vs. 28.5?±?3.5, p?=?0.04) and subsequent need for cesarean delivery (69 vs. 33?%, p?=?0.02) when compared with their younger counterparts. Although younger teens were more successful in having a vaginal delivery (67?%) with an OP/OT position, it was at the expense of a 25?% rate of severe perineal laceration (third/fourth degree).

Conclusion

Obesity, and not young maternal age or pelvic immaturity, is associated with fetal malposition. The direct association with increasing pre-pregnancy BMI and the long-term impacts of the high rates of cesarean delivery in this young population underscores the need for more public health focus.     

Expression pattern of PAX2 in hyperplastic and malignant endometrium

Background

PAX2 is a member of paired box gene family and expressed during development of urogenital system. This study aimed to evaluate PAX2 expression pattern in hyperplastic and malignant endometrial tissues in comparison to non-pathological endometrial changes and to investigate the presence of any correlation between the PAX2 expression and tumor behavior.

Methods

The study was performed on the archival material of 121 endometrial tissues including complex hyperplasia (n?=?18), complex atypical hyperplasia (n?=?20), and endometrioid type adenocarcinoma (n?=?47) as study groups, and proliferative endometrium (n?=?21) and atrophic endometrium (n?=?16) as control groups. One representative block for each case was selected for immunohistochemical evaluation. Sections with 4??m thickness were cut from the blocks and incubated with PAX2 rabbit anti-human polyclonal antibody.

Results

PAX2 nuclear staining was detected in all of the endometrial tissues. The mean percentages of PAX2 staining cells were 80.8, 96.7, 88.6, 92.7, and 99.2% with proliferative endometrium, atrophic endometrium, complex hyperplasia, complex atypical hyperplasia, and adenocarcinoma, respectively (Kruskal?CWallis; P?Conclusions PAX2 is expressed in hyperplastic and malignant endometrium as well as proliferative and atrophic endometrium. As the neoplastic lesion progresses from a premalignant state to endometrial cancer, PAX2 expression increases. These findings suggest that PAX2 may contribute to the development of endometrial cancer.     

p53 codon 72 polymorphism and endometriosis: a meta-analysis

Background

p53 tumour suppressor gene Arg72Pro polymorphism has been associated with endometriosis. However, the current available data were inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and endometriosis.

Methods

Electronic screening of PubMed library was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association.

Results

Six published studies, including 749 endometriosis and 857 controls were identified. The overall results suggested that the variant genotypes were not associated with the endometriosis risk (Pro/Pro?+?Arg/Pro vs. Arg/Arg: OR?=?1.552, 95% CI 0.916–2.632, p?=?0.103). In the stratified analysis, individuals carried the Pro allele in a dominant model had increased risk of endometriosis (OR?=?2.595, 95% CI 1.005–6.702, p?=?0.049) in Asian subjects. The symmetric funnel plot, the Egger’s test (p?=?0.602), and the Begg’s test (p?=?0.167) were all suggestive of the lack of publication bias. However, the association was not significant between this polymorphism and endometriosis in Caucasian (OR?=?1.005, 95% CI 0.755–1.337, p?=?0.972).

Conclusion

This meta-analysis suggests that p53 codon 72 Pro/Pro?+?Arg/Pro genotypes are associated with increased risk of endometriosis in Asian. To validate the association between p53 codon 72 polymorphism and endometriosis, further studies with larger participants worldwide are needed.     

Does obesity complicate perioperative course in patients undergoing abdominal hysterectomy?

Aim

Obesity is traditionally believed to increase the incidence of perioperative complications in abdominal surgery. Recently this paradigm has been challenged mainly by observations from surgical specialties other than gynecology. Our aim was to assess the impact of obesity on perioperative course in women undergoing total abdominal hysterectomy.

Methods

We analyzed medical charts of 126 patients who underwent total abdominal hysterectomy for benign gynecological conditions through a low transverse incision in the Department of Obstetrics and Gynecology of the Provincial Specialist Hospital in Czestochowa, Poland. Perioperative course was compared between obese [n?=?55; body mass index (BMI)????30?kg/m²: mean 32.6?±?3.2?kg/m²] and non-obese patients (n?=?71; mean BMI 24.3?±?3?kg/m²).

Results

The mean operative time in obese women was significantly prolonged (112?±?32 vs. 100?±?31?min, P?=?0.036). However, complication rates and other perioperative outcomes were comparable between the groups.

Conclusion

In our study, mild obesity does not significantly affect the perioperative course in women undergoing total abdominal hysterectomy.     

Coexisting ovarian malignancy in patients with clinical stage I endometrial carcinoma

Aim

To evaluate the feasibility of ovarian preservation at the time of operation in patients with clinical stage I endometrial carcinoma.

Materials and methods

The data of 499 consecutive patients with clinical stage 1 endometrial cancer operated between January 2001 and December 2011 were retrospectively reviewed. Clinical and pathologic information and the intraoperative inspection findings of ovaries were evaluated to find the factors associated with the coexisting ovarian malignancy.

Results

The mean age of patients was 56.8?±?9.8?years. Coexisting ovarian tumors were detected in 38 patients (7.6?%), and 28 (5.6?%) of them were malignant (12 metastatic and 16 synchronous primaries). Most of the patients were postmenopausal (n?=?371, 74.3?%) and 60 (12?%) of the patients were at the age of 45?years or less. Coexisting malignancy was detected in 9?% (n?=?11) of the premenopausal patients and in 5?% (n?=?3) of the patients aged 45?years or less. Multivariate analysis revealed that serosal invasion, tubal involvement, and positive abdominal cytology were independent risk factors for coexisting ovarian malignancy. The sensitivity, specificity, positive predictive value and negative predictive value of the intraoperative examination for the diagnosis of benign/normal ovary was 99.6, 78.8, 98.5 and 92.9?%, respectively.

Conclusion

The incidence of coexisting ovarian malignancy in clinical stage I endometrial carcinoma is low. Although occult metastasis cannot be excluded at all, careful intraoperative inspection of ovaries seems valuable for the prediction of co-existing ovarian malignancy.     

Sialic acid levels in the blood in pregnant women with impaired glucose tolerance test

Purpose

Gestational diabetes (GDM) is a metabolic disease characterized by the impairment of glucose tolerance during pregnancy. Sialic acid (SA) is a component of glycolipid and glycoproteins found in hormone and enzymes in serum and tissues and high serum SA levels are observed in diabetic patients.

Methods

Serum SA levels were investigated in three groups, namely 61 normal pregnant women with normal 50 gr glucose loading test (group 1: gr 1), 36 patients with high 50 gr test values and normal 100 gr test (group 2: gr 2: group with impaired glucose tolerance test, IGT), and 8 patients with diagnosis of GDM (group 3:gr 3).

Results

According to Kruskal–Wallis test, significant difference was observed in SA levels between gr1 and gr2–gr3 (p?=?0.001). Difference was observed between groups with respect to age (p?p?=?0.001), BMI (p?=?0.001), and diabetes history in the family (p?=?0.001) (Table?1).

Is tumor size the limiting factor in a laparoscopic management for large ovarian cysts?

Purpose

To assess the feasibility and short-term surgical outcome of laparoscopic surgery among women with large ovarian cysts.

Methods

We retrospectively evaluated consecutive 81 patients who received laparoscopic management for ovarian cysts with diameter?≥?10?cm and without radiologic features suggestive of malignancy, from March 2008 to September 2011.

Results

Laparoscopic surgery was successful in 77 (95.1?%) of the total patients. The mean (range) operative time, estimated blood loss (EBL) and hospital stay were 107.6 (55–250?min), 226.9 (10–1300?mL) and 6.1 (4–15?days), respectively. The surgical procedures performed included salpingooophorectomy (SO) (n?=?44), ovarian cystectomy (OC) (n?=?22), adhesiolysis (n?=?1), salpingectomy (n?=?2) and total laparoscopic hysterectomy (TLH) with SO (n?=?8). Conversion to laparotomy occurred with four patients. One patient had postoperative bleeding and one had minor complications associated with wound oozing at the umbilical port site. Histopathological examination revealed benign tumors in 76 patients (93.8?%), borderline ovarian tumor in three patients (3.7?%) and invasive epithelial ovarian cancer in two patients (2.5?%). Clinicopathological variables according to tumor size were not statistically different. Complications did not appear in any patients during the follow-up period.

Conclusion

With proper patient selection, laparoscopy is a feasible and safe treatment for women with large ovarian cysts and tumor size did not have effect on laparoscopic management. However, surgeons should carefully consider the potential risk of malignancy in such patients.     

Massive hemothorax due to diaphragmatic endometriosis after a laparoscopic cystectomy of an ovarian endometrioma in a patient without a history of thoracic endometriosis

Background

Severe hemothorax is a rare complication after laparoscopic surgery for endometriosis, and the causes and proper management are not well understood.

Case

We report here the extremely rare case with massive hemothorax after laparoscopic surgery for ovarian endometrioma. A 40-year-old woman, gravida 1, para 1, underwent laparoscopic cystectomy of ovarian endometrioma. On postoperative day 2, she had progressive anemia (Hb 5.3) as well as dyspnea. A chest X-ray and computed tomography showed massive fluid collection in the right thoracic cavity, suggestive of intrapleural bleeding.

Treatment

Thoracoscopic operation was performed and a total of 930?ml of blood retention in the right thoracic cavity was found. Scattered small endometriotic lesions were present on the pleural surface of the right diaphragm; pulsatile active bleeding was confirmed from one of these. Furthermore, two endometriotic lesions had perforated into the intraperitoneal cavity. The diaphragm containing bleeding spots was thoracoscopically resected and sutured. After thoracoscopic surgery, the dyspnea and anemia resolved. On postoperative day 5, the patient left the hospital.

Conclusion

The present report reminds us of the importance of paying special attention to postoperative-thoracic complications caused by diaphragmatic endometriosis if the patient shows respiratory symptoms.     

Estimating risk factors for development of preeclampsia in teen mothers

Purpose

Our objective was to identify potentially modifiable risk factors for preeclampsia in a contemporary American teen population.

Methods

We conducted a retrospective cohort analysis of all teenage deliveries (≤18?years old) at one institution over a 4-year-period. All cases of preeclampsia were identified using the National Working Group for Hypertension in Pregnancy diagnostic criteria and compared to normotensive teenage mothers.

Results

Of the 730 included teen deliveries, 65 (8.9?%) women developed preeclampsia and demonstrated a higher prepregnancy body mass index when compared with controls (32.9?±?8.4 vs. 30.3?±?6.1?kg/m², p?=?0.002). Maternal obesity (body mass index ≥30?kg/m², RR 1.6, 95?% CI 1.0–2.8) and gestational weight gain above the Institute of Medicine recommended levels (RR 2.6, 95?% CI 1.5–4.4) were associated with higher risk for development of preeclampsia. When evaluating by severity or onset of disease, excessive weight gain in pregnancy was the strongest risk factor for mild (n?=?58) or late onset (n?=?54) preeclampsia (RR 2.5, 95?% CI 1.4–3.4).

Conclusions

Maternal obesity and excessive gestational weight gain place the gravid teen at increased risk for preeclampsia. The modifiable nature of these risk factors permits the possibility of intervention and prevention.