Effect of clindamycin treatment on vaginal inflammatory markers in pregnant women with bacterial vaginosis and a positive fetal fibronectin test

Objective

To compare the levels of interleukin (IL)-1β, IL-6, and matrix metalloproteinase (MMP)-8 in the vaginal secretions of pregnant women with a positive fetal fibronectin (fFN) test result with or without asymptomatic bacterial vaginosis (BV) before and after treatment with oral clindamycin.

Methods

A prospective cohort study was conducted among 43 pregnant women with a positive fFN test result. All patients were treated with clindamycin, and the pre- and post-treatment levels of IL-1β, IL-6, and MMP-8 were compared.

Results

Before treatment, levels of IL-1β and MMP-8 were significantly higher in women with BV compared with women without BV (P < 0.05). Vaginal levels of IL-1β and IL-6, but not MMP-8, decreased after treatment in pregnant women with BV.

Conclusions

The inability of clindamycin to decrease MMP-8 vaginal levels may explain why it is ineffective in reducing preterm birth in pregnant women with positive fFN and BV.     

Changes of nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) in human myometrium before and during term labor

Objective

To investigate the changes of nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) in human term myometrium before and during term labor.

Study design

Myometrium was obtained from women undergoing cesarean delivery at term before (n = 16) and after labor (n = 12). Immunostaining of NF-κB subunits (p65/p50) and Western blot analysis of NF-κB subunits, MMP-9 and COX-2 proteins were compared. Human term myocyte cultures were stimulated with IL-1β. Activation of NF-κB was assessed by evaluating changes in the inhibitory protein IκB; regulation of COX-2 and MMP-9 levels was studied using Western blot analysis and gelatin zymography.

Results

In contrast to a significant increase in the level of COX-2 and MMP-9 proteins, p65 and p50 decreased significantly in the after-labor group compared to the before-labor group. After treatment with IL-1β, IκB was degraded by almost 90% within 5 min and became undetectable by 15 min. IL-1β stimulation increased the levels of COX-2 protein and the gelatinolytic activities of MMP-9, both of which were inhibited by NF-κB inhibitors.

Conclusions

Human term labor is associated with changes in NF-κB and increased expression of COX-2 and MMP-9 in the myometrium. NF-κB pathway activation and subsequent increments of COX-2 and MMP-9 were observed in human term myocyte cultures.     

Comparison of Burch colposuspension and transobturator tape when combined with abdominal sacrocolpopexy

Objective

To compare the treatment outcomes of Burch colposuspension and transobturator tape (TOT) when each is combined with abdominal sacrocolpopexy (ASC) to treat stress urinary incontinence (SUI) with pelvic organ prolapse (POP).

Methods

Consecutive cases of Burch colposuspension and TOT combined with ASC were retrospectively reviewed. Patients with SUI and POP beyond stage III—according to the POP-quantification system—were included.

Results

Mean hospital stay was longer in the Burch group (n = 49) than in the TOT group (n = 60) (11.3 vs 7.8 days; P < 0.001), as was operation time (202.7 vs 170.1 minutes; P < 0.001); furthermore, there were higher rates of urinary retention (53.1% vs 11.7%; P < 0.001), de novo urgency (18.4% vs 3.3%; P = 0.01), and recurrent SUI (18.4% vs 1.7%; P = 0.003) in the Burch group. The cure rate was significantly higher in the TOT group than in the Burch group (98.3% vs 69.7%; P < 0.001).

Conclusion

The use of TOT with ASC resulted in higher cure rates and better functional outcomes than did Burch colposuspension with ASC.     

Completion surgery or not after concurrent chemoradiotherapy for locally advanced cervical cancer?

Objectives

The role of additional surgery in patients responding to radiation and chemotherapy for locally advanced cervical cancer is controversial. The goal of this study was to compare disease-free survival (DFS) and overall survival (OS) of two groups of patients, with or without additional surgery.

Study design

One hundred and eleven patients with advanced cervical cancer who responded to chemoradiotherapy followed by brachytherapy were included in a retrospective, multicenter series.

Results

Of the patients who had completion surgery (Group 1), 22.4% (15/67) had recurrence compared with 36.4% (16/44) of those who did not have surgery (Group 2). The difference is statistically significant (p = 0.01). The relative risk of disease progression or death was 0.41 (95% confidence interval 0.20-0.85) (p = 0.01) in favor of completion surgery. After multivariate analysis, only age, pathology and initial tumor size remained significant (respectively p = 0.003, p = 0.001 and p = 0.03). Among the locations of recurrence in Group 1, 46.7% were pelvic (7/15) compared with 56.2% in Group 2 (9/16). In Group 1, 16.4% (11/67) of the patients died of disease compared to 20.4% (9/44) in Group 2. Of these, 45.4% (5/11) in Group 1 died after pelvic recurrence as compared to 77.8% (7/9) in Group 2.

Conclusion

Completion surgery does not improve OS but may improve DFS. There is no consensus regarding completion surgery in advanced cervical cancer with a good response to the standard treatment but we think it is safer to propose it.     

Timing of fertility preservation procedures in a cohort of female patients with cancer

Objective

Comparison of time intervals from diagnosis to chemotherapy between patients opting for embryo cryopreservation or ovarian tissue cryopreservation.

Study design

Retrospective analysis.

Setting

University hospital in the Netherlands.

Patients and methods

Thirty-five female patients undergoing fertility preservation procedures before treatment with chemotherapy for cancer. Embryo cryopreservation was performed in 12 patients and ovarian tissue cryopreservation in 23 patients. We investigated differences in time intervals (from diagnosis to start of chemotherapy) between patients opting for embryo cryopreservation and patients opting for ovarian tissue cryopreservation. We calculated time intervals between the moment of diagnosis, the moment of referral, the moment of consultation, the moment of finishing of the fertility preservation procedure and the start of chemotherapy.

Results

The median time between diagnosis and referral (median = 18 days) and between referral and consultation (median = 5 days) was comparable in both groups. A significant difference was found between ovarian tissue cryopreservation and embryo cryopreservation for the time interval between consultation and cryopreservation (p = 0.001). Ovarian tissue cryopreservation was completed for half of the patients within 6 days after consultation with the gynecologist, and the hormonal stimulation for embryo cryopreservation was completed for all patients within four weeks (median = 18 days), with a median of 11 days of hormonal stimulation. A significant difference was found between ovarian tissue cryopreservation and embryo cryopreservation in the time interval between fertility preservation and start of chemotherapy (median = 7 vs 19 days, p = 0.019). In sum, the total duration between diagnosis and chemotherapy was significantly shorter for ovarian tissue cryopreservation patients than for embryo cryopreservation patients (median = 47 vs 69 days, p = 0.042).

Conclusion

Embryo cryopreservation can be performed within the standard timeframe of cancer care in patients with breast cancer receiving adjuvant chemotherapy, but if delay of the start of chemotherapy is harmful, ovarian tissue cryopreservation can be done within one week.     

Arterial stiffness, central hemodynamics and wave reflection in normal pregnancy and control nonpregnant women

Objectives

Pregnancy is accompanied by different physiological adaptations in the cardiovascular system. However, information on central blood pressures, wave reflection, arterial stiffness in uncomplicated pregnancy compared with nonpregnant women is limited.

Study design

Forty-six women (mean age 28 years) in the third trimester of pregnancy and 45 healthy age- and height-matched controls were evaluated. Arterial stiffness, central hemodynamics and wave reflection was assessed with the use of digital volume pulse analysis and pulse wave analysis.

Results

In comparison with nonpregnant participants, pregnant women had significantly lower mean (p = 0.04) and central systolic (p = 0.02) blood pressure, central pulse pressure (p = 0.02), augmentation index (p = 0.02) and augmentation pressure (p = 0.002), whereas their pulse pressure amplification was significantly higher (p = 0.001). Similarly, arterial stiffness index was higher in pregnant women than in healthy nonpregnant controls (p = 0.006). This index was correlated significantly with central augmentation index and augmentation pressure (r = 0.5, p = 0.0005 and r = 0.52, p = 0.0002, respectively) but only in nonpregnant women.

Conclusions

Healthy pregnancy is associated with increased pulse pressure amplification as well as diminished wave reflection, which results in lower central augmentation index and augmentation pressure. Women in the third trimester of pregnancy have slightly higher arterial stiffness in comparison with healthy nonpregnant, age- and height-matched controls. The increased value of measures of arterial stiffness might be secondary to a known physiological increase of cardiac output and the amount of circulating blood.     

Short-range clinical, dynamic magnetic resonance imaging and P-QOL questionnaire results after mesh repair in female pelvic organ prolapse

Objective

To evaluate clinical, quality-of-life (QoL) and dynamic magnetic resonance imaging (dMRI) results in patients with pelvic organ prolapse (POP) preoperatively, and 4 and 12 weeks after anterior and/or posterior mesh repair.

Study design

Thirty-six patients (mean age 65 years) with symptomatic pelvic floor descent underwent mesh repair. The prolapse was quantified using the POP-Q system. Before surgery as well as 4 and 12 weeks after surgery, the pelvic organ positions were measured on dynamic magnetic resonance imaging during Valsalva manoeuvre in relation to the pubococcygeal and mid-pubic lines to assess surgery outcome. Patients also completed the P-QOL questionnaire to evaluate subjective changes at each visit.

Results

Four and 12 weeks after surgery patients showed improvement of the POP on clinical examination and on dynamic MRI. The latter demonstrated high significance (p < 0.001) especially in bladder and vaginal cuff/cervix positions during maximal straining. All quality-of-life domains and some symptom questions of the P-QOL questionnaire significantly improved (p < 0.05) 12 weeks after surgery.

Conclusion

Significant anatomical and quality-of-life improvement was demonstrated after anterior and/or posterior mesh repair for POP using dynamic MRI and the P-QOL questionnaire.     

Expression of matrix metalloproteinase-2 and tissue inhibitors of metalloproteinase-1 (TIMP-1, TIMP-2 and TIMP-3) in women with uterine prolapse but without urinary incontinence

Objective

To investigate the activities of matrix metalloproteinase-2 (MMP-2) and its inhibitors, tissue inhibitor of metalloproteinase-1, -2 and -3 (TIMP-1, TIMP-2 and TIMP-3), in the pelvic support and nonsupport tissue of women with uterine prolapse but without urinary incontinence.

Study design

Paired samples of uterosacral ligament and cervical tissue were obtained from 11 postmenopausal and 8 premenopausal women with severe uterine prolapse. Nine premenopausal women without prolapse were selected as normal controls. Immunoreactivity of MMP-2 and TIMPs was demonstrated by immunohistochemistry. Steady state of MMP-2 as well as TIMPs messenger RNA (mRNA) expression was analyzed by polymerase chain reaction (PCR) with quantitative expression determined by multiplex PCR.

Results

A significantly higher expression of MMP-2 mRNA and lower expression of TIMP-2 mRNA were found in uterosacral ligament in uterine prolapse women compared to controls. In the cervical tissue, however, the MMP-2 and TIMPs mRNA expression was comparable between prolapse and control groups. With regard to menopausal status, there was no significant difference in MMP-2 and TIMPs mRNA expression between premenopausal and postmenopausal women with uterine prolapse.

Conclusions

An increase in MMP-2 mRNA and a decrease in TIMP-2 mRNA expression in uterosacral ligament are related to uterine prolapse in women without urinary incontinence.     

Maternal serum protein S forms in pregnancies complicated by intrauterine growth restriction

Objectives

The clinical relevance of protein S deficiency in pregnant women remains controversial. Major debate exists regarding which parameter (total protein S antigen, free protein S antigen or functional protein S) should be evaluated in order to define protein S deficiency. The present study aimed to identify which of these parameters correlate with intrauterine growth restriction (IUGR).

Study design

A retrospective case-control study of women with IUGR (n = 27) and healthy controls (n = 123) in the third trimester of pregnancy.

Results

The maternal serum of women in the IUGR group had significantly lower levels of functional and free protein S compared with the control group: 54.07 ± 24.72% vs 65.20 ± 17.95% (p < 0.005) and 42.88 ± 11.01% vs 56.64 ± 13.30% (p < 0.0001), respectively. No significant correlation was found between total protein S and IUGR.

Conclusions

Levels of functional and free protein S are correlated with IUGR.     

Immunoexpression of B7-H3 in endometrial cancer: relation to tumor T-cell infiltration and prognosis

Objective

B7-H3, a member of the B7 family of immune regulatory ligands regulates T cell-mediated peripheral immune response. The purpose of this study was to correlate the expression of B7-H3 and number of lymphocytes in patients with endometrial cancer.

Material and methods

A total of 107 patients with primary endometrial carcinoma (type I/endometrioid, n = 81; type II, n = 18) and endometrial hyperplasia (n = 8) were investigated. Expression of B7-H3 in endometrial hyperplasia, endometrial carcinoma, and the endothelium of tumor-associated vasculature was assessed using immunohistochemistry from paraffin-embedded tissue blocks. Detection of CD8-positive tumor-infiltrating lymphocytes (TIL) and CD8-positive tumor-associated lymphocytes (TAL) was correlated with the expression of B7-H3.

Results

Patients with high grade tumors and patients with type II carcinomas expressed significantly more B7-H3 than low grade and endometrioid tumors (p = < 0.0001 and p = 0.0001, respectively). The expression of B7-H3 in the endothelium of identified vasculature in the tumor specimens showed similar results with strong relation to high grade tumors (p = 0.001) and type II carcinomas (p = 0.004). We found a significant correlation between B7-H3 expression on cancer cells and tumor T-cell infiltration (TIL) (p = 0.017). In a univariate survival analysis, overexpression of B7-H3 in tumor cells was associated with shortened overall survival (p = 0.005).

Conclusions

B7-H3 is overexpressed on cancer cells and in the endothelium of tumor-associated vasculature in high grade tumors (G3) and type II carcinomas. B7-H3 expression on cancer cells is correlated with the number of T cells infiltrating the tumor. Endometrium tumor development and progression may be associated with downregulation of T-cell-mediated antitumor immunity through B7-H3.     

Circulating ghrelin levels and the polycystic ovary syndrome: correlation with the clinical, hormonal and metabolic features

Objectives

Dysregulation of ghrelin levels may lead to physiological problems including obesity and polycystic ovary syndrome (PCOS). The aim of the study was to compare ghrelin levels in women with and without PCOS.

Study design

Serum ghrelin levels (pre- and post-prandial) were compared between 30 Saudi women suffering from PCOS and 30 healthy controls. The relationship between circulating ghrelin levels and other hormones was investigated. Anthropometric measurements were made for all subjects. Biochemical and hormonal investigations included plasma glucose, insulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17β-estradiol (E2), progesterone, testosterone and sex hormone binding globulin (SHGB), and serum ghrelin levels. The data were statistically analyzed using independent T-test and ANOVA. Correlation studies were performed between ghrelin levels and other variables.

Results

No differences were observed in the levels of ghrelin during fasting and the postprandial period in the PCOS (p = 0.487) and control groups (p = 0.378). A significant inverse correlation was observed in ghrelin levels (fasting and postprandial) levels and BMI (PCOS: r = −0.529; p = 0.009, controls: r = −0.670; p = 0.005); PCOS: r = −0.421; p = 0.007, controls: r = −0.491; p = 0.004 respectively). No correlations between ghrelin levels and other parameters were observed.

Conclusion

The findings of the study suggest that circulating plasma ghrelin levels were found to be normal and were inversely related to BMI in women with PCOS. No relationship between circulating ghrelin levels and the abnormal hormonal pattern of the PCOS were observed.     

A 60-month non-comparative study on bleeding profiles with the levonorgestrel intrauterine system from the late transition period to estrogen supplemented menopause

Objective

To investigates the effect of sphingosine-1-phosphate (S1P) supplementation on follicular integrity and apoptosis in vitrified-warmed mouse ovarian grafts.

Study design

Ovaries from 4-week-aged ICR mice were vitrified using a vitrification solution with or without 2 μM S1P. After warming, follicular normality was assessed by histological analysis and TUNEL assay. A part of ovaries vitrified with or without 2 μM S1P was transplanted, and 2 weeks later, gross and microscopic follicular morphology was assessed.

Results

During vitrification and warming, inclusion of 2 μM S1P into the vitrification solution significantly raised the rate of morphologically intact follicles compared to controls (36.6% vs. 30.8%, p = 0.047). This protective effect was profound especially in primordial follicles (45.5% vs. 34.6%, p = 0.034). After transplantation of vitrified-warmed ovaries, the morphological integrity of primordial follicles was superior in the S1P-treated group (55.0% vs. 39.4%, p = 0.035). The rates of non-apoptotic follicles (TUNEL-negative) were similar in the two groups in either non-transplanted or transplanted ovaries.

Conclusion

Inclusion of S1P in the vitrification solution during transplantation of vitrified-warmed ovary had a beneficial effect on preservation of the primordial follicular pool.     

Disparities in treatment and survival between African American and White women with vaginal cancer

Objective

The study aims to compare the difference in treatment and survival between White (W) and African American (AA) patients with vaginal cancer (VC).

Methods

Patients with a diagnosis of invasive vaginal cancer were identified from Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2007 and were divided into White (W) and African American (AA) subgroups. Student's t test, Kaplan-Meier survival methods, and Cox regression proportional hazards were performed.

Results

A total of 2675 patients met the inclusion criteria, with histologic distribution of squamous cell carcinoma (SCC; 2190, 82%) and adenocarcinoma (AC; 485, 18%); 2294 (85.8%) were W, and 381 (14.2%) were AA. Median age was 69 for W and 65 for AA (p < 0.001). SCC and AC were equally distributed between W and AA. Advanced stage disease (FIGO III and IV) was more prominent in AA compared with W (30.4% vs. 23.1%, p = 0.019). Radiation therapy was utilized equally in both racial groups; however, surgical treatment alone or combined with radiation therapy was more frequent in W compared with AA (27.7% vs. 17.5%, p < 0.001).The 5-year survival was 45% in W and 38.6% in AA (p = 0.008). In multivariate analysis, AA had significantly poorer survival compared with Whites when controlling for age, histology, stage, grade and treatment modality (HR 1.2, 95% CI 1.1-1.4, p = 0.007).

Conclusions

African American women with vaginal cancer were more likely to present, at a younger age, advanced stage and less likely to receive surgical treatment. Our data suggests that AA race is an independent predictor of poor survival in vaginal cancer.     

Withdrawal from familial ovarian cancer screening for surgery: findings from a psychological evaluation study (PsyFOCS)

Objective

A prospective psychological evaluation study of familial ovarian cancer screening (PsyFOCS) is underway in partnership with the UK Familial Ovarian Cancer Screening Study (UK FOCSS Phase 2). One of the aims of PsyFOCS is to examine factors associated with withdrawal from the UK FOCSS prior to the onset of 4-monthly screening.

Method

1999 of 3224 women completed a baseline questionnaire. 110 (5.5%) women withdrew from screening prior to their first routine Phase 2 screen, of which 73 (66.4% of withdrawals) had withdrawn because they had undergone removal of their ovaries and fallopian tubes (withdrawn group). The comparison group consisted of 1868 women who remained on screening. The baseline questionnaire included measures of cancer-specific distress, anxiety, depression and illness perceptions.

Results

Logistic regression analysis indicated that having had prior annual (Phase 1) screening (OR = 13.34, p < .01), past experience of further tests (OR = 2.37, p < .01) and greater cancer-specific distress (OR = 1.38, p < .01) were associated with withdrawal for surgery. Belief in ageing as a cause of ovarian cancer was also associated with withdrawal (OR = 1.32, p = .05).

Conclusion

These cross-sectional data suggest that withdrawal from familial ovarian cancer screening may be influenced by both clinical and psychological factors. These may reflect women's experience of the drawbacks of screening and increased concern about ovarian cancer risk, as well as having opportunities to consider surgery as an alternative risk management strategy whilst using screening as an interim measure.     

The value of hysteroscopy in diagnosis of chronic endometritis in patients with unexplained recurrent spontaneous abortion

Objectives

We performed this study in order to investigate the role of chronic endometritis (CE) in unexplained recurrent spontaneous abortion (RSA) and to determine the correlation between hysteroscopic and histologic findings of CE in patients with unexplained RSA. We also tried to find out the relation between CE and primary vs. secondary RSA.

Study design

One hundred and forty-two consecutive patients with unexplained RSA and 154 fertile women were enrolled in this study. All the patients and controls underwent hysteroscopy and, at the same time, endometrial biopsy. CE was suspected when hysteroscopy revealed signs of focal or diffuse endometrial hyperemia or endometrial endopolyps (less than 1 mm in size). Histopathologic diagnosis of CE was based on superficial stromal edema, increased stromal density, and pleomorphic stromal inflammatory infiltrate dominated by lymphocytes and plasma cells. Results were compared between cases and controls as well as those with primary (n = 61) and secondary (n = 81) RSA.

Results

Patients with RSA had a significantly higher incidence of CE both hysteroscopically (67.6% vs. 27.3%; p < 0.0001) and pathologically (42.9% vs. 18.2%; p < 0.0001). The sensitivity, specificity, positive predictive value and negative predictive value of hysteroscopy in the diagnosis of CE were found to be 98.4%, 56.23%, 63.5% and 97.82% respectively. Patients with secondary RSA had a higher prevalence of CE both pathologically (83.9% vs. 45.9%; p < 0.0001) and hysteroscopically (58.1% vs. 24.6%; p < 0.0001).

Conclusion

CE is associated with unexplained RSA. Hysteroscopy, with high sensitivity and acceptable specificity, is suitable for the diagnosis of CE in those with unexplained RSA. CE should be taken into consideration in those with secondary unexplained RSA.     

Is older age a poor prognostic factor in stage I and II endometrioid endometrial adenocarcinoma?

Objective

Prior studies have shown that age ≥ 70 years is associated with more aggressive non-endometrioid histology and worse survival in endometrial cancer. The purpose of this study is to assess if age is an independent poor prognostic factor in endometrioid histologies.

Methods

Under an IRB-approved protocol, we identified patients with surgical stage I to II endometrioid endometrial adenocarcinoma from 1995 to 2008 at two institutions. Patients were divided into two groups based on age at diagnosis: Group A (age 50-69 years) and Group B (age ≥ 70 years). All patients underwent hysterectomy, bilateral salpingoophorectomy, +/−pelvic/aortic lymphadenectomy and adjuvant therapy. Prognostic factors were evaluated by univariate and multivariate analyses.

Results

We identified 338 patients with stage IA to IIB endometrioid endometrial adenocarcinoma. The median age in Group A was 59 years (range 50-69) and Group B was 75 years (range 70-92). Patients in Group B were more likely to have hypertension (51% vs. 68%, p = 0.006) and coronary artery disease (9% vs. 18%, p = 0.03). There were no differences in progression-free or disease-specific survival, however, Group B had a worse overall survival (OS) (50.1 vs. 62.6 months, p = 0.03). On univariate analysis, age (p = 0.04), grade (p = 0.006), and coronary artery disease (p = 0.01) were associated with worse OS. After adjusting for grade and coronary artery disease, age was no longer a significant variable for OS (p = 0.17).

Conclusions

After adjusting for other poor prognostic factors, age ≥ 70 years alone may not be a significant variable affecting overall survival in patients with early stage endometrioid endometrial adenocarcinoma.     

DNA ploidy, nuclear size, proliferation index and DNA-hypomethylation in ovarian cancer

Objective

The present study was undertaken to analyze the impact of epigenetic alterations with a main focus on nuclear area, aneuploidy, hyperploidy, and proliferation in 70 ovarian cancer specimens.

Methods

Morphometric changes and somatic chromosomal ploidy status were assessed by Feulgen spectrophotometry. DNA-hypomethylation of LINE1 repeats was analyzed by means of MethyLight PCR, and methylation levels of satellite 2 (Sat2) and satellite alpha (Satα) DNA sequences in chromosome 1 were measured by Southern blot analysis. These parameters were analyzed with regard to correlations as well as to recurrence and survival.

Results

We identified a significant association between LINE1 DNA-hypomethylation and patient age (p = 0.029). Furthermore, LINE1 DNA-hypomethylation was positively correlated with the nuclear area (r = 0.47; p < 0.001) and the proliferation index (r = 0.36; p < 0.001). Univariate survival analysis showed that the nuclear area and LINE1 DNA-hypomethylation were prognostic factors for overall (p = 0.015 and  = 0.006, respectively) and progression-free survival (p = 0.020 and p = 0.001 respectively), the percentage of aneuploidy only for overall survival (p = 0.031). Subgroup survival analyses revealed that the prognostic value of these factors is strictly confined to mucinous cancers. In serous cancers no prognostic value could be pointed out for any analyzed parameter. Multivariate analysis of the entire cohort showed that the percentage of hyperploidy was an independent prognostic parameter for overall survival (p = 0.003) and LINE1 DNA-hypomethylation for progression-free survival (p = 0.03). In mucinous cancers nuclear area and LINE1 DNA-hypomethylation were found to be independent predictors of progression-free and overall survival.

Conclusions

In this study we identified the correlations between early cancer-associated genome DNA-hypomethylation, nuclear morphometric changes, somatic chromosomal ploidy status and the proliferation index. Prognostic relevance of nuclear area and LINE1 DNA-hypomethylation was revealed exclusively in mucinous ovarian cancers.     

Comparison of the acute alterations in serum bone turnover markers and bone mineral density among women with surgical menopause

Objective

To determine the effect of a sudden decrease in estrogen levels via bilateral oophorectomy on serum turnover markers and to examine their correlation with bone mineral density (BMD).

Study design

This study included 51 women who had regular menses preoperatively and underwent bilateral oophorectomy for benign reasons. These women did not have any systemic disease or drug use that would influence bone metabolism. For each woman, spine and femur BMD were measured preoperatively and sixth months after surgery. Serum C-terminal telopeptide (CTX) and bone alkaline phosphatase (BAP) were measured preoperatively and at the first and sixth months after surgery. Correlations between bone turnover markers and BMD were pre- and post-operatively analyzed.

Results

The mean serum CTX and BAP concentrations at the first and sixth postoperative months were significantly higher compared to the preoperative measurements (p = 0.001). Spine BMD values at the sixth postoperative month was significantly lower compared to preoperative period (p = 0.0001). There was a significant negative correlation between spine BMD values and BAP levels both in the preoperative period and at the sixth postoperative month (r = −0.407, p = 0.001), whereas a significant positive correlation between serum CTX and BAP was noted at this time periods (r = 0.615, p < 0.001).

Conclusions

The results of this study showed that serum BAP and CTX levels rapidly increase in women after bilateral oophorectomy. Therefore, these markers (especially BAP) could be useful in the evaluation of osteoporosis risk in the early period of surgical menopause.     

Impact of beta blockers on epithelial ovarian cancer survival

Objective

Stress may promote ovarian cancer progression through mechanisms including autonomic nervous system mediators such as norepinephrine and epinephrine. Beta blockers, used to treat hypertension, block production of these adrenergic hormones, and have been associated with prolonged survival in several malignancies. We sought to determine the association between beta blocker use and epithelial ovarian cancer (EOC) disease progression and survival.

Methods

We performed an institutional retrospective review of patients with EOC treated between 1996 and 2006. Patients underwent cytoreductive surgery followed by platinum-based chemotherapy. Women were considered beta blocker users if these medications were documented on at least two records more than 6 months apart. Statistical tests included Fisher's exact, Kaplan-Meier, and Cox regression analyses.

Results

248 met inclusion criteria. 68 patients used antihypertensives, and 23 used beta blockers. Median progression-free survival for beta blocker users was 27 months, compared with 17 months for non-users (p = 0.05). Similarly, overall disease-specific survival was longer for beta blocker users (56 months) compared with non-users (48 months, p = 0.02, hazard ratio = 0.56). Multivariate analysis identified beta blocker use as an independent positive prognostic factor, after controlling for age, stage, grade, and cytoreduction status (p = 0.03). Overall survival remained longer for beta blocker users (56 months) when compared with hypertensive patients on other medications (34 months) and patients without hypertension (51 months) (p = 0.007).

Conclusions

In this cohort of patients with EOC, beta blocker use was associated with a 54% reduced chance of death compared with that of non-users.