Prognosis of ovarian clear cell carcinoma compared to other histological subtypes: a meta-analysis

Objective

To compare the survival outcome between clear cell carcinoma (CCC) and other histological subtypes in epithelial ovarian carcinoma (EOC).

Methods

From January 1974 to February 2011, we identified a total of 31,800 (CCC; 2152, non-CCC; 29648) patients from 12 studies meeting the inclusion criteria.

Results

Heterogeneity tests demonstrated significant between-study variation (I² = 92.1%) with no significant difference in hazard ratio (HR) for death between CCC and non-CCC (HR; 1.16, 95% CI; 0.85-1.57, random-effects model). Comparing the HR based on stage I + II, and stage III + IV, between CCC and non-CCC, showed that CCC patients had a higher hazard rate for death than those with non-CCC of the ovary (stage I + II; HR; 1.17, 95% CI; 1.01-1.36, stage III + IV; HR; 1.65, 95% CI; 1.52-1.79). In a comparison of CCC and serous EOC, advanced stage (III and IV) CCC only showed a poorer hazard rate for death than serous EOC (HR; 1.71, 95% CI; 1.57-1.86).

Conclusion

This analysis suggests that ovarian CCC patients had poorer prognosis than those with other histological subtypes of EOC, especially in advanced EOC stages. Different treatment strategies may be needed for patients with ovarian CCC.     

A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Purpose

This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC).

Patients and methods

Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated.

Results

Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p = 0.342).

Conclusion

A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.     

The incision angle of mediolateral episiotomy before delivery and after repair

Objective

To assess the relevance of the suture angle when evaluating mediolateral episiotomy, and the safety of the accepted lower limit of 40° for the incision angle.

Method

The angles formed by the incision and suture lines with the midline were measured, and any perineal tear noted, in 50 consecutive women undergoing their first vaginal delivery.

Results

The angles were significantly different (40° and 22.5°, respectively; P < 0.001). The only variable significantly linked to the difference was the timing of the episiotomy.

Conclusion

The suture angle cannot currently be used to assess the adequacy of the incision angle; moreover, an incision angle of 40° is probably too acute to prevent potential sphincter damage.     

Incidence of and risk factors for postoperative ileus in women undergoing primary staging and debulking for epithelial ovarian carcinoma

Objective

Thorough primary cytoreduction for epithelial ovarian carcinoma (EOC) improves survival. The incidence of postoperative ileus (POI) in these patients may be underreported because of varying POI definitions and the evolving, increasingly complex contemporary surgical approach to EOC. We sought to determine the current incidence of POI and its risk factors in women undergoing debulking and staging for EOC.

Methods

We retrospectively identified the records of women who underwent primary staging and cytoreduction for EOC between 2003 and 2008. POI was defined as a surgeon's diagnosis of POI, return to nothing-by-mouth status, or reinsertion of a nasogastric tube. Perioperative patient characteristics and process-of-care variables were analyzed. Univariate analyses were used to identify POI risk factors; variables with P ≤ .20 were included in multivariate analysis.

Results

Among 587 women identified, the overall incidence of POI was 30.3% (25.9% without bowel resection, 38.5% with bowel resection; P = .002). Preoperative thrombocytosis, involvement of bowel mesentery with carcinoma, and perioperative red blood cell transfusion were independently associated with increased POI. Postoperative ibuprofen use was associated with decreased POI risk. Women with POI had a longer length of stay (median, 11 vs 6 days) and increased time to recovery of the upper (7.5 vs 4 days) and lower (4 vs 3 days) gastrointestinal tract (P < .001 for each).

Conclusions

The rate of POI is substantial among women undergoing staging and cytoreduction for EOC and is associated with increased length of stay. Modifiable risk factors may include transfusion and postoperative ibuprofen use. Alternative interventions to decrease POI are needed.     

Expression of 67-kDa laminin receptor was associated with tumor progression and poor prognosis in epithelial ovarian cancer

Objective

67-kDa laminin receptor (67LR) has been identified as a prognostic biomarker for a variety of human cancers. We investigated the clinical significance of 67LR expression and its functional role in epithelial ovarian cancer (EOC).

Methods

67LR expression was evaluated by immunohistochemistry in 62 patients with EOC. We assessed the correlation of 67LR expression with clinical characteristics. In vitro experiment was performed for 67LR with inhibition using siRNA to evaluate its role in cell survival, apoptosis, and invasion in EOC cells.

Results

67LR was predominantly expressed on the cell membrane in the majority of EOC samples (45/62, 73%). 67LR expression was significantly correlated with advanced stage (P = 0.001). Patients with 67LR expression had shorter progression-free survival among all the patients (P = 0.010) and in particular among patients with advanced stages (P = 0.046). When 67LR expression was inhibited by siRNA in EOC cells (HeyA8 and A2780), there was a significant decrease of cell proliferation and invasion as well as increase of apoptosis.

Conclusion

These findings suggest that 67LR expression may play an important role in tumor progression into advanced stage with poor prognosis in EOC and down-regulation of 67LR on tumor cells may be a therapeutic target in those patients.     

Prevalence of cysts in epithelial ovarian cancer

Objective

Ovarian carcinomas mostly appear as large cystic masses. However, the exact prevalence of cysts in epithelial ovarian cancer (EOC) has never been documented as well as the tumor factors that are related to the presence of cysts. Demonstrating the prevalence of cysts in EOC is essential for research focused on predictive and prognostic biomarkers in ovarian cyst fluid.

Study design

From 233 patients with primary EOC who underwent surgery, pathological data were collected from pathology reports. Univariate and multivariate logistic regression were used to analyze the relationship between the presence of cysts and other tumor characteristics.

Results

Cysts in EOC were present in 83.7% of the patients and were mostly (61%) multilocular. The most common histological subtypes (serous, mucinous, endometrioid, clear cell) contained cysts in more than 85% of the cases. In univariate regression analysis, early FIGO stage, low tumor grade and a large tumor size were significantly associated with the presence of cysts (OR (95% CI) = 5.312 (1.81-15.57), 6.906 (2.31-20.66) and 1.169 (1.08-1.27), respectively). In multivariate regression analysis, apart from tumor size, only tumor grade was independently associated with the presence of cysts (adjusted OR (95% CI) = 4.234 (1.36-13.22)).

Conclusions

The large majority of all EOCs contained cysts. Histological subtype, FIGO stage, tumor necrosis and age were not associated with the presence of cystic EOC. In contrast, tumor grade and tumor size were independently related to the presence of cystic EOC. This means that cystic EOCs represent a subgroup of larger and more well-differentiated tumors. The evident relationship between the presence of cysts and differentiation grade is interesting from a clinical point of view as grading is especially important for the prognosis and treatment of patients with stage I EOC.     

MMP-1-PAR1 axis mediates LPA-induced epithelial ovarian cancer (EOC) invasion

Objectives

MMP-1 is over-expressed in many cancers, with high expression often associated with poor survival. In the present study, we examined the expression of MMP-1 in EOC and its role in EOC invasion. Moreover, we evaluated the role of a newly identified MMP-1-protease activated receptor (PAR)-1 axis in LPA-induced EOC invasion.

Methods

MMP-1 and PAR1 mRNA expression in EOC cell lines was determined by real time PCR. MMP-1 mRNA expression in 96 normal and carcinoma ovarian tissue specimens was analyzed using a TissueScan real time PCR array. MMP-1 concentration in conditioned medium was measured by MMP-1 ELISA. PAR1 protein expression was detected by Western blotting. Cell invasion was evaluated by in vitro Matrigel invasion assay.

Results

In ovarian tumor tissues more MMP-1 expression was observed than in normal ovarian tissues (p < 0.05), and its expression correlated with tumor grade (grade 3 > grade 2 > grade 1). Human recombinant MMP-1 as well as serum free conditioned medium containing high levels of MMP-1 from DOV13 and R182 cells significantly promoted DOV13 cell invasion (p < 0.05), implicating a direct role of MMP-1 in EOC invasion. Moreover, MMP-1 induced DOV13 invasion was significantly blocked by PAR1 siRNA silencing. Furthermore, MMP-1 and PAR1 were both significantly induced by LPA (20 μM), and siRNA silencing of MMP-1 and PAR1 both significantly reduced LPA's invasion-promoting effect in DOV13 cells (p < 0.05).

Conclusions

Our results suggest that the MMP-1-PAR1 axis is involved in EOC invasion and at least partially mediates LPA-induced EOC invasion. Therefore, blocking MMP-1 or PAR1 may represent a new therapeutic option for metastatic EOC.     

Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study

Purpose

Efflux transporters of the ATP-binding cassette (ABC) family are major determinants of chemoresistance in tumor cells. This study examined associations between functional variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes in patients with epithelial ovarian/primary peritoneal cancer (EOC/PPC) following platinum and taxane-based chemotherapy.

Methods

Sequenom iPLEXTMGOLD Assay and MALDI-TOF platform were used to genotype the non-synonymous G2677T/A (rs2032582; encoding Ala893Ser/Thr) and synonymous C3435T (rs1045642; encoding Ile1145Ile) variants in ABCB1, the non-synonymous G1249A variant in ABCC2 (rs2273697; encoding Val417Ile), and the non-synonymous C421A variant in ABCG2 (rs2231142; encoding Q141K, Gln141Lys) in normal DNA from up to 511 women in Gynecologic Oncology Group (GOG) phase III trials, GOG-172 or GOG-182. Progression-free survival (PFS) and overall survival (OS) were analyzed in relation to genetic polymorphisms using Kaplan-Meier and Cox proportional hazards model.

Results

The C421A variant (CA + AA versus CC) in ABCG2 was associated with a 6-month longer median PFS (22.7 versus 16.8 months, p = 0.041). In multivariate analysis, patients with variant genotypes were at a reduced risk of disease progression (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.59-0.96, p = 0.022). The association between C421A and OS was not statistically significant (HR = 0.88, 95% CI = 0.67-1.15, p = 0.356). None of the other variants measured in either ABCB1 or ABCC2 was associated with PFS or OS.

Conclusion

The C421A variant in ABCG2, previously shown to be associated with enhanced protein degradation and drug sensitivity, was associated with longer PFS in advanced stage EOC/PPC patents treated with platinum + taxane-based chemotherapy. This finding requires further validation.     

Bilateral uterine artery ligation via minilaparotomy for heavy menstrual bleeding

Objective

To assess the safety and short-term efficacy of bilateral uterine artery ligation (UAL) via minilaparotomy for the management of heavy menstrual bleeding (HMB).

Methods

A prospective study of 30 women with HMB who underwent UAL. The primary outcome was cumulative treatment failure 12 months after the procedure. Treatment failure was defined as the need for hysterectomy during the follow-up period.

Results

At 12 months, 6 women had undergone hysterectomy for bleeding, for a cumulative failure rate of 20% (95% CI, 9%-38%). The number of bleeding days was significantly reduced by 11.9 ± 1.5 days (P < 0.001) and hemoglobin level significantly increased by 1.3 ± 0.15 g/dL (P < 0.001). Of the 30 women, 24 (80%) were satisfied with the results. No major complications were reported during the procedure or median follow-up period of 13.2 months.

Conclusion

Bilateral UAL is a safe and effective minimally invasive procedure that can provide an alternative treatment for HMB.     

Does human papillomavirus infection imply a different prognosis in vulvar squamous cell carcinoma?

Background

Two independent pathways in the development of vulvar squamous cell carcinoma (VSCC) have been described, one related to and the other independent of high-risk human papillomavirus (HR-HPV). The aim of our study was to evaluate whether the HPV status has a prognostic significance or can predict response to radiotherapy.

Methods

All VSCC diagnosed from 1995 to 2009 were retrospectively evaluated (n = 98). HPV infection was detected by amplification of HPV DNA by PCR using SPF-10 primers and typed by the INNO-LIPA HPV research assay. p16^INK4a expression was determined by immunohistochemistry. Disease-free and overall survival (DFS and OS) were estimated by Kaplan-Meier analysis with the log-rank test and a multivariate Cox proportional hazard's model.

Results

HR-HPV DNA was detected in 19.4% of patients. HPV16 was the most prevalent genotype (73.7% of cases). p16^INK4a stained 100% HPV-positive and 1.3% HPV-negative tumors (p < .001). No differences were found between HPV-positive and -negative tumors in terms of either DFS (39.8% vs. 49.8% at 5 years; p = .831), or OS (67.2% vs. 71.4% at 5 years; p = .791). No differences in survival were observed between HPV-positive and -negative patients requiring radiotherapy (hazard ratio [HR] 1.04, 95% confidence interval [CI] .45 to 2.41). FIGO stages III-IV (p = .002), lymph node metastasis (p = .030), size ≥ 20 mm (p = .023), invasion depth (p = .020) and ulceration (p = .032) were associated with increased mortality but in multivariated only lymph node metastasis retained the association (HR 13.28, 95% CI 1.19 to 148.61).

Conclusions

HPV-positive and -negative VSCCs have a similar prognosis. Radiotherapy does not increase survival in HPV-positive women.     

Single nucleotide polypmorphisms in ERCC1 are associated with disease progression, and survival in patients with advanced stage ovarian and primary peritoneal carcinoma; a Gynecologic Oncology Group study

Objective

This study evaluated common polymorphisms in excision repair cross-complementation group 1 (ERCC1) involved in repair of platinum-induced DNA damage in advanced-stage, epithelial ovarian/peritoneal/tubal cancer (EOC/PPC/FTC) patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy.

Methods

Pyrosequencing was performed to examine single nucleotide polymorphisms (SNPs) in codon 118 and C8092A in ERCC1 in leukocyte DNA from the Gynecologic Oncology Group phase III protocol, GOG-182. Kaplan-Meier method and adjusted Cox regression modeling were used to examine associations between ERCC1 polymorphisms and progression-free survival (PFS) and overall survival (OS).

Results

The genotype distribution at codon 118 (n = 278) in ERCC1 for CC, CT, and TT was 23%, 45% and 32%, and the median OS was 32, 47 and 43 months, respectively. Patients with the CT + TT versus CC genotype in codon 118 in ERCC1 were at a reduced risk of death (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.49-0.95, p = 0.025). The genotype distribution for C8092A in ERCC1 (N = 280) was 50%, 42% and 8%, and the median OS was 45, 40 or 30 months for CC, CA and AA, respectively. Women with the CA + AA versus CC genotype in C8092A in ERCC1 had a trend suggesting an increased risk of death (HR = 1.29, 95% CI = 0.97-1.72, p = 0.077).

Conclusions

The polymorphism in codon 118 in the DNA repair gene ERCC1 was an independent predictor for better survival in EOC/PPC/FTC patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. The relationship between the C8092A polymorphisms in ERCC1 and survival was modest with an effect size that was not always statistically significant.     

Changes in tumor blood flow as measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) may predict activity of single agent bevacizumab in recurrent epithelial ovarian (EOC) and primary peritoneal cancer (PPC) patients: an exploratory analysis of a Gynecologic Oncology Group Phase II study

Objective

To explore feasibility of measuring tumor blood flow as marker for antiangiogenic activity using DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging) in women with recurrent EOC/PPC treated with bevacizumab.

Methods

In a phase II study, 62 patients with recurrent/persistent EOC/PPC were treated with bevacizumab (15 mg/kg IV q21days) until disease progression. DCE-MRI was performed pre-cycle 1 and 4 of bevacizumab. Images were analyzed retrospectively by a single experienced blinded radiologist. Tumor and muscle contrast enhancement was measured by region of interest signal intensity within the same DCE-MRI images. Flow rates were obtained with concentration of dye as a function of time. Relative blood flow (RBF) was calculated as a ratio of average blood flow into tumor to muscle tissue. Associations between RBF and characteristics/outcomes were explored.

Results

Sixty-two patients were eligible for study. Unfortunately, only 14 (23%) patients had imaging data available for analysis at baseline and 13 of those same patients (21%) had imaging data available for analysis pre-cycle 4. The RBF distribution was similar from pre-cycle 1 to 4. RBF remained stable for the majority of the cases (median change -0.21). Baseline RBF was not significantly associated with being progression-free at 6 months, microvessel density, 17 month overall survival, tumor response, or platinum sensitivity. However, increases in blood flow rates were associated with likelihood to be progression-free at 6 months.

Conclusion

Functional imaging of tumor blood flow is a potential research endpoint that may be explored further. Consideration should be given to timing of endpoint and standardizing the technique.     

Comparison study of single-port (Octoport™) and four-port total laparoscopic hysterectomy

Objective

To evaluate the clinical utility of PCR compared with other available diagnostic modalities in prompt diagnosis of female genital tuberculosis causing infertility.

Study design

Prospective case-controlled trial. Premenstrual endometrial biopsy specimens were collected from 150 infertile women of reproductive age group suspected of having genital tuberculosis. All patients underwent diagnostic endoscopy (laparoscopy and hysteroscopy) and the samples obtained were subjected to microscopy, culture by the BACTEC 460 TB System, histopathology and polymerase chain reaction (PCR) for detection of 165 bp region of 65 kDa gene of Mycobacterium tuberculosis. The results were correlated with the laparoscopic findings.

Results

While the laparoscopy/hysteroscopy findings were indicative of tuberculosis in 12.6% of cases, 14.6% of the specimens showed evidence of 65 kDa gene of M. tuberculosis and only 3.33%, 1.33% and 0.66% were positive by culture, smear and histopathology, respectively.

Conclusion

Since laparoscopy, hysteroscopy other endoscopic procedures are associated with operative risks and may cause flaring of infection, and other conventional laboratory tests including histopathology have poor sensitivity, PCR-based detection of 65 kDa gene of M. tuberculosis in endometrial biopsy specimens could be a promising molecular diagnostic technique compared to conventional methods of diagnosis.     

Interaction between preoperative CA-125 level and survival benefit of neoadjuvant chemotherapy in advanced epithelial ovarian cancer

Objective

This study aims to determine whether neoadjuvant chemotherapy (NAC) has survival benefit in selected patients with advanced epithelial ovarian cancer (EOC) who have high risk of suboptimal cytoreduction which is represented by high serum CA-125 level.

Methods

We retrospectively reviewed records of 314 patients with EOC including 94 patients who received NAC. After stratification by preoperative CA-125 levels, the progression-free survival (PFS) was compared between the NAC group and the primary debulking surgery (PDS) group.

Results

The NAC group had more FIGO stage IV disease (P < 0.001) and higher CA-125 levels (P < 0.001). Although suboptimal resection rate was higher in the PDS group (50% vs. 18%, P < 0.001), however, NAC was not associated with increased PFS in multivariate Cox analysis (P = 0.334). Nevertheless, after stratification according to CA-125 levels, NAC showed survival benefit in the subgroup with high CA-125 levels (> 2000 U/ml; HR 0.62, P = 0.037).

Conclusion

Our preliminary data suggests the possible interaction between CA-125 levels and survival benefit of NAC. The randomized trial data about NAC should be stratified by the reproducible and relevant criteria such as preoperative serum CA-125 level to elucidate true survival benefit of NAC in ovarian cancer.     

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.     

Compared effects of surgical and natural menopause on climacteric symptoms, osteoporosis, and metabolic syndrome

Objective

To compare the effects of surgical (ie, earlier) and natural (ie, later) menopause on climacteric symptoms, osteoporosis, and metabolic syndrome.

Method

The study was conducted with 94 women who underwent hysterectomy and bilateral oophorectomy and 95 women who were older than 40 years and in natural menopause. None had received hormone theraphy or osteoporosis treatment. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III.

Results

The rates of hot flushes (P = 0.001), sweating (P = 0.001), poor memory (P = 0.04), change in sexual desire (P = 0.04), and osteoprosis (diagnosed in the hip bone, P = 0.005) were significantly higher among the women in surgical menopause, but the rate of metabolic syndrome was similar in the 2 groups (47.8% and 40%; P = 0.28).

Conclusion

Compared with natural menopause, surgical menopause was found to be associated with highter rates of climacteric symptoms and osteoporosis but not of of metabolic syndrome.     

Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers

Objective

There are few validated relapse prediction biomarkers for epithelial ovarian cancer (EOC). We have shown progranulin (PGRN) and secretory leukocyte protease inhibitor (SLPI) are up regulated, overexpressed survival factors in EOC. We hypothesized they would predict presence of occult EOC.

Method

PGRN, SLPI, and the known biomarker HE4 were measured in EOC patient plasma samples, prospectively collected every 3 months from initial remission until relapse. Clinical data and CA125 results were incorporated into statistical analyses. Exploratory Kaplan-Meier estimates, dividing markers at median values, evaluated association with progression-free survival (PFS) and overall survival (OS). Area-under-the-curve (AUC) statistics were computed from receiver operating characteristic (ROC) curves to evaluate discrimination ability. A Cox proportional hazards model assessed the association between PFS, OS, and biomarkers, adjusting for clinical prognostic factors.

Results

Samples from 23 advanced stage EOC patients were evaluated. PGRN at 3 months was the only biomarker independently associated with PFS (P < 0.0001) and OS (P < 0.003). When used to predict progression by 18 months, sensitivity and specificity were 93% and 100%, respectively, with AUC = 0.944. The Cox model hazard ratio for PFS, divided at 59 ng/ml by ROC analysis and adjusted for clinical factors, was 23.5 (95% CI: 2.49-220). Combinations with SLPI, HE4, and/or CA125 did not improve the model.

Conclusions

We report pilot data indicating a potential independent association of PGRN on EOC patient PFS and OS. A validation study will be required to confirm this finding and to inform whether PGRN warrants evaluation as a potential screening biomarker.     

Doppler analysis of uterine perfusion and ovarian stromal blood flow in polycystic ovary syndrome

Objective

To investigate blood flow velocity in the ovarian stromal artery and uterine artery in women with polycystic ovary syndrome (PCOS) and to correlate these velocities with clinical and biochemical parameters.

Methods

A prospective study was carried out in 55 patients with PCOS and 42 age-matched women who did not have PCOS. Clinical, biochemical, and hormonal characteristics, and utero-ovarian Doppler ultrasound blood flow parameters were determined, and correlations between the parameters were evaluated.

Results

Ovarian stromal blood flow was higher (P < 0.01) and uterine perfusion was lower (P < 0.01) in women with PCOS compared with women who did not have PCOS. Ovarian stromal artery pulsatility index (PI) was inversely correlated with levels of dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor-1, and with the luteinizing hormone/follicle-stimulating hormone ratio. There was a positive correlation between uterine artery PI and DHEAS level.

Conclusion

Doppler analysis of the uterine and intraovarian arteries may provide additional information about the etiopathogenesis of PCOS and partly explain the clinical implications of the condition.     

Factors associated with operative hysteroscopy outcome in patients with uterine adhesions or submucosal myomas

Objective

To determine the factors associated with hysteroscopic surgery long-term outcome in patients with intrauterine adhesions or submucosal myomas.

Methods

Factors thought to be associated with outcome were retrospectively evaluated from the records of 591 patients who were followed up for at least 5 years after undergoing hysteroscopic adhesiolysis (n = 203) or myomectomy (n = 388).

Results

The major factors affecting outcome were degree of adhesion (OR, 1.91; P = 0.03) in the former group and parity (OR, 0.55; P = 0.005) and depth of intramural penetration of the myoma (OR, 30.74; P < 0.001) in the latter. Severe intrauterine adhesion, low parity, and deep intramural penetration of submucosal myoma had an associated increase risk of poor outcome. The overall complication rate was 1.35% and, respectively, 12.8% and 9.3% of the patients who underwent hysteroscopic adhesiolysis or myomectomy needed a second intervention.

Conclusion

Hysteroscopic surgery is a safe and effective procedure. Degree of adhesion or parity and depth of intramural penetration of myomas are the major factors affecting outcome in patients with these lesions.