A collagen-fibrin patch for the prevention of symptomatic lymphoceles after pelvic lymphadenectomy in women with gynecologic malignancies: A randomized clinical trial.

OBJECTIVE: To evaluate the efficacy of a collagen-fibrin patch for the prevention of symptomatic lymphoceles after pelvic lymphadenectomy in women with gynecologic malignancies. METHODS: In a multicenter, randomized, clinical trial, 164 women with pelvic lymphadenectomy were allocated either to bilateral pelvic application of two collagen-fibrin patches or no intervention. Main outcome was efficacy, defined as reduction of symptomatic lymphocele rate diagnosed within four weeks after surgery. Secondary outcomes were asymptomatic lymphoceles and subsequent interventions. Sample size was based on the assumption that application of a collagen-fibrin patch reduces the prevalence of symptomatic lymphoceles by at least 66%. The study was single-blinded, i.e., patients and primary outcome assessors, but not surgeons, were blinded to the treatment allocation. RESULTS: A total of 75 women were randomized to the intervention and 89 to the control group. All women received the allocated intervention. In total, 42 (27.4%) lymphoceles and 8 (5.2%) symptomatic lymphoceles were observed. Symptomatic lymphoceles were observed in 5/68 (7.4%) women in the intervention group and 3/85 (3.5%) women in the control group (p = 0.47). Asymptomatic lymphoceles were observed in 16 (23.5%) women in the intervention group compared to 18 (21.2%) in the control group (p = 0.85). In a multivariate logistic regression model, no independent risk factor for the development of a symptomatic lymphocele was ascertained. DISCUSSION: Intraoperative application of collagen-fibrin patches to the pelvic side walls does not reduce the incidence of symptomatic lymphoceles in women with gynecologic malignancies undergoing pelvic lymphadenectomy.

Preoperative C-reactive protein serum levels as a predictive diagnostic marker in patients with adnexal masses.

OBJECTIVE: To evaluate C-reactive protein (CRP) serum levels as a preoperative predictive marker for ovarian cancer in patients with adnexal masses. METHODS: CRP serum levels of 1843 adnexal masses and subsequent surgery were investigated (patients with benign ovarian tumors: n=1423; borderline tumor of the ovary [BTO]: n=83; EOC: n=337). Test characteristics and predictive values of CRP serum levels were investigated by univariate analysis and multivariate binary logistic regression models. RESULTS: Median (interquartile range) serum CRP levels in patients with benign ovarian tumors, BTO, and EOC were 0.4 (0.1-0.6)mg/dL, 0.5 (0.2-0.9)mg/dL, and 1.6 (0.5-5.4)mg/dL, respectively (p<0.001). Sensitivity and specificity of the combination of CRP and CA-125 was 80.1% and 90.8%, negative predictive value (NPV) and positive predictive value (PPV) was 92.2% and 76.9%, respectively. In univariate and multivariate analysis, CRP serum levels were independently associated with presence of BTO and EOC (HR 6.7 [5.2-8.5], p<0.001 and HR 2.2 [1.4-3.3], p<0.001). The combination of CRP and CA-125 serum levels resulted in a number needed to treat of 2.11 to detect one case of EOC or BTO. CONCLUSION: CRP serum levels independently predicted the presence of BTO and EOC in patients with suspicious adnexal masses. CRP serum levels seem to be of additional value to CA-125 in the preoperative differential diagnosis of adnexal masses and might be particularly in combination with CA-125 clinically useful.

The Prevalence of Fallopian Tube Occlusion in Women with Polycystic Ovary Syndrome Seems Similar to Non-Subfertile Women: A Retrospective Cohort Study.

There are limited data on how non-infectious risk factors influence tubal patency in women with subfertility. With hormonal shifts influencing tubal secretions, it has been argued that subfertile women with polycystic ovary syndrome (PCOS) have lower tubal patency. In a retrospective study, 216 women, who underwent diagnostic evaluation for PCOS and infertility, were included. Fallopian tube patency was tested using HSG, HyCoSy, and laparoscopic chromopertubation in 171 (79.2%), 28 (13.0%), and 17 (7.9%), respectively. Bilateral patency was found in 193 women (89.4%), unilateral patency in 13 (6.0%) and bilateral occlusion in 10 (4.6%) patients. Women with PCOS phenotypes C (odds ratio, OR 0.179, 95% CI: 0.039-0.828) and D (OR 0.256, 95% CI: 0.069-0.947) demonstrated lower risks for Fallopian tube occlusion. In conclusion, our data suggest that about 5% of infertile women with PCOS also have bilateral tubal occlusion, which seems similar to the rate in non-subfertile women. With 11% of participants having unilateral or bilateral tubal occlusion, this should reassure women with PCOS that their hormonal challenges do not seem to increase their risk for tubal factor subfertility.

Gamma-glutamyltransferase as a preoperative differential diagnostic marker in patients with adnexal mass.

OBJECTIVE: Gamma-glutamyltransferase (GGT) is involved in tumor development, progression and chemotherapy resistance. The present study evaluated GGT serum levels as a preoperative predictive marker for ovarian cancer in patients with adnexal mass. STUDY DESIGN: Preoperative GGT serum levels of 2235 patients with adnexal mass and subsequent surgery were ascertained (patients with benign ovarian tumors: n = 1811; borderline tumor of the ovary [BTO]: n = 85; epithelial ovarian cancer [EOC]: n = 339). Standardized expert transvaginal ultrasound was documented. RESULTS: Median (interquartile range) GGT serum levels in patients with benign ovarian tumors, BTO, and EOC were 15.0 U/l (11.0-23.0), 17.0 U/l (10.0-23.5), and 20.0 U/l (13.0-34.0), respectively (p = 0.002). Elevated GGT serum levels were associated with the presence of BTO/EOC in univariate analysis (p < 0.0001, hazard ratio 1.8, confidence interval 1.5-2.3). GGT did not outperform established tools for preoperative prediction of BTO/EOC in patients with adnexal mass, such as CA-125 measurement or transvaginal ultrasound. CONCLUSION: Elevated GGT serum levels were not associated with the presence of BTO/EOC in women with suspicious adnexal mass in multivariate analysis. GGT serum levels did not outperform established risk factors and therefore might add only limited additional value to CA-125 serum levels in the differential diagnosis between benign and malignant adnexal masses.

Prognostic value of serum creatine level in patients with vulvar cancer.

Vulvar cancer is a rare malignancy with poor prognosis that generally occurs in elderly patients. The individual prognosis is difficult to assess. Serum creatinine levels are frequently elevated in elderly patients. Recent evidence have shown shown that - besides indicating kidney impairment - serum creatinine levels may be used to predict the survival in cancer patients. Several studies observed an association between elevated serum creatinine levels and poor prognosis in patients with solid tumors. In this retrospective cohort study, serum creatinine levels were evaluated in 170 patients with invasive vulvar cancer. Serum creatinine levels were correlated to established clinicopathologic factors. Univariate and multivariate survival analysis were performed. Elevated serum creatinine levels (>1.2 mg/dl) were significantly associated with both poor disease specific and overall survival. Three year overall survival rates were 74.8% and 32.5% for patients with serum creatinine levels of ≤ and >1.2 mg/dl, respectively. In a multivariate survival model, serum creatinine levels were significantly associated with overall survival independent of tumor stage and patients' age. In conclusion, pretherapeutic serum creatinine levels may be useful as an independent prognostic parameter in patients with vulvar cancer.

Efficient leukocyte depletion by a novel microfluidic platform enables the molecular detection and characterization of circulating tumor cells.

RT-qPCR is a highly sensitive approach to detect rare transcripts, as derived from circulating tumor cells (CTCs) in the blood of cancer patients. However, the presence of unwanted leukocytes often leads to false positive results. Here, we evaluated whether the micro-fluidic Parsortix™ technology is appropriate to remove these leukocytes and thereby finally to improve the overall approach. In this study, we established a workflow including the micro-fluidic Parsortix™ technology for the molecular detection of CTC related transcripts. Background levels of EpCAM, PPIC, TUSC3, and MAL2 were efficiently removed due to an up to 106-fold depletion of leukocytes. The presence of these gene markers was observed in Parsortix™-enriched blood samples from patients with primary and recurrent gynecological cancer (32% and 14%), as well as in 86% of the metastatic breast cancer samples, at a very high specificity. In the ovarian cancer samples, PPIC was the most prominent gene marker, contributing to all positive cases and at least to 70% of the positive cases after pre-amplification of the respective target genes. Expanding the analytical panel up to 29 gene markers further increased the positivity rate (primary gynecological cancer: 95%, recurrent gynecological cancer: 100%, metastatic breast cancer: 92%). The established workflow strongly improved the overall molecular analysis of the target cells by the efficient removal of contaminating cells, and, thereby offers great promise for the molecular characterization of CTCs.

Development of a tool for prediction of ovarian cancer in patients with adnexal masses: Value of plasma fibrinogen.

OBJECTIVE: To develop a tool for individualized risk estimation of presence of cancer in women with adnexal masses, and to assess the added value of plasma fibrinogen. STUDY DESIGN: We performed a retrospective analysis of a prospectively maintained database of 906 patients with adnexal masses who underwent cystectomy or oophorectomy. Uni- and multivariate logistic regression analyses including pre-operative plasma fibrinogen levels and established predictors were performed. A nomogram was generated to predict the probability of ovarian cancer. Internal validation with split-sample analysis was performed. Decision curve analysis (DCA) was then used to evaluate the clinical net benefit of the prediction model. RESULTS: Ovarian cancer including borderline tumours was found in 241 (26.6%) patients. In multivariate analysis, elevated plasma fibrinogen, elevated CA-125, suspicion for malignancy on ultrasound, and postmenopausal status were associated with ovarian cancer and formed the basis for the nomogram. The overall predictive accuracy of the model, as measured by AUC, was 0.91 (95% CI 0.87-0.94). DCA revealed a net benefit for using this model for predicting ovarian cancer presence compared to a strategy of treat all or treat none. CONCLUSION: We confirmed the value of plasma fibrinogen as a strong predictor for ovarian cancer in a large cohort of patients with adnexal masses. We developed a highly accurate multivariable model to help in the clinical decision-making regarding the presence of ovarian cancer. This model provided net benefit for a wide range of threshold probabilities. External validation is needed before a recommendation for its use in routine practice can be given.