Prognostic Value of Serum Creatinine Levels in Patients with Epithelial Ovarian Cancer.

AIM: To evaluate preoperative serum creatinine level as a prognostic parameter in patients with primary epithelial ovarian cancer (EOC). PATIENTS AND METHODS: In a retrospective cohort study, serum levels of creatinine were evaluated in 498 patients with EOC. Data were extracted from our prospectively maintained database. Results were correlated with clinicopathological parameters and patient survival. RESULTS: The mean pre-therapeutic serum creatinine level in patients with EOC was 0.84±0.40 mg/dI. A serum creatinine level of 1.2 mg/dl or higher was found in 22 (4.4%) patients and associated with poor survival. In a multivariate logistic regression analysis, the serum creatinine level was a significant independent prognostic parameter of overall survival. CONCLUSION: The preoperative serum level of creatinine may be useful as an additional independent prognostic parameter in patients with EOC.

Prognostic value of preoperative hyponatremia and thrombocytosis in patients with epithelial ovarian cancer.

BACKGROUND: Preoperative hyponatremia and thrombocytosis are associated with perioperative morbidity in patients with epithelial ovarian cancer (EOC). The aim of the present study was to evaluate preoperative hyponatremia and thrombocytosis as prognostic parameters in patients with EOC. METHODS: In a retrospective cohort study, serum levels of sodium and thrombocyte counts were evaluated in 498 patients with EOC. Data were extracted from the prospectively maintained database. Results were correlated with clinicopathological parameters and patient survival. RESULTS: Mean (standard deviation) overall pretherapeutic serum sodium levels and thrombocyte counts in patients with EOC were 138.8 (2.9) mmol/l and 340.1 (122.6)â€¯× 103/µl, respectively. Hyponatremia (serum sodium levels ≤ 134 mmol/l) was found in 33 (6.7%) patients and thrombocytosis (thrombocytes ≥ 450/µl) in 88 (17.7%) patients. Serum sodium levels were associated with the presence or absence of residual tumor tissue after primary surgery. Thrombocyte counts were associated with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) tumor stage, presence/absence of residual tumor, histological grade and histological type. Patients with thrombocytosis presented with advanced tumor stage, a higher rate of postoperative residual tumor mass, higher tumor grade, and a higher rate of serous ovarian cancer. In a multivariate logistic regression analysis, only the established clinicopathological parameters but not serum sodium and thrombocyte count were independent predictors of patient overall survival. CONCLUSION: Preoperative hyponatremia and thrombocytosis are not useful as additional independent prognostic parameters in patients with EOC.

Compartment syndrome after gynecologic laparoscopy: systematic review of the literature and establishment of normal values for postoperative serum creatine kinase and myoglobin levels.

PURPOSE: To evaluate published evidence in the literature on compartment syndrome (CS) in association with gynecologic surgery and to establish postoperative normal values for serum creatine kinase (CK) and myoglobin. METHODS: The present study consists of a case report of a patient with CS, a systematic review including 37 studies and 86 patients with CS, and a retrospective cohort study of 300 patients undergoing various types of laparoscopy for benign or malignant diseases in order to establish postoperative normal values. RESULTS: We report on a patient with early-stage ovarian cancer, who developed CS after laparoscopic surgery with massively elevated serum CK and myoglobin levels, i.e., 1109 U/L and 18151 µg/L, respectively. In our systematic review, median serum CK and myoglobin levels among women with CS were 19,223 (177-27,412) U/L and 1248 (285-1360) µg/L, respectively. In our cohort study, the median postoperative serum CK and myoglobin levels were 68 (14-1576) U/L and 45 (14-1040) µg/L, respectively. The 95th and 99th percentile of serum CK and myoglobin levels were 158 and 391.5 U/L, and 152.3 and 298.9 µg/L, respectively. CONCLUSION: Markedly elevated postoperative serum levels of CK and myoglobin levels might raise the suspicion for CS and could therefore aid in the rapid diagnosis of CS.

One-stop clinical assessment of risk for endometrial hyperplasia (OSCAR-Endo): a fast-track protocol for evaluating endometrial pathologies.

PURPOSE: To evaluate a one-stop clinical assessment of risk for assessing endometrial pathologies (OSCAR-Endo), consisting of a fast-track protocol with hysteroscopy, dilation and curettage (D&C) with intraoperative frozen section analysis of the removed tissue in cases of hysteroscopic suspicion of malignancy. METHODS: In this prospective clinical trial, a total of 304 consecutive women with sonographically suspected endometrial hyperplasia and/or postmenopausal bleeding, underwent D&C with intraoperative frozen section analysis between May 2013 and September 2015. Based on the results of the hysteroscopy and/or frozen section, the OSCAR-Endo score was reported: negative, when no frozen section was regarded necessary or the frozen section yielded a negative result; equivocal, when the frozen section reported an equivocal result; positive, when frozen section reported either complex hyperplasia with atypia or cancer. RESULTS: Frozen sections were required by the surgeons in 59 (19.4%) of cases. When compared with the final histology after D&C, frozen section showed a sensitivity, specificity, PPV, NPV, and overall test accuracy of 91.3, 100, 100, 94.1, and 96.3% for predicting malignant disease, respectively. The OSCAR-Endo score showed a sensitivity, specificity, PPV, NPV, and overall test accuracy of 84, 100, 100, 98.6, and 98.7% for predicting malignant disease, respectively. CONCLUSION: The OSCAR-Endo protocol is easy to perform in daily clinical practice reaching an excellent test accuracy. It helps in immediate postoperative counseling of affected patients. Clinical Trial Registration http://www.clinicaltrials.gov ; NCT01961102.

Serologic markers of autoimmunity in women with recurrent pregnancy loss.

PROBLEM: Various autoimmunologic mechanisms have been shown to be involved in recurrent pregnancy loss (RPL). This study aimed to evaluate whether women with RPL have elevated serum levels of common autoimmunologic parameters. METHOD OF STUDY: Serum levels of antinuclear antibodies (ANAs) were measured in 114 women with RPL, and 107 healthy controls using a qualitative immunometric enzyme immunoassay, serum levels of IgG class autoantibodies against histone, IgG class autoantibodies against nucleosomes, and IgG class autoantibodies against double-stranded (ds) DNA were measured by quantitative enzyme immunoassays. RESULTS: No differences were ascertained regarding serum levels of ANAs (P=.9), serum levels of antibodies against histones (P=.1), antibodies against nucleosomes (P=.4) and antibodies against dsDNA (P=.6) between women with RPL and healthy controls. No associations were found between serum levels and clinical characteristics of affected women. CONCLUSION: Our study shows that serologic parameters of autoimmunity are not elevated in women with RPL and are not associated with clinical characteristics of affected women.

Gamma-glutamyltransferase as novel biomarker in patients with uterine leiomyosarcoma.

Gamma-glutamyltransferase (GGT) is an established marker for proliferative/apoptotic balance and has been associated with cancer risk and prognosis. The aim of this study was to evaluate the value of pre-treatment GGT serum levels as prognostic biomarker in patients with primary uterine leiomyosarcoma (ULMS). Data of women with ULMS were extracted from a multi-center database. Pre-treatment GGT serum levels were measured and patients assigned to predefined GGT risk groups. GGT values were correlated with clinico-pathological parameters and univariate and multivariable survival analyses were performed. A total of 44 patients with ULMS were analyzed. Mean (SD) pre-therapeutic GGT serum level was 33.8 (39.8) U/L. In Figo Stage I versus II-IV mean (SD) GGT values were 28.8 (34.0) U/l and 43.5 (49.2) U/l, respectively (p = 0.25). Five-year overall survival (OS) rates in ULMS patients with normal low versus higher GGT levels were 70% and 37%, respectively (p = 0.043). Univariate and multivariable analyses revealed that higher GGT serum levels (p = 0.043, p = 0.005) and high histological grade (p = 0.029, p = 0.012) were independently associated with impaired OS, respectively. Higher pre-treatment GGT serum levels were independently associated with unfavorable prognosis in women with ULMS. Thus, GGT seems to be a useful novel biomarker in ULMS.

Plasma fibrinogen levels in patients with benign and malignant ovarian tumors.

OBJECTIVE: Plasma fibrinogen is a key acute phase protein and known to be elevated in ovarian cancer. We aimed to investigate the association between plasma fibrinogen and malignant and benign ovarian tumors. METHODS: In a retrospective, single-center study, we evaluated preoperative plasma fibrinogen levels in 471 patients with benign and in 224 patients with malignant (borderline ovarian tumor [BOT]: n=36, epithelial ovarian cancer [EOC]: n=188) ovarian tumors. The association between preoperative plasma fibrinogen levels and clinico-pathological parameters was investigated. A multivariate logistic regression model was performed to identify an independent association. RESULTS: Mean (standard deviation) preoperative plasma fibrinogen levels in patients with benign ovarian tumors, BOT, and invasive ovarian cancers were 346.7 (99.7), 372.8 (114), and 472.6 (148.4) mg/dL, respectively (p<0.001). Within the EOC cohort, patients with advanced stage disease had higher plasma fibrinogen levels (485.5 [151.3] mg/dL) than patients with early stage disease (430.9 [130.3] mg/dL; p=0.03). In a multivariate model plasma fibrinogen was identified to be independently associated with the presence of BOT and EOC. In the subgroup of patients <50 years, plasma fibrinogen levels remained independently associated with malignant ovarian tumors in CA 125 positive and negative patients. CONCLUSION: Plasma fibrinogen levels are independently associated with malignant ovarian tumors. Plasma fibrinogen levels showed an independent association with malignant ovarian tumors in the subgroup of patients <50 years, in whom differential diagnosis of ovarian tumors is particularly challenging.

The impact of plasma fibrinogen levels on patients with vulvar cancer.

OBJECTIVE: To investigate the association between plasma fibrinogen levels and clinico-pathological parameters of patients with vulvar cancer and to determine their value as prognostic parameters. STUDY DESIGN: In this retrospective study, we evaluated pretreatment plasma fibrinogen levels in 120 patients with invasive squamous cell vulvar cancer and correlated them with clinico-pathological parameters and patients' survival. RESULTS: Pretreatment plasma fibrinogen levels were directly associated with tumor stage (pT1a vs. pT1b vs. pT2 vs. pT3-4, p=0.001), lymph node involvement (pN0 vs. pN1, p=0.04), and histological grade (G1 vs. G2 vs. G3, p=0.03), but not with patients' age (≤ 70 years vs. >70 years, p=0.6). In a multivariate survival analysis, tumor stage (p=0.006/p=0.02) and lymph node involvement (p<0.001/p<0.001), but neither histological grade (p=0.2/p=0.9) nor plasma fibrinogen levels (p=0.6/p=0.6) were associated with disease-free and overall survival, respectively. In a multivariate analysis, patient's age (≤ 70 years vs. >70 years) was associated with overall survival (p=0.03) but not with disease-free survival (p=0.1). CONCLUSION: Pretreatment plasma fibrinogen levels were directly associated with tumor stage, lymph node involvement and histological grade. Although we could demonstrate a prognostic value of pretreatment plasma fibrinogen levels on survival, we were unable to establish fibrinogen as an independent prognostic parameter in patients with vulvar cancer.

The inflammation-based modified Glasgow Prognostic Score in patients with vulvar cancer.

OBJECTIVES: To evaluate the prognostic potential of the modified Glasgow Prognostic Score (mGPS), known to reflect the degree of tumor-associated inflammation and cachexia, in patients with vulvar cancer. STUDY DESIGN: We included 93 consecutive patients with vulvar cancer into our study. As previously published, the pre-therapeutic mGPS was calculated as follows: patients with elevated C-reactive protein (CRP) serum levels (>10 mg/L) and hypoalbuminaemia (<35 g/L) were allocated a score of 2, patients with elevated CRP serum levels without hypoalbuminaemia were allocated a score of 1, patients with normal CRP serum levels with or without hypoalbuminaemia were allocated a score of 0. The mGPS was correlated with clinico-pathological parameters. The association between mGPS and prognosis was evaluated by univariate and multivariate survival analysis. RESULTS: Mean (SD) pretreatment CRP and albumin serum levels were 9.5 (9.6) mg/L and 41.4 (5.3) g/L, respectively. mGPS was associated with tumor stage (p=0.01), but not with lymph node involvement (p=0.4), histological grade (p=0.8), and patients' age (p=0.7). In univariate analyses, mGPS (p=0.006, p=0.001), tumor stage (p<0.001, p<0.001), lymph node involvement (p<0.001, p<0.001), and patients' age (p=0.04, p=0.007), but not histological grade (p=0.1, p=0.3) and year of surgery (1995-2001 vs. 2002-2008, p=0.7, p=0.3) were associated with disease-free and overall survival, respectively. In a multivariate analysis, tumor stage (p=0.01, p=0.02) and lymph node involvement (p<0.001, p=0.001), but not mGPS (p=0.7, p=0.8), patients' age (p=0.6, p=0.4), histological grade (p=0.2, p=0.1), and year of surgery (p=0.4, p=0.8) were associated with disease-free and overall survival, respectively. CONCLUSIONS: Despite being associated with prognosis in a univariate analysis, mGPS cannot be used as an independent inflammation-based predictor for survival in patients with vulvar cancer.

Serologic markers of autoimmunity in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether women with the polycystic ovary syndrome (PCOS) have an increased rate of elevated serum levels of common autoimmunologic parameters. DESIGN: Prospective case-control study. SETTING: Academic research institution. PATIENT(S): One hundred nine women with PCOS and 109 age-matched healthy controls. INTERVENTION(S): Peripheral venous puncture, ultrasonography, questionnaire. MAIN OUTCOME MEASURE(S): Serum levels of antinuclear antibodies (ANAs) were measured by immunometric enzyme immunoassay, serum levels of IgG class autoantibodies against histone, IgG class autoantibodies against nucleosomes, and IgG class autoantibodies against double-stranded (ds) DNA were measured by enzyme immunoassays. RESULT(S): Women with PCOS had significantly elevated serum levels of antihistone and anti-dsDNA antibodies, whereas serum levels of ANAs and antinucleosome antibodies were similar between the two groups. When serum levels of ANAs, antihistone, antinucleosomes, and anti-dsDNA antibodies were correlated with clinical and biochemical parameters, a significant correlation between serum levels of ANAs and serum TSH was established. CONCLUSION(S): Our study shows that serologic parameters of autoimmunity (i.e., antihistone and anti-dsDNA antibodies) are elevated in women with PCOS. A role of autoimmunologic processes in PCOS can be suspected.

The presence of postmenopausal bleeding as prognostic parameter in patients with endometrial cancer: a retrospective multi-center study.

BACKGROUND: To date, there is no consensus on the utility of screening procedures for the early detection of endometrial cancer. The value of transvaginal ultrasound for screening of asymptomatic endometrial cancer has been discussed controversially. This study was conducted to evaluate whether asymptomatic patients with endometrial cancer have a better prognosis than symptomatic patients with endometrial cancer diagnosed after postmenopausal bleeding. METHODS: In the present multi-center study, the effect of the presence of postmenopausal bleeding on prognosis was evaluated retrospectively in 605 patients with endometrial cancer using patients' files. 543 patients (133 patients were asymptomatic, 410 patients were symptomatic) with endometrioid endometrial cancer were enrolled in all further analysis. Student's t-test, Cox regression analysis and Kaplan-Meier analysis were used were appropriate. RESULTS: Presence/absence of a postmenopausal bleeding was not associated with tumor stage (p = 0.2) and age at diagnosis (p = 0.5). Asymptomatic patients with endometrial cancer had a significantly higher rate of well and moderate-differentiated tumors compared to symptomatic patients (p = 0.008). In univariable and multivariable survival analysis, tumor stage, tumor grade, and patients' age at diagnosis, but not presence/absence of a postmenopausal bleeding, were associated with disease free and overall survival. CONCLUSION: Asymptomatic patients with endometrial cancer have a higher rate of well differentiated tumors compared to patients with a postmenopausal bleeding prior to diagnosis. The prognosis of both groups of patients was similar.

Plasma fibrinogen levels and prognosis in patients with ovarian cancer: a multicenter study.

INTRODUCTION: To evaluate pretherapeutic plasma fibrinogen levels as a prognostic parameter in patients with epithelial ovarian cancer (EOC). Materials and Methods. In the present multicenter study, pretherapeutic plasma fibrinogen levels were evaluated in 422 patients with EOC. Plasma fibrinogen levels were correlated with clinicopathological parameters and patient survival. RESULTS: The mean (standard deviation) pretherapeutic plasma fibrinogen level was 450.0 (150.1) mg/dl. Elevated plasma fibrinogen levels were associated with advanced tumor stage (p = .01) and the presence of a postoperative residual tumor mass (p < .001), but not with histological grade (p = .1) and histological type (p = .8). In a multivariate Cox regression model, tumor stage (p < .001 and p < .001), postoperative residual tumor mass (p = .001 and p = .008), and plasma fibrinogen level (p < .001 and p = .002), but not histological type (p = .8 and p = .2), patient age (p = .9 and p = .9), and serum cancer antigen 125 (p = 0.2 and p = 0.3) and C-reactive protein (p = .2 and p = .3) levels, were associated with disease-free and overall survival, respectively. Histological grade was associated with overall but not with disease-free survival (p = .01 and p = .8), respectively. CONCLUSIONS: Pretherapeutic plasma fibrinogen levels can be used as an independent prognostic parameter in patients with EOC.

Serum C-reactive protein in the differential diagnosis of ovarian masses.

OBJECTIVE: A number of serum tumor markers have been investigated to aid clinicians in the differential diagnosis of ovarian masses. Serum C-reactive protein (CRP) is a widely used biomarker of inflammation and has been previously shown to be a promising biomarker in patients with ovarian cancer. STUDY DESIGN: In a retrospective single-center study, we evaluated serum CRP in 576 patients with benign and in 242 patients with malignant (ovarian tumors of low malignant potential [LMP]: n=44, epithelial ovarian cancer [EOC]: n=198) ovarian masses. Results were correlated to clinical data. RESULTS: Median (25th, 75th percentiles) serum CRP in patients with benign ovarian tumors, with ovarian tumors of LMP, and with EOC were 0.5 (0.5, 0.6)mg/dL, 0.5 (0.5, 0.9)mg/dL, and 1.36 (0.5, 4.9)mg/dL, respectively (p<0.001). In the subgroup of patients with EOC, serum CRP significantly correlated with FIGO stage (p<0.001), residual tumor mass (p<0.001), and patients' age (p=0.04), but not with tumor grade (p=0.2) and histologic type (p=0.4). In univariable and multivariable models including serum CRP, serum CA 125, and patients' age, serum CRP independently predicted the presence of malignant ovarian masses (p<0.0001; Odds Ratio [OR] 5.3, 95% Confidence Interval [CI] 3.8-7.4). Serum CRP had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying malignant ovarian masses of 49.8%, 84.1%, 57.1%, and 79.8%, respectively. CONCLUSION: Serum CRP is associated with the presence of malignant ovarian tumors independent of serum CA 125 and patients' age and can therefore be used as additional diagnostic marker in the differential diagnosis of ovarian masses.

Fibrinogen plasma levels are an independent prognostic parameter in patients with cervical cancer.

OBJECTIVE: The purpose of this study was to evaluate the association between fibrinogen plasma levels on disease-free patients and overall survival in patients with cervical cancer. STUDY DESIGN: Pretherapeutic fibrinogen plasma levels were examined in 313 patients with cervical cancer who were treated at the Department of Obstetrics and Gynecology, Medical University of Vienna. Fibrinogen plasma levels were correlated with clinical-pathologic findings and patient survival. RESULTS: Mean (+/- SD) pretherapeutic fibrinogen plasma levels were 417.4 mg/dL (+/- 130.3 mg/dL). Elevated fibrinogen plasma levels were associated with advanced tumor stage (P < .001) and patient age (P < .001), but not with histologic type (P = .4), histologic grade (P = .1), and pelvic lymph node involvement (P = .9). In a multivariate survival analysis, fibrinogen plasma levels (P < .001 and < .001) and lymph node involvement (P < .001 and = .001), but not patients' age (P = .8 and .4) and histologic type (P = .7 and .5) were associated with overall or disease-free survival, respectively. Histologic grade was associated with disease-free (P = .01), but not with overall, survival (P = .2). CONCLUSION: Fibrinogen plasma levels are an independent prognostic parameter in patients with cervical cancer.

Polymorphisms of the endothelial nitric oxide synthase gene in premenopausal women with polycystic ovary syndrome.

OBJECTIVES: To investigate the association of two common genetic polymorphisms of the gene encoding for endothelial nitric oxide synthase (Nos3), the enzyme catalyzing the production of nitric oxide (NO), with occurrence of the polycystic ovary syndrome (PCOS). METHODS: In a prospective case-control study, we analyzed 2 polymorphisms of the Nos3 gene cluster (Nos 3 exon 7 Glu298Asp and 27-base pair repeat in intron 4 of Nos3) in a series of 210 premenopausal Caucasian women with PCOS and 171 healthy controls using pyrosequencing and PCR, respectively. Women completed a detailed questionnaire and underwent a peripheral venous puncture, ultrasonography, and a standardized oral glucose tolerance test (OGTT). RESULTS: Genotype frequencies were not significantly different among women with PCOS and controls for the exon 7Nos3 and the intron 4Nos3 polymorphism (p=0.3 and 0.2, respectively). CONCLUSIONS: In our series, two common polymorphisms of the Nos3 gene cluster were not associated with occurrence of PCOS.