Katrin Hefler-Frischmuth

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.

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.

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.

Serologic markers of autoimmunity in women with recurrent pregnancy loss

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.

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.

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.

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

AbstractPurposeTo 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.MethodsIn 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.ResultsFrozen 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.ConclusionThe 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 Registrationhttp://www.clinicaltrials.gov; NCT01961102.