Christine Staudigl

Cytokeratin-19 as a biomarker in urine and in serum for the diagnosis of endometriosis--a prospective study.

Abstract Endometriosis compromises the quality of life of countless women worldwide and is a leading cause of disability. Clinical symptoms of endometriosis can be very heterogeneous leading to a long interval between onset of symptoms and surgical diagnosis. A noninvasive, rapid diagnostic test is urgently needed. In this prospective study, we evaluated the usefulness of Cytokeratin-19 (CK19) as a biomarker for the diagnosis of endometriosis through urine and serum ELISA. 76 reproductive-aged women undergoing laparoscopy for benign conditions were included to this study and divided into two groups by the presence (n = 44) or absence (n = 32) of endometriosis. There was no statistically significant correlation between the concentration of CK19 in urine (p = 0.51) or in serum (p = 0.77) and the diagnosis of endometriosis. Assigning the samples to the proliferative or secretory cycle stage did not sufficiently lower the p values. In this study, the promising data reported in the recent literature about CK19 serving as a sufficient biomarker for endometriosis could not be verified when tested in a larger sample size. Further studies are warranted to explore the usefulness of CK19 in the diagnosis of endometriosis.

Prognostic relevance of pretherapeutic gamma-glutamyltransferase in patients with primary metastatic breast cancer.

Background Gamma-glutamyltransferase (GGT) is a known marker for apoptotic balance and cell detoxification. Recently, an association of baseline GGT levels and breast cancer incidence, tumor progression and chemotherapy resistance was shown. The purpose of this study was to evaluate the association of pre-therapeutic GGT levels, clinical-pathological parameters and survival in patients with primary metastatic breast cancer (PMBC). Methods In this multicenter analysis, pre-therapeutic GGT levels and clinical-pathological parameters of 114 patients diagnosed with PMBC between 1996 and 2012 were evaluated. The association between GGT levels and clinical-pathological parameters were analysed. Patients were stratified into four GGT risk-groups (GGT < 18.00 U/L: normal low, 18.00 to 35.99 U/L: normal high, 36.00 to 71.99 U/L: elevated and ≥ 72.00 U/L: highly elevated) and survival analyses were performed. Findings Patients in the high risk GGT group had a poorer overall survival, when compared to the low risk group with five-year overall survival rates of 39.5% and 53.7% (p = 0.04), respectively. Patients with larger breast tumors had a trend towards higher GGT levels (p = 0.053). Pre-therapeutic GGT levels were not associated with indicators of aggressive tumor biology such as HER2-status, triple negative histology, or poorly differentiated cancers. Conclusion Pre-therapeutic GGT serum level might serve as a novel prognostic factor for overall-survival in patients with PMBC.

Prevalence and severity of cyclic leg pain in women with endometriosis and in controls - effect of laparoscopic surgery

OBJECTIVE In addition to dysmenorrhea, dyspareunia, and subfertility, pain in the lower extremities has been described to be a further complaint in women affected by endometriosis, and lysis of nerve entrapment was thought to be associated with amelioration of leg pain. Therefore, we aimed to compare the prevalence of cyclic leg pain and pain intensity between women with endometriosis and without endometriosis, and to evaluate the effect of laparoscopic surgery. STUDY DESIGN Forty-four women with endometriosis and 58 controls were included in a prospective, controlled clinical trial at a University hospital/tertiary referral center. Participants were asked to complete questionnaires the day before and six to nine weeks after laparoscopy. The prevalence and intensity of leg pain and improvement after laparoscopic surgery, quantified according to a visual analog scale (VAS) score, were evaluated. We also recorded involvement of dermatomes, the presence and intensity of dysmenorrhea, and correlations between age, stage of endometriosis (rAFS-score), and preoperative VAS scores. RESULTS Before surgery, more women were affected by leg pain in the endometriosis group, compared to the control group (45.5% and 25.9%, respectively). Preoperative VAS scores for leg pain, however, were not significantly different between the two groups. A moderate correlation in the preoperative VAS scores between leg pain and dysmenorrhea was observed. After laparoscopy, we found a significant improvement in leg pain intensity in both groups. The mean difference in the VAS score for pain reduction between the study group and the control group was 0.74 (95% CI: -0.61-2.08), which was not statistically significant. CONCLUSIONS The prevalence of leg pain is increased in endometriosis, while leg pain intensity is not, compared to women without endometriosis. Laparoscopic surgery-even without preparation and decompression of nerve tissue-is associated with an improvement in pain intensity in women with endometriosis, as well as in the group without endometriosis.

Response Prediction to Neoadjuvant Chemotherapy: Comparison between Pre-Therapeutic Gene Expression Profiles and In Vitro Chemosensitivity Assay

Although the use of (neo-)adjuvant chemotherapy in breast cancer patients has resulted in improved outcome, not all patients benefit equally. We have evaluated the utility of an in vitro chemosensitivity assay in predicting response to neoadjuvant chemotherapy. Pre-therapeutic biopsies were obtained from 30 breast cancer patients assigned to neoadjuvant epirubicin 75 mg/m2 and docetaxel 75 mg/m2 (Epi/Doc) in a prospectively randomized clinical trial. Biopsies were subjected to a standardized ATP-based Epi/Doc chemosensitivity assay, and to gene expression profiling. Patients then received 3 cycles of chemotherapy, and response was evaluated by changes in tumor diameter and Ki67 expression. The efficacy of Epi/Doc in vitro was correlated with differential changes in tumor cell proliferation in response to Epi/Doc in vivo (p = 0.0011; r = 0.73670, Spearmańs rho), but did not predict for changes in tumor size. While a pre-therapeutic gene expression signature identified tumors with a clinical response to Epi/Doc, no such signature could be found for tumors that responded to Epi/Doc in vitro, or tumors in which Epi/Doc exerted an antiproliferative effect in vivo. This is the first prospective clinical trial to demonstrate the utility of a standardized in vitro chemosensitivity assay in predicting the individual biological response to chemotherapy in breast cancer.

Changes of Socio-demographic data of clients seeking genetic counseling for hereditary breast and ovarian cancer due to the “Angelina Jolie Effect”

BackgroundThe purpose of this study was to evaluate socio-demographic characteristics of clients claiming genetic counseling for hereditary breast and ovarian cancer (HBOC) in Austria. Furthermore, changes of these parameters before and after Angelina Jolie’s (AJ) disclosure of carrying a BRCA mutation were evaluated.MethodsIn this prospective, nonrandomized study 268 consecutive clients seeking genetic counseling for HBOC at the Medical University of Vienna, Department of Obstetrics and Gynecology, Vienna, Austria between June 2012 and June 2014 were included. Socio-demographic data and source of information about HBOC and genetic counseling were evaluated. First, socio-demographic parameters were compared to the general Austrian population. Second, changes in these parameters after AJ’s public disclosure of carrying a BRCA mutation were analyzed.ResultsSubjects were more frequent female, younger and higher educated in comparison to Austria’s general population (p < 0.001). Furthermore, level of education in participants was higher before than after AJ’s disclosure (p = 0.046). Most clients were informed about genetic counseling by physicians. As expected, after AJ’s public announcement patients were more frequent advised to genetic counseling by social media (p = 0.043) and family or friends (p = 0.010) than before.ConclusionsIn this present study we could demonstrate that particularly younger and female participants with high educational level attended significantly more often genetic counseling for HBOC. Increased presence of HBOC in media since AJ’s disclosure of carrying a BRCA mutation had lead that information and awareness about HBOC was obtained by a wider audience from different social background.

The Prognostic Value of C-Reactive Protein Serum Levels in Patients with Uterine Leiomyosarcoma

Objective C-reactive protein (CRP) has previously been shown to serve as a prognostic parameter in women with gynecologic malignancies. Due to the lack of valid prognostic markers for uterine leiomyosarcoma (ULMS) this study set out to investigate the value of pre-treatment CRP serum levels as prognostic parameter. Methods Data of women with ULMS were extracted from databases of three Austrian centres for gynaecologic oncology. Pre-treatment CRP serum levels were measured and correlated with clinico-pathological parameters. Univariate and multivariable survival analyses were performed. Results In total, 53 patients with ULMS were included into the analysis. Mean (SD) CRP serum level was 3.46 mg/dL (3.96). Solely, an association between pre-treatment CRP serum levels and tumor size (p = 0.04) but no other clinic-pathologic parameter such as tumor stage (p = 0.16), or histological grade (p = 0.07), was observed. Univariate and multivariable survival analyses revealed that CRP serum levels (HR 2.7 [1.1–7.2], p = 0.037) and tumor stage (HR 6.1 [1.9–19.5], p = 0.002) were the only independent prognostic factors for overall survival (OS) in patients with ULMS. Patients with high pre-treatment CRP serum levels showed impaired OS compared to women with low levels (5-year-OS rates: 22.6% and 52.3%, p = 0.007). Conclusion High pre-treatment CRP serum levels were independently associated with impaired prognosis in women with ULMS and might serve as a prognostic parameter in these patients.

Results of a prospective dose intensity and neutropenia prophylaxis evaluation programme (DIEPP) in cancer patients at risk of febrile neutropenia due to myelosuppressive chemotherapy

SummaryObjectiveTo describe the incidence of febrile neutropenia (FN) and use of pegfilgrastim in cancer patients with high overall risk of FN and to investigate the relationship between granulocyte-colony stimulating factor (G-CSF) guideline adherence and chemotherapy delivery in Central and Eastern Europe (CEE) and Austria.MethodsDose Intensity Evaluation Program and Prophylaxis (DIEPP) was a multicentre, prospective, and observational study of adult patients with breast cancer, lymphoma, lung cancer, gastric cancer, and ovarian cancer, who received chemotherapy with pegfilgrastim support and who had an overall risk of FN ≥ 20 %. Physicians assessed patient risk factors and reported their reasons for administering pegfilgrastim.ResultsPatients were enrolled from 113 centres in CEE and Austria between August 2010 and July 2013, and data were analysed from 1072 patients. The most common tumour types were breast cancer (50 %) and lymphoma (24 %). FN incidence was 5 % overall. FN occurred in 3 % of patients (28/875) who received pegfilgrastim as primary prophylaxis (PP) and 13 % of patients (19/142) who received it as secondary prophylaxis (SP); 79 % of FN events in SP patients occurred in the first cycle before pegfilgrastim was administered. The three most frequently chosen reasons for using pegfilgrastim were planned chemotherapy with high FN risk, female gender, and advanced disease. Overall, 40 % of patients received > 90 % of their planned chemotherapy dose within 3 days of the planned schedule.ConclusionFN incidence was relatively low with pegfilgrastim PP in patients with a physician-assessed overall FN risk of ≥ 20 %. The most important reasons for pegfilgrastim use were consistent with the investigators’ risk assessment and international guidelines.

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.

Improving comprehension of genetic counseling for hereditary breast and ovarian cancer clients with a visual tool

Objective Genetic counseling and testing can be offered to individuals who are at high risk of carrying a breast cancer (BRCA) gene mutation. However, the content of genetic counseling could be difficult to understand due to complex medical information. The aim of this study was to investigate if comprehension can be improved with a new genetic counseling tool (NGCT hereafter; a tool that combines complex medical information with pictures, diagrams and tables) as compared to conventional oral-only genetic counseling (CGC). Methods 207 clients attended genetic counseling for hereditary breast and ovarian cancer at the Medical University of Vienna between February 2015 and February 2016. Seventy clients participated in this study and were allocated into two groups: the first 36 participants received conventional (oral only) genetic counseling (CGC) and the following 34 participants received genetic counseling using a new genetic counseling tool (NGCT), which combines complex information with pictures, diagrams and tables. After genetic counseling, all consenting participants were invited to complete a questionnaire with seven questions evaluating their comprehension of the medical information provided. Results Socio-demographic backgrounds were comparable in both groups. Correct responses were significantly higher in the NGCT group compared to the CGC group (p = 0.012). NGCT also statistically improves correct response of Q1 (p = 0.03) and Q7 (p = 0.004). Conclusion The NGCT leads to an overall better understanding of the content of a genetic counseling session than CGC alone.

Adverse Mucocutaneous Reaction to Pertuzumab in a Patient with HER2-Positive Metastatic Breast Cancer

A 26-year-old Caucasian woman presented with a 5 cm palpable mass of the right breast. The analysis of the core biopsy revealed an invasive ductal carcinoma (IDC), G2, pT1, HR 3+, HER2 3+, Ki-67 30%. Diagnostic imaging showed no signs of distant metastases. The patient received neo-adjuvant chemotherapy with four cycles epirubicin plus cyclophosphamide, followed by four cycles paclitaxel, which was coadministered with trastuzumab for HER2-positive disease. Subsequently, she underwent skin-sparing mastectomy with immediate reconstruction through superior gluteal artery perforator flap (S-GAP) and axillary lymph-node dissection. The tumor histology found remaining IDC with DCIS, G2, ypT1c (2 cm), ypN0 (0/25), L0, V0, R0, M0. Trastuzumab was given for the remainder of 12 months, coadministered with goserelin for 2 years and tamoxifen for 5 years. After 3 years of routine follow-up, a cutaneous lesion was found on the reconstructed right breast. Excision confirmed local recurrence of the primary tumor: IDC, G2, rpT1b (6 mm), L0, V0, R1 (HR 3+, HER2 3+, Ki-67 20%). Treatment was continued with 36 additional doses of local radiotherapy, as well as trastuzumab and goserelin for another 2 years. Seven years after primary diagnosis, the patient was admitted for progressive pain in the right upper abdomen. Abdominal CT-scan revealed diffuse liver lesions (Fig. 1). Hepatic core biopsy identified cells that derived from a ductal adenocarcinoma (HR 3+, HER2 3+, Ki-67 70%). She was then scheduled for palliative therapy with docetaxel plus trastuzumab and pertuzumab. While receiving the trastuzumab loading dose, she developed acute fever chills, followed by papulopustular rash, affecting her face, trunk, and back (Fig. 2). Throughout the next days, we observed worsening of the rash, mucositis, dehydration and poor general condition. Exudate from the papules formed crusts in the periorbital area (Fig. 3).