Tumoral PD-L1 expression defines a subgroup of poor-prognosis vulvar carcinomas with non-viral etiology

Vulvar cancer is rare but incidence rates are increasing due to an aging population and higher frequencies of young women being affected. In locally advanced, metastatic or recurrent disease prognosis is poor and new treatment modalities are needed. Immune checkpoint blockade of the PD-1/PD-L1 pathway is one of the most important advancements in cancer therapy in the last years. The clinical relevance of PD-L1 expression in vulvar cancer, however, has not been studied so far. We determined PD-L1 expression, numbers of CD3+ T cells, CD20+ B cells, CD68+ monocytes/macrophages, Foxp3+ regulatory T cells and CD163+ tumor-associated macrophages by immunohistochemistry in 103 patients. Correlation analysis with clinicopathological parameters was undertaken; the cause-specific outcome was modeled with competing risk analysis; multivariate Cox regression was used to determine independent predictors of survival. Membranous PD-L1 was expressed in a minority of tumors, defined by HPV-negativity. Its presence geographically correlated with immunocyte-rich regions of cancer islets and was an independent prognostic factor for poor outcome. Our data support the notion that vulvar cancer is an immunomodulatory tumor that harnesses the PD-1/PD-L1 pathway to induce tolerance. Accordingly, immunotherapeutic approaches might have the potential to improve outcome in patients with vulvar cancer and could complement conventional cancer treatment

Significance of intraperitoneal Chemotherapy in advanced Ovarian Cancer

Patientinnen mit Ovarialkarzinom werden in etwa 70% der Falle im fortgeschrittenen Tumorstadium FIGO III oder IV diagnostiziert. Die 5-Jahres-uberlebensraten fur diese Patientinnen sind hierbei mit etwa 32% (FIGO IIIC) und 19% (FIGO IV) begrenzt 1. Die Standardtherapie besteht aus der primaren Operation mit Entfernung beider Adnexe, Hysterektomie, infragastrischer Omentektomie und systematischer Lymphonodektomie im Bereich der gro ss en Bauchgefa ss e bis zum Nierenstiel, der pelvinen Lymphonodektomie, Peritonektomie und Entfernung des sichtbaren Tumors. Ziel ist die makroskopische Tumorfreiheit am Ende der Operation, die in spezialisierten Zentren in etwa 65-74% erreicht wird 2. In der Regel erfolgt hiernach eine Chemotherapie mit 6 Zyklen Carboplatin und Paclitaxel oder, seltener, Docetaxel. Die Hinzunahme von Bevazicumab wird von der Organkommission Ovar der Arbeitsgemeinschaft Gynakologische Onkologie (AGO) seit Januar 2012 empfohlen, sie gehort in anderen Landern, wie den USA, noch nicht zur Empfehlung der Fachgesellschaften. In Untergruppen kann die Sequenz zugunsten einer neoadjuvanten Chemotherapie von 2-3 Zyklen vor der Operation verandert werden 3,4

Development of obstetrical and gynecological journals, 2007 to 2013: a trend analysis

To analyze the trends and developments among journals in the specialty of obstetrics and gynecology. Using the Journal Citation Reports from 2007 to 2013, we analyzed the impact factor (IF), Eigenfactor(A (R)) Score (ES), and Article Influence(A (R)) Score (AIS) of 43 journals in the field of obstetrics and gynecology published in this time period. From 78 journals of the Journal Citation Report 2013, 43 were selected for this study. The mean IF grew from 1.68 +/- A 0.97 in 2007 to 2.12 +/- A 1.05 in 2013, the ES from 0.0113 +/- A 0.0169 to 0.0114 +/- A 0.0140, and the AIS from 0.513 +/- A 0.302 to 0.663 +/- A 0.359. Differences in the IF, ES, and AIS between journals from the United States versus Europe could be observed. In most cases, the IF, ES, and AIS increased between 2007 and 2013. Strong correlations could be found between IF, AIS, and ES. The overall mean IF for obstetrical and gynecological journals increased over the analyzed time period. The IF remains the standard measure to compare scientific journals. It correlates well with two major alternative measures of scientific impact, the ES and especially the AIS. Other measures are evolving and might show superior usage in the future

Impact of Open Laparoscopy in Patients Under Suspicion of Ovarian Cancer

Background/Aim: Feasibility and value of diagnostic open laparoscopy (DOL) was assessed in patients presenting under suspicion of advanced ovarian cancer (AOC) mostly with large-volume ascites. Patients and Methods: This retrospective study analyzed 143 consecutive patients who underwent DOL for histopathological verification of AOC performed from 2002 to 2012. Results: Out of the 143 patients presenting at our Center with an ovarian mass and mostly with ascites under suspicion of ovarian cancer, we diagnosed 125 AOCs, three AOCs with three concomitant tumors of other origin, and 15 other diseases causing an ovarian mass and ascites mimicking AOC (e.g. gastrointestinal malignancies, tuberculosis, mesothelioma, endometrial cancer and benign conditions). Conclusion: DOL can be considered a valid and safe diagnostic tool for histopathologically verifying epithetlial ovarian cancer and preventing patients with other diagnoses undergoing the wrong course of therapy

c-myc copy number gain is a powerful prognosticator of disease outcome in cervical dysplasia

Cervical carcinoma develops from preneoplasia by a multistep process. Although most low-grade dysplastic lesions will regress without intervention and even highgrade changes exhibit a substantial rate of regression, a small percentage of dysplasia will progress over time. Thus, indicators are needed to estimate the biological risk and to help avoid overtreatment in women who desire to preserve fertility. In addition to the classical biomarkers, PCR-ELISA-determined HPV genotype and immunohistochemically assessed p16(INK4a) and Ki-67 expression, cells with integrated HPV and copy number gain of TERC and c-myc were quantified in a panel of 104 benign, intraepithelial neoplastic (CIN I, II, III) and cancerous lesions using fluorescence in situ hybridization. Optimal cut-off values were calculated; Kaplan-Meier curves and a Cox proportional hazard regression model were used to evaluate prognostic signatures. The assay reliably identified HPV integration, TERC and c-myc copy number gain as determined by comparisons with established biomarkers. All biomarker levels increased with the progression of the disease. However, only c-myc copy number gain independently prognosticated a low probability of dysplastic regression. Our results suggest that c-myc plays a key role in the process of dysplastic transformation and might thus be exploited for treatment and follow-up decision-making of cervical dysplasia

Ribavirin in Acute Hepatitis E Infection in Patients with Gynecological Cancer: A Case Series

Hepatitis E virus infection is usually a self-limited disease. However, during the last years there has been growing evidence for prolonged and chronic infection occurring in patients with immunosuppression. Also patients with malignant and rheumatic diseases have been identified to be at risk for chronic hepatitis E. However, their course and prognosis are not well characterized and there have been no reports of hepatitis E virus infection in patients with gynecological cancer. Here, we report three Caucasian females with breast and ovarian cancers presenting with elevation of aminotransferase levels during anticancer treatment. Although only few or no clinical hints suggested hepatitis E virus infection, the diagnosis of hepatitis E virus infection was confirmed by seroconversion, which might occur with some delay, and/or by polymerase chain reaction. While two patients had a selflimited course, the third patient with a high-risk oncological constellation required ribavirin in order to resume chemotherapy. These cases highlight the need for hepatitis E virus testing in patients with gynecological cancer and elevated aminotransferase levels. Further, these cases show that in selected high-risk patients, ribavirin treatment may be necessary based on the decision of a multidisciplinary team

No evidence to support the impact of migration background on treatment response rates and cancer survival: a retrospective matched-pair analysis in Germany

Background!#!Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany.!##!Methods!#!Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002-December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression).!##!Results!#!Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar's test, P = 0.346) between both collectives.!##!Conclusion!#!Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis