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Background Dual antiplatelet therapy consisting of aspirin and clopidogrel is the standard of care for neurointerventional stenting and flow diversion. Platelet function testing has been increasingly performed to identify patients with a hypo- or hyper-response to clopidogrel. Ticagrelor has been a popular alternative antiplatelet agent for such patients. We assessed the role of platelet function testing in patients receiving ticagrelor and undergoing stenting or flow diversion. Methods The data from patients who had undergone stent-assisted coiling or Pipeline flow diversion of a cerebral aneurysm with ticagrelor therapy at any point during their treatment course from May 2017 to August 2019 at a single academic institution in the United States were retrospectively reviewed. Platelet function testing was used to determine the P2Y12 reactive units (PRUs), and the results were correlated with the procedural complications. Results A total of 28 patients with 29 aneurysms were treated while receiving ticagrelor. Of the 29 aneurysms, 16 (55.2%) were treated with flow diversion and 13 (44.8%) with stent-assisted coiling. Four thromboembolic complications (13.8%) and no hemorrhagic complications developed. Of the 8 patients with ≥1 PRU value >100, 4 (50%) had experienced a thromboembolic complication. The patients without a PRU value >100 did not experience any complications. Conclusion A risk of thromboembolic complications exists for patients receiving ticagrelor, which correlated with the PRUs in the present preliminary study. The findings from the present study suggest that the safe PRU range for patients receiving ticagrelor should be shifted to 0–100, which is lower than that of clopidogrel, thought to be 60–210. Further validation of the optimal PRU range for patients receiving ticagrelor is necessary.

Background: Neoadjuvant chemotherapy (NACT) (+/- anti HER2) is the preferred therapy for triple negative and HER2 positive subtype breast tumors. In Luminal subtype breast tumors, NACT is used to downstage large inoperable tumors and enable breast conserving therapy. However, this subgroup of patients may be overtreated as many Luminal subtype tumors do not respond to NACT due to the low rate of proliferating tumor cells. Herein, we tested the MammaTyper® pCR score as a predictor of therapy success measured as pCR in a retrospective analysis of archived samples from a single center. Methods: 85 FFPE biopsy samples from the years 2012-2018 were sourced from the archive. Samples with >20% tumor cell content were subjected to RNA extraction. Relative mRNA expression levels of ERBB2, ESR1, PGR and MKI67 were determined by RT-qPCR using the CE-IVD MammaTyper® kit. The continuous expression values were integrated into a prediction score (pCR-score) using a pre-defined algorithm and cutoff. The association of continuous and binary pCR-score results with pCR (defined as ypT0/Tis) and partial response was analyzed. Results: Marker positivity rates of the 75 samples included in the final analysis were 62.7% for ER, 53.3% for PR, 40.0% for HER2 and 94.7% for Ki67 (≥20% positive cells). 42.7% of patients were pre-menopausal and all samples except one were grade 3. pCR rates over all samples and in hormone receptor (HR) positive/HER2 negative patients only were 48.0% and 20.0%, respectively. Binary pCR-score result was significantly associated with pCR over all patients (Sensitivity: 88.9%, Specificity: 51.3%, PPV: 62.8%, NPV: 83.3%) and also in HR positive/HER2 negative patients only (Sensitivity: 83.3%, Specificity: 70.8%, PPV: 41.7%, NPV: 94.4%). ROC analysis revealed a good association of the continuous pCR-score with achievement pCR over all patients (AUC=0.756) and in the subgroup of HR+/HER2- patients (AUC=0.774). pCR rates according to St Gallen surrogate subtype definition were similar for IHC and RT-qPCR defined subtypes in Triple Negative (80.0% and 78.6% respectively) and in the HER2+ non luminal subtype (75.0%, and 70.0% respectively). In tumors with incomplete response the continuous pCR-score was significantly associated with residual tumor size (Spearman rs: -0.477 p-value: 0.0021) and %-decrease of tumor size (Spearman rs: 0.388, p-value: 0.0147). Conclusion: The MammaTyper® pCR score may serve as a standardized tool to predict response to NACT based on a pre-treatment biopsy. For patients with inoperable Luminal tumors and low predicted probability of pCR, neo-adjuvant aromatase inhibitor alone or combined with the new generation of TKIs such as CDK4/6 inhibitors or Pi3KCa/mTOR inhibitors may be an alternative for downstaging of tumors. Citation Format: Silvana Saracchini, Anna Bassini, Wally Marus, Serena Corsetti, Ilaria Specogna, Manuela Bertola, Elvia Micheli, Ralph M Wirtz, Mark Laible, Ugur Sahin, Daniele Generali, Sandro Sulfaro. Prediction of pathological complete response (pCR) upon neoadjuvant chemotherapy by MammaTyper® pCR score [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-23.

68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) has shown superiority over111Indium-octreotide scanning for the detection of phosphaturic mesenchymal tumors (PMTs). We report a case of tumor-induced osteomalacia resulting from PMT which, although initially clinically suspected, was not localized on octreotide scintigraphy performed several years prior. Subsequent surgical excision of a presumed benign osseous lesion a few years later revealed the diagnosis on pathology. Imaging assessment using 68Ga-DOTATATE PET/CT following recent clinical suspicion for recurrence revealed an intense tracer-avid lesion at the primary tumor site. DOTATATE imaging plays an important role in localizing tumors with high somatostatin receptor expression, such as neuroendocrine tumors (pheochromocytoma, paraganglioma, and neuroblastoma), meningioma, and mesenchymal tumors, causing oncogenic osteomalacia.

Background Thromboembolic complications are the primary risks of stent-coiling of cerebral aneurysms. The utility of platelet function testing in stent-assisted aneurysm coiling remains controversial. This study aimed to assess a pharmacy-mediated antiplatelet management protocol for stent-assisted coiling. Methods Stent-coiled aneurysms at an academic institution in the United States between 2015 and 2018 were retrospectively reviewed. All patients were managed using a pharmacy-mediated antiplatelet protocol, which required repeated platelet function testing and subsequent dose adjustments. Medication dosage, number of adjustments, aspirin reaction units (ARU) and P2Y12 reaction units (PRU), as well as complication rates, angiographic and functional outcome were analyzed. Results A total of 56 aneurysms (median size 5 mm, range 2.6–14.0 mm) in 54 patients (median age 58.5 years) were treated with stent-assisted coil embolization. Most aneurysms were located at the basilar tip (28.6%). Median pre-procedure ARU and PRU were 442.5 (range 363–594) and 123.5 (range 1–252), respectively. Approximately two-thirds of all procedures required at least one aspirin dose adjustment and 88.5% of procedures required at least one clopidogrel dose adjustment. There were two (3.6%) thromboembolic complications. One of the thromboembolic complications occurred in a patient where the pharmacy-mediated protocol was violated. There were no hemorrhagic complications. Last imaging follow-up demonstrated complete aneurysm occlusion in 83.9%. Conclusion In patients where the pharmacy-mediated antiplatelet protocol was followed, the thromboembolic complication rate was 1.8%. This complication rate compares favorably to those reported in large contemporary series. Nevertheless, the pharmacy-mediated protocol places a significant burden on both the patient and healthcare system.

The role of postoperative irradiation to contralateral non-involved neck nodes in lateralized carcinoma of the head and neck is not clear. The contralateral neck failure rate in head and neck carcinoma treated postoperatively with ipsilateral neck irradiation only was evaluated. Patients with carcinoma of the oral cavity, oropharynx, or hypopharynx without midline extension treated between 1990 and 2016 were analyzed. After tumor resection and neck dissection (ND), radiotherapy was given to the primary tumor site and ipsilateral neck. High-risk patients additionally received concurrent chemotherapy. Freedom from contralateral neck recurrence (FCNR), locoregional control rate (LRC), overall survival (OS), and disease-free survival (DFS) were evaluated. 197 patients (median age 60.7 years, 66.5% males, 52.8% oropharyngeal carcinomas) were analyzed. Complete resection (R0) was achieved in 85.8% of cases. Ipsilateral ND was performed in all patients and contralateral ND in 144 patients (73.1%). Concurrent chemotherapy was given to 59 patients (30.0%). After a median follow-up of 45.5 months, OS and DFS of all patients were 73.6% and 70.9% at 5 years, respectively. A total of 45 patients (22.8%) suffered from a locoregional recurrence, lymph node metastases of the contralateral neck developed in 12 patients (6.1%) only. There was no significant difference in contralateral nodal failure rate with or without performance of contralateral ND. Regional failure of the contralateral neck was low after surgery and ipsilateral neck irradiation in head and neck carcinomas without midline extension, supporting evidence that contralateral neck radiotherapy can safely be omitted in selected cases.

Eltern haben viele Kontakte mit dem Gesundheitssystem und sehen sich mit einer beträchtlichen Menge an Informationen zur Gesundheit ihres Kindes konfrontiert. Elterliche GK gilt als wichtige Voraussetzung für viele Aspekte des Gesundheitsverhaltens. Allerdings ist noch unklar, wie sich die[zum vollständigen Text gelangen Sie über die oben angegebene URL], 19. Deutscher Kongress für Versorgungsforschung (DKVF)

The role of the androgen receptor (AR) in non-muscle-invasive bladder cancer (NMIBC) remains controversial. We retrospectively analyzed the mRNA expression of AR using RT-qPCR in 95 patients with high-risk NMIBC treated with a bladder-sparing approach and correlated AR with clinical data and recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). The mRNA expression of AR and KRT5, i.e., the basal-like subtype, was strongly correlated (rs = 0.456, p &lt, 0.001). AR (p = 0.053) and KRT5 (p = 0.029) mRNA expression was negatively correlated with tumor grade. Kaplan–Meier analyses indicated significantly prolonged CSS (p = 0.020) and OS (p = 0.015) and a trend towards longer RFS (p = 0.051) in patients with high AR expression. High KRT5 expression was associated with significantly longer RFS (p = 0.033), CSS (p = 0.029) and OS (p = 0.030), while high KRT20 expression was associated with reduced RFS (p = 0.042). In multivariable analysis, none of the molecular markers was an independent prognostic factor. When performing a substratification with regard to molecular markers and clinicopathological parameters, high AR expression showed improved OS in patients with high KRT20 mRNA expression (p = 0.041). Women showed significantly longer OS in cases with high AR expression (p = 0.011). High AR was associated with significantly improved CSS in males (p = 0.044) and patients with instillation therapy (p = 0.040), while OS was improved regardless of instillation therapy. Younger patients with high AR expression had significantly improved RFS (p = 0.021), CSS (p = 0.014) and OS (p = 0.007). RFS was also improved in patients with high AR and low expression of either KRT5 (p = 0.003) or KRT20 (p = 0.014), but not in patients with high expression of KRT5 or KRT20. In conclusion, high AR mRNA expression is correlated with KRT5 mRNA expression and is associated with an improved outcome in high-risk NMIBC.

Background: Recent results from the prospective validation of the Oncotype DX® recurrence score (RS) have underlined the clinical validity of the assay for the prediction of chemotherapy benefit in ER+/HER2- early stage breast cancer patients. Due to health economic restrictions, some patients have no easy access to the test. A pre-selection of tumor samples may help identify patients with a high likelihood to be spared chemotherapy. Histology and semi-quantitative IHC are hence used to select samples for Oncotype testing, but these suffer from intra- and inter-observer variability, especially for Ki-67 which is a main factor in most RS prediction algorithms. We have established and validated a tool for the prediction of RS risk classes (TAILORx cutoff RS ≤25) based on highly standardized, reproducible and locally performed RT-qPCR measurements of ERBB2, ESR1, PGR and MKI67 mRNA using the CE-marked IVD MammaTyper®. Methods: Total RNA was extracted from whole surface 10μm sections from FFPE breast cancer samples with a known RS result and a tumor cell content ≥20%. ERBB2, ESR1, PGR and MKI67 mRNA expression was measured by RT-qPCR on a CFX96 qPCR cycler using the MammaTyper® kit. A prediction model for an RS ≤25 result was established using multivariable logistic regression. Based on this model and the training data two cutoffs for confident prediction of low chemotherapy benefit patients in a clinical setting were established at 95% and 97.5% specificity. The model and the cutoffs were then fixed and validated in a second, separate set of breast cancer samples. ROC analysis was used to characterize predictive power of the continuous values resulting from the prediction model. Positive and negative predictive values for detection of an RS ≤25 result were also determined on the validation samples using the two pre-defined cutoffs. Results: The sample set for training of the prediction model encompassed 202 samples including 29 samples (14.4%) with an RS >25. In an initial multivariable model with all four markers, PGR and MKI67 were the strongest predictors while the influence of ESR in the model was lower, but still significant. ERBB2 was no significant predictor in this set of ERBB2 negative samples and was therefore excluded from the final model which was based on three markers only. This three marker model achieved an AUC of 0.920 (95% CI: 0.871-0.968) in the training samples. When applying the fixed model from the training dataset to a second separately collected set of 104 samples containing 20 samples (19.2%) with an RS >25, an AUC of 0.883 (95% CI: 0.810-0.955) was documented. When further applying the two predefined cutoffs established in the training set, 45 and 36 of the 104 validation samples (43.3% and 34.6%) had a predicted low chemotherapy benefit result (RS ≤25). Even with the less stringent cutoff, not a single one of the RS >25 cases from the validation cohort was falsely predicted as RS ≤25 sample. Conclusion: We have established a highly reliable method for prediction of Oncotype DX® low chemotherapy benefit results based on local and cost effective mRNA measurements. This method enables local pathologies to pre-assess routine samples using a highly precise molecular tool and thereby reserve the Oncotype DX® test for cases with ambiguous cancer biology. Citation Format: Lehr H-A, Aulmann S, Etzrodt A, Laible M, Hartmann K, Gürtler C, Wirtz RM, Sahin U, Varga Z. Standardized prediction of Oncotype DX® risk classes by local RT-qPCR [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-08.

Background Analysis of exhaled air is a risk-free option for bedside diagnostics. Modern breath analysis can detect very low concentrations of volatile components. Current research focuses on drug monitoring and diagnosis of various diseases. Objectives Presentation and discussion of current breath research relevant to intensive care medicine. Materials and methods The literature in PubMed was searched using the following terms: "breath analysis", "volatile organic compounds", "critically ill" combined with "drug monitoring", "propofol", "heart failure", "pneumonia", "ARDS", "renal failure", "liver failure", "sepsis" or "hemorrhage". Results Intravenously administered propofol can now be measured reliably in exhaled air. Functional impairments of the heart, lungs, kidneys and liver show characteristic influences on the exhaled air, which could serve as a new diagnostic tool in the future. Animal experiments already show promising results to detect sepsis, hemorrhage and ventilator-induced lung injury. Conclusions In the future, modern breath analysis could enable non-invasive drug monitoring and diagnostics of medical conditions relevant to intensive care medicine.

Patients with muscle-invasive bladder cancer (MIBC) that underwent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) show improved overall survival, especially those with pathological complete response (pCR). The response to NAC according to molecular subtypes has been discussed. Molecular targets such as estrogen receptor (ESR1) and human epidermal growth factor receptor 2 (ERBB2) play an important role in breast cancer management and have also been associated with urothelial bladder cancer. Hence, the association of Keratin 20 (KRT20) Keratin 5 (KRT5), ESR1, and ERBB2 mRNA expression in MIBC at transurethral resection (TUR-BT) with pCR after NAC was analyzed retrospectively. Formalin-fixed paraffin-embedded tumour tissue samples from TUR-BT of 54 patients (42 males, 12 females, median age of 64) with MIBC were analyzed for KRT20, KRT5, ESR1, and ERBB2 mRNA expression. After NAC, RC was performed, and the specimens were evaluated for pCR. Statistical analyses comprised nonparametric and chi2 testing, partition models, and Spearman correlation analyses. After NAC, 22 out of 54 patients (40.7%) had pCR. Tumours with an elevated expression of markers associated with luminal differentiation (KRT20, ERBB2, ESR1) were associated with a higher chance of pCR (55% vs. 15.8%, p = 0.009). Elevated ERBB2 expression was positively correlated with luminal expression features such as KRT20, and negatively with basal characteristics such as KRT5. Patients with MIBC showing a high expression of ERBB2, ESR1, or KRT20 have a significantly higher chance of pCR following NAC. These findings might improve patient selection for NAC in MIBC., publishedVersion

Molecular markers associated with breast cancer are assumed to be associated with outcome in non-muscle-invasive bladder cancer (NMIBC).We retrospectively investigated the association of the mRNA expression of estrogen receptor 1 (ESR1) and 2 (ESR2), progesterone receptor (PGR), MKI67, and HER2 (ERBB2) with recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) in 80 patients with stage T1 NMIBC.High expression of ESR2 (P = 0.003), ERBB2 (P0.001), and MKI67 (P = 0.029) was associated with shorter RFS. Only high ERBB2 was an independent prognostic factor for reduced RFS (HR = 2.98; P = 0.009). When sub stratifying the cohort, high ESR2 was associated with reduced RFS (P0.001), CSS (P = 0.037) and OS (P = 0.006) in patients without instillation therapy. High ESR2 was associated with reduced CSS (P = 0.018) and OS (P = 0.029) in females and with shorter RFS in both sexes (males: P = 0.035; females: P = 0.010). Patients with high ERBB2 showed reduced CSS (P = 0.011) and OS (P = 0.042) in females and reduced CSS (P = 0.012) in those without instillation, while RFS was significantly reduced irrespective of sex or instillation.High mRNA expression of ERBB2 is an independent predictor of reduced RFS in patients with stage T1 NMIBC. High ERBB2 and ESR2 are associated with reduced outcomes, especially in females and patients without instillation therapy.

Objective To examine the disease-specific survival(DSS) after checkpoint inhibitor(CPI) therapy based on FGFR alterations and FGFR mRNA expression levels in patients with metastatic urothelial cancer(mUCa) within a multi-center cohort. Methods Within a cohort of 72 patients with mUCa from five academic centers in Germany FGFR alterations, as well as FGFR1-4 mRNA expression levels in tumor samples from the primary tumor or metastatic sites. Spearman rank correlations, logistic regression, as well as Kaplan-Meier survival analyses and univariate Cox proportional hazards regression models were employed to examine the impact of different FGFR patterns on the DSS after CPI treatment. Results FGFR3 mutations or gene fusions (gene alterations) were detected in 16.9% of all samples. Patients with or without FGFR3 gene alterations did not show different oncological outcomes undergoing CPI treatment. Low expression of FGFR2 mRNA alone, as well as the combination of either low FGFR2mRNA expression and FGFR3 gene alteration or high FGFR3mRNA expression (P = 0.027), identified a subgroup of patients with unfavorable outcomes, comprising 40% of the total cohort. This trend was also observed in univariate Cox proportional hazards regression analysis(FGFR3 gene alteration: Hazard ratio(HR) 5.33, 95%Confidence interval(CI)1.76-15.0, P = 0.004; FGFR3mRNA expression:HR 3.04, 95%CI 1.40-7.13, P = 0.005). Conclusion Assessment of FGFR mRNA expression identified a high-risk subgroup of patients with mUCa. These patients showing overexpression of FGFR3 mRNA were found to have unfavorable DSS after CPI treatment. Using this approach may be suitable for identifying a patient population with poor response to CPI treatment, which may benefit from early FGFR inhibition.

Simple Summary We examined the relevance of immunoglobulin kappa C (IGKC), an important part of the humoral immune system, in early breast cancer. To our knowledge, our results confirm for the first time previous retrospective findings of a cancer recurrence protective role of IGKC in a large cohort of early breast cancer patients who were treated in the prospective, randomized FinHer clinical trial. We show that an increased amount of IGKC in the tumor is linked to longer distant metastasis-free survival, especially in patients whose breast cancer does not express hormone receptors or human epidermal growth factor receptor-2. This type of breast cancer often has poor prognosis. Since an improved outcome is associated with the presence of tumor-infiltrating IGKC expressing immune cells, this may be a further argument for the use of immunotherapies in these patients. We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis also including age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870-0.995, p = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724-0.983, p = 0.029), but not in luminal (HR 0.957, 95% CI 0.867-1.056, p = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826-1.055, p = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (P-interaction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

Background In metastatic clear cell renal cell carcinoma (ccRCC), different combination therapies, each including anti-PD-1 immune checkpoint blockade (ICB), are applied as first-line treatment. Robust predictive biomarkers for rational upfront therapy decisions are lacking, although they are urgently needed. Recently, we showed that CTLA4 promoter methylation predicts response to ICB in melanoma. Here, we aimed to investigate CTLA4 methylation in ccRCC and its utility to serve as a predictive biomarker for anti-PD-1 based ICB in metastatic ccRCC. Methods CTLA4 methylation was analyzed with regard to transcriptional gene activity (mRNA expression), intratumoral immune cell composition, and clinical course in two ccRCC cohorts obtained from The Cancer Genome Atlas (TCGA cohort, n=533) and the University Hospital Bonn (UHB Non-ICB Cohort, n=116). In addition, CTLA4 methylation as well as CD8+ T cell infiltrates and PD-L1 expression were evaluated in pre-treatment samples from a multicenter cohort (RCC-ICB Cohort, n=71). Patients included in the RCC-ICB Cohort were treated with either first line anti-PD-1 based combination therapy (n=25) or monotherapy post–tyrosine kinase inhibition in second line or later. Analyses were performed with regard to treatment response according to RECIST, progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) following treatment initiation. Results CTLA4 promoter hypomethylation was significantly correlated with CTLA4 mRNA expression, lymphocyte infiltration, and poor OS in both primary ccRCC cohorts (TCGA: HR 0.30 (95% CI 0.18 to 0.49), p, publishedVersion

OBJECTIVE To investigate the role of forkhead box protein M1 (FOXM1) mRNA expression and its prognostic value in stage pT1 non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS Clinical data and formalin-fixed paraffin-embedded tissues from transurethral resection of the bladder from patients with stage pT1 NMIBC, treated with an organ-preserving approach, were analysed retrospectively. Total RNA was isolated using commercial RNA extraction kits, and mRNA expression of FOXM1, MKI67, KRT20 and KRT5 was measured by single-step quantitative RT-PCR using RNA-specific TaqMan Assays. Statistical analysis was performed using Spearman's Rho, Wilcoxon or Kruskal-Wallis tests, Kaplan-Meier estimates of recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS) and Cox regression analysis. RESULTS Data from 296 patients (79.4% men, median age 72 years) were available for the final evaluation. Spearman correlation analysis showed that mRNA expression of FOXM1 was significantly correlated with MKI67 (ρ: 0.6530, P < 0.001) and with the luminal subtype, reflected by the positive correlation with KRT20 (ρ: 0.2113, P < 0.001). Furthermore, there was also a strong correlation of FOXM1 expression with adverse clinical and pathological variables, such as concomitant carcinoma in situ (P = 0.05), multifocal tumours (P = 0.005) and World Health Organization 1973 grade 3 disease (P < 0.001). Kaplan-Meier analysis showed overexpression of FOMX1 to be associated with worse PFS (P = 0.028) and worse CSS (P = 0.015). FOXM1 overexpression was also shown to be a predictive risk factor for CSS (hazard ratio 1.61 [1.13-2.34], L-R chi-squared: 7.19, P = 0.007). FOXM1 overexpression identified a subgroup of patients within the luminal subtype with worse RFS (P = 0.017), PFS (P < 0.001) and CSS (P = 0.015). Patients with low FOXM1 expression had better outcomes, irrespective of instillation therapy, whereas patients with high FOXM1 expression benefitted from intravesical chemotherapy with mitomycin C. CONCLUSION High FOXM1 expression was associated with adverse clinical and pathological features and worse outcomes, and predicted response to intravesical instillation therapy in patients with stage pT1 NMIBC.

Objective Digital subtraction angiography is the gold standard for diagnosis of vascular pathology. The value of angiography of non-target vessels following mechanical thrombectomy for the treatment of acute ischemic stroke (AIS) is unknown. Patients and Methods Consecutive patients treated with mechanical thrombectomy for AIS due to large vessel occlusion (LVO) at an academic institution between February 2016 and December 2018 were retrospectively reviewed. Demographic information, clinical data, and procedure details were recorded. Descriptive statistics were used to evaluate the utility of non-target vessel angiography. Results One hundred and fifty-six patients presenting with AIS due to LVO were treated with 159 mechanical thrombectomy procedures. Median age was 71.5 years. Ninety-one (57.2%) procedures were followed with a diagnostic cerebral angiogram of non-target vessels. Previously unknown findings were identified in 4 (4.4%) procedures. Management change due to the non-target vessel angiogram finding occurred in 3 (3.3%) cases and included one contralateral mechanical thrombectomy. No complications occurred as a result of the non-target vessel angiogram. Conclusion Angiographic imaging of non-target vessels following mechanical thrombectomy identified previously unknown vascular pathology in 4.4% of procedures and resulted in a clinical management change in 3.3% of cases.

Introduction Cervical cancer is the fourth most frequent cancer in women worldwide. Addition of the VEGF antibody bevacizumab in combination with platinum-containing chemotherapy achieved an improvement in overall survival in advanced cervical cancer. To date there are no data on neoadjuvant use of bevacizumab. We therefore studied the benefit of neoadjuvant combined therapy with bevacizumab in a group of cervical cancer patients. Patients and Methods This retrospective cohort study analysed 14 patients with cervical cancer FIGO stages 1b1 to IV who received neoadjuvant platinum-containing chemotherapy in combination with bevacizumab. The comparative cohort consisted of 16 patients who were treated with neoadjuvant platinum-containing chemotherapy alone. The response rates were determined by means of preoperative clinical examination, diagnostic imaging (RECIST), changes in tumour markers (SCC) and by histopathology. Results A clinical response was found in 93.8% (n = 15) of patients after bevacizumab-free therapy and in 100% (n = 14) of the patients who were treated with bevacizumab in addition. Combined therapy with bevacizumab led to a higher rate of clinical complete remission (42.9 vs. 12.5%; p = 0.072) and significantly improved the reduction in tumour size (Δ longest diameter: 3.7 vs. 2.5 cm; p = 0.025). Downgrading was observed in 100% of all patients treated with bevacizumab compared with 75% in the control arm. The rate of pathological complete remission (pCR) was not altered significantly (28.6% [n = 4] vs. 37.5% [n = 6]; p = 0.460). Discussion Overall, combined therapy with bevacizumab led to a better clinical response. Operability was therefore improved more often. Because of the small patient cohort, larger prospective studies are necessary to validate the effect of neoadjuvant combined therapy with bevacizumab.

Background/aims Prevalent dialysis patients have low scores of health-related quality of life (HRQOL) which are associated with increased risk of hospitalization and mortality. Also in CKD-5 non-dialysis patients, HRQOL scores seem to be lower as compared with the general population. This study firstly aimed to compare HRQOL between CKD-5 non-dialysis and prevalent dialysis patients in a cross-sectional analysis and to assess longitudinal changes over 1 year after the dialysis initiation. Secondly, the correlation between HRQOL and physical activity (PA) was explored. Methods Cross-sectional 44 CKD-5 non-dialysis, 29 prevalent dialysis, and 20 healthy controls were included. HRQOL was measured by Short Form-36 questionnaires to measure physical and mental domains of health expressed by the physical component summary (PCS) and mental component summary (MCS) scores. PA was measured by a SenseWear™ pro3. Longitudinally, HRQOL was assessed in 38 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before dialysis initiation until 1 year after dialysis initiation. Results PCS scores were significantly lower both in CKD-5 non-dialysis patients and in prevalent dialysis patients as compared with healthy controls (p

// Markus Eckstein 1, * , Ralph M. Wirtz 2, 3, * , Carolin Pfannstil 1, * , Sven Wach 4, * , Robert Stoehr 1, * , Johannes Breyer 6, * , Franziska Erlmeier 7, * , Cagatay Gunes 8, * , Katja Nitschke 5, * , Wilko Weichert 7, * , Wolfgang Otto 6, * , Bastian Keck 4, * , Sebastian Eidt 3, * , Maximilian Burger 6, * , Helge Taubert 4, * , Bernd Wullich 4, * , Christian Bolenz 8, * , Arndt Hartmann 1, * and Philipp Erben 5, * 1 Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany 2 STRATIFYER Molecular Pathology GmbH, Cologne, Germany 3 Institute of Pathology at The St. Elisabeth Hospital Koln-Hohenlind, Cologne, Germany 4 Department of Urology, University of Erlangen-Nuremberg, Erlangen, Germany 5 Department of Urology Mannheim, University of Heidelberg, Mannheim, Germany 6 Department of Urology, University of Regensburg, Regensburg, Germany 7 Institute of Pathology, Technical University Munich, Munich, Germany 8 Department of Urology, University of Ulm, Ulm, Germany * On behalf of the BRIDGE-Consortium Germany Correspondence to: Markus Eckstein, email: markus.eckstein@uk-erlangen.de Keywords: bladder cancer; PD-L1; checkpoint inhibitors; molecular therapy stratification; immunohistochemistry Received: October 26, 2017 Accepted: February 10, 2018 Epub: February 19, 2018 Published: March 13, 2018 ABSTRACT Background: Immunohistochemical PD-L1 assessment is currently used to identify responders towards checkpoint inhibitors although it is limited by inter-observer effects. Here, we conducted a multi-center round robin test to prove the possibility of assessing the PD-L1 status by gene expression to avoid inter-observer effects. Patients and methods: Gene expression of PD-L1 was analyzed in a total of 294 samples (14 cases non-muscle invasive and muscle-invasive bladder cancer; MIBC) in seven centers by a RT-qPCR kit and compared with immunohistochemical scoring of three pathologists (DAKO, 22c3). Both assays were compared towards prognosis prediction in a cohort of 88 patients with MIBC. Results: PD-L1 gene expression revealed very high inter center correlation (centrally extracted RNA: r = 0.68–0.98, p ≤ 0.0076; locally extracted RNA: r = 0.81–0.98, p ≤ 0.0014). IHC Inter-observer concordance was moderate to substantial for immune cells (IC), fair for combined IC/ tumor cell (TC) (IC: κ = 0.50–0.61; IC + TC: κ = 0.50), and fair for TC scoring (κ = 0.26–0.35). Gene expression assessment resulted in more positive cases (9/14 cases positive vs. 6/14 cases [IHC]) which could be validated in the independent cohort. Positive mRNA status was associated with significantly better overall and disease-specific survival (5-year OS: 50% vs. 26%, p = 0.0042, HR = 0.48; 5 year DSS: 65% vs. 40%, p = 0.012, HR = 0.49). The 1% IHC IC cut-off also revealed significant better OS (5 year OS: 58% vs. 31%, p = 0.036, HR = 0.62). Conclusion: Gene expression showed very high inter-center agreement. Gene expression assessment also resulted in more positive cases and revealed better prognosis prediction. PD-L1 mRNA expression seems to be a reproducible and robust tool for PD-L1 assessment.

Background: Tumor-infiltrating lymphocytes (TILs) have been shown to be of prognostic value in several cancer types. In early breast cancer, TILs have a prognostic utility, as well, especially in HER2-positive and triple-negative breast cancer (TNBC). TILs presence is broadly associated with improved survival, however there is controversy regarding TILs subpopulations. In general, T cell infiltration is higher in non-luminal and more aggressive tumors, like the basal-like subtype. Among TILs subpopulations, CD8-positive T cell infiltration is associated with better outcome, whereas high numbers of FOXP3-positive T regulatory cells are associated with worse outcome in ER-positive tumors and better outcome in HER2-positive and TNBC tumors. Patients and Methods: Early breast cancer patients, treated with anthracycline-based chemotherapy within two randomized trials (HE10/97 and HE10/00) were included in the study. We evaluated, by qRT-PCR, 826 macrodissected formalin-fixed paraffin-embedded tumor tissue samples for mRNA expression of CD3, CD8 and FOXP3for potential prognostic significance in terms of disease-free survival (DFS) and overall survival (OS). TILs were evaluated in whole sections as percent of total cells. Results: Median age was 52.7 years, while 54.2% of the patients were postmenopausal and 79.0% ER/PgR-positive. After a median follow-up of 133.0 months, 255 patients (30.9%) had died and 314 (38.0%) had disease progression. All three mRNA markers were positively correlated with TILs (Spearman's r=0.52 for CD3, 0.41 for CD8 and 0.47 for FOXP3, all p-values Conclusions: High CD3 and CD8 mRNA expression in early breast cancer patients is of prognostic value for decreased risk for relapse and, in the future, could potentially be of importance in deciding the most appropriate therapeutic strategy in light of the recent immune-related treatment developments. Citation Format: Tsiatas M, Kalogeras KT, Manousou K, Wirtz RM, Gogas H, Veltrup E, Zagouri F, Lazaridis G, Koutras A, Christodoulou C, Pentheroudakis G, Petraki C, Bafaloukos D, Pectasides D, Kosmidis P, Samantas E, Karanikiotis C, Papakostas P, Dimopoulos M-A, Fountzilas G. Evaluation of the prognostic value of CD3, CD8 and FOXP3 mRNA expression in early breast cancer patients treated with anthracycline-based adjuvant chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-03.

Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification. We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS). We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p

Paragangliomas are predominantly benign tumors, but in some cases invasive growth and also metastasis are observed. Given the limited number of nonsurgical treatment options, novel target structures for diagnostics and therapy of this tumor entity are urgently needed. In the present study, expression of all five somatostatin receptor (SST) subtypes, chemokine receptor CXCR4 and endothelin receptor type A (ETA) was assessed by means of immunohistochemistry in a total of 66 paraffin-embedded paraganglioma samples from 55 patients. The stainings were rated by means of the Immunoreactive Score and correlated to clinical data and to succinate dehydrogenase subunit B (SDHB) expression. SST2A was by far the most prominent receptor in the paragangliomas investigated. It was present in 89% of the tumors at a high intensity, followed by SST5, SST3, SST1 and SST4, which were detected in 47%, 35%, 35% and 13% of the samples, respectively. SDHB positive tumors exhibited significantly higher SST2A and SST3 expression as compared to SDHB negative cases. There was no correlation between SST and Ki-67 expression or grading of the tumors and no difference in SST expression between primary tumors and metastases. Cell surface expression of CXCR4 and ETA was detected only in few samples. On tumor capillaries, however, exceptionally strong staining for these two receptors was noticed in the vast majority of the tumors. In conclusion, paragangliomas are well suited for SST2A-based diagnostics and treatment modalities. An indirect targeting of these highly vascularized tumors via CXCR4 or ETA may also represent a promising future strategy.

INTRODUCTION: High-risk non–muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder. The mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured by reverse transcription quantitative real-time polymerase chain reaction. AR expression was also correlated to KRT5 and KRT20 mRNA expression. RESULTS: Kaplan-Meier analysis indicated that high AR1 mRNA expression ≥35.47 is associated with statistically significant better recurrence-free survival (RFS) (P = .0007), progression-free survival (PFS) (P = .0420), and cancer-specific survival (CSS) (P = .0050). Multivariate Cox regression analysis revealed that high AR1 mRNA expression is an independent prognostic marker for RFS (P = .0029) and CSS (P = .0119). Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 (rs: 0.3171, P

Thrombotic microangiopathy (TMA) is a pattern of endothelial damage that can be found in association with diverse clinical conditions such as malignant hypertension. Although the pathophysiological mechanisms differ, accumulating evidence links complement dysregulation to various TMA syndromes and in particular the atypical hemolytic uremic syndrome. Here, we evaluated the role of complement in nine consecutive patients with biopsy-proven renal TMA attributed to severe hypertension. Profound hematologic symptoms of TMA were uncommon. In six Out of nine patients, we found mutations C3 in three, CFI in one, CD46 in one, and/or CFH in two patients either with or without the risk CFH-H3 haplotype in four patients. Elevated levels of the soluble C5b-9 and renal deposits of C3c and C5b-9 along the vasculature and/or glomerular capillary wall, confirmed complement activation in vivo. In contrast to patients without genetic defects, patients with complement defects invariably progressed to end-stage renal disease, and disease recurrence after kidney transplantation seems common. Thus, a subset of patients with hypertension-associated TMA falls within the spectrum of complement-mediated TMA, the prognosis of which is poor. Hence, testing for genetic complement abnormalities is warranted in patients with severe hypertension and TMA on renal biopsy to adopt suitable treatment options and prophylactic measures.

BACKGROUND: Prevention of bone metastases is a major issue for breast cancer patients, as it would improve quality of life in a population where long survival is anticipated. PATIENTS AND METHODS: Early breast cancer patients, who had been treated with anthracycline-based chemotherapy within two randomized trials, were included in the study. We evaluated, by quantitative reverse transcription–polymerase chain reaction, 819 formalin-fixed paraffin-embedded tumor tissue samples for mRNA expression of RANK, OPG, and RANKL, as well as their ratios, for potential prognostic significance for the development of bone metastases and also for disease-free survival (DFS) and overall survival. RESULTS: Median age was 52.7 years, whereas 54.2% of the patients were postmenopausal and 78.3% estrogen receptor/progesterone receptor positive. After a median follow-up of 119.9 months, 226 patients (27.6%) had died and 291 patients (35.5%) had disease progression. Low mRNA expression of RANKL was associated with postmenopausal status and greater number of positive lymph nodes (P = .002 and P

// Sebastien Rinaldetti 1 , Ralph Markus Wirtz 2 , Thomas Stefan Worst 3 , Markus Eckstein 4 , Cleo Aaron Weiss 5 , Johannes Breyer 6 , Wolfgang Otto 6 , Christian Bolenz 7 , Arndt Hartmann 4 and Philipp Erben 3 1 Department of Hematology and Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany 2 Stratifyer Molecular Pathology GmbH, 50935 Koln, Germany 3 Department of Urology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany 4 Institute of Pathology, University Erlangen-Nuremberg, 91054 Erlangen, Germany 5 Institute of Pathology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany 6 Department of Urology, University of Regensburg, 93053 Regensburg, Germany 7 Department of Urology, University of Ulm, 89075 Ulm, Germany Correspondence to: Sebastien Rinaldetti, email: sebastienrinal@hotmail.com Keywords: FOXM1, muscle invasive bladder cancer, KI67, subclassification, survival prediction Received: December 28, 2016 Accepted: April 10, 2017 Published: April 24, 2017 ABSTRACT Forkhead box M1 (FOXM1) is a late cell cycle gene that plays a crucial role in carcinogenesis and chemotherapeutic drug resistance. In this study, the impact of FOXM1 expression on patient outcome was investigated for the first time in formalin fixed and paraffin embedded (FFPE) samples of chemotherapy naive muscle-invasive bladder cancer (MIBC) patients. Expression analyses were performed on the Mannheim cohort (n=84) and validated on the independent Chungbuk cohort (n=61). In a Cox’ proportional hazards model, a distinct FOXM1 expression cut-off dividing both cohorts in a ‘high-risk’ and ‘low-risk’ group has been determined. Multivariate analyses showed that FOXM1 is an independent risk factor for outcome prediction superior to the TNM system. The FOXM1 ‘high-risk’ group had a 4- to 7-fold increased risk of death (p

Background Quantitative determination of estrogen receptor mRNA expression in luminal breast tumors is predictive for benefit from adjuvant tamoxifen compared to placebo treatment as has been shown in the large randomized NSABP B-14 trial, while protein determination by IHC or LBA is not (Kim et al JCO 2011). Interestingly, the ultrahigh expression of ESR1 mRNA (above ER score 10 by Oncotype test) has been indicative for tamoxifen benefit. This predictive cut-off value of mRNA expression is significantly higher than the diagnostic cut-off (at ER score 6.5). Here we tested wether the ultrahigh expression of ESR1 mRNA determined by commercial MammaTyper® testing is predictive for survival after neoadjuvant chemotherapy treatment of advanced breast cancer. Materials and Methods Pretreatment core cut biopsies from n=54 patients with PBC treated within a randomized phase II trial (2) of anthracyline/taxane based NAC with available clinical follow-up information were examined. RNA was extracted from the FFPE sections and ESR1 mRNA from each section was measured by commercial assays. For technical comparison of ESR1 mRNA values by Oncotype DX versus MammaTyper® from n=113 surgical samples were analyzed by both commercial assays in a blinded fashion. Statistical analysis was performed using the SAS JMP® 9.0.0 software. Results Quantification of ESR1 mRNA expression after RNA extraction from separate slices of 113 primary breast tumors and determination by different commercial RT-qPCR assays resulted in high correlation of continuous expression results (Spearman r=0,85; p Conclusion Previous data suggest that ultrahigh expression of ESR1 mRNA is predictive for improved overall survival and tamoxifen benefit (1). Here we show that ultrahigh expression of ESR1 mRNA is also prognostic in more advanced breast tumors after neoadjuvant chemotherapy. These findings validate the importance of quantitative determination of estrogen receptor expression and substantiate the understanding of receptor expression being a continuous determinant with indication specific cut-off values. Ultrahigh expression of ESR1 seems to identify a distinct subset of luminal breast tumors with superior prognosis and benefit from tamoxifen treatment. These findings warrant further investigation, which are currently being done in independent large breast cancer cohorts. Citation Format: Wirtz RM, Scheffen I, Marme F, Laible M, Sclombs K, Schumacher C, Schneeweiss A, Eidt S, Sinn H-P. Predictive value of ultra-high ESR1 mRNA expression in early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-25.

Differential expression of cytokeratins (CK) is a characteristic feature of chemoresistant luminal (KRT20) and chemosensitive intrinsic aggressive basal (KRT5) subtypes in muscle-invasive bladder cancer (MIBC). We investigated mRNA expression of KRT5 and KRT20 and its predictive value in stage pT1 bladder cancer. In retrospective analysis of clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder, a single-step RT-qPCR was used to measure mRNA expression. Furthermore, immunohistochemical (IHC) staining of CK20, panCK, and MIB1 was performed. Valid measurements were obtained from 231 samples out of a series of 284 patients. Spearman correlation revealed significant associations between mRNA and protein expression of KRT20/CK20 (ρ 0.6096, p

Background: Chemotherapy with anthracyclines is associated with life-threatening electrocardiographic alterations including corrected QT (QTc) interval prolongation. Patients and Methods: In this study we assessed the effect of epirubicin, cyclophosphamide, and docetaxel (EC-Doc) on the QTc interval in 10 patients with early breast cancer. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography (ECG), and serum cardiac markers at baseline and after 4 cycles of EC and 4 cycles of docetaxel. To evaluate the influence of interobserver variation, the QTc interval was analyzed by a cardiologist, a gynecologist, and with automated ECG interpretation software. Results: There was a significant QTc prolongation after EC treatment independent of the investigator. In addition, a significant increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels was noted after EC treatment. QTc prolongation and NT-proBNP levels normalized after docetaxel treatment. Other biochemical markers were within normal ranges. No clinically relevant effect on left ventricular ejection fraction was observed. Conclusion: This prospective study demonstrated that EC treatment increases the QTc interval and NT-proBNP levels in women with early breast cancer. This effect was reversible and independent of docetaxel administration. Moreover, the treating physician can safely perform QTc interval evaluation as part of clinical routine independent of his/her specialty. Due to the small number of patients, further conclusions are limited at this point.

IntroductionEnd-stage renal disease (ESRD) strongly associates with cardiovascular disease (CVD) risk. This risk is not completely mitigated by renal replacement therapy. Endothelial dysfunction (ED) and low-grade inflammation (LGI) may contribute to the increased CVD risk. However, data on serum biomarkers of ED and LGI during the transition to renal replacement therapy (dialysis and kidney transplantation) are scarce.MethodsWe compared serum biomarkers of ED and LGI between 36 controls, 43 participants with chronic kidney disease (CKD) stage 5 non-dialysis (CKD5-ND), 20 participants with CKD stage 5 hemodialysis (CKD5-HD) and 14 participants with CKD stage 5 peritoneal dialysis (CKD5-PD). Further, in 34 and 15 participants repeated measurements were available during the first six months following dialysis initiation and kidney transplantation, respectively. Serum biomarkers of ED (sVCAM-1, E-selectin, P-selectin, thrombomodulin, sICAM-1, sICAM-3) and LGI (hs-CRP, SAA, IL-6, IL-8, TNF-α) were measured with a single- or multiplex array detection system based on electro-chemiluminescence technology.ResultsIn linear regression analyses adjusted for potential confounders, participants with ESRD had higher levels of most serum biomarkers of ED and LGI than controls. In addition, in CKD5-HD levels of serum biomarkers of ED and LGI were largely similar to those in CKD5-ND. In contrast, in CKD5-PD levels of biomarkers of ED were higher than in CKD5-ND and CKD5-HD. Similarly, in linear mixed model analyses sVCAM-1, thrombomodulin, sICAM-1 and sICAM-3 increased after PD initiation. In contrast, incident HD patients showed an increase in sVCAM-1, P-selectin and TNF-α, but a decline of hs-CRP, SAA and IL-6. Further, following kidney transplantation sVCAM-1, thrombomodulin, sICAM-3 and TNF-α were lower at three months post-transplantation and remained stable in the three months thereafter.ConclusionsLevels of serum biomarkers of ED and LGI were higher in ESRD as compared with controls. In addition, PD initiation and, less convincingly, HD initiation may increase levels of selected serum biomarkers of ED and LGI on top of uremia per se. In contrast to dialysis, several serum biomarkers of ED and LGI markedly declined following kidney transplantation.

OBJECTIVEMechanical thrombectomy is the established treatment for acute ischemic stroke due to large vessel occlusion (LVO). The authors sought to identify early predictors of a favorable outcome in stroke patients treated with mechanical thrombectomy.METHODSConsecutive patients with ischemic stroke due to LVO who underwent mechanical thrombectomy at a Comprehensive Stroke Center in the US between 2016 and 2018 were retrospectively reviewed. Demographics, stroke and treatment characteristics, as well as functional outcome at 90 days were collected. Clinical predictors of 90-day functional outcome were assessed and compared to existing indices for prompt neurological improvement. Analyses of area under the receiver operating characteristic curve were performed to estimate the optimal thresholds for absolute 24-hour and delta (change in) National Institutes of Health Stroke Scale (NIHSS) scores for functional outcome prediction.RESULTSA total of 156 patients (median age 71.5 years) underwent 159 mechanical thrombectomies. The M1 segment of the middle cerebral artery was the most frequent site of occlusion (57.2%). The median NIHSS score before thrombectomy was 18 (IQR 14–24). A postthrombectomy Thrombolysis in Cerebral Infarction score of 2B or 3 was achieved in 147 procedures (92.4%). The median NIHSS score 24 hours after thrombectomy was 14 (IQR 6–22). Good functional outcome at 90 days (modified Rankin Scale score 0–2) was achieved in 37 thrombectomies (23.9%). An absolute 24-hour NIHSS score ≤ 10 (OR 25.929, 95% CI 8.448–79.582, p < 0.001) and a delta NIHSS score ≥ 8 between baseline and 24 hours (OR 4.929, 95% CI 2.245–10.818, p < 0.001) were associated with good functional outcome at 90 days. The 24-hour NIHSS score cutoff of 10 outperformed existing indices for prompt neurological improvement in the ability to predict 90-day functional outcome.CONCLUSIONSAn NIHSS score ≤ 10 at 24 hours after mechanical thrombectomy was independently associated with good functional outcome at 90 days.

Background Current evidence suggests that patients with Luminal A early breast cancer can skip chemotherapy or extended endocrine therapy, but immunohistochemistry-based biomarker analysis for St Gallen subtyping may not be reproducible. We asked whether RT-qPCR can be used instead to address this clinical question. Methods RNA was extracted from tumor material derived from ER+/HER2- patients receiving adjuvant endocrine treatment for low-risk cancers and was semi-quantified by RT-qPCR with the MammaTyper®. St Gallen subtypes were based on the mRNA expression of ERBB2/HER2, ESR1/ER, PGR/PR and MKI67/Ki67 after dichotomizing at predefined cut-offs. Differences in distant disease-free survival (DDFS) were assessed by Kaplan Meier analysis and Cox regression. Results With a median follow up of 7.8 years, there were ten events in the group of 195 Luminal A-like tumors (5.1%) and 18 events in the remaining 127 tumors (14.1%), consisting mostly of Luminal B-like cases (N = 119). Luminal A-like had significantly better DDFS over the entire follow-up period (HR 0.35, 95% CIs 0.16–0.76, p = 0.0078) with a trend towards reduced probability of recurrences also in the late phase (> 5 years) (HR 0.20, p = 0.052). The survival advantage spanning the entire follow-up period persisted in the pN0 or pN0-N1 subgroups or after correcting for clinicopathological parameters. MKI67 alone significantly predicted for worse DDFS (HR 2.62, 95% CIs 1.24–5.56, p = 0.0088). Conclusions St Gallen Luminal A-like tumors identified by RT-qPCR display markedly low rates of distant recurrence at ten years follow-up. Patients with such tumors could be spared chemotherapy due to the obviously unfavourable benefit/toxicity ratio.

BackgroundCardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited.MethodsWe examined cross-sectional Spearman's rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N-is an element of-(carboxymethyl) lysine (CML), N-is an element of-(carboxyethyl) lysine (CEL), N-delta-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-alpha.ResultsAfter adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI.ConclusionsIn individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI.

INTRODUCTION: Gender-specific differences have led to the androgen receptor (AR) being considered a possible factor in the pathophysiology of urothelial carcinoma of the bladder (UCB), but the exact role remains unclear. MATERIALS AND METHODS: The association of AR mRNA expression with clinicopathological features was retrospectively analyzed in two previously described cohorts. The first cohort consisted of 41 patients with all stages of UCB treated at Aarhus University Hospital, Denmark. The second cohort consisted of 323 patients with muscle-invasive bladder cancer (MIBC) accumulated by the Cancer Genome Atlas (TCGA) Research Network. RESULTS: AR mRNA expression is significantly higher in non-muscle-invasive bladder cancer (NMIBC) when compared to MIBC (P =.0004), with no relevant changes within the different stages of MIBC. AR mRNA expression was significantly associated with TCGA molecular subtypes (P

e16532 Background: The objective of the present study was to assess FGFR mutattions and fusions from matched urine and tissue samples from patients suspicious of bladder cancer and undergoing first TURB at the pilot center of the multicentric BRIDGister RealWorld Experience trial Methods: For this pilot study paraffin fixed pretreatment tissue samples from the first TURB of 28 pts participating in the BRIDGister trial and matched urine samples were prospectively collected and analyzed. RNA from FFPE tissues were extracted by commercial kits and analyzed by Therascreen FGFR IVD kit (Qiagen GmbH, Hilden). In addition urine samples were shipped for central isolation of extracellular vesicles and extraction of RNA (exoRNA.Exosome Diagnostics GmbH, Martinsried) and subsequently centrally analyzed by QIAcuity digital PCR (Qiagen, Hilden). Additional urine testing was performed by further technologies including central cytology. Concordance, Kruskal-Wallis, MannWhitney and Sensitivity/Specificity tests were analyzed by JMP 9.0.0 (SAS software). Results: The pilot cohort of the BRIDGister trial consisted of 28 patients (median age: 73, male 71% vs female 29%) of diverse clinical stages (Benign lesions/no tumor 21%, pTa 32%, pT1 21%, pT2 21%) and WHO 1973 grade (G1 7%, G2 43%, G3 21%). Based on FFPE tissue testing using Therascreen FGFR IVD kit 9 out of 28 patients exhibited FGFR alterations (32%). Based on exosomal RNA (exoRNA) and subsequent dPCR testing 8 out of 21 matched urine sampels were FGFR positive (38%). Comparison with tissue testing as probable gold standard revealed 71% sensitivity, 78% specificity, 63% PPV and 85%NPV. There were 3 patients being FGFR positive for exoRNA from urine with no mutation found in the corresponding TUR biopsy. One of these mutations could be validated by independent urine test. Furthermore one tumor harbored two tissue mutations (R248C, Y373C) but three urine mutations (R248C, Y373C, G370C) indicating substantial tumor heterogeneity. One FGFR3-TACC3 fusion was detected from a benign lesion, which was not found by the exosomal urine test. Conclusions: Extraction of exosomal RNA from urine followed by highly sensitive dPCR mutation testing is feasible with good concordance to matched tissue testing. Urine testing bears the potential of detecting additional mutations in a real world setting and might evolve as alternative approach for FGFR3 screening in a non invasive fashion without the need of transurethral biopsy. Discordant cases are further followed up and might reveal validation of mutation status in upcoming recurrences.Further exploration is warranted and includes the potential of monitoring patients with FGFR before and after therapeutic intervention. By the time of the congress an update of the data with approximately 50 matched pairs will be presented.

e16533 Background: The objective of the present study was to identify molecular charactersitics associated with FGFR positive tumors in matched urine and TUR biopsy samples from patients being suspicious of bladder cancer and undergoing first TURB at the pilot center of the multicentric BRIDGister Real World Experience trial that are helpful for patient management and prognosis. Methods: For this pilot study paraffin fixed pretreatment tissue samples from the first TURB of 28 pts participating in the BRIDGister trial and matched urine samples were prospectively collected and analyzed. RNA from FFPE tissues were extracted by commercial kits and analyzed by Therascreen FGFR IVD kit (Qiagen GmbH, Hilden). Relative gene expression of subtyping markers (KRT5, KRT0) as well as FGFR1, FGFR2, FGFR3, FGFR4, ERBB2 was centrally tested by standardized test systems (STRATIFYER Molecular Pathology GmbH, Cologne). In addition urine samples were analyzed by commercially available urine tests (UBC Rapid, BTA stat, NMP22). Spearman correlation, Kruskal-Wallis, MannWhitney and Sensitivity/Specificity tests were done by JMP 9.0.0 (SAS software). Results: The pilot cohort of the BRIDGister trial consisted of 28 patients (median age: 73, male 71% vs female 29%) of diverse clinical stages (Benign lesions/no tumor 21%, pTa 32%, pT1 21%, pT2 21%) and WHO 1973 grade (G1 7%, G2 43%, G3 21%). Based on FFPE tissue testing using Therascreen FGFR IVD kit 9 out of 28 patients exhibited FGFR alterations (32%). FGFR positive tumors were associated with high expression of FGFR3 mRNA (r = 5.951, p = 0.0011) but low FGFR1 mRNA as well as FGFR4 mRNA (r = -0.3882, p = 0.0412 and r = -0.6305, p = 0.0004, respectively). Interestingly, FGFR alteration was positively associated with the basal marker KRT5 (r = 0.3929, p = 0.0386), but not with luminal KRT20 mRNA expression (r = -0.0208, p = 0.9179). Moreover FGFR3 altered bladder cancer was associated with elevated NMP22 levels in pretreatment urine (r = 0.3978, p = 0.0361). Conclusions: In early bladder cancer FGFR3 alterations are tightly associated with a characteristic FGFR mRNA signature. Mutation/Fusion of FGFR3 results in high FGFR3 but low FGFR1 and FGFR4 mRNA expression, which might be i.a. relevant for the response to FGFR inhibition and important to predict outcome of FGFR inhibitors. Morever FGFR alteration was associated with elevated NMP22 urine levels, which might be helpful for detecting and monitoring FGFR altered bladder cancer in a non invasive fashion. These results warrant further investigation and its impact on outcome prediction (BCG responsiveness, recurrence, proegression, etc) will be prospectively analyzed in the framework of the ongoing multicenter BRIDGister Real World Experience trial.

Pathological staging and grading are crucial for risk assessment in non-muscle-invasive bladder cancer (NMIBC). Molecular grading might support pathological evaluation and minimize interobserver variability. In this study, the well-established breast cancer markers ESR1, PGR, ERBB2, and MKI67 were evaluated as potential molecular markers to support grading and staging in NMIBC. We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with NMIBC. Messenger RNA (mRNA) expression of the aforementioned markers was measured by single-step reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) using RNA-specific TaqMan assays. Relative gene expression was determined by normalization to two reference genes (CALM2 and B2M) using the 40-ΔΔCT method and correlated to histopathological stage and grade. Pathological assessment was performed by an experienced uropathologist. Statistical analysis was performed using the SAS software JMP 9.0.0 version and GraphPad Prism 5.04. Of 381 cases of NMIBC, samples of 100 pTa and 255 pT1 cases were included in the final study. Spearman rank correlation revealed significant correlations between grade and expression of MKI67 (r = 0.52, p

Background Recently, the Food and Drug Administration (FDA)/European Medicines Agency (EMA) restricted first-line use of atezolizumab and pembrolizumab in patients with metastasised urothelial carcinoma by defining distinct programmed cell death ligand-1 cut-offs. We analysed the diagnostic performance of all FDA/EMA-approved programmed cell death ligand-1 assays with emphasis on new restrictions for first-line treatment with atezolizumab and pembrolizumab. Patients and methods Two hundred fifty-one urothelial carcinomas were analysed on tissue microarrays with four cores of each tumour. Stains were performed in certified laboratories on Ventana Benchmark Ultra and Dako Link 48 autostainers. Stains were read on an assay-by-assay basis by two trained pathologists. Overall percentage agreement (OPA) was calculated across the preset cut-offs. Positive percentage agreement (PPA) and negative percentage agreement (NPA) were calculated across different scoring algorithms. Venn diagrams were constructed to illustrate discordance according to the recent FDA/EMA guidelines. Results The Dako 28-8, 22c3 and the Ventana SP263 assays showed high interassay correlation (r-range 0.83–0.91). Interassay correlation between the Ventana SP142 and the three other assays was moderate (r-range 0.66–0.75). OPA of 93.3% was achieved between the Dako 28-8, 22c3 and Ventana SP263 assays. OPA including the SP142 was 84.1%. Pooled PPA and NPA of different scoring algorithms was 89.4% and 95.3% for the Dako 28-8, 22c3 and the SP263 assays, respectively. With the SP142 assay, pooled PPA was 59.1%. The SP142 assay identifies fewer eligible patients for first-line treatment with atezolizumab/pembrolizumab. Conclusion Dako 28-8, 22c3 and SP263 assays show interchangeable performance. The SP142 assay shows divergent staining results. Interassay variability leads to different detection rates of eligible patients for first-line treatment with atezolizumab and pembrolizumab.

Muscle-invasive urothelial carcinoma of the urinary bladder (UCB) often recurs following radical cystectomy (RC). An altered expression of sex-steroid hormone receptors has been associated with oncological outcomes of UCB and may represent therapeutic targets. Here the expression of different hormone receptors was measured on mRNA levels in patients treated by RC and associated with outcomes. Androgen receptor (AR), estrogen receptor 1 (ESR1), and progesterone receptor (PGR) mRNA expression was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in RC samples of 87 patients with a median age of 66 (39–88) years. Univariate and multivariate analyses were performed to test associations with pathological and clinical characteristics as well as recurrence-free (RFS) and disease-specific survival (DSS). AR mRNA expression was lower in comparison with ESR1 and PGR expression (p

Plasma is a partially or fully ionized gaseous state of matter containing chemically active species, such as ions, electrons, photons, reactive oxygen and nitrogen species, and UV light. Cold atmospheric plasma (CAP) can be applied onto vital, heat-sensitive surfaces and is currently used in surgery, endoscopic procedures, and wound care with proven antimicrobial efficacy and the ability to deactivate pathogens, stop bleeding and stimulate cell proliferation 1 2. Recent pre-clinical observations suggested an anti-tumoral potential, for example in melanoma, glioma and colorectal carcinoma cells 3 4. This article is protected by copyright. All rights reserved.

Comprehensive molecular analyses of urothelial bladder cancer (UBC) have defined distinct subtypes with potential therapeutic implications. In this study, we focused on micropapillary urothelial carcinoma (MPUC), an aggressive, histomorphologically defined rare variant. Apart from genetic alterations shared with conventional UBC, alterations of the HER2 gene have been reported in higher frequencies. However, only small cohorts of MPUCs have been analyzed, and the real impact is still unclear. We collected a cohort of 94 MPUCs and immunohistochemically tested HER2, basal (CD44, CK5, EGFR, p63) and luminal (CD24, FOXA1, GATA3, CK20) markers to allocate MPUC to a molecular subtype. Additionally, HER2 amplification status was assigned by chromogenic in situ hybridization. Sanger sequencing of exon 4 and 8 was used to test for HER2 mutations. Kruskal-Wallis test was calculated to compare marker distribution between proportions of the MPUC component. HER2 2+/3+ staining scores were identified in 39.6% of 91 analyzed MPUCs and were not differentially distributed among the proportion of the MPUC component (P = .89). Additionally, CISH analysis revealed 30% of HER2-amplified tumors independently of the MPUC fraction. In 6/90 evaluable MPUCs, a p.S310F HER2 mutation was detected. Overexpression of luminal markers was observed in the majority of MPUC. Our investigations of the largest cohort of analyzed MPUC demonstrate that HER2 overexpression and amplifications are common genetic alterations and identification of overexpressed luminal markers allows subclassification to the luminal subtype. These findings highlight the need of histomorphological recognition of MPUC and analysis of HER2 status and the luminal molecular subtype for potential targeted therapeutic strategies.

Background In the era of individualized oncological therapy in bladder cancer, FGFR3 mutations, FGFR2/FGFR3 gene fusions and FGFR mRNA expression as potential oncological targets and their association to anti-PD-1/anti-PD-L1 (IO) treatment outcomes in patients with advanced urothelial cancer of the bladder (UCB) were studied in a German patient cohort. Methods Within a cohort of 72 patients with metastatic UCB from 5 academic centers in Germany (collected between 2016 and 2018) FGFR3 mutations, FGFR2 and FGFR3 gene fusions as well as FGFR expression in formalin-fixed, paraffin embedded (FFPE) tumour samples and their association to survival were examined using SNaPshot PCR, RT-qPCR as well as Next Generation Sequencing. Statistical analyses comprised Kaplan-Meier survival analyses, Spearman rank correlations, non-parametric testing. Results In 17% of all patients FGFR3 mutations or gene fusions could be detected. Patients with FGFR3 alterations did not have better outcome after immunoncology (IO) treatment, but rather tended to have inferior disease specific survival. All alterations of FGFR3 resulted in overexpression of FGFR3 mRNA. Combination of FGFR mutation analysis and FGFR mRNA assessment improved IO outcome prediction. Overexpression of FGFR3 mRNA was negatively associated with PDL1 expression (mRNA and protein level). High FGFR2 mRNA expression in primary tumors predicted better disease specific survival of UCB patients receiving IO therapy, whereas high FGFR3 mRNA expression was associated with tumor specific death in patients exhibiting of low FGFR2 mRNA expressions (p Conclusions The assessment of FGFR mRNA by standardized RT-qPCR identified a high risk UCB patient cohort, which does have inferior disease specific survival despite IO treatment and does overexpress FGFR3 mRNA. The assessment of FGFR mRNA levels by using this standardized, locally applicable FGFR test system could identify an FGFR inhibitor target population with poor response to IO treatment which is twice the size as currently detected by FGFR genomic alterations alone. Legal entity responsible for the study BRIDGE Consortium e.V. Funding Janssen. Disclosure F. Roghmann: Advisory / Consultancy: Janssen; Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Ipsen. All other authors have declared no conflicts of interest.

Background Immunotherapy (IO) with antibodies against PD1 or PD-L1 has been approved for 1st and 2nd line treatment of metastasized urothelial bladder cancer (mUC). Here we evaluated efficacy in a retrospective Real-World-Phase IV trial based on molecular subtypes and PD-L1 status. Methods Cancer specific survival from start of IO treatment to death was retrospectively analyzed in a multicenter cohort of 65 patients having received palliative immune checkpoint inhibition for mUC in 1st and 2nd line setting. Intrinsic molecular subtypes were assessed by CK5, CK20, GATA3, FOXA1 and CD44 immunohistochemistry and RT-qPCR of KRT5 and KRT20. PD-L1 status was determined using the 28-8 Dako-assay. Stromal tumor infiltrating lymphocytes were assessed on HE slides (Salgado et al, 2015). Survival analyses were performed by applying clinically relevant cut-offs and using Kaplan-Meier analysis and logistic regression for cancer specific survival (CSS). Results Altogether, 43% of tumors presented with basal differentiation, 57% were luminal. As expected, basal tumors exhibited significantly higher levels of PD-1 and PD-L1 gene expression, higher amounts of sTILs and PD-L1+ immune and tumor cells. Hierarchical clustering of all immunological biomarkers revealed three cluster: “Inflamed high” (n = 13, 20%), “Inflamed low” (n = 22, 33.8%), and “Uninflamed” (n = 30, 46.2%). There were no significant survival differences for any of these groups (CSS). However, patients with good performance status (ECOG 0) and low PD-L1 expression showed significantly better CSS compared to those with ECOG0 / PD-L1 high and ECOG1 or ECOG2, respectively (30.3 months vs. 16.33, 12.07 and 15.13 months; p = 0.0047). Conclusions Immunological determinants of mUC show comparable distributions and correlations with subtypes of localized curatively treated MIBC patients. Interestingly, data indicate improved CSS after PD-1/PD-L1 treatment in patients with good performance and low PD-L1 expression, which warrants validation in larger cohorts. Clinical trial identification DRKS00016925. Legal entity responsible for the study STRATIFYER Molecular Pathology GmbH. Funding Janssen-Cilag GmbH. Disclosure R. Wirtz: Leadership role: CEO & CSO, STRATIFYER Molecular Pathology GmbH. All other authors have declared no conflicts of interest.

Immunohistochemical (IHC) assessment of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) has become important since the development of anti-PD-1/-PD-L1 directed drugs. Various PD-L1 antibodies and cut-offs have been used in different trials to predict response to these drugs, thus comparison of those studies is difficult. We compared PD-L1 mRNA expression measured by RT-qPCR with PD-L1 protein expression evaluated by IHC. Moreover, we investigated the impact of different tumour tissue acquisition methods on the reliability of PD-L1 measurement techniques.NSCLC cases (N=22), including n=9 mediastinal lymph node biopsies acquired by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and n=5 metastases, were evaluated prospectively for PD-L1 protein on tumor cells (TC) and immune cells (IC) using E1L3N and 28-8 antibodies and PD-L1 mRNA using the CheckPoint TYPER® assay.In primary NSCLC tissues, agreement between PD-L1 mRNA and TC staining using the 28-8 antibody was excellent (ĸ=0.85, p=0.0002). Comparing both PD-L1 antibodies against each other showed a kappa value of 0.58 (p=0.0106). In EBUS-TBNA, PD-L1 mRNA correlated perfectly with the 28-8 antibody (ĸ=1.0, p=0.0023). PD-L1 mRNA levels significantly differed when comparing 28-8 TC staining of tumours >49% with 1-49% and 0% (p=0.0040; p=0.0081, respectively). In metastatic lesions, differences between PD-L1 mRNA and IHC became apparent (ĸ=0.2, p=0.2525).Testing of PD-L1 mRNA and 28-8 IHC showed an excellent agreement in NSCLC samples including mediastinal lymph node biopsies. Since PD-L1 expression in >50% TC detected by 28-8 IHC can be reliably detected by RT-qPCR, quantitative PD-L1 mRNA determination should be considered as an alternative to IHC as there is no interobserver variability in RNA results.

Inguinal lymph node (LN) metastasis is a crucial prognostic factor in vulva carcinoma. The aim of this study was to determine the prognostic value of the number of resected LNs in patients with vulvar carcinoma on recurrence rates. This retrospective study includes patients with vulvar squamous cell carcinoma who underwent inguinofemoral lymphadenectomy (IFL) between 1998 and 2011. Dissected groins were stratified by the number of removed lymph nodes (

„Illumination & Innovation – transforming data into learning“ so lautete das Motto der ASCO-Jahrestagung (29.5.–2.6.2015) in Chicago mit mehr als 37.000 Teilnehmern aus uber 80 Landern und fast 6.000 eingereichten Abstracts. Aus einer Vielzahl von Beitragen zur gynakologischen Onkologie haben unsere Experten einige neue Daten ausgewahlt, welche die Behandlungsstandards in den nachsten Jahren verandern konnten.