A.S. Merseburger

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets

Background:Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets.Methods:Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules – HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models.Results:In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial–mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with β-catenin, Twist and Snail expression, but negatively with E-cadherin expression.Conclusions:This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.

Systemic and surgical management of metastatic renal cell carcinoma

Several targeted therapies have become available for first-line (sunitinib, bevacizumab, pazopanib, temsirolimus) and second-line (sorafenib, pazopanib, everolimus) use in recent years. The superior outcomes achieved with these targeted agents have led to replacement of the formerly administered cytokines. New developments have raised the question of whether patients benefit from sequential therapies with tyrosine kinase inhibitors and/or whether combination regimes can improve clinical outcomes. This review gives an overview of the current therapeutic options for first- and second-line treatment in metastatic RCC as well as sequential and combination therapies. Adjuvant and neoadjuvant treatment options are being discussed. Furthermore, this review addresses surgical alternatives in the treatment of RCC.

Lübecker Konsilkoffer@@@The Lubeck medical consultation bag

Die richtige Ausstattung bei urologischen konsiliarischen Tätigkeiten kann imDienst viel kostbare Zeit sparen.Währendaufder eigenenStation und in der Notaufnahme in der Regel alle Utensilien zur Behebung urologischer Probleme vorhanden sind, muss man sich für Konsile auf externen Stationen häufig aus eigenem Bestand bedienen. Typische Konsilanfragen an den Dienstarzt sind Katheterdysfunktionen, schwierige Kathetereinlagen, Makrohämaturie oder die Paraphimose.

C-reaktives Protein vor radikaler Zystektomie@@@C-reactive protein prior to radical cystectomy: Präoperative Bestimmung von CRP@@@Preoperative determination of CRP

BACKGROUND Numerous studies have shown a positive correlation between elevated C-reactive protein (CRP) and systemic spread of malignancies. The goal of the current study was to assess the predictive significance of preoperative CRP in patients undergoing radical cystectomy (RC). MATERIAL AND METHODS Preoperative CRP values were measured in 194 patients undergoing RC because of urothelial carcinoma between 1996 and 2005. Elevated CRP level was defined as ≥ 5 mg/l. RESULTS Preoperative increased CRP values were detected in 89 (45.9%) patients and these patients were more likely to have advanced tumor stages (pT3-4), positive resection margins and positive lymph nodes. Advanced urinary diversions were more common in patients with normal CRP values. In multivariate analysis, CRP was identified as an independent prognostic indicator for poor cancer-specific survival. CONCLUSION The results confirm previous reports that showed a prognostic significance of preoperative CRP elevation.

Systemische und operative Therapie des metastasierten Nierenzellkarzinoms@@@Systemic and surgical management of metastatic renal cell carcinoma

Several targeted therapies have become available for first-line (sunitinib, bevacizumab, pazopanib, temsirolimus) and second-line (sorafenib, pazopanib, everolimus) use in recent years. The superior outcomes achieved with these targeted agents have led to replacement of the formerly administered cytokines. New developments have raised the question of whether patients benefit from sequential therapies with tyrosine kinase inhibitors and/or whether combination regimes can improve clinical outcomes. This review gives an overview of the current therapeutic options for first- and second-line treatment in metastatic RCC as well as sequential and combination therapies. Adjuvant and neoadjuvant treatment options are being discussed. Furthermore, this review addresses surgical alternatives in the treatment of RCC.

Ewing-Sarkom der Niere bei gleichzeitig vorliegendem Seminom@@@Ewing’s sarcoma of the kidneys with simultaneous seminoma

Extraosseous Ewings sarcoma (EOE) is rarely observed in the urinogenital tract, which results in only sporadic descriptions of primary EOE of the kidneys in the literature with cytologic analyses. A timely diagnosis and differentiated therapy of this aggressive disease are compromised by its infrequent appearance and scarce available data. With a simultaneously diagnosed seminoma our case report supports and extends further the data collected so far.ZusammenfassungExtraossäre Ewing-Sarkome (EOE) manifestieren sich äußerst selten in der Niere. Daher existieren nur sporadisch Berichte mit zytologischer Analyse. Sowohl die zügige Diagnosestellung, als auch die adäquate Behandlung dieser aggressiven Tumorerkrankung wird durch ihr seltenes Auftreten und die geringe Datenlage erschwert. Der vorliegende Fallbericht unterstützt die bisher erhobenen Beobachtungen zum EOE und erweitert bei gleichzeitig vorliegendem Seminom die Datenlage zum synchronen Vorliegen von Sekundärmalignomen.AbstractExtraosseous Ewing’s sarcoma (EOE) is rarely observed in the urinogenital tract, which results in only sporadic descriptions of primary EOE of the kidneys in the literature with cytologic analyses. A timely diagnosis and differentiated therapy of this aggressive disease are compromised by its infrequent appearance and scarce available data. With a simultaneously diagnosed seminoma our case report supports and extends further the data collected so far.