S. Waalkes

Overweight is an advantageous prognostic marker in patients with clear cell kidney cancer

OBJECTIVES Obesity increases the risk of developing renal cell carcinoma (RCC). We assessed whether different body mass index (BMI) levels and the body surface area (BSA) at the time of surgery had an effect on aggressiveness and long-term prognosis of RCC. METHODS The study included 1,595 RCC patients with complete information about their BMI who had undergone surgery for renal cell cancer at the University Hospitals in Hannover (MHH) and Marburg between 1990 and 2005. The mean follow-up was 5.0 years. RESULTS A higher BMI and a higher than average BSA were significantly associated with younger age. A high BMI value was additionally related to a lower tumor grade, the clear cell histological subtype, and metastasis at the time of diagnosis. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 76.9% (BMI>30) and 72.6% (BMI 25-30) as opposed to 63.5% for patients with a BMI below 25 (p<0.001). However, the positive correlation between a high BMI and tumor-specific survival could be confirmed in multivariable analyses for localized clear cell RCC only. CONCLUSION We identified BMI as an independent prognostic marker of improved cancer-specific survival in patients with RCC, particularly with organ-confined clear cell cancer.

Current state of systemic therapy of metastatic renal cell carcinoma

The past 5 years were marked by fundamental changes in the systemic therapy of metastatic renal cell carcinoma. Up to the end of the last decade cytokine-based chemotherapy was the only, even if only moderately effective systemic therapy for metastatic renal cell carcinoma. Currently there are five new approved drug releases of so-called targeted substances, which function on a molecular based therapeutic mechanism. Sunitinib (Sutent) and sorafenib (Nexavar) as multikinase inhibitors, everolimus (Afinitor) and temsirolimus (Torisel) as mTOR inhibitors, and bevacizumab as an antibody against VEGF in combination with interferon-alpha (IFN-alpha). The following article will give an overview of the currently available substances and critically discuss therapy plans and future trends.

[Galectin expression in urological cancer. Diagnostic, prognostic and therapeutic potential].

ZusammenfassungGalectine sind eine Gruppe von 15 Proteinen, die sowohl intra- als auch extrazellulär an bestimmte Kohlenhydratreste binden können und dabei eine wichtige Rolle bei der Regulation des Zellzyklus spielen. So wurden durch molekularbiologische Untersuchungen spezifische Expressionsmuster in Zusammenhang mit Prozessen wie Metastasierung und Apoptose feststellt, weshalb die Galectine potentielle Tumormarker im Rahmen einer optimierten Früherkennung, Langzeitprognose und Therapiewahl darstellen könnten. Gegenstand der vorliegenden Übersicht ist die Bedeutung der Galectine für die Entwicklung von Nieren-, Harnblasen- und Prostatakarzinomen darzustellen, wobei die Galectine-1 und -3 bislang auf Transkriptions- und Translationsebene am intensivsten untersucht wurden. Beim klarzelligen Nierenzellkarzinom wurde beispielsweise innerhalb mehrerer Untersuchungen eine erniedrigte Expression von Galectin-3 belegt, wobei diese zudem mit einer schlechteren Prognose korreliert werden konnte. Bei Patienten mit Harnblasenkarzinom war im Gegensatz hierzu insbesondere der Galectin-3-Spiegel im Serum deutlich erhöht. Analysen von Tumorgewebe aus Prostatakarzinomen ergaben weiterhin, dass eine veränderte Galectin-1-Expression im Stroma ein unabhängiger Prädiktor für ein PSA-Rezidiv sein kann. Darüber hinaus konnten auch bei nicht urologischen Tumoren, beispielsweise dem Mammakarzinom, pathologische Expressionsmuster festgestellt werden. Obgleich diese Ergebnisse darauf hindeuten, dass die Galectine in Zukunft als klinisch relevante Biomarker bei urologischen Tumoren fungieren könnten, werden weitere Untersuchungen erforderlich sein, um insbesondere die pathogenetische entwicklungsabhängige Funktion der Galectine bei der Tumorgenese für Tumoren des urologischen Formenkreises genauer beschreiben zu können.AbstractGalectins are a family of 15 proteins. They interact with glycoproteins in both the extracellular and intracellular milieu and regulate various biological cycles including cell growth, cell differentiation, cell adhesion and apoptosis. In biomolecular studies certain patterns of expression showed a correlation with metastasis and apoptosis. Therefore, galectins could be used as potential markers for early tumour recognition, long-term prognosis and a better-founded choice of therapy. Acknowledging these possibilities this review points out the standing of galectins with all currently available data in the development and progression of renal, bladder and prostatic tumours. The expression patterns of galectin-1 and -3 have been researched extensively. For example, several studies could show a decreased expression of galectin-3 in clear renal cell carcinoma, which correlated with a poor clinical prognosis. On the contrary, patients with a bladder tumour showed an elevated serum level of galectin-3. Furthermore, in analysis of prostatic tumour tissue galectin-1 was found to be an independent predictor of a PSA relapse. In addition, pathological patterns of galectin expression could be detected in non-urological malignancies such as breast cancer. Though all findings indicate a future significance of galectins as markers of urological malignancies with clinical relevance, more research will be necessary to particularly assess the evolutional-dependent function of galectins in the process of tumourigenesis.

Aktuelles zur Systemtherapie des metastasierten Nierenzellkarzinoms

The past 5 years were marked by fundamental changes in the systemic therapy of metastatic renal cell carcinoma. Up to the end of the last decade cytokine-based chemotherapy was the only, even if only moderately effective systemic therapy for metastatic renal cell carcinoma. Currently there are five new approved drug releases of so-called targeted substances, which function on a molecular based therapeutic mechanism. Sunitinib (Sutent) and sorafenib (Nexavar) as multikinase inhibitors, everolimus (Afinitor) and temsirolimus (Torisel) as mTOR inhibitors, and bevacizumab as an antibody against VEGF in combination with interferon-alpha (IFN-alpha). The following article will give an overview of the currently available substances and critically discuss therapy plans and future trends.

[Incidence and long-term prognosis of papillary renal cancer. Results of a retrospective multicenter study].

OBJECTIVES Papillary renal cell carcinoma (pRCC) represents the largest subgroup of non-clear-cell kidney cancer. In this retrospective multicenter study, we assessed tumor characteristics and long-term prognosis of patients with pRCC in comparison with conventional clear-cell cancer (ccRCC). METHODS We evaluated 2,804 patients who had undergone renal surgery for pRCC or ccRCC between 1990 and 2006. The mean follow-up was 65 months. RESULTS Both pRCC and ccRCC groups were comparable concerning age, tumor grade and the incidence of regional lymph node metastasis at diagnosis. The percentage of male patients was higher in pRCC than in ccRCC (76.0% vs. 63.6%), pRCC patients suffered less often from advanced tumors (22.3% vs. 38.1%), visceral metastasis at diagnosis (8.1% vs. 14.5%) and died less frequently due to RCC progression (16.3% vs. 29.6%). Applying multivariable analyses pRCC was found to be an independent predictor of a favorable clinical course for patients with organ-confined RCC. In contrast in advanced disease papillary histology was significantly associated with a poor prognosis and early tumour-related death. CONCLUSIONS pRCC seem to be stratified into two different prognostic groups. Localized pRCC has a significantly better prognosis than ccRCC. In contrast, advanced pRCC is characterized by a worse clinical outcome. Whether these two different pRCC cohorts are consistent with the recently defined types 1 and 2 pRCC subtypes or are characterized by other typical genetic alterations, which would lead to a novel pRCC subclassification is currently under investigation within the German Renal Cancer Network.

Übergewicht ist ein günstiger Prognosefaktor für Patienten mit Nierenzellkarzinom

OBJECTIVES Obesity increases the risk of developing renal cell carcinoma (RCC). We assessed whether different body mass index (BMI) levels and the body surface area (BSA) at the time of surgery had an effect on aggressiveness and long-term prognosis of RCC. METHODS The study included 1,595 RCC patients with complete information about their BMI who had undergone surgery for renal cell cancer at the University Hospitals in Hannover (MHH) and Marburg between 1990 and 2005. The mean follow-up was 5.0 years. RESULTS A higher BMI and a higher than average BSA were significantly associated with younger age. A high BMI value was additionally related to a lower tumor grade, the clear cell histological subtype, and metastasis at the time of diagnosis. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 76.9% (BMI>30) and 72.6% (BMI 25-30) as opposed to 63.5% for patients with a BMI below 25 (p<0.001). However, the positive correlation between a high BMI and tumor-specific survival could be confirmed in multivariable analyses for localized clear cell RCC only. CONCLUSION We identified BMI as an independent prognostic marker of improved cancer-specific survival in patients with RCC, particularly with organ-confined clear cell cancer.

Ewing-Sarkom der Niere bei gleichzeitig vorliegendem Seminom

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.

Galectin-Expression an urologischen Tumoren

ZusammenfassungGalectine sind eine Gruppe von 15 Proteinen, die sowohl intra- als auch extrazellulär an bestimmte Kohlenhydratreste binden können und dabei eine wichtige Rolle bei der Regulation des Zellzyklus spielen. So wurden durch molekularbiologische Untersuchungen spezifische Expressionsmuster in Zusammenhang mit Prozessen wie Metastasierung und Apoptose feststellt, weshalb die Galectine potentielle Tumormarker im Rahmen einer optimierten Früherkennung, Langzeitprognose und Therapiewahl darstellen könnten. Gegenstand der vorliegenden Übersicht ist die Bedeutung der Galectine für die Entwicklung von Nieren-, Harnblasen- und Prostatakarzinomen darzustellen, wobei die Galectine-1 und -3 bislang auf Transkriptions- und Translationsebene am intensivsten untersucht wurden. Beim klarzelligen Nierenzellkarzinom wurde beispielsweise innerhalb mehrerer Untersuchungen eine erniedrigte Expression von Galectin-3 belegt, wobei diese zudem mit einer schlechteren Prognose korreliert werden konnte. Bei Patienten mit Harnblasenkarzinom war im Gegensatz hierzu insbesondere der Galectin-3-Spiegel im Serum deutlich erhöht. Analysen von Tumorgewebe aus Prostatakarzinomen ergaben weiterhin, dass eine veränderte Galectin-1-Expression im Stroma ein unabhängiger Prädiktor für ein PSA-Rezidiv sein kann. Darüber hinaus konnten auch bei nicht urologischen Tumoren, beispielsweise dem Mammakarzinom, pathologische Expressionsmuster festgestellt werden. Obgleich diese Ergebnisse darauf hindeuten, dass die Galectine in Zukunft als klinisch relevante Biomarker bei urologischen Tumoren fungieren könnten, werden weitere Untersuchungen erforderlich sein, um insbesondere die pathogenetische entwicklungsabhängige Funktion der Galectine bei der Tumorgenese für Tumoren des urologischen Formenkreises genauer beschreiben zu können.AbstractGalectins are a family of 15 proteins. They interact with glycoproteins in both the extracellular and intracellular milieu and regulate various biological cycles including cell growth, cell differentiation, cell adhesion and apoptosis. In biomolecular studies certain patterns of expression showed a correlation with metastasis and apoptosis. Therefore, galectins could be used as potential markers for early tumour recognition, long-term prognosis and a better-founded choice of therapy. Acknowledging these possibilities this review points out the standing of galectins with all currently available data in the development and progression of renal, bladder and prostatic tumours. The expression patterns of galectin-1 and -3 have been researched extensively. For example, several studies could show a decreased expression of galectin-3 in clear renal cell carcinoma, which correlated with a poor clinical prognosis. On the contrary, patients with a bladder tumour showed an elevated serum level of galectin-3. Furthermore, in analysis of prostatic tumour tissue galectin-1 was found to be an independent predictor of a PSA relapse. In addition, pathological patterns of galectin expression could be detected in non-urological malignancies such as breast cancer. Though all findings indicate a future significance of galectins as markers of urological malignancies with clinical relevance, more research will be necessary to particularly assess the evolutional-dependent function of galectins in the process of tumourigenesis.

Transarterielle superselektive Coil-Embolisation zur Therapie des High-flow-Priapismus

We present the case of a 22 year old man who developed a permanent penile erection after a blunt perineal trauma. Conservative treatment in terms of cooling, compression and puncture of the cavernosal corpora with blood aspiration failed to resolve the priapism. Angiography confirmed the diagnosis of high-flow priapism caused by an arteriovenous fistula. Interventional coil embolization of the fistula was effective meaning that complete detumescence was achieved and erectile function was preserved.

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.