15644 Background: Combined immunochemotherapy with interleukin-2 (IL-2), interferon-alpha (IFN-a) and 5-fluorouracil (5-FU) is an established first-line therapy for metastatic renal cell carcinoma (RCC). However, data on histologic parameters predictive of clinical benefit are rare. Methods: Treatment courses of 164 patients consisted of IFN-a at 9 x 106 IU on day 1 of weeks 1 and 4 and days 1, 3, 5 of weeks 2 and 3; and at 18 x 106 IU on days 1, 3, 5 of weeks 5–8. Interleukin-2 was administrated at 18 x 106 IU twice daily on days 3–5 of weeks 1 and 4; and at 9 x 106 IU on days 1, 3, 5 of weeks 2 and 3. Additionally, patients received 5-FU at 750 mg m-2 on day 1 of weeks 5–8. In 153 patients, radical nephrectomy had revealed 22 cases of papillary RCC (pRCC, 13.4%) and 131 cases of clear cell RCC (ccRCC, 79.9%). In the remaining 11 (6.7%) their disease was inoperable. The overall response rates were evaluated according to WHO criteria. Results: For ccRCC and inoperable disease, responses of 34.4% and 27.3% after one cycle and 28.8% and 16.7% after two cycles, respectively, were noted. In contrast, no patient with pRCC showed any response after two cycles of combined immunochemotherapy. Conclusions: No objective response was seen in patients with pRCC. Hence, immunotherapeutic agents must be questioned in this histologic subtype. No significant financial relationships to disclose.

14571 Background: Combined immunochemotherapy with interleukin 2, interferon alpha and 5-fluorouracil in patients with metastatic renal cell carcinoma has shown objective response rates up to 30% and more. The therapeutic effect of adding 13-cis-retinoic acid still remains controversial. Methods: Between 05/2001 and 11/2003 we randomly assigned patients with metastatic renal cell carcinoma either to receive a combined immunochemotherapy of interleukin 2 (s.c.), interferon alpha (s.c.) and 5-fluorouracil (i.v.) = group A or the same regimen plus 3 × 20 mg 13-cis-retinoic acid daily (p.o.) = group B. 83 patients were eligible (41 in group A and 43 in group B). All patients had ECOG 0 or 1 and no prior systemic therapy. Objective response (OR = Complete response, CR + Partial response, PR + Stable disease, SD), time to progression (TTP) and median survival were determined. Results: Patient characteristics were well balanced between both groups. There was no significant difference in objective response between both groups (A/B: CR 2%/2%, PR 22%/5%, SD 46%/69%, p = 0.8). The responders in both groups showed no significant difference in TTP (A/B: 11.5/9.5 months, p = 0.4). Median survival was 23 months for all patients with no significant difference between the two groups (A/B: 26/22 months, p = 0.42). Slightly more therapeutic side effects (e.g. mucositis) were seen in group B. Conclusions: The addition of 13-cis-retinoic acid to a combined immunochemotherapy of interleukin 2, interferon alpha and 5-fluorouracil in patients with metastatic renal cell carcinoma does not seem to have a therapeutic benefit. No significant financial relationships to disclose.

Urinary tract obstruction is a common clinical problem. The obstruction of the urinary flow may be acute or chronic, partial or complete, unilateral or bilateral, and may occur at any site of the urinary tract. The major causes of urinary tract obstruction vary with the age of the patient. Anatomic abnormalities, e. g. ureteropelvic junction obstruction, account for the majority of cases in children. In comparison, calculi are most common in young adults, while prostatic hyperplasia or carcinoma, retroperitoneal or pelvic neoplasms, and calculi are the primary causes in older patients. Urinary tract obstruction results in different pathophysiological changes causing various symptoms. In addition to the aetiology, pathophysiology and clinical presentation of obstructive uropathy in adults, modern diagnostic and therapeutic options are presented in this review.

Renal angiomyolipomas are mesenchymal tumors that are composed of fat tissue, smooth muscle cells and vessels. These are benign tumors, but in rare cases they show a more aggressive growth pattern with invasion into the venous system but without revealing any signs of malignancy. We report a new case of bilateral renal angiomyolipomas with a caval thrombus in a 36 year old female patient with tuberous sclerosis, and give a brief review of the related literature.

Urinary tract obstruction is a common clinical problem. The obstruction of the urinary flow may be acute or chronic, partial or complete, unilateral or bilateral, and may occur at any site of the urinary tract. The major causes of urinary tract obstruction vary with the age of the patient. Anatomic abnormalities, e. g. ureteropelvic junction obstruction, account for the majority of cases in children. In comparison, calculi are most common in young adults, while prostatic hyperplasia or carcinoma, retroperitoneal or pelvic neoplasms, and calculi are the primary causes in older patients. Urinary tract obstruction results in different pathophysiological changes causing various symptoms. In addition to the aetiology, pathophysiology and clinical presentation of obstructive uropathy in adults, modern diagnostic and therapeutic options are presented in this review.

Overexpression of endothelin-1, endothelin-A- and endothelin-B-receptors has been shown in various human tumors. To assess the role of the ET-axis in bladder cancer, we analyzed its expression in tumor specimens and bladder cancer cell lines. Samples were obtained by radical cystectomy at two urologic institutions. ET-axis expression was investigated by reverse-transcription polymerase chain reaction (RT-PCR) (n=22) and immunohistochemistry (n=42). Additionally, four bladder cancer cell lines were analyzed. RT-PCR analysis for the ET-axis showed positive signals in the majority of cDNA probes. Signals for endothelin-1 (ET-1), endothelin-A-receptor (ET(A)R) and endothelin-B-receptor (ET(B)R), as identified semiquantitatively and by densitometry, were found in 22, 22 and 15 of 22 cases, respectively. Immunohistochemistry revealed expression of ET-1, ET(A)- and ET(B)-receptor in 18, 29 and 37 of the 42 cases, respectively, whereas normal urothelium was negative. All cell lines expressed ET-1, and all but the RT-112 cell line produced ETAR, whereas no cell line expressed ET(B)R. The identification of the ET-axis at the mRNA and protein level in the majority of bladder tumor samples suggests a role in the carcinogenesis of bladder cancer. Further studies on regulation of the ET-axis and the future use of selective ET(A)-receptor inhibitors for targeted molecular therapy in bladder cancer are in progress.

Renale Angiomyolipome sind mesenchymale Tumoren, die sich aus Fettgewebe, glatten Muskelzellen und Gefäßen zusammensetzen. Es handelt sich um benigne Tumoren, die aber in seltenen Fällen ein aggressiveres Wachstumsverhalten mit Invasion ins venöse Gefäßsystem und Tumorthrombenbildung zeigen können, ohne dass in diesen Fällen Malignitätskriterien nachgewiesen werden konnten. Wir berichten über einen neuen Fall eines bilateralen renalen Angiomyolipoms mit einem Kavathrombus bei einer 36-jährigen Patientin mit tuberöser Hirnsklerose und geben einen kurzen Literaturüberblick.

Die schmerzlose Makrohämaturie gilt als Kardinalsymptom von Malignomen des Harntrakts. Das Vorliegen hierzu passender Begleitbefunde wie Nikotinabusus und dem bildgebenden Nachweis einer Raumforderung schließt jedoch einen in seltenen Fällen zugrunde liegenden benignen Tumor nicht aus. Die vorliegende Arbeit belegt dies am Beispiel eines 38-jährigen Patienten mit einem Fibroepitheliom des linken Harnleiters. Im Rahmen der Erörterung des differenzialdiagnostischen und therapeutischen Vorgehens wird auf den selbst im Zeitalter der modernen, nichtinvasiven Schnittbildgebung immer noch besonderen Stellenwert der retrograden Ureteropyelographie für die Abklärung des oberen Harntrakts hingewiesen.

PURPOSE:Cyclooxygenase-2 (Cox-2) contributes to the carcinogenesis of human tumors by various mechanisms. As Cox-2-expression has been found in most human neoplasms, selective Cox-2-inhibitors could be used as a molecular targeted therapy, and first clinical trials have already been initiated. Moreover, Cox-2-inhibitors have been shown to add to the activity of conventional cytotoxic therapies in experimental and clinical studies. We analyzed Cox-2-expression in bladder cancer and its implications on clinical parameters.MATERIALS AND METHODS:Cox-2-expression was evaluated immunohistochemically in 157 patients undergoing radical cystectomy. Sixty-two patients had received cisplatin-based treatment during follow-up, either as adjuvant therapy or for metastatic disease. Cox-2-expression was correlated with clinical and pathological parameters, survival data and outcome of chemotherapy.RESULTS:Cox-2 was expressed in 83.4 % of tumors. No association was found with TNM-staging and histological grading, but a significant relation to the histologic subtype (transitional vs. squamous cell carcinoma, p = 0.038) was present. Survival analysis showed no impact of Cox-2-expression on overall or disease-free survival. However, a subgroup of chemotherapy patients demonstrated a significant correlation of strong Cox-2-expression with worse overall survival time (p = 0.01).CONCLUSIONS:Cox-2-expression was found in the majority of invasive bladder tumors. For patients who underwent chemotherapy, a significant relation of Cox-2-expression and worse overall survival was demonstrated. Cox-2 seems to be an interesting molecular target for the diagnosis and therapy of bladder cancer. Further experimental and clinical studies are warranted to elucidate whether Cox-2-inhibition can serve as an additive therapy to chemotherapy of bladder cancer.

Gross hematuria without pain is a classical symptom of malignancy in the urinary tract. Despite the presence of other symptoms such as a history of heavy smoking or radiologic evidence of tumor growth, it may still be caused by a benign lesion. This is demonstrated by the case of a 38 year old man with a fibroepithelioma of the left ureter. While discussing the differential diagnostic and treatment procedures it is shown that even in the era of modern non-invasive imaging techniques there is still an important place for retrograde ureteropyelography in the evaluation of the upper urinary tract.

Bei 5–10% der Patienten mit Nierentumoren wird eine Beteiligung im Sinne einer Infiltration oder eines intraluminalen Tumorwachstums in der Vena cava inferior (VCI) und/oder des rechten Vorhofes beobachtet. Wenn der Nierentumor einen sogenannten Cavazapfen gebildet hat, nimmt die Höhe der cavoatrialen Ausbreitung keinen Einfluss auf das Überleben. Die radikale Entfernung des Tumors mitsamt Tumorzapfen stellt heute bei Patienten ohne lokale Lymphknotenmetastasen und ohne Fernmetastasen die Primärtherapie der Wahl dar. Wir berichten über den Verlauf und die Therapie von 17 Patienten mit einem Nieren-Zell-Karzinom und cavoatrialer Tumorbeteiligung sowie über 6 weitere Patienten mit anderen Tumorarten. Trotz aufwändiger Operation mit Herz-Lungenmaschine, tiefer Hypothermie und Kreislaufstillstand kommt es im Vergleich zur Tumornephrektomie ohne Beteiligung der Vena cava zu einer vertretbaren Erhöhung der perioperativen Morbidität und Letalität. Ein Langzeitüberleben ist trotz fortgeschrittenem Tumorstadium mit cavoatrialer Ausdehnung nach radikaler Resektion möglich.