[Endourological lithotripsy for stone removal: accidental fragmentation of dormia basket and guidewire - a brief overview]. / Endourologische Steinlithotripsie : Akzidentielle Zerstörung von Dormiakörbchen und Guidewire - eine Kurzübersicht.

Endoscopic lithotripsy of stones is one of the most frequently performed procedures in urology. Sometimes dormia baskets and guidewire will be fragmented accidentally by the laser (Hol:YAG), by ultrasound, or by mechanical lithotripsy (electromechanical or pneumatic).A search for articles on this subject was performed. The aim of this article is to provide a review about the literature on this subject and how this subject can be managed. In this article we describe the energy needed for destroying specific foreign bodies and what currently and in the future will be the best way to avoid this problem.

[Fluorescence diagnosis in patients with non-muscle invasive bladder cancer: results of a metaanalysis]. / Fluoreszenzdiagnostik bei Patienten mit nicht muskelinvasivem Harnblasenkarzinom: Ergebnisse einer Metaanalyse.

PURPOSE: Heterogeneous results of single studies with photodynamic diagnosis (PDD) in bladder cancer have been reported. A metaanalysis of prospective studies has now been performed. MATERIAL AND METHODS: The effect of PDD in addition to WLC on a) the diagnosis and b) the therapeutic outcome of primary or recurrent non-muscle invasive bladder cancer (NMIBC) investigated by cystoscopy or transurethral resection was analysed. An electronic database search was performed. Trials were included if they prospectively compared WLC with PDD in bladder cancer. Primary endpoints were additional detection rate, residual tumour at second resection and recurrence-free survival. RESULTS: Significantly more tumour-positive patients were detected with PDD in all patients with non-muscle invasive tumours (= 20 %) [95 % confidence interval (CI): 8 to 35 %] and in CIS patients (= 39 %) (CI: 23 to 57 %). Residual tumour was significantly less often found after PDD (odds ratio 0.28, CI: 0.15 to 0.52, p < 0.0001). Recurrence-free survival was significantly higher at 12 and 24 months in the PDD groups than in WLC only groups. CONCLUSIONS: More bladder tumour-positive patients are detected by PDD. Best results were found in CIS patients. Diagnosis with PDD results in a more complete resection and a longer recurrence-free survival.

[Atypical metastasis of renal cell carcinoma. Contribution of comparative genomic hybridisation to diagnosis]. / Atypische Metastasierung eines Nierenzellkarzinoms. Beitrag der komparativen genomischen Hybridisierung zur Diagnosefindung.

In patients younger than 40 years, renal cell carcinoma and metastases to the bladder are rare. Comparative genomic hybridisation (CGH) may be useful to differentiate between metastatic renal cell carcinoma and secondary malignancies of the genitourinary tract, which can occur in all histologic types. We report the case of a 35-year-old patient with renal cell carcinoma in whom only CGH could help differentiate between a second primary malignancy in the bladder and an atypical bladder metastasis.

[BCG versus photodynamic therapy (PDT) for nonmuscle invasive bladder cancer-a multicentre clinical phase III study]. / BCG versus Photodynamische Therapie (PDT) beim nicht muskelinvasiven Harnblasenkarzinom--eine multizentrische Phase-III-Studie.

PURPOSE: This multicentre phase III study was designed to compare the efficacy of Bacillus Calmette Guérin (BCG) instillations and photodynamic therapy (PDT) in the treatment of patients with intermediate and high-risk nonmuscle invasive bladder cancer. MATERIAL AND METHODS: Inclusion criteria were multifocal pTaG1-G2 tumours, recurrent pTaG1-2 tumours, pTa / 1G3 tumours, and primary or recurrent carcinoma in situ (CIS). All patients were centrally randomised after transurethral resection (TUR) to receive BCG induction and maintenance therapy or a single PDT with Photofrin. The primary endpoint of the trial was recurrence-free survival. Secondary endpoints were the 2-year recurrence rate, the 2-year progression rate, survival, and quality of life. RESULTS: 124 patients (63 PDT group, 61 BCG group) were enrolled at 7 institutions in Germany and Austria. Each patient had a follow-up for 2 years. Of the 124 enrolled patients 105 were eligible for this analysis. Kaplan-Meier curves demonstrated no statistically significant differences between the two therapy arms with respect to recurrence-free survival after randomisation (p = 0.4598). After intention-to-treat analysis and after as-treated analysis, the estimated median recurrence-free survival periods were 24.9 (BCG) versus 16.6 months (PDT) and 25.8 (BCG) versus 14.7 (PDT) months, respectively. CONCLUSIONS: A single PDT with Photofrin(R) in intermediate and high-risk nonmuscle invasive bladder cancer patients could not be shown to be superior to BCG maintenance therapy. Vice versa, the results of this study cannot exclude a superiority of BCG.

[Squamous cell carcinoma of the renal pelvis. Therapeutic options for a rare entity]. / Plattenepithelkarzinom des Nierenbeckens. Therapieoptionen einer seltenen Tumorentität.

Squamous cell carcinoma (SCC) of the upper urinary tract is a rare condition. The late stage of the tumour at diagnosis and the absence of evidence-based guidelines for therapy give rise to a poor prognosis in most cases. The patient with SCC described here showed an above-average survival of 18 months after adjuvant radiochemotherapy. Treatment was initiated according to the guidelines for squamous cell carcinoma in non-urological localisations.

[Spontaneous hemorrhage of the adrenal gland during pregnancy]. / Spontane Nebennierenblutung während der Schwangerschaft.

INTRODUCTION: Spontaneous hemorrhage is a rare cause of masses in the adrenal gland and must be differentiated from hemorrhage caused by trauma, neoplasm or metastases. CASE REPORT: A 41-year-old pregnant woman presented with nausea and right flank pain. Under suspicion of a pyelonephritis she was referred to the urological department with a normal obstetric evaluation. Ultrasound revealed an inhomogeneous mass above the right kidney, which seemed to be an abscess. An MRI scan showed an adrenal hemorrhage, but a bleeding caused by a neoplasm was excluded by a post-partum MRI control only. Upon conservative therapy the clinical condition improved and the parameters of inflammation normalized. There was no evidence of a hormone-producing adrenal tumor, an adrenal insufficiency caused by the hemorrhage, or a coagulopathy. CONCLUSION: Spontaneous hemorrhage in the adrenal gland is a rare condition in pregnancy. The diagnosis is confirmed by MRI. If conservative treatment fails, adrenalectomy will be necessary. Adrenal function should be controlled during pregnancy and post-partum. Recurrent hemorrhage and a neoplasm must be excluded by a post-partum MRI.

[Localized amyloidosis of the ureter]. / Lokalisierte Amyloidose des Harnleiters.

Localized amyloidosis of the ureter is a rare condition. Because of the difficulty in differentiating between localized amyloidosis and an obstruction due to other benign or malignant conditions of the urinary tract, in some cases even an unnecessary nephroureterectomy is performed. We describe a patient with obstructive amyloidosis of the right ureter. Diagnosis was confirmed by endoscopy with biopsies. The patient was treated successfully by partial ureterectomy and ureteroneocystostomy. No systemic involvement of other organs was detected and after a 2-year follow-up no local recurrence developed.

[Bone formation in the ureter. Osseous metaplasia of an obstructed ureter]. / Der Harnleiterknochen. Knöcherne Metaplasie eines obstruierten Harnleiters.

Bone formation outside the skeleton is well known. Yet, ossification within the urogenital tract is rare. The case of a patient with distal ureteral obstruction, hydronephrosis, and subsequent circular osseous metaplasia of the ureter is presented. Open transperitoneal right-sided nephrectomy with partial resection of the ureter was performed. Intraoperatively and in histopathologic examination circular bone formation adjacent to the ureteral wall was detected. There was no evidence of malignancy. Early animal experiments in the twentieth century showed that bone metaplasia may be induced by epithelium of the urinary tract under certain conditions such as ischemia, inflammation, necrosis, sclerosis, and trauma. Osseous metaplasia may therefore be considered a differential diagnosis of calcification of the upper urinary tract in the absence of urolithiasis.

[Noninvasive and invasive bladder cancer: diagnostics and treatment]. / Nichtinvasives und invasives Harnblasenkarzinom: Diagnostik und Therapie.

Therapy of superficial bladder tumors is transurethral resection (TUR), and in cases of pT1 or high-grade tumors a re-TUR is indicated. Patients with carcinoma in situ receive intravesical chemotherapy or BCG for at least 3 months. Persistent carcinoma in situ may be treated by radical cystectomy. With the provision of a functionally adequate urinary diversion, cystectomy represents an effective treatment for patients with muscle-invasive bladder cancer without metastatic spread. Regional lymph node metastases can be found in up to 15% of stage T1 disease and are present in 33% of stage T3/4 lesions. Thus, lymphadenectomy gains diagnostic and possibly also therapeutic importance. For selected patients, who cannot be treated by radical cystectomy, multimodal concepts aiming to preserve the bladder are discussed. After or prior to cystectomy systemic chemotherapy may become necessary for some patients to positively affect the course of the disease in cases of locally advanced or metastatic lesions.

[Vaccine therapy of prostate cancer]. / Vakzinetherapie des Prostatakarzinoms.

Vaccine therapy of prostate cancer has been increasingly studied in trials over the past few years. The different vaccine techniques are quite variable and are predominantly used in patients with advanced hormone-refractory prostate cancer. In this review, vaccine techniques using tumor cells, dendritic cells or poxvirus are analyzed. For theses approaches phase-III trials are being planned, have been initiated or are already completed. Many trials demonstrate the efficacy with regard to endpoints such as stimulation of the immune system and/or biochemical response and/or clinical response. Recently, one vaccine approach using autologous dendritic cells demonstrated a statistically significant prolongation of overall survival compared to placebo in patients with hormone-refractory prostate cancer. Side effects of vaccination are generally mild. At present, there are trials are being planned or are already ongoing that combine vaccine with other treatment strategies or enroll patients with earlier disease stages.

Spontaneous external drainage of renal abscess through persistent nephrostomy tract eleven years after percutaneous nephrolithotomy.

A unique case of spontaneous external drainage of a renal abscess through a persistent nephrostomy tract is reported in a patient with a history of two subsequent percutaneous nephrolithotomies 11 years earlier. Nephrostomy tracts can open up even after several years to provide an exit path for infected urine or renal abscess drainage.

[Ki-67 antisense therapy in murine renal cell carcinoma models]. / Ki-67 Antisense-Therapie in murinen Nierenzellkarzinom-Modellen.

PURPOSE: The Ki-67 antigen is only expressed in proliferating cells. Previously, it was shown that Ki-67 derived antisense oligonucleotides (asONs) specifically inhibit the proliferation of tumor cells and tumour growth in vitro and in subcutaneous bladder and prostate tumor models. We intended to evaluate the effects of this therapeutic concept in two renal cell carcinoma (RCC) models. MATERIAL AND METHODS: Human RCC cells (SK-RC 35) were initially transfected with FITC-labeled ONs and diffferent cationic lipids to analyze the transfection efficacy by flow cytometry (FACS). The potency of 14 different ONs sequences was compared by quantitative RT-PCR in vitro. For in vivo testing, ONs were administered to immunocompetent Balb/c mice bearing orthotopic RENCA tumors as well as to SCID mice bearing subcutaneous RCC SK-RC 35 xenografts. Tumor sizes and final tumor weights were documented. Additionally, several immunohistochemical staining procedures were performed. RESULTS: FACS analysis showed highly effective transfection conditions in vitro. Systemic administration of asONs significantly decreased the tumour growth in the RENCA model (p < 0.05) and in the SCID mouse model (p = 0.009). Immunohistochemical staining of tumor specimens revealed a marked down-regulation of target protein and a slight increase in apoptotic cells after antisense treatment while the microvessel count was not significantly altered. CONCLUSION: These results demonstrate that the Ki-67 antigen represents a suitable antiproliferative target and that asONs directed against this target are potent drugs that induce a significant inhibition of renal tumor growth in different mouse models.

[Combination treatment with antisense oligonucleotides and chemotherapy in vitro]. / Kombinationsbehandlung mit Antisense-Oligonukleotiden und Chemotherapeutika in vitro.

Oncological therapy strategies are increasingly concentrating on the causal, molecular changes involved in carcinogenesis. So called "smart drugs" such as antisense oligoneucleotide (AsON) can be used as specific inhibitors of individual genes. AsONs have shown their effectiveness in many studies. Clinical studies have demonstrated, however, that for many tumours the inhibition of a single gene is, due to multigenetic alteration, largely ineffective. The combination of AsONs with conventional chemotherapeutic agents is currently being investigated in phase III studies. In these studies, chemotherapeutic agents have been evaluated in cell culture together with AsON against the proliferation associated Ki-67 gene, as well as against the apoptosis associated bcl-2 gene via RT-PCR, immunochemistry and MTT cell viability assay. For both AsONs, significant target inhibition was achieved in cell culture with a high target gene expression. The prior treatment of tumour cells with bcl-2 AsON significantly increased the effectiveness of chemotherapy, while the combination of conventional chemotherapeutic agents with Ki-67 AsON showed no synergistic effects.

Inhibition of bcl-2 enhances the efficacy of chemotherapy in renal cell carcinoma.

OBJECTIVES: Renal cell cancer (RCC) is highly resistant to chemotherapy. Increased expression of the antiapoptotic gene bcl-2 in tumors is known to be associated with poor responses to systemic treatment of cancer. Down-regulation of bcl-2 expression using antisense oligonucleotides (asON) has been shown to increase chemosensitivity in clinical phase I-III studies with various cancers. However, no studies on the efficacy of this approach in RCC have been reported so far. This study aimed to evaluate whether bcl-2 asON could enhance efficacy of chemotherapy in human RCC. MATERIAL AND METHODS: Expression of bcl-2 mRNA and protein was analyzed in different RCC cell lines by RT-PCR and Western blot. Cells with high or low bcl-2 mRNA and protein expression were treated with different concentrations of bcl-2 asON in combination with cisplatin. AsON-induced down-regulation of bcl-2 mRNA and protein was documented by RT-PCR and Western blot. Treatment effects on cell viability were analyzed by colorimetric tetrazolium (MTT) assay. Immunohistochemical staining of M30-positive cells was performed for quantification of apoptotic cells. RESULTS: Transfection of high bcl-2 expressing cells with bcl-2 asON alone induced no reduction of cell viability at a concentration range from 100-1000 nM. In combination therapy, pretreatment with asON significantly enhanced MTT reduction after cisplatin treatment. IC50 concentrations of cisplatin were 1 microg/ml with and 2.7 microg/ml without prior incubation. The marked reduction of cell viability correlated with an 8-fold increase of apoptotic cells after combination treatment. Only a minor increase of cisplatin effectivity was noted after asON preincubation of cells with lower bcl-2 expression. CONCLUSIONS: The combination of cisplatin and bcl-2 antisense ON exerts significantly greater effects on cell viability and apoptosis than either agent used alone on human RCC cells. These data indicate that inhibition of bcl-2 expression may be an attractive therapeutic strategy in RCC tumors with high bcl-2 expression.

Ki-67-directed antisense therapy in an orthotopic renal cell carcinoma model.

PURPOSE: The Ki-67 antigen is only present in proliferating cells. We have shown previously that phosphorothioate-modified antisense oligonucleotides (ON) against this antigen are potent antitumoral agents in bladder and prostate cancer-derived cells. Since ON are known to accumulate in vivo in the kidney, high local effectivity may be expected. Here, we evaluated and characterized antitumoral effects in an orthotopic renal cell cancer (RENCA) model. MATERIAL AND METHODS: RENCA cells were incubated with antisense and control ON in the presence of a cationic lipid. Uptake studies were performed with FITC-labeled ON. Ki-67 protein analysis after ON treatment was performed by immunohistochemical staining. For animal studies, 1 x 10(5) RENCA cells were implanted under the renal capsule of Balb/c mice. Antisense and control ON were injected intraperitoneally daily for 14 days. Tumor weights and status of metastasis were documented after sacrifice. Furthermore, vessel density in tumor tissues was determined by CD31 immunolabeling. RESULTS: Antisense treatment of RENCA cells resulted in specific reduction of the Ki-67 protein and inhibition of cell growth. A substantial cellular uptake of labeled ON was noted in vitro and in vivo. The growth of orthotopically implantated syngeneic kidney tumors in immunocompetent mice was significantly inhibited in antisense-treated animals (p < 0.05). Furthermore, lung metastases were noted in 10% of antisense-treated animals compared to 30-40% in control groups. Immunohistochemical staining of the vessel density showed no significant difference among treatment groups. CONCLUSIONS: The results demonstrate that Ki-67-directed antisense oligonucleotides are potent inhibitors of target protein expression and proliferation of tumor cells in vitro, and of tumor growth and lung metastasis formation in murine renal cell carcinoma whereas tumor vascularization is not significantly affected.

Elevation of CA 19-9 in giant hydronephrosis induced by a renal calculus.

CA 19-9 is a tumor marker of pancreatic and gastrointestinal cancer. Elevation in nonmalignant disease is rare. The case of a patient with a partial staghorn calculus, giant hydronephrosis, and elevated CA 19-9 serum levels is presented. Open transperitoneal right-sided nephrectomy was performed. In immunohistochemical analysis, CA 19-9 was expressed in the renal tubular epithelium and the renal pelvis. During postoperative follow-up, the CA 19-9 levels returned to normal. Hydronephrosis might cause false-positive results when CA 19-9 measurement is used to screen for malignant disease. Posttreatment CA 19-9 levels of patients with hydronephrosis have to be monitored closely to safely exclude malignant disease.

[Basics of antisense oligonucleotide therapy and current therapeutical strategies in urology]. / Grundlagen der Antisense-Oligonukleotid-Therapie und derzeitige Therapiestrategien in der Urologie.

Antisense oligonucleotides are short DNA sequences designed to modulate the information transfer from gene to protein. Sequence-related hybridisation with the mRNA of a specific protein results in selective inhibition of gene expression and downregulation of protein expression. This allows the study of gene function and therapy on a molecular level. Antisense oligonucleotide inhibitors can be designed directly from genomic sequence information by simply making the reversed complement of the desired sequence. In this review, we focus on the mechanisms of action of antisense oligonucleotides and summarize the progress in urological antisense therapy. The ability to inhibit individual gene expression with antisense oligonucleotides has been promising in preclinical cancer models. Current clinical studies test antisense compounds targeted against various cancer related genes. Although some of these studies comprise patients with urological tumors, such as advanced prostate cancer, experimental antisense therapy in urology is still in its infancy.

[Non-invasive urinary diagnosis of bladder cancer. What do we know?]. / Nichtinvasive Urindiagnostik des Harnblasenkarzinoms. Was ist gesichert?

Although the current system of classifying bladder cancer by stage and histological grade is very useful, it is still difficult to predict the natural progression of the disease either with or without therapy. Cystoscopy and urine cytology are currently the gold standards in the monitoring and diagnosis of bladder cancer. Classical urine cytology is, however, at least in the diagnosis of G1-tumors, characterized by a relatively low sensitivity. In the last few years, the molecular biological investigation of the basic mechanisms involved in carcinogenesis has provided a host of markers which are of potential diagnostic value for bladder cancer. We provide a current, comprehensive review of the literature on bladder tumor markers and summarize their diagnostic and prognostic potential. At present, no diagnostic marker with a comparable sensitivity and specificity to cystoscopy exists, given that cystoscopy has never been evaluated. The combined analysis of several tumor markers seems to be the most promising approach as an adjunct to cystoscopy. Moreover, the increasing simplification of test systems will increase their acceptance by clinicians.