G. Staehler

Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: A gene expression analysis on total and microdissected prostate tissue

Information on over- and underexpressed genes in prostate cancer in comparison to adjacent normal tissue was sought by DNA microarray analysis. Approximately 12,600 mRNA sequences were analyzed from a total of 26 tissue samples (17 untreated prostate cancers, 9 normal adjacent to prostate cancer tissues) obtained by prostatectomy. Hierarchical clustering was performed. Expression levels of 63 genes were found significantly (at least 2.5-fold) increased, whereas expression of 153 genes was decreased (at least 2.5-fold) in prostate cancer versus adjacent normal tissue. In addition to previously described genes such as hepsin, overexpression of several genes was found that has not drawn attention before, such as the genes encoding the specific granule protein (SGP28), alpha-methyl-acyl-CoA racemase, low density lipoprotein (LDL)-phospholipase A2, and the anti-apoptotic gene PYCR1. The radiosensitivity gene ATDC and the genes encoding the DNA-binding protein inhibitor ID1 and the phospholipase inhibitor uteroglobin were significantly down-regulated in the cancer samples. DNA microarray data for eight genes were confirmed quantitatively in five normal and five cancer tissues by real-time reverse transcriptase-polymerase chain reaction with a high correlation between the two methods. Laser capture microdissection of epithelial and stromal compartments from cancer and histological normal specimens followed by an amplification protocol for low levels of RNA (<0.1 microg) allowed us to distinguish between gene expression profiles characteristic of epithelial cells and those typical of stroma. Most of the genes identified in the nonmicrodissected tumor material as up-regulated were indeed overexpressed in cancerous epithelium rather than in the stromal compartment. We conclude that development of prostate cancer is associated with down-regulation as well as up-regulation of genes that show complex differential regulation in epithelia and stroma. Some of the gene expression alterations identified in this study may prove useful in the development of novel diagnostic and therapeutic strategies.

The role of radical surgery for renal cell carcinoma with extension into the vena cava.

PURPOSE New operative technologies, such as the bypass procedures that have become established in the last decade, have led to improved prognosis in patients with renal cell carcinoma and vena caval thrombi. We report the outcome of stage dependent surgical strategies in patients with renal cell carcinoma extending into the vena cava. MATERIALS AND METHODS From January 1987 to August 1998, 93 patients with renal cell carcinoma invading the inferior vena cava were seen at our institution. Of the patients 79 underwent radical nephrectomy, phlebotomy and thrombus extraction, including 74 who underwent surgical treatment with cardiopulmonary bypass and deep hypothermic circulatory arrest. In 2 patients with retrohepatic thrombi we placed a pump driven femoro-axillary shunt during surgical resection of the retrohepatic tumor portion. RESULTS Distant metastases and lymph node involvement proved to be highly significant prognostic factors for survival, while the cranial extent of the tumor thrombi had no prognostic impact. Patients without distant metastases had a 5-year survival rate of 34%, which improved to 39% if regional lymph nodes were not involved. There were 5 perioperative deaths (6.3%) and the highest perioperative mortality rate (40%) was seen in patients with supradiaphragmatic thrombi. CONCLUSIONS Radical surgery for renal cell carcinoma extending to the vena cava is justified when the tumor thrombus does not extend beyond the level of the diaphragm in the cranial direction. In view of the high perioperative mortality decisions about radical surgery must be made individually in patients with level IV thrombi, even if long-term survival is possible.

Mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinomas

To define the possible role of the VHL gene in the development of sporadic renal cell carcinomas, 91 different parenchymal tumours of the kidney have been investigated for mutation of the VHL gene by single strand conformation polymorphism (SSCP) and/or heteroduplex (HD) techniques. Chromosome 3p deletion was detected in 98 per cent of non‐papillary renal cell carcinomas and in 25 per cent of chromophobe renal cell carcinomas. In 22 of the 43 non‐papillary renal cell carcinomas, abnormally migrating DNA bands were detected by SSCP and/or HD analysis. No mobility shift was seen in any of the 23 chromophobe renal cell carcinomas. In addition, 15 papillary renal cell tumours and ten renal oncocytomas, which are characterized by genetic changes other than loss of chromosome 3p sequences, were analysed for mutation of the VHL gene. None of these tumours showed abnormal migration patterns. The results indicate that mutation of the VHL gene is associated exclusively with the development of non‐papillary renal cell carcinoma.

Failure of subureteral bovine collagen injection for the endoscopic treatment of primary vesicoureteral reflux in long-term follow-up

OBJECTIVES To evaluate the long-term efficacy of subureteral glutaraldehyde cross-linked collagen injection (GAX 35) for endoscopic treatment of primary vesicoureteral reflux (VUR). METHODS We prospectively studied 36 patients (58 ureteral renal units), 30 girls and 6 boys with a median age of 6 years (range 2 months to 18 years). All patients had primary VUR and were treated with a single subureteral collagen injection (GAX 35). The patients were followed up by voiding cystography. RESULTS According to the International Reflux Study Classification, we found the following reflux grades preoperatively: grade I, 2 ureteral units; grade II, 21 units; grade III, 28 units; grade IV, 4 units, and grade V, 3 units. All patients were treated with subureteral bovine collagen injection (GAX 35, mean volume 1.7 mL, range 0.7 to 3.5). All but 3 cases of reflux resolved initially. The mean follow-up was 13 months (range 1 to 108). After 37 months of follow-up, only 5 (9%) of 57 treated units remained reflux free. One unit was followed up for 17 months and also remained reflux free. CONCLUSIONS These data suggest that a single endoscopic subureteral collagen injection is not effective in the long-term follow-up of patients with primary VUR. In the future, it will be important to determine whether the new, currently used, and soon be approved bulking agents show better long-term clinical results to prevent VUR recurrence than bovine collagen does.

DETECTION OF HEMATOGENOUS MICROMETASTASIS IN PATIENTS WITH TRANSITIONAL CELL CARCINOMA

PURPOSE Cytokeratin 20 (CK 20) is selectively expressed in urothelium, gastric intestinal epithelium, in Merkel cells and in a variety of malignant neoplasms. CK 20 RT-PCR assay has been extensively used to detect isolated cancer cells in peripheral blood, lymph nodes and bone marrow samples of patients with colorectal carcinoma. Since CK-20 is also actively expressed in transitional cell carcinoma (TCC), we analyzed, whether CK 20 Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is suitable to detect residual tumor cells in patients with transitional cell carcinoma of the bladder and the upper urinary tract. MATERIALS AND METHODS Nested Reverse Transcriptase Polymerase Chain Reaction assay was used to analyze CK 20 transcripts in peripheral venous blood samples and tumor biopsies of 49 patients with transitional cell carcinoma. Blood samples of 22 healthy volunteers served as negative controls. RESULTS CK 20 mRNA was detectable in blood samples of 12 of 49 patients with TCC. All blood samples of the control group tested negative. The detection rate for CK 20 mRNA significantly correlated (p = 0.0019, Cochran-Armitage Trend Test) to the stage of disease and increased from 0% in stage pTa to 63% in stage pT4. CONCLUSIONS These results suggest that CK 20 is a suitable marker for the detection of disseminated TCC cells in peripheral venous blood samples and may be helpful in the molecular staging of TCC patients. The prognostic relevance has to be evaluated in further followup.

LONG-TERM EFFICACY OF SUBURETERAL COLLAGEN INJECTION FOR ENDOSCOPIC TREATMENT OF VESICOURETERAL REFLUX IN NEUROGENIC BLADDER CASES

PURPOSE We evaluated the long-term efficacy of subureteral glutaraldehyde cross-linked collagen injection (GAX 35) for endoscopic treatment of vesicoureteral reflux in patients with neurogenic bladder dysfunction due to meningomyelocele. MATERIALS AND METHODS We prospectively studied 12 women and 8 men (26 ureteral renal units) with a median age of 8 years (range 1 to 51) who had neurogenic bladder due to meningomyelocele. Reflux into single collecting systems was treated with subureteral collagen injection (GAX 35). Followup with video urodynamics included voiding cystography. RESULTS All patients performed intermittent catheterization to control the bladder. During the study all bladders were areflexic with normal compliance. Preoperative reflux according to the International Reflux Study Classification was grade I in 1, II in 9, III in 10, IV in 4 and V in 2 ureteral renal units. All patients were treated with subureteral collagen injection (mean volume 1.9 ml., range 0.7 to 3.5). Reflux resolved initially in all but 2 cases. Mean followup was 16 months (range 1 to 71). Reflux was still absent in only 15% of treated units after 24 months. CONCLUSIONS Our data suggest that endoscopic subureteral collagen injection in neurogenic bladder cases is not effective with long-term followup. New biocompatible and biodegradable materials should be tested to control vesicoureteral reflux.

Aetiology, diagnosis and management of spontaneous perirenal haematomas

This study focuses on the diagnostic and therapeutic challenge posed by spontaneous perirenal haematomas (SPHs). The medical records of 18 patients with SPHs seen in the past 8 years were reviewed with respect to aetiology, diagnosis and therapeutic management. SPH was secondary to angiomyolipoma (n = 4), polycystic kidneys (n =4), panarteritis nodosa (n = 3), renal cell carcinomas (RCCs, n = 2), glomerulonephritis, pyelonephritis, Morbus Wegener and cortical adenoma (one each). One case remained unclear. With appropriate imaging techniques (computed tomography and angiography) the underlying disorder was detected in 72%; in 4 cases the diagnosis was revealed by exploration and biopsy. Surgery was necessary in 16 patients. The cause of bleeding can be revealed by appropriate imaging in most cases. When imaging procedures fail to reveal the cause of SPH, exploration and biopsy are mandatory to exclude RCC. If the cause of SPH remains unclear even after exploration, patient monitoring by CT is justified.

The use of Neodymiuim-Yag Lasers in Urology: Indications, Technique and Critical Assessment

After development and experimental approval of suitable equipment for endoscopic and external use, the neodymium-YAG laser has been used routinely to treat tumors of the bladder and external genitalia in our department. A 2-year followup of 60 patients revealed a significant decrease in local bladder tumor recurrence (5 per cent). Successful laser therapy also was applied in cases of stage T1/T2 penile carcinomas, female urethral carcinomas and condylomata acuminata. Laser application offers an additional useful therapeutic procedure in the treatment of urological malignancies.

Surgical treatment of invasive penile cancer : The Heidelberg experience from 1968 to 1994

OBJECTIVES This study was performed to establish oncological guidelines for the surgical treatment of invasive penile cancer. MATERIALS AND METHODS The medical records of 51 patients with invasive penile cancer seen between 1968 and 1994 were reviewed in respect to treatment and long-term outcome. RESULTS For stage T1 tumors treated with organ-preserving procedures the local recurrence rats was 56%, whereas no patient experienced a local recurrence after partial amputation. For stage T2 tumors, local recurrence rate was 100% (organ preservation) versus 20% (amputative procedures). There was no significant difference related to regional recurrence between surveillance, inguinal radiation and lymphadenectomy for stage N0 tumors. For N+ stages, survival was related to the extent of inguinal metastasis after dissection (5-year survival rate for N1: 71 vs. 33% for N2/3). CONCLUSIONS Organ-preserving procedures include a high risk of local and regional recurrence. Adjuvant regional lymphadenectomy seems beneficial only in patients with solitary metastasis.

Präoperatives Staging von Nierenzellkarzinomen mit Kavazapfen: welches diagnostische Verfahren?

ZusammenfassungZiel dieser Untersuchung war die Evaluation der optimalen und effektiven Diagnostik beim präoperativen Staging von Nierenzellkarzinomen mit Kavazapfen. Ist der Einsatz der MRT gerechtfertigt? Es wurden 7 Nierenzellkarzinome der Tumorstadien T3b und T3c präoperativ in der CT und MRT untersucht und das Staging mit dem histopathologischen Ergebnis korreliert. In der MRT wurden 4 von 7 Kavazapfen in ihrer Ausdehnung korrekt und sicher beurteilt, in der CT keiner korrekt und sicher. Die MRT mit Gadolinium ist der CT im Staging von Nierenzellkarzinomen der hohen Tumorstadien überlegen und kann hier die Kavographie ersetzen. Die MRT ist in den Fällen, in denen sonographisch ein hohes Tumorstadium mit Kavazapfen vermutet wird, als präoperative Diagnostik gerechtfertigt.SummaryTo evaluate whether MRI is usefull in staging renal cell carcinomas with caval thrombus the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in staging renal tumors with caval thrombus were preoperatively examined. Tumor staging by CT and MR imaging were correlated with histopathological tumor stadium. In MRI 4 out of 7 thrombi were correctly diagnosed with high accuracy, in CT none. In advanced renal carcinoma MRI with Gadolinium was superior to CT imaging, especially in diagnosing tumor thrombus. Consequently the extent of tumor thrombus may be assessed by MRI which therefore may replace conventional cavography.