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Objective: The initial objective of this renal cancer study was to identify gene sets in clear cell renal cell carcinoma (ccRCC) to support grading of ccRCC histopathology., Materials and Methods: Preselected ccRCC tumor tissues of grade 1 (G1, n = 14) and grade 3 (G3, n = 15) as well es 14 normal kidney tissues thereof were subjected to microarray expression analysis using Human Genome U133 Plus 2.0 Array. Event ratio scoring, hierarchical clustering and principal component analysis were used to determine gene sets that distinguish expression profiles from normal kidney tissue, G1 and G3 tumor tissues., Results: An initial set of 73 genes provided seven gene subclusters (SC01 to SC07) that distinguish RNA expression profiles from G1, G3 tumor and normal kidney tissues. A ranked list of 24 genes was determined that separated G1 from G3 tumors in high concordance with histopathological grading confirmed by immunohistochemical analysis of ceruloplasmin protein expression., Conclusion: A final set of 24 genes has been determined awaiting further validation on the RNA as well as on the protein level by studying an additional cohort of ccRCC patients. A reliable separation of G1 and G3 tumor grades will be instrumental to foster and direct the administration of upcoming targeted therapeutics of ccRCC tumors in a more predictive and reliable manner., (Copyright © 2011 S. Karger AG, Basel.)

Introduction: The regulation proteins retinoblastoma protein (pRb) and p16 play an important role in the cell cycle as tumor suppressors. pRb is the main substrate for the function of cyclin-dependent kinases during the cell cycle in the transition from G(1) to S phase. In this study, the immunohistochemical expression of pRb and p16 in renal cell carcinoma (RCC) were examined., Methods: Paraffin-embedded specimens from 94 patients with RCC were examined immunohistologically, using primary antibodies for p16 and pRb (Novocastra) and a biotin-conjugated anti-mouse IgG secondary antibody. Microscopically, the expression of p16 and pRb was evaluated by examination of the staining intensity of 100 cells of each specimen, and compared with epidemiological parameters (tumor size, TNM, nuclear grade and follow-up). Statistical analyses were conducted by SPSS, version 15.0 (SPSS® Inc., Chicago, Ill., USA), the χ(2) test (Fisher's exact test), the Kaplan-Meier method and Mantel's log rank test., Results: All 94 tumors showed a positive reaction for pRb (weakly positive in 67.0%; strongly positive in 33.0%). p16 was expressed in only 52.1% (weakly positive in 48.9%; intermediately positive in 3.2%; no strongly positive expression). The expression of p16-positive tumors was significantly associated with the expression of pRb (p = 0.040). Tumor size, grading, lymph node and distant metastases did not correlate with p16/pRb expression., Conclusion: pRb and p16 control the cell cycle as tumor suppressors. Therefore, in many tumors they are dysregulated. There are distinct differences in expression in various individual RCC. However, in a limited number of cases there was no significant correlation with clinical parameters., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: To investigate the effects of serotonin and melatonin (MLT) on the regulation of malignant growth and the activity of serotonin receptors (5HTR1a/-1b) in prostate cancer (PCa) cell lines., Materials and Methods: In four PCa cell lines (LNCaP, 22RV1, PC3, DU145) and two reference cell lines 5HTR1a and -1b, relative mRNA expression levels were assessed. Different serotonin and MLT receptor agonists and antagonists were used in stimulation and inhibition experiments., Results: mRNA expression of 5HTR1b was higher than that of 5HTR1a in all PCa cell lines. Serotonin showed a significant growth stimulatory effect in all PCa lines. The 5HTR1a and -1b agonists/antagonists did not significantly affect viability. MLT inhibited viability only in PC3 cells. Similarly, the 5HTR1a antagonist induced apoptotic changes in PC3 cells only at 10(-4)M, while the 5HTR1b antagonist induced necrosis at 10(-4)M in all cell lines. Cell cycle alterations were seen in PC3 and DU145 cells under the influence of the 5HTR1a antagonist., Conclusions: Serotonin receptor antagonists and agonists as well as MLT influence viability and apoptosis of PCa cell lines at supraphysiologic concentrations. In contrast to other reports, our results do not support a regulatory role of serotonin or MLT receptor activation or inhibition in PCa growth., (Copyright (c) 2010 S. Karger AG, Basel.)

The prognosis of patients with advanced penile carcinoma is poor. There are only few studies, mostly with a low number of patients, which show a low response rate with severe toxicity. While adjuvant and palliative chemotherapy for penile cancer is universally characterized by low efficacy, neoadjuvant approaches for patients with fixed lymph node metastases have shown some response. Overall, recent experiences with new chemotherapeutic approaches (i.e. taxane-based combinations) have shown some encouraging results. Therefore, these combinations should be investigated in larger and multi-center studies., ((c) 2009 S. Karger AG, Basel.)

Ovarian type surface epithelial carcinomas of the testis and paratestis are rare. The most frequent form is the serous subtype while only a few cases of the mucinous subtype have been reported in the literature. A 67-year-old patient with a mucinous ovarian type surface carcinoma of the testis is presented. The histopathological and immunohistochemical details of this rare lesion are discussed., ((c) 2008 S. Karger AG, Basel.)

Injuries of the penis are uncommon but represent urological emergencies. We report 3 cases of penile trauma illustrating the diversity of penile injury presentation. Radiological investigations are only mandatory if there is any suspicion of a urethral injury. Primary surgical approach is recommended in cases of penile fracture or local wound infection. An immediate operative exploration with removal of hematoma and primary defect closure should be done in every case. Surgical management should not be delayed to avoid late complications., (2008 S. Karger AG, Basel)

Introduction: Extracorporeal shock wave lithotripsy (ESWL) is the standard stone treatment. Increased excretion of tubular enzymes and hypercalciuria has been reported after ESWL. We investigated the importance of renally induced hypercalciuria after ESWL., Material and Methods: 30 calcium oxalate stoneformers (23 men, 7 women), mean age 53.3 (range 30-71) years, were evaluated prospectively. Plasma calcium and creatinine concentrations and 8-hour overnight urine were measured before ESWL and on the 1st and 2nd days after ESWL. To estimate the changes of tubular reabsorption, the calcium/creatinine clearance ratios were calculated., Results: Hypercalciuria (>5 mmol/24 h) was seen in 5/30 (16.7%) before, in 12/30 (40.0%) on day 1 and in 13/30 (43.3%) on day 2 after ESWL. The mean plasma levels of calcium were significantly decreased from 2.36 mmol/l before to 2.28 mmol/l on day 2 after ESWL (p< 0.01). The mean calcium/creatinine clearance ratio was significantly increased from 0.012 before to 0.019 after ESWL (p< 0.01). Before and on day 2 after ESWL, the calcium/creatinine clearance ratio was significantly correlated with the age of the patients (r = 0.33, p< 0.04)., Conclusion: Our data show an age-related significantly increased urine calcium excretion after ESWL possibly due to decreased tubular calcium reabsorption., ((c) 2008 S. Karger AG, Basel.)

Objective: Primary transitional cell carcinoma (TCC) of the upper urinary tract represents 6-8% of all TCC cases. Nephroureterectomy with removal of a bladder cuff is the treatment of choice. The rates of TCC recurrence in the bladder after primary upper urinary tract surgery described in the literature range between 12.5 and 37.5%. In a retrospective analysis we examined the occurrence of TCC after nephroureterectomy for upper tract TCC in patients without a previous history of bladder TCC at the time of surgery., Methods: Between 1990 and 2002, 29 patients underwent primary nephroureterectomy for upper tract TCC. The mean age of the patients was 69.5 years. In 5 cases upper urinary tract tumors were multilocular, in the remaining cases unilocular in the renal pelvis (n=12) or the ureter (n=12). The follow-up was available for 29 patients with a mean follow-up of 3.37 (0.1-11.2) years., Results: 11/29 (37.9%) patients had TCC recurrence with 9/11 patients having bladder TCC diagnosed within 2.5 years (0.9-6.0) after nephroureterectomy. 13/29 patients are alive without TCC recurrence, 3/29 patients died due to systemic TCC progression and 5/29 died of unrelated causes without evidence of TCC recurrence., Conclusion: Our data indicate a high incidence of bladder TCC after nephroureterectomy for primary upper tract TCC of up to 6 years after primary surgery. Because of the high incidence of bladder TCC within the first 3 years of surgery, careful follow-up is needed over at least this period., (copyright 2004 S. Karger AG, Basel)

Background: Radiotherapy alone or in combination with radical hysterectomy remains a potentially curative treatment for cervical carcinoma. Late urological complications after curative radiotreatment are rare but often present difficult problems of management due to the progressive nature of radiogenic tissue damage. We reviewed all cases of radiogenic urologic complications after radiotherapy for cervical carcinoma treated at our institution over the past 10 years., Patients and Methods: In a retrospective analysis, out of all female patients treated for hydronephrosis (n = 543), 93 patients with hydronephrosis occurring after curative treatment for gynecological malignancies were identified. The most frequent cause was progressive disease (n = 55); 30 patients without recurrence had severe radiogenic urological complications (study population)., Results: Out of 30 patients with a mean age of 44.9 years at the time of treatment for cervical cancer, 6 had undergone primary radiotherapy and 24 had received adjuvant radiotreatment after radical hysterectomy. The observed late urological complications were: distal ureteral stenoses (bilateral in 4 cases, unilateral in 15 cases), distal ureteral necrosis (n = 1), bilateral ureteral reflux (n = 3), vesico-vaginal fistulae (n = 5), vesico-intestinal fistula (n = 1), severe fibrotic bladder shrinkage (n = 6) and urethral stenosis (n = 2). Marked signs of radiogenic cystitis were observed in almost all patients. The mean latency time between radiotherapy and manifestation of severe radiogenic urological sequelae was 19.4 years (range 0.5-41.5). Primary treatment of urological complications consisted in temporary urinary diversion by percutaneous nephrostomies or insertion of internal ureteral stents. Permanent treatment for radiogenic ureteral stenosis in all patients with sufficient general health consisted of surgical or endourological urinary diversion or reconstruction. However, the majority of patients were managed by permanent endourological measures. Lower tract fistulae were treated by distal ureteral occlusion and diversion., Conclusions: Although severe late urological sequelae of curative radiotherapy for cervical carcinoma are rare they represent major complications, result in considerable distress for the patient, and often present difficult therapeutic problems for the urologist. As these urological complications can have extremely long latency times, focussed follow-up for early detection may be advisable., (Copyright 2003 S. Karger GmbH, Freiburg)

The increasing use of interstitial brachytherapy for the treatment of prostate cancer has made it necessary to discuss and establish guidelines for the application of this treatment modality. A group of experts representing the four professional and scientific societies of urologic surgeons and radiation oncologists in Germany was formed by the German Society of Urology (Deutsche Gesellschaft für Urologie, DGU), the Association of German Urologists (Berufsverband der Deutschen Urologen e.V., BDU), the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) and the Association of German Radiotherapists (Berufsverband der Deutschen Strahlentherapeuten, BVDSt). This group has formulated a consensus statement consisting of recommendations and guidelines for the indications, planning, implementation and follow-up of permanent interstitial brachytherapy by seed implantation for the treatment of localized prostate cancer. These recommendations also define the responsibilities of the two medical disciplines involved in the use of this interdisciplinary treatment., (Copyright 2003 S. Karger AG, Basel)

Introduction: Primary renal lymphoma (PRL) as a clinical entity is not undisputed because the kidneys do not contain lymphatic tissue and the mechanism of development of PRLs is unclear. Most of the few cases reported showed rapid systemic progression and a poor prognosis. Although there are no clearly defined diagnostic criteria for renal lymphomas, abdominal and thoracic computed tomography as well as renal and bone marrow biopsy are recommended. 3 cases of renal lymphoma are reported and their diagnosis and management discussed., Case Reports: Between 1996 and 2001, 3 male patients with renal lymphoma were diagnosed and treated at our institution. In patient No. 1, because of persisting macroscopic hematuria a bilateral PRL was diagnosed by renal biopsy, without any detectable lesions on CT imaging. Patient No. 2 presented with a large renal mass which, on biopsy, was diagnosed as a lymphoma. Patient No. 3 showed lymphoma on renal biopsy and bone marrow involvement. All 3 patients were treated with systemic chemotherapy which resulted in death of disease in 2 patients and a complete remission in 1 patient after adjuvant radiotherapy and nephrectomy., Conclusion: PRL represents a rare entity which must nevertheless be considered in cases of unusual renal masses or otherwise unexplained renal symptoms. If diagnosed early, cure is possible, and multimodal treatment should be considered., (Copyright 2002 S. Karger GmbH, Freiburg)

Background: Primary urethral carcinoma is a very rare condition, and no large-scale experience with such cases has been published. Treatment will therefore have to follow rules established for the treatment of similar conditions., Patients: Six cases of primary urethral carcinoma (5 male, 1 female) who had been treated at our institution between 1995 and 1999 were retrospectively analyzed. In 3 male cases, a primary urothelial carcinoma of the distal urethra was treated by distal urethrectomy only. In 3 other cases with locally advanced tumors and/or lymph node metastases surgical treatment was followed by adjuvant cisplatinum-containing chemotherapy., Results: In the 3 cases with distal urethral carcinoma, partial urethrectomy with preservation of the penis resulted in cure, with a follow-up of 12-71 months. In the cases with advanced disease, adjuvant chemotherapy after surgery has resulted in complete remissions in all 3 cases, with a follow-up of 4-47 months at present., Conclusions: In localized, noninvasive carcinoma of the distal male urethra, partial urethrectomy seems adequate and the avoidance of penile amputation justified. In advanced cases, after local excision and lymphadenectomy adjuvant chemotherapy which by necessity must follow the guidelines established for the treatment of other urothelial or squamous cell malignancies seems to be beneficial., (Copyright 2001 S. Karger GmbH, Freiburg)

The rare case of a 65-year-old male with a cervical lymph node manifestation as the only tumour manifestation is reported. The diagnostic and therapeutic management of the case is discussed. This represents the fourth case with such a condition reported in the literature., (Copyright 2001 S. Karger AG, Basel.)

Objectives: To investigate the prevalence and distribution of comorbidity and its association with perioperative complications in patients undergoing radical prostatectomy (RPE)., Methods: In 431 unselected RPE patients, the American Society of Anesthesiologists Physical Status classification (ASA-PS), the New York Heart Association classification of cardiac insufficiency (NYHA), the classification of angina pectoris of the Canadian Cardiovascular Society (CCS), height, weight, the body mass index (BMI), and the number of concomitant diseases (NCD) were assessed and related to perioperative cardiovascular complications., Results: In RPE patients less than 70 years old, comorbidity rose nearly continuously with increasing age. However, after reaching an age of 70 years, the proportion of NYHA-0 patients increased (60-64 years, 86%; 65-69 years, 85%; >or=70 years, 87%). Furthermore, the severe comorbidities decreased in patients selected for RPE aged 70 or more years. There was a nonsignificant trend towards higher comorbidity in patients with perioperative cardiovascular complications., Conclusions: These data suggest that documentation of the distribution of ASA-PS, CCS, NYHA and of concomitant diseases might be helpful to characterize the general health status and the degree of selection of prostate cancer treatment populations especially in series with a high portion of patients aged 70 or more years. Concerning perioperative complications, the individual predictive value of comorbidity seems to be poor in the radical prostatectomy setting., (Copyright 2001 S. Karger AG, Basel)

Transition zone biopsies have been found to increase the detection rates of cancer of the prostate in patients with negative digital rectal examination. There are however no data available whether the higher biopsy rate is associated with greater morbidity. The present study was therefore designed to evaluate the complication rate of extended sextant biopsy. In this prospective study, 162 consecutive patients who presented for prostatic evaluation were included. After starting prophylactic antibiotic treatment 48 h prior to the procedure, transrectal ultrasound-guided core biopsies were obtained from each lobe: three each from the peripheral zone (apex, mid-zone and base) and two from the transition zone of each prostatic lobe. In all patients a questionnaire was obtained 10-12 days after the procedure. Major complications occurred in 3 patients. In 2 of the 3 cases major macroscopic hematuria was treated by an indwelling catheter for 1 or 2 days and 1 patient developed fever >38.5 degrees C for 1 day. Minor macroscopic hematuria was present in 68.5% of the patients. In 17.9% of these cases, the hematuria lasted for more than 3 days. Hematospermia was observed in 19.8% and minor rectal bleeding occurred in 4.9%. Ten-core biopsies did not lead to an increase in adverse effects or complications when compared to the results of sextant biopsies reported in the literature., (Copyright 2001 S. Karger AG, Basel)

Background: The optimal extent of the prostate biopsy remains controversial. There is a need to avoid detection of insignificant cancer but not to miss significant and curable tumors. In alternative treatments of prostate cancer, repeated sextant biopsies are used to estimate the response. The aim of this study was to investigate the reliability of a repeated systematic sextant biopsy as the standard biopsy technique in patients with significant tumors which are being considered for curative treatment., Methods: Systematic sextant biopsy was performed in vitro in 92 radical prostatectomy specimens. Of these patients, 81 (88.0%) had palpable lesions., Results: Of the 92 investigated patients, 70 (76.1%) had potentially curable pT2-3pN0 prostate cancers. In these patients, the cancer was detected only in 72.9% of cases by a repeated in vitro biopsy. In the pT2 tumors, there was a detection rate of only 66.7%., Conclusions: This study underlines the fact that a considerable number of significant and potentially curable tumors remain undetected by the conventional sextant biopsy. A negative sextant biopsy does not rule out significant prostate cancer., (Copyright 2000 S. Karger AG, Basel)

Incidentally discovered adrenal masses often pose a diagnostic challenge in the asymptomatic patient. The majority represent functional adrenal adenomas but primary or secondary malignancy must be considered. Bilateral incidentalomas are rare, and a case of asymptomatic bilateral adrenal melanoma metastases is presented. The diagnostic and treatment strategies relevant to this clinical problem are presented and discussed., (Copyright 2000 S. Karger AG, Basel)

The guidelines for the curative treatment of prostate cancer presented by the German Society of Urology are discussed. They are based on the current knowledge of the outcomes of surgical and radiotherapeutic treatment for prostate cancer. Radical prostatectomy is recommended as the first-line treatment for organ-confined prostate cancer in patients with an individual life expectancy of at least 10 years. Radiotherapy can be considered as an alternative treatment modality, although current knowledge does not allow a definite assessment of the relative value of radiotherapy compared to radical prostatectomy. Locally advanced cT3 prostate cancer is overstaged in about 20% and curative treatment is possible in selected cases. Guidelines represent rules based on the available evidence. This implies that exceptions must be made whenever appropriate and that guidelines have to be reviewed regularly as new information becomes available., (Copyright 1999 S. Karger AG, Basel)

An uncommon case with semi-spheric perivesical calcification after pelvic radiotherapy is reported and the possible pathogenesis of this phenomenon is discussed.

Objective: In this study, 22 cases of locally recurrent urological malignant fibrous histiocytoma were reviewed considering therapeutic options, follow-up and prognosis., Patients and Methods: In the available literature on this topic we identified 19 cases of locally recurrent genitourinary malignant fibrous histiocytoma. Three additional cases are discussed, primarily arising from the kidney, the bladder and the paratesticular region., Results: The prognosis of locally recurrent urological malignant fibrous histiocytoma was found to be extraordinarily poor. Only 2 of 22 patients have survived for longer than 3.5 years. One of them reported herein is still alive 10 years after extensive lymphatic spread accompanying the first local recurrence. In this case, late local recurrence occurred after an 8-year interval free of disease., Conclusion: Malignant fibrous histiocytoma is an unusual urological malignancy with a high rate of local recurrence. The latter is frequently accompanied by metastatic disease and unrelenting progression. Despite the poor prognosis early detection of local failure and aggressive salvage therapy might offer the chance of long-term survival in selected cases. Close and life-long follow-up is advisable for patients once treated for recurrent urological malignant fibrous histiocytoma.