Claus R. Riedl

hTERT alone immortalizes epithelial cells of renal proximal tubules without changing their functional characteristics

Telomere-dependent replicative senescence is one of the mechanisms that limit the number of population doublings of normal human cells. By overexpression of telomerase, cells of various origins have been successfully immortalized without changing the phenotype. While a limited number of telomerase-immortalized cells of epithelial origin are available, none of renal origin has been reported so far. Here we have established simple and safe conditions that allow serial passaging of renal proximal tubule epithelial cells (RPTECs) until entry into telomere-dependent replicative senescence. As reported for other cells, senescence of RPTECs is characterized by arrest in G1 phase, shortened telomeres, staining for senescence-associated beta-galactosidase, and accumulation of gamma-H2AX foci. Furthermore, ectopic expression of the catalytic subunit of telomerase (TERT) was sufficient to immortalize these cells. Characterization of immortalized RPTEC/TERT1 cells shows characteristic morphological and functional properties like formation of tight junctions and domes, expression of aminopeptidase N, cAMP induction by parathyroid hormone, sodium-dependent phosphate uptake, and the megalin/cubilin transport system. No genomic instability within up to 90 population doublings has been observed. Therefore, these cells are proposed as a valuable model system not only for cell biology but also for toxicology, drug screening, biogerontology, as well as tissue engineering approaches.

Hexaminolevulinate-Guided Fluorescence Cystoscopy in the Diagnosis and Follow-Up of Patients with Non–Muscle-Invasive Bladder Cancer: Review of the Evidence and Recommendations

CONTEXT Compared with standard white-light cystoscopy, photodynamic diagnosis with blue light and the photosensitiser hexaminolevulinate has been shown to improve the visualisation of bladder tumours, reduce residual tumour rates by at least 20%, and improve recurrence-free survival. There is currently no overall European consensus outlining specifically where hexaminolevulinate is or is not indicated. OBJECTIVE Our aim was to define specific indications for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION A European expert panel was convened to review the evidence for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of NMIBC (identified through a PubMed MESH search) and available guidelines from across Europe. On the basis of this information and drawing on the extensive clinical experience of the panel, specific indications for the technique were then identified through discussion. EVIDENCE SYNTHESIS The panel recommends that hexaminolevulinate-guided fluorescence cystoscopy be used to aid diagnosis at initial transurethral resection following suspicion of bladder cancer and in patients with positive urine cytology but negative white-light cystoscopy for the assessment of tumour recurrences in patients not previously assessed with hexaminolevulinate, in the initial follow-up of patients with carcinoma in situ (CIS) or multifocal tumours, and as a teaching tool. The panel does not currently recommend the use of hexaminolevulinate-guided fluorescence cystoscopy in patients for whom cystectomy is indicated or for use in the outpatient setting with flexible cystoscopy. CONCLUSIONS Evidence is available to support the use of hexaminolevulinate-guided fluorescence cystoscopy in a range of indications, as endorsed by an expert panel.

Bacterial Colonization of Ureteral Stents

Objectives: The aim of this study was to assess the frequency of bacterial stent colonization and stent-associated bacteriuria, and to evaluate the significance of urinary cultures for identification of colonizing microorganisms. Methods: A total of 93 ureteral stents from 71 patients were examined: 9 patients with permanent ureteral stenting due to malignant ureteral obstruction (27 stents), and 62 patients with temporary ureteral stents (66 stents). Results: Bacteriuria and bacterial stent colonization were found in all patients with permanent stents. In patients with temporary stents, colonized stents were found in 69.3% (43/62), mainly in combination with sterile urine (45.2%, 28/62). Mean indwelling times did not differ between patients with sterile urine and sterile stents (11.8 days) and patients with sterile urine and colonized stents (11.2 days). Prophylactic antibiosis in 42/62 temporarily stented patients did not reduce colonization rates compared to patients without antibiotics (70 vs. 65%). Enterococci were the bacteria most frequently cultured from urine and stents. Conclusions: In the present study, ureteral stent colonization rates were 100% in permanently and 69.3% in temporarily stented patients. Antibiotic prophylaxis did not prevent stent colonization and should not be routinely administered. Since urinary cultures correctly identified all colonizing microorganisms in only 21%, removal/replacement and bacteriologic evaluation of ureteral stents may be necessary in case of urosepsis.

Heparin coating reduces encrustation of ureteral stents: a preliminary report

The present study evaluated the inhibition of ureteral stent encrustation by heparin coating. In contrast to uncoated polyurethane stents, heparin coated ureteral stents did not show any organic (biofilms) or anorganic (crystals) deposits after being in situ for up to 6 weeks and effectively inhibited the encrustation process.

Iontophoresis for treatment of Peyronie's disease

PURPOSE We evaluate the efficacy of iontophoresis of dexamethasone, lidocaine and verapamil to treat Peyronies disease. MATERIALS AND METHODS In an uncontrolled prospective study 100 unselected patients with Peyronies disease were treated with 3 weekly courses of iontophoresis. The drug mixture was administered by an electrical current of 5 mA. and a self-adhesive receptacle fixed to the penile skin overlying the plaque. RESULTS Resolution of pain was observed in 96% of patients, plaque diminution in 53% and improvement of penile deviation in 37%. Impaired sexual function was improved in 19 of 43 patients (44%). The benefit of iontophoresis therapy was more pronounced in patients with a short history of disease. Because of lack of side effects and painless administration iontophoresis was well tolerated and accepted by all patients. CONCLUSIONS Iontophoresis of dexamethasone, lidocaine and verapamil may be regarded as first line nonsurgical treatment for Peyronies disease.

Intravesical electromotive drug administration technique: Preliminary results and side effects

PURPOSE We performed intravesical electromotive drug administration (EMDA) for various bladder disorders during a 3-year period and assessed the technique, possible applications, complications and outcomes of this procedure. MATERIALS AND METHODS Intravesical EMDA was performed with local anesthetics for transurethral surgery and in combination with dexamethasone for the treatment of noninfectious chronic cystitis (interstitial/radiation cystitis), with mitomycin C for recurrence prophylaxis of high risk superficial bladder cancer and with oxybutynin/bethanechol for the hyperreflexive/acontractile detrusor. A standardized power source and electrode catheter were used for 215 treatments in 84 patients. RESULTS Transurethral bladder tumor resections were pain-free in 10 of 12 patients. Of the 25 patients with chronic noninfectious cystitis 15 were free of symptoms for a mean of 6.6 months, and there was a 73% increase in mean bladder capacity from 244 before to 421 cc after EMDA. Of the 16 patients with superficial bladder cancer 9 were free of recurrence for a mean of 14.1 months. In 10 of 14 patients with acontractile detrusors urodynamic examination showed detrusor contraction during EMDA of bethanechol. There were no contractions without electric current. EMDA of oxybutynin reduced detrusor hyperreflexia. A bladder ulcer was the single severe local complication and 4.6% of patients, mainly those with chronic cystitis, reported significant post-EMDA bladder/urethral pain. Minor side effects accounted for 23% of all treatments. No systemic side effects occurred. CONCLUSIONS Intravesical EMDA is effective and innocuous. The therapeutic concept combines the advantages of increased drug administration without systemic side effects.

Long-term followup after laparoscopic nephropexy for symptomatic nephroptosis.

PURPOSE Symptomatic nephroptosis is a rare disease requiring surgical therapy only in select cases. Laparoscopic nephropexy has been reported as minimally invasive treatment for symptomatic patients. We evaluated our long-term outcome after laparoscopic fixation of the kidney with an alloplastic mesh graft. MATERIALS AND METHODS Since 1992, 30 patients have undergone laparoscopic transperitoneal nephropexy for symptomatic nephroptosis. All patients were preoperatively investigated by excretory urography (IVP) and split renal scan in the supine and upright positions. For fixing the kidney to the abdominal wall a polyglactin and polypropylene mesh graft was used in 6 and 24 cases, respectively. A total of 17 patients with a minimum followup of 5 years participated in an assessment of long-term outcome. Clinical examination, IVP and split renal function testing were performed with patients lying and standing. Patients were further questioned about postoperative satisfaction and whether they would undergo the procedure again. RESULTS Of 17 patients 10 completed all investigations, 3 were contacted by telephone and 4 were lost to followup. Median followup was 5.9 years. Improvement in symptoms was reported in all cases with complete relief in 11 and intermittent flank pain requiring no medication in 2. There were no postoperative urinary tract infections or hematuria observed with improved hypertension requiring no postoperative medication in 1 case. Postoperatively IVP showed no recurrence in 8 of 10 patients but there was 5 cm. or greater recurrent ptosis in 2. Recurrence developed after using the polyglactin and polypropylene mesh grafts. Comparing preoperative and postoperative (123)iodine renal scans revealed significant improvement in renal function in 9 cases (p <0.05). There was no postoperative difference in split renal function and only 1 patient did not improve. No complications were noted except 1 symptomatic recurrence 3 months after the initial operation that required open surgical fixation. A total of 11 patients were completely satisfied with the long-term outcome and 2 were moderately satisfied. Of the patients 12 would undergo the procedure again, including 2 with persistent slight flank pain. One patient was inconsistent in regard to whether she would undergo the procedure again. CONCLUSIONS Symptomatic nephroptosis is a bothersome disease requiring therapy only after thorough evaluation, including IVP and split renal scan with patients supine and upright. The good clinical outcome and highly satisfactory cosmetic result support laparoscopic nephropexy as the treatment of choice. Short-term and long-term results prove the efficacy of renal fixation with alloplastic mesh graft as minimally invasive therapy with a high success rate.

ELECTROMOTIVE ADMINISTRATION OF INTRAVESICAL BETHANECHOL AND THE CLINICAL IMPACT ON ACONTRACTILE DETRUSOR MANAGEMENT:: INTRODUCTION OF A NEW TEST

PURPOSE It is often difficult to determine the functional status of the detrusor muscle in patients with detrusor areflexia. We performed a clinical study to establish a test defining residual detrusor capacity in such patients. MATERIALS AND METHODS In phase 1, 5 controls with detrusor areflexia were tested with an intravesical instillation of 20 mg. bethanechol in 150 cc of sodium chloride 0.3% with and without 20 mA. of pulsed current applied via an electrode catheter through the saline. Cystometry simultaneously recorded intravesical pressure changes. In phase 2, 45 patients with detrusor areflexia were tested with electromotive administration of intravesical bethanechol. In phase 3, 25 mg. bethanechol given orally once daily were prescribed for 15 patients and voiding control was assessed after 6 weeks of therapy. RESULTS Neither bethanechol without current nor current through saline only led to increased intravesical pressure. However, we noted a mean pressure increase of 34 cm. water during the electromotive administration of bethanechol in 24 of 26 patients with areflexia and neurological disease compared to only 3 cm. water in 3 of 11 with a history of chronic bladder dilatation. Oral bethanechol restored spontaneous voiding in 9 of 11 patients who had had a positive response to the electromotive administration of bethanechol, whereas all 4 without a pressure increase during the electromotive administration of bethanechol did not void spontaneously. CONCLUSIONS Electromotive administration of intravesical bethanechol identifies patients with an atonic bladder and adequate residual detrusor muscle function who are candidates for restorative measures, such as oral bethanechol and intravesical electrostimulation. Those who do not respond to the electromotive administration of bethanechol do not benefit from oral bethanechol and are candidates for catheterization.

Unilateral or bilateral testicular biopsy in the era of intracytoplasmic sperm injection.

PURPOSE Intracytoplasmic sperm injection has significantly improved the treatment of male infertility. Since only single vital spermatozoa are required for successful fertilization, the value of unilateral or bilateral diagnostic testicular biopsies in patients with azoospermia is controversial. We evaluated differences in bilateral testicular biopsies in azoospermic patients with regard to testicular histology and focal spermatogenesis. MATERIALS AND METHODS Histopathological results of 100 testicular biopsies from 50 patients (mean age 33.3 years) were reviewed. In all cases azoospermia was the indication for diagnostic testicular biopsy. Intra-individual differences of bilateral testicular biopsies were retrospectively reviewed by determining the latest stage of spermatogenesis. RESULTS After bilateral biopsy a difference in testicular histology was found in 28% and identical histopathology was noted in 70% of patients. An unsuspected burned out seminoma with maturation arrest in the contralateral testis was seen in 2% of cases. Testicular symmetry determined by a Prader orchidometer was noted in 54.8% of patients whereas 45.2% had asymmetrical testis. The frequency of divergent histopathologies in relation to testicular symmetry was 21.7 and 26.3%, respectively. Spermatozoa were found in 42% of right and 44% of left testes (p >0.05), and spermatids as the latest stage of differentiation were detected in 14 and 16%, respectively (p >0.05). Differentiation of testicular histologies according to the side of biopsy revealed spermatozoa and/or spermatids in 56% of right and 58% of left testes (p >0.05). Bilateral biopsies increased the detection of focal spermatogenesis to 68%. If only unilateral diagnostic testicular biopsies had been performed, in 20% of patients focal spermatogenesis in the contralateral testis would have been missed. CONCLUSIONS Bilateral testicular biopsies are superior to unilateral biopsies in the evaluation of patients with azoospermia. A 28% intra-individual difference in testicular pathology was seen after bilateral biopsies, and in 20% of patients focal spermatogenesis would have been missed after unilateral biopsy only. Due to the prognostic relevance of testicular biopsies for successful sperm retrieval before assisted reproduction, bilateral diagnostic testicular biopsies are recommended in the evaluation of patients with azoospermia.

Chronic asymptomatic inflammation of the prostate type IV and carcinoma of the prostate: Is there a correlation?

Abstract Objective. The aim of this study was to detect possible correlations between chronic asymptomatic inflammation of the prostate type IV and prostate cancer in patients undergoing radical prostatectomy (RPE). Material and methods. Between January and December 2010, 57 RPE specimens were prospectively evaluated with regard to histological signs of chronic inflammation. This RPE group was compared to specimens of 82 men undergoing transurethral resection of the prostate (TURP) or transvesical enucleation (TVE) of a benign prostate (BPH group). To characterize inflammatory changes, inflammatory “hot spots” were defined according to the histological criteria of Irani et al. (J Urol 1997;157:1301–3). Total prostate-specific antigen (PSA), cholesterol, triglycerides, uric acid, International Prostate Symptom Score and body mass index (BMI) were evaluated preoperatively and were correlated to the histological findings. Results. Chronic inflammation was verified in 43.86% of the RPE group, compared to 70.74% of the BPH group (p < 0.001). Multivariate analysis found a significant correlation between older patients and the inflammation score (p < 0.03) and prostate volume (p < 0.03). There was no difference in the PSA values between the inflammation and non-inflammation groups: mean PSA was 5.7 vs 6.1 ng/ml in the RPE group (p < 0.89), and 2.8 vs 2.9 ng/ml in the BPH group (p < 0.94). Gleason score distribution (5–9) and tumour stage (TNM) were similar in the inflammation and non-inflammation groups (p < 0.99, p < 0.21). Conclusions.No significant correlation between chronic prostatic inflammation and carcinoma of the prostate was detected. Contrary to expectations, a significantly higher score of inflammatory changes was found in BPH patients; also, total PSA levels were lower in the inflammation group.