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The location of stem cells in the epithelium of the prostatic acinus remains uncertain, as does the cellular origin of prostatic neoplasia. Here, we apply lineage tracing to visualize the clonal progeny of stem cells in benign and malignant human prostates and understand the clonal architecture of this epithelium. Cells deficient for the mitochondrially-encoded enzyme cytochrome c oxidase (CCO) were identified in 27 frozen prostatectomy specimens using dual colour enzyme histochemistry and individual CCO-normal and -deficient cell areas were laser-capture microdissected. PCR-sequencing of the entire mitochondrial genome (mtDNA) of cells from CCO-deficient areas found to share mtDNA mutations not present in adjacent CCO-normal cells, thus proving a clonal origin. Immunohistochemistry was performed to visualize the three cell lineages normally present in the prostatic epithelium. Entire CCO-deficient acini, and part-deficient acini were found. Deficient patches spanned either basal or luminal cells, but sometimes also both epithelial cell types in normal, hyperplastic or atrophic epithelium, and prostatic intraepithelial neoplasia (PIN). Patches comprising both PIN and invasive cancer were observed. Each cell area within a CCO-deficient patch contained an identical mtDNA mutation, defining the patch as a clonal unit. CCO-deficient patches in benign epithelium contained basal, luminal and endocrine cells, demonstrating multilineage differentiation and therefore the presence of a stem cell. Our results demonstrate that the normal, atrophic, hypertrophic and atypical (PIN) epithelium of human prostate contains stem cell-derived clonal units that actively replenish the epithelium during ageing. These deficient areas usually included the basal compartment indicating the basal layer as the location of the stem cell. Importantly, single clonal units comprised both PIN and invasive cancer, supporting PIN as the pre-invasive lesion for prostate cancer.

OBJECTIVE To compare the efficacy of two types of botulinum toxin type A (BTX-A; DysportTM, Ipsen Ltd, Slough, UK) or BotoxTM (Allergan Inc., Irvine, CA, USA) and examine the possible dose-effect relation for Dysport in those patients, as multifocal detrusor injections with BTX-A are effective for severe neurogenic detrusor overactivity in adults. PATIENTS AND METHODS This was an open-label, observational case-control study comparing Dysport and Botox, and the dose-effect relation for Dysport. The patients included were treated with either Dysport (cases; 500, 750, or 1000 IU), or with Botox (controls: 300 IU, and exceptionally 200 or 400 IU). The continence volume (primary), mean and maximum catheterized volume, and antimuscarinic use were assessed, and cystometric variables measured were overactivity volume (primary), detrusor compliance, and cystometric capacity. All variables were assessed at baseline, 3 and 9 months after treatment, and results analysed using analysis of variance (paired) t-tests, chi-square tests and regression analysis. RESULTS There were 28 cases and 28 matched controls; their demographic characteristics, bladder management, and baseline values were comparable between the groups. At 3 months there was a significant improvement in cystometric variables and continence volume in both groups, but in mean catheterized volume and reduced use of antimuscarinics in cases only. At 9 months there was no significant improvement over baseline except for the continence volume in the cases. There were no significant differences in results between the groups except for the continence volume at 3 months (459 mL after Dysport and 396 mL after Botox; P = 0.015). There was no dose-related response for Dysport at 3.8 months of follow-up. The interval between injections (9.5, 14.5 and 16.1 months for Dysport 500, 750, and 1000 IU; 10.1 months for Botox) was not significant. There were nine non-responders in the Dysport group and seven in the Botox group; the patient characteristics and baseline data were comparable to those of the responders. There was transient hypoasthenia in one of the responders (750 IU Dysport). CONCLUSIONS A single treatment session with either Dysport or Botox in a setting combined with antimuscarinics might improve the patient’s condition for up to a year. There was no clear dose-related effect for Dysport in adults.

The aim of the study was to compare intra-operative and postplanning at different intervals with special focus on sources placed close to the rectal wall.In 61 consecutive patients, CT scans were performed on day 1 and day 30 after an I-125 implant with stranded seeds. The number of sourcesor =7 mm to the rectal wall was determined, and displacements were analyzed. The angulation of strands relative to rectal wall was compared between intra-operative transrectal ultrasound (TRUS) and both postplanning CT scans.Sources close to the rectum on day 1 (n=204) have been the most apical in a strand in 98.5% (n=201). By comparing day 1 and day 30 data, significant inferior source displacements (mean 3.6 mm; p=0.02) relative to pelvic bones and a decreasing distance to the rectal wall (mean 1.2 mm; p0.01)--consequentially increasing rectal dose--were determined only for sources initiallyor =3 mm to the rectum. In contrast to an almost parallel arrangement of the needle track and the rectal wall in TRUS, strands and rectal wall converged towards the apex in the postplanning CT scans (mean30 degrees).Posterior preplanning margins around the prostate should be particularly limited at the level of the prostate apex.

Contains fulltext : 81147.pdf (Publisher’s version ) (Closed access) CONTEXT: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC. EVIDENCE ACQUISITION: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS: The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on (1) natural timing of recurrence, (2) probability of disease recurrence, (3) functional deterioration at particular sites, and (4) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. CONCLUSIONS: These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.

Obstructive uropathy such as ureteropelvic junction obstruction in the newborn is a major diagnostic and therapeutic dilemma. We investigated whether urinary sodium dodecyl sulfate electrophoresis with polyacrylamide gel electrophoresis with silver staining could be used to discriminate between children requiring and those not requiring pyeloplasty.In a pilot study we analyzed the urine of 18 children (mean age 2.7 years) with grade III or IV hydronephrosis according to the Society for Fetal Urology classification. A total of 44 healthy children were studied as controls. Children with hydronephrosis were followed using ultrasound, (99m)technetium mercaptoacetyltriglycine diuretic renography and voiding cystourethrography. Urine was obtained by spontaneous voiding and studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis with silver staining using Melzer's modification. After the study period test results were compared to outcomes, ie whether patients required surgery, and to normalization of previously abnormal protein excretion patterns.All but 1 of the healthy controls had a normal electrophoresis assessment. Of 9 patients followed for hydronephrosis 7 had an abnormal electrophoresis result preoperatively. One child had to be operated on twice because of relapse of ureteropelvic junction obstruction. Six children returned to a normal electrophoresis result postoperatively, including the child who was operated on twice. All children with an initially normal electrophoresis assessment displayed persistent normal values, except 1. Children shifting from a normal to an abnormal electrophoresis result underwent surgery after exclusion of urinary tract infection.Sodium dodecyl sulfate polyacrylamide gel electrophoresis with silver staining seems to be a good predictive test for clinically relevant ureteropelvic junction obstruction. Further studies are being performed to see whether the test can stand against the gold standard, (99m)technetium mercaptoacetyltriglycine diuretic renography.

The aim of the study was to analyze source displacements and dose-volume changes in the first month after a permanent implant.In 51 consecutive patients, CT scans were performed at the postoperative day (day 1) and one month (day 30) after an (125)I implant with stranded seeds. Seed positions were determined relative to pelvic bones for five seeds at the base and five seeds at the apex for each patient (n=510) and compared. To verify these results, treatment margins (TM=distance of prescription isodose to prostate) and displacements of the prostate surface (anterior/posterior/right/left/superior/inferior) relative to pelvic bones were measured.Seed positions have moved significantly between day 1 and 30 in the posterior (mean 1.0mm; p0.001) and inferior (mean 3.8mm; p0.001) directions. TM increased particularly at the posterior (mean 2.2mm; p0.001) and apical (median 3.0mm; p0.001) prostate contour with decreasing oedema. With a stable apex position and a mean inward posterior surface displacement of 1.1mm (p0.001) relative to pelvic bones, seed displacements could be well correlated with prescription isodose displacements (Pearson correlation coefficientsor=0.81; p0.001).Both changes of prostate volume and seed displacements need to be considered to explain dosimetric changes after permanent prostate brachytherapy.

Histological tumor subtyping, staging, and grading are of utmost importance to stratify patients with bladder cancer for treatment and should be as precise as possible. In the presented study, we investigated the prognostic impact of standard clinicopathological parameters in cystectomy patients and compared embedding of the entire bladder with standard partial embedding via a virtual superimposed approach. The study included 121 cystectomy specimens, which were completely embedded. Clinical and histopathological data of patients were obtained (median follow-up 21.5 months; range 1–67 months). For 88 patients two-dimensional tumor maps (macrophotographs and histology-based maps) were prepared, and embedding of the entire bladder was compared with a virtual standard partial embedding, created by a virtual overlay and data extraction of the tumor maps. Kaplan-Meier plots, Cox regression estimators, Chi-square, and McNemar tests were used. In a multivariate Cox regression model for overall survival, only venous invasion (p = 0.008, HR = 3.35, 95 % CI 1.375–8.161) and organ-confined (pTis–pT2) versus non-organ-confined diseases (pT3–pT4; p = 0.021, HR 2.669, 95 % CI 1.157–6.159) were found significant. Advanced versus standard embedding revealed significant improvement in the detection of carcinoma in situ (50 versus 61, p = 0.003) and lymphatic invasion (18 versus 24, p = 0.041), but no significant advantage in the detection of tumor stage, tumor multifocality, or venous invasion (all p > 0.05). TNM classification, including lymphatic and venous invasion, is of utmost importance to stratify patients with advanced invasive bladder cancer. Histopathological details are detected more reliably by whole organ embedding, but this approach showed no significant benefit in terms of outcome-related parameters (max. tumor stage, venous invasion) in our cohort.

To determine dosimetric risk factors for increased toxicity after permanent interstitial brachytherapy for prostate cancer.Quality of life questionnaires (Expanded Prostate Cancer Index Composite) of 60 and 56 patients were analyzed after a median posttreatment time of 6 weeks (A-acute) and 16 months (L-late). The corresponding CT scans were performed 30 days after the implant. The prostate, rectal wall, and base of seminal vesicles were contoured. Prostate volume, number of seeds and needles as well as dosimetric parameters were correlated with the morbidity scores.For a prostate volume of 38 +/- 12 cm(3) (mean +/- standard deviation), 54 +/- 7 (125)I sources (Rapid Strands), activity of 22.6 +/- 3.0 MBq [0.61 +/- 0.08 mCi]) were implanted using 20 +/- 6 needles. Improved late urinary function scores resulted from a higher number of sources per cm(3) (or = 1.35). A prostate D(90)170 Gy (A)/185 Gy (L) and base of seminal vesicle D(10)190 Gy (A and L) were associated with higher urinary function scores. Late rectal function scores were significantly higher for patients with a prostate V(200)50% and V(150)75%. Patients with a prostate volume40 cm(3) reached better sexual function scores (A and L). A higher number of needles per cm(3) (or = 0.5) resulted in improved late urinary, bowel and sexual function scores.Quality of life after a permanent implant can be improved by using an adequate amount of sources and needles. With an increasing number of seeds per cm(3), dose homogeneity is improving. A prostate D(90)170 Gy and a base of seminal vesicle D(10)190 Gy (as an indicator of the dose to the bladder neck and urethral sphincter) can be recommended to maintain a satisfactory urinary function.

Objectives To characterize the influence of neoadjuvant hormonal therapy (NHT) on health-related quality of life after permanent iodine-125 brachytherapy (BT) for prostate cancer. Methods A cross-sectional survey using the Expanded Prostate Cancer Index Composite health-related quality-of-life instrument was administered to 134 consecutive patients a median of 29 months after BT. A separate group of 111 patients with comparable demographic characteristics without any prior treatment for prostate cancer rendered the baseline information (control group). The scores and symptom rates were compared. The effect of NHT was tested for independence in a multivariate analysis. Results In contrast to patients who received NHT, prostatic edema was hardly detectable 30 days after implantation in patients who received BT alone (comparing median preimplant and postimplant volumes), resulting in a greater dose to the prostate and anterior rectal wall. However, compared with the control group and the patients who received BT alone, the addition of NHT to BT led to lower health-related quality-of-life scores in all domains. Score differences of more than 10 points with a statistical significance were found for the urinary bother, sexual function/bother, and hormonal function/bother domains. Apart from the sexual function scores (patient age shown to be the crucial factor), the influence of NHT remained independent on multivariate analysis. Conclusions The results stress the need for well-considered administration of NHT before BT and the need for reporting the use of NHT in studies dealing with BT-related toxicity.

Objective: To evaluate the potency in patients after radical perineal prostatectomy with wide excision of both neurovascular bundles. Material and Methods: In this prospective study, a quality-of-life questionnaire was completed by 128 patients at the preoperative stage, and 6 and 12 months postoperatively. Ten questions concerning the patient’s sexuality were included on the pre- and both postoperative questionnaires. In addition, 6 patients who recorded some erectile function were sent a separate questionnaire containing eight more detailed questions. Results: Preoperatively, 74/128 (57.8%) patients reported erections sufficient for sexual intercourse, and of these 74, 6 (8.1%) described having spontaneous erections 1 year postoperatively. These spontaneous erections occurred 1–5 times per week. The reply to the separate mailing made clear that the reported erections were insufficient for intercourse. Conclusions: Patients undergoing standardized radical prostatectomy with wide excision of the neurovascular bundle have a very small chance of spontaneous erections sufficient for intercourse postoperatively.

The aim of the present study was to test the value of urinary cytology in the diagnosis of bladder cancer.One thousand three hundred and eighty voided urine and bladder wash specimens of 495 patients were evaluated by urinary cytology. All patients then underwent transurethral resection of suspicious bladder areas if cystoscopy and/or preceding biopsy were positive. Statistical differences were analysed using the two-sided Fisher's exact test and Cochran's test (p0.05).In 495 patients including 142 patients with bladder cancer urinary cytology revealed a sensitivity of 38.0% and a specificity of 98.3% with a positive and negative predictive value of 90.6 and 78.6, respectively. Sensitivity increased significantly with malignancy grade (p0.05). In high grade tumours sensitivity improved from initial 52.2% up to 78.3% after the third sample. In sensitivity and specificity of voided urine and barbotage washing samples no significant difference was detected.Urinary cytology has its place as an additive diagnostic tool to cystoscopy. None of the currently available urinary markers can replace cystoscopy but are helpful for specific diagnostic problems.

Objectives To assess, in a prospective study, the incidence of fecal incontinence after radical perineal prostatectomy. Methods Bowel symptoms were evaluated with questionnaires mailed to 132 patients preoperatively and 6 months postoperatively, and annually thereafter. All patients had undergone extrafascial perineal prostatectomy for Stage cT1-cT3N0M0 prostate cancer. The data of 116 patients (88%), who answered at least the preoperative and 12-month questionnaires, were analyzed. Reduced sensibility, reduced discrimination, urgency, or stool smearing were symptoms indicative of fecal incontinence. Patients with one symptom of fecal incontinence were evaluated further with a structured telephone interview. Results Daily stool smearing was reported preoperatively by 4% of the patients. Two symptoms related to fecal incontinence were present preoperatively in 6% of the patients. At 12 months postoperatively, 15 patients (13%) reported at least two symptoms of fecal incontinence. The structured telephone interview revealed that 6 of these 15 patients had symptoms of fecal incontinence that were related to the perineal prostatectomy; 9 patients had newly developed symptoms not related to surgery or symptoms due to tumor recurrence or radiotherapy. Patients with the presence of at least one symptom of fecal incontinence before surgery had an almost fourfold increased risk of developing at least two symptoms of fecal incontinence postoperatively compared with patients without any symptom of fecal incontinence. Conclusions Significant fecal incontinence after radical extrafascial perineal prostatectomy is a rare event. The results of questionnaires should be supplemented by additional interviews to obviate wrong interpretations.

Aim: We determine the efficacy of unilateral nerve-sparing radical perineal prostatectomy in preserving the sexual function. Patients and Methods: Ninety-two patients with histologically confirmed unilateral prostate cancer were scheduled for contralateral nerve preservation. The perioperative morbidity was assessed using the patients’ chart reviews. Postoperative health-related quality of life, urinary continence, and potency were evaluated prospectively with questionnaires provided before surgery and then after 6, 12, and 24 months. Results: Unilateral nerve preservation was performed in 88 of the 92 patients. Due to extensive scarring or prostatic size, the procedure was terminated as regular radical prostatectomy in 4 other patients. The perioperative complication rate was low and of minor significance, except in 1 patient who experienced a significant myoglobulinuria due to a prolonged procedure. Blood transfusions were necessary in 5 (5.4%) patients. Ureteral reimplantation was performed in 1 patient because of ureteral stricture. Positive surgical margins were present in 12 (18%) of 67 pT2 patients and in 8 (35%) of 23 pT3 patients. A proportion of 48% (15/31) of the patients followed for more than 24 months and who had a good erectile function prior to surgery reported unassisted sexual intercourse. However, only 4 of these patients were completely satisfied with all aspects of sexual performance, as asked in a short version of the International Index of Erectile Function questionnaire. Conclusions: Unilateral nerve-sparing radical perineal prostatectomy is technically feasible and yields excellent results in terms of potency preservation for prostates

To assess the quality of life in patients with prostate cancer after permanent brachytherapy (BT) or radical perineal prostatectomy (RP).The American Brachytherapy Society recommends the permanent implantation of radioactive seeds as a monotherapy for patients with T1-T2aN0M0 prostate cancer and a prostate-specific antigen (PSA) level ofor = 10 ng/mL, a Gleason score of7 and a prostate volume of60 mL. Using these criteria, 132 patients with low-risk prostate cancer were selected; 52 had BT with 125I-seed implantation, 38 had RP with unilateral nerve-sparing (RP + NS) and 42 extended RP (RP group). Only patients with unilateral tumour on biopsy were considered. Before therapy and 6, 12 and 24 months afterward, patients completed questionnaires to assess perceived health and function. PSA relapse was diagnosed with a PSA of0.1 ng/mL for patients in the RP groups, and three consecutive PSA increases for those after BT.Extraprostatic tumours were found in 18% of specimens taken during RP, and bilateral tumours in 63% of patients. After a mean follow-up of 27 months, there was PSA relapse in two of the 80 patients in the RP and RP + NS groups, and six of the 52 patients in the BT group; a significant difference, with a hazard ratio of 5.2. The acute morbidity was low in all groups. At 1 year, more than two incontinence pads were used by 5% of patients after RP and by 4% after BT. Similarly, at 1 year 15% of patients after RP and 13% after BT were bothered by urinary incontinence. Newly-developed fecal soiling was reported by 4%, 5% and 11% of the RP, RP + NS and BT groups respectively; none of the patients after RP and 4% after BT were bothered by this symptom. The duration and stiffness of erection was assessed after 1 year and reported to be equal or slightly decreased by a third after RP + NS and 38% after BT. Taking a 5-10 point difference as clinically relevant, role, emotional and social functioning were improved considerably after RP + NS than after BT, but sexual activity was impaired significantly after RP + NS than after BT.Both therapies showed typical acute and late morbidity; the most bothersome late symptoms were urinary incontinence for patients after RP and fecal soiling after BT. Sexual function was impaired significantly in patients who were potent before RP + NS, whereas after BT men reported only a minor change in sexual performance at 1 year. Tumour control after a median follow-up of 27 months was better after RP but biochemical recurrence may still occur afteror = 5 years; therefore the present results are not mature enough and there were too few patients to provide a more definitive statement. As approximately 18% of patients considered to be appropriate candidates for BT had tumours extending beyond the prostate capsule or invading the seminal vesicles, nomograms are needed for more accurate information before therapy.

The aim of this study was to investigate the utility of different gadolinium-enhanced T1-weighted gradient-echo techniques in excretory MR urography. In 74 urologic patients, excretory MR urography was performed using various T1-weighted gradient-echo (GRE) sequences after injection of gadolinium-DTPA and low-dose furosemide. The examinations included conventional GRE sequences and echo-planar imaging (GRE EPI), both obtained with 3D data sets and 2D projection images. Breath-hold acquisition was used primarily. In 20 of 74 examinations, we compared breath-hold imaging with respiratory gating. Breath-hold imaging was significantly superior to respiratory gating for the visualization of pelvicaliceal systems, but not for the ureters. Complete MR urograms were obtained within 14–20 s using 3D GRE EPI sequences and in 20–30 s with conventional 3D GRE sequences. Ghost artefacts caused by ureteral peristalsis often occurred with conventional 3D GRE imaging and were almost completely suppressed in EPI sequences (p < 0.0001). Susceptibility effects were more pronounced on GRE EPI MR urograms and calculi measured 0.8–21.7 % greater in diameter compared with conventional GRE sequences. Increased spatial resolution degraded the image quality only in GRE-EPI urograms. In projection MR urography, the entire pelvicaliceal system was imaged by acquisition of a fast single-slice sequence and the conventional 2D GRE technique provided superior morphological accuracy than 2D GRE EPI projection images (p < 0.0003). Fast 3D GRE EPI sequences improve the clinical practicability of excretory MR urography especially in old or critically ill patients unable to suspend breathing for more than 20 s. Conventional GRE sequences are superior to EPI in high-resolution detail MR urograms and in projection imaging.

Clonal chromosome aberrations identified after short-term culture are presented for three cases of chromophobe renal cell carcinomas (RCC). All tumors revealed abnormal karyotypes with a varying proportion of polyploid tumor cells. Common numerical abnormalities were combined losses of chromosomes 1, 2, 6, 10, 13, and 17. Clonal karyotypic evolution was demonstrated in one case in which several related clones could be identified. An additional balanced translocation t(3;14)(p24;q22) observed in this case proved to be of constitutional nature by cytogenetic analysis of normal kidney cells and peripheral blood lymphocytes. These cytogenetic findings provide further evidence that chromophobe renal cell carcinomas are characterized by a highly specific combination of chromosomal losses most commonly including chromosomes 1, 2, 6, 10, 13, and 17.

Objective: To examine whether prostate-specific antigen (PSA) is present in amniotic fluid, whether the amniotic fluid PSA concentration changes with gestational age, and whether there is an association between amniotic fluid PSA and fetal sex. Methods: The PSA concentration was measured in the amniotic fluid of 48 pregnant women. Thirty-four samples were obtained during routine amniotic fluid analyses performed during gestational weeks 16–18, whereas 14 samples were obtained during cesarean section performed after gestational week 36. Results: PSA was detected in all amniotic fluid samples. The median amniotic fluid PSA was 0.193 ng/ml during gestational weeks 16–18 and 0.39 ng/ml after gestational week 36 (p = 0.1). Furthermore, no significant association was seen between amniotic fluid PSA and fetal sex. The median amniotic fluid PSA level was 0.233 ng/ml for the 21 boys and 0.222 ng/ml for the 27 girls investigated (p = 0.72). Conclusions: These results confirm recent literature reports that PSA may serve as a growth regulator during normal fetal development. However, further studies are necessary to elucidate the exact role of PSA during fetal development.

To evaluate the clinical utility and morphologic accuracy of gadolinium-enhanced excretory magnetic resonance (MR) urography after low-dose diuretic injection and to correlate the results with those of conventional urography.In 71 patients with urologic symptoms, excretory MR urography was performed after intravenous injection of 5-10 mg furosemide and, 30-60 seconds later, 0.1 mmol of gadopentetate dimeglumine per kilogram of body weight. The MR urograms were interpreted by three radiologists, who were blinded to the clinical outcome, and subsequently compared with conventional urograms.Injection of furosemide before contrast material led to rapid, uniform gadolinium distribution inside a sufficiently distended collecting system such that there was no excessive concentration of gadolinium in the urine. In patients with normal or moderately reduced excretory function, this effect allowed complete visualization of the urinary tract within 5-20 minutes of contrast material injection while minimizing gadolinium-related endoluminal T2* effects. The clinical course helped verify almost all MR urographic results. The MR urographic technique was significantly superior to conventional urography in the assessment of the ureters and bladder (P.0001). Delineation of small caliceal abnormalities is still problematic. The best depiction of the pelvicaliceal system was obtained with fat-suppressed MR imaging, although it was still slightly inferior to conventional urography (P.05).Gadolinium-enhanced excretory MR urography performed after low-dose diuretic injection is a promising and accurate alternative to conventional excretory urography for imaging the morphology of the urinary tract.

Purpose: To study the efficacy of prostate-specific antigen (PSA) and skeletal alkaline phosphatase (SAP) as staging markers in discriminating patients with cancer of the prostate (CaP) with (M+) and without bone metastases (M0). Material and Methods: 73 patients with untreated CaP entered the study. After staging the patients were divided into 3 groups: group I, patients with CaP and bone metastases (n = 21); group II, patients with locally advanced CaP without bone metastases (n = 26), and group III, patients with clinically localized CaP without bone metastases (n = 26). Results: None of the M0 patients but 71% of the M+ patients exhibited an increased SAP. A corresponding cutoff point of 100 ng/ml for PSA showed that 19% of M0 patients and 71% of the M+ patients exhibited a value of >100 ng/ml. This resulted in a sensitivity and specificity of 71 and 100% of SAP and 71 and 81% for PSA, respectively. Conclusion: SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it provides additional information concerning the skeletal status of these patients.

We report about laparoscopic examination and treatment of 19 patients with 25 non-palpable testes. Thirteen patients presented with unilateral and six patients with bilateral absent testes, respectively. In all cases of non-palpable testes laparoscopy was able to determine the exact localization and supported the surgical approach. Six testicles were treated by open orchiectomy after diagnostic laparoscopy; three testes were fixed by laparoscopically assisted orchiopexy. Three patients (three testicles) were treated by standard orchiopexy after laparoscopy and in three cases microvascular autotransplantation was performed. Laparoscopically, five aplastic testicles without vas and vessels were diagnosed. Three testes were considered as vanishing and in two patients (two testes) due to previous surgical exploration elsewhere testicular remnants were totally atrophic and were resected with the adjacent vas. All laparoscopic findings except the vanishing testis syndrome were proven either by open surgery or by laparoscopic preparation of the internal inguinal ring.

Infection of the obstructed upper urinary tract is a severe complication of stone disease. Early detection and therapy is crucial to prevent septicemia. The authors investigated prospectively whether C-reactive protein (CRP) might act as a marker for the early detection of infected upper urinary tract obstruction. The serum concentration of CRP was compared with the classic markers of inflammation--white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and temperature--in the follow-up of 85 patients undergoing 173 extracorporeal shockwave lithotripsy (SWL) treatments. Post-SWL, 69% of the patients showed dilation of the upper tract on ultrasonography and 16.5% became symptomatic and required intervention. In this group, the mean CRP value was increased 18-fold, whereas the WBC count, ESR, and temperature were not markedly raised. In contrast, patients with no need for additional treatment showed no more than a 2-fold increase in CRP. C-Reactive protein seems to be a useful indicator for the early detection of infected upper urinary tract obstruction.

Objective To determine whether the proportion of total serum prostate-specific antigen (tPSA) which is unbound or free (free PSA) offers a better discriminant for the detection of patients with prostate cancer (CaP) and those with benign prostatic hyperplasia (BPH) than does serum tPSA alone. Patients and methods In a retrospective analysis, the proportion of free PSA was determined in the sera of 60 patients with histologically confirmed localized (n=39; pT1–3NoMo) and metastatic (n=21; T2–4NxM+) CaP and 45 patients with BPH. Forty patients with urolithiasis served as a control group. Serum levels of free and total PSA were determined using a chemiluminescent enzyme immunoassay. Results Patients with CaP had a lower percentage of free PSA (localized CaP median 8.8%; metastatic CaP median 7.1%) than patients with BPH (median 19.5%) and those with urolithiasis (median 18.8%; P

To compare the efficacy of two tests, prostate-specific antigen (PSA) and skeletal alkaline phosphatase (SAP) as staging markers to discriminate patients with cancer of the prostate (CaP) with bone metastases (M+) from those without bone metastases (M0).Thirty-nine untreated patients with CaP M0 (n = 22) and CaP M+ (n = 17) along with 10 patients with benign prostatic hyperplasia, who served as controls, were entered in this study. Serum concentrations for SAP and PSA were determined using two immunoassays. Receiver operating characteristic (ROC) curves were constructed to compare the ability of SAP and PSA to discriminate patients with CaP M+ from CaP M0.None of the M0 patients but 65% of the M+ patients exhibited an SAP value above the reference range (19 ng/ml). A corresponding cutoff point of 100 ng/ml for PSA demonstrated that 27% of M0 patients and only 65% of the M+ patients exhibited a value100 ng/ml. This resulted in a sensitivity of 65% for both markers. However, SAP revealed a higher specificity than PSA (100 vs. 73%). The ROC curve comparing SAP and PSA demonstrated the superiority of SAP as a marker for bone metastases.Our findings suggest that SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it seems to provide additional information concerning the skeletal status of these patients.

Objectives To determine the efficacy and possible beneficial effects of the Catalyst® vacuum device (VD) in the treatment of impotence, the ischaemic state of the penis after application of a constriction ring and the origin of the blood in the corpus cavernosum after application of the VD. Patients and methods Thirty men (mean age 62 years; range 46-76) suffering from erectile dysfunction were selected for the trial after using the VD for 2 weeks at home. Changes in penile tumescence and rigidity before, during and after using the VD were assessed using the Rigiscan® monitor. Blood gas analysis (BGA) was performed in selected patients whilst using the VD, allowing calculation of the proportional contribution of venous and arterial blood to the increase in penile volume. The efficacy of the VD was also assessed by questionnaires completed before treatment and at the 6 month follow-up. Results Four patients were lost to follow-up but the 26 impotent men who used the VD for 6 months were able to have sexual intercourse after using the VD. The average rigidity measured at the base and tip of the penis after application of the VD was > 80%. The duration and extent of nocturnal penile tumescence and rigidity at the start and the end of the study improved, although only one variable increased significantly. Patients reporting spontaneous morning erections showed significant improvements in total erection-time, erection-phase and plateau-phase duration, effective rigidity and tumescence increase. BGA determined 30 min after applying a constriction ring showed ischaemia of the penile blood and the mean contribution of arterial and venous blood to penile blood volume was by 58 and 42%, respectively. Conclusion The efficacy of the Catalyst® vacuum device was objectively determined and the quality of the nocturnal erections improved in some patients. After application of a constriction ring an ischaemia of the penis developed. In contrast to previous reports, the increased penis volume during the application of the VD is caused not only by arterial inflow but also by venous backflow.

Thirty G1-urothelial carcinomas of the bladder were investigated using DNA cytophotometry. Specimens obtained by tumour resection and quadrantic biopsy were first fixed in formalin and then embedded in paraffin. The cells were then separated using the method developed by Hedley. The DNA content was established after Feulgen staining using a TV-based image analysis system. DNA aneuploidy, a marker for neoplasia, was investigated using the so-called stemline interpretation developed by Böcking. This method compares the DNA content of the G0/1 tumour cells in the cell population to be analysed with the reference cell population, using the Kolmogoroff-Smirnow test (p0.001). On this basis, 23 tumours (76.6%) were DNA aneuploid, whereas if DNA aneuploidy is defined (as conventionally) as a DNA content of2.2c, only 17 tumours (56.6%) were found to be DNA aneuploid. The mean stemline value was 2.4c (range 1.85-3.96). By using a more precise TV-based image analysis system and this new DNA stemline interpretation, the rate of detection of DNA aneuploidy was improved by 20%. The diagnosis of G1-urothelial carcinomas by DNA cytophotometry is at least 25% more sensitive than that using conventional cytology (20-50%). We suggest that modified DNA cytophotometry could be a useful, additional diagnostic tool in examining doubtful urinary samples.

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? In this study we observed courses of micturition symptoms and differentiated degrees of symptoms for each point in time while also considering the impact of bothersomeness. Our data show that not only significantly more patients who have undergone BT suffer from OAB than those who have undergone RP, but also that those affected show significantly higher values for severity of OAB symptoms throughout the whole observation period of 36 months. Our data analysis further shows that variability of OAB symptoms as well as fluctuation of severity of OAB symptoms vary to a significantly higher degree after BT than after RP. Looking only at mean figures at a given point in time clearly underestimates the underlying problem. This fact is not reflected in the literature.• To look at individual courses of postoperative micturition symptoms, especially urgency, in patients treated either with radical prostatectomy (RP) or with brachytherapy (BT).• In a prospective longitudinal study we investigated individual changes in micturition symptoms before treatment, and 6, 12, 24 and 36 months after treatment. • All patients received the European Organization for the Research and Treatment of Cancer quality-of-life questionnaire, QLQ-C30, and the International Continence Society male questionnaire at each assessment. • We looked at long-term results as well as changes in time using repeated measures analysis of variance. We further analysed fluctuation of symptoms using sum of changes.• Of the 389 patients treated consecutively in our clinic over the last few years, 99 patients with a mean (sd) age of 65 (6.3) years had completed all five questionnaires and thus were further analysed. Of these, 66 (66.7%) were treated with RP and 33 (33.3%) with BT. • With the exception of age, no significant difference was found between the treatment groups either in physical functioning or in prevalence and severity of overactive bladder (OAB) symptoms. • Adjusted for age and pretreatment symptoms in analysis of covariance, we found that there were statistically more symptoms of OAB 36 months after BT compared with those patients treated with RP (P0.025). Whereas 30% of patients complained about severe symptoms of urgency after BT, only 11% did so after RP. • Changes of severity of OAB symptoms over the course of time (P0.007) using analysis of repeated measures as well as variability of OAB symptoms (P0.033) using the two-sided Wilcoxon t-test were significantly higher in patients treated with BT than in patients treated with RP.• Independently of age and physical functioning, BT is significantly associated with higher rates of long-term urgency symptoms, even after 3 years. • Repeated measurements show that OAB symptoms are highly fluctuating and that in patients treated with BT, severity of symptoms as well as variability of symptoms was significantly higher than in those patients treated with RP. • Persistent OAB seems to be an underestimated problem after treatment for localized prostate cancer, especially in patients treated with BT.

Summary Recent publications report increased cardiovascular morbidity and mortality after transurethral prostatic resection (TURP). Repeated breath-ethanol monitoring with a new infrared device permits a highly sensitive peroperative registration of fluid absorption. A prospective study in 52 patients revealed surprisingly high rates of intravascular fluid loads without clinical manifestations. Only 4 patients developed clinical signs of the TUR syndrome. Immunological work-up in 41 patients demonstrated circulating endotoxins and significant rise of endogenous tumour necrosis factor (TNF) in 3 of these patients. In 11 patients transient endotoxins could be detected during resection under prophylactic parenteral antibiosis. In the face of less invasive approaches to benign prostatic hyperplasia, close intraoperative monitoring and antibiotic coverage should be demanded as a routine procedure during TURP. Elective surgery should be delayed until appropriate antibiotic therapy has been given.

Objective: Identification of patients in whom the perineal route is the optimal approach to perform radical prostatectomy. Material and Methods: During 1992–1999, 376 patients with prostate cancer underwent radical perineal prostatectomy. Four patients were identified in whom the perineal approach was indicated because of previous bilateral groin hernia repair using synthetic meshes. In addition, 1 patient underwent perineal prostatectomy elsewhere for similar reasons. Results: The perineal approach offered an uneventful surgical solution for an adequate and straightforward radical perineal prostatectomy without complications and without biochemical recurrence during the follow-up. Conclusion: Radical perineal prostatectomy is suggested to be the optimal approach in patients with previous bilateral groin hernia repair using synthetic, nonabsorbable meshes.

Background Interpretation of comparative health-related quality of life (HRQOL) studies following different prostate cancer treatments is often difficult due to differing patient ages. Furthermore, age-related changes can hardly be discriminated from therapy-related changes. The evaluation of age-and comorbidity-related changes was in focus of this study. Methods HRQOL of 528 prostate cancer patients was analysed using a validated questionnaire (Expanded Prostate Cancer Index Composite) before a curative treatment. Patients were divided into age groups ≤65, 6670, 7175 and >75 years. The impact of specific comorbidities and the Charlson Comorbidity Index (CCI) were evaluated. The questionnaire comprises 50 items concerning the urinary, bowel, sexual and hormonal domains for function and bother. For assessment of sexual and hormonal domains, only patients without prior hormonal treatment were included (n = 336). Results Urinary incontinence was observed increasingly with higher age (mean function scores of 92/88/85/87 for patients ≤65, 6670, 7175 and >75 years) complete urinary control in 78%/72%/64%/58% (p < 0.01). Sexual function scores decreased particularly (48/43/35/30), with erections sufficient for intercourse in 68%/50%/36%/32% (p < 0.01) a decrease of more than a third comparing patients ≤65 vs. 6670 (36%) and 6670 vs. 7175 years (39%). The percentage of patients with comorbidities was lowest in the youngest group (48% vs. 66%/68%/63% for ages 6670/7175/>75 years; p < 0.05). A multivariate analysis revealed an independent influence of both age and comorbidities on urinary incontinence, specifically diabetes on urinary bother, and both age and diabetes on sexual function/bother. Rectal domain scores were not significantly influenced by age or comorbidities. A CCI>5 particularly predisposed for lower urinary and sexual HRQOL scores. Conclusion Urinary continence and sexual function are the crucial HRQOL domains with age-related and independently comorbidity-related decreasing scores. The results need to be considered for the interpretation of comparative studies or longitudinal changes after a curative treatment.

Modern LDR brachytherapy has drastically reduced rectal toxicity and decreased the occurrence of rectourethral fistulas to 125I seed implantation.

To evaluate seed displacements after permanent prostate brachytherapy considering different prostate levels. In 61 patients, postimplant CT scans were performed 1 day and 1 month after an implant with stranded seeds. Seed and prostate surface displacements were determined relative to pelvic bones. Four groups of seed locations were selected: seeds at the base (n = 305; B), at the apex (n = 305; A), close to the urethra (n = 306; U), and close to the rectal wall (n = 204; R). The length of two strands (always containing four seeds) per patient was measured in all CT scans and compared. The largest inferior seed displacements were found at the base: mean 5.3 mm (B), 2.2 mm (A), 2.7 mm (U), 3.3 mm (R; p < 0.001). Posterior displacements predominated both at the base and the central region: mean 2.2 mm (B), 2.0 mm (U), 0.8 mm (A), –0.6 mm (R; p < 0.001). With a decreasing edema between day 1 and 30 (mean prostate volume of 51 cm3 vs. 41 cm3; p < 0.001), a mean caudal prostate base displacement of 3.9 mm was found, whereas the mean inward displacement ranged from 1.2 to 1.6 mm at the remaining borders (lateral, anterior, posterior, apical). The analysis of the strand lengths revealed an implant compression between day 1 and 30 (mean 1.7 mm; p < 0.001). The largest prostate tissue and seed displacements were observed at the prostate base, associated with an implant compression. Predominantly inferior and posterior displacements implicate consequential smaller preplanning margins at the apex and the posterior prostate.

The aim of the study was to compare quality of life after permanent I-125 brachytherapy (BT) and external beam radiotherapy (EBRT) for prostate cancer.A group of 104 patients (52 in each group) have been surveyed prospectively before EBRT/BT (time A), at the last day of EBRT (70.2-72.0 Gy) or one month after BT (time B), and a median time of 16 months after EBRT/BT (time C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs were matched according to the following criteria: age +/-5 years, prostate volume +/-10 cc, use of antiandrogens, and erectile function.Urinary function/bother scores decreased significantly more after BT both at time B and time C. Bowel function/bother scores tended to be higher after BT, with a lower percentage of patients with painful bowel movements (BT: 12%/27%/15%; EBRT: 19%/52%/35% at time A/B/C; p0.05 for differences at times B/C) and rectal bleeding (BT: 12%/12%/12%; EBRT: 8%/14%/17%). No difference concerning erectile dysfunction was found (67% vs. 61% with preserved erections firm enough for intercourse after BT vs. EBRT at time C).BT was associated with higher urinary, but lower rectal toxicity. The risk of treatment-associated erectile dysfunction did not differ between these methods.

Prostate cancer has become one of the most common malignancies worldwide. Although lacking in specificity its diagnosis is still based partially on the serum- based test for prostate-specific antigen. As its pathogenesis has not yet been deciphered, the ongoing search for new and more reliable biomarkers remains a challenge to stratify disease onset and progression. Matrix-assisted laser desorption/ ionization (MALDI)-Imaging is a promising technique to assist in this endeavor. It delivers accurate mass spectrometric information of the sample's proteins and enables the visualization of the spatial distribution of protein expression profiles and correlation of the information with the histo- morphological features of the same tissue section. This study describes the analysis of 22 prostate sections (11 with and 11 without prostate cancer) by MALDI-Imaging. Specific protein expression patterns were obtained for normal and cancerous regions within the tissue sections. Applying a 'support vector machine' algorithm to classify the cancerous from the non- cancerous regions, an overall cross-validation, a sensitivity and specificity of 88, 85.21 and 90.74%, respectively, was achieved. Additionally four distinctively overexpressed peaks were identified: 2,753 and 6,704 Da for non-cancerous glands, and 4,964 and 5,002 Da for cancerous glands. The results of this first clinical study utilizing the new technique of MALDI-Imaging underline its vast potential to identify candidates for more reliable prostate cancer tumor markers and to enlighten the pathogenesis of prostate cancer.

OBJECTIVES To characterize the kinetics of prostate-specific antigen (PSA) after radiotherapy (RT) and neoadjuvant hormonal therapy (NHT) for localized prostate cancer. METHODS The PSA kinetics of 75 consecutive patients who had undergone RT and NHT (median time 4 months) were followed up for a minimum of 24 months after treatment. RT included a permanent iodine-125 implant (n = 29), a temporary iridium-192 implant as a boost to external beam RT (n = 21), and sole external beam RT (n = 25). A median number of 11 PSA levels per patient were analyzed. RESULTS After a first nadir (median level 0.1 ng/mL 3 months after RT), rising PSA levels were found in 83% of patients and progressively rising PSA levels until the end of follow-up or salvage hormonal therapy for 21% of patients. The PSA levels dropped again after one (23%), two (21%), or more (17%) consecutive increases up to a median level of 0.6 ng/mL (median time 16 months after RT), so that a nadir of 0.1 ng/mL was reached for a second time (median time 35 months after RT). A first nadir of less than 0.1 ng/mL, a PSA increase of less than 1 ng/mL, and a longer PSA doubling time (median time 10 months) were strongly predictive for long-term biochemical control. CONCLUSIONS Temporarily rising PSA levels can be expected for most patients after primary RT and NHT following a first nadir. The increasing effects of testosterone owing to NHT withdrawal have a stronger effect than RT in the first months after treatment.

We report a unique case of a duplex kidney and ectopic ureter presenting as a cystic tumor of the seminal vesicle with consecutive dysuria in an adult. The medical history of the patient, the diagnostic pathway and the laparoscopic treatment as well as the key points in laparoscopic surgery are described.

Background and purpose Evaluation of dose-volume–time-related factors in 64 patients treated with high-dose-rate brachytherapy (HDR-BT) as a boost to external beam radiotherapy (EBRT) for localized prostate cancer. Patients and methods Clinical parameters were correlated with morbidity scores of the EPIC (Expanded Prostate Cancer Index) questionnaire. Median time after radiotherapy (HDR-BT up to 18 Gy in two fractions and EBRT up to a median dose of 50.4 Gy) was 1.5 and 3 years (first and second questionnaire). Results A significant impact of a urethra D1 exceeding 15 Gy in at least one HDR fraction concerning urinary morbidity and a rectum D1 exceeding 6 Gy to the rectal mucosa in the first and second HDR fraction concerning the rectal bleeding rate was found. A higher number of needles was associated with lower urinary and bowel scores after 1.5 years. A prostate length >4.8 cm and a longer duration of EBRT (independently of the dose) predisposed for lower urinary and bowel scores. In contrast to a urethra D1>15 Gy as an independent factor, a rectum D1>6 Gy per HDR fraction correlated with a higher number of needles and an increased prostate length. Conclusions To minimize morbidity in HDR-BT for prostate cancer, a maximum dose to the urethra of 15 Gy and a maximum dose to the rectal mucosa of 6 Gy is advisable. Treatment- and patient-related factors have a major impact on toxicity.

109 patients with locally confined prostate cancer underwent radical perineal prostatectomy. In 12 (11%) patients a rectal laceration was noted intraoperatively and closed in two layers. No patient had complications or prolonged hospital stay associated with the laceration.

We evaluated clinical characteristics, patient outcome (mean follow-up, 47 months), and cytogenetic abnormalities in the largest as yet reported cytogenetic series of 47 primary and 11 secondary papillary renal cell carcinomas for differences between the recently proposed type 1 and type 2 subtypes. Secondary tumors were more often of type 2 morphology (P = 0.02), whereas primary type 2 tumors were associated with higher clinical stage (P = 0.001) and worse patient outcome (P = 0.02). Although both subtypes had at least one of the primary chromosomal gains at 17q, 7, and 16q, type 2 tumors had moderately lower frequencies of primary gains at 17p (61 versus 94%; P = 0.007) and 17q (72 versus 97%; P = 0.02). On the other hand, type 2 tumors overall had more chromosomal alterations than type 1 tumors (P = 0.01), particularly gains of 1q (28 versus 3%; P = 0.02) and losses of 8p (33 versus 0%; P = 0.001), 11 (28 versus 3%; P = 0.02), and 18 (44 versus 9%; P = 0.01). Hierarchical clustering suggested cytogenetic patterns common but not restricted to type 2 morphology, one characterized by multiple additional gains, and another predominantly showing additional losses. These findings provide genetic evidence that type 1 and type 2 tumors arise from common cytogenetic pathways and that type 2 tumors evolve from type 1 tumors. Independently of type, losses of 9p were statistically correlated with advanced disease (P = 0.0008) and may serve as a potential adverse prognostic marker in papillary renal cell carcinomas.

Spontaneous rupture of the kidney is an uncommon entity. In most cases the non-traumatic rupture is associated with underlying diseases of the kidney, the most frequent being renal tumours. We report the case of a spontaneous kidney rupture due to a renal metastasis from an adenocarcinoma of the colon.

Radical prostatectomy is a procedure performed with increasing frequency in patients with localized prostate cancer. Although, the operative morbidity is considerably low, urinary incontinence and erectile dysfunction remain an important and persistent problem. Since several years the impact of radical prostatectomy on the quality of life (HRQOL) is investigated. However, there are only few prospective studies dealing with rather small groups of patients. These studies indicate that urinary and sexual function have major impact on HRQOL. Although, there is a steady improvement in urinary function and decrease in urinary bother only about 65% of the patients reach the baseline at the end of the first year. In spite of this almost 90% of patients reach baseline in all other HRQOL domains such as general health perception, physical and social function after a mean period of 5 months. The importance of sexual desire and erectile capacity decreases with age; being important in 75 and 84% of men at the 5th decenium and 48 and 59% at the 6th decenium. After standard radical prostatectomy almost all of the patients are impotent. Applying so-called nerve sparing techniques erectile function may be preserved in careful selected patients. It is the common theme that preservation of the 'neurovascular bundles' equals a high rate, but still age depended postoperative potency; however difficulties in regaining urinary control may embarrass the patient to such an extent to withdraw from sexual activity. Furthermore, the change of sexual ability and quality may have impact on the partner who do not want to initiate sexual activity because of the possible failure. This may cause an increased level of emotional distance, which again is deleterious for sexual activities. Patients who are sexually active prior to surgery report major distress in case of postoperative erectile impotence, but even in case of maintained erectile capacity some patients are bothered by the sexual dysfunction. Sexual counselling and providing the optimal erectile aid is therefore very important. Psychological distress of spouses may be significantly greater than that of the patients; general cancer distress, treatment related worries, concerns on physical limitations and pain are the main reasons. However, it may well be that women are willing to report their problems more often than their partners who may have a grin-and-bear-it attitude. In spite of this caveate, it is important to include the patient's spouse into the discussions on therapy and associated morbidity early on. Since radical prostatectomy for localized prostate cancer is only one of the possible treatment options, the patient has to be informed about the incidence and various types of morbidity which is associated with treatment and their possible impact on HRQOL. Appropriate and honest counselling will have significant influence on the well being of the patient after completing therapy.

Local recurrence (LR) of renal cell carcinoma (RCC) after nephrectomy is a rare event with a poor prognosis. The clinical outcome of 15 patients with LR after tumor nephrectomy was analyzed retrospectively. Within a mean follow-up of 28 months (1-110 months) the mean time to recurrence (TTLR) was 23 months. Mean time to further tumor progression (TTP) after surgery was 22.2 months (11-32 months), after surgery and adjunctive therapy 6.8 months (3-15 months+) and after chemoimmunotherapy alone 3.6 months (3-6 months). Tumor specific survival (TSS) rate was 47% at 1 year and 33% at 3 years. Mean TSS after surgery was 62.2 months (38-110 months), after resection and adjunctive treatment 26 months (8-74 months) and after chemoimmunotherapy 9.2 months (7-15 months). In conclusion, surgery is recommended for treatment of LR. Additional benefit is not confirmed for any adjuctive therapy.

This phase II study was designed to assess the response rate, side effects and long-term efficacy of BCG in the treatment of carcinoma in situ (Cis) of the urinary bladder.103 eligible patients with Cis were treated with 6 consecutive weekly intravesical instillations of 120 mg BCG-Connaught. In case of no response, a second 6-week course was given.A complete response (CR) was observed in 77 of the 103 eligible patients (75%) and 93 evaluable patients (83%). In 6 of 10 patients the CR was induced by a second cycle of 6 weekly instillations. After a median follow-up of 7.6 years, 39 of the 77 CR patients (50%) are still alive and have retained their bladder, 31 (40%) without tumor recurrence. Another 7 patients underwent cystectomy and are still alive while 16 (20%) have died due to bladder cancer. Ten patients stopped treatment due to toxicity. In 2 patients, cystectomy was done because of severe cystitis and reduced bladder capacity. Drug cystitis, bacterial cystitis and fever occurred in 45, 15 and 15% of the patients, respectively. Severe drug cystitis was noted in 3 out of 10 patients receiving more than 6 instillations, necessitating cystectomy in 1 case.Intravesical short-term BCG is an effective treatment modality in Cis, yielding a high CR rate. This therapy may however be suboptimal in some patients as the 5-year disease-free rate in complete responders drops to 60%. Still, this is an acceptable result for patients in whom cystectomy would otherwise be performed in virtually all cases.

Perioperative morbidity is an essential indicator for the quality of an operative technique. This fact is especially important in radical prostatectomy since different treatment modalities may provide similar outcome in terms of local tumor control.The conventional type of radical perineal prostatectomy is associated with a significant percentage of positive surgical margins and was therefore substituted by a modified extended radical perineal prostatectomy at our institution. This procedure which includes partial resection of the dorsal vein complex and extrafascial resection of the seminal vesicals was performed in 200 patients with clinical T1 to T3 prostate cancer. The medical records were retrospectively reviewed for perioperative morbidity.There was no perioperative mortality and only 7% of the patients experienced postoperative complications. Blood substitution was indicated in 14% of the patients and could be reduced to 4% in the last 50 patients. The reintervention rate was 2.5% including 3 patients in whom a rectocutaneous fistula had to be repaired. The suction drainage was removed in 92% patients within 5 days. The indwelling catheter stayed in place for less than 14 days in 89% of all patients and was removed as early as after 2-7 days in 92% of the last 50 patients. Anastomotic strictures were observed in 8 (5%) of 160 patients followed for more than 6 months. 87.4% of patients were considered continent after at least 6 months follow-up. However, pad use was reported in 33.6%.The extended type of radical perineal prostatectomy provides excellent results in terms of perioperative morbidity, although a significant learning curve can be noted, which is indicated by blood substitution and duration of necessary catheter drainage. Since the rate of positive surgical margins in pT3 tumors is low (21%) and iatrogenic positive margins in pT2 tumors are avoided, this type of prostatectomy should be performed in case a potency sparing procedure is not indicated.

Prostate stem cell antigen (PSCA) is a member of the LY-6 family of surface proteins that is overexpressed in prostate cancer. Using serial analysis of gene expression (SAGE), we identified PSCA as one of the most abundant transcripts in a differentiated urothelial tumor. As assessed by Northern blotting, PSCA is highly expressed in normal urothelium and noninvasive urothelial tumors. In contrast to the previously reported overexpression of PSCA in progressive and invasive forms of prostate cancer, we found a markedly reduced expression in undifferentiated bladder carcinoma. In addition, several aberrant splicing products derived from the PSCA gene were found in urothelial tumors. Furthermore, PSCA mRNA was highly abundant in normal esophagus and stomach, but was undetectable in esophageal or gastric tumors. The PSCA expression appeared to depend on cell contact, since mRNA levels were increased when RT112 bladder carcinoma cells were grown to confluence. Our data suggest that PSCA could serve as a potential marker for the early carcinogenesis in urothelial and gastric tissues and that its expression is specific for epithelial cells.

Objectives. To compare positron emission tomography (PET) using 18-fluoro-2-deoxyglucose (FDG) with conventional clinical staging in unselected patients with germ cell cancer. Methods. Fifty patients underwent PET scans of the abdomen (n = 50) and chest (n = 41) after the initial diagnosis. PET images were evaluated qualitatively and quantitatively using standardized uptake values (SUVs). The results were compared with computed tomography (CT) results and tumor markers (human chorionic gonadotropin, alpha-fetoprotein, and lactate dehydrogenase). Retroperitoneal lymphadenectomy in 12 patients and clinical staging, including follow-up data in all patients, were taken as a reference standard. Results. PET detected metastases in 13 (87%) of 15 patients and excluded metastases in 33 (94%) of 35 patients. A sensitivity of 73% and a specificity of 94% were obtained using CT. The respective values for tumor marker determination were 67% and 100%. Retroperitoneal metastases were detected in 2 patients by PET only and in 1 patient by CT only. In the latter patient, surgery of a residual mass after chemotherapy revealed a well-differentiated teratoma. False-negative findings with PET and CT occurred in 2 patients with retroperitoneal metastases approximately 10 mm in size. False-positive findings were due to sarcoidosis or to muscular activity of the neck. Quantitative FDG uptake was very heterogeneous, with an SUV ranging from 1.8 to 17.3. Conclusions. FDG PET has the potential to improve clinical staging of testicular cancer. However, PET, as well as CT, is limited in the detection of small retroperitoneal lymph node metastases.

Combined therapy of gemcitabine with interferons on patients with histologically confirmed metastatic renal cell carcinoma is reported. Patients had an unfavourable disease due to documented tumor progression after various interferon-alpha-based immunotherapy (26 weeks on average). The median number of metastatic sites was 6.1 per patient and 78% of the patients exhibited >/= 4 lesions. Nine evaluable patients received at least 6 doses of gemcitabine and 8 doses of interferon-gamma. Overall, therapy resulted in a remission rate of 15% (4 x partial response; 4 x minor response) for single measurable lesions (n=53). Remissions were more often found for lesions, that did not progress at baseline evaluation (n=30; OR: 20%), compared to 8.7% for sites in progression (n=23). However, as a result of therapy, 43.5% of the progressive lesions did not continue to progress. Although only one of nine patients finally overall achieved a minor remission and one patient a stable disease, the median time to tumor progression (6.1 months) and the median survival (13.5 months) was favourable. In conclusion, the combination of gemcitabine and interferon demonstrated cytotoxic and cytostatic effects on metastases of renal cell carcinoma at a tolerable toxicity, thus controlled clinical studies for first line therapy with gemcitabine and interferon are in progress.

Objectives: Recently, tissue polypeptide-specific antigen (TPS), a cytokeratin 18 marker, was described to be discriminative between cancer of the prostate (CaP) and benign prostatic hyperplasia (BPH). Cyfra 8/18, a marker which recognizes both cytokeratin 8 and 18 fragments, is discussed to improve sensitivity and specificity of TPS. We investigated whether Cyfra 8/18 serum concentration discriminates between patients with clinically localized CaP and BPH. Methods: Serum Cyfra 8/18 levels were determined in patients with untreated CaP before radical prostatectomy (pT1-3pNoMo; n = 11) and with histologically confirmed BPH (n = 22). Cyfra 8/18 concentration was correlated to the prostate-specific antigen (PSA) concentration. Results: Median Cyfra 8/18 level was 0.64 ng/ml in CaP patients and 0.57 ng/ml in BPH patients. This difference is statistically not significant (p = 0.91). Furthermore, no correlation to PSA levels could be established (CaP: r = 0.036; BPH: r = 0.09). Conclusion: In contrast to a recent report we found the Cyfra 8/18 serum concentration to be a nondiscriminative parameter between CaP and BPH.