Anterior Urethroplasty Using a New Tissue Engineered Oral Mucosa Graft: Surgical Techniques and Outcomes.

PURPOSE: We investigated whether tissue engineered material may be adopted using standard techniques for anterior urethroplasty. MATERIALS AND METHODS: We performed a retrospective multicenter study in patients with recurrent strictures, excluding those with failed hypospadias, lichen sclerosus, traumatic and posterior strictures. A 0.5 cm2 oral mucosa biopsy was taken from the patient cheek and sent to the laboratory to manufacture the graft. After 3 weeks the tissue engineered oral mucosal MukoCell® graft was sent to the hospital for urethroplasty. Four techniques were used, including ventral onlay, dorsal onlay, dorsal inlay and a combined technique. Cystourethrography was performed 1 month postoperatively. Patients underwent clinical evaluation, uroflowmetry and post-void residual urine measurement every 6 months. When the patient showed obstructive symptoms, defined as maximum urine flow less than 12 ml per second, the urethrography was repeated. Patients who underwent further treatment for recurrent stricture were classified as having treatment failure. RESULTS: Of the 38 patients with a median age of 57 years who were included in study the strictures were penile in 3 (7.9%), bulbar in 29 (76.3%) and penobulbar in 6 (15.8%). Median stricture length was 5 cm and median followup was 55 months. Treatment succeeded in 32 of the 38 patients (84.2%) and failed in 15.8%. Success was achieved in 85.7% of ventral onlay, 83.3% of dorsal onlay, 80% of dorsal inlay and 100% of combined technique cases. No local or systemic adverse reactions due to the engineered material were noted. CONCLUSIONS: Our findings show that a tissue engineered oral mucosa graft can be implanted using the same techniques suggested for anterior urethroplasty and native oral mucosa, and guaranteeing a similar success rate.

Cancer-related fatigue in patients before and after radical prostatectomy. Results of a prospective multi-centre study.

PURPOSE: A multi-centre, longitudinal study was conducted to assess the prevalence of fatigue amongst men with localized prostate cancer, to describe several dimensions of fatigue and to explore the predictability of fatigue by psychological distress and physical function. METHODS: The prevalence of fatigue was evaluated using the Multidimensional Fatigue Inventory in 329 prostate cancer patients before, 3, 6 and 12 months after surgery. Psychological distress was assessed using the Hospital Anxiety and Depression Scale. Physical function was measured using the EORTC QLQ-C30. RESULTS: After surgery, about 14 % of the patients were screened with chronic fatigue. For all dimensions of fatigue, only small longitudinal changes could be observed. Psychological distress could be identified as a good predictor of fatigue after but not before surgery. CONCLUSIONS: Radical prostatectomy has no or little impact on the prevalence of fatigue. However, about 14 % of patients with chronic fatigue could possibly benefit from psychosomatic interventions. Interventions should consider the simultaneous appearance of fatigue and psychological distress and a reduced physical function.

Urolithiasis through the ages: data on more than 200,000 urinary stone analyses.

PURPOSE: The incidence and prevalence of urolithiasis are increasing but clinicians also have the impression that gender and age distributions of stone formers are changing. Moreover, regional differences in stone occurrence and composition have been observed. We analyzed such trends based on a large series of urinary stone analyses. MATERIALS AND METHODS: A total of 224,085 urinary stone analyses from 22 German centers were evaluated to determine the incidence of stone composition and identify age and gender distributions from 1977 to 2006. A subset of 58,682 stone analyses from 1993 to 2006 was available to identify regional differences in stone composition in Germany. RESULTS: Calcium containing calculi were most common in each gender. The overall male-to-female ratio of 2.4:1 increased from 1977 (1.86:1) to 2006 (2.7:1). The predominance of male calcium stone formers was even higher among elderly patients with a 3.13:1 ratio at ages 60 to 69. Since 1997, we observed a tendency toward an increasing incidence in middle-aged patients at ages 40 to 49 years. While the rate of infection stones constantly decreased, the incidence of uric acid calculi remained stable with an overall rate of 11.7% in males and 7.0% in females with a peak at higher ages. Cystine stones remained rare at 0.4% in males and 0.7% in females. In terms of regional analyses we noted great variation in stone composition in the 2 genders. Uric acid stones were more common in the eastern and southern regions but infection stones were mostly seen in eastern regions. CONCLUSIONS: In what is to our knowledge the largest series of stone analysis reported to date we identified an age and gender relationship of stone formation and composition. Regional variations are common and underline the influence of living habits, diet and standard of medical care on urinary stone formation.

Laparoscopic adrenalectomy in urological centres - the experience of the German Laparoscopic Working Group.

OBJECTIVE: To evaluate the safety and feasibility of laparoscopic adrenalectomy (LA) performed in several German centres with different laparoscopic experience, as LA has become the gold-standard approach for benign surgical adrenal disorders; however, for solitary metastasis or primary adrenal cancer its precise role is uncertain. PATIENTS AND METHODS: The data of 363 patients who underwent a LA were prospectively collected in 23 centres. All centres were stratified into three groups according to their experience: group A (<10 LAs/year), group B (10-20 LAs/year) and group C (>20 LAs/year). In all, 15 centres used a transperitoneal approach, four a retroperitoneal approach and four both approaches. Demographic data, perioperative and postoperative variables, including operating time, surgical approach, tumour size, estimated blood loss, complications, hospital stay and histological tumour staging, were collected and analysed. RESULTS: The transperitoneal approach was used in 281 cases (77.4%) and the retroperitoneal approach was used in 82 patients (22.6%). In all, 263 of 363 lesions (72.5%) were benign and 100 (27.5%) were malignant. The mean (sd) operating time was 127.22 (55.56) min and 130.16 (49.88) min after transperitoneal and retroperitoneal LA, respectively. The mean complication rates for transperitoneal and retroperitoneal LA were 5% and 10.9%, respectively. CONCLUSION: LAs performed by urologists experienced in laparoscopy is safe for the removal of benign and malignant adrenal masses. LA for malignant adrenal tumours should be performed only in high-volume centres by a surgeon performing at least >10 LAs/year.

[The assessment of therapy success after radical prostatectomy]. / Die Beurteilung des Behandlungserfolges nach Radikaler Prostatektomie.

OBJECTIVES: Patient satisfaction plays an important role in the outcome quality of treatment for localized prostate carcinoma. This paper identifies factors that impact patients' assessment of therapy success one year after surgery. METHODS: Patient assessment of therapy success was measured with the Hamburger Fragebogen zum Krankenhausaufenthalt (Lecher et al. 2002). Also, several sociodemographic, clinical and quality-of-life factors were tested for their impact on the patient assessment of therapy success. RESULTS: 25 % of patients gave a negative assessment of therapy success. Factors with the strongest impact were urinary incontinence, sexual impotence, younger age and higher risk of recidive. CONCLUSIONS: Especially the prevention of urinary continence and sexual dysfunction may lead to a better assessment of therapy. Moreover, the patients' expectations have a great impact on the assessment of therapy success.

Radical retropubic vs. radical perineal prostatectomy: a comparison of relative benefits in four urban hospitals.

INTRODUCTION: The purpose of this study was to evaluate the oncological and functional outcome of retropubic and perineal approaches to radical prostatectomy. METHOD: Data from 1,304 patients who underwent either radical retropubic (RRP) or radical perineal prostatectomy (RPP) over a 12-year period were compared. Variables included age, prostate-specific antigen (PSA) level preoperative, prostate volume, Gleason score, estimated blood loss (EBL), blood transfusion rate (BTR), operative duration, surgical margin, pathological stage, short and long-term complication rates, impotence, and incontinence rates. RESULTS: RRP had a longer operative duration, higher EBL, higher BTR, and longer hospital stay. The 5-year biochemical-free survival rates were not significantly different between the two techniques. CONCLUSIONS: These results indicate there are no significant differences in oncological and functional outcomes between RRP and RPP. However, RPP demonstrates minimal EBL, low BTR, and shorter operative duration.

Delayed Radiographic Manifestation of Renal Pseudoaneurysms After Blunt Trauma.

Pseudoaneurysms may cause recurrent hematuria after blunt renal trauma. We report on an 18-year-old patient with radiographic manifestation of pseudoaneurysm 41 days after blunt renal trauma. Initial and follow-up imaging for recurrent hematuria, including angiography, was without signs of pseudoaneurysm or active bleeding. This case illustrates that recurrent gross hematuria as a typical symptom of pseudoaneurysm may be present initially in the absence of radiographic signs. Repeat angiography should be taken into consideration if recurrent bleeding persists.

Results of Use of Tissue-Engineered Autologous Oral Mucosa Graft for Urethral Reconstruction: A Multicenter, Prospective, Observational Trial.

BACKGROUND: Harvest of oral mucosa for urethroplasty due to urethral stricture is associated with donor-site-morbidity. We assessed functionality and safety of an authorized tissue-engineered oral mucosa graft (TEOMG) under routine practice in stricture recurrences of any etiology, location, length and severity (real-world data). METHODS: 99 patients from eight centers with heterogenous urethroplasty experience levels were included in this prospective, non-interventional observational study. Primary and secondary outcomes were success rate (SR) and safety at 12 and 24months. FINDINGS: All but one patient had ≥1, 77.1% (64 of 83)≥2 and 31.3% (26 of 83)≥4 previous surgical treatments. Pre- and postoperative mean±SD peak flow rate (Qmax) were 8.3±4.7mL/s (n=57) and 25.4±14.7mL/s (n=51). SR was 67.3% (95% CI 57.6-77.0) at 12 and 58.2% (95% CI 47.7-68.7) at 24months (conservative Kaplan Meier assessment). SR ranged between 85.7% and 0% in case of high and low surgical experience. Simple proportions of 12-month and 24-month SR for evaluable patients in all centers were 70.8% (46 of 65) and 76.9% (30 of 39). Except for one patient, no oral adverse event was reported. INTERPRETATIONS: TEOMG is safe and efficient in urethroplasty.

Tumor heterogeneity as a rationale for a multi-epitope approach in an autologous renal cell cancer tumor vaccine.

PURPOSE: An autologous tumor vaccine already used successfully in the immune therapy of renal cell carcinoma was investigated in detail. The evaluation of potential tumor markers should allow for the assessment of potency according to pharmaceutical regulations. METHODS: A panel of 36 tumor-associated antigens and cellular marker proteins was characterized in a total of 133 tumor cell lysates by methods such as ELISA, Western blots, and topological proteomics. The induction of tumor-associated antigen-specific antibodies was demonstrated by immunization in mice. RESULTS: Tumor heterogeneity was demonstrated: none of the tumor-associated antigens investigated were detectable in each tumor lysate. In parallel, the coincidental presence of potential danger signals was shown for HSP-60 and HSP-70. The presence of both antigen and danger signal allowed a successful induction of an immune response in a murine model. CONCLUSION: The verified tumor heterogeneity indicates the need for a multi-epitope approach for the successful immunotherapy in renal cell carcinoma.

Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial.

BACKGROUND: Organ-confined renal-cell carcinoma is associated with tumour progression in up to 50% of patients after radical nephrectomy. At present, no effective adjuvant treatment is established. We aimed to investigate the effect of an autologous renal tumour cell vaccine on risk of tumour progression in patients with stage pT2-3b pN0-3 M0 renal-cell carcinoma. METHODS: Between January, 1997, and September, 1998, 558 patients with a renal tumour scheduled for radical nephrectomy were enrolled at 55 institutions in Germany. Before surgery, all patients were centrally randomised to receive autologous renal tumour cell vaccine (six intradermal applications at 4-week intervals postoperatively; vaccine group) or no adjuvant treatment (control group). The primary endpoint of the trial was to reduce the risk of tumour progression, defined as progression or death. All patients were assessed after standardised diagnostic investigations at 6-month intervals for a minimum of 4.5 years. FINDINGS: By preoperative and postoperative inclusion criteria, 379 patients were assessable for the intention-to-treat analysis. At 5-year and 70-month follow-up, the hazard ratios for tumour progression were 1.58 (95% CI 1.05-2.37) and 1.59 (1.07-2.36), respectively, in favour of the vaccine group (p=0.0204, log-rank test). 5-year and 70-month progression-free survival rates were 77.4% and 72%, respectively, in the vaccine group and 67.8% and 59.3%, respectively, in the control group. The vaccine was well tolerated, with only 12 adverse events associated with the treatment. INTERPRETATION: Adjuvant treatment with autologous renal tumour cell vaccine in patients with renal-cell carcinoma after radical nephrectomy seems to be beneficial and can be considered in patients undergoing radical nephrectomy due to organ-confined renal-cell carcinoma of more than 2.5 cm in diameter.

Regulatory challenges for autologous tissue engineered products on their way from bench to bedside in Europe.

Since the late eighties of last century the high potential of tissue engineered products (TEP)s has been shown for the treatment of various diseases and many scientific publications appeared in this field. However, only few products reached the market since. Development of TEPs is a promising but owing to its novelty a very challenging task that requires experts in this still developing field as well as ample financial resources. This paper summarises relevant regulatory challenges during quality, preclinical and clinical development of autologous TEPs in Europe. Selected strategies on how to manage major issues are presented, together with some examples from the development of an autologous TEP for urethroplasty. Considering these aspects may help other investigators with potential strategies during the development of novel TEPs.

Early continence in patients with localized prostate cancer. A comparison between open retropubic (RRPE) and endoscopic extraperitoneal radical prostatectomy (EERPE).

OBJECTIVE: The study examined and compared continence rates in prostate cancer patients who had undergone either open retropubic prostatectomy (RRPE) or endoscopic extraperitoneal radical prostatectomy (EERPE). The core question was whether the surgical approach had an effect on the patients' continence status 3 months after surgery. METHODS: We conducted a multicentric, longitudinal study in 7 German hospitals. Three hundred fifty prostate cancer patients (166 EERPE, 184 RRPE) were asked to self-assess symptoms associated with urinary incontinence (UI) 1 day before and 3 months after prostatectomy. Symptoms of UI were assessed using the EORTC QLQ-PR25 questionnaire. Urinary continence was defined according to (1) the use of no protective pad, (2) the use of up to a single protective pad in a 24-hour period, and (3) according to the patient's self-assessment. A binary regression model was employed to predict early continence status. RESULTS: Three months after prostatectomy, 44% of patients who underwent EERPE and 40% of patients who underwent RRPE were completely continent. Patients who underwent nerve-sparing prostatectomy and patients younger than 65 years had a better chance of regaining urinary continence earlier. The surgical approach had no significant impact on the patients' continence status. Limitations of the study are a drop-out rate of 39% and sociodemographic and clinical differences between both treatment groups. CONCLUSIONS: Three months after prostatectomy, there were no significant differences between both treatment groups regarding urinary continence. The surgical approach had no significant effect on the patients' continence status. Higher age and non-nerve-sparing surgery are associated with a longer period of convalescence.

Laparoscopic treatment of urachal remnants in children.

PURPOSE: Urachal remnants are generally treated with the open method. We evaluated the role of laparoscopy for this anomaly in a consecutive series of 27 children treated during a 12-year period. MATERIALS AND METHODS: A total of 27 children with a median age of 4.7 years presented with urachal remnants between 1993 and 2006. Two different laparoscopic approaches were used. In the first 9 children a 5 mm laparoscope was inserted at the umbilicus, with working trocars in the left and right upper abdominal wall. In the remaining patients the laparoscope was placed at the left lower abdominal wall, with working ports placed at the left lower and upper abdomen. The working ports were 2 mm trocars. The urachal remnants were ligated and excised by electrocautery, and the bladder-sided stump was ligated with 2 sutures. No drains were used. The specimen were exteriorized via the umbilicus. RESULTS: Median operative time was 35 minutes. There were no intraoperative or postoperative complications, and no recurrences. Cosmetic results were excellent. CONCLUSIONS: The laparoscopic approach for urachal remnants is safe, allows for better visualization of the anatomy and yields a cosmetic result that is superior to the open approach.

Validity of the CAPRA score to predict biochemical recurrence-free survival after radical prostatectomy. Results from a european multicenter survey of 1,296 patients.

PURPOSE: The CAPRA (Cancer of the Prostate Risk Assessment) score from the University of California, San Francisco provides a new statistical model to predict recurrence-free survival and pathological tumor stage after radical prostatectomy. It was originally developed using data from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry. To calculate the score, which ranges from 0 to 10, 5 clinical variables are needed, ie prostate specific antigen, Gleason sum, clinical tumor grade, percentage of positive biopsies and patient age. To date, the only external validation of the CAPRA score has been conducted using the SEARCH (Shared Equal Access Regional Cancer Hospital) database. The present study uses a German database to contribute to existing validation work and to test transferability of the CAPRA score to a sample that differs fundamentally from the SEARCH sample in terms of clinical features. MATERIALS AND METHODS: Data from 1,296 German patients after radical prostatectomy were used for validation. Mean followup was 56.5 (+/-35.4) months. Accuracy of prediction of recurrence-free survival and pathological tumor stage with the CAPRA score was analyzed using Kaplan-Meier analysis, proportional hazards regression, logistic regression and graphic representation. RESULTS: For the external validation of the CAPRA score, the underlying clinical variables of our study group were unfavorable compared to the original cohort from the CaPSURE data set. The recurrence-free survival rate decreased after 3 and 5 years from 100% to 97%, respectively, in the CAPRA score 0 to 1 group, and from 44% to 31%, respectively, in the CAPRA score of 7 or higher group. The hazard ratios of a biochemical recurrence per 1-group increase were 1.50 (95% CI 1.43-1.56) for the CAPRA sum score, 1.62 (95% CI 1.53-1.71) for the 7-group CAPRA score and 3.52 (95% CI 3.00-4.12) for the 3-group CAPRA score. Concordance indices between 0.78 and 0.81 suggested good predictive accuracy. Of the 5 CAPRA constituents 4 independently predicted recurrence-free survival, ie prostate specific antigen, Gleason sum, cT stage and percent of positive biopsies. Positive margins occurred in 13.1% of patients with a CAPRA score of 0 to 1 vs 62% of patients with a score of 7 to 10 (p <0.001). Organ confined tumors were present in 97.7% of patients with a CAPRA score of 0 to 1 vs 19.3% of those with a score of 7 to 10 (p <0.001). CONCLUSIONS: Despite different clinical features in the present patient cohort and the CaPSURE data set, the accuracy of the CAPRA nomogram in predicting recurrence-free survival was high. These results underscore the effectiveness and the clinical applicability of the CAPRA score which, in addition to patient counseling, may also be used for risk stratification in clinical studies.