Dirk Fahlenkamp

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.

COMPLICATIONS OF LAPAROSCOPIC PROCEDURES IN UROLOGY: EXPERIENCE WITH 2,407 PROCEDURES AT 4 GERMAN CENTERS

PURPOSE The 4 most active centers of the laparoscopy working group of the German Urologic Association collected data about the complications associated with laparoscopic surgery in urology. MATERIALS AND METHODS At 4 centers 2,407 laparoscopies or retroperitoneoscopies were performed as of May 1998, including 776 for varicocelectomy, 259 for cryptorchidism, 481 for pelvic lymph node dissection, 351 for nephrectomy/heminephrectomy renal pathology, 139 for renal cyst resection, 58 for ureteral procedures, 44 for adrenalectomy, 41 for nephropexy, 41 for lymphocele fenestration, 40 for retroperitoneal para-aortic lymphadenectomy and 187 for other operations. The complications were evaluated, listed according to the anatomical specificity and grouped with respect to the surgical step during laparoscopy. RESULTS A total of 107 complications (4.4%) occurred. The re-intervention rate was 0.8% and the mortality rate was 0.08%. The complication rate depended on the difficulty of the procedure and averaged 1.0, 3.9 and 9.2%, respectively, for easy, difficult and very difficult operations. The majority were vascular injuries (1.7%) and visceral lesions (1.1%) followed by complications of healing and infection (0.8%). Only 0.2% of complications was associated with the access technique (trocar insertion), whereas most occurred during dissection (2.9%). The complication rate was 13.3% for the first 100 procedures and subsequently averaged 3.6%. CONCLUSIONS Critical documentation of experience from several institutions, especially for an analysis of complications of urological laparoscopy, is important for the development of this surgical technique. The overall complication rate is comparable to other specialties. Future technical developments in trocar insertion, tissue dissection and control of bleeding with our improved training program will further reduce the complication rate.

Laparoscopic nephrectomy: The experience of the laparoscopy working group of the German Urologic Association

PURPOSE The centers of the laparoscopy working group of the German Urologic Association collected data to prove the efficacy, safety and reproducibility of laparoscopic nephrectomy. MATERIALS AND METHODS At 14 centers 482 laparoscopic nephrectomies have been performed until December 1996 via a transperitoneal approach in 344 (71%) and a retroperitoneal approach in 138 (29%). All 482 laparoscopic nephrectomies were performed by a total of 20 surgeons with an average of 24 procedures per surgeon (range 4 to 105). The indications for nephrectomy were benign renal pathology in 444 patients (92%), including renovascular disease in 28%, hydronephrosis in 20%, reflux nephropathy in 15%, chronic pyelonephritis in 12%, end stage nephrolithiasis in 11%, renal dysplasia in 4% and renal tuberculosis in 1%. Of the remaining 38 patients (8%) laparoscopic radical nephrectomy was performed for renal cell carcinoma in 5% and for upper tract transitional cell carcinoma in 3%. RESULTS Operating time depended mainly on the pathology of the kidney (that is small dysplastic organ versus large hydronephrosis) and the learning curve of the surgeon. However, the average operating time did not vary significantly among the different centers (maximum 277.6 and minimum 81.9 minutes). Intraoperative or perioperative complications were noted in 29 patients (6.0%), including bleeding in 22 (4.6%), bowel injury in 3, hypercarbia in 2 and pleura lesion in 1 and pulmonary embolism in 1. The conversion rate was 10.3% (bleeding, bowel injury, difficult dissection), including 4 patients with renal tuberculosis, 2 with xanthogranulomatous nephritis, and 1 each following renal trauma and embolization. The re-intervention rate was 3.4% due to bleeding in 6 cases, abscess formation in 3, intestinal stenosis in 2 and a pancreatic fistula and port hernia in 1. Mean hospital stay was 5.4 days. CONCLUSIONS Laparoscopic nephrectomy has become a well established procedure in those urology departments focusing on laparoscopy. The indications and results are reproducible at these centers. However, for patients with severe perinephritis (that is renal tuberculosis, xanthogranulomatous nephritis, posttraumatic atrophy) a higher likelihood of open conversion must be considered.

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

Study Type – Practice patterns (retrospective cohort)

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.

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 24 months. 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 ± 4.7 mL/s (n = 57) and 25.4 ± 14.7 mL/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 24 months (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.

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.