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Redo-urethroplasty is a challenge for any genitourethral surgeon, with a number of techniques previously described. This systematic review aims to identify the surgical techniques described in the literature and evaluate the evidence for their effectiveness in managing recurrent urethral strictures. A systematic review of the MEDLINE and EMBASE databases from 1945 to July 2018 was performed and the urethroplasty procedures were classified according to the site and surgical technique. Primary outcomes included success rates measured via re-stricture rates and the post-op maximum urinary flow rate. Secondary outcomes included complication rates and patient-reported quality of life. A total of 39 identified studies met the inclusion criteria. Twenty-two studies described the use of excision and primary anastomotic urethroplasty with success rates showing wide variability (58–100%). Success rates reported according to the site of the stricture also varied: bulbar (58–100%) and posterior (69–100%) recurrent strictures. One-stage substitution urethroplasty was described in 25 studies with success rates of 18–100%, with the best outcomes reported for bulbar (58–100%) and hypospadias-related (78.6–82%) strictures. Two-stage substitution urethroplasty was described in 12 studies with the success rates of 20–100%, with the best evidence related to hypospadias-related and posterior urethral strictures. The buccal mucosa graft was the graft source with the best evidence for substitution urethroplasty (18–100%). Trends of effectiveness were identified for redo-urethroplasty modalities in different locations. However, the current levels of evidence are limited to small observational studies, highlighting the need for further larger prospective data to evaluate different techniques used for recurrent urethral strictures.

Aging increases oxidative stress, which can have delirious effects on smooth and striated muscle resulting in bladder dysfunction. Consequently, in women aged over 60 years, urinary incontinence (UI) is a prevalent health problem. Despite the prevalence and consequences, UI continues to be undertreated simply because there are few therapeutic options. Here we investigated whether 8-aminoguanine (8-AG), a purine nucleoside phosphorylase (PNPase inhibitor), would restore urethra and external sphincter (EUS) muscle morphology in the aged rat. Aged (> 25 months) female Fischer 344 rats were randomized to oral treatment with 8-AG (6 weeks) or placebo, and the urethra and EUS were evaluated by electron microscopy and protein expression (western immunoblotting). Aging was associated with mitochondrial degeneration in smooth and striated muscle cells as compared to young rats. We also observed a significant increase in biomarkers such as PARP, a downstream activator of oxidative/nitrosative stress. Treatment of aged rats with 8-AG normalized all abnormalities to that of a younger state. 8-AG, a potent inhibitor of PNPase, reverses age-related lower urinary tract morphological and biochemical changes. Our observations support the concept that 8-AG will reverse age-induced lower urinary tract disorders such as UI. These initial findings could have therapeutic implications for the prevention and treatment of age-related UI.

CT imaging is widely used for response evaluation of immunotherapy in patients with advanced stage renal cell carcinoma (RCC). However, this kind of treatment may not immediately be cytoreductive, although the treatment is successful. This poses new demands on imaging modalities. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) proved to be useful in monitoring the effect of several antitumour treatments. We investigated the potential of FDG-PET for the evaluation of response to immunotherapy. In seven patients with metastasized RCC, who were treated with either interferon-alpha (IFN-α) monotherapy or a combination of IFN-α, interleukin-2 and 5-fluorouracil, FDG-PET was performed prior and after 5 and 9 weeks of treatment. Quantitative changes of glucose metabolic rate (MRGlu) were compared with changes in tumour size on CT imaging using Response Evaluation Criteria in Solid Tumors (RECIST) and to survival and progression-free survival. No consistent changes in MRGlu were observed within different response groups. And no correlation with CT imaging, neither with survival or progression-free survival, was found. In contrast to the positive results reported on (chemo) therapy response evaluation with FDG-PET in different malignancies, this imaging modality appears not useful in response monitoring of immunotherapeutic modalities in RCC.

We conducted a phase I/II clinical trial evaluating the sequential outpatient combination of S.C. recombinant human interleukin-2 (rIL-2; given at 10 MIU/m2 b.i.d. on days 3–5 of weeks 1 and 4 and at 5 MIU/m2 on days 1, 3, and 5 of weeks 2 and 3), s.c. recombinant human alpha-interferon (rIFN-α; given at 6 MIU/m2 on day 1 of weeks 1 and 4 and on days 1, 3, and 5 of weeks 2 and 3 and at 9 MIU/m2 on days 1, 3, and 5 of weeks 5–8), i.v. bolus 5-fluorouracil (5-FU; given at 1,000 mg/m2 once weekly during weeks 5–8), and i.v. bolus vinblastine (given at 6 mg/m2 once weekly during weeks 5 and 8) in conjunction with p.o. 13-cis-retinoic acid (13-C-RA; given at 35 mg/m2 daily during weeks 1–8). Therapy was always given in the outpatient setting. Grade 3 constitutional symptoms (malaise, chills, fevers, anorexia) were observed in 4%–8% of treatment cycles and required a 50% reduction in the doses of rIL-2 and rIFN-α. None of the patients experienced major 5-FU-related toxicities such as severe diarrhea and/or stomatitis; up to 20% of patients developed vinblastine-associated peripheral polyneuropathy, which was reversible after the cessation of therapy. 13-cis-Retinoic acid produced no significant side effect; no toxic death occurred. Among 24 patients with progressive metastatic disease, there were 4 complete remissions (lung, lymph nodes) and 6 partial remissions (lung, pleura, liver, lymph nodes, and peritoneal carcinosis), for an overall objective response rate of 42% (95% confidence interval, 22%–63%). An additional 13 patients achieved disease stabilization (54%). The median time to response was 3–4 months (range, up to 6 months); all responses are continuous. In summary, although the potential synergy of biochemotherapy plus 13-cis-retinoic acid requires further preclinical investigation, the current outpatient combination regimen (rIL-2, rIFN-a, 5-FU, vinblastine, and 13-C-RA) proved to be both safe and highly effective in patients with advanced metastatic renal-cell carcinoma. A current multiinstitutional prospectively randomized trial is comparing biochemotherapy with and without concomitant 13-C-RA against rIFN-α plus vinblastine.

Retroperitoneal lymph node dissection (RPLND) for germ cell tumours is a challenging procedure that may present relevant complications. The purpose was to analyse postoperative complications and identify risk factors for major complications. This is a retrospective unicentric analysis of a large cohort of 295 RPLNDs from 1992 to 2020. Early complications (30 days) and late complications (31–180 days) were classified according to the Clavien‒Dindo classification. The influence of surgical, patient-specific, and tumour-specific parameters on grade III–V complications was analysed in univariate and multivariate logistic regression models. A total of 232 were postchemotherapy RPLNDs, and 63 were primary RPLNDs. Early postoperative complications were found to be grades I–II in 58.6% (173/295), grades III–IV in 9.8% (29/295), and grade V in 0.3% (1/295). In 20% (58/295), additional surgical procedures were needed. Grade III–V complications were associated with ≥ 4 cycles of preoperative chemotherapy (OR 3.7 (1.5–8.9); p = 0.004), RPLND specimen (nonseminoma or immature teratoma) (OR 3.1 (1.4–6.6); p = 0.005), transfusions (OR 2.4 (1.1–5.4); p = 0.03), salvage RPLND (OR 4.1 (1.8–9.3); p < 0.001), and preoperatively elevated AFP (OR 5 (2.2–11.7); p < 0.001). In multivariate analysis, the only independent predictor for grade III–V complications was preoperative AFP elevation (OR 3.3 (1.2–9.2); p = 0.02). Limitations include the retrospective study design. Our results demonstrate that RPLND is a demanding surgical procedure. Patients with a complex tumour history have a higher risk of complications. We recommend treatment of these complex cases in high-volume centres.

In majority of patients who are subjected to prostate biopsies, no prostate cancer (PCa) is found. It is important to prevent unnecessary biopsies since serious complications may occur. An artificial neural network (ANN) may be able to predict the risk of the presence of PCa. Included were all patients, who underwent transrectal ultrasound-guided prostate biopsies between June 2006 and June 2007 with a total PSA (tPSA) level between 2 and 20 μg/l. The patients were divided into two groups according to their tPSA level (2–10 μg/l and 10–20 μg/l). The ANN Prostataclass of the Universitätsklinikum Charité in Berlin was used. The predictions of the ANN were compared to the pathology results of the biopsies. Overall 165 patients were included. PCa was diagnosed in 53 patients, whereas the ANN predicted “no risk” in 19 of these patients (36%). The ANN output receiver operator characteristic (ROC) plots for the range of tPSA 2–10 μg/l and tPSA 10–20 μg/l showed an area under the curve (AUC) of 63 and 88% for the initial biopsy group, versus 69 and 57%, respectively, for the repeat biopsy group. The ANN resulted in a false negative rate of 36%, missing PCa in 19 patients. For use in an outpatient-clinical setting, this ANN is insufficient to predict the risk of presence of PCa reliably.