Prognostic impact of tumor-associated immune cell infiltrates at radical cystectomy for bladder cancer

Objectives: To assess whether the presence and location of tumor-associated immune cell infiltrates (TAIC) on histological slides obtained from cystectomy specimens impacts on oncological outcomes of patients with bladder cancer (BC). Material and methods: A total of 320 consecutive patients staged with cM0 bladder cancer underwent radical cystectomy (RC) between 2004 and 2013. The presence of TAIC (either located peritumorally [PIC] and/or intratumorally [IIC]) on histological slides was retrospectively assessed and correlated with outcomes. Kaplan-Meier analyses were used to estimate the impact of TAIC on recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). Multivariable Cox-regression analysis was carried out to evaluate risk factors of recurrence. The median follow-up was 37 months (IQR: 10-55). Results: Of the 320 patients, 42 (13.1%) exhibited IIC, 141 (44.1%) PIC and 137 (42.8%) no TAIC in the cystectomy specimens. Absence of TAIC was associated with higher ECOG performance status (P = 0.042), histologically advanced tumor stage (≥pT3a; P < 0.001), lymph node tumor involvement (pN+; P = 0.022), positive soft tissue surgical margins (P = 0.006), lymphovascular invasion (P < 0.001), and elevated serum C-reactive protein levels (P < 0.001). The rate of never smokers was significantly higher in the IIC-group (64.3%) compared to the PIC-group (39.7%, P = 0.007) and those without TAIC (35.8%, P = 0.001). The 3-year RFS/CSS/OS was 73.9%/88.5%/76.7% for patients with IIC, 69.4%/85.2%/70.1% for PIC and 47.6%/68.5%/56.1% for patients without TAIC (P < 0.001/<0.001/0.001 for TAIC vs. no TAIC). In multivariable analysis, adjusted for all significant parameters of univariable analysis, histologically advanced tumor stage (P = 0.003), node-positive disease (P = 0.002), and the absence of TAIC (P = 0.035) were independent prognosticators for recurrence. Conclusions: In this analysis, the presence and location of TAIC in cystectomy specimens was a strong prognosticator for RFS after RC. This finding suggests that the capability of immune cells to migrate into the tumor at the time of RC is prognostically important in invasive bladder cancer

Evidence for benefits and risks of tadalafil as a non-prescription medicine: review and evaluation using the Group Delphi technique to achieve consensus amongst clinical experts

An evidence-based consensus meeting was held with urologists, a pharmacist and a cardiologist to perform a structured benefit-risk analysis of reclassifying tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor for treatment of erectile dysfunction (ED), to be available without prescription in Germany. As per the Brass process endorsed by regulatory authorities, an evidence-based Brass value tree was developed, which identified the incremental benefits and risks that should be considered above the safety and efficacy evidence required for prescription medicines. During the Group Delphi consensus meeting, the expert panel rated the likelihood and clinical impact of each benefit and risk on a scale of 0 (none) to 3 (high). Overall attribute scores were calculated from the product of the mean likelihood and mean clinical impact scores giving a possible score of 0–9. The overall benefit attribute scores ranged from 2.8 to 5.4. The overall risk attribute scores ranged from 0.2 to 2.2 though most were 1.0 or less (3 or more is generally considered to be of concern). On balance, the independent meeting scored the benefits of reclassification of tadalafil higher than the risks and considered the risk mitigation strategies of the packaging label and patient information leaflet (PIL) sufficient

Long-Term Results after Surgical Treatment of Congenital Penile Curvature Using a Modified Nesbit Technique

Purpose: Congenital penile curvature (CPC) is a rare condition with surgical correction being the standard therapy. In the current study, we report long-term results analyzing the surgical and functional outcomes using a modified Nesbit technique. Materials and Methods: Patients with CPC were included. After penile degloving and mobilization of the neurovascular bundle an artificial erection was performed. An ellipsoid part of the tunica albuginea was excised at the point of maximum curvature on the convex side of deviation. The tunical defect was then closed by interrupted absorbable sutures with inverted knots. Results of correction were documented intra- and postoperatively by artificial erection. Pre- and postoperative evaluation included measurement of penile length and curvature after pharmacological erection. Erectile function, alteration in glans sensation, palpable suture as well as short- and long-term complication were also recorded using validated questionnaires and objective examinations. Results: Fifty-five patients with mean age 26.93 years (14–66 years) and mean curvature 69.81° (25°–90°) were included in the study. Ventral or ventrolateral curvature was observed in 83.6%. Mean operative time was 106.8 minutes (55–169 minutes). Totally straightness of the penis was achieved in 51/55 patients (92.8%). After a mean long-term follow-up of 36.68 months (4–87 months), erectile function worsened in 3.6% of patients. Median penile length loss associated with this technique was 1.7 cm (0–3.0 cm). Conclusions: Surgical therapy of CPC using our modified Nesbit technique is feasible, safe and provides reliable long-term outcomes, representing an alternative for surgical correction of CPC