Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis.

PURPOSE: The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy. MATERIALS AND METHODS: A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed. The primary outcomes were stenosis recurrence and development of de novo stress urinary incontinence. Secondary outcomes were surgical complications, changes in voiding, and patient-reported satisfaction. RESULTS: Forty-five men were treated with D-BMGU for stenosis following prostatectomy and radiation. There was a total of 7 recurrences. Median follow-up in patients without recurrence was 21 months (IQR 12-24). There were no incidents of de novo incontinence, 28 patients were incontinent pre- and postoperatively, and of the 6 patients managed with suprapubic catheter preoperatively, 4 were continent after repair. Following repair, men had significant improvement in postvoid residual, uroflow, International Prostate Symptom Score, and International Prostate Symptom Score quality-of-life domain. Overall satisfaction was +2 or better in 86.6% of men on the Global Response Assessment. CONCLUSIONS: D-BMGU is a safe, feasible, and effective technique in patients with urethral stenosis after a combination of prostatectomy and radiation therapy. Although our findings suggest this technique may result in lower rates of de novo urinary incontinence compared to conventional urethral transection and excision techniques, head-to-head comparisons are needed.

The Expression of Alamandine Receptor MrgD in Clear Cell Renal Cell Carcinoma Is Associated with a Worse Prognosis and Unfavorable Response to Antiangiogenic Therapy.

Renal cell carcinoma (RCC) ranks among the most prevalent malignancies in Western countries, marked by its notable heterogeneity, which contributes to an unpredictable clinical trajectory. The insufficiency of dependable biomarkers adds complexity to assessing this tumor progression. Imbalances of several components of the intrarenal renin-angiotensin system (iRAS) significantly impact patient prognoses and responses to first-line immunotherapies. In this study, we analyzed the immunohistochemical expression of the Mas-related G-protein-coupled receptor D (MrgD), which recognizes the novel RAS peptide alamandine (ALA), in a series of 87 clear cell renal cell (CCRCCs), 19 papillary (PRCC), 7 chromophobe (ChRCC) renal cell carcinomas, and 11 renal oncocytomas (RO). MrgD was expressed in all the renal tumor subtypes, with a higher mean staining intensity in the PRCCs, ChRCCs, and ROs. A high expression of MrgD at the tumor center and at the infiltrative front of CCRCC tissues was significantly associated with a high histological grade, large tumor diameter, local invasion, and locoregional node and distant metastasis. Patients with worse 5-year cancer-specific survival and a poorer response to antiangiogenic tyrosine-kinase inhibitors (TKIs) showed higher MrgD expression at the center of their primary tumors. These findings suggest a possible role of MrgD in renal carcinogenetic processes. Further studies are necessary to unveil its potential as a novel biomarker for CCRCC prognosis and response to frontline therapies.

Claudin-3 Loss of Expression Is a Prognostic Marker in Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) development is the foremost concern after treatment of patients with high risk with locally advanced or metastatic prostate cancer. Androgen receptor (AR) is the main driver of CRPC development, through its interaction with epigenetic modifier genes, placing epigenetics modifications in the forefront of CRPC development. Comparing the DNA methylation and expression profile of androgen-sensitive and -refractory prostate cancer cells, we describe the epigenetic silencing of claudin-3 (CLDN3) in AR positive cells resistant to androgen deprivation (LNCaP-abl). CLDN3 silencing was associated with DNA methylation, loss of histone acetylation and H3K27 methylation, and was re-expressed by the combined treatment with the epigenetic modulators Aza and SAHA. From a functional point of view, CLDN3 loss was associated with increased cellular invasion. Immunohistochemical analysis showed decreased CLDN3 expression in samples from CRPC patients. Interestingly, CLDN3 expression was significantly decreased in samples from patients with high total Gleason score (≥8) and locally advanced tumors. Finally, CLDN3 loss of expression was associated with worse disease-free survival and time to clinical progression. In conclusion, our findings strongly indicate that epigenetic silencing of CLDN3 is a common event in CRPC that could be useful as a molecular marker for the prognosis of prostate cancer patients and to discriminate aggressive from indolent prostate tumors.

A buccal mucosal graft subcoronal resurfacing technique to treat recurrent penile adhesions: the buccal belt.

OBJECTIVE: To outline our step-by-step surgical technique using a subcoronal buccal mucosal graft (BMG) resurfacing technique for the treatment of recurrent penile adhesions. METHODS: To perform the 'buccal belt' procedure a subcoronal circumferential segment of diseased skin was excised. An appropriately sized BMG was circumferentially secured subcoronally with a proximal and distal anastomosis to the edges of the wound. Quilting stitches were also placed to allow proper graft fixation. A petroleum jelly bolster was secured as a tie-over dressing. Patients were discharged with a Foley catheter and the bolster dressing in place. The bolster and Foley catheter were removed 7 days postoperatively. The patients were then seen for follow-up at 4- to 6-month intervals. A retrospective, international multi-institutional review was conducted to include all patients who underwent this procedure. Surgical complications, evidence of recurrence, and patient-reported outcome measures including visual analogue scale (VAS) and global response assessment (GRA) questionnaires were reviewed. RESULTS: Thirty-one men underwent the procedure across six institutions between March 2014 and September 2020. The mean (range) surgical time was 59 (25-95) min. At the mean (range) follow-up of 27 (4-79) months all patients reported resolution of presenting symptoms and no recurrence of adhesions. The mean VAS score was 8.9 and 9.0 for aesthetics and functional outcomes, respectively. On GRA, overall improvement was reported by all patients (61%, +3; 25%, +2; 14%, +1). CONCLUSION: There are limited options for the treatment of recurrent penile adhesions. A subcoronal BMG resurfacing is feasible, with no recurrence and overall high satisfaction seen in an initial patient cohort.

Influence of ATOMS implant on the voiding phase of patients with post-prostatectomy urinary incontinence.

OBJECTIVE: To assess changes in voiding phase, especially urethral resistance after post-prostatectomy urinary incontinence (PPI) treatment with the Adjustable TransObturator Male System (ATOMS). MATERIAL AND METHODS: A longitudinal prospective study was performed on 45 men treated with ATOMS for PPI, with the intention to evaluate the changes produced by the implant on the voiding phase. Patients with preoperative urodynamic study were offered postoperative urodynamic evaluation, and both studies were compared. The following urodynamic date were evaluated: maximum voiding detrusor pressure, detrusor pressure at maximum flow rate, maximum flow rate (Qmax), voiding volume, post-void residue, bladder outlet obstruction index (BOOI), urethral resistance factor (URA), and bladder contractility index (BCI). The statistical analysis used were the mean comparison test for dependent groups (Student's t test) for parametric variables and the Wilcoxon test for non-parametric variables. The signification level was set at 95% bilateral. RESULTS: A total of 37 patients (82.2%) used zero pads/day at the time of urodynamic postoperative evaluation and pad-test evolved from 592 ± 289 ml baseline to 25 ± 40 ml (p = 0.0001). Significant differences were observed in Qmax (15 ± 8.3 before and 11 ± 8.3 after surgery; p = 0.008), voiding volume (282 ± 130.7 before and 184 ± 99.92 after surgery). BOOI (-12 ± 23.9 before and -2 ± 21.4 after surgery; p = 0.025) and BCI (93 ± 46.4 before and 76 ± 46.0 after surgery; p = 0.044). In no case did we observe postoperative bladder outlet obstruction, according to URA parameter below 29 cm H2 O in all cases. There was not a significant variation either in post-void urinary residual volume (15 ± 47.4 before and 14 ± 24.2 after surgery, p = 0.867). CONCLUSIONS: The ATOMS implant induces a decrease of Qmax, voided volume, and bladder contractility and an increase of BOOI. However, our findings suggest that ATOMS device does not cause bladder outlet obstruction.

Effect of LHRH analogs on lower urinary tract symptoms associated with advanced prostate cancer in real clinical practice: ANALUTS study.

AIMS: To estimate the prevalence of lower urinary tract symptoms (LUTS) in patients with prostate cancer scheduled to receive LHRH analogs, and to assess the effectiveness of LHRH analogs on LUTS in patients presenting moderate/severe symptoms. METHODS: Prospective, noninterventional, multicenter study conducted at 28 centers in Spain and Portugal. LUTS were evaluated using the International Prostate Symptom Score (IPSS) at baseline, 24 and 48 weeks after initiation of treatment. Subanalyses were performed according to age and concomitant treatment (radiotherapy, alpha-blockers, and antiandrogens). RESULTS: A total of 354 patients were treated with LHRH analogs for 48 weeks. The percentage of patients with moderate/severe LUTS (IPSS > 7) decreased from 60.2% (n = 213/354) at baseline to 52.8% (n = 187/354) at Week 48. Among patients with moderate/severe LUTS at baseline: 73.7% (n = 157/213) still had moderate/severe LUTS at Week 48; percentage reductions of patients with LUTS at Week 48 were statistically significant (p < 0.05) overall and by age or concomitant treatment, except for alpha-blockers (84.2% patients receiving them still had moderate/severe LUTS at Week 48). All IPSS items, including quality of life for urinary symptoms, improved throughout the study. The only predictor of response to treatment with LHRH analogs that improved IPSS by 3 points after 48 weeks was baseline testosterone levels. Lower baseline testosterone levels were associated with greater improvement in IPSS after treatment with LHRH analogs (odds ratio 0.998, 95% confidence interval 0.996-1.000, p = 0.0277). CONCLUSION: LHRH analogs have a positive effect in patients with locally advanced or metastatic prostate cancer presenting moderate/severe LUTS regardless of age or concomitant treatment received (radiotherapy, antiandrogens, or alpha-blockers).

Clear Cell Renal Cell Carcinomas with Aggressive Behavior Display Low Intratumor Heterogeneity at the Histological Level.

PURPOSE OF REVIEW: Intratumor heterogeneity (ITH) is an inherent characteristic of most tumors and its detection remains a key task for pathologists. However, the clinical significance of the degree of development of this feature is still poorly understood. RECENT FINDINGS: A series of 28 clear cell renal cell carcinomas (CCRCC) have been exhaustively analyzed with two different sampling protocols [multisite tumor sampling (MSTS) and total sampling] to evaluate to what point the level (low vs. high) of histological ITH detected in routine practice influences tumor behavior and patients' survival. All CCRCC (n = 14) pursuing an aggressive clinical course presented low levels of ITH. A significant worse survival was detected in CCRCC with low ITH (p < 0.001). The simple quantification of the level of ITH using extensive sampling protocol may be of help in predicting tumor evolution, since all CCRCC with aggressive behavior demonstrated low levels of histological ITH.

Systematic review and meta-analysis comparing Adjustable Transobturator Male System (ATOMS) and male Readjustment Mechanical External (REMEEX) system for post-prostatectomy incontinence.

OBJECTIVE: To assess the efficacy and safety of Adjustable Transobturator Male System (ATOMS) compared to male Readjustment Mechanical External (REMEEX) system for post-prostatectomy incontinence (PPI). MATERIAL AND METHODS: A systematic review and meta-analysis on adjustable device ATOMS compared to male REMEEX is presented. Studies on female or neurogenic incontinence were excluded. Primary objectives were evaluation of dryness (the proportion of patients with no-pad or one safety pad/day after device adjustment) and improvement between devices. Secondary objectives were complications and explant rate. They were estimated using a random-effect model. Statistical heterogeneity among studies was assessed using Cochran's Q test, Higgins's I2 statistics and tau2. RESULTS: Combined data of 29 observational studies with 1919 patients showed an equivalent proportion of patients treated with radical prostatectomy (p = .125) and previous radiation (p = .126). Dryness rate was 69.3% for ATOMS and 53.4% for male REEMEX (p = .008). Improvement rate was 90.8% for ATOMS and 80.2% for REMEEX (p = .007). Complication rate was 18.9% for ATOMS and 35.8% for REMEEX (p = .096) and explant rate was 5.5% for ATOMS and 13.9% for REMEEX (p = .027). Significant heterogeneity was evidenced, due to absence of randomized studies, variable incontinence severity baseline, difficulties for a common reporting of complications and difference in the follow-up. Differences observed between devices remained statistically significant when only studies with silicone-covered scrotal port (SSP) ATOMS and male REMEEX system II were considered. CONCLUSIONS: Despite the absence of direct comparison and the limitations observed ATOMS appears more effective than male REMEEX to treat PPI, and with less explant rate as reported in the literature.

A multi-institutional critical assessment of dorsal onlay urethroplasty for post-radiation urethral stenosis.

PURPOSE: To critically evaluate a multi-institutional patient cohort undergoing Dorsal-Onlay Buccal Mucosal Graft Urethroplasty (D-BMGU) for recurrent post-radiation posterior urethral stenosis. METHODS: Retrospective multi-institutional review of patients with posterior urethral stenosis from 10 institutions between 2010-2019 was performed. Patients with at least 1-year follow-up were assessed. Patient demographics, stenosis characteristics, peri-operative outcomes, and post-operative clinical and patient-reported outcomes were analyzed. The primary outcomes were stenosis recurrence and de-novo stress urinary incontinence (SUI). Secondary outcomes were changes in voiding, sexual function, and patient-reported satisfaction. RESULTS: Seventy-nine men with post-radiation urethral stenosis treated with D-BMGU met inclusion criteria. Median age and stenosis length were 72 years, (IQR 66-75), and 3.0 cm (IQR 2.5-4 cm), respectively. Radiation modalities included: 36 (45.6%) external beam radiotherapy (EBRT), 13 (16.5%) brachytherapy (BT), 10 (12.7%) combination EBRT/BT, and 20 (25.3%) EBRT/radical prostatectomy. At a median follow-up of 21 months (IQR 13-40), 14 patients (17.7%) had stenosis recurrence. Among 37 preoperatively-continent patients, 3 men (8.1%) developed de-novo SUI following dorsal onlay urethroplasty. Of 29 patients with preoperative SUI all but one remained incontinent post-operatively (96.6%). Following repair, patients experienced significant improvement in PVR (92.5 to 26 cc, p = 0.001) and Uroflow (4.6 to 15.9 cc/s, p = 0.001), and high overall satisfaction, with 91.9% reporting a GRA of + 2 or better). CONCLUSION: Dorsal onlay buccal mucosa graft urethroplasty is a safe and feasible technique in patients with post-radiation posterior urethral stenosis. This non-transecting approach may confer low rates of de-novo SUI. Further research is needed to compare this technique with excisional urethroplasty.

Artificial urinary sphincter or a second adjustable transobturator male system offer equivalent outcomes in patients whom required revision on the initial ATOMS device: An international multi-institutional experience.

AIM: To evaluate treatment options after surgical revision of adjustable transobturator male system (ATOMS) and the results of further incontinence implantation. MATERIALS AND METHODS: A retrospective multicenter study evaluating patients with surgical revision of ATOMS in academic institutions. Causes and factors affecting revision-free interval were studied and also the frequency of device explant and placement of second ATOMS or artificial urinary sphincter (AUS) at surgeon discretion. Operative results, complications (Clavien-Dindo), and efficacy (postoperative pad-test, pad-count, patient satisfaction, and patient global impression of improvement [PGI-I scale]) of each treatment option were compared. RESULTS: Seventy-eight out of 902 patients (8.65%) with ATOMS underwent surgical revision at 4.1 ± 2.4 years mean follow-up and 75 (8.3%) were explanted. The main causes for revision included persistence of incontinence (35.9%) and scrotal port erosion (34.6%). Independent risk factors of the shortened revision-free interval were previous anti-incontinence surgery (HR, 1.83; 95% CI, 1.06-3.16; p = 0.007) and port erosion (HR, 1.83; 95% CI, 1.06-3.16; p = 0.0027). Fifty-eight (6.4%) received a second implant: 31 repeated ATOMS and 27 AUS. Operative time was longer for AUS (p = .003). The visual analog scale of pain at hospital discharge (p = 0.837) and postoperative complications (p = 0.154) were equivalent. The predominant cuff size for AUS was 4.5 cm (59.3%). Mean follow-up after the second implant was 29.1 ± 25.8 months. Postoperative efficacy of secondary treatment results favored ATOMS based on pad-test (p = 0.016), pad-count (p = 0.029), patient satisfaction (p = 0.04), and PGI-I (p = 0.025). CONCLUSIONS: ATOMS surgical revision due to different reasons generally leads to device explant. Rescue treatment is possible with ATOMS or AUS. No difference in postoperative complications was detected between secondary devices, but efficacy favors repeating ATOMS implantation.

Urorectal fistula repair using different approaches: operative results and quality of life issues.

PURPOSE: To evaluate efficacy of urorectal fistula (URF) repair using different approaches and the clinical factor determinant of success, and also the morbidity associated to the procedure and health-related quality of life (HRQoL) in male survivors of pelvic malignancies. MATERIAL AND METHODS: Retrospective evaluation of 39 patients with URF primarily intervened in three institutions using different surgical approaches. Success was defined as effective fistula closure. Variables evaluated included demographics, previous treatments, surgical approach, ancillary surgeries, complications and HRQoL by using a standardized non-validated specific questionnaire. Median follow-up from surgery to interview was 55 months (interquartile range 49, range 4-112). Factors determinant of success were investigated using logistic regression. Safety of the procedure was evaluated by Clavien-Dindo scale. Deterioration of continence and erectile function and other HRQoL issues were evaluated. RESULTS: Prostate cancer treatment was the predominant etiology. The success rate for fistula repair was 89.5%. The surgical approach was not related to failed repair (p=0.35) or complications (p=0.29). Factors associated with failure were complications (p=0.025), radiotherapy (p=0.03), fistula location (p=0.04) and fistula size (p=0.007). Multivariate analysis revealed fistula size was the only independent determinant of failure (OR 6.904, 1.01-47.75). Complications occurred in 46.2% and severe complications in 12.8%. The mortality related to the procedure was 2.6%. Urinary incontinence was present before repair in 26.3% and erectile dysfunction in 89.5%. Fistula repair caused de novo urinary incontinence in 7.9% and deterioration of erectile status in 44.7%. Globally 79% were satisfied after repair and only 7.9% rated HRQoL as unhappy. Trans-sphincteric approach was related to less deterioration of erectile function (p=0.003), and higher perceived satisfaction in QoL (p=0.04). CONCLUSIONS: The surgical approach elected to correct URF is not determinant of success nor of complications. Fistula size appears as independent determinant for failure. Trans-sphincteric approach could be advantageous over other procedures regarding HRQoL issues.

Complications of the urinary incontinence system ATOMS: description of risk factors and how to prevent these pitfalls.

BACKGROUND: We report on our multicentre evaluation of the occurrence and management of complications with the ATOMS device (A.M.I., Austria). PATIENTS AND METHODS: Between 10/09 and 09/18, a total of 187 patients with persistent postoperative stress urinary incontinence received an ATOMS device in Madrid (n = 101) or Halle (n = 86). This prospective evaluation was carried out consecutively. In addition to complications, patient age, BMI, comorbidities and previous treatments for prostate cancer and urinary incontinence were examined. Statistical analysis was performed with GraphPad Prism 7® (GraphPad Software, Inc., La Jolla, USA); p < 0.05 was considered significant. RESULTS: The average age of the overall population was 69.4 years, with a mean CCI of 4.3. In total, 18.2% of the patients had diabetes mellitus, 21.9% were irradiated, and 14.1% and 22.9% underwent previous surgery for urinary incontinence and urethral stricture, respectively. The overall success rate of the device was 80.2%. A total of 51 postoperative complications (51/187, 27.3%) were observed, with 18 grade I (9.6%), 1 grade II (0.5%), 3 grade IIIa (1.6%) and 29 grade IIIb (15.5%) complications. The most serious postoperative complications were primary wound infection (8/187, 4.3%) and long-term cutaneous erosion with subsequent infection (15/187, 8.02%). The main risk factors for complications were previous radiotherapy (p = 0.003) and surgery for urethral stricture (p = 0.017). No other parameters were significant in bivariate analysis (p > 0.05). CONCLUSION: The most severe complications of ATOMS implantation were primary wound infection and cutaneous erosion, especially in the presence of previous radiotherapy. Particular focus on performing hygienic and accurate implantation techniques is recommended.

Transurethral ventral buccal mucosa graft inlay for treatment of distal urethral strictures: international multi-institutional experience.

PURPOSE: To critically evaluate a multi-institutional patient cohort undergoing single-stage distal urethral repair using a novel transurethral buccal mucosa graft inlay urethroplasty technique (TBMGI). METHODS: A retrospective multi-institutional review of consecutive patients with fossa navicularis (FN) strictures treated with a single-stage TBMGI technique at 12 institutions from March 2014-March 2018 was performed. Patient demographics, stricture characteristics, clinical and patient-reported outcomes were analyzed. The primary outcomes were stricture recurrence and complications. Secondary outcomes were change in maximum urinary flow rate (Qmax), PVR, and changes in IPSS, SHIM and global response assessment (GRA) questionnaire responses. Descriptive statistical analysis was used for evaluation of outcomes. RESULTS: Sixty-eight men met inclusion criteria. Median age and stricture length were 60 years (IQR 48-69) and 2 cm (IQR 2-3), respectively. Most common stricture etiology was lichen sclerosus (34%). Median operative time and EBL were 72 min (IQR 50-120) and 20 mL (IQR 10-43), respectively. Fifty-seven men completed ≥ 12-month follow-up. At a median follow-up of 17 months (IQR 13-22), 54 patients (95%) remained stricture-free. Median Qmax improved from 5 to 18 mL/s (p < 0.0001), PVR 76-21 mL (p < 0.0001), and IPSS 15-5 (p < 0.0001); IPSS-QOL score: 5-1 (p < 0.0001). SHIM score did not significantly change following repair (median 22-21 p = 0.85). On GRA assessment, a majority of men reported "marked" (64%) or "moderate" (28%) overall improvement. No patient developed fistula, glanular dehiscence, graft necrosis or chordee. CONCLUSIONS: This novel minimally invasive transurethral urethroplasty technique is feasible and has demonstrated generalizable outcomes in a multi-institutional cohort with varying etiologies.

Do voiding urodynamic parameters predict the success of adjustable transobturator male system (ATOMS) to treat postprostatectomy urinary incontinence?

OBJECTIVE: To evaluate whether urodynamic voiding risk factors can be predictive of failure of postprostatectomy urinary incontinence (PPI) treatment with adjustable transobturator male system (ATOMS). MATERIALS AND METHODS: We carried out a longitudinal study on 77 males treated for PPI with ATOMS. Patients were submitted preoperatively to a urodynamic study. The postoperative outcome was checked by pad-test. Treatment success was defined as daily pad-test below 10 mL. Statistical analysis used were Fisher exact test, χ2 lineal by lineal test, Student t test, and logistic regression analysis. The signification level was set at 95% bilateral. RESULTS: Treatment was successful in 54 patients (70%) achieving continence. The urodynamic parameters that related to postoperative continence outcome were the cystometric bladder capacity (direct relationship with continence (P = .019), type of voiding (more probability to achieve continence in patients who voided voluntarily followed by patients with involuntary voiding and abdominal straining voiding) (P = .034), Bladder Outlet Obstruction Index (BOOI) (inversely related with continence) (P = .025), and maximum voiding abdominal pressure (inversely related with continence) (P = .049). Multivariate analysis showed that cystometric bladder capacity (odds ratio [OR], 1.01; confidence interval [CI], 1.02-1.00), BOOI (OR, 0.97; CI, 0.99-0.94), and maximum abdominal bladder pressure (OR, 0.97; CI, 0.98-0.94) were independent risk factors to predict treatment success after ATOMS implant. CONCLUSIONS: The study of functional voiding parameters is useful to know the risk factors that influence postoperative outcome of PPI with ATOMS device. These findings could be of primary importance to facilitate optimum patient selection for this implant and therefore improve operative results.

Long-term outcome of adjustable transobturator male system for stress urinary incontinence in the Iberian multicentre study.

AIM: The aim of this study is to evaluate long-term durability and effectiveness of the adjustable transobturator male system (ATOMS). MATERIALS AND METHODS: The retrospective multicenter Iberian ATOMS study (n = 215) was updated to evaluate long-term continence status, complications, explants, and secondary treatments. Mean follow-up from surgery to March 2020 was 60.6 ± 18.4 months (range, 39-91). Eleven patients deceased of an unrelated causes. Kaplan-Meier curves were performed to evaluate device durability and incontinence free of recurrence interval. The multivariate analysis defined the population at risk of device explant. RESULTS: A total of 155 patients were dry at the last follow-up visit (72.1%); 99 (46%) used no pads and 56 (26%) used a security pad/day with urine loss less than 10 mL; 96% of dry patients after adjustment remained free of incontinence 1 year later, 93.6% 2 years later, 91.1% 3 years later, 89.2% 5 years later, and 86.7% 8 years later. Complications during follow-up occurred in 43 of 215 (20%). In total, 25 (11.6%) devices were explanted and causes were inefficacy 11 (44%), inefficacy and pain 3 (12%), port erosion 10 (40%), and wound infection 1 (4%). The secondary implant was performed in 11 (5.1%) cases, 6 artificial urinary sphincter and 5 repeated ATOMS. Time to explant was associated to complications (P < .0001), baseline stress urinary incontinence (SUI) severity (P = .01), and former irradiation (P = .03). Multivariate analysis revealed complications (hazard ratio [HR] = 8.71; 3.83-19.82), baseline SUI severity (>5 compared to 1-2 pads/day; HR = 14.9; 1.87-125), and irradiation before ATOMS (HR = 2.26; 1.02-5.18) predicted earlier ATOMS explant. Three cases received radiation after implant without complication. CONCLUSIONS: ATOMS device is efficacious and safe in the long term. Determinants for device explant include complications, baseline severity of incontinence, and previous irradiation. Currently, the durability of the device after 5 years is reassuring.

Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: a Role Regulating Tumor Growth.

Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors.

Patient satisfaction with adjustable transobturator male system in the Iberian multicenter study.

BACKGROUNDS: Patient-reported outcome measurements are important for urinary incontinence. We analyze self-assessed patient satisfaction and define the clinical profile of patient with highest satisfaction with the adjustable transobturator male system (ATOMS). METHODS: Patient perception of results was evaluated in a series of 181 patients after ATOMS adjustment. Baseline incontinence severity was defined in pads-per-day (PPD) as mild (2), moderate (3-5) or severe (≥ 6), and dryness as use of none or one security PPD. Post-operative pain at discharge was evaluated by 0-10 visual analogue scale and complications by Clavien-Dindo classification. Multivariate analysis was performed to anticipate "very much better" than baseline perception on patient global impression of improvement and a predictive nomogram was developed. RESULTS: Dryness was achieved in 80.7% (94.9% mild, 80.8% moderate and 65.8% severe groups). Mean pad-test and pad-count decrease with respect to baseline was 458 ± 330 ml and 3.2 ± 1.9 PPD, respectively (both p < .0001). Complications presented in 25 (13.8%). The proportion of patients that self-declared satisfied with the procedure was 87.1%; 90.6% perceived their situation "better" and 48.1% "very much better" than before. Multivariate analysis revealed best perception is defined by dryness after adjustment (p < .0001), baseline severity of incontinence (p = .007), low post-operative pain at discharge (p = .0018) and lack of complications (p = .007). CONCLUSIONS: Self-assessed satisfaction with ATOMS is very high. Factors that predict best perception of improvement include dryness, baseline SUI severity, presence of complications and pain level during admission. Radiotherapy and device generation were not independent predictors. A nomogram to predict patients that are completely satisfied with ATOMS after adjustment is proposed.

A Critical Insight into the Clinical Translation of PD-1/PD-L1 Blockade Therapy in Clear Cell Renal Cell Carcinoma.

PURPOSE OF REVIEW: Targeting PD-1/PD-L1 immune checkpoints is a new therapeutic tool in patients with locally advanced and metastatic clear cell renal cell carcinoma (CCRCC). The purpose of this review is to offer clinicians an updated translational insight into the current status of a therapeutic alternative that may impact significantly patient's life. RECENT FINDINGS: Immune checkpoint inhibition has recently demonstrated promising results in selected CCRCC patients with respect to tumor progression and survival. The decision to treat these patients with immune checkpoint inhibitors (ICI) relies on the immunohistochemical detection of PD-1/PD-L1 positivity in inflammatory cells in the tumor, which makes the role of the pathologist crucial, but clinical concern upon the reliability to use immunohistochemistry (IHC) to predict therapeutic response is increasing. We review the state of the art of the immune checkpoint inhibition in CCRCC, from the basic science and its fundamentals to the daily application in clinical routine.

Efficacy and safety of a hexanic extract of Serenoa repens (Permixon® ) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta-analysis of randomised controlled trials and observational studies.

OBJECTIVES: To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens (HESr, Permixon® ; Pierre Fabre Médicament, Castres, France), at a dose of 320 mg daily, as monotherapy for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective observational studies in patients with LUTS/BPH identified through searches in Medline, Web of Knowledge (Institute for Scientific Information), Scopus, the Cochrane Library, and bibliographic references up to March 2017. Articles studying S. repens extracts other than Permixon were excluded. Data were collected on International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax ), nocturia, quality of life, prostate volume, sexual function, and adverse drug reactions (ADRs). Data obtained from RCTs and observational studies were analysed jointly and separately using a random effects model. A sub-group analysis was performed of studies that included patients on longer-term treatment (≥1 year). RESULTS: Data from 27 studies (15 RCTs and 12 observational studies) were included for meta-analysis (total N = 5 800). Compared with placebo, the HESr was associated with 0.64 (95% confidence interval [CI] -0.98 to -0.31) fewer voids/night (P < 0.001) and an additional mean increase in Qmax of 2.75 mL/s (95% CI 0.57 to 4.93; P = 0.01). When compared with α-blockers, the HESr showed similar improvements on IPSS (weighted mean difference [WMD] 0.57, 95% CI -0.27 to 1.42; P = 0.18) and a comparable increase in Qmax to tamsulosin (WMD -0.02, 95% CI -0.71 to 0.66; P = 0.95). Efficacy assessed using the IPSS was similar after 6 months of treatment between the HESr and 5α-reductase inhibitors (5ARIs). Analysis of all available published data for the HESr showed a mean improvement in IPSS from baseline of -5.73 points (95% CI -6.91 to -4.54; P < 0.001). HESr did not negatively affect sexual function and no clinically relevant effect was observed on prostate-specific antigen. Prostate volume decreased slightly. Similar efficacy results were seen in patients treated for ≥1 year (n = 447). The HESr had a favourable safety profile, with gastrointestinal disorders being the most frequent ADR (mean incidence of 3.8%). CONCLUSION: The present meta-analysis, which includes all available RCTs and observational studies, shows that the HESr (Permixon) reduced nocturia and improved Qmax compared with placebo and had a similar efficacy to tamsulosin and short-term 5-ARI in relieving LUTS. HESr (Permixon) appears to be an efficacious and well-tolerated therapeutic option for the long-term medical treatment of LUTS/BPH.