Mid-term outcomes of minimally invasive infrapubic approach for inflatable penile prosthesis implantation: A single-center study and literature review.

BACKGROUND: The minimally invasive infrapubic approach (MIIA) for inflatable penile prosthesis (IPP) placement has shown favorable peri-operative safety and efficacy profile, but scarce data exist on long-term follow-up. OBJECTIVES: We investigated the safety and efficacy of IPP implantation via the MIIA after a minimum 5-year follow-up. MATERIALS AND METHODS: We identified data of implanted patients prospectively included in our institutional database. Complications and functional outcomes were assessed by using validated tools. Specifically, quality of life and patient satisfaction were evaluated by the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire. Kaplan-Meier method was used to analyze IPP survival (defined as a working IPP). RESULTS: Overall, 67 patients implanted by MIIA with a median (IQR) age of 64 years (61-70) were included. The median (IQR) follow-up duration was 71 months (63-80). Fifteen (22%) patients experienced complications: minor (Clavien ≤2) events included changes in penile sensitivity (n = 1; 1.5%), orgasmic dysfunction (n = 1; 1.5%), pain (n = 5; 7%), urinary tract infection (n = 2; 3%), and chronic discomfort (n = 1; 1.5%); major (Clavien 3) complications were represented by mechanical failure (n = 3; 4.5%), IPP infection (n = 1; 1.5%), and cylinder protrusion (n = 1; 1.5%). The estimated IPP survival was 94% (95% CI, 91.4-96.6), 92.5% (95% CI, 89.7-95.3), and 92.5% (95% CI, 89.7-95.3) at 3, 5, and 7 years after implantation, respectively. In patients using the device at follow-up (n = 61; 91%), median (IQR) scores for QoLSPP domains demonstrated favorable functional outcomes and patient satisfaction: functional 21 (19-23), personal 16 (15-18), relational 14 (12-15), and social 12 (11-14). DISCUSSION AND CONCLUSION: This study represents the longest follow-up using validated tools to assess the outcomes of IPP implantation via MIIA so far. IPP placement via MIIA confirms to be safe and to offer high satisfaction to both patients and partners at mid-term evaluation.

Primary versus revision implant for inflatable penile prosthesis: A propensity score-matched comparison.

Inflatable penile prosthesis (IPP) provides excellent outcomes after virgin implants. However, few data on IPP after revision surgery are available. This study aimed at comparing the outcomes of IPP in patients undergoing primary or revision implant surgery. Patients who underwent revision implant surgery (Group 1) between 2013 and 2020 were identified. Overall, 20 patients (Group 1) could be matched with a contemporary matched pair cohort of surgery-naive patients (Group 2) in a 1:1 ratio. Patients in Group 2 had a significantly shorter operative time [median (IQR): 84 (65-97) vs. 65 (51-75) min; p = .01] and lower rate of overall complications (25% vs. 10%; p = .01). Of note, mean (SD) scores for the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire demonstrated high satisfaction and IPP efficacy in both Groups 1 and 2: functional domain [3.9 (1.0) vs. 4.0 (1.2); p = .4], personal [3.9 (1.1) vs. 4.0 (1.1); p = .3], relational [3.8 (1.3) vs. 3.9 (1.1); p = .5] and social [3.9 (1.1) vs. 4.0 (1.2); p = .2]. These results suggest that in experienced hands, IPP offers high satisfaction to both patients and partners even in the setting of revision implant. However, it is mandatory to inform those patients about the increased risk of perioperative complications.

Atypical granular cell tumor of the urinary bladder: A case report and literature review.

Granular cell tumors (GCTs) are rare neoplasms of neural origin and usually tend to have a benign behaviour. We report a case of a 54 years old woman with severe gross hematuria caused by an atypical granular cell tumor which was successfully managed with a transurethral resection of the bladder (TURB). No local recurrence was observed after a three-year follow-up. The appropriate histological characterization and subclassification (benign, atypical and malignant neoplasm) is mandatory for an optimal patient management, in order to offer an appropriate treatment and a correct follow-up.

Diabetic Cardiomiopathy Progression is Triggered by miR122-5p and Involves Extracellular Matrix: A 5-Year Prospective Study.

OBJECTIVES: The purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis. BACKGROUND: The evolution of diabetic cardiomyopathy to heart failure affects patients'morbidity and mortality. CMR is the gold standard to assess cardiac remodeling, but there is a lack of markers linked to the mechanism of diabetic cardiomyopathy progression. METHODS: Five-year longitudinal study on patients with type 2 diabetes mellitus (T2DM) enrolled in the CECSID (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes) trial compared with nondiabetic age-matched controls. CMR with tagging together with metabolic and molecular assessments were performed at baseline and 5-year follow-up. RESULTS: A total of 79 men (age 64 ± 8 years) enrolled, comprising 59 men with T2DM compared with 20 nondiabetic age-matched controls. Longitudinal CMR with tagging showed an increase in ventricular mass (ΔLVMi = 13.47 ± 29.66 g/m2; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m2; p = 0.056) in men with T2DM. Cardiac strain worsened (Δσ = 1.52 ± 3.85%; p = 0.033) whereas torsion was unchanged (Δθ = 0.24 ± 4.04°; p = 0.737), revealing a loss of the adaptive equilibrium between strain and torsion. Contraction dynamics showed a decrease in the systolic time-to-peak (ΔTtP = -35.18 ± 28.81 ms; p < 0.001) and diastolic early recoil-rate (ΔRR = -20.01 ± 19.07 s-1; p < 0.001). The ejection fraction and metabolic parameters were unchanged. Circulating miR microarray revealed an up-regulation of miR122-5p. Network analysis predicted the matrix metalloproteinases (MMPs) MMP-16 and MMP-2 and their regulator (tissue inhibitors of metalloproteinases) as targets. In db/db mice we demonstrated that miR122-5p expression is associated with diabetic cardiomyopathy, that in the diabetic heart is overexpressed, and that, in vitro, it regulates MMP-2. Finally, we demonstrated that miR122-5p overexpression affects the extracellular matrix through MMP-2 modulation. CONCLUSIONS: Within 5 years of diabetic cardiomyopathy onset, increasing cardiac hypertrophy is associated with progressive impairment in strain, depletion of the compensatory role of torsion, and changes in viscoelastic contraction dynamics. These changes are independent of glycemic control and paralleled by the up-regulation of specific microRNAs targeting the extracellular matrix. (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes [CECSID]; NCT00692237).

Comparison of Infrapubic vs Penoscrotal Approaches for 3-Piece Inflatable Penile Prosthesis Placement: Do We Have a Winner?

BACKGROUND: The 3-piece inflatable penile prosthesis (IPP) is the gold standard treatment for male erectile dysfunction when other less invasive approaches are contra-indicated or unacceptable for the patient. There are currently 2 surgical approaches for IPP implantation: the penoscrotal (PS) and the infrapubic (IP) incision. AIM: To assess the most recent evidence on the impact of surgical approach for 3-piece IPP implantation in patients with erectile dysfunction. METHODS: A systematic literature review was performed using the MEDLINE (PubMed) and Cochrane Libraries databases in November 2017 to identify all studies investigating 3-piece IPP with a specified surgical access. OUTCOMES: The following key words were used in combination: "infrapubic," "transcrotal," "penoscrotal," "peno-scrotal," and "penile prosthesis." Additional references were obtained from the reference lists of full-text manuscripts. We used a narrative synthesis for the analyses of the studies. RESULTS: 22 Studies reporting data on 3-piece IPP implantation with a specified surgical approach were found in the literature. While IPPs are most commonly positioned through a PS incision, the IP approach is a faster procedure. No cases of glans hypoesthesia after IPP placement with an IP approach were reported, and the overall peri-prosthetic infection rate was 3.3% or less. Patient satisfaction rates were higher than 80% in both groups. CONCLUSIONS: Both the IP and PS approaches are viable and effective strategies for a 3-piece IPP placement, and result in high satisfaction rates. To date there is no evidence that an incision strategy may reduce infection rates. Penile sensory loss following an IP approach remains a virtual risk. It is recommended that the surgeon executing the implant have knowledge of both accesses and be capable of tailoring the incision strategy for complex cases. The chosen method should be based on the patient's specific anatomy, surgical history, and surgeon experience. Palmisano F, Boeri L, Cristini C, et al. Comparison of Infrapubic vs Penoscrotal Approaches for 3-Piece Inflatable Penile Prosthesis Placement: Do We Have a Winner? Sex Med Rev 2018;6:631-639.

Penoscrotal versus minimally invasive infrapubic approach for inflatable penile prosthesis placement: a single-center matched-pair analysis.

PURPOSE: To compare perioperative results, safety and efficacy profile in patients receiving inflatable penile prosthesis (IPP) via penoscrotal (PS) or minimally invasive infrapubic (MII) approach for erectile dysfunction. METHODS: A matched-pair analysis was performed including 42 patients undergoing IPP implantation via PS (n = 21) or MII (n = 21) between 2011 and 2016. Clinical and surgical data were prospectively collected. Patients' and partners' outcomes were assessed by the International Index of Erectile Function (IIEF), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaires. RESULTS: Mean (SD) operative time was 128 (40.6) min in group PS and 91 (43.0) min in group MII (p = 0.041). Complications occurred in 3/21 (14%) and 2/21 (10%) patients in groups PS and MII (p = 0.832). Overall, no differences were observed concerning the device utilisation (p = 0.275). However, in group MII 4/21 (19%) patients were able to resume sexual activity prior to 4 postoperative weeks, while in group PS no patient was (p = 0.012). Mean (SD) scores for questionnaires were similar between groups PS and MII: IIEF [20.9 (7.3) vs. 20.7 (4.8); p = 0.132], patient EDITS [76.0 (25.6) vs. 74.7 (20.8); p = 0.256] and partner EDITS [72.5 (29.1) vs. 73.1 (21.4); p = 0.114]. Similarly, QoLSPP showed comparable results among the groups PS and MII: functional domain [3.9 (1.4) vs. 4.0 (1.2); p = 0.390], personal [4.0 (1.2) vs. 4.1 (1.0); p = 0.512], relational [3.7 (1.5) vs. 3.9 (1.2); p = 0.462] and social [4.0 (1.2) vs. 3.9 (1.2); p = 0.766]. CONCLUSIONS: PS and MII demonstrated to be safe and efficient techniques, leading to high level of both patients and partners satisfaction. Additionally, the minimally invasive infrapubic approach showed a shorter operative time and a tendency for a faster return to sexual activity.

Urethral pseudodiverticulum secondary to penile fracture and complete urethra dissection.

A 22-year-old man reported cracking sound and acute pain during sexual intercourse followed by rapid penile detumescence and ecchymosis. He experienced more pain because he could not urinate and had a palpably full bladder. Moreover, his urethra was bleeding. Physical examination revealed swollen, ecchymotic and deviated penis and penis ultrasonography showed an injury of the tunica albuginea and Buck's fascia with an expanding hematoma. Suprapubic catheter was positioned. Surgical exploration revealed a tear of tunica albuginea of both corpora cavernosa and complete urethral dissection. End-to-end urethral anastomosis and suture of corpora cavernosa lesion were performed. Vescical catheter was mantained for 6 days and suprapubic catheter for 3 months to allow a complete urethral healing. A pseudodiverticulum was found at anastomosis level on the urethrocistography 1 month after surgery. It disappeared by allowing micturition via the suprapubic catheter. The patient presented regular urinary flow and physiological erections 30 days later. In our experience, prompt surgical repair preserved erectile function and keeping the suprapubic catheter protected the urethra; this was the correct management for repairing the urethral lesion.

Safe digital isolation of the santorini plexus during radical retropubic prostatectomy.

BACKGROUND: We describe a safe and easily reproducible technique to control Santorini plexus during radical retropubic prostatectomy (RRP) which uses simple digital dissection. METHODS: We retrospectively reviewed 56 consecutive patients who underwent RRP for clinically localised prostate cancer from November 2008 to November 2010. Santorini plexus was isolated and secured in all patients using a new technique of simple digital dissection in which the index finger is used not to only localize the catheter inside the urethra, but also to develop the right plane between Santorini plexus and urethra. This is obtained by gentle bilateral digital dissection through the lateral aspects of periprostatic fascia which are eventually breached by the fingers, developing a right plane just above the urethra. Santorini plexus is then easily ligated and divided. Indicators of outcomes included estimated blood loss, transfusion requirements, operative time, positive margins and complication rates of the technique. RESULTS: The maneuver was successful in 53/56 (95%) patients. Mean (range) blood loss and overall operative time for RRP were 620 ml (100-1500) and 130 min. (80-190), respectively. Transfusion rate was 8,9% (5/56). Positive surgical margin rate was 14% (8/56). No complication related to the employed technique was recorded. CONCLUSIONS: Digital dissection of Santorini plexus during RRP is simple and easily feasible. It speeds up the process of finding the right plane just above the urethra allowing good haemostasis in the surgical field and proper apical dissection.

Current and emerging strategies in bladder cancer.

Urothelial cell carcinoma is one of the most common malignancies of the urinary tract. The standard of care, intravesical chemo- and immunotherapy, while effective, is associated with a considerable side-effect profile and approximately 30% of patients either fail to respond to treatment or suffer recurrent disease within 5 years. In the setting of muscle-invasive urothelial carcinoma, use of neoadjuvant chemotherapy is associated with overall survival benefit. Muscle invasive bladder cancer is life threatening, showing modest chemosensitivity, and usually requires radical cystectomy. Although bladder cancer is fairly well-genetically characterized, clinical trials with molecularly targeted agents have, in comparison to other solid tumors, been few in number and largely unsuccessful. Hence, bladder cancer represents a considerable opportunity and challenge for alternative therapies. In this review, we will focus on promising global or pathway-based approaches (epigenetic modulators, kinase inhibitors, angiogenesis blockage, peroxisome proliferator-activated receptor γ agonists, apoptosis inductors, virus therapy) supported by a deeper understanding of molecular biology of urothelial carcinoma, which have been recently tested in clinical trials.

Bladder cancer: a simple model becomes complex.

Bladder cancer is one of the most frequent malignancies in developed countries and it is also characterized by a high number of recurrences. Despite this, several authors in the past reported that only two altered molecular pathways may genetically explain all cases of bladder cancer: one involving the FGFR3 gene, and the other involving the TP53 gene. Mutations in any of these two genes are usually predictive of the malignancy final outcome. This cancer may also be further classified as low-grade tumors, which is always papillary and in most cases superficial, and high-grade tumors, not necessarily papillary and often invasive. This simple way of considering this pathology has strongly changed in the last few years, with the development of genome-wide studies on expression profiling and the discovery of small non-coding RNA affecting gene expression. An easy search in the OMIM (On-line Mendelian Inheritance in Man) database using "bladder cancer" as a query reveals that genes in some way connected to this pathology are approximately 150, and some authors report that altered gene expression (up- or down-regulation) in this disease may involve up to 500 coding sequences for low-grade tumors and up to 2300 for high-grade tumors. In many clinical cases, mutations inside the coding sequences of the above mentioned two genes were not found, but their expression changed; this indicates that also epigenetic modifications may play an important role in its development. Indeed, several reports were published about genome-wide methylation in these neoplastic tissues, and an increasing number of small non-coding RNA are either up- or down-regulated in bladder cancer, indicating that impaired gene expression may also pass through these metabolic pathways. Taken together, these data reveal that bladder cancer is far to be considered a simple model of malignancy. In the present review, we summarize recent progress in the genome-wide analysis of bladder cancer, and analyse non-genetic, genetic and epigenetic factors causing extensive gene mis-regulation in malignant cells.

Randomized trial comparing an anterograde versus a retrograde approach to open radical prostatectomy: results in terms of positive margin rate.

OBJECTIVES: Surgical technique, patient characteristics and method of pathological review may influence surgical margin (SM) status. Positive surgical margin (SM+) rates of 14% to 46% have been reported in different radical retropubic prostatectomy (RRP) series. We evaluated the effect of an anterograde versus retrograde approach to RRP and specifically focused on the incidence of SM+. METHODS: From January 2003 to November 2007, we randomly assigned 200 patients with clinically localized prostate adenocarcinomas to undergo a retrograde (Group A) versus an anterograde (Group B) open RRP. All RRPs were performed at our institution by 2 surgeons. For all 200 patients, we evaluated a panel of clinical and pathological variables relating to their association with SM status. RESULTS: In Group A, 22% of cases after RRP showed a pT3 tumour and 39% of cases with a Gleason score >/=7 (4+3); in Group B, 20% of cases showed a pT3 tumour and 37% of cases with a Gleason score >/=7 (4+3) (p > 0.10). The incidence of SM+ was 18% in Group A and 14% in Group B (p = 0.0320). In Group A, 22.2% of cases with SM+ had multiple positive margins, whereas no cases in Group B showed multiple SM+. Regarding the localization of SM+, no difference was found between the 2 groups. In the multivariate analysis, only prostate-specific antigen (p = 0.0090 and p = 0.0020, respectively in the 2 groups) and pathological stage (p < 0.0001 in both groups) were significant and independently associated with SM+ occurrence. CONCLUSION: In our experience, the anterograde approach to open RRP is associated with lower SM+ rates and no risk of multiple SM+ when compared with the retrograde approach.

Prognostic significance of survivin-expressing circulating tumour cells in T1G3 bladder cancer.

OBJECTIVE: To evaluate the prognostic significance of survivin in tumour tissues and that of survivin-expressing circulating tumour cells (CTCs) in T1G3 bladder tumours, as the prognosis of T1G3 bladder cancer is highly variable and unpredictable from clinical and pathological prognostic factors. PATIENTS AND METHODS: The study included 54 patients with T1G3 non-muscle-invasive bladder cancer. Additional inclusion criteria were: tumour size <3 cm, absence of carcinoma in situ and multifocality. The planned follow-up was 24 months. Survivin was evaluated by reverse transcription-polymerase chain reaction in tumour tissues. CTCs were isolated from blood by CELLection Dynabeads (Invitrogen, Carlsbad, CA, USA) coated with the monoclonal antibody towards the human epithelial cell adhesion molecule. Cells were lysed and Dynabeads Oligo(dT) was used to capture poly A + mRNA. cDNA was synthesized and analysed for the expression of CD45, CK8 and survivin. The primary endpoint was disease-free survival (DFS); the favourable group at 24 months was defined as that with no clinical evidence of disease; the unfavourable group was that with evidence of recurrent disease or progressive disease. Tumour survivin expression and presence of CTC were correlated with DFS. Multivariate analysis was used to investigate whether the presence of CTC was an independent indicator of DFS. RESULTS: Survivin was found in half of the tumours; patients with survivin-negative tumours had a longer DFS than those with survivin-positive tumours (chi-square, P = 0.029). CTCs were found in 24/54 patients (44%); 92% of CTC expressed survivin. The difference in DFS between CTC-ve and CTC+ve patients was statistically significant (chi-square, P < 0.001). The presence of CTC was an independent prognostic factor for DFS (P < 0.001). CONCLUSION: The presence of CTC is an independent prognostic factor in patients with T1G3 bladder cancer.

A chemosensitivity test to individualize intravesical treatment for non-muscle-invasive bladder cancer.

OBJECTIVE: To describe the design of a new chemosensitivity assay based on the expression of genes involved in the resistance to standard intravesical regimens, to allow individualization of therapy for high-risk non-muscle-invasive bladder cancer. PATIENTS AND METHODS: To date, 35 patients with high-risk non-muscle-invasive bladder cancer have been enrolled, all candidates for transurethral resection of the bladder (TURB) followed by intravesical treatment. The intravesical regimen was chosen according to the risk profile of each patient. All patients were evaluated by cystoscopy 3 and 6 months after TURB. According to the molecular characterization of each tumour, our team of molecular oncologists determined for each patient a molecular profile of chemosensitivity to BCG, mitomycin c, anthracyclines and gemcitabine. This profile was then correlated to the response to intravesical therapy 6 months after TURB. RESULTS: This chemosensitivity test was able to predict response to treatment in 96% of patients. The assay is easy to perform, inexpensive and quick. CONCLUSION: Our results, although preliminary, are encouraging for the future of an individualized therapeutic approach, with the aim to provide a higher treatment success rate while sparing patients unnecessary toxicity from drugs that are not suited for their tumours.

Characterization of circulating blood dendritic cell subsets DC123+ (lymphoid) and DC11C+ (myeloid) in prostate adenocarcinoma patients.

PURPOSE: We verified whether prostate adenocarcinoma produces specific modifications in DC subsets count. METHODS: Twenty-one untreated prostate adenocarcinomas were divided on the basis of clinical stage in localized and metastatic disease. As control we used a population of 18 healthy male subjects. For DCs enumeration, peripheral blood (PB) samples were obtained in all cases. A single-platform flow cytometric assay based on Tru-COUNT was used for the enumeration of the two DCs subsets, myeloid (mDCs) and plasmacytoid (pDCs). RESULTS: We showed a statistically significant reduction in pDCs count in prostate cancer population when compared to healthy controls (P = 0.002). Comparing each clinical stage with healthy controls, significant differences were found between controls and the metastatic group in both pDCs and mDCs (P = 0.005 and P = 0.023 respectively) but not between controls and the localized group (P = 0.055 and P = 0.829 respectively). CONCLUSIONS: We showed that DCs count in PB is significantly affected by prostate adenocarcinoma progression in a metastatic disease.