The Model of Interstitial Cystitis for Evaluating New Molecular Strategies of Interstitial Regeneration in Humans.

Given the recent evidence in the clinical application of regenerative medicine, mostly on integumentary systems, we focused our interests on recent bladder regeneration approaches based on mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), and hyaluronic acid (HA) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. IC/BPS is a heterogeneous chronic disease with not-well-understood etiology, characterized by suprapubic pain related to bladder filling and urothelium dysfunction, in which the impairment of immunological processes seems to play an important role. The histopathological features of IC include ulceration of the mucosa, edema, denuded urothelium, and increased detection of mast cells and other inflammatory cells. A deeper understanding of the molecular mechanism underlying this disease is essential for the selection of the right therapeutic approach. In fact, although various therapeutic strategies exist, no efficient therapy for IC/BPS has been discovered yet. This review gives an overview of the clinical and pathological features of IC/BPS, with a particular focus on the molecular pathways involved and a special interest in the ongoing few investigational therapies in IC/BPS, which use new regenerative medicine approaches, and their synergetic combination. Good knowledge of the molecular aspects related to stem cell-, PRP-, and biomaterial-based treatments, as well as the understanding of the molecular mechanism of this pathology, will allow for the selection of the right and best use of regenerative approaches of structures involving connective tissue and epithelia, as well as in other diseases.

New concept in urologic surgery: The total extended genital sparing radical cystectomy in women.

INTRODUCTION AND OBJECTIVES: The aim of the study was to evaluate genital sparing radical cystectomy surgery in female patients from the point of view of both oncologic and functional outcomes (with emphasis on urinary and sexual outcomes) in a single high-volume center for the treatment of muscular invasive bladder cancer. MATERIALS AND METHODS: Between January 2014 and January 2018, 14 female patients underwent radical cystectomy with preservation of genital organs (the entire vagina, uterus, fallopian tubes, ovaries) and orthotopic urinary neobladder (Padua neobladder). Inclusion criteria were recurrent T1G3 tumors; refractory tumors after BCG therapy without associated carcinoma in situ (CIS); T2 or T3a tumors entirely resected at endoscopic transurethral resection of the bladder and not involving urethra/bladder trigone. Exclusion criteria were: T3b or higher bladder cancer, associated CIS and involvement of urethra or bladder trigone. Oncological and histopathological outcomes (Overall Survival - OS, Recurrence Free Survival - RFS), urinary outcomes (day and night incontinence, intermittent catheterization use, Sandvik Score) and sexual outcomes (Female Sexual Function Index 19 FSFI-19) were considered. The average follow-up time was 56 months. RESULTS: Considering oncological outcomes, histologic examination reported urothelial carcinoma in 13/14 patients; 8/13 patients (61.5%) had high grade T1 stage, 3/13 patients (23%) had high grade T2 stage and finally 2/13 patients (15.5%) had high-grade T3 stage. One patient presented with embryonal rhabdomyosarcoma completely excised after surgery (PT2aN0M0). No patient developed local or metastatic recurrence (RFS 100%); OS was 100%. Considering urinary continence outcomes, 12/14 patients retained daytime and nighttime continence (85.5%); 2/14 (14.5%) complained of low stress urinary incontinence daily and nighttime urinary leakage. The Sandvik Score showed complete continence in 7/14 patients (50%); mild degree incontinence in 6/14 patients without use of incontinence devices (43%); moderate degree of incontinence in one patient (7%). The FSFI administered at 1 year from the surgery showed sexual desire in all patients (100%); subjective arousal, achievement of orgasm and sexual satisfaction in 12/14 patients (85.5%); sufficient lubrication in 11/14 patients (78.5%). Only one patient (7%) complained about dyspareunia during sexual intercourse. CONCLUSIONS: Our study aims to demonstrate that genital-sparing radical cystectomy is a safe surgery in terms of oncologic outcomes and, most importantly, that it is beneficial in terms of urinary and sexual function. Indeed, patients' quality of life together with their psychological and emotional health should be put on the same level as oncological safety. However, it is a treatment reserved for selected patients who are strongly motivated to preserve fertility and sexual function and thoroughly informed about the benefits and complications of such a procedure.

Sexual and functional outcomes after prolapse surgery: a randomized prospective comparison of trocarless transvaginal mesh and pelvic organ prolapse suspension.

PURPOSE: Stress urinary incontinence (SUI) related to pelvic organ prolapse represents a common condition that negatively impacts female sexual activity. Laparoscopic pelvic organ prolapse surgery (POPs) and the anterior repair with a trocar-less trans-vaginal mesh (TTMs) represent two different surgical techniques to treat SUI secondary to POP. This study aimed to report the results of these techniques comparing the sexual and functional outcome improvement. MATERIALS AND METHODS: Fifty-nine sexually active female patients, complaining of urodynamic stress incontinence, were enrolled in this prospective study, and simply randomized in two groups: 29 POPs and 30 TTMs. All patients were studied at baseline and 6 months after surgery. Preoperative evaluation included medical history, urodynamic test, Female Sexual Function Index (FSFI), and pelvic magnetic resonance defecography. Six months after surgery, all patients completed the FSFI and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and were investigated with a uroflowmetry test with post-void residual volume (PVR). RESULTS: At 6 months after surgery, 87% of POPs patients and 79% of TTMs subjects resulted dry. No statistically significant results were obtained in terms of urinary outcomes between the two surgical groups. Regarding sexual function, POPs group exhibited a significant greater improvement of global FSFI (mean: 27.4; SD: 4.31) compared to TTMs group (mean FSFI: 23.56; SD: 2.28; p-value ≤ 0.0001). CONCLUSIONS: Our results indicated that POPs and TTMs lead to satisfactory and safe functional outcomes with a good recovery of urinary continence. Furthermore, POPs, when compared to TTMs, led to a greater improvement of sexual function.

Possible role of 5-alpha reductase inhibitors in non-invasive bladder urothelial neoplasm: multicenter study.

BACKGROUND: About 75% of urothelial bladder cancers are non-muscle invasive (NMIBC), and limited to mucosa (Ta or CIS) or sub-mucosa (T1). An increase of androgen expression and androgen receptors has a positive effect on oncogenic expression. We aimed to evaluate whether 5-alpha reductase inhibitors (5-ARI) have a role in NMIBC. METHODS: We retrospectively evaluated the clinical and pathological data of 423 patients with NMIBC who underwent transurethral bladder resection. We considered the number of resections, number of total recurrences, time of recurrences, and histopathology details. The population was classified into two groups: treated and untreated with 5-ARIs. The enrolled patients were in treatment with 5ARIs for symptomatic prostatic hyperplasia for at least 12 months. Mean follow-up time was 30.43 months. RESULTS: Patients treated with 5-ARIs had a lower rate of recurrence (14%) than the untreated group (37%). There was a significant difference in the mean number of recurrences between the untreated and the treated group (P=0.006). Furthermore, the treated group showed a significantly greater number of low than high grade tumors, compared to the untreated group (P≤0.05). There was a significant decrease in the number of muscle invasive tumors in treated patients (P=0.032). The recurrence-free survival rate of patients treated with 5-ARIs was significantly higher (P=0.0001). CONCLUSIONS: Long-term treatment with 5-ARIs might reduce the risk of bladder tumor recurrence, extension of lesions and increase the recurrence-free survival rate. A long-term, randomized prospective study could definitively assess the possible role of these drugs.

Feasibility of local anaesthesia for varicocele correction in one-day-surgery setting. A single center experience.

OBJECTIVE: In this study, we compared postoperative outcomes of patients submitted to varicocele correction under general or local anesthesia at a single center. METHODS: All patients underwent varicocele surgical treatment with the Colpi-modified Marmar subinguinal technique. They were managed with either general (Group A) or local with ileo-inguinal and ileo-hypogastric nerves block (Group B) anesthesia. The two groups were compared in terms of timing of discharge and post-operative pain as assessed with the numeric rating scale (NRS) at both rest and movement (NRSm). § Results: Overall, 63 patients were included with a mean (SD) age of 25 years ± 5 yrs. The NRS mean score was significantly lower for Group B during the first 4 days after surgery at both rest and movement (all p < 0.05). Patients receiving local anesthesia showed a faster time to first urination (210 vs. 240 min; p = 0.02), although the time to discharge was comparable between the two groups (250 vs. 250 min). CONCLUSIONS: These results suggest that local anetshesia for varicocele surgical treatment is feasible and provide better pain control and faster recovery after surgery.

Shear wave elastography in varicocele patients: Prospective study to investigate correlation with semen parameters and histological findings.

AIMS: Shear wave elastosonography (SWE) is a non-invasive ultrasound imaging modality used to assess the mechanical properties of tissues such as rigidity and elasticity. In this prospective study, we investigated the effect of laparoscopic varicocelectomy on the elasticity, degree of fibrosis and function of the testes through SWE and we evaluated the correlation with semen parameters and histology findings. METHODS: Male patients with monolateral left varicocele and progressive alteration of the semen quality were enrolled prospectively. Patients were evaluated before varicocelectomy, 3 and 6 months after surgery with semen analysis, ecocolordoppler US and SWE. In all patients, a left testicular biopsy was performed at the time of varicocelectomy and it was repeated after 6 months in 55% of patients in order to investigate the histological findings and to correlate with SWE results. RESULTS: The study was conducted on 82 patients. SWE showed a statistically significant difference between left and right testicles. Three months after surgery the mean left testicular volume increased, mean left SWE features decreased, and sperm count increased (P values < .0001). The SWE parameters, testicular volume and semen analysis values showed a statistically significant positive correlation between the pre and postoperative results (P value < .0001). The histological alterations were significantly changed 6 months postoperative with a complete morphology recovery in accordance with SWE results. CONCLUSIONS: SWE showed a statistically significant positive correlation with testicular volume, semen analysis and histological findings. This study represents the first investigation that correlates the varicocele, the testis volume, the quality of the seminal fluid ant the histological findings with the ultrasound and SWE values.

Holmium laser enucleation of prostate versus minimally invasive simple prostatectomy for large volume (≥120 mL) prostate glands: a prospective multicenter randomized study.

BACKGROUND: The aim of this study was to compare the perioperative and functional results between laparoscopic and robot-assisted simple prostatectomy (LSP and RASP) and Holmium laser enucleation of prostate (HoLEP) in prostate volumes ≥120 mL. The primary endpoint was to investigate and compare minimally invasive techniques in the management of large prostate gland volume, and the secondary endpoint was to evaluate the frequency and type of postoperative complications according to Clavien Dindo Classification. METHODS: This multicenter study was conducted on male patients with LUTS associated with BPO candidates for surgical treatment. The surgery approach choice in relation to the prostatic volume ≥120 mL was HoLEP or minimally-invasive simple prostatectomy (LSP or RASP). All patients were prospectively randomized into three groups, according to a simple computed randomization: HoLEP, LSP and RASP groups. During the follow-up, all patients underwent postoperative control at 1, 3, 6, 12 and 24 months from the surgical procedure. RESULTS: One hundred ten male patients were randomized in three homogeneous groups: 36 in LSP, 32 in RASP and 42 in HoLEP group. During the follow-up (mean 26.15 months), despite the significant improvement compared to baseline results, no significant differences were shown, between the groups in terms of functional and perioperative outcomes. The only statistically significant data was reported for catheterization time, that resulted longer in the LSP group than RASP and HoLEP groups (P=0.002). Furthermore, MISP resulted in longer hospitalization, and lower rate of patients with new-onset irritative symptoms. CONCLUSIONS: This prospective randomized study is the first to compare extraperitoneal LSP, RASP and HoLEP in the treatment of LUTS secondary to benign prostatic hyperplasia for prostate volumes ≥120 mL. Our findings confirm the safety and efficacy of MISP, demonstrating its equivalence in functional outcomes and perioperative morbidity in comparison to HoLEP.

Robot-assisted retroperitoneal lymphadenectomy in patient with type I papillary renal cancer recurrence after 5 years of follow-up.

Papillary renal cell carcinoma (PRCC) is a rare cancer and is the second most frequent histologic type among all renal cell carcinoma, accounting for up to 15%. A 72-year-old man underwent a right radical nephrectomy 7 years ago with final histopathology diagnosis of type 1 PRCC with negative surgical margins. Five years after surgery, computed tomography scan imaging showed the presence of multiple masses suspicious for node recurrences disease localized in the renal lodge, in the inter-aorto-caval space, at the iliac vessels bifurcation and right common iliac vessels. Patient underwent a robotic retroperitoneal lymphadenectomy. The histopathological examination confirmed the recurrence of type I papillary renal cancer in all the specimens. No further recurrences have been observed at 24-month follow-up after surgery. This report is the first describing a robot-assisted minimally invasive surgical excision for type I papillary renal cancer nodal and renal fossa recurrences.

Sexual and functional outcomes of prostate artery embolisation: A prospective long-term follow-up, large cohort study.

AIM OF THE STUDY: Among minimally invasive procedures for treating benign prostate hyperplasia (BPH) prostate artery embolisation (PAE) is described as safe and effective. Aim of this study is to report our results, focusing on sexual outcomes (erectile and ejaculatory functions sparing) of PAE in patients suffering from bladder outlet obstruction (BOO) secondary to BPH. METHODS: We prospectively enrolled and submitted to PAE subjects suffering from BOO secondary to BPH. All patients were not suitable for surgery or declined invasive approaches. All subjects were preoperatively and postoperatively (3, 6, 12 and 18 months after) evaluated by urinary flowmetry, post voiding residual volume, prostate volume, serum PSA levels, International Index of Erectile Function, International Prostate Symptom Score and QoL scores. RESULTS: PAE was performed in 147 patients (mean age 72.5 y.o.). PAE was technically successful in all patients. The procedure lasted a mean time of 94.3 minutes, with a mean fluoroscopic time of 42.5 minutes. Twelve months follow-up data were available for all patients, while 126 patients (85%) completed the 18 months follow up. At 12 months follow up, the mean IPSS and QoL scores significantly decreased, and all the objective parameters (mean Qmax, PVR and prostate volume) reported a significant improvement. A total of 130 patients (88.5%) at 12 months reported the antegrade ejaculation preserved, and a slight not significant improvement of IIEF scores. The 18 months after PAE outcomes confirmed the significant improvement of all the variables evaluated (even for PSA values and IIEF scores). No major complications occurred. CONCLUSIONS: Our results evidence prostate artery embolisation as highly feasible and safe procedure with interesting outcomes. In particular, in our study PAE reported promising results in preserving antegrade ejaculation and erectile function. Our data are in line with the literature, confirming how PAE reduces obstructive symptoms in BPH patients not suitable or refusing standard surgical approaches.

Successful treatment with pollen extract of hematospermia in patients with xanthogranolomatous prostatitis.

INTRODUCTION: The aim of this study was to report our experience in the management of hematospermia observed in 16 patients suffering from xanthogranulomatous prostatitis. METHODS: Recurrent episodes of hematospermia were the onset symptom in all patients, and in 25% of patients it was combined with fever. All patients reported PSA value elevation and the digital rectal examination (DRE) revealed an increase of the gland size and of its consistency in all cases. In all patients, the hematospermia was treated with the oral administration of two tablets of pollen extract in a single (1 g) dose daily for 30 days. RESULTS: Sixteen patients were observed between 2008 and 2016, referring hematospermia, progressive lower urinary tract symptoms (LUTS), and serum PSA level increase. To exclude the prostate cancer presence all patients were submitted to transperineal TRUS guided biopsy. In all the patients complete resolution of hematospermia was achieved treatment with pollen extract. All patients were subsequently treated for LUTS (alpha-adrenergic blockers), but none reported any significant improvement of symptoms. Basing on these pieces of evidence, after 90 days of alpha-blockers therapy, all patients underwent bipolar TURP. Histological examination of resected prostatic tissue revealed in all patients the diagnosis of xanthogranulomatous prostatitis. CONCLUSIONS: Patients with xanthogranulomatous prostatitis especially experience irritative symptoms, sometimes combined with fever or hematospermia. Hematospermia as the onset symptom has not been reported so far. The administration of the pollen extract for 30 days was associated with a complete resolution of hematospermia.