Outcomes of primary ureteroscopic lithotripsy: The role of maximum ureteral wall thickness at the site of stone impaction.

OBJECTIVES: To verify if the maximum thickness of the ureteral wall at the stone site (m-UWT) can affect the outcomes of primary retrograde ureteroscopic lithotripsy (P-URSL) within a single-center dataset. MATERIAL AND METHODS: We retrospectively reviewed data on 354 consecutive URSL performed from January 2020 to May 2022 at "Fondazione Poliambulanza" in Brescia (Italy). We included patients older than 18 years who underwent URSL for a single ureteral stone with a maximum diameter ranging from 5 to 10 mm. Patients with anatomical abnormalities, a positive preoperative urinary culture, or without a NCCT performed during the acute event were excluded. Patients were treated in an emergency setting (P-URSL within 48 h from the diagnosis of acute ureteral colic) or in a delayed one (D-URSL after a period of maximum 90 days of ureteral double-j stenting). For the resulting 139 patients we recorded demographic, clinical and stone-related features and perioperative data. We processed these data by univariate and multivariate analysis, and with a logistic regression analysis. RESULTS: Of the 139 included procedures, 63 were P-URSL and 76 D-URSL. At the univariate analysis we found that stone diameter (OR 0.845, p = 0.017), stone volume (OR 0.023, p = 0.001), stone density (OR 0.998, p = 0.000) and m-UWT (OR 0.499, p = 0.013) are predictors of P-URSL. Stone density (OR 0.998, p = 0.002) is an independent predictor of P-URSL at the multivariate analysis. At a logistic regression analysis, a distal ureteric position (OR 0.189, p = 0.014), stone diameter (OR 1.289, p = 0.006), and m-UWT (OR 2.297, p = 0.02) were found to be statistically significant predictors of incomplete stone clearance in patients undergoing P-URSL. m-UWT is the only predictor of short-term postoperative adverse events in patients undergoing P-URSL (OR 3.386, p < 0.001). From a descriptive analysis, it emerged that an increased m-UWT (>2 mm) significantly correlates to an endoscopic finding of ureteritis' signs and to an increase in operative time, hospital stay and post-procedural stenting time. A m-UWT greater than 2 mm also correlates with a lower stone free rate (SFR) and with a significant increase in both short and long-term postoperative complications. CONCLUSIONS: Our study confirmed a connection between m-UWT and poor endoscopic findings, as well as a direct correlation with the main morphometric parameters of the stone and finally with the outcomes of P-URSL itself. Further studies are necessary to validate our results, so that m-UWT might be routinely considered a useful tool in the decision-making process for P-URSL.

Age represents the main driver of surgical decision making in patients candidate to radical cystectomy.

BACKGROUND AND OBJECTIVES: Age might influence the choice of surgical approach, type of urinary diversion (UD) and lymph node dissection (LND) in patients candidate to radical cystectomy (RC) for urothelial bladder cancer (UBC). Similarly, age may enhance surgical morbidity and worsen perioperative outcomes. We tested the impact of age (octogenarian vs. younger patients) on surgical decision making and peri- and postoperative outcomes of RC. METHODS: Non-metastatic muscle-invasive UBC patients treated with RC at 18 high-volume European institutions between 2006 and 2021 were identified and stratified according to age (≥80 vs. <80 years). Intraoperative Complications Assessment and Reporting with Universal Standards and European Association of Urology guidelines recommendations were accomplished in collection and reporting of, respectively, intraoperative and postoperative complications. Multivariable logistic regression models (MVA) tested the impact of age on outcomes of interest. Sensitivity analyses after 1:3 propensity score matching were performed. RESULTS: Of 1955 overall patients, 251 (13%) were ≥80-year-old. Minimally invasive RC was performed in 18% and 40% of octogenarian and younger patients, respectively (p < 0.001). UD without bowel manipulation (ureterocutaneostomy, UCS) was performed in 31% and 7% of octogenarian and younger patients (p < 0.001). LND was delivered to 81% and 93% of octogenarian and younger patients (p < 0.001). At MVA, age ≥80 years independently predicted open approach (odds ratio [OR]: 1.55), UCS (OR: 3.70), and omission of LND (OR: 0.41; all p ≤ 0.02). Compared to their younger counterparts, octogenarian patients experienced higher rates of intraoperative (8% vs. 4%, p = 0.04) but not of postoperative complications (64% vs. 61%, p = 0.07). At MVA, age ≥80 years was not an independent predictor of length of stay, intraoperative or postoperative transfusions and complications, and readmissions (all p values >0.1). These results were replicated in sensitivity analyses. CONCLUSIONS: Age ≥80 years does not independently portend worse surgical outcomes for RC. However, octogenarians are unreasonably more likely to receive open approach and UCS diversion, and less likely to undergo LND.

Robot-assisted vesico-vaginal fistula repair: technical nuances

ABSTRACT Introduction: Vesico-vaginal fistula (VVF) is a rare event in Western countries and are mainly consequent to iatrogenic injuries (1, 2). When conservative management fails, surgical repair is needed, although timing and surgical approach (open or minimally invasive (3)) are still controversial (4, 5). Herein we present a step-by-step description of robot-assisted vesico-vaginal fistula repair. Material and Methods: From 2015 to 2018 six patients underwent robotic vesico-vaginal fistula repair. Pre-operative cystoscopy was performed to identify the fistulous tract. The ureters were stented. A small catheter was inserted in the fistula. A longitudinal cystotomy was performed, then a dissection of the posterior bladder from the anterior vaginal wall was performed and the fistolous tract was excised. The vagina was sutured horizontally. Four patients underwent omental flap and two pericolic fat interposition. The bladder was closed with a double-layer suture. Results: All the vesico-vaginal fistulas developed after previous gynaecological surgery. The median operative time was 160 minutes [interquartile range (IQR) (146-177)]. Intraoperative blood loss was 25 (IQR 0-50) mL. No post-operative complications were recorded. Ureteral stents were removed at 4th post-operative day. Catheter was removed 13 (IQR 11-15) days after surgery after cystography assessment. One patient had Clavien I complication (ileus). Surgical pathology report was negative. No fistula recurrence was reported during follow-up. Conclusions: In our experience, robot-assisted fistula repair is a feasible and safe procedure. It presents the advantages of minimally invasive approaches and seems to provide low morbidity and good outcomes. Compared to transvaginal approach, the robotics allows to manage more complex cases with high success rate (6).

Applicability of COVID-19 Pandemic Recommendations for Urology Practice: Data from Three Major Italian Hot Spots (BreBeMi).

BACKGROUND: Lombardy has been the first and one of the most affected European regions during the first and second waves of the novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). OBJECTIVE: To evaluate the impact of coronavirus disease 2019 (COVID-19) on all urologic activities over a 17-wk period in the three largest public hospitals in Lombardy located in the worst hit area in Italy, and to assess the applicability of the authorities' recommendations provided for reorganising urology practice. DESIGN SETTING AND PARTICIPANTS: A retrospective analysis of all urologic activities performed at three major public hospitals in Lombardy (Brescia, Bergamo, and Milan), from January 1 to April 28, 2020, was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Join-point regression was used to identify significant changes in trends for all urologic activities. Average weekly percentage changes (AWPCs) were estimated to summarise linear trends. Uro-oncologic surgeries performed during the pandemic were tabulated and stratified according to the first preliminary recommendations by Stensland et al (Stensland KD, Morgan TM, Moinzadeh A, et al. Considerations in the triage of urologic surgeries during the COVID-19 pandemic. Eur Urol 2020;77:663-6) and according to the level of priority recommended by European Association of Urology guidelines. RESULTS AND LIMITATIONS: The trend for 2020 urologic activities decreased constantly from weeks 8-9 up to weeks 11-13 (AWPC range -41%, -29.9%; p < 0.001). One-third of uro-oncologic surgeries performed were treatments that could have been postponed, according to the preliminary urologic recommendations. High applicability to recommendations was observed for non-muscle-invasive bladder cancer (NMIBC) patients with intermediate/emergency level of priority, penile and testicular cancer patients, and upper tract urothelial cell carcinoma (UTUC) and renal cell carcinoma (RCC) patients with intermediate level of priority. Low applicability was observed for NMIBC patients with low/high level of priority, UTUC patients with high level of priority, prostate cancer patients with intermediate/high level of priority, and RCC patients with low level of priority. CONCLUSIONS: During COVID-19, we found a reduction in all urologic activities. High-priority surgeries and timing of treatment recommended by the authorities require adaptation according to hospital resources and local incidence. PATIENT SUMMARY: We assessed the urologic surgeries that were privileged during the first wave of coronavirus disease 2019 (COVID-19) in the three largest public hospitals in Lombardy, worst hit by the pandemic, to evaluate whether high-priority surgeries and timing of treatment recommended by the authorities are applicable. Pandemic recommendations provided by experts should be tailored according to hospital capacity and different levels of the pandemic.

Standard vs delayed ligature of the dorsal vascular complex during robot-assisted radical prostatectomy: results from a randomized controlled trial.

PURPOSE: Prospective randomized trial to compare standard vs delayed approach to dorsal vascular complex (s-DVC vs d-DVC) in robot-assisted radical prostatectomy (RARP). METHODS: Patients scheduled for RARP were randomized into a 1:1 ratio to receive either s-DVC or d-DVC by two experienced surgeons. In s-DVC arm an eight-shaped single stitch was given at the beginning of the procedure and the DVC was subsequently cut at time of apical dissection; in d-DVC arm the plexus was transected at the end of prostatectomy, prior to apex dissection and then sutured. Primary endpoint was difference in estimated blood loss (EBL) and a sample size of 226 cases was calculated; ad interim analysis was planned after 2/3 of recruitment. RESULTS: Endpoint was reached at ad interim analysis after 162 cases (81 s-DVC, 81 d-DVC) and recruitment was, therefore, interrupted. Baseline and tumor characteristics were overlapping. EBL was significantly higher in d-DVC arm (mean EBL 107 vs 65 ml, p = 0.003), but without differences in post-operative hemoglobin, transfusions and complications. Overall PSM rate was higher in d-DVC arm (21.0 vs 14.8%, p = 0.323), with statistical significance relatively to organ-confined disease (15.5 vs 3.6%, p = 0.031). Apical involvement was instead significantly higher in s-DVC arm (prevalence in PSM patients 66.7 vs 23.5%, p = 0.020). Post-operative PSA, continence and potency rates were similar between groups. CONCLUSIONS: Standard and delayed approaches to DVC are safe and lead to similar functional outcomes. A delayed approach exposes to a higher risk of PSM in organ-confined disease but with a lower risk of apical involvement.

Holographic Reconstructions for Preoperative Planning before Partial Nephrectomy: A Head-to-Head Comparison with Standard CT Scan.

BACKGROUND: Preoperative surgical planning before partial nephrectomy (PN) is a time-consuming and fragmentary process. OBJECTIVES: To evaluate the differences in the perception of renal anatomy between holographic reconstruction (HR) versus computed tomography (CT) in patients who are candidate to PN. METHODS: CT scans of 10 consecutive patients with intermediate/high complexity renal masses (R.E.N.A.L. score > 8) scheduled for robot-assisted PN were translated into HR. Seven raters independently described how they interpreted several anatomical details from CT and HR respectively. The exams were presented unpaired and randomly. Inter-observer agreement and evaluation time were assessed. A questionnaire inquired clinical utility of CT and HR. Inter-observer agreement was measured by the Cohen's kappa test. Evaluation time for CT and HR was compared by the Kruskal-Wallis test, overall and per rater. Examiners answered to the questionnaire following a Likert scale. RESULTS: HR showed a higher inter-observer agreement, reaching a good level (k > 0.6) for almost all the anatomical details considered. Conversely, CT generally provided a fair or poor agreement (k < 0.6). The evaluation time was shorter for HR (mean 1.7 vs. 3.4 min, p < 0.0001). All raters declared that HR could facilitate preoperative planning before PN. CONCLUSIONS: HR can be useful for preoperative surgical planning before PN to ease the understanding of anatomy.

Positive surgical margins and early oncological outcomes of robotic vs open radical prostatectomy at a medium case-load institution.

BACKGROUND: The aim of this study was to analyze the rates of positive surgical margins (PSM) after radical prostatectomy in patients undergoing robotic surgery (robot assisted laparoscopic prostatectomy [RALP]) compared with those undergoing open surgery (radical retropubic prostatectomy [RRP]), at an institution with medium case load. METHODS: Retrospective consultation of a perspectively-maintained database that stores the data of all the patients submitted to radical prostatectomy at our institution since 1/2008. The indication to RRP vs. RALP was based almost exclusively on the period of the study: RRP was the sole available option between 1/2008 and 3/2010 and afterwards RALP become the standard of treatment, once a learning curve of 50 cases was concluded. A PSM was defined as the presence of cancer at the inked surface of prostate. A univariate and multivariate binary logistic regression estimated which factors were related to PSMs. RESULTS: The data of 576 patients (285 RRP, 291 RALP) were evaluated. The overall PSM rate was 28.1% (162/414 patients; 20.6% for pT2 stage, 51.8% for pT>2); overall PSM rate for RRP vs. RALP was 31.9% vs. 24.4 % (P=0.044). At multivariable analysis the factors related to the risk of PSM were stage pT>2 (RR 2.979, P=0.001), Gleason Score >6 (RR 1.662, P=0.026), the volume of tumor (RR 1.019, P=0.008) and the surgical technique (RALP vs. RRP, RR 0.647, P=0.039). CONCLUSIONS: In a series from a medium case-load institution, once data are adjusted for local staging, tumor volume and Gleason score, the risk of PSM is lower for RALP than RRP. This evidence could be of support for health-care practitioners to introduce robotic systems.

[Short and medium term oncological results after robot-assisted prostatectomy: a comparative prospective non randomized study]. / Risultati oncologici a breve-medio termine dopo prostatectomia robotica: studio comparativo prospettico non randomizzato.

BACKGROUND: Our aim was to compare both the perioperative and the short/medium-term post-operative oncological results after radical prostatectomy between two groups of prostate cancer patients: one group treated with radical retropubic prostatectomy (RRP), the other one with robot-assisted laparoscopic prostatectomy (RALP). METHODS: We collected all the clinical, surgical, pathological and follow-up data of the patients who underwent radical prostatectomy with the two different surgical methods in a dedicated database. The positive surgical margins were defined by the presence of disease at the resection margin marked with China ink. The biochemical persistence of disease was defined as a PSA value >0.1 ng/mL 30 days after surgery, while the biochemical recurrence of the neoplasia was defined as a PSA value >0.2 ng/mL. RESULTS: The positive surgical margins (PSM) were identified as follows: 29.3% (RRP) versus 25.4% (RALP) in pT2 cancer (p 0.563), and 63.6% (RRP) versus 50.0% (RALP) in case of >pT2 cancer (p 0.559). If stratified by surgical approach, the results are: 53.3% (RRP) versus 25.6% (RALP) (p <0.001) in case of nerve-sparing technique. The persistence of disease is detectable in 5.4% (RRP) versus 4.6% (RALP), while the data on biochemical recurrence are: 2.7% (RRP) versus 0% (RALP). CONCLUSIONS: In our experience, in two groups of patients matched for clinic-pathological features who underwent RRP and RALP, oncological results are slightly better in the second group; this figure is even more significant when evaluating surgeries conducted with nerve-sparing technique. In this study we analyzed data of RALP, recently introduced in our center, comparing with RRP, a surgical technique consolidated through the decades. Therefore it can be said that even during the learning curve, RALP provides oncological results comparable to RRP.

Robot-assisted laparoscopic removal of perirenal lymphangioma: a case report.

The lymphangioma is a congenital malformation caused by abnormal development of the lymphatic vessels. The perirenal lymphangioma is extremely rare, and very few cases have been described in literature. A case of retroperitoneal perirenal lymphangioma is reported. Following recurring episodes of colic-like, right side back pain, a 16 year woman underwent an ultrasound which detected a multiloculated cystic lesion of 5 x 1 cm surrounding the lower pole of the right kidney. Subsequently a CT scan and an MRI detected, in the right perirenal space, a liquid multiloculated lesion, with no enhancement. Surgery was performed using the Da Vinci robotic system with transperitoneal access. Once dissection was concluded it was possible to identify a lymphatic duct coming from the renal pedicle, which likely drained the lesion, and selectively close it using clips. In conclusion, the cystic lymphangioma, must be considered among the differential diagnoses of retroperitoneal cystic lesions. These rare tumours have an excellent prognosis, with full remission of the symptomatology following complete surgical excision.

[Sliding-clip robotic nephropexy]. / Sliding-clip robotic nephropexy.

BACKGROUND: Nephroptosis is a clinical condition characterized by an abnormal caudal movement of the kidney that descends more than 2 vertebral bodies (or more than 5 cm) during a position change from supine to upright. In the last decade, the availability of laparoscopic surgery has led to a revival of interest in nephroptosis and nephropexy. We describe our technique for transperitoneal laparoscopic robotic-assisted nephropexy. METHODS: The surgery was performed on a 78-year-old woman with a BMI of 18 and ASA 2. The diagnosis of nephroptosis was preoperatively confirmed by excretory urography in the supine and upright positions. The patient was placed in Trendelemburg position on the left side. The laparoscopic surgery was performed, through a transperitoneal approach, using the daVinci system: the ptosic kidney was fixed using two separated stiches of non-absorbable prolene 2.0 between the superior surface of the kidney and the quadratus lumborum muscle. The sutures were fixed using Hem-o-lok clips. RESULTS: Intra- or post-operative complications have not occurred. The effectiveness of treatment was demonstrated by an intravenous urography 60 days after. CONCLUSIONS: Robotic-assisted nephropexy is a safe and effective procedure that leads to both clinical and aesthetic excellent results, comparable to the ones obtained with the laparoscopic approach for the treatment of symptomatic renal ptosis. The robotic-assisted nephropexy appears to be easier, with the particular advantages of the intracorporeal suturing and a better intraoperative view; the sliding-clips method allows reducing the organ trauma to the minimum.

[High-intensity focused ultrasound (HIFU): our experience in the treatment of prostate cancer relapsing after radiotherapy]. / Ultrasuoni focalizzati ad alta intensità (HIFU): la nostra esperienza nel trattamento del carcinoma prostatico recidivo a radioterapia.

The aim of the study is to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with local prostate cancer recurrence after radiotherapy. From February 2009 to June 2010, 14 patients with prostate cancer recurrence after radiotherapy were selected for HIFU treatment; all patients had a positive TRUS-guided biopsy and the absence of distant metastases was confirmed by computer tomography, PET choline or bone scintigraphy. We classified all patients in 3 groups using D'Amico's classification: 4 patients high risk (PSA >20 ng/ml - 8≤ Gleason Score≤ 10 - clinical stage≥T2c), 8 patients intermediate risk (10 PSAnadir+1.2ng/ml) or after adjuvant therapy introduction. All complications were recorded. Of the 14 patients selected, 12 patients underwent HIFU treatments; 2 patients were excluded because of rectal strictures induced by radiotherapy. At a mean 13 months' follow-up, biochemical success rate was obtained in 1 of the high risk patients and in 5 of the low and intermediate risk patients; 1 man died for a disease not correlated with prostate cancer recurrence. Complications included urinary tract infection, acute urinary retentions, urethral strictures and light stress incontinence. In our experience salvage HIFU is a safe treatment option for local relapse after radiotherapy; its efficacy depends on a careful patient selection.

Detection of muscarinic receptor subtypes in human urinary bladder mucosa: age and gender-dependent modifications.

AIMS: Muscarinic receptor subtypes expressed in the human urinary bladder mucosa were characterized, investigating whether there were gender-dependent differences and if aging could induce changes in their expression. METHODS: The study was carried out on 34 subjects, 22 men and 12 women, divided in four groups, based on gender and age. Gene expression was evaluated by quantitative RT-PCR. The Western blot was performed using the 4-12% NuPAGE Bis-Tris Gel System. RESULTS: The molecular expression of each subtype of the M(1) receptor family was observed and it was not influenced either by gender or age. M(2) receptor family transcripts revealed that both M(2) and M(4) were detected and that the M(2) transcripts were modified by both gender and age. Indeed, M(2) mRNA was lower in old rather than adult men (P < 0.05), but higher in rather old than adult women (P < 0.05). Further, adult men expressed more M(2) mRNA than adult women (P < 0.05), while the opposite was detected in old age (P < 0.05). The Western blot followed by quantification confirmed that the mRNAs were translated into proteins, and that the M(2) subtype showed similar modifications found at molecular level. DISCUSSION: The selective modification of M(2) receptors observed at the urinary bladder mucosa levels indicates that this anatomical structure could play an active role in the pathophysiology of micturition and supports evidence suggesting an effect of antimuscarinic drugs at this level. Whether these results may influence the age-dependent development of micturition disorders remains to be determined.

Fistulas between lower urinary tract and bowel: our experience in 15 years.

OBJECT: Fistulas between bowel and low urinary tract are not frequent and could be due to different causes. Diagnosis and treatment need a particular care to assure to patient a good result. Authors report their last 15-years experience. MATERIALS AND METHODS: From 1990 and 2005 22 patients have been quite carefully investigated and surgically treated; 17 men and 5 women of age between 39 and 81 years old. In particular 2 vesico-ileal fistulas, 12 colo-vesical have been treated: in all these situations we proceed by intestinal resection and fistulas repairing at the same time. Three rectovesical and 3 recto-urethral fistulas have been treated by fistula's way removal (with different approaches) and in a case by preparing a definitive urinary derivation. Finally, 2 complex fistulas have been treated by preparing a definitive urinary derivation. RESULTS: The typical symptoms presence must be carefully researched because it could be useful in diagnosis; radiological and endoscopic procedures could be useful for treatment planning, also if they have a quite low sensibility. In 20 cases, the treatment has achieved a good and lasting result. In 1 case we had a relapse, in another one patient died for sepsis. CONCLUSION: Diagnosis of fistulas has to be quite careful and it is necessary to plan the treatment, that is always surgical, also considering that sometimes it's leading to serious complications.

Evidence for the presence of alpha1 adrenoceptor subtypes in the human ureter.

AIM: Several studies have proposed a role for alpha1 adrenoceptors (ARs) in ureteral physiology, indicating that they are present in the ureter; however, few studies have been done to identify alpha1 AR subtypes present in this area. Thus, this study was carried out to characterize the alpha1 AR subtype gene and protein expression in proximal, medial, and distal region of the human ureter. METHODS: Molecular characterization of alpha1 AR subtypes were analyzed by semi-quantitative RT-PCR. alpha1 AR protein expression was studied by saturation binding curves and by competition binding curves with selective antagonists. Analysis of data was performed using the GraphPad PRISM 4 software. RESULTS: Analysis of saturation binding curves revealed a heterogeneous distribution of alpha1 AR binding sites, the B(max) for the distal ureter was indeed 52.5 +/- 5.4 fmol/mg prot, while a lower similar density of alpha1 ARs was demonstrated in the medial (25.2 +/- 1.7 fmol/mg prot) and proximal (23.4 +/- 0.4 fmol/mg prot) ureters. Molecular and pharmacological characterization of alpha1 AR subtypes indicated that each receptor was present, although with differences in terms of the amount expressed. CONCLUSIONS: Human ureter was endowed with each alpha1 AR subtype, although alpha1D and alpha1A ARs were prevalent over alpha1B ARs. Radioligand binding results revealed that there were no significant differences in the K(d) between ureteral regions, while a heterogeneous distribution of alpha1 AR binding sites was detected, with the highest density of alpha1 ARs in the distal ureter and a lower similar density in the medial and proximal ureters.

Alpha1 adrenoceptor subtypes in human urinary bladder: sex and regional comparison.

A detailed study of the presence of alpha1 AR binding sites and alpha1 AR subtype mRNA expression in human urinary bladder areas involved in the micturition (i.e. detrusor, trigone and neck) is reported here, investigating whether or not there are differences between sexes. Results obtained indicated that alpha1 AR proteins were detectable in each bladder area. In both sexes, the detrusor and the neck expressed similar levels of alpha1 ARs: respectively, detrusor: 14.6 +/- 1.2 in men and 13.1 +/- 1.1 fmol/mg prot in women; neck: 16.9 +/- 3.2 in men and 17.5 +/- 4.1 fmol/mg prot in women. In the trigone, significantly higher alpha1ARs were found in women compared to men (20.6 +/- 1.1 vs 11.7 +/- 0.7 fmol/mg prot). Subtype analysis indicated that in women, each area was endowed with mRNA encoding for each alpha1 AR subtype. The men detrusor expressed alpha1a and alpha1d ARs, while in the trigone and the neck, each subtype was present. Since the detrusor muscle hypertrophy is a marker of bladder obstructive outlet, the selective alpha1 AR subtype targeting arouses much interest, as evidence indicates that there are differences in signalling pathways among the subtypes. Furthermore, the significance of the alpha1 ARs coexpression is still unknown; interestingly, recent papers demonstrate that alpha1 AR subtypes could dimerize. Thus, in the human urinary bladder it may be suggested a potential level of alpha1 AR complexity that could have an impact on drug development.

Differential gene expression of cholinergic muscarinic receptor subtypes in male and female normal human urinary bladder.

OBJECTIVES: To study the mRNA expression of each muscarinic receptor subtype in bladder areas involved in micturition, such as the bladder dome, neck, and trigone. Our study focused on the analysis of the gene expression of muscarinic receptors in the human male and female urinary bladder. Other than the well-known role of bladder parasympathetic innervation, an extensive study of the muscarinic receptor mRNA distribution in male and female urinary bladder is still lacking. METHODS: The study was carried out on 5 female (age 56 +/- 10 years) and 5 male (age 70 +/- 9 years) patients. The patients selected for this study did not have any lower urinary tract symptoms, as determined by International Prostate Symptom Score questionnaire. The mRNAs encoding muscarinic receptor subtypes were assessed by reverse transcription-polymerase chain reaction, followed by Southern blot analysis. RESULTS: Using a molecular approach, we demonstrated the presence of all muscarinic receptor subtypes in the different urinary bladder areas involved in micturition; in particular, our data indicated that mRNAs encoding muscarinic receptors are largely expressed in all examined bladder areas, both in men and women, although with some remarkable differences and a peculiar distribution. CONCLUSIONS: Our results indicate that the pharmacology of the human bladder may be more complex than previously recognized. Furthermore, the choice to study each biopsy as a single sample and not use a pool of tissues allowed us to point out the individual variability between subjects and sex-related differences in the expression profile of muscarinic receptor subtype mRNAs.