Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial

Background

Urinary tract infection (UTI) is a prevalent condition in women during their lifetime with a high rate of recurrence within 3–6 mo.

Objectives

Our aim was to investigate the efficacy and tolerability of the intravesical administration of combined hyaluronic acid (HA) and chondroitin sulphate (CS) in female patients with a history of recurrent UTI.

Design, setting, and participants

We conducted a prospective, randomised, double-blind, placebo-controlled study comparing the intravesical instillation of HA-CS with placebo in women with recurrent UTI.

Intervention

Participants were randomised to receive 50 ml of sterile sodium HA 1.6% and CS 2.0% solution (IALURIL^®) weekly for 4 wk and then monthly for 5 mo.

Measurements

The primary end point of the study was defined as the mean number of UTI per patient per year. Participants were evaluated addressing UTI status/urinary symptoms and with a general health-related quality-of-life (QoL) questionnaire at baseline and after 3, 6, 9, and 12 mo.

Results and limitations

In the intention-to-treat analysis, 57 women were randomly allocated to HA-CS (n = 28) or placebo (n = 29). The UTI rate per patient per year at the end of the study (12 mo) (mean ± SD: −86.6% ± 47.6 vs −9.6% ± 24.6; mean difference: 77%; 95% confidence interval, 72.3–80.8; p = 0.0002) and the mean time to UTI recurrence (52.7 ± 33.4 vs 185.2 ± 78.7 d; p < 0.001) were significantly reduced after treatment with HA-CS compared with placebo. Overall urinary symptoms and QoL measured by questionnaires significantly improved compared with placebo (Pelvic Pain and Urgency/Frequency questionnaire symptom score: 14.53 ± 4.32 vs 9.88 ± 6.77; p = 0.004; SF-36 QoL score: 78.6 ± 6.44 vs 53.1 ± 4.72; p < 0.001). No serious adverse event was reported.

Conclusions

Compared with placebo, HA-CS intravesical instillations significantly reduced UTI rate without severe side effects while improving symptoms and QoL over a 12-mo period in patients with recurrent UTI.

Trial registration

ISRCTN 76354426.     

Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades

Background

Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns.

Objective

To assess the relation of biopsy and RP grade in the largest study to date.

Design, setting, and participants

A total of 7643 totally embedded RP and corresponding needle biopsies (2004–2010) were analyzed according to the updated Gleason system.

Interventions

All patients underwent prostate biopsy prior to RP.

Measurements

The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression.

Results and limitations

A total of 36.3% of cases were upgraded from a needle biopsy GS 5–6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3 + 4 = 7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4 + 3 = 7, RP GS was almost equally 3 + 4 = 7 and 4 + 3 = 7. Biopsy GS 8 led to an almost equal distribution between RP GS 4 + 3 = 7, 8, and 9–10. A total of 58% of the cases had matching GS 9–10 at biopsy and RP. In multivariable analysis, increasing age (p < 0.0001), increasing serum prostate-specific antigen level (p < 0.0001), decreasing RP weight (p < 0.0001), and increasing maximum percentage cancer/core (p < 0.0001) predicted the upgrade from biopsy GS 5–6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient.

Conclusions

Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy.     

Laparoendoscopic Single-Site Nephrectomy Compared with Conventional Laparoscopic Nephrectomy: A Systematic Review and Meta-analysis of Comparative Studies

Context

Laparoendoscopic single-site (LESS) surgery has increasingly been used to perform radical, partial, simple, or donor nephrectomy to reduce the morbidity and scarring associated with surgical intervention. Studies comparing LESS nephrectomy (LESS-N) and conventional laparoscopic nephrectomy (CL-N) have reported conflicting results.

Objective

To assess the current evidence regarding the efficiency, safety, and potential advantages of LESS-N compared with CL-N.

Evidence acquisition

We comprehensively searched PubMed, Embase, and the Cochrane Library and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and retrospective comparative studies assessing the two techniques.

Evidence synthesis

Two RCTs and 25 retrospective studies including a total of 1094 cases were identified. Although LESS-N was associated with a longer operative time (weighted mean difference [WMD]: 9.87 min; 95% confidence interval [CI], 3.37–16.38; p = 0.003) and a higher conversion rate (6% compared with 0.3%; odds ratio: 4.83; 95% CI, 1.87–12.45; p = 0.001), patients in this group might benefit from less postoperative pain (WMD: −0.48; 95% CI, −0.95 to −0.02; p = 0.04), lower analgesic requirement (WMD: −4.78 mg; 95% CI, −8.59 to −0.97; p = 0.01), shorter hospital stay (WMD: −0.32 d; 95% CI, −0.55 to −0.09; p = 0.007), shorter recovery time (WMD: −5.08 d; 95% CI, −8.49 to −1.68; p = 0.003), and better cosmetic outcome (WMD: 1.07; 95% CI, 0.67–1.48; p < 0.00001). Perioperative complications, estimated blood loss, warm ischemia time, and postoperative serum creatinine levels of graft recipients did not differ significantly between techniques.

Conclusions

LESS-N offers a safe and efficient alternative to CL-N with less pain, shorter recovery time, and better cosmetic outcome. Given the inherent limitations of the included studies, future well-designed RCTs are awaited to confirm and update the findings of this analysis.     

Effects of the gonadotropin-releasing hormone antagonist ganirelix on normal micturition and prostaglandin E(2)-induced detrusor overactivity in conscious female rats

Background

Gonadotropin-releasing hormone (GnRH) antagonists have been reported to have beneficial effects on lower urinary tract symptoms in patients with benign prostatic hyperplasia.

Objective

Our aim was to investigate the effects of ganirelix, a GnRH receptor antagonist, on bladder function and detrusor overactivity (DO) in female rats.

Design, setting, and participants

Female Sprague-Dawley rats received 2 wk of daily systemic (0.1 mg/kg) or acute intravesical administration (IVES; 0.14 mg/l or 1.4 mg/l) ganirelix or vehicle (controls).

Measurements

Assessments were obtained using cystometry in awake rats, organ bath studies, enzyme-linked immunosorbent assay, and western blot (WB).

Results and limitations

Luteinising hormone levels were lower in rats treated systemically with ganirelix than in controls. No differences were observed in body or bladder weights. Micturition interval (MI), micturition volume (MV), residual volume, and bladder capacity (BC) were similar in both groups at baseline. No differences in urodynamic pressure parameters were observed between groups at baseline. Intravesical prostaglandin E₂ reduced MI, MV, and BC, and it increased basal pressure (BP), threshold pressure (TP), flow pressure (FP), and maximum pressure (MP) in all rats. MI, MV, and BC were reduced by 43% ± 4%, 50% ± 4%, and 43% ± 4% (controls) versus 22% ± 3%, 23% ± 3%, and 21% ± 3% (ganirelix-treated rats; p < 0.001). TP and FP increased by 38% ± 8% and 30% ± 4% (controls) versus 16% ± 7% and 16% ± 5% (ganirelix; p < 0.05). The maximal force of contractions for carbachol was larger in detrusor from ganirelix-treated rats (231% vs 177% of 60 mM K+-induced contractions). At 0.14 mg/l, but not 0.14 mg/l, IVES ganirelix increased MI, MV, and BC and decreased BP, TP, FP, and MP. In vitro, ganirelix had no effect on detrusor function. The gonadotropin-releasing hormone receptor was expressed (by WB) in the bladder mucosa.

Conclusions

Systemic treatment with ganirelix counteracted experimental DO in female rats. Because bladder preparations from these rats exhibited larger contractions to carbachol and because intravesical ganirelix affected both micturition intervals and urodynamic pressure profiles, a peripheral site of action of ganirelix in the urinary bladder cannot be excluded.     

Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial

Background

Acupuncture therapy has been used by many researchers in both male and female sexual dysfunction studies.

Objective

To determine whether acupuncture is effective as a premature ejaculation (PE) treatment compared with paroxetine and placebo.

Design, setting, and participants

The study was conducted with methodologic rigor based on Consolidated Standards of Reporting Trials (CONSORT) criteria. Ninety patients referred to the urology clinic at a tertiary training and research hospital with PE were included in this randomized controlled trial and randomly assigned into paroxetine, acupuncture, and placebo groups. Heterosexual, sexually active men aged between 28 and 50 yr were included. Men with other sexual disorders, including erectile dysfunction; with chronic psychiatric or systemic diseases; with alcohol or substance abuse; or who used any medications were excluded.

Intervention

The medicated group received paroxetine 20 mg/d; the acupuncture or sham-acupuncture (placebo) groups were treated twice a week for 4 wk.

Measurements

Intravaginal ejaculation latency times (IELTs) and the Premature Ejaculation Diagnostic Tool (PEDT) were used to assess PE. IELTs were calculated by using a partner-held stopwatch. Data were analyzed statistically.

Results and limitations

Median PEDT scores of paroxetine, acupuncture, and placebo groups were 17.0, 16.0, and 15.5 before treatment, and 10.5, 11.0, and 16.0 after treatment, respectively (p = 0.001, p = 0.001, and p = 0.314, respectively). Subscores after treatment were significantly lower than subscores before treatment in the paroxetine and acupuncture groups but remained the same in the placebo group. Significant differences were found between mean-rank IELTs of the paroxetine and placebo groups (p = 0.001) and the acupuncture and placebo groups (p = 0.001) after treatment. Increases of IELTs with paroxetine, acupuncture, and placebo acupuncture were 82.7, 65.7, and 33.1 s, respectively. Extent of ejaculation delay induced by paroxetine was significantly higher than that of acupuncture (p = 0.001). The most important limitation of the study was the lack of follow-up.

Conclusions

Although less effective than daily paroxetine, acupuncture had a significant stronger ejaculation-delaying effect than placebo.     

Botulinum toxin a versus placebo for refractory detrusor overactivity in women: a randomised blinded placebo-controlled trial of 240 women (the RELAX study)

Background

Emerging data suggest botulinum toxin is an effective treatment for detrusor overactivity (DO), but large studies confirming efficacy and safety are lacking.

Objective

Study the efficacy and safety of onabotulinumtoxinA (onaBoNTA) for the treatment of DO.

Design, setting, and participants

A double-blind placebo-controlled randomised trial in eight UK urogynaecology centres was conducted between 2006 and 2009. A total of 240 women with refractory DO were randomised to active or placebo treatment and followed up for 6 mo.

Intervention

Treatment consisted of 200 IU onaBoNTA or placebo injected into the bladder wall (20 sites; 10 IU per site in 1 ml saline).

Measurements

Primary outcome was voiding frequency per 24 h at 6 mo. Secondary outcomes included urgency and incontinence episodes and quality-of-life data. Intention-to-treat analysis was used with imputation of missing data.

Results and limitations

A total of 122 women received onaBoNTA and 118 received the placebo. Median (interquartile range) voiding frequency was lower after onaBoNTA compared with placebo (8.3 [6.83–10.0] vs 9.67 [8.37–11.67]; difference: 1.34; 95% confidence interval [CI], 1.00–2.33; p = 0.0001). Similar differences were seen in urgency episodes (3.83 [1.17–6.67] vs 6.33 [4.0–8.67]; difference: 2.50; 95% CI, 1.33–3.33; p < 0.0001) and leakage episodes (1.67 [0–5.33] vs 6.0 [1.33–8.33]; difference: 4.33; 95% CI, 3.33–5.67; p < 0.0001). Continence was more common after botulinum toxin type A (BoNTA; 31% vs 12%; odds ratio [OR]: 3.12; 95% CI, 1.49–6.52; p = 0.002). Urinary tract infection (UTI; 31% vs 11%; OR: 3.68; 95% CI, 1.72–8.25; p = 0.0003) and voiding difficulty requiring self-catheterisation (16% vs 4%; OR: 4.87; 95% CI, 1.52–20.33; p = 0.003) were more common after onaBoNTA.

Conclusions

This randomised controlled trial of BoNTA for refractory DO, the largest to date, confirms efficacy and safety of the compound. UTI (31%) and self-catheterisation (16%) are common. A third of women achieved continence.

Trial registration

The study received ethical committee approval from the Scottish Multicentre Research Ethics Committee (reference: 04/MRE10/67). The trial has a EudraCT number (2004-002981-39), a clinical trial authorisation from the UK Medicines and Healthcare Regulatory Agency, and it was registered on Current Controlled Trials (ISRCTN26091555) on May 26, 2005.     

Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial

Background

Tadalafil improved lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH; LUTS/BPH) in clinical studies but has not been evaluated together with an active control in an international clinical study.

Objective

Assess tadalafil or tamsulosin versus placebo for LUTS/BPH.

Design, setting, and participants

A randomised, double-blind, international, placebo-controlled, parallel-group study assessed men ≥45 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥13, and maximum urinary flow rate (Q_max) ≥4 to ≤15 ml/s. Following screening and washout, if needed, subjects completed a 4-wk placebo run-in before randomisation to placebo (n = 172), tadalafil 5 mg (n = 171), or tamsulosin 0.4 mg (n = 168) once daily for 12 wk.

Measurements

Outcomes were assessed using analysis of covariance (ANCOVA) or ranked analysis of variance (ANOVA) (continuous variables) and Cochran-Mantel-Haenszel test or Fisher exact test (categorical variables).

Results and limitations

IPSS significantly improved versus placebo through 12 wk with tadalafil (−2.1; p = 0.001; primary efficacy outcome) and tamsulosin (−1.5; p = 0.023) and as early as 1 wk (tadalafil and tamsulosin both −1.5; p < 0.01). BPH Impact Index significantly improved versus placebo at first assessment (week 4) with tadalafil (−0.8; p < 0.001) and tamsulosin (−0.9; p < 0.001) and through 12 wk (tadalafil −0.8, p = 0.003; tamsulosin −0.6, p = 0.026). The IPSS Quality-of-Life Index and the Treatment Satisfaction Scale–BPH improved significantly versus placebo with tadalafil (both p < 0.05) but not with tamsulosin (both p > 0.1). The International Index of Erectile Function–Erectile Function domain improved versus placebo with tadalafil (4.0; p < 0.001) but not tamsulosin (−0.4; p = 0.699). Q_max increased significantly versus placebo with both tadalafil (2.4 ml/s; p = 0.009) and tamsulosin (2.2 ml/s; p = 0.014). Adverse event profiles were consistent with previous reports. This study was limited in not being powered to directly compare tadalafil versus tamsulosin.

Conclusions

Monotherapy with tadalafil or tamsulosin resulted in significant and numerically similar improvements versus placebo in LUTS/BPH and Q_max. However, only tadalafil improved erectile dysfunction.

Trial registration

Clinicaltrials.gov ID NCT00970632     

Is There a Role for Tamsulosin in the Treatment of Distal Ureteral Stones of 7 mm or Less? Results of a Randomised,Double-Blind,Placebo-Controlled Trial

Background

Numerous randomised trials have confirmed the efficacy of medical expulsive therapy with tamsulosin in patients with distal ureteral stones; however, to date, no randomised, double-blind, placebo-controlled trials have been performed.

Objective

The objective of this trial was to evaluate the efficacy of medical expulsive therapy with tamsulosin in a randomised, double-blind, placebo-controlled setting.

Design, setting, and participants

Patients presenting with single distal ureteral stones ≤7 mm were included in this trial.

Intervention

Patients were randomised in a double-blind fashion to receive either tamsulosin or placebo for 21 d. The medication was discontinued after either stone expulsion or intervention. Abdominal computed tomography was performed to assess the initial and final stone status.

Measurements and limitations

The primary end point was the stone expulsion rate. Secondary end points were time to stone passage, the amount of analgesic required, the maximum daily pain score, safety of the therapy, and the intervention rate.

Results

Ten of 100 randomised patients were excluded from the analysis. No statistically significant differences in patient characteristics and stone size (median: 4.1 mm [tamsulosin arm] vs 3.8 mm [placebo arm], p = 0.3) were found between the two treatment arms. The stone expulsion rate was not significantly different between the tamsulosin arm (86.7%) and the placebo arm (88.9%; p = 1.0). Median time to stone passage was 7 d in the tamsulosin arm and 10 d in the placebo arm (log-rank test, p = 0.36). Patients in the tamsulosin arm required significantly fewer analgesics than patients in the placebo arm (median: 3 vs 7, p = 0.011). A caveat is that the exact time of stone passage was missing for 29 patients.

Conclusions

Tamsulosin treatment does not improve the stone expulsion rate in patients with distal ureteral stones ≤7 mm. Nevertheless, patients may benefit from a supportive analgesic effect.

Clinicaltrials.gov

NCT00831701.     

Age-adjusted incidence, mortality, and survival rates of stage-specific renal cell carcinoma in North America: a trend analysis

Background

The rising incidence of renal cell carcinoma (RCC) has been largely attributed to the increasing use of imaging procedures.

Objective

Our aim was to examine stage-specific incidence, mortality, and survival trends of RCC in North America.

Design, setting, and participants

We computed age-adjusted incidence, survival, and mortality rates using the Surveillance Epidemiology and End Results database. Between 1988 and 2006, 43 807 patients with histologically confirmed RCC were included.

Measurements

We calculated incidence, mortality, and 5-yr survival rates by year. Reported findings were stratified according to disease stage.

Results and limitations

Age-adjusted incidence rate of RCC rose from 7.6 per 100 000 person-years in 1988 to 11.7 in 2006 (estimated annual percentage change [EAPC]: +2.39%; p < 0.001). Stage-specific age-adjusted incidence rates increased for localized stage: 3.8 in 1988 to 8.2 in 2006 (EAPC: +4.29%; p < 0.001) and decreased during the same period for distant stage: 2.1 to 1.6 (EAPC: −0.57%; p = 0.01). Stage-specific survival rates improved over time for localized stage but remained stable for regional and distant stages. Mortality rates varied significantly over the study period among localized stage, 1.3 in 1988 to 2.4 in 2006 (EAPC: +3.16%; p < 0.001), and distant stage, 1.8 in 1988 to 1.6 in 2006 (EAPC: −0.53%; p = 0.045). Better detailed staging information represents a main limitation of the study.

Conclusions

The incidence rates of localized RCC increased rapidly, whereas those of distant RCC declined. Mortality rates significantly increased for localized stage and decreased for distant stage. Innovation in diagnosis and management of RCC remains necessary.     

Tension-free vaginal tape for the treatment of urodynamic stress incontinence: efficacy and adverse effects at 10-year follow-up

Background

One of the most effective and popular current procedures for the surgical treatment of stress urinary incontinence (SUI) is tension-free midurethral slings.

Objective

To evaluate the outcomes of women with retropubic tension-free vaginal tape (TVT) for urodynamic stress incontinence (USI) after 10-yr follow-up.

Design, setting, and participants

This was a prospective observational study. Consecutive women with proven USI were treated with TVT. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded.

Intervention

Standard retropubic TVT.

Measurements

Patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. Multivariable analyses were performed to investigate outcomes.

Results and limitations

A total of 63 women were included. After 10 yr, 5 patients (8%) were lost or no longer evaluable. The 10-yr subjective, objective, and urodynamic cure rates were 89.7%, 93.1%, and 91.4%, respectively. These rates were stable across the whole study period (p > 0.99). De novo overactive bladder was reported by 30.1% and 18.9% of patients at 3-mo and 10-yr follow-up, respectively (p for trend = 0.19). A total of 84.2% of women with detrusor overactivity received antimuscarinic drugs, but 43.8% were nonresponders 12 wk later. At multivariable analysis, maximum detrusor pressure during the filling phase >9 cm H₂O (hazard ratio [HR]: 16.2; p = 0.01) and maximum detrusor pressure during the voiding phase ≤29 cm H₂O (HR: 8.0; p = 0.01) were independent predictors for the recurrence of SUI, as well as obesity was for the recurrence of objective SUI (HR: 17.1; p = 0.01) and of USI (HR: 8.9; p = 0.02), respectively. Intraoperatively, bladder perforation occurred in two cases; no severe bleeding or other complications occurred.

Conclusions

The 10-yr results of this study seem to demonstrate that TVT is a highly effective option for the treatment of female SUI, recording a very high cure rate with low complications after a 10-yr follow-up.     

Prostate cancer antigen 3 score accurately predicts tumour volume and might help in selecting prostate cancer patients for active surveillance

Background

The optimal selection of prostate cancer (PCa) patients for active surveillance (AS) is currently being debated.

Objective

To assess the impact of urinary prostate cancer antigen 3 (PCA3) score as an AS criterion instead of and in addition to the current criteria.

Design, setting, and participants

We prospectively studied 106 consecutive low-risk PCa patients (prostate-specific antigen [PSA] ≤10 ng/ml, clinical stage T1c–T2a, and biopsy Gleason score 6) who underwent a PCA3 urine test before radical prostatectomy (RP).

Measurements

Performance of AS criteria (biopsy criteria, PCA3 score, PSA density, and magnetic resonance imaging [MRI] findings) was tested in predicting four prognostic pathologic findings in RP specimens: (1) pT3–4 disease; (2) overall unfavourable disease (OUD) defined by pT3–4 disease and/or pathologic primary Gleason pattern 4; (3) tumour volume <0.5 cm³; and (4) insignificant PCa.

Results and limitations

The PCA3 score was strongly correlated with the tumour volume in a linear regression analysis (p < 0.001, r = 0.409). The risk of having a cancer ≥0.5 cm³ and a significant PCa was increased three-fold in men with a PCA3 score of ≥25 compared with men with a PCA3 score of <25 with most AS biopsy criteria used. There was a trend towards higher PCA3 scores in patients with unfavourable and non–organ-confined disease and Gleason >6 cancers. In a multivariate analysis taking into account each AS criterion, a high PCA3 score (≥25) was an important predictive factor for tumour volume ≥0.5 cm³ (odds ratio [OR]: 5.4; p = 0.010) and significant PCa (OR: 12.7; p = 0.003). Biopsy criteria and MRI findings were significantly associated with OUD (OR: 3.9 and 5.0, respectively; p = 0.030 and p = 0.025, respectively).

Conclusions

PCA3 score may be a useful marker to improve the selection for AS in addition to the current AS criteria. With a predictive cut-off of 25, PCA3 score is strongly indicative for tumour volume and insignificant PCa.     

TVT-O for the Treatment of Pure Urodynamic Stress Incontinence: Efficacy,Adverse Effects,and Prognostic Factors at 5-Year Follow-up

Background

Inside-out tension-free vaginal transobturator tape (TVT-O) is currently one of the most effective and popular procedures for the surgical treatment of female stress urinary incontinence (SUI), but data reporting long-term outcomes are scarce.

Objective

To evaluate the efficacy and safety of TVT-O 5-yr implantation for management of pure SUI in women.

Design, setting, and participants

A prospective observational study was conducted in four tertiary reference centers. Consecutive women presenting with urodynamically proven, pure SUI treated by TVT-O were included. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded.

Intervention

TVT-O implantation without any associated procedure.

Outcome measurements and statistical analysis

Data regarding subjective outcomes (International Consultation on Incontinence-Short Form [ICIQ-SF], Patient Global Impression of Improvement, patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow-up. Multivariable analyses were performed to investigate outcomes.

Results and limitations

Of the 191 women included, 21 (11.0%) had previously undergone a failed anti-incontinence surgical procedure. Six (3.1%) patients were lost to follow-up. The 5-yr subjective and objective cure rates were 90.3% and 90.8%, respectively. De novo overactive bladder (OAB) was reported by 24.3% of patients at 5-yr follow-up. Median ICIQ-SF score significantly improved from 17 (interquartile range [IQR]:16–17) preoperatively to 0 (IQR: 0–2) (p < 0.0001).Failure of a previous anti-incontinence procedure was the only independent predictor of subjective recurrence of SUI (hazard ratio [HR]: 4.4; p = 0.009) or objective (HR: 3.7; p = 0.02). No predictive factor of de novo OAB was identified.

Conclusions

TVT-O implantation is a highly effective option for the treatment of women with pure SUI, showing a very high cure rate and a low incidence of complications after 5-yr follow-up.     

Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging

Background

Knowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial.

Objective

Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen.

Design, setting, and participants

Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n = 305) and computer-assisted planimetrically measured tumor volume data (n = 160) were available.

Intervention

All patients were treated with RP.

Measurements

PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3.

Results and limitations

PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p = 0.4) or SVI (p = 0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p < 0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size.

Conclusions

PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3.     

Effects of Once-Daily Tadalafil on Erectile Function in Men with Erectile Dysfunction and Signs and Symptoms of Benign Prostatic Hyperplasia

Background

Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH; BPH-LUTS) may be associated with erectile dysfunction (ED).

Objective

To evaluate the effects of once-daily tadalafil on erectile function in men with ED and BPH-LUTS.

Design, setting, and participants

Post hoc analysis of a phase 2–3, multinational, randomized, double-blind, placebo-controlled, parallel-group study of men with ED and moderate-to-severe LUTS secondary to BPH who reported being sexually active. In contrast to typical ED trials, no sexual activity threshold was required to participate.

Interventions

Screening and 4-wk washout period for patients taking BPH and/or ED treatments; 4-wk placebo run-in period; then once-daily placebo or tadalafil 2.5, 5, 10, or 20 mg for 12 wk.

Measurements

International Index of Erectile Function–Erectile Function (IIEF-EF) domain score, International Prostate Symptom Score (IPSS), peak urinary flow rate (Q_max), and postvoid residual volume (PVR). Analyses were performed in men who reported being sexually active with a female partner and who expected to remain so throughout the study. IIEF-EF data are presented for the BPH/ED population overall and for subgroups stratified by baseline age group, body mass index, BPH-LUTS severity, prostate-specific antigen, prior α-blocker use, and prior ED therapy.

Results and limitations

Overall, 581 men were included (placebo, n = 115; tadalafil 2.5 mg, n = 113; tadalafil 5 mg, n = 117; tadalafil 10 mg, n = 120; tadalafil 20 mg, n = 116). IIEF-EF domain score improvements from baseline to end point with tadalafil were 5.4 (2.5 mg), 6.8 (5 mg), 7.9 (10 mg), and 8.2 (20 mg) versus 2.0 with placebo (least-squares means; all p values <0.001). IIEF-EF domain score improvements were observed with tadalafil for all subgroup analyses, with no significant differences between subgroup or subgroup-by-treatment interaction terms. IPSS improvements from baseline to end point were significantly greater for all tadalafil doses versus placebo (all p values <0.05). Changes in Q_max and PVR were small and not clinically meaningful.

Conclusions

These data support the use of once-daily tadalafil in men with ED and BPH-LUTS.

Trial registration

http://www.clinicaltrials.gov: NCT00384930.     

The effects of splinting on shoulder function in adult burns

Introduction

Exercises are commonly prescribed to improve shoulder range following axillary burns, but the effect of additional splinting is unclear.

Aim

To compare splinting and exercise to exercise alone in adults with axillary burns.

Method

Prospective randomised study allocating participants to a splinting (n = 27) or no splinting group (n = 25). Outcomes measured at six and twelve weeks were shoulder abduction and flexion range, quality of life using the Burn Specific Health Scale-Brief (BSHS-B) questionnaire and upper limb function using the Upper Extremity Functional Index (UEFI) and the Grocery Shelving Task (GST).

Results

At week twelve, there was no difference between groups for shoulder abduction (mean difference 0°, 95% CI −22 to 22°), flexion (mean difference 2°, 95% CI −18 to 23°), BSHS-B (mean difference −2 points, 95% CI −23 to 18 points), UEFI (mean difference −3 points, 95% CI −19 to 14 points) and GST (mean difference −9 s, 95% CI −20 to 3 s). Adherence to splinting decreased from 77% of participants at week one to 16% at week twelve.

Conclusion

Shoulder splints did not improve clinical outcomes in this study population and low adherence rates suggest splinting may be unacceptable to patients and makes drawing firm conclusions difficult.     

Real-time MRI of orthotopic ileal neobladder voiding: preliminary findings

Objectives

The purpose of this preliminary study was to analyze the dynamic changes in the configuration of the neobladder and naïve bladder during voiding using real-time MRI.

Methods

This study included 10 male patients who had a radical cystectomy and an ileal orthotopic neobladder due to organ-confined bladder cancer and had good urinary function, and 5 male control volunteers. With the subjects in the lateral decubitus position, real-time MRI was performed during micturition. A sagittal slice orientation was used to depict the bladder and the entire length of the urethra; individual movements along the X-axis and Y-axis of the bottom and top of the neobladder and the naïve bladder were recorded and analyzed. Urodynamic studies (UDS) and video voiding cystourethrography were performed in patients.

Results

Five of the 10 neobladder patients could void in the lateral decubitus position. In normal controls and patients who could void, the bladder outlet bladder moved ventrocranially during micturition. The ileal bladder outlet moved a significantly longer distance than the naïve bladder during micturition (X-axis, −13.4 ± 1.5 vs. −3.6 ± 4.3 cm, p = 0.0014; Y-axis, −10.6 ± 0.5 vs. −2.0 ± 6.5 cm, p = 0.0187). The distance that the bladder top moved between the naïve bladders and the neobladder did not differ. UDS did not show a difference between patients who could and could not void at lateral position.

Conclusions

During micturition, the neobladder was found to rotate and move more dynamically than the naïve bladder. Real-time MRI is useful for assessing dynamic voiding function of orthotopic neobladders.     

Prospective randomised controlled trial of transobturator tapes in management of urodynamic stress incontinence in women: 3-year outcomes from the evaluation of transobturator tapes study

Background

There is a lack of information on the long-term outcomes of transobturator tension-free vaginal tape (TO-TVT) in the surgical treatment of female stress urinary incontinence (SUI).

Objectives

To assess the 3-yr outcomes following TO-TVT and to compare the effectiveness of inside-out versus outside-in approaches.

Design, setting, and participants

A 3-yr follow-up study of the Evaluation of Transobturator Tapes (E-TOT) trial, a randomised controlled trial (RCT) conducted with women undergoing TO-TVT as a sole procedure between April 2005 and April 2007 in a tertiary urogynaecology centre in the United Kingdom.

Intervention

Patients (n = 341) were randomised to undergo either TVT-O (Ethicon Inc., Somerville, NJ, USA) for the inside-out approach or TOT-Aris (Coloplast Corp., Minneapolis, MN, USA) for the outside-in approach.

Outcome measurements and statistical analysis

The primary outcome was patient-reported success rate. Secondary outcomes included further treatment for SUI, improvement in quality of life, late complications, and risk factors for late failures. Categorical variables were compared using the chi-square or Fisher exact test. Within-group comparison was undertaken using Wilcoxon and Mann-Whitney tests. Risk factors for late failures were assessed in a multivariate regression model. All statistical analysis was performed using SPSS v.18.0 (IBM Corp., Armonk, NY, USA).

Results and limitations

The 3-yr follow-up was completed by 238 of the 341 women (70%). The overall success rate, based on Patient's Global Impression of Improvement response, was 73.1%, with no significant difference between the inside-out and the outside-in TO-TVT (73.18% vs 72.3%; odds ratio: 0.927; 95% confidence interval, 0.552–1.645; p = 0.796). Compared with the 1-yr follow-up, there was a significant reduction in the patient-reported success rate (p = 0.005); however, no independent risk factors were identified. A clinically significant improvement (≥10 points) was seen in 80% (n = 191) of women, with no significant difference between both groups (p = 0.113). Twenty-two women (6%) underwent further surgical treatment within 3 yr. The lack of an objective outcome assessment is a potential limitation of this RCT.

Conclusions

The E-TOT RCT showed a 73% patient-reported success rate for TO-TVT at 3-yr follow-up, with no significant differences between inside-out and outside-in approaches. There was a significant drop in patient-reported success rates between 1 and 3 yr.     

The impact of prostate size, median lobe, and prior benign prostatic hyperplasia intervention on robot-assisted laparoscopic prostatectomy: technique and outcomes

Background

Large prostate size, median lobes, and prior benign prostatic hyperplasia (BPH) surgery may pose technical challenges during robot-assisted laparoscopic prostatectomy (RALP).

Objective

To describe technical modifications to overcome BPH sequelae and associated outcomes.

Design, settings, and participants

A retrospective study of prospective data on 951 RALP procedures performed from September 2005 to November 2010 was conducted. Outcomes were analyzed by prostate weight, prior BPH surgical intervention (n = 59), and median lobes >1 cm (n = 42).

Surgical procedure

RALP.

Measurements

Estimated blood loss (EBL), blood transfusions, operative time, positive surgical margin (PSM), and urinary and sexual function were measured.

Results and limitations

In unadjusted analysis, men with larger prostates and median lobes experienced higher EBL (213.5 vs 176.5 ml; p < 0.001 and 236.4 vs 193.3 ml; p = 0.002), and larger prostates were associated with more transfusions (4 vs 1; p = 0.037). Operative times were longer for men with larger prostates (164.2 vs 149.1 min; p = 0.002), median lobes (185.8 vs 155.0 min; p = 0.004), and prior BPH surgical interventions (170.2 vs 155.4 min; p = 0.004). Men with prior BPH interventions experienced more prostate base PSM (5.1% vs 1.2%; p = 0.018) but similar overall PSM. In adjusted analyses, the presence of median lobes increased both EBL (p = 0.006) and operative times (p < 0.001), while prior BPH interventions also prolonged operative times (p = 0.014). However, prostate size did not affect EBL, PSM, or recovery of urinary or sexual function.

Conclusions

Although BPH characteristics prolonged RALP procedure times and increased EBL, prostate size did not affect PSM or urinary and sexual function.     

The prognostic significance of capsular incision into tumor during radical prostatectomy

Background

The prognostic significance of capsular incision (CapI) into tumor during radical prostatectomy (RP) with otherwise organ-confined disease remains uncertain.

Objective

To evaluate the impact of CapI into tumor on oncologic outcome.

Design, setting, and participants

A retrospective review of 8110 consecutive patients with prostate cancer treated at Ottawa Hospital and at Memorial Sloan–Kettering Cancer Center, both tertiary academic centers, between 1985 and 2008.

Intervention

All patients underwent an open, laparoscopic or robotic RP.

Measurements

Patients were divided into four pathologic categories: group 1 (CapI group), positive surgical margins (PSMs) without extraprostatic extension (EPE); group 2, negative surgical margins (NSMs) without EPE; group 3, NSM with EPE; group 4, PSMs with EPE. Estimates of recurrence-free survival were generated with the Kaplan-Meier method. Recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/ml and rising. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for recurrence controlling for pretreatment PSA, RP date, RP Gleason sum, seminal vesicle invasion, and lymph node involvement. Pathologic categories were defined in the model by including the variables EPE and surgical margins (SMs) as well as their interaction.

Results and limitations

Median follow-up was 37.3 mo. The 5-yr recurrence-free probability after RP for the CapI group was 77% (95% confidence interval [CI], 72–83). This was not only inferior to patients with NSMs and no EPE (log rank p < 0.0001) but also to those with NSMs and EPE (log rank p = 0.0002). In multivariate analysis the interaction between EPE and SM was not significant (p = 0.26). In the adjusted model excluding the interaction term, patients with EPE had an increased risk for recurrence (HR: 1.80; 95% CI, 1.49–2.17; p < 0.0001) as did those with positive margins (HR: 1.81; 95% CI, 1.51–2.15; p < 0.0001). This was a retrospective study.

Conclusions

CapI into tumor has a significant impact on patient outcome following RP. Patients, who otherwise would have organ-confined disease, will now have a higher probability of recurrence than those with completely resected extraprostatic disease.     

Mortality and prognostic factors of the cirrhotic patients with hepatic encephalopathy admitted to medical intensive care unit

Objective

To assess mortality and to identify variables that could predict it in cirrhotic patients hospitalized to the medical intensive care unit (MICU) for hepatic encephalopathy (HE).

Study design

Retrospective cohort study.

Patients and methods

From January 1995 to December 2004, the cirrhotic patients admitted consecutively in MICU were screened and those with altered level of consciousness were included. The MICU mortality rate was assessed. Nearly 80 variables were analyzed and compared between survivors and non-survivors. Statistical analysis: t test, χ² or Fisher exact tests, Kaplan-Meier and log rank, Cox regression analysis.

Results

A total of 180 patients (42 women - 138 men, mean age: 59 ± 10 years) were admitted (incidence: 2.6%). The SAPS II was 30.1 ± 11, Acute Physiology Age and Chronic Health Evaluation II (APACHE II): 16.5 ± 5.3, Child-Pugh score: 9.1 ± 1.9 and GCS: 11 ± 2.8. The causes of liver cirrhosis was identified in 41.2% of cases (viral: 35.6%, alcohol: 5.6%). Nearly 18% of patients had an antecedent of HE. The causes of HE were: infection (65.6%), upper gastrointestinal bleeding (32.2%), drugs (5%) and metabolic cause (5%). MICU mortality rate was 33.3% and seemed higher in gastrointestinal bleeding. Eighteen variables were significantly associated with poor prognosis in univariate analysis. Only three variables remained significant in multivariate analysis: systolic blood pressure < 90 mmHg (RR = 4; IC95% = 2–8.1), total WBC > 12 000 n/mm³ (RR = 3.1; IC95% = 1.8–5.3) and use of mechanical ventilation (RR = 3.1; IC95% = 1.7–5.6).

Conclusion

The MICU mortality of cirrhotic patients with HE was high and significantly associated with haemodynamic instability, hyperleucocytosis and mechanical ventilation.