Intakes of vitamins and minerals in relation to urinary incontinence, voiding, and storage symptoms in women: a cross-sectional analysis from the Boston Area Community Health survey

Background

Whether lower urinary tract symptoms (LUTS), including voiding, storage, and urinary incontinence, are affected by dietary micronutrients is uncertain.

Objective

To test the hypothesis that carotenoid, vitamin C, zinc, and calcium intakes are associated with LUTS and urinary incontinence in women.

Design, setting, and participants

During an observational, cross-sectional, population-based epidemiologic study of 2060 women (30–79 yr of age) in the Boston Area Community Health (BACH) survey (2002–2005), data were collected by validated food frequency questionnaire and in-person interviews and analyzed using multivariate regression.

Measurements

LUTS, storage, and voiding symptoms were assessed using the American Urological Association Symptom Index (AUASI) and a validated severity index for urinary incontinence.

Results and limitations

Women who consumed high-dose vitamin C from diet and supplements were more likely to report storage symptoms, especially combined frequency and urgency (≥500 vs <50 mg/d; odds ratio [OR]: 3.42; 95% confidence interval [CI], 1.44–8.12). However, greater consumption of dietary vitamin C or β-cryptoxanthin was inversely associated with voiding symptoms (p_trend ≤ 0.01). Both dietary and supplemental calcium were positively associated with storage symptoms (eg, supplement ≥1000 mg/d vs none; OR: 2.04; 95% CI, 1.35–3.09; p_trend = 0.0002). No consistent associations were observed for β-carotene, lycopene, or other carotenoids, although smokers using β-carotene supplements were more likely to report storage problems. Whether the observed associations represent direct causes of diet on LUTS is uncertain.

Conclusions

High-dose intakes of vitamin C and calcium were positively associated with urinary storage or incontinence, whereas vitamin C and β-cryptoxanthin from foods and beverages were inversely associated with voiding symptoms. Results indicate that micronutrient intakes may contribute to LUTS in dose-dependent and symptom-specific ways. Further study is needed to confirm these findings and their relevance to clinical treatment decisions.     

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     

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.     

Two modes of acupuncture as a treatment for hot flushes in men with prostate cancer--a prospective multicenter study with long-term follow-up

Background

Hot flushes are common and distressing among men with castrational treatment for prostate cancer. Of the few treatments, most have side effects.

Objective

Assess changes in hot flushes of electrostimulated (EA) and traditional acupuncture (TA).

Design, Setting, and Participants

Thirty-one men with hot flushes due to prostate cancer treatment were recruited from three urological departments in Sweden, from 2001 to 2004.

Intervention

Thirty-one men were randomized to EA (12 needle points, with 4 electrostimulated) or TA (12 needle points) weekly for 12 wk.

Measurements

Primary outcome: number of and distress from hot flushes in 24 h and change in “hot flush score.” Secondary outcome: change in 24-h urine excretion of CGRP (calcitonin gene–related peptide).

Results and Limitations

Twenty-nine men completed the treatment. Hot flushes per 24 h decreased significantly, from a median of 7.6 (interquartile range [IQR], 6.0–12.3) at baseline in the EA group to 4.1 (IQR, 2.0–6.5) (p = 0.012) after 12 wk, and from 5.7 (IQR, 5.1–9.5) in the TA group to 3.4 (IQR1.8–6.3) (p = 0.001). Distress by flushes decreased from 8.2 (IQR, 6.5–10.7) in the EA group to 3.3 (IQR, 0.3–8.1) (p = 0.003), and from 7.6 (IQR, 4.7–8.3) to 3.4 (IQR, 2.0–5.6) (p = 0.001) in the TA group after 12 wk, (78% and 73% reduction in “hot flush score,” respectively). The effect lasted up to 9 mo after treatment ended. CGRP did not change significantly. Few, minor side effects were reported.Limitations: small number of patients; no placebo control, instead a small group controlled for 6 wk pretreatment.

Conclusions

EA and TA lowered number of and distress from hot flushes. The hot flush score decreased 78% and 73%, respectively, in line with or better than medical regimens for these symptoms. Acupuncture should be considered an alternative treatment for these symptoms, but further evaluation is needed, preferably with a non- or placebo-treated control group.     

A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia

Context

Several randomized controlled trials (RCTs) on phosphodiesterase type 5 inhibitors (PDE5-Is) have showed significant improvements in both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in men affected by one or both conditions, without a significant increase in adverse events. However, the results are inconsistent.

Objective

Perform a systematic review and meta-analysis of available prospective and cross-sectional studies on the use of PDE5-Is alone or in combination with α1-adrenergic blockers in patients with LUTS/benign prostatic hyperplasia (BPH).

Evidence acquisition

A systematic search was performed using the Medline, Embase, and Cochrane Library databases through September 2011 including the combination of the following terms: LUTS, BPH, PDE5-Is, sildenafil, tadalafil, vardenafil, udenafil, α-blockers, and α1-adrenergic blocker. The meta-analysis was conducted according to the guidelines for observational studies in epidemiology.

Evidence synthesis

Of 107 retrieved articles, 12 were included in the present meta-analysis: 7 on PDE5-Is versus placebo, with 3214 men, and 5 on the combination of PDE5-Is with α1-adrenergic blockers versus α1-adrenergic blockers alone, with 216 men. Median follow-up of all RCTs was 12 wk.Combining the results of those trials, the use of PDE5-Is alone was associated with a significant improvement of the International Index of Erectile Function (IIEF) score (+5.5; p < 0.0001) and International Prostate Symptom Score (IPSS) (−2.8; p < 0.0001) but not the maximum flow rate (Q_max) (−0.00; p = not significant) at the end of the study as compared with placebo. The association of PDE5-Is and α1-adrenergic blockers improved the IIEF score (+3.6; p < 0.0001), IPSS score (−1.8; p = 0.05), and Q_max (+1.5; p < 0.0001) at the end of the study as compared with α-blockers alone.

Conclusions

The meta-analysis of the available cross-sectional data suggests that PDE5-Is can significantly improve LUTS and erectile function in men with BPH. PDE5-Is seem to be a promising treatment option for patients with LUTS secondary to BPH with or without ED.     

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.     

Temporal national trends of minimally invasive and retropubic radical prostatectomy outcomes from 2003 to 2007: results from the 100% Medicare sample

Background

Although the use of minimally invasive radical prostatectomy (MIRP) has increased, there are few comprehensive population-based studies assessing temporal trends and outcomes relative to retropubic radical prostatectomy (RRP).

Objective

Assess temporal trends in the utilization and outcomes of MIRP and RRP among US Medicare beneficiaries from 2003 to 2007.

Design, setting, and participants

A population-based retrospective study of 19 594 MIRP and 58 638 RRP procedures was performed from 2003 to 2007 from the 100% Medicare sample, composed of almost all US men ≥65 yr of age.

Intervention

MIRP and RRP.

Measurements

We measured 30-d outcomes (cardiac, respiratory, vascular, genitourinary, miscellaneous medical, miscellaneous surgical, wound complications, blood transfusions, and death), cystography utilization within 6 wk of surgery, and late complications (anastomotic stricture, ureteral complications, rectourethral fistulae, lymphocele, and corrective incontinence surgery).

Results and limitations

From 2003 to 2007, MIRP increased from 4.9% to 44.5% of radical prostatectomies while RRP decreased from 89.4% to 52.9%. MIRP versus RRP subjects were younger (p < 0.001) and had fewer comorbidities (p < 0.001). Decreased MIRP genitourinary complications (6.2–4.1%; p = 0.002), miscellaneous surgical complications (4.7–3.7%; p = 0.030), transfusions (3.5–2.2%; p = 0.005), and postoperative cystography utilization (40.3–34.1%; p < 0.001) were observed over time. Conversely, overall RRP perioperative complications increased (27.4–32.0%; p < 0.001), including an increase in perioperative mortality (0.5–0.8%, p = 0.009). Late RRP complications increased, with the exception of fewer anastomotic strictures (10.2–8.8%; p = 0.002). In adjusted analyses, RRP versus MIRP was associated with increased 30-d mortality (odds ratio [OR]: 2.67; 95% confidence interval [CI], 1.55–4.59; p < 0.001) and more perioperative (OR: 1.60; 95% CI, 1.45–1.76; p < 0.001) and late complications (OR: 2.52; 95% CI, 2.20–2.89; p < 0.001). Limitations include the inability to distinguish MIRP with versus without robotic assistance and also the lack of pathologic information.

Conclusions

From 2003 to 2007, there were fewer MIRP transfusions, genitourinary complications, and miscellaneous surgical complications, whereas most RRP perioperative and late complications increased. RRP versus MIRP was associated with more postoperative mortality and complications.     

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.     

Vardenafil decreases bladder afferent nerve activity in unanesthetized, decerebrate, spinal cord-injured rats

Background

Phosphodiesterase type 5 inhibitors (PDE5-Is) improve storage symptoms in benign prostatic hyperplasia patients, despite a lack of effect on peak urinary flow rate. Moreover, vardenafil improves urodynamic parameters in spinal cord-injured (SCI) patients with neurogenic detrusor overactivity (NDO). SCI rats also display NDO characterized by nonvoiding contractions (NVCs) during bladder filling, resulting in an increased bladder afferent nerve firing (BANF).

Objective

We postulated that vardenafil could improve urodynamic parameters by reducing BANF. The effect of vardenafil has been investigated on intravesical pressure by cystometry experiments while recording BANF in response to bladder filling.

Design, setting, and participants

Complete T7–T8 spinalization was performed in 15 female adult Sprague-Dawley rats (250–275 g).

Measurements

At 21–29 d postspinalization, fine filaments were dissected from the L6 dorsal roots and placed across a bipolar electrode. Bladder afferent nerve fibers were identified by electrical stimulation of the pelvic nerve and bladder distension. SCI rats were decerebrated before cystometry experiments. Bladders were filled to determine the maximal bladder filling volume (BFV) for each rat. Then, after bladder stabilization at 75% of maximal BFV, saline (n = 7) or vardenafil 1 mg/kg (n = 8) was delivered intravenously. NVCs and BANF were recorded for 45 min.

Results and limitations

In all SCI rats, BANF was already present and regular at resting conditions (26.2 ± 4.1 spikes per second). During bladder filling, intravesical pressure (IVP) slowly increased with transient NVCs superimposed. Concomitantly, BANF progressively increased up to 2.4-fold at maximal BFV (2.08 ± 0.24 ml). After stabilization at submaximal BFV, BANF was increased by 186 ± 37%. Vardenafil injection induced an immediate decrease in NVCs compared to saline (p < 0.001) and BANF (52% decrease vs 28% in saline after 45 min; p < 0.001).

Conclusions

Systemic vardenafil reduced both NVCs and BANF in unanesthetized, decerebrate, SCI rats. These findings provide new insights into the mechanism of action by which PDE5-Is improve storage symptoms in SCI patients.     

Duloxetine for mild to moderate postprostatectomy incontinence: preliminary results of a randomised, placebo-controlled trial

Background

Duloxetine is effective in the management of stress urinary incontinence (SUI) in women but has been poorly evaluated in the treatment of SUI following radical prostatectomy (RP).

Objective

To establish the superiority of duloxetine over placebo in SUI after RP.

Design, setting, and participants

We conducted a prospective, randomised, placebo-controlled, double-blind, monocentric superiority trial. After a placebo run-in period of 2 wk, patients with SUI after RP were randomised to receive either 80 mg of duloxetine daily or matching placebo for 3 mo.

Measurements

The primary outcome measure was the relative variation in incontinence episodes frequency (IEF) at the end of study compared to baseline. Secondary outcomes included quality of life (QoL) measures (Incontinence Impact Questionnaire Short Form [IIQ-SF], Urogenital Distress Inventory Short Form [UDI-SF], Incontinence Quality of Life [I-QoL]), symptom scores (Urinary Symptom Profile [USP] questionnaire, International Consultation on Incontinence/World Health Organisation Short Form questionnaire [ICIQ-SF], the Beck Depression Inventory [BDI-II] questionnaire), 1-h pad test, and assessment of adverse events.

Results and limitations

Thirty-one patients were randomised to either the treatment (n = 16) or control group (n = 15). Reduction in IEF was significant with duloxetine compared to placebo (mean ± standard deviation [SD] variation: −52.2% ± 38.6 [range: −100 to +46] vs +19.0% ± 43.5 [range: −53 to +104]; mean difference: 71.2%; 95% confidence interval [CI] for the difference: 41.0–101.4; p < 0.0001). IIQ-SF total score, UDI-SF total score, SUI subscore of the USP questionnaire, and question 3 of the ICIQ-SF questionnaire showed improvement in the duloxetine group (p = 0.006, p = 0.02, p = 0.0004, and p = 0.003, respectively). Both treatments were well tolerated throughout the study period.

Conclusions

Duloxetine is effective in the treatment of incontinence symptoms and improves QoL in patients with SUI after RP.     

Near-infrared spectroscopy: a novel, noninvasive, diagnostic method for detrusor overactivity in patients with overactive bladder symptoms--a preliminary and experimental study

Background

Near-infrared spectroscopy (NIRS) is an optical technology. It detects the hemodynamic changes in tissues via noninvasive measurement of changes in the concentration of tissue chromophores such as oxyhemoglobin (O₂Hb) and deoxyhemoglobin (HHb). Involuntary bladder contractions may cause changes detectable by NIRS.

Objective

To address the accuracy and reproducibility of NIRS to detect the hemodynamic effects of detrusor overactivity (DO).

Design, setting, and participants

A prospective cohort study was carried out on 41 patients with overactive bladder symptoms.

Measurements

Forty-one patients underwent one or more filling cystometries with simultaneous NIRS of the bladder. The separated graphs representing both tests were presented to three urodynamicists on two occasions, 3 wk apart. The graphs showed curves with and without DO episodes with the bladder sensations marked. Thirteen of 47 graphs (28%) with DO and 16 of 58 graphs (28%) without DO were excluded due to motion artifacts. The urodynamicists marked pressure changes suggestive of DO on the cystometry curves. For NIRS curves they marked definite deviations from baseline. The sensitivity and specificity of NIRS for DO were determined. The inter- and intraobserver agreements were determined.

Results and limitations

Valid data from 33 of 41 patients (80%) were included in the analysis. The interobserver agreement to trace the effect of DO on NIRS curves was “substantial” (κ_f > 0.6). The sensitivity of the Hb_sum (O₂Hb + HHb) curves for DO was 62–97% with a specificity of 62–79% (area under the curve [AUC]: 0.80–0.82; p < 0.001). O₂Hb curves had 79–85% sensitivity and 82–91% specificity for DO (AUC: 0.80–0.85; p < 0.001). The sensitivity and specificity of the HHb curves for DO were 71–82% and 77–82%, respectively (AUC: 0.73–0.84; p < 0.001). These values represent the performance of NIRS in the data sample that is not contaminated with motion artifacts; they are not representative of a general clinical setting.

Conclusion

NIRS is a potential noninvasive, reproducible, diagnostic method to detect DO.     

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.     

Prospective study of the role of transurethral resection of the prostate in patients with an elevated prostate-specific antigen level, minor lower urinary tract symptoms, and proven bladder outlet obstruction

Background

Deciding on strategy for patients with minor lower urinary tract symptoms (LUTS), elevated prostate-specific antigen (PSA) levels, unsuspicious digital rectal examination (DRE) and/or transrectal ultrasound (TRUS), and multiple negative extended prostate biopsies is complex.

Objectives

To define the role and clinical significance of transurethral resection of the prostate (TURP) in these patients.

Design, settings, and participants

Thirty-three patients with elevated PSA; minor LUTS, as assessed by the International Prostate Symptoms Score (IPSS); no suspicion for prostate cancer on DRE and/or TRUS; and negative extended prostate biopsies were prospectively enrolled in a cohort study at a tertiary care institution.

Intervention

After full urodynamic investigation showing all patients to be bladder outlet obstructed, TURP was performed.

Measurements

Resected tissue was histologically examined for presence of prostate cancer. Within 6 mo after TURP, patients were clinically reevaluated by means of IPSS and PSA level.

Results and limitations

Preoperatively, mean PSA and IPSS values were 8.2 ng/ml and 6.8, respectively. Mean detrusor pressure at maximum flow was 80.3 cm H₂O. Histological examination after TURP revealed benign prostate hyperplasia in 81.8% (subgroup 1) and aggressive prostate cancer in 6.1% of patients (subgroup 2). In 12.1% of patients, only a few chips of nonaggressive prostate cancer (T1a) were detected. In patients without signs of aggressive prostate cancer (93.9% = 12.1% + 81.8%, subgroup 3), mean postoperative PSA and IPSS values were 0.6 ng/ml and 2.4, respectively, while these values were 0.6 ng/ml and 2.5 ng/ml in subgroup 1 (p < 0.0001). This study is limited in sample size, requiring more research to confirm these results.

Conclusions

This prospective study shows that, in patients with minor LUTS and no suspicion for prostate cancer, bladder outlet obstruction can result in elevated PSA levels. These patients will benefit from TURP regarding symptomatology and supernormalisation of PSA levels. Moreover, albeit in few cases, histological examination will reveal aggressive prostate cancer.     

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 factor age and the recovery of severely burned children

Purpose

It is not known if the recovery of pediatric burn patients is age-dependent. The aim of this study was to investigate the effect of age on the recovery of body composition of severely burned children.

Procedures

Pediatric patients with massive burns, ≥40% of total body surface area, were followed over 2 years. Patients were divided into two age groups: 0–3.9 years old and 4–17.9 years old at the time of burn.Body composition was determined at hospital discharge, 6, 9, 12, 18, and 24 months after burn using dual-X-ray absorptiometry. Data analysis was performed using a two way ANOVA followed by Tukey's correction when appropriate. Significance was accepted at p < 0.05.

Findings

Twenty-four patients were enrolled (age 0–3.9: n = 9; age 4–17.9: n = 15). Percent changes in height and bone mineral content were significantly increased in the younger age group, p < 0.05. In contrast, percent changes in lean body mass were significantly lower in younger patients, p < 0.05. Percent changes in total body fat mass were not affected.

Conclusion

Patterns of recovery in pediatric burn patients are determined by age. This observation should be considered in the development of therapeutic approaches.     

Anatomic Bladder Neck Preservation During Robotic-Assisted Laparoscopic Radical Prostatectomy: Description of Technique and Outcomes

Background

Robotic-assisted laparoscopic radical prostatectomy (RALP) has been rapidly adopted despite a daunting learning curve with bladder neck dissection as a challenging step for newcomers.

Objective

To describe an anatomic, reproducible technique of bladder neck preservation (BNP) and associated perioperative and long-term outcomes.

Design, settings, and participants

From September 2005 to May 2009, data from 619 consecutive RALP were prospectively collected and compared on the basis of bladder neck dissection technique with 348 BNP and 271 standard technique (ST).

Surgical procedure

RALP with BNP.

Measurements

Tumor characteristics, perioperative complications, and post-operative urinary control were evaluated at 4, 12 and 24 months using (1) the Expanded Prostate Cancer Index (EPIC) urinary function scale scored from 0–100; and (2) continence defined as zero pads per day.

Results and limitations

Mean age for BNP versus ST was 57.1 ± 6.6 yr versus 58.9 ± 6.7 yr (p = 0.033), while complication rates did not vary significantly by technique. Estimated blood loss was 183.7 ± 95.8 ml versus 224.6 ± 108 ml (p = 0.938) in men who underwent BNP versus ST. The overall positive margin rate was 12.8%, which did not differ at the prostate base for BNP versus ST (1.4% vs. 2.2%, p = 0.547). Mean urinary function scores for BNP versus ST at 4, 12, and 24 mo were 64.6 versus 57.2 (p = 0.037), 80.6 versus 79.0 (p = 0.495), and 94.1 versus 86.8 (p < 0.001). Similarly, BNP versus ST continence rates at 4, 12, and 24 mo were 65.6% versus 26.5% (p < 0.001), 86.4% versus 81.4% (p = 0.303), and 100% versus 96.1% (p = 0.308).

Conclusions

BNP versus ST is associated with quicker recovery of urinary function and similar cancer control.     

Thirty-Day Mortality After Nephrectomy: Clinical Implications for Informed Consent

Background

The existing literature suggests that the surgical mortality (SM) observed with nephrectomy for localised disease varies from 0.6% to 3.6%.

Objective

To examine age- and stage-specific 30-d mortality (TDM) rates after partial or radical nephrectomy.

Design, setting, and participants

We relied on 24 535 assessable patients from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database.

Measurements

In 12 283 patients, logistic regression models were used to develop a tool for pretreatment prediction of the probability of TDM according to individual patient and tumour characteristics. External validation was performed on 12 252 patients.

Results and limitations

In the entire cohort of 24 535 patients, 219 deaths occurred during the initial 30 d after nephrectomy (0.9% TDM rate). TDM increased with age (≤49 yr: 0.5% vs 50–59 yr: 0.7% vs 60–69 yr: 0.9% vs 70–79 yr: 1.2% vs ≥80 yr: 2.0%; χ² trend p < 0.001) and stage (0.3% for T1–2N0M0 vs 1.3% for T3–4N0–2M0 vs 4.2% for T1–4N0–2M1; χ² trend p = <0.001). TDM decreased in more recent years (1988–1993: 1.3% vs 1994–1998: 0.9% vs 1999–2002: 0.7% vs 2003–2004: 0.6%; χ² trend p < 0.001) and was lower after partial versus radical nephrectomy (RN) (0.4% vs 0.9%; p = 0.008). Only age (p < 0.001) and stage (p < 0.001) achieved independent predictor status. The look-up table that relied on the regression coefficients of age and stage reached 79.4% accuracy in the external validation cohort.

Conclusions

Age and stage are the foremost determinants of TDM after nephrectomy. Our model provides individual probabilities of TDM after nephrectomy, and its use should be highly encouraged during informed consent prior to planned nephrectomy.     

The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial

Objective

The ongoing REDUCE trial is a 4-yr, phase 3, placebo-controlled study to determine if daily dutasteride 0.5 mg reduces the risk of biopsy detectable prostate cancer. Prostate biopsies performed in all men prior to entry were centrally reviewed, thus allowing an examination of the relationship between inflammatory changes and lower urinary tract symptoms (LUTS).

Methods

Eligible men were aged 50–75 yr, with serum prostate-specific antigen ≥2.5 ng/ml and ≤10 ng/ml (50–60 yr), or ≥3.0 ng/ml and ≤10 ng/ml (>60 yr) and an International Prostate Symptom Score (IPSS) < 25 (or <20 if already on alpha-blocker therapy). Acute prostatitis was an exclusion criterion. For a given individual, inflammation was assessed across all cores and the amount of inflammation scored as none (0), mild (1), moderate (2), or marked (3). LUTS was assessed with the use of the IPSS. The relationship between inflammation scores (averaged over all cores) and total IPSS; grouped IPSS (0–3, 4–7, 8–11, 12–15, 16–19, ≥20); and irritative, obstructive, and nocturia subscores was determined by Spearman rank correlations. The relative contribution of inflammation, age, and body mass index was then examined with the use of linear regression analyses.

Results

Data were available for 8224 men. Statistically significant but relatively weak correlations were found between average and maximum chronic inflammation and IPSS variables (correlation coefficients, 0.057 and 0.036, respectively; p < 0.001 for total IPSS). Both age and average chronic inflammation were significant in the linear regression after adjustment for other covariates; for both variables, more severe inflammation was associated with higher IPSS scores.

Conclusions

In the REDUCE population, there is evidence of a relationship between the degree of LUTS and the degree of chronic inflammation. Study entry criteria that selected older men and decreased enrolment of men with a greater degree of inflammation and LUTS may have limited the strength of this relationship. The impact of baseline prostate inflammation on progression of LUTS and/or associated complications will be determined during 4-yr longitudinal follow-up.     

Influence of the analgesic strategy on the respiratory function after thoracic surgery for lobectomy

Objective

To compare the influence of thoracic epidural analgesia (TEA) with intravenous patient-controlled analgesia with morphine (PCA) on the early postoperative respiratory function after lobectomy.

Study design

Prospective and comparative observational study.

Patients and methods

Fourty-four patients scheduled for lobectomy (n = 22 per group) were studied on the evolution of the postoperative respiratory function assessed by the forced vital capacity (FVC) and the forced expired volume (FEV₁) during the first two postoperative days and the analysis of noctural arterial desaturation during the three first postoperative nights.

Results

The use of TEA resulted in fewer decrease both in FEV₁ (1.01 ± 0.34 versus 1.31 ± 0.51 l/s for Day 1, P = 0.03; 1.13 ± 0.37 versus 1.53 ± 0.59 l/s for Day 2, P = 0.01) and in FVC (1.23 [1.05-1.51] versus 1.57 [1.38–2.53] l for day 1, P = 0.008; 1.33 ± 0.43 versus 2.24 ± 0.87 l for day 2, P < 0.001). Moreover, the duration of arterial desaturation < 90% were longer in the PCA group during the first (8.6 [0.8–28.2] versus 1.3 [0–2.6] min, P = 0.02) and the second postoperative night (13.5 [3.5–54] versus 0.4 [0–2.6] min, P = 0.025).

Conclusion

The results of this study suggest that the use of TEA is associated with a better preservation of respiratory function assessed by spirometric data and noctural arterial desaturation recording after thoracic surgery for lobectomy.     

A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma

Background

Nephron-sparing surgery (NSS) can safely be performed with slightly higher complication rates than radical nephrectomy (RN), but proof of oncologic effectiveness is lacking.

Objective

To compare overall survival (OS) and time to progression.

Design, setting, and participants

From March 1992 to January 2003, when the study was prematurely closed because of poor accrual, 541 patients with small (≤5 cm), solitary, T1–T2 N0 M0 (Union Internationale Contre le Cancer [UICC] 1978) tumours suspicious for renal cell carcinoma (RCC) and a normal contralateral kidney were randomised to NSS or RN in European Organisation for Research and Treatment of Cancer Genito-Urinary Group (EORTC-GU) noninferiority phase 3 trial 30904.

Intervention

Patients were randomised to NSS (n = 268) or RN (n = 273) together with limited lymph node dissection (LND).

Measurements

Time to event end points was compared with log-rank test results.

Results and limitations

Median follow-up was 9.3 yr. The intention-to-treat (ITT) analysis showed 10-yr OS rates of 81.1% for RN and 75.7% for NSS. With a hazard ratio (HR) of 1.50 (95% confidence interval [CI], 1.03–2.16), the test for noninferiority is not significant (p = 0.77), and test for superiority is significant (p = 0.03). In RCC patients and clinically and pathologically eligible patients, the difference is less pronounced (HR = 1.43 and HR = 1.34, respectively), and the superiority test is no longer significant (p = 0.07 and p = 0.17, respectively). Only 12 of 117 deaths were the result of renal cancer (four RN and eight NSS). Twenty-one patients progressed (9 after RN and 12 after NSS). Quality of life and renal function outcomes have not been addressed.

Conclusions

Both methods provide excellent oncologic results. In the ITT population, NSS seems to be significantly less effective than RN in terms of OS. However, in the targeted population of RCC patients, the trend in favour of RN is no longer significant. The small number of progressions and deaths from renal cancer cannot explain any possible OS differences between treatment types.