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     

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.     

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 Pollen Extract (Cernilton) in Patients with Inflammatory Chronic Prostatitis–Chronic Pelvic Pain Syndrome: A Multicentre, Randomised, Prospective, Double-Blind, Placebo-Controlled Phase 3 Study

Background

National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists.

Objectives

To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS.

Design, setting, and participants

We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres.

Intervention

Participants were randomised to receive oral capsules of the pollen extract (two capsules q8 h) or placebo for 12 wk.

Measurements

The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post–prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk.

Results and limitations

In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n = 70) or placebo (n = 69). The individual domains pain (p = 0.0086) and quality of life (QoL; p = 0.0250) as well as the total NIH-CPSI score (p = 0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p = 0.0141), respectively. Adverse events were minor in all patients studied.

Conclusions

Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.     

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.     

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.     

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.     

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.     

Propensity-score-matched comparison of perioperative outcomes between open and laparoscopic nephroureterectomy: a national series

Background

Nephroureterectomy (NU) represents the primary management for patients with nonmetastatic upper tract urothelial carcinoma (UTUC). Either an open NU (ONU) or a laparoscopic NU (LNU) may be considered. Despite the presence of several reports comparing perioperative and cancer-control outcomes between the two approaches, no reports relied on a population-based cohort.

Objectives

Examine intraoperative and postoperative morbidity of ONU and LNU in a population-based cohort.

Design, setting, and participants

We relied on the US Nationwide Inpatient Sample (NIS) to identify patients with nonmetastatic UTUC treated with ONU or LNU between 1998 and 2009. Overall, 7401 (90.8%) and 754 (9.2%) patients underwent ONU and LNU, respectively. To adjust for potential baseline differences between the two groups, propensity-score-based matching was performed. This resulted in 3016 (80%) ONU patients matched to 754 (20%) LNU patients.

Intervention

All patients underwent NU.

Measurements

The rates of intra- and postoperative complications, blood transfusions, prolonged length of stay (pLOS), and in-hospital mortality were assessed for both procedures. Multivariable logistic regression analyses were performed within the cohort after propensity-score matching.

Results and limitations

For ONU versus LNU respectively, the following rates were recorded: blood transfusions, 15% versus 10% (p < 0.001); intraoperative complications, 4.7% versus 2.1% (p = 0.002); postoperative complications, 17% versus 15% (p = 0.24); pLOS (≥5 d), 47% versus 28% (p < 0.001); in-hospital mortality, 1.3% versus 0.7% (p = 0.12). In multivariable logistic regression analyses, LNU patients were less likely to receive a blood transfusion (odds ratio [OR]: 0.6; p < 0.001), to experience any intraoperative complications (OR: 0.4; p = 0.002), and to have a pLOS (OR: 0.4; p < 0.001). Overall, postoperative complications were equivalent. However, LNU patients had fewer respiratory complications (OR: 0.4; p = 0.007). This study is limited by its retrospective nature.

Conclusions

After adjustment for potential selection biases, LNU is associated with fewer adverse intra- and perioperative outcomes than ONU.     

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.     

Comparative analysis of outcomes and costs following open radical cystectomy versus robot-assisted laparoscopic radical cystectomy: results from the US Nationwide Inpatient Sample

Background

Although robot-assisted laparoscopic radical cystectomy (RARC) was first reported in 2003 and has gained popularity, comparisons with open radical cystectomy (ORC) are limited to reports from high-volume referral centers.

Objective

To compare population-based perioperative outcomes and costs of ORC and RARC.

Design, setting, and participants

A retrospective observational cohort study using the US Nationwide Inpatient Sample to characterize 2009 RARC compared with ORC use and outcomes.

Outcome measurements and statistical analysis

Propensity score methods were used to compare inpatient morbidity and mortality, lengths of stay, and costs.

Results and limitations

We identified 1444 ORCs and 224 RARCs. Women were less likely to undergo RARC than ORC (9.8% compared with 15.5%, p = 0.048), and 95.7% of RARCs and 73.9% of ORCs were performed at teaching hospitals (p < 0.001). In adjusted analyses, subjects undergoing RARC compared with ORC experienced fewer inpatient complications (49.1% and 63.8%, p = 0.035) and fewer deaths (0% and 2.5%, p < 0.001). RARC compared with ORC was associated with lower parenteral nutrition use (6.4% and 13.3%, p = 0.046); however, there was no difference in length of stay. RARC compared with ORC was $3797 more costly (p = 0.023). Limitations include retrospective design, absence of tumor characteristics, and lack of outcomes beyond hospital discharge.

Conclusions

RARC is associated with lower parenteral nutrition use and fewer inpatient complications and deaths. However, lengths of stay are similar, and the robotic approach is significantly more costly.     

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.     

Preoperative serum sex hormone-binding globulin as a predictive marker for extraprostatic extension of tumor in patients with clinically localized prostate cancer

Objectives

We investigated the relationships of serum sex hormone-binding globulin (SHBG) level with known prognostic factors for prostate cancer in men who received radical retropubic prostatectomy (RRP) for clinically localized prostate cancer.

Methods

Preoperative serum levels of SHBG were analyzed in 288 consecutive patients who were scheduled to undergo RRP for clinically localized prostate cancer. We investigated the potential associations of preoperative serum SHBG level with various clinical and pathological factors. Accuracy of variables in predicting adverse pathological features was assessed via receiver operator characteristics (ROC) curves.

Results

In univariate analysis, preoperative serum SHBG level was observed to be significantly associated with extraprostatic extension of a tumor (p = 0.019) and with pathological Gleason score (p = 0.001). In multivariate analysis, serum SHBG level (p = 0.039) along with serum PSA (p < 0.001) level, biopsy Gleason score (p < 0.001), and clinical stage (p = 0.004) was observed to be an independent predictor of the extraprostatic extension of prostate cancer. The area under ROC curve that demonstrated the performance of a multivariate logistic regression model (MLRM), which included serum SHBG level and other preoperative variables, in predicting extraprostatic extension of tumor was larger than that of MLRM without SHBG (0.797 vs. 0.758, p = 0.121). Meanwhile, serum SHBG level was not observed to be significantly associated with pathological Gleason score in multivariate analysis (p = 0.303).

Conclusions

Our data showed that serum SHBG level is an independent predictive factor for extraprostatic extension of tumor in patients with clinically localized prostate cancer.     

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.     

Amino-Terminal Pro-C-Type Natriuretic Peptide is Associated with the Presence, Severity, and Duration of Vasculogenic Erectile Dysfunction

Background

Endothelial dysfunction is a key event in the pathophysiology of erectile dysfunction (ED) and generalized vascular disease. C-type natriuretic peptide (CNP) is a paracrine molecule that effects endothelial integrity and vascular tone.

Objective

To determine the role of CNP in men with vasculogenic ED.

Design, setting, and participants

Fifty-two consecutive men (age: 57 ± 10 yr) with nonpsychogenic and nonhormonal ED for >6 mo and free of cardiovascular disease who were referred to the Cardiovascular Diseases and Sexual Health Unit of our Department for evaluation of ED were compared with 31 subjects with normal erectile function matched for age, body mass index, and traditional risk factors.

Measurements

Vasculogenic ED was diagnosed according to comprehensive history, physical examination, Sexual Health Inventory for Men (SHIM-5) scoring, hormonal testing, and penile color-Doppler ultrasound. Amino-terminal proCNP (NT-proCNP) was measured in plasma with enzyme-linked immunosorbent assay (ELISA).

Results and limitations

Compared to controls, ED patients had significantly lower NT-proCNP levels (0.21 ± 0.08 pmol/l in ED patients vs 0.34 ± 0.07 pmol/l in control subjects; p < 0.001). NT-proCNP levels were associated with erectile performance as expressed by SHIM-5 score (r = 0.57; p < 0.001), even after adjusting for confounders. There was also an inverse linear relationship between ED duration and NT-proCNP levels (p < 0.05). In patients with arteriogenic ED, there was a positive correlation of NT-proCNP levels with peak systolic velocity (PSV) (r = 0.51; p = 0.01).

Conclusions

CNP levels are associated with the presence, severity, and duration of ED. These findings provide further insight into the role of CNP in the pathophysiology of ED.     

A non-cancer-related survival benefit is associated with partial nephrectomy

Background

Partial nephrectomy (PN) may better protect against other-cause mortality (OCM) when compared with radical nephrectomy (RN) in patients with localized renal cell carcinoma (RCC).

Objective

Test the effect of treatment type on OCM.

Design, setting, and participants

Using the Surveillance Epidemiology and End Results–Medicare-linked database, 4956 RN patients (82%) and 1068 PN patients (18%) with T1a RCC were identified (1988–2005).

Measurements

To adjust for inherent differences between treatment types, we relied on propensity-matched analyses. One-to-one matching was performed according to age, sex, race, baseline Charlson comorbidity index (CCI), baseline diagnosis of hypercalcemia and hyperlipidemia, socioeconomic status (SES), population density, tumor size, and year of surgery. The 2- and 5-yr OCM rates were computed using cumulative incidence. Univariable and multivariable competing-risks regression analyses for prediction of OCM were performed according to treatment type. Adjustment was made for cancer-specific mortality (CSM), patient age, CCI, sex, race, SES, tumor grade, and year of surgery.

Results and limitations

Following propensity-based matching, 1068 RN patients were matched with 1068 PN patients. The 2- and 5-yr OCM rates after nephrectomy were 5.0% and 16.0% for PN versus 6.9% and 18.1% for RN, respectively. In the postpropensity multivariable analyses, patients who underwent PN were significantly less likely to die of OCM compared with their RN-treated counterparts (hazard ratio [HR]: 0.83; 95% confidence interval, 0.69–0.98; p = 0.04). Increasing age (HR: 1.08, p < 0.001), higher CCI (HR: 1.14, p < 0.001), female gender (HR: 0.79, p = 0.02), baseline hypercalcemia (HR: 2.05, p = 0.03), baseline hyperlipidemia (HR: 0.73, p = 0.003), and year of surgery (HR: 0.95, p = 0.003) were independent predictors of OCM.

Conclusions

Compared with PN-treated patients, RN-treated patients are more likely to die of OCM after surgery, even after adjusting for CSM, as well as baseline CCI. Consequently, PN should be offered whenever technically feasible.     

Robotic partial nephrectomy versus laparoscopic cryoablation for the small renal mass

Background

Open partial nephrectomy (OPN) remains the gold standard for treatment of small renal masses (SRMs). Laparoscopic cryoablation (LCA) has provided encouraging outcomes. Robotic partial nephrectomy (RPN) represents a new promising option but is still under evaluation.

Objective

Compare the outcomes of RPN and LCA in the treatment of patients with SRMs.

Design, setting, and participants

We retrospectively analyzed the medical charts of patients with SRMs (≤4 cm) who underwent minimally invasive nephron-sparing surgery (RPN or LCA) in our institution from January 1998 to December 2010.

Intervention

RPN and LCA.

Measurements

Perioperative complications and functional and oncologic outcomes were analyzed.

Results and limitations

A total of 446 SRMs were identified in 436 patients (RPN, n = 210; LCA, n = 226). Patients undergoing RPN were younger (p < 0.0001), had a lower American Society of Anesthesiologists score (p < 0.001), and higher baseline preoperative estimated glomerular filtration rate (eGFR) (p < 0.0001). Mean tumor size was smaller in the LCA group (2.2 vs 2.4 cm; p = 0.004). RPN was associated with longer operative time (180 vs 165 min; p = 0.01), increased estimated blood loss (200 vs 75 ml; p < 0.0001), longer hospital stay (72 vs 48 h; p < 0.0001), and higher morbidity rate (20% vs 12%, p = 0.015). Mean follow-ups for RPN and LCA were 4.8 mo and 44.5 mo, respectively (p < 0.0001). Local recurrence rates for RPN and LCA were 0% and 11%, respectively (p < 0.0001). Mean eGFR decrease after RPN and LCA was insignificant at 1 mo, at 6 mo after surgery, and during last follow-up. Limitations include retrospective study design, length of follow-up, and selection bias.

Conclusions

Both techniques remain viable treatment options in the management of SRMs. A higher incidence of perioperative complications was found in patients undergoing RPN. However, the technique was not predictive of the occurrence of postoperative complications. Early oncologic outcomes are promising for RPN, which also seems to be associated with better preservation of renal function. Long-term follow-up and well-designed prospective comparative studies are awaited to corroborate these findings.     

Occlusion of seminal vesicles increases sexual activity in a mouse model

Background

Little is known about the physiologic role of seminal vesicles beyond their fertility function. It has been suggested repeatedly that seminal vesicles have an impact on sexual activity. Although this has been investigated in various animal models, such a role has never been found.

Objective

To assess in a novel mouse model whether occlusion of seminal vesicles affects sexual activity.

Design, setting, and participants

Adult male CD1 mice (n = 77) were assigned randomly to the experimental groups: (1) seminal vesicle occlusion (SVO) (n = 24), (2) seminal vesicle resection (SVR) (n = 23), and (3) sham operation (SO) (n = 30). Adult females were brought into estrus by the Whitten effect. After recuperation, mouse pairs were observed during sessions of 3 h each. Sexual activity was analyzed separately by three observers blinded to the experimental conditions.

Intervention

SVO, SVR, and SO.

Outcome measurements and statistical analysis

The primary end point was percentage of sessions with intromission; secondary end points were number of intromissions and latency until first intromission. A logistic regression model and the Kruskal-Wallis test were used.

Results and limitations

A total of 141 sessions for a total of 423 h were analyzed. Intromission was scored in 20 of 42 sessions (48%) with SVO mice, a significantly higher rate than the 8 of 39 sessions (21%) with SVR mice (p = 0.001) and 18 of 60 sessions (30%) with SO mice (p = 0.004). Secondary end points were comparable in all three groups (p = 0.303 and 0.450, respectively).

Conclusions

Males with SVO were significantly more often sexually active than males undergoing SVR or SO. This suggests that occluded, and thus engorged, seminal vesicles increase sex drive in male mice. Since the potential clinical benefit might be highly relevant, further studies should confirm these promising results and investigate the potential application in men.     

Perioperative efficacy of laparoscopic partial nephrectomy for tumors larger than 4 cm

Background

Laparoscopic partial nephrectomy (LPN) is typically reserved for kidney tumors ≤4 cm in size. The use of LPN in patients with larger tumors (>4 cm) has not been systematically evaluated.

Objective

To examine technical feasibility and perioperative safety and efficacy of LPN for clinical stage pT1b–T2 tumors >4 cm.

Design, setting, and participants

This is a retrospective review of data from an Institutional Review Board–approved, prospectively maintained database of 425 LPN procedures over a 6-yr period (September 1999 through December 2005). Patients were grouped according to tumor size: control group1: <2 cm (n = 89; 21% of patients); control group 2: 2–4 cm (n = 278; 65% of patients); and study group 3: >4 cm (n = 58; 14% of patients).

Intervention

Retroperitoneal and transperitoneal LPN.

Measurements

Serum creatinine levels, estimated glomerular filtration rates.

Results and limitations

For groups 1, 2, and 3, mean tumor size was 1.5 cm, 2.9 cm, and 6 cm in diameter, respectively (p < 0.001). Study group 3 patients more often had an American Society of Anesthesiologists score ≥3 (p < 0.05), central tumors (p < 0.001), pelvicalyceal repair (p = 0.004), and heminephrectomy (p < 0.001). Total operative time, estimated blood loss, and duration of hospital stay were equivalent. Mean warm ischemia time was 30 min, 32 min, and 38 min in groups 1, 2, and 3, respectively (p = 0.007). Tumor size >4 cm did not increase significant risk for positive tumor margins, intraoperative complications, or postoperative genitourinary complications. In each group preoperative stage ≥3 chronic kidney disease (CKD) was present in 31%, 35%, and 44% of patients in groups 1, 2, and 3, respectively (p = 0.15); postoperatively, stage 3–5 CKD incidence increased to 52%, 52%, and 63% in groups 1, 2, and 3, respectively (p = 0.20). Patients with tumor size >4 cm and preoperative stage 3–5 CKD had an 8-fold increase in risk for CKD stage progression. Limitations of the study include retrospective analysis and a relatively low number of patients in group 3.

Conclusions

Given laparoscopic expertise and appropriate patient selection, LPN is feasible and efficacious for kidney tumors >4 cm. Indications for LPN should be expanded to include patients with amenable tumors >4 cm in order to maximally preserve kidney function in these patients.     

The Extent of Lymphadenectomy Seems to Be Associated with Better Survival in Patients with Nonmetastatic Upper-Tract Urothelial Carcinoma: How Many Lymph Nodes Should Be Removed?

Background

The role and extent of lymphadenectomy in patients with upper-tract urothelial carcinoma (UTUC) is debated.

Objective

To establish whether the number of lymph nodes (LNs) removed might be associated with better cause-specific survival in patients with UTUC.

Design, setting, and participants

The study included 552 consecutive patients who underwent radical nephroureterectomy (RNU) and lymphadenectomy between 1992 and 2006.

Intervention

Patients were treated with RNU and lymphadenectomy.

Measurements

Univariable and multivariable Cox proportional hazards regression models addressed the association between the number of LNs removed and cause-specific mortality (CSM). The number of LNs removed was coded as a cubic spline to allow for nonlinear effects. Finally, the most informative cut-off for the number of removed LNs was identified.

Results and limitations

In the entire population, the number of LNs removed was not associated with CSM in univariable (hazard ratio [HR]: 0.99; p = 0.16) or in multivariable (HR: 0.97; p = 0.12) analyses. In contrast, in the subgroup of pN0 patients (n = 412), the number of LNs removed achieved the independent predictor status of CSM (HR: 0.93; p = 0.02). Eight LNs removed was the most informative cut-off in predicting CSM (HR: 0.42; p = 0.004). The inclusion of the variable defining dichotomously the number of removed LNs (<8 vs ≥8) in the base model (age, Eastern Cooperative Oncology Group performance status, pathologic stage, grade, architecture, and lymphovascular invasion) significantly increased the accuracy in predicting CSM (+1.7%; p < 0.001).

Conclusions

The extension of the lymphadenectomy in pN0 UTUC patients seems to be associated with CSM. Longer survival was observed in patients in whom at least eight LNs had been removed.