Influence of obesity on tumour volume in patients with prostate cancer

Study Type – Prognosis (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Obesity is associated with more aggressive prostate cancer. Prostate cancer tumour volume is affected by excess weight, after adjustment for all possible clinical and pathological confounders.

OBJECTIVE

• ? To investigate the association between body mass index and tumour volume at radical prostatectomy in a large European population.

PATIENTS AND METHODS

• ? Recent data support the hypothesis that the hormonal environment in overweight and obese men may alter androgen‐dependent prostate growth. Body mass index (BMI) has been implicated in prostate cancer pathophysiology.
• ? We analysed 1275 patients with prostate cancer who underwent radical prostatectomy at a single tertiary care institution. Mean tumour volume (TV) was evaluated according to BMI WHO categories (normal <25 kg/m² vs overweight 25–30 kg/m² vs obese 30–35 kg/m² vs severely obese >35 kg/m²).
• ? Univariable linear regression analyses targeted the association between BMI and TV at radical prostatectomy. Multivariable analyses were adjusted for age, prostate‐specific antigen value, biopsy Gleason sum, clinical stage and prostate volume.

RESULTS

• ? Mean BMI was 26.3 kg/m² (median 26; range 16.7–42.0). Mean TV was 5.6 mL (median 3.3; range 0.1–61.2). The mean prostate‐specific antigen value was 10.3 ng/dL (median 6.6; range 0.3–327).
• ? The mean TV was 5.0, 5.8, 6.3 and 9.2 mL in normal, overweight, obese and severely obese patients, respectively (P= 0.03). TVs in men with a normal BMI were 84% smaller than in severely obese men (5.0 vs 9.2 mL).
• ? On univariable analysis, BMI was correlated with TV at radical prostatectomy (P < 0.001). On multivariable analysis, BMI reached the independent predictor status after adjustment for age, prostate‐specific antigen value, biopsy Gleason score, clinical stage and prostate volume (P= 0.03).

CONCLUSION

• ? We showed that BMI is independently associated with prostate cancer volume at radical prostatectomy. The present results confirm that obesity may play a key role in prostate cancer pathophysiology.

     

Obesity is associated with castration-resistant disease and metastasis in men treated with androgen deprivation therapy after radical prostatectomy: results from the SEARCH database

Study Type – Prognosis (cohort series) Level of Evidence 2a What's known on the subject? and What does the study add? The incidence and prevalence of obesity in the USA and Europe is increasing. Higher body mass index is associated with a lower risk of overall prostate cancer diagnosis but also with an increased risk of high grade prostate cancer. Obese men undergoing primary therapy with radical prostatectomy or external beam radiation are more likely to experience a biochemical recurrence after treatment compared with normal weight men. Finally, obesity is associated with increased prostate‐cancer‐specific mortality. We hypothesized that obese men on androgen deprivation therapy may be at increased risk for prostate cancer progression. Previous studies have shown that obese men have lower levels of testosterone compared with normal weight men. Additionally, one previous study found that obese men have higher levels of testosterone on androgen deprivation therapy. Men with higher levels of testosterone on androgen deprivation therapy are at increased risk of prostate cancer progression. We found that men with higher body mass index were at increased risk of progression to castration‐resistant prostate cancer, development of metastases and prostate‐cancer‐specific mortality. When we adjusted for various clinicopathological characteristics, obese men were at increased risk of progression to castration‐resistant prostate cancer and development of metastases. The results of our study help generate hypotheses for further study regarding the mechanisms between obesity and aggressive prostate cancer.

OBJECTIVE

• ? To investigate whether obesity predicts poor outcomes in men starting androgen deprivation therapy (ADT) before metastasis, since previous studies found worse outcomes after surgery and radiation for obese men.

METHODS

• ? A retrospective review was carried out of 287 men in the SEARCH database treated with radical prostatectomy between 1988 and 2009.
• ? Body mass index (BMI) was categorized to <25, 25–29.9 and ≥30 kg/m2.
• ? Proportional hazards models were used to test the association between BMI and time to castration‐resistant prostate cancer (PC), metastases and PC‐specific mortality adjusting for demographic and clinicopathological data.

RESULTS

• ? During a median 73‐month follow‐up after radical prostatectomy, 403 men (14%) received early ADT.
• ? Among 287 men with complete data, median BMI was 28.3 kg/m2.
• ? Median follow‐up from the start of ADT was 52 months during which 44 men developed castration‐resistant PC, 34 developed metastases and 24 died from PC.
• ? In multivariate analysis, higher BMI was associated with a trend for greater risk of progression to castration‐resistant PC (P= 0.063), a more than threefold increased risk of developing metastases (P= 0.027) and a trend toward worse PC‐specific mortality (P= 0.119).
• ? Prognostic biomarkers did not differ between BMI groups.

CONCLUSIONS

• ? Among men treated with early ADT, our results suggest that obese men may have increased risk of PC progression.
• ? These data support the general hypothesis that obesity is associated with aggressive PC, although validation of these findings and further study of the mechanisms linking obesity and poor PC outcomes are required.

     

Automatic evaluation of ultrasonography-estimated bladder weight and bladder wall thickness in community-dwelling men with presumably normal bladder function

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The diagnostic potential of ultrasound derived measurements of bladder wall thickness and bladder weight in men with LUTS and varying degrees of BOO have been explored. However, there is a paucity of such measurements in the asymptomatic population with which to compare such patients. This study investigates these measurements in community‐dwelling men with presumably normal bladder function.

OBJECTIVE

• ? To identify measurements of ultrasonography (US)‐derived bladder wall thickness (BWT) and bladder weight in community‐dwelling men with presumably normal bladder function.

SUBJECTS AND METHODS

• ? A total of 100 male volunteers underwent transabdominal US measurements of BWT and bladder weight, using the BVM 9500 bladder scanner (Verathon Medical, Bothell, WA, USA), at a variety of bladder filling volumes.
• ? The data were explored for any correlation between measurements of BWT and US‐estimated bladder weight (UEBW) with subject age, height, weight, body mass index (BMI), International Consultation on Incontinence Questionnaire – Male Lower Urinary Tract Symptoms (ICIQ M‐LUTS) score, International Prostate Symptom Score (IPSS) and IPSS Quality of Life index (IPSS QoL).

RESULTS

• ? Several statistically significant but weak correlations were observed: BWT and weight (r= 0.216, P= 0.032); BWT and BMI (r= 0.246, P= 0.014); UEBW and weight (r= 0.304, P= 0.002); and UEBW and BMI (r= 0.260, P= 0.009).
• ? Bladder filling volume appeared to have a greater effect on BWT than on UEBW, although this could not be determined accurately.
• ? There was a substantial difference in measurements of BWT and UEBW in the assessment of inter‐ and intra‐observer reliability testing.

CONCLUSION

• ? Further studies are required to validate automated measurements of BWT and UEBW and to investigate such measurements in the symptomatic and asymptomatic male population.

     

A novel cost-effective approach to post-vasectomy semen analysis

Study Type – Diagnostic (cost minimisation analysis)
Level of Evidence 3b

OBJECTIVE

• ? To examine compliance, clearance rates and cost‐effectiveness of a novel approach to managing men following vasectomy based on the testing of sperm viability.

PATIENTS AND METHODS

• ? Between January 2003 and March 2005, 832 men undergoing vasectomy were followed prospectively for a minimum of 12 months.
• ? Post‐vasectomy semen analysis (PVSA) was carried out at 16 weeks with repeat at 20 weeks only if sperm were detected on initial PVSA i.e. a single clear PVSA on simple microscopy was deemed sufficient for declaring vasectomy successful.
• ? In men with persistent non‐motile sperm (PNMS) in the second specimen, comprehensive analysis of number and viability of sperm using a fluorescent probe was carried out on a fresh semen specimen taken in accordance with British Andrology Society (BAS) guidelines.

RESULTS

• ? Overall compliance with the PVSA protocol was 81.3% (95% CI 78.5 to 83.8). No sperm were seen in 540 (78.8%) and 70 (10.3%) at the initial and 2^nd PVSA respectively.
• ? Persistent spermatozoa at 20 weeks were present in 66 (9.8%, 7.8 to 12.2) cases with 58 (8.6%, 6.7 to 11.0) having PNMS and 8 (1.2%, 0.6 to 2.3) having motile sperm.
• ? Fluorescent viability testing in 53 of the 58 with PNMS showed viable sperm in 2 (3.8%, 1.0 to 12.8). The failure rate of vasectomy defined by PVSA (8 with motile sperm on 2^nd PVSA and 2 with viable non‐motile sperm on fluorescent testing) was 1.2% (0.7 to 2.2).
• ? Average cost per vasectomy of PVSA using this protocol was £10.77 (US$ 16.67) compared with a minimum likely average cost using BAS guidelines of £18.10 (US$ 28).

CONCLUSION

• ? Demonstrating absence of sperm on simple light microscopy in a single specimen of semen at 16 or 20 weeks post‐vasectomy and reserving comprehensive testing of sperm viability for only the higher risk group with PNMS improves compliance and represents a cost‐effective strategy for declaring surgical success. This reduces the costs of PVSA by least 40% compared with adherence with BAS guidelines without compromising success in determining outcome after vasectomy.

     

Pregnancy rate after vasectomy reversal in a contemporary series: influence of smoking, semen quality and post-surgical use of assisted reproductive techniques

Study Type – Outcomes (cohort series) Level of Evidence 2b What's known on the subject? and What does the study add? Microsurgical vasectomy reversal is an effective and cost‐effective method of reinstating fertility in a man who has previously had a vasectomy. The current literature indicates that the success rate (i.e. potency and pregnancy rates) are dependent primarily on the time elapsed since vasectomy and the age of the female partner. Using a multivariate Cox regression model, evaluation of the influence of preoperative data (including smoking) and semen parameters indicates a significant influence of post‐surgical sperm motility only, on time to first pregnancy. The use of assisted reproductive techniques, when natural pregnancy failed, was successful in ≈50% of couples who attempted this procedure and accounted for an absolute increase in pregnancy rate of 14%.

OBJECTIVE

• ? To determine the influence of smoking, postoperative semen characteristics and the use of an assisted reproductive technique (ART) on pregnancy rate in a contemporary series of men undergoing vasectomy reversal.

PATIENTS AND METHODS

• ? Between January 2002 and January 2009, 186 vasectomy reversals were performed. Of the 171 patients who could be contacted for follow‐up, 162 attempted pregnancy and constitute the study group.
• ? Semen analysis was performed 3 months after the procedure and at subsequent 3‐monthly intervals.
• ? Patient characteristics and surgical information were obtained from a computerized database, and follow‐up data were collected by telephone interview.
• ? A multivariate Cox regression model was used to discern possible prognosticators with respect to pregnancy outcome.

RESULTS

• ? The overall patency rate was 91.4%, with a natural pregnancy rate of 44.4% and a subsequent 14.2% of patients conceiving using a ARTs resulting in a total pregnancy rate of 58.6%. Multiple pregnancies were obtained by 20.4% of couples.
• ? Smoking of the male or female partner did not influence the probability of conception.
• ? In a multivariate model that included, among other factors, time since vasectomy, female age and semen characteristics, only sperm motility was significantly related to natural pregnancy outcome.
• ? The probability of obtaining a natural pregnancy within 2 years after surgery is 53% for men with sperm motility >20% (WHO a+b) compared to 19% for men with sperm motility <5% (P= 0.003).

CONCLUSIONS

• ? A clear and significant association between sperm motility and the probability of conception was found, whereas smoking, female age and time since vasectomy appeared to have no influence on pregnancy outcome in this patient cohort.
• ? The use of ARTs accounted for an absolute increase in pregnancy rate of 14.2%.

     

Comparison of the rate, location and size of positive surgical margins after laparoscopic and robot-assisted laparoscopic radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

• ? To review and compare the rate, location and size of positive surgical margins (PSMs) after pure laparoscopic radical prostatectomy (LRP) and robot‐assisted laparoscopic radical prostatectomy (RALP).

PATIENTS AND METHODS

• ? The study comprised 200 patients who underwent RALP and 200 patients who underwent LRP up to January 2008.
• ? We compared patient age, body mass index, preoperative prostate‐specific antigen (PSA), preoperative stage and grade, prostate size, pathological stage and grade and neurovascular bundle preservation, as well as PSM rate, size and location.
• ? Continuous and categorical data were compared using Student’s t‐test and Pearson’s chi‐squared test.
• ? Multivariate regression analyses were used to identify preoperative and intraoperative predictors of PSMs.

RESULTS

• ? Although the PSM rate was similar between the two groups (LRP: 12% vs RALP: 13.5%; P= 0.76), location and size were not. PSMs after LRP were mostly at the apex (58.3%; P= 0.038), while most PSMs after RALP were posterolateral ([PL] 48%; P= 0.046).
• ? In addition, the median margin size after RALP was significantly smaller than after LRP (RALP: 2 mm vs LRP: 3.5 mm; P= 0.041).
• ? In univariate and multivariate analyses, tumour‐node‐metastasis (TNM) stage and preoperative PSA were the only independent preoperative predictors of PSMs (P= 0.044 and P= 0.01, respectively).

CONCLUSION

• ? The PSM risk is dependent on TNM stage and preoperative PSA and not the surgical technique, when comparing LRP with RALP.

     

Prostate laser vaporization in men with urinary retention

Study Type – Therapy (cohort) Level of Evidence 2b

OBJECTIVE

• ? To evaluate the safety and efficacy of laser vaporization of the prostate (LVP) with several different wavelengths for urinary retention.

PATIENTS AND METHODS

• ? A cohort study of patients undergoing LVP from 2005 to 2009 at a single institution was performed.
• ? Outcomes were compared in those patients with urinary retention versus those without, using t‐tests, Mann–Whitney U‐test, chi‐squared test and Fisher’s exact test as appropriate.

RESULTS

• ? During the study period, 122 patients underwent LVP, of which 39 (32%) presented with refractory urinary retention requiring indwelling or intermittent catheterization.
• ? The mean ± SD period of postoperative follow‐up was 11.2 ± 9.6 months. Comparing patients with and without urinary retention, there were no significant preoperative differences in median body mass index (25.6 versus 26.4 kg/m²; P= 0.40) or prostate‐specific antigen (2.3 versus 2 ng/mL; P= 0.27).
• ? Patients with urinary retention were significantly more likely to be diabetic (33% versus 12%; P= 0.01), have heart disease (36% versus 15%; P= 0.01) and be taking anticoagulants (61% versus 31%; P= 0.003).
• ? Following LVP, retention patients were more likely than non‐retention patients to fail an initial voiding trial (28.2% versus 7.2%; P= 0.002).
• ? In total, 36 of 39 (92%) retention patients no longer required catheterization after postoperative recovery. No patients required perioperative transfusion.
• ? Compared to those without preoperative retention, retention patients had a longer median duration of postoperative catheterization (3 versus 1 days; P= 0.01).
• ? There were similar rates of low‐ and high‐grade complications (P= 0.275 and 1.000, respectively) and no significant difference in median hospital stay (1 versus 0 days; P= 0.212).

CONCLUSIONS

• ? In the present study cohort, LVP was an effective and safe therapy for urinary retention.
• ? Compared to patients without retention, those with retention had a higher prevalence of heart disease, diabetes and anticoagulant use.
• ? Because the morbidity of LVP is low, and the prevalence of co‐morbid disease high, LVP should be considered for the surgical management of refractory urinary retention.

     

Side effects of intradetrusor botulinum toxin injections on ejaculation and fertility in men with spinal cord injury: preliminary findings

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The beneficial effect of intradetrusor botulinum toxin (BT) injections on hyperactive bladders in individuals with spinal cord injury is known from the literature, but its potential effect on ejaculation and fertility through diffusion is not. As BT injection paralyses the bladder muscle, it may also paralyse the muscular envelopes of the adjacent reproductive organs and lead to potential negative side effects, which have not been studied yet. This study provides preliminary data on the potential negative side effects of BT injections on semen volume and retrograde ejaculation, as well as some potential beneficial effects on semen quality.

OBJECTIVE

• ? To investigate the effect of botulinum neurotoxin A on ejaculation potential and fertility. Intradetrusor injection of botulinum neurotoxin A is most commonly used nowadays to treat overactive bladder in patients with spinal cord injury (SCI).

PATIENTS AND METHODS

• ? Retrospective analyses were carried out of 11 patients with complete lesions from C5 to T6 who had received botulinum (BT) injections for their overactive bladder and who had undergone ejaculation tests before and after BT treatment.

RESULTS

• ? BT treatment was found effective in improving bladder function in up to 85% of the cases.
• ? While no patients maintained natural ejaculation following their SCI, BT treatment was found to increase the incidence of retrograde ejaculation (vibrostimulation) in 46% of cases and to diminish semen volume in 77% of cases, from an average of 1.8 mL to 1 mL.
• ? Semen quality was slightly improved following BT treatment, sperm mobility increased in 67% of cases, sperm vitality in 50% and semen culture improved in 43%.

CONCLUSIONS

• ? BT treatment has beneficial and detrimental effects on ejaculation function. The detrimental effects involve retrograde ejaculation and reduced semen volume, which are explained by the spread of toxin to the bladder neck, reducing its tonus, and to the smooth muscle sexual accessory organs, reducing the strength of their contraction.
• ? The beneficial effects are explained by the reduced contamination of the semen by urinary infection, which may improve spermatogenesis and subsequent semen quality.
• ? The results are discussed in terms of their clinical implications and advice to patients.

     

The value of urinary prostate cancer gene 3 (PCA3) scores in predicting pathological features at radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? PCA3 scores correlate to numerous histoprognostic factors, specifically tumour volume and positive surgical margins. These results may have a clinical impact in the near future on the selection of patients eligible to undergo active surveillance and nerve‐sparing surgery.

OBJECTIVE

• ? To assess correlations between Prostate CAncer gene 3 (PCA3) levels and pathological features of radical prostatectomy (RP) specimens, which define cancer aggressiveness.

PATIENTS AND METHODS

• ? After digital rectal examination (DRE), first‐catch urine was collected from 160 patients with localized prostate cancer. The PCA3 score was calculated using the Gene Probe Progensa^? assay.
• ? PCA3 scores were then correlated to the pathological features of the RP specimens.

RESULTS

• ? PCA3 scores correlated significantly with tumour volume (r= 0.34, P < 0.01). A PCA3 score of >35 was an independent predictor in a multivariate analysis of a tumour volume >0.5 mL (odds ratio [OR] 2.7, P= 0.04).
• ? It was also an independent predictor of positive surgical margins (OR 2.4, P= 0.04). Receiver–operator characteristic curves indicated PCA3 as the most accurate predictor of positive margins (area under the curve [AUC] 0.62), in addition to a positive biopsy percentage (AUC 0.52).
• ? There was also a significant difference in the mean PCA3 score between Gleason score patient groups (6 vs ≥7) and pathological stage groups (pT0/2 vs pT3/4).

CONCLUSIONS

• ? PCA3 scores correlate to numerous histoprognostic factors, specifically tumour volume and positive surgical margins.
• ? These results may have a clinical impact in the near future on the selection of patients eligible to undergo active surveillance and nerve‐sparing surgery.

     

Redefining abnormal follicle-stimulating hormone in the male infertility population

Study Type – Diagnostic (validating cohort) Level of Evidence 2a What's known on the subject? and What does the study add? FSH is a hormone released by the anterior pituitary gland via stimulation from gonadotrophin‐releasing hormone and potentially other factors. FSH reflects the status of spermatogenesis (i.e. the ability to produce sperm) as a result of the feedback between the testis and hypothalamus/pituitary glands. An elevated FSH level is indicative of abnormal spermatogenesis and may indicate primary testicular failure. The range for ‘normal’ FSH varies somewhat between institutions but has been defined by the Strong Memorial Hospital (Rochester, NY, USA) clinical laboratory as 1.4–18.1 IU/L based on the ADVIA Centaur (Siemens Medical Solutions, Tarrytown, NY, USA) FSH assay. The findings obtained in the present study could be helpful for predicting male factor infertility in patients with a borderline high FSH level (≈4.5 IU/L) and a low testosterone level compared to someone with a borderline high FSH level and a normal testosterone level. Although the ‘normal’ range for FSH is qualified as a value in the range 1.4–18.1 IU/L, the present study shows that an FSH level >4.5 IU/L was associated with abnormal semen analysis in terms of morphology and sperm concentration in the present patient population. Therefore, these findings suggest that FSH values lower than those currently considered normal may be associated with abnormal semen analysis, and that the ‘normal’ range for FSH used in clinical settings may need to be reconsidered.

OBJECTIVE

• ? To examine the correlation between follicle‐stimulating hormone (FSH) and testosterone/FSH levels with semen analysis parameters to evaluate whether the range for judging normal FSH levels should be reconsidered.

PATIENTS AND METHODS

• ? The present study included 610 male infertility patients from a single urology infertility clinic between 2004 and 2008.
• ? Patients (n = 153) were excluded for obstructive azoospermia, hypogonadotrophic hypogonadism, steroid use or failure to complete testing.
• ? Abnormal semen analysis values were based on the WHO 1999 criteria.
• ? We performed t‐tests, anova , chi‐squared tests and logistic regression to statistically examine the association between the FSH (or testosterone/FSH ratio) level and semen parameters.

RESULTS

• ? The FSH level showed statistically significant associations, as well as evidence of a dose response, with abnormal sperm concentration and morphology but not with semen volume.
• ? In men with FSH levels >7.5 IU/L, the risk of abnormal semen quality was five‐ to thirteen‐fold higher than that of men with FSH levels <2.8 IU/L depending on the specific semen parameter.
• ? Similarly, semen parameters were had a greater probability of being abnormal with decreasing testosterone/FSH ratios.

CONCLUSION

• ? A significantly increased risk of abnormal semen analyses among men with FSH levels >4.5 IU/L and decreasing testosterone/FSH ratios suggests that redefining normal FSH in infertile men would be valuable.

     

Percutaneous vs surgical cryoablation of the small renal mass: is efficacy compromised?

Study Type – Therapy (systematic review)
Level of Evidence 1b What’s known on the subject? and What does the study add? Cryoablation of the small renal mass is one amongst many minimally invasive approaches to treatment. Cryoablation can be performed both surgically and percutaneously; direct comparison of the two approaches has proven the percutaneous approach to be cheaper, less morbid, result in shorter procedure times, and shorter hospital stays, all with equal efficacy. Our study examines the decision as well as reporting process for the selection of treatment approach to determine if patients are being unnecessarily exposed to more invasive therapeutic options.

OBJECTIVE

• ? To review and analyse the cumulative literature to compare surgical and percutaneous cryoablation of small renal masses (SRMs).

METHODS

• ? A MEDLINE search was performed (1966 to February 2010) of the published literature in which cryoablation was used as therapy for localized renal masses.
• ? Residual disease was defined as persistent enhancement on the first post‐ablation imaging study, while recurrent disease was defined as enhancement after an initially negative postoperative imaging study, consistent with the consensus definition by the Working Group on Image‐Guided Tumor Ablation.
• ? Data were collated and analysed using the two‐sample Mann–Whitney test and random‐effects Poisson regression, where appropriate.

RESULTS

• ? In all, 42 studies, representing 1447 lesions treated by surgical (n= 28) or percutaneous (n= 14) cryoablation were pooled and analysed.
• ? No significant differences were detected between approaches regarding patient age (median 67 vs 66 years, P= 0.55), tumour size (median 2.6 vs 2.7 cm, P= 0.24),or duration of follow‐up (median 14.9 vs 13.3 months, P= 0.40).
• ? Differences in rates of unknown pathology also failed to reach statistical significance (14 vs 21%, P= 0.76). The difference in the rate of residual tumour was not statistically different (0.033 vs 0.046, P= 0.25), nor was the rate of recurrent tumour (0.008 vs 0.009, P= 0.44).
• ? The reported rate of metastases was negligible in both groups, precluding statistical analysis.

CONCLUSIONS

• ? Cryoablation has shown acceptable short‐term oncological results as a viable strategy for SRMs.
• ? Analysis of the cumulative literature to date shows that surgical and percutaneous cryoablation have similar oncological outcomes.

     

The impact of nerve sparing on incidence and location of positive surgical margins in radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Nerve sparing radical prostatectomy has been associated with increased risk of positive surgical margins due to the close anatomical relationship of the neurovascular bundle to the posterolateral aspect of the prostatic fascia. Our study of 945 men who underwent radical prostatectomy be one experienced surgeon found no increased risk of positive surgical margins, whether the cancer was organ confined or extracapsular extension was present.

OBJECTIVE

• ? To examine whether nerve‐sparing surgery (NSS) is a risk factor for positive surgical margins (PSMs) in patients with either organ‐confined prostate cancer or extracapsular extension (ECE).

PATIENTS AND METHODS

• ? Clinicopathological outcome data on 945 consecutive patients treated with radical prostatectomy (RP) were prospectively collected.
• ? All patients underwent RP (bilateral, unilateral or non‐NSS) by one surgeon between 2002 and 2007.
• ? Risk of PSMs and their locations with respect to NSS was determined by multivariate logistic regression analysis adjusting for preoperative risk factors for PSMs within pT2, pT3a and pT3b tumours.

RESULTS

• ? Overall a PSM was identified in 19.6% of patients in an unscreened population with mean prostate‐specific antigen (PSA) level of 8.1 ng/mL.
• ? There was no significant difference in rates of PSMs between NSS groups on multivariate analysis (P= 0.147).
• ? There was no significant difference in pT2 (P= 0.880), pT3a (P= 0.175) or pT3b (P= 0.354) tumours.
• ? The only significant predictor of PSMs was preoperative PSA level (risk ratio 1.289, P= 0.006).
• ? There was no significant difference in the location of PSMs except for the pT3a group, where the patients that had bilateral NSS were at higher risk of a posterolateral PSM (P= 0.028).

CONCLUSIONS

• ? With appropriate selection of patients, NSS does not increase the risk of PSMs, whether the cancer is organ confined or ECE is present.
• ? The adverse impact of the NSS procedure in the hands of an experienced surgeon is minimal and is a realistic compromise to obtain the increase in health‐related quality of life offered by NSS.

     

Prospective multi-centre study of adjustable single-incision mini-sling (Ajust(®) ) in the management of stress urinary incontinence in women: 1-year follow-up study

Study Type – Therapy (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? A number of SIMS have been introduced into clinical practice in 2006 and has been so far shown to be inferior to standard mid urethral‐slings. Adjustable SIMS (Ajust) have been recently introduced into clinical practice however with little evidence on its safety and efficacy in surgical treatment of female SUI. SIMS‐Ajust^® is associated with low rates of postoperative pain and peri‐operative morbidity and is both feasible and acceptable under local anaesthesia. The patient reported success rate at 1‐year is 80%.

OBJECTIVES

• ? To determine whether an adjustable single‐incision mini‐sling (SIMS, Ajust^®) is safe and effective in the management of female stress urinary incontinence (SUI) at 12 months follow‐up.
• ? To determine whether it is feasible to be performed under local anesthesia (LA).

MATERIALS AND METHODS

• ? The present study is a multicentre prospective cohort study in which 90 female patients underwent SIMS‐Ajust^® using a standardized insertion technique.
• ? The last 45 women were offered the procedure under LA.
• ? All patients completed their 12‐month follow‐up.

RESULTS

• ? The patient‐reported success rate, using Patient Global Impression of Improvement (PGI‐I), was 80% at 12 months follow‐up and a further 6% (n= 5) reported themselves to be ‘improved’.
• ? In all, 32/45 (71%) patients agreed to undergo the procedure under LA while one patient required conversion to general anaesthetic.
• ? There was no organ damage or requirement for blood transfusion.
• ? Significantly lower rates of blood loss (P= 0.025) and postoperative voiding difficulties (P= 0.026) were seen in the LA group.
• ? The re‐operation rate for SUI was 6% at 12 months.

CONCLUSIONS

• ? SIMS (Ajust) appears to be a safe procedure, which is feasible under LA.
• ? SIMS (Ajust) have an 80% patient‐reported success rate at 12 months follow‐up.

     

Frequency of regulatory T cells in peripheral blood and in tumour‐infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma

What’s known on the subject? and What does the study add? Treg overexpression has been demonstrated in several neoplasms, including liver, breast, pancreas and melanoma, while it has not been well evaluated in renal cancer. In renal cancer patients versus controls we found an increased expression of these cells, especially in tumour‐infiltrating lymphocytes. Moreover, Treg frequency significantly correlated with pathological stage, nuclear grade and prognostic models.

OBJECTIVE

• ? To compare the frequency of T regulatory cells (Tregs) in peripheral blood of patients (pPB) affected by renal cell carcinoma (RCC) both with the frequency of Tregs found in PB of healthy donors (hPB) and that of Tregs present in tumour infiltrating lymphocytes (TILs). To verify in vitro the inhibitory activity of tumour isolated Tregs on the effector T cells and, finally, to assess the prognostic role of Treg frequency determination.

PATIENTS AND METHODS

• ? Treg frequency in hPB, pPB and TILs was evaluated in 30 patients and 20 healthy controls by measuring both membrane‐CD25 and intracytoplasmic‐Foxp3 expression by flow cytometry.
• ? Treg inhibitory activity was evaluated by an in vitro proliferation assay performed on total, CD25‐depleted mononuclear cells (MNC) and CD25‐depleted MNC cultured in the presence of purified CD25⁺ Tregs.
• ? Finally, Treg frequency in pPB and TIL were correlated with conventional prognostic factors and scores of University of California Los Angeles and Kattan predictive models.

RESULTS

• ? Treg frequency was higher in TILs than in pPB (P= 0.002), whereas there were no important differences between hPB and pPB. CD25⁺ cells isolated either from PB and tumours showed the ability to significantly suppress in vitro both proliferation and interferon‐γ production by CD25‐depleted MNC, thus demonstrating that they are active Tregs.
• ? Treg frequency was found to significantly correlate both with pathological stage (pPB, P= 0.03; TIL, P= 0.04) and nuclear grade (TIL, P= 0.005), both for UCLA and Kattan models (all: P < 0.05 for both pPB and TIL).

CONCLUSION

• ? Treg frequency is significantly higher in TIL than in pPB of patients with RCC. Tregs showed in vitro an inhibitory activity on effector T cells isolated from kidney tumours. The increase in both peripheral and intratumoral Tregs in subjects affected with RCC were associated with worse prognosis.

     

Randomized, crossover study evaluating patient preference and the impact on quality of life of urisheaths vs absorbent products in incontinent men

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVE

• ? To evaluate the impact of urisheaths vs absorbent products (APs) on quality of life (QoL) in men with moderate to severe urinary incontinence (UI).

PATIENTS AND METHODS

• ? A randomized, controlled, crossover trial in 61 outpatient adult men with stable, moderate to severe UI, with no concomitant faecal incontinence, was conducted from June 2007 to February 2009 in 14 urology centres.
• ? Participants tested Conveen Optima urisheaths (Coloplast, Humlebaek, Denmark) with collecting bags and their usual AP in random order for 2 weeks each.
• ? The impact of each on QoL was measured using the King’s Health Questionnaire (KHQ) and the short form‐12 acute questionnaire, and each patient’s preference was recorded.
• ? A 10‐item patient questionnaire was also used to assess the product main advantages on an 11‐point scale (0: worst; 10: best). A 72‐h leakage diary was used to record the number and severity of leaks and daily product consumption. Safety was measured as the number of local adverse events.

RESULTS

• ? All dimensions of the KHQ were scored lower with urisheaths, indicating an improvement in QoL. The greatest mean score reductions were in Limitations of Daily Activities (?10.24, P= 0.01) and Incontinence Impact (?7.05, P= 0.045).
• ? The majority (69%) of patients preferred Conveen Optima urisheaths to their usual AP (P = 0.002).
• ? Urisheaths scored significantly higher for all categories in the patient questionnaire (efficacy, self‐image, odour management, discretion, skin integrity) except ease of use.
• ? Safety was considered to be good.

CONCLUSIONS

• ? Conveen Optima urisheaths showed a positive impact on QoL (according to the KHQ results) in moderate to severe incontinent men, who were long‐term users of APs, and participants largely preferred urisheaths.
• ? Conveen Optima urisheaths should be recommended to incontinent men in preference to APs.

     

Secondary cancers after intensity‐modulated radiotherapy,brachytherapy and radical prostatectomy for the treatment of prostate cancer: incidence and cause‐specific survival outcomes according to the initial treatment intervention

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Radiation Therapy for prostate cancer can increase the risk for the development of second cancers after treatment. This study highlights the fact that such second cancers within the pelvis do occur but are not as common as previously reported. In this report we also note that even among patients who develop second cancers, if detected earlier, the majority are alive 5 years after the diagnosis.

OBJECTIVE

• ? To report on the incidence of secondary malignancy (SM) development after external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer and to compare this with a cohort contemporaneously treated with radical prostatectomy (RP).

MATERIALS AND METHODS

• ? Between 1998 and 2001, 2658 patients with localized prostate cancer were treated with RP (n= 1348), EBRT (n= 897) or BT (n= 413).
• ? Using the RP cohort as a control we compared the incidence of SMs, such as rectal or bladder cancers noted within the pelvis, and the incidence of extrapelvic SMs.

RESULTS

• ? The 10‐year SM‐free survival for the RP, BT and EBRT cohorts were 89%, 87%, and 83%, respectively (RP vs EBRT, P= 0.002; RP vs BT, P= 0.37).
• ? The 10‐year likelihoods for bladder or colorectal cancer SM development in the RP, BT and EBRT groups were 3%, 2% and 4%, respectively (P= 0.29).
• ? Multivariate analysis of predictors for development of all SMs showed that older age (P= 0.01) and history of smoking (P < 0.001) were significant predictors for the development of a SM, while treatment intervention was not found to be a significant variable.
• ? Among 243 patients who developed a SM, the 5‐year likelihood of SM‐related mortality among patients with SMs in the EBRT and BT groups was 43.7% and 15.6%, respectively, compared with 26.3% in the RP cohort; P= 0.052).

CONCLUSIONS

• ? The incidence of SM after radiotherapy was not significantly different from that after RP when adjusted for patient age and smoking history.
• ? The incidence of bladder and rectal cancers was low for both EBRT‐ and BT‐treated patients.
• ? Among patients who developed a SM, the likelihood of mortality related to the SM was not significantly different among the treatment cohorts.

     

Utility of the RENAL nephrometry scoring system in the real world: predicting surgeon operative preference and complication risk

Study Type – Prognosis (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? RENAL nephrometry is a quantitative, reproducible scoring system that characterizes RENAL masses and standardizes reporting. Previous work has suggested that the system may be useful in predicting outcomes after partial nephrectomy. This study is the first to correlate RENAL nephrometry score with operative approach or risk of complication in patients undergoing either partial or radical nephrectomy.

OBJECTIVE

• ? To evaluate the utility of the RENAL scoring system in predicting operative approach and risk of complications. The RENAL nephrometry scoring system is designed to allow comparison of renal masses based on the radiological features of (R)adius, (E)xophytic/endophytic, (N)earness to collecting system, (A)nterior/posterior and (L)ocation relative to polar lines.

METHODS

• ? A retrospective review of all patients at a single institution undergoing radical nephrectomy (RN) or partial nephrectomy (PN) for a renal mass between July 2007 and May 2010 was carried out.
• ? Preoperative RENAL score was calculated for each patient. Surgical approach and operative outcomes were then compared with the RENAL score.

RESULTS

• ? In all, 249 patients underwent either RN (158) or PN (91) with average RENAL scores of 8.9 and 6.3, respectively (P < 0.001).
• ? Patients who underwent RN were more likely to have hilar tumours (64% vs 10%, P < 0.001) than patients who underwent PN, but were no more likely to have posteriorly located tumours (50% each).
• ? There were more complications among patients with RN (58%) vs patients with PN (42%, P= 0.02).
• ? RENAL scores were higher in patients with PN who developed complications than in patients with PN who did not develop complications (6.9 vs 6.0, P= 0.02), with no difference noted among patients with RN developing complications (8.9 vs 8.9, P= 0.99).

CONCLUSION

• ? The RENAL system accurately predicted surgeon operative preference and risk of complications for patients undergoing PN.

     

Impact of comorbidity on complications after nephrectomy: use of the Clavien Classification of Surgical Complications

Study Type – Retrospective (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Tumour characteristics, physical status and comorbidities are considered important for surgical outcome and prognosis. The present study objectively evaluates the association between comorbidity and postoperative complications after nephrectomy for RCC, by using the modified Clavien Classification of Surgical Complications to grade complications after nephrectomy.

OBJECTIVE

• ? To present a single‐centre experience of open nephrectomy for lesions suspected for renal cell carcinoma (RCC), evaluating the association between comorbidity and postoperative complications using a standardized classification system for postoperative complications.

PATIENTS AND METHODS

• ? Clinicopathological data of 198 patients undergoing open radical or partial nephrectomy for lesions suspected of RCC were retrospectively analysed.
• ? Comorbidity scored by the Charlson comorbidity index (CCI), body mass index, age, gender, surgical procedure and surgical history were examined as predictive factors for postoperative complications, which were scored using the modified Clavien Classification of Surgical Complications (CCSC).

RESULTS

• ? The overall complication rate was 34%: 7% grade I, 15% grade II, 5% grade III, 3% grade IV and 4% grade V. Preoperative comorbidities were present in 51% of all patients.
• ? There were significantly more major complications (CCSC >2) in patients with major comorbidities (CCI >2), at 16% vs 7% (P= 0.018).
• ? Patients with high‐stage RCC had significantly more severe complications than low‐stage RCC (P= 0.018).
• ? In multivariable analysis, comorbidity (odds ratio [OR] 7.55, P= 0.004) and tumour stage 3–4 (OR 6.23, P= 0.007) were independent predictive factors for major complications.

CONCLUSIONS

• ? Major complications occur significantly more often when major comorbidities are present.
• ? Comorbidity scores can be used in risk stratification for complications and should be considered during decision‐making and counselling of patients before nephrectomy.

     

Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Tumour location has been shown to be of prognostic importance in UUT‐TCC, with tumours of renal pelvis having a better prognosis than ureteral tumours. Patients from Balkan Endemic Nephropathy (BEN) areas had a higher frequency of pelvis tumours. Also, we found that belonging to a BEN area is an independent predictor of disease recurrence.

OBJECTIVE

• ? To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT‐TCC).

PATIENTS AND METHODS

• ? A single‐centre series of 189 consecutive patients who were treated surgically for UUT‐TCC between January 1999 and December 2009 was evaluated.
• ? Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT‐TCC were excluded.
• ? In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour.
• ? Recurrence‐free probabilities and cancer‐specific survival were estimated using the Kaplan–Meier method and Cox regression analyses.

RESULTS

• ? The 5‐year recurrence‐free and cancer‐specific survival estimates for the cohort in the present study were 66% and 62%, respectively.
• ? The 5‐year bladder‐only recurrence‐free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P= 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non‐Balkan endemic nephropathy areas; 95% confidence interval, 1.37–5.98; P= 0.005) were associated with disease recurrence
• ? Tumour location was not associated with disease recurrence in any of the analyses.
• ? There was no difference in cancer‐specific survival between renal pelvis and ureteral tumours (P= 0.476).
• ? Using multivariate analysis, pT classification (HR, 8.04; P= 0.001) and lymph node status (HR, 4.73; P= 0.01) were the only independent predictors associated with a worse cancer‐specific survival.

CONCLUSION

• ? Tumour location is unable to predict outcomes in a single‐centre series of consecutive patients who were treated with radical nephroureterectomy for UUT‐TCC.

     

Comparison of oncological outcomes of transperitoneal and retroperitoneal laparoscopic radical nephrectomy for the management of clear‐cell renal cell carcinoma: a multi‐institutional study

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Laparoscopic radical nephrectomy (LRN) can be performed by a retroperitoneal approach with similar efficacy compared to the transperitoneal approach. However, the oncological acceptance of LRN has been based on studies which have been carried out primarily by transperitoneal approach, and oncological results of the retroperitoneal approach alone are lacking. Our study confirmed that retroperitoneal laparoscopic radical nephrectomy is oncologically‐equivalent to transperitoneal approach in homogeneous group with the final pathological diagnosis of clear cell RCC.

OBJECTIVE

• ? To investigate the oncological efficacy of retroperitoneal laparoscopic radical nephrectomy (RLRN) compared with transperitoneal laparoscopic radical nephrectomy (TLRN) for the management of clear‐cell renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? With emphasis on survival and disease recurrence, a retrospective analysis was made of 580 patients who underwent TLRN (472 patients) or RLRN (108 patients) at 23 institutions between January 1997 and December 2007.
• ? Inclusion criteria were clear‐cell RCC, stage pT1 to pT2 without any nodal involvement, and metastasis.
• ? Overall survival and recurrence‐free survival curves were estimated using the Kaplan–Meier method.
• ? To assess the association between the surgical approach and survival outcomes, Cox proportional hazard models were constructed.

RESULTS

• ? The median follow‐up was 30 months in the TLRN group and 35.6 months in the RLRN group. Both groups were comparable regarding age, gender, body mass index (BMI), Fuhrman’s grade, size of tumours and stage.
• ? Kaplan–Meier curves and the log‐rank test showed no significant difference between the TLRN and RLRN groups in 5‐year overall (92.6% vs 94.5%; P = 0.669) and recurrence‐free survival (92.0% vs 96.2%; P = 0.244).
• ? In a Cox regression model with age, gender, Eastern Cooperative Oncology Group performance status, BMI, nuclear grade and T‐stage adjusted variables, no significant difference was found between the two surgical approaches.

CONCLUSION

• ? The present study is the largest oncological analysis for laparoscopic radical nephrectomy (LRN) comparing transperitoneal and retroperitoneal approaches. The data from it provide the objective evidence to suggest similar oncological outcomes for both approaches to LRN.