IL-23 gene therapy for mouse bladder tumour cell lines

OBJECTIVES

• ? To evaluate the antitumour effects of IL‐23 gene transfer into mouse bladder carcinoma (MBT2) cells.
• ? To investigate the mechanisms underlying the subsequent constitutive secrection of IL‐23 by the MBT2 cells

MATERIALS AND METHODS

• ? An expression vector containing IL‐23 gene was introduced into MBT2 cells by liposome‐mediated gene transfer, and secretion of IL‐23 was confirmed by ELISA.
• ? The in vivo antitumour effect of IL‐23‐secreting MBT2 cells (MBT2/IL‐23) was examined by injecting the cells into syngeneic C3H mice.
• ? A tumour vaccination study using mitomycin C (MMC)‐treated IL‐23‐secreting MBT2 cells was carried out, and the usefulness of in vivo CD25 depletion for an additional vaccine effect was also investigated.
• ? The mechanisms underlying the antitumour effects were investigated by antibody depletion of CD8 or CD4 T cells, or natural killer cells, and cells infiltrating the tumour sites in vivo were assessed using immunohistochemistry.

RESULTS

• ? Stable transformants transduced with MBT2/IL‐23 secreted IL‐23 into the culture supernatant.
• ? Genetically engineered IL‐23‐secreting MBT2 cells were rejected in syngeneic mice.
• ? MBT2/IL‐23‐vaccinated mice inhibited the tumour growth of parental MBT2 cells injected at a distant site and this vaccine effect was enhanced by combination with in vivo CD25 depletion by an antibody.
• ? The main effector cells for the direct antitumour effect of MBT2/IL‐23 were CD8 T cells, which was shown by in vivo depletion and immunohistochemical study.

CONCLUSIONS

• ? IL‐23‐secreting MBT2 cells were rejected in syngeneic mice by the activation of CD8 T cells.
• ? MMC‐treated MBT2/IL‐23 can have a tumour vaccine effect for parental MBT2 cells, and this effect was enhanced by combination with in vivo CD25 depletion.

     

Characteristics and clinical significance of prostate cancers missed by initial transrectal 12-core biopsy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 3a What's known on the subject? and What does the study add? Initial transrectal 12‐core biopsy has a small but definite risk of missing anterior significant prostate cancers irrespective of age, PSA, prostate volume and DRE findings. Our study yields valuable information for diagnosis and treatment decision of prostate cancer based on transrectal 12‐core biopsy.

OBJECTIVE

• ? To characterize prostate cancers missed by initial transrectal 12‐core biopsy.

PATIENTS AND METHODS

• ? Between 2002 and 2008, 715 men with prostate‐specific antigen levels in the range 2.5–20 ng/mL or abnormal digital rectal examination underwent three‐dimensional 26‐core prostate biopsy (i.e. a combination of transrectal 12‐core biopsy and transperineal 14‐core biopsy) on initial examination.
• ? Of the 257 patients diagnosed with cancer, 120 patients subsequently underwent radical prostatectomy.
• ? Cancers were grouped into TR12‐negative cancers (i.e. not detected through transrectal 12‐core biopsy but detected through transperineal 14‐core biopsy) and TR12‐positive (i.e. detected through transrectal 12‐core biopsy) cancers.
• ? Clinicopathological characteristics of the TR12‐negative and TR12‐positive cancers were evaluated.

RESULTS

• ? TR12‐negative cancers comprised 21% of the three‐dimensional 26‐core biopsy‐detected cancers.
• ? The frequency of cancers with a biopsy Gleason score ≤6 and that of cancers with a biopsy primary Gleason grade ≤3 was higher in TR12‐negative cancers, at 58% and 83%, respectively, than in TR12‐positive cancers, at 25% (P < 0.001) and 53% (P < 0.001), respectively.
• ? The median number of positive cores in TR12‐negative cancers was two out of 26.
• ? TR12‐negative cancers were more frequently located anteriorly than posteriorly.
• ? The incidence of the TR12‐negative cancers was not associated significantly with any clinical variable.

CONCLUSION

• ? Many of the cancers missed by initial transrectal 12‐core biopsy are probably low‐grade and low‐volume diseases, although initial transrectal 12‐core biopsy has a small but definite risk of missing anterior significant cancers.

     

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.

     

Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy

Study Type – Prognosis (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Cardiovascular disease is a leading cause of death in prostate cancer patients. Pretreatment ED is a surrogate for vascular pathology. Aggressive treatment of medical co‐morbidity in prostate cancer patients may positively impact overall survival.

OBJECTIVE

• ? To evaluate the relationship between pre‐treatment erectile function and all‐cause mortality in patients with prostate cancer treated with brachytherapy.

PATIENTS AND METHODS

• ? In all, 1279 consecutive patients with clinically localized prostate cancer and pre‐implant erectile function assessed by the International Index of Erectile Function‐6 (IIEF‐6) underwent brachytherapy.
• ? Potency was defined as an IIEF‐6 score of ≥13 without pharmacological or mechanical support.
• ? Patients were stratified into IIEF‐6‐score cohorts (≤12, 13–23 and 24–30).
• ? The median follow‐up was 5.0 years.

RESULTS

• ? The 8‐year overall survival (OS) of the study population was 85.1%.
• ? The 8‐year OS for IIEF‐6scores ≤12, 13–23 and 24–30 were 78.0%, 92.8% and 91.4%, respectively (P < 0.001).
• ? Cardiovascular events accounted for a significant portion of deaths in each IIEF‐6 group.
• ? When combined with other risk factors for cardiovascular disease, an IIEF‐6 score of ≤12 had an additive effect on all‐cause mortality (IIEF‐6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%).

CONCLUSIONS

• ? A pre‐implant IIEF‐6score of ≤12 was associated with a higher incidence of all‐cause mortality.
• ? Pre‐treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients.
• ? Aggressive treatment of medical co‐morbidity is warranted to impactOS.

     

Magnetic resonance imaging does not improve the prediction of misclassification of prostate cancer patients eligible for active surveillance when the most stringent selection criteria are based on the saturation biopsy scheme

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

OBJECTIVE

• ? To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS).

PATIENTS AND METHODS

• ? We identified prostate cancers patients who had undergone a 21‐core biopsy scheme and fulfilled the criteria as follows: prostate‐specific antigen (PSA) level ≤10 ng/mL, T1–T2a disease, a Gleason score ≤6, <3 positive cores and tumour length per core <3 mm.
• ? We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery.
• ? The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion.

RESULTS

• ? Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases.
• ? The rate of unfavourable disease (pT3–4 and/or Gleason score ≥4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%).
• ? MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314).
• ? In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen.
• ? After a mean follow‐up of 29 months, the recurrence‐free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1–T2 disease (P = 0.853).

CONCLUSION

• ? The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21‐core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high‐risk and/or non organ‐confined disease in a RP specimen.

     

The use of estramustine phosphate in the modern management of advanced prostate cancer

What’s known on the subject? and What does the study add? Estramustine phosphate has anti‐tumour properties and it improves patient outcomes if combined with other chemotherapy agents such as doeetaxel. The efficacy of estramustine phosphate in selected patients and its safety profile, provided used with any low‐molecular‐weight heparin support its use as a second‐line treatment in hormone‐resistant prostate cancer.

OBJECTIVES

• ? Estramustine phosphate is a nitrogen mustard derivative of estradiol‐17β‐phosphate and has anti‐tumour properties.
• ? Interest in estramustine has been renewed because of the results of clinical studies showing improved patient outcomes if estramustine is combined with other chemotherapy agents such as docetaxel.

PATIENTS AND METHODS

• ? Relevant clinical studies using chemotherapy combinations including estramustine are discussed.
• ? Efficacy and safety outcomes are summarized.

RESULTS

• ? Combination therapy with estramustine and docetaxel can increase PSA response rates, improve quality of life and increase median patient survival compared with chemotherapy regimens that do not include estramustine.
• ? Although the overall tolerability of estramustine is favourable, its use can be associated with an increased risk of thromboembolic events.

CONCLUSIONS

• ? The identification of suitable patient groups and the effective management of the risk of thromboembolism with the adjunct of low‐molecular‐weight heparins support the use of estramustine as an effective second‐line treatment strategy in hormone‐resistant prostate cancer.
• ? These promising findings warrant further investigation in a randomized clinical trial.

     

Natural history of lower urinary tract symptoms in Japanese men from a 15-year longitudinal community-based study

Study Type – Symptom prevalence (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? There have been few longitudinal community‐based studies on LUTS suggestive of BPH. It is important to determine the natural history of LUTS suggestive of BPH among men in various countries because it is known that there are differences according to race. Although we previously reported a cross‐sectional community‐based survey on LUTS suggestive of BPH in Japanese men, no longitudinal data were available. The present study provides 15‐year longitudinal data on LUTS suggestive of BPH and related variables in Japanese men.

OBJECTIVE

• ? To report the natural history of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in Japanese men.

PATIENTS AND METHODS

• ? From 1992 to 1993, we conducted a cross‐sectional community‐based study on LUTS suggestive of BPH in Japanese men aged 40–79 years.
• ? After 15 fifteen years, a follow‐up study was conducted to determine their longitudinal changes of LUTS.
• ? Of the 319 participants taking part in the initial study, 135 participated again in the follow‐up study.
• ? We investigated International Prostate Symptom Score (IPSS), quality of life index and bother score using a questionnaire, and measured prostate volume (PV), prostate‐specific antigen (PSA) level and peak urinary flow rate (Q_max) using a method that we have employed previously.

RESULTS

• ? The change in the total IPSS during 15 years was significant (P= 0.001) and its mean (sd ) annual change was 0.11 (0.40).
• ? Although there was little change in the bother score, a significant correlation was observed between changes in the IPSS and bother score (r= 0.528, P < 0.001).
• ? For the individual IPSS and bother scores, only changes in urgency, weak stream and nocturia were significant.
• ? The changes in PV, PSA level and Q_max were significant.
• ? The change in the total IPSS did not correlate with the changes in these variables.

CONCLUSION

• ? In a 15‐year‐longitudinal community‐based study for Japanese men, we have shown that the IPSS and quality of life index deteriorated, PV and PSA level increased, and Q_max decreased.

     

Complications after bladder augmentation or substitution in children: a prospective study of 86 patients

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? A lot of information has been gathered on the subject of complications following urinary bladder augmentation and/or substitution in the recent years. The present study, based on the analysis of 86 patients, gives a critical analysis of these complications (stone formation, bowel obstruction, hematuria‐dysuria syndrome, small bowel bacterial overgrowth, persistent vesico‐ureteral reflux, obstruction at the site of ureteral reimplantation, reservoir perforation, premalignant histological changes, decreased bladder capacity/compliance requiring reaugmentation, etc.). The study adds one more new complication (small bowel colonization following colocystoplasty performed with the cecum and ascending colon) and reports complications in a fairly big (by European standards) cohort of patients with a long follow‐up.

OBJECTIVE

• ? To evaluate complications after urinary bladder augmentation or substitution in a prospective study in children.

PATIENTS AND METHODS

• ? Data of 86 patients who underwent urinary bladder augmentation (80 patients) or substitution (6 patients) between 1988 and 2008 at the authors’ institute were analysed.
• ? Ileocystoplasty occurred in 32, colocystoplasty in 30 and gastrocystoplasty in 18. Urinary bladder substitution using the large bowel was performed in six patients.
• ? All patients empty their bladder by intermittent clean catheterization (ICC), 30 patients via their native urethra and 56 patients through continent abdominal stoma. Mean follow‐up was 8.6 years.
• ? Rate of complications and frequency of surgical interventions were statistically analysed (two samples t‐test for proportions) according to the type of gastrointestinal part used.

RESULTS

• ? In all, 30 patients had no complications. In 56 patients, there were a total of 105 complications (39 bladder stones, 16 stoma complications, 11 bowel obstructions, 5 reservoir perforations, 7 VUR recurrences, 1 ureteral obstruction, 4 vesico‐urethral fistulae, 4 orchido‐epididymitis, 4 haematuria‐dysuria syndrome, 3 decreased bladder capacity/compliance, 3 pre‐malignant histological changes, 1 small bowel bacterial overgrowth and 7 miscellaneous).
• ? In 25 patients, more than one complication occurred and required 91 subsequent surgical interventions. Patients with colocystoplasty had significantly more complications (P < 0.05), especially more stone formation rate (P < 0.001) and required more post‐ operative interventions (P < 0.05) than patients with gastrocystoplasty and ileocystoplasty.

CONCLUSIONS

• ? Urinary bladder augmentation or substitution is associated with a large number of complications, particularly after colocystoplasty.
• ? Careful patient selection, adequate preoperative information and life‐long follow‐up are essential for reduction, early detection and management of surgical and metabolic complications in patients with bladder augmentation or substitution.

     

Low pretreatment total testosterone (< 3 ng/mL) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer

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

OBJECTIVE

• ? To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well‐studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer.

PATIENTS AND METHODS

• ? A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution.
• ? The results were classified into two groups based on the total serum testosterone: group1, <3 ng/mL; group 2, ≥3 ng/mL.
• ? Student’s t‐test was used to compare continuous variables, and Fisher’s exact test or the chi‐squared test was used to compare categorical variables.
• ? Survival curves were established using the Kaplan–Meier method and compared using the log‐rank test. In all tests, P < 0.05 was considered to indicate statistical significance.

RESULTS

• ? All patients had localized prostate cancer based on digital rectal examination (DRE) and preoperative magnetic resonance imaging (MRI). Groups 1 and 2 were similar in terms of age, body mass index, preoperative co‐morbidities (cardiovascular and diabetes mellitus), clinical stage of prostate cancer and preoperative PSA levels.
• ? In pathological specimens, low total testosterone (<3 ng/mL) was an independent risk factor for high Gleason score (>7) and for locally advanced pathological stage (pT3 and pT4).
• ? Higher preoperative testosterone correlated with disease confined to the gland.
• ? There was no association between serum testosterone levels and surgical margin status, on the one hand, and biochemical recurrence on the other.

CONCLUSION

• ? Low serum testosterone appears to be predictive of aggressive disease (Gleason score >7 and extraprostatic disease, pathological stage >pT2) in patients who underwent RP for localized prostate cancer.

     

Use of fluorescein isothiocyanate-human serum albumin for the intravesical photodiagnosis of non-muscle-invasive bladder cancer: an in vitro study using multicellular spheroids composed of normal human urothelial and urothelial cell carcinoma cell lines

OBJECTIVE

• ? To evaluate human serum albumin (HSA), fluorescently labelled with fluorescein isothiocyanate (FITC), as a potential intravesical photodiagnostic method for the early detection of non‐muscle‐invasive bladder cancer.

PATIENTS AND METHODS

• ? By using multicellular spheroids prepared from normal human urothelial (NHU) cells and from different urothelial cell carcinoma (UCC) cell lines (T24, J82), we simulated three‐dimensionally the normal urothelium and non‐muscle‐invasive UCCs present in the bladder of patients.
• ? The distribution of FITC‐HSA in these spheroids was investigated.

RESULTS

• ? Our data showed that fluorescently labelled albumin is quite evenly dispersed throughout the spheroids. However, in the case of the 10 mg/mL incubations, the fluorescence intensity seems to increase slightly towards the spheroid core.
• ? Using 1 mg/mL, the penetration of FITC‐HSA in T24 differed significantly from the penetration in NHU spheroids, but this was not the case for J82 spheroids.
• ? When the concentration of FITC‐HSA was increased 10‐fold, all UCC spheroids exhibited a significantly different accumulation of FITC‐HSA.

CONCLUSIONS

• ? As spheroids represent a suitable in vitro model for predicting the in vivo behaviour of compounds, our data suggest that FITC‐HSA could be used for the early detection of non‐muscle‐invasive bladder cancer.
• ? Human serum albumin conjugates of new or already available intravesical drugs could be generated to create alternative bladder cancer therapies with increased selectivity.

     

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.

     

Association between smoking cessation and sexual health in men

Study Type – Prevention (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Tobacco use is the single most preventable cause of disease and death, and – among other medical sequelae – is associated with elevated rates of erectile dysfunction. This is the first study that shows that quitting smoking enhances both physiological and self‐reported indices of sexual health in long‐term male smokers. It is hoped that these results may serve as a novel means to motivate men to quit smoking.

OBJECTIVE

• ? To provide the first empirical investigation of the association between smoking cessation and indices of physiological and subjective sexual health in men.

SUBJECTS AND METHODS

• ? Male smokers, irrespective of erectile dysfunction status, who were motivated to stop smoking (‘quitters’), were enrolled in an 8‐week smoking cessation programme involving a nicotine transdermal patch treatment and adjunctive counselling.
• ? Participants were assessed at baseline (while smoking regularly), at mid‐treatment (while using a high‐dose nicotine transdermal patch), and at a 4‐week post‐cessation follow‐up.
• ? Physiological (circumferential change via penile plethysmography) and subjective sexual arousal indices (continuous self‐report), as well as self‐reported sexual functioning were assessed at each visit.

RESULTS

• ? Intent‐to‐treat analyses indicated that, at follow‐up, successful quitters (n= 20), compared with those who relapsed (n= 45), showed enhanced erectile tumescence responses, and faster onset to reach maximum subjective sexual arousal.
• ? Although successful quitters displayed across‐session enhancements in sexual function, they did not show a differential improvement compared with unsuccessful quitters.

CONCLUSIONS

• ? Smoking cessation significantly enhances both physiological and self‐reported indices of sexual health in long‐term male smokers, irrespective of baseline erectile impairment.
• ? It is hoped that these results may serve as a novel means to motivate men to stop smoking.

     

Laparoscopic partial nephrectomy for multiple tumours: feasibility and analysis of peri-operative outcomes

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Laparoscopic nephron‐sparing procedures have been increasingly utilized. However, in the presence of multiple tumours the procedure choice is usually shifted to radical nephrectomy. In view of favourable perioperative outcomes, the benefits of minimally‐invasive, nephron‐sparing surgery in experienced hands could be safely extended to patients presenting with multiple ipsilateral renal masses.

OBJECTIVE

• ? To describe our experience with laparoscopic partial nephrectomy (LPN) for multiple kidney tumours and compare the outcomes with LPN performed for single masses.

PATIENTS AND METHODS

• ? Retrospective analysis of medical records of patients undergoing LPN at our institution between 2005 and 2009 was performed.
• ? The cohort was divided in two groups based on tumour focality: group 1, LPN for a single tumour (n= 99) and group 2, LPN for multiple ipsilateral tumours (n= 12).
• ? The groups were compared with regards to demographic and peri‐operative variables.

RESULTS

• ? Demographic variables were not different between the groups. Median dominant tumour size was 3.1 cm (interquartile range [IQR] 2.4–4.0) and 4.0 cm (2.3–5.9) in groups 1 and 2, respectively.
• ? Median secondary tumour size in group 2 was 1.0 cm (1.0–1.8).
• ? Operative times were longer in group 2 compared with group 1 (220 vs 160 min, P= 0.009).
• ? Warm ischaemia times (WIT) (23 vs 22 min) and estimated blood loss (EBL) (100 vs 85 mL) were similar.

CONCLUSIONS

• ? LPN is a viable option for the treatment of multiple ipsilateral renal tumours.
• ? Peri‐operative outcomes are similar to standard LPN with the exception of longer operative time.
• ? In experienced hands, the advantages of minimally invasive surgery may be extended to select patients with ipsilateral multifocal renal tumours.

     

Early infectious complications with transponder placement for external beam radiation therapy for prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Little has been published related to transponders per se, but a number of studies relating to prostate biopsy‐related infections and the increased incidence of quinolone‐resistant Escherichia coli have been published. The study alerts the practising urologist to the risk of quinolone‐resistant E. coli in the setting of transrectally placed transponders. Furthermore, it proposes an antibiotic regimen that should reduce this risk.

OBJECTIVE

• ? To report our series of early infectious complications after placement of Calypso® transponders (Calypso Medical, Seattle, WA, USA) into the prostate.

PATIENTS AND METHODS

• ? Between February 2008 and October 2010, 50 consecutive patients underwent placement of Calypso® transponders into the prostate.
• ? Patients were administered ciprofloxacin 500 mg every 12 h, starting the night before the procedure and for 2 days after the procedure.
• ? Data were collected via chart review, and complications were classified according to the Clavien classification system.

RESULTS

• ? Of the 50 patients undergoing the procedure, five (10%) developed infectious complications, and three (6%) developed a grade II complication with a UTI requiring antibiotic therapy. One patient (2%) developed a grade IIIb complication with an epidural abscess and osteomyelitis of the lumbar vertebrae requiring open debridement and a lumbar fusion. One patient (2%) developed a prostatic abscess with methicillin‐resistant Staphylococcus aureus and subsequently died of an unrelated lower GI bleed.
• ? In 4/50 patients (8%), a culture confirmed the responsible bacteria, of which three cases were quinolone‐resistant Escherichia coli.

CONCLUSION

• ? As with prostate biopsy, the emergence of quinolone‐resistant E. coli remains a challenging infectious complication with transrectal prostate procedures. We propose an alternative strategy of double antibiotic coverage with one dose of oral ciprofloxacin 500 mg and gentamicin 80 mg i.m. before this procedure.

     

Ureteroscopy assisted retrograde nephrostomy: a new technique for percutaneous nephrolithotomy (PCNL)

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Retrograde nephrostomy was first developed by Lawson et al. in 1983, and Hunter et al. reported 30 cases of retrograde nephrostomy in 1987. This procedure uses less radiation exposure and has a shorter duration compared with the previous percutaneous nephrostomy techniques. Retrograde nephrostomy using Lawson's procedure was reported in the late 1980s by several authors. But since then, few studies have been reported about this procedure due to the development of ultrasonography assisted percutaneous nephrostomy. With the arrival and development of the flexible ureteroscope (URS) both observation and manipulation in the renal pelvis are now easily achieved. The present procedure provides less radiation exposure, less bleeding, and a shorter procedure than previous percutaneous nephrostomy techniques. Using this procedure, after the needle has exited through the skin, no further steps are required in preparation for dilatation. In the present study, we continuously visualised from puncture to inserting the nephron‐access sheath with the URS.

OBJECTIVE

• ? To describe a technique for ureteroscopy assisted retrograde nephrostomy.

PATIENTS AND METHODS

• ? Under general and epidural anaesthesia, the patient is placed in a modified‐Valdivia position. Flexible ureteroscopy is carried out, and a Lawson retrograde nephrostomy puncture wire is placed in the ureteroscope (URS).
• ? After the needle has exited through the skin, no further steps are required in preparation for dilatation.

RESULTS

• ? After informed consent was obtained, two patients (a 43‐year‐old man with left renal stones and a 57‐year‐old woman with right renal stones) underwent this procedure.
• ? The URS was positioned in the middle posterior calyx and punctured toward the skin.

CONCLUSIONS

• ? This procedure involves less radiation exposure and shorter surgery than the previous percutaneous nephrostomy technique.
• ? Our technique represents another new option for percutaneous nephrolithotomy in patients with a non‐dilated intrarenal collecting system.

     

Targeting castration‐induced tumour hypoxia enhances the acute effects of castration therapy in a rat prostate cancer model

What’s known on the subject? and What does the study add? Castration therapy has rather modest effects on cell death in tumours but can be enhanced by other treatments targeting tumour stroma and vasculature. This study shows that the prostate becomes hypoxic following castration and that targeting hypoxic cells during castration therapy potently enhances the effects of castration.

OBJECTIVE

• ? To explore the effects of castration therapy, the standard treatment for advanced prostate cancer, in relation to tumour hypoxia and to elicit its importance for the short‐ and long‐term therapeutic response.

MATERIAL AND METHODS

• ? We used the androgen‐sensitive rat Dunning H prostate tumour model that transiently responds to castration treatment followed by a subsequent relapse, much like the scenario in human patients.
• ? Tumour tissues were analysed using stereological methods in intact, 1 and 7 days after castration therapy.

RESULTS

• ? Hypoxia was transiently up‐regulated after castration therapy and correlated with the induction of tumour cell apoptosis.
• ? When castration therapy was combined with tirapazamine (TPZ), a drug that targets hypoxic cells and the vasculature, the effects on tumour cell apoptosis and tumour volume were enhanced in comparison to either castration or TPZ alone.

CONCLUSION

• ? The present study suggests that castration‐induced tumour hypoxia is a novel target for therapy.

     

Contemporary trends of in-hospital complications and mortality for radical cystectomy

Study Type – Therapy (trend analysis) Level of Evidence 2b What's known on the subject? and What does the study add? Radical cystectomy (RC) carries significant risks of morbidity and mortality. Little is known whether in‐hospital outcomes are improving for RC. Using a contemporary population‐based cohort, the present study suggests minimal improvement in postoperative complications and mortality overall or by hospital‐volume category from 2001 to 2008. About 29% and 2% of patients undergoing RC will experience a postoperative complication or die during hospitalisation, respectively.

OBJECTIVE

• ? To characterise the contemporary trends of in‐hospital complications and mortality for radical cystectomy (RC) from a contemporary population‐based cohort, as patients undergoing RC for bladder cancer are at significant risk for complications and mortality and the degree to which in‐hospital outcomes have changed over time is unknown.

PATIENTS AND METHODS

• ? We identified 50 625 individuals who underwent RC for bladder cancer between 2001 and 2008 from the Nationwide Inpatient Sample.
• ? Multivariable regression models were used to identify hospital and patient covariates associated with in‐hospital complications and mortality and to estimate predicted probabilities of each outcome.
• ? Temporal trends of in‐hospital mortality and complications were assessed by Wilcoxon rank‐sum test.

RESULTS

• ? The proportion of patients with in‐hospital complications remained stable at 28.3% in 2001–2002 compared with 28.0% in 2007–2008 (P= 0.81 for trend).
• ? In‐hospital mortality was also unchanged from 2.4% in 2001–2002 compared with 2.3% in 2007–2008 (P= 0.87 for trend).
• ? While high‐volume hospitals were associated with lower odds of in‐hospital complications (odds ratio [OR] 0.77, P= 0.01) and mortality (OR 0.60, P= 0.02) compared with low‐volume hospitals, the predicted probabilities of in‐hospital complications or mortality were unchanged within each volume category between 2001 and 2008.

CONCLUSIONS

• ? In‐hospital complications and mortality for RC remain unchanged from 2001 to 2008.
• ? While high‐volume hospitals continue to have better outcomes, there is little evidence that postoperative mortality and morbidity are improving among low‐, medium‐ and high‐volume hospitals.
• ? Increased attention is needed to identify the modifiable aspects of postoperative care to improve in‐hospital outcomes and safety for patients undergoing RC.

     

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.

     

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.

     

Open radical prostatectomy in the elderly: a case for concern?

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Adverse outcomes after radical prostatectomy are more often recorded in the elderly. In the USA, elderly patients undergoing radical prostatectomy are treated at institutions where suboptimal outcomes are recorded.

OBJECTIVE

• ? To assess the rate of adverse outcomes after open radical prostatectomy (ORP) in the elderly and to examine the effect of annual hospital caseload (AHC) and academic institutional status on adverse outcomes in these of patients.

PATIENTS AND METHODS

• ? Within the Health Care Utilization Project Nationwide Inpatient Sample, we focused on ORPs performed between 1998 and 2007. Subsequently, we restricted to patients aged ≥75 years.
• ? In both datasets, we examined transfusion rates, intra‐operative and postoperative complication rates, and in‐hospital mortality rates.
• ? Stratification was performed according to AHC tertiles and academic status.
• ? Multivariable logistic regression analyses were fitted.

RESULTS

• ? Of 115 554 ORP patients, 2109 (1.8%) were aged ≥75 years.
• ? In multivariable analyses performed in the entire cohort, elderly age increased homologous blood transfusion rates (P < 0.001), intra‐operative (P= 0.001) and postoperative (P < 0.001) complication rates, and the mortality rate (P= 0.007).
• ? Most elderly were treated at low or intermediate AHC (68.5%) and non‐academic centres (56.2%).
• ? Within the elderly cohort, intra‐operative (2.9%) and postoperative (22.2%) complications tended to be highest at low AHC institutions compared to institutions of intermediate (2.7% and 17.4%) and high AHC (1.7% and 14.5%). Similarly, intra‐operative (2.7% vs 2.1%) and postoperative complications (19.1% vs 13.9%) tended to be higher at non‐academic than academic centres.
• ? In multivariable analyses performed in the elderly subgroup, low AHC predicted higher intra‐operative complications and higher homologous transfusions, whereas non‐academic status predicted higher postoperative complications.

CONCLUSIONS

• ? Adverse outcomes are more often recorded in the elderly.
• ? Most elderly are treated at institutions where suboptimal outcomes are recorded.