Outcomes of the management of post-chemotherapy retroperitoneal lymph node dissection-associated anejaculation

Study Type – Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Modern surgical techniques have allowed preservation of fertility in most patients after post‐chemotherapy retroperitoneal lymph node dissection (PC‐RPLND), but some patients still have infertility after surgery. We reviewed our experience treating infertility in 26 men after PC‐RPLND. Using a structured clinical pathway we obtained sperm in 81% of men for use in assisted reproduction.

OBJECTIVE

• ? To evaluate the effectiveness of a clinical pathway on sperm retrieval outcomes in patients presenting with infertility after post‐chemotherapy (PC) retroperitoneal lymph node dissection (RPLND).

PATIENTS AND METHODS

• ? We carried out a retrospective review of patients with advanced testicular cancer, presenting with infertility after PC‐RPLND in a large reproductive urology practice.
• ? We implemented a clinical pathway where pseudoephedrine was first administered. If this medication failed, electroejaculation (EEJ) and/or testicular sperm extraction (TESE) was carried out.
• ? The primary outcome was retrieval of sperm for use in assisted reproduction.

RESULTS

• ? Four men had retrograde ejaculation, of whom two converted to antegrade ejaculation with medical therapy.
• ? In all, 22 patients had failure of emission (FOE) and, of these, no patient converted to antegrade ejaculation with medication.
• ? In patients with FOE, sperm was found in 15/20 of those experiencing a successful EEJ.
• ? Seven patients underwent TESE for azoospermia on EEJ or no ejaculate on EEJ, three of whom had sperm found on TESE.
• ? Sperm was found for assisted reproduction in 81% (21/26) patients.

CONCLUSIONS

• ? There appears to be no role for the use of pseudoephedrine therapy in patients with FOE after PC‐RPLND.
• ? The use of a structured clinical pathway may optimize patient care.

     

Assessing and conceptualizing orgasm after a spinal cord injury

Study Type – Aetiology (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? This study provides the first questionnaire on the specific bodily sensations that can be perceived at orgasm thereby complementing the subjective phenomenological experience of orgasm.

OBJECTIVES

• ? To provide a questionnaire for assessing the sensations characterizing orgasm.
• ? To test the hypothesis that orgasm is related to autonomic hyperreflexia (AHR) in individuals with a spinal cord injury (SCI).

SUBJECTS AND METHODS

• ? A total of 97 men with SCI, of whom 50 showed AHR at ejaculation and 39 showed no AHR, were compared.
• ? Ejaculation was obtained through natural stimulation, vibrostimulation or vibrostimulation combined with midodrine (5–25 mg).
• ? Cardiovascular measures were recorded before, at, and after each test.
• ? Responses to the questionnaire were divided into four categories: cardiovascular, muscular, autonomic and dysreflexic sensations.

RESULTS

• ? Significantly more sensations were described at ejaculation than with sexual stimulation alone.
• ? Men with SCI who experienced AHR at ejaculation reported significantly more cardiovascular, muscular, autonomic and dysreflexic responses than those who did not.
• ? There was no difference between men with complete and those with incomplete lesions.

CONCLUSIONS

• ? The findings show that the questionnaire is a useful tool to assess orgasm and to guide patients in identifying the bodily sensations that accompany or build up to orgasm.
• ? The findings also support the hypothesis that orgasm may be related to the presence of AHR in individuals with SCI. Data from able‐bodied men also suggest that AHR could be related to orgasm, as increases in blood pressure are observed at ejaculation along with cardiovascular, autonomic and muscular sensations.

     

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.

     

Evaluation of maximum voided volume in Korean children by use of a 48-h frequency volume chart

Study Type – Diagnostic (validating cohort) Level of Evidence 2a What's known on the subject? and What does the study add? The relationship between the maximum voided volume followed a linear curve. The formula presented, bladder capacity (mL) = 12 ×[age (years) + 11], is thought to be a reasonable one for Korean children. Korean children have a smaller bladder capacity than that reported in previous Western studies.

OBJECTIVE

• ? To develop practical guidelines for the prediction of normal bladder capacity in Korean children measured by a frequency volume chart (FVC), maximum voided volume (MVV) is an important factor in the diagnosis of children with abnormal voiding function.

SUBJECTS AND METHODS

• ? In all, 298 children, aged 3–13 years, with no history of voiding disorders volunteered for the study. The MVV was determined in 219 subjects by use of a completely recorded FVC.

RESULTS

• ? Linear regression analysis was used to define the exact relationship between age and bladder capacity. An approximate formula related age to bladder capacity as follows: bladder capacity (mL) = 12 ×[age (years) + 11].

CONCLUSIONS

• ? The relationship between the MVV measured by a FVC by age (3–13 years) of Korean children followed a linear curve.
• ? When applied to normal voiding patterns, the formula presented appears to be a reasonable one for Korean children.

     

Reversing bladder outlet obstruction attenuates systemic and tissue oxidative stress

What's known on the subject? and What does the study add? Oxidative damage in bladder tissue and systemic oxidative biomarkers were both found to be increased in rabbits with partial bladder outlet obstruction. It is shown that the reversal of partial bladder outlet obstruction will attenuate the systemic oxidative stress.

OBJECTIVE

• ? To investigate whether partial bladder outlet obstruction (PBOO) increases systemic oxidative stress and whether relief of PBOO could attenuate this stress.

MATERIALS AND METHODS

• ? Surgically created PBOO in male New Zealand white rabbits was assessed after 4 weeks in one group of rabbits (n = 4), and was relieved in two additional groups of rabbits (n = 4 each) that were assessed at 4 and 8 weeks after relief of PBOO.
• ? Four sham‐operated rabbits served as controls. The assessed oxidative stress biomarkers included urinary and plasma 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) and plasma malondialdehyde (MDA), total anti‐oxidant capacity (TAC) and glutathione (GSH).
• ? In addition, the copy number of mitochondrial DNA and the 8‐OHdG content in bladder tissues from these rabbits were also determined at the beginning and at indicated time points in the experiments.

RESULTS

• ? There were significant increases in both the 8‐OHdG levels of urine, plasma and bladder tissue and the plasma MDA after induction of PBOO.
• ? There were also significant decreases in the TAC, in GSH levels and in mitochondrial DNA copy number in bladder tissues after PBOO.
• ? Most importantly, all of the values returned toward the control levels after the PBOO was reversed at 8 weeks.

CONCLUSION

• ? PBOO increases systemic and oxidative stress and its reversal results in a progressive reduction of both systemic and tissue oxidative stress.

     

Evans blue as a selective dye marker for white-light diagnosis of non-muscle-invasive bladder cancer: an in vitro study

What's known on the subject? and What does the study add? We found that Evans blue preferentially accumulate in spheroids prepared from urothelial cell carcinoma (UCC) cells as compared to spheroids composed of normal human urothelial (NHU) cells. The present findings could be important for future developments in clinical diagnostics for early bladder cancer detection staging and grading involving white light cystocopy.

OBJECTIVE

• ? To develop a diagnostic method relying on the preferential accumulation of a dye in non‐muscle‐invasive bladder cancer (NMIBC) that is visible in conjunction with white‐light cystoscopy (WLC).

MATERIALS AND METHODS

• ? We investigated in detail the permeation of Evans blue in urothelial cell carcinoma (UCC) spheroids prepared from T24, J82 and RT‐112 human cell lines and spheroids composed of normal human urothelial (NHU) cells.
• ? To gain more insight into the differential accumulation, all spheroids were investigated ultrastructurally using transmission electron microscopy (TEM).

RESULTS

• ? We found that, after exposure to Evans blue for 2 h, UCC spheroids accumulated dramatically more dye than spheroids composed of NHU cells.
• ? Using TEM it was found that the malignant spheroids contain similar ultrastructural characteristics, i.e. a wide intercellular space and a decreased number of desmosome‐like cell attachments, to those from clinical samples of non‐papillary carcinoma in situ of the bladder.

CONCLUSION

• ? We believe the present findings could be important for future developments in clinical diagnostics for early bladder cancer detection, staging and grading involving WLC.

     

Bilateral pudendal afferent stimulation improves bladder emptying in rats with urinary retention

Study Type – Therapy (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Previous study demonstrated that unilateral electrical stimulation of the proximal transected sensory pudental nerve during distention‐evoked voiding contractions significantly improved voiding efficiency. The current study extends previous study from unilateral (UniES) to bilateral (BiES) stimulation of pudental afferent nerve fibres to determine whether this approach further enhances the improved voiding efficiency (VE) that we reported previously which unilateral stimulation. Our results show in most instances BiES consistently generated more efficient bladder emptying than did UniES but these differences were not significant.

OBJECTIVE

• ? To determine whether bilateral electrical stimulation (BiES) of the transected pudendal sensory nerves could further enhance the voiding efficiency beyond that produced by unilateral electrical stimulation (UniES) of transected pudendal afferents in rats with urinary retention.

MATERIALS AND METHODS

• ? The efficiency of bladder emptying with either UniES or BiES of pudendal nerve afferents was measured after acute bilateral transection of the sensory branch of the pudendal nerve.
• ? The effects of UniES and BiES on voiding in a partially denervated bladder and acute spinal transection, respectively, were determined.

RESULTS

• ? The voiding efficiency (VE) was reduced from 69 to 22% after bilateral transection of the sensory branch of the pudendal nerve. UniES or BiES increased the VE to 49–62%.
• ? Although in most instances BiES consistently generated more efficient bladder emptying than did UniES, these differences were not significant.
• ? Both UniES and BiES increased VE after unilateral pelvic nerve transection, demonstrating efficacy in a partially denervated bladder.
• ? The enhancement of VE by either UniES or BiES was preserved after acute T₉–T₁₀, demonstrating the spinal origin of this augmenting reflex.

CONCLUSIONS

• ? The results of the present study are consistent with an essential role for pudendal sensory feedback in efficient bladder emptying, and unilateral and bilateral electrical activation of pudendal nerve afferents are equally efficient in improving bladder emptying in an animal model of urinary retention.
• ? This could provide an approach to improve bladder emptying in patients with non‐obstructive urinary retention.

     

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.

     

Confocal laser endomicroscopy for the diagnosis of urothelial bladder neoplasia: a technology of the future?

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Bladder cancer is initially diagnosed by white light cystoscopy followed by histopathological evaluation after transurethral resection of tissue suspicious for cancer. Difficulties may occur especially in the assessment of flat lesions or in discrimination between CIS and inflammatory disease. Confocal endomicroscopy during diagnostic colonoscopy has been a valuable tool for in vivo microscopic visualization and detection of colonic neoplasias and has contributed to optimized detection rates of up to 99%. We evaluated resected bladder urothelium of 18 patients by confocal endomicroscopy and correlated microscopic findings with standard histopathology. Typical tumour growth patterns such as altered nuclear to cytoplasmic ratio, pseudopapillar tissue stratification and neoangiogenesis were readily visible. As nuclear and subnuclear architecture of healthy bladder tissue could be discriminated against neoplastic tissue, confocal endomicroscopy is a promising novel tool for the in vivo microscopic visualization of bladder cancer.

OBJECTIVE

• ? To evaluate bladder urothelium by confocal laser endomicroscopy (CLE) and correlate microscopic findings with standard histopathology.

PATIENTS AND METHODS

• ? Fresh bladder urothelium tissue specimens were topically stained with acriflavine for instantaneous microscopic imaging.
• ? A single‐line laser in a handheld CLE probe delivered an excitation wavelength of 488 nm providing a high resolution of 0.7 µm and an adjustable imaging depth of 0–250 µm.
• ? Resection specimens of 18 patients were investigated with 1000‐fold magnification and ex vivo findings were compared with targeted histopathology (haematoxylin and eosin staining).

RESULTS

• ? Typical tumour growth patterns such as altered nuclear to cytoplasmic ratio, pseudopapillar tissue stratification and neoangiogenesis were readily visible.
• ? Nuclear and subnuclear architecture of healthy bladder tissue could be discriminated against neoplastic tissue.

CONCLUSIONS

• ? In addition to white light cystoscopy, CLE is a promising novel tool for the in vivo microscopic visualization of bladder cancer; first results of the present study show its potential to define microscopic characteristics of bladder cancer tissue.
• ? Further in vivo studies are necessary to determine sensitivity and specificity of the technique.

     

Secondary bladder cancer after upper tract urothelial carcinoma in the US population

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? It is known that a certain percentage of patients treated for upper tract urothelial carcinoma (UTUC) will go on to develop a secondary bladder cancer; however, the risk factors for developing a secondary bladder tumour have not been studied in a population‐based setting. Given the large changes in how UTUC has been diagnosed and managed in recent years, this study aimed to evaluate the natural history of UTUC in the US population over a 30‐year period, with a particular emphasis on the development of secondary bladder cancer.

OBJECTIVE

• ? To assess the natural history of upper tract urothelial carcinoma (UTUC) and the development of lower tract secondary cancer.

PATIENTS AND METHODS

• ? Patients diagnosed with UTUC between 1975 and 2005 were identified within nine Surveillance, Epidemiology and End Results registries.
• ? Baseline characteristics of patients with and without secondary bladder cancer were compared.
• ? A multivariate logistic regression model was fitted to test if the year of diagnosis predicted the likelihood of developing a secondary bladder cancer.

RESULTS

• ? Of the 5212 patients with UTUC, 242 (4.6%) had a secondary bladder cancer (range: 1.7–8.2%).
• ? There was a mean interval of 26.5 (95% CI: 22.2–30.8) months between cancer diagnoses.
• ? Compared with those without secondary tumours, patients with secondary bladder malignancy were more likely to present with larger tumours (4.2 vs 3.1 cm, P < 0.001) and with tumours located in the ureter (P < 0.001).
• ? Year of diagnosis was not a predictor of the likelihood of having a secondary bladder malignancy in a multivariate analysis controlling for demographic and tumour characteristics (odds ratio: 0.99; 95% CI: 0.95–1.03)

CONCLUSIONS

• ? Patients with larger urothelial tumours located in the ureter were those most likely to develop a secondary lower tract tumour.
• ? No longitudinal changes in the rate of secondary bladder cancer were noted among patients with UTUC over the 30‐year study period.

     

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.

     

Temporal diabetes and diuresis-induced alteration of nerves and vasculature of the urinary bladder in the rat

What’s known on the subject? and What does the study add? Diabetes mellitus seriously affects urinary bladder function. Diabetes induces time‐dependent bladder hypertrophy and altered tissue composition. However, the alterations of the density of nerves and vasculatures in bladder under diabetes remains poorly studied. Diabetes induced time‐dependent changes of density of the nerves and vasculatures in the bladder tissues. In addition, diabetes‐related polyuria plays an important role in this alteration.

OBJECTIVE

• ? To characterize the temporal changes of the nerves and vasculature of the bladder in diabetic rats.

MATERIALS AND METHODS

• ? A total of 36 Sprague–Dawley rats were divided into three groups: streptozotocin‐induced diabetics, 5% sucrose‐induced diuretics and age‐matched controls.
• ? The characteristics of the nerves and vasculature in the equatorial cross‐sectional areas of the bladder were examined by immunofluorescence staining of their specific markers, neurofilament 200 (NF200) and CD31, at 1, 9 or 20 weeks after induction.
• ? The distributions of the nerves and blood vessels were observed and the densities were quantified.

RESULTS

• ? Diabetes caused a significant reduction in body weight. Bladder weight increased in diabetic and diuretic rats, but not in controls.
• ? The total cross‐sectional wall area and detrusor muscle area at the equatorial midline were greater in bladders of diabetic and diuretic rats than in controls.
• ? Neurofilament 200‐immunoreactive (NF200‐IR) nerves were mainly distributed in the detrusor muscle. CD31‐immunoreactive blood vessels were mainly distributed in the mucosa/submucosa.
• ? There were no significant differences in the NF200‐IR nerve terminal area among control, diabetic and diuretic groups. However nerve density was decreased at 9 and 20 weeks in the muscle, and at 20 weeks in the mucosa/submucosa in diabetic and diuretic animals.
• ? Blood vessel density decreased in the diabetic and diuretic groups at 20 weeks in the muscle.

CONCLUSIONS

• ? Diabetes induced time‐dependent changes in the density of the nerves and vasculature in the bladder tissues.
• ? Diabetes‐related polyuria plays an important role in these changes.

     

Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.

OBJECTIVE

• ? To investigate the long‐term oncological outcome, during the PSA era, of patients with prostate cancer who were treated using high‐dose‐rate (HDR) brachy therapy (BT) combined with external beam radiation therapy (EBRT).

PATIENTS AND METHODS

• ? From June 1998 to April 2007, 313 patients with localized prostate cancer were treated with 46 Gy of EBRT to the pelvis with a HDR‐BT boost.
• ? The mean (median) follow‐up was 71 (68) months.
• ? Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, V.4.

RESULTS

• ? The 10‐year actuarial biochemical control was 100% for patients with no high‐risk criteria, 88% for patients with two intermediate‐risk criteria, 91% with one high‐risk criterion and 79% for patients with two to three high‐risk criteria (P= 0.004).
• ? The 10‐year cancer‐specific survival was 97% (standard deviation ±1%).
• ? The multivariate Cox regression analyses identified, Gleason score and T stage as independent prognostic factors for biochemical failure.
• ? Gleason score was the only factor to significantly affect distant metastases.
• ? Grade ≥3 late toxicity was not detected.

CONCLUSION

• ? The 10‐year results confirm the feasibility and effectiveness of EBRT with conformal HDR‐BT boost for patients with localised prostate cancer.

     

Inhibition of bladder overactivity by stimulation of feline pudendal nerve using transdermal amplitude-modulated signal (TAMS)

What's known on the subject? and What does the study add? It is known that direct stimulation of pudenal nerve using a cuff electrode can inhibit normal bladder activity. This study further indicates that overactive bladder activity can be inhibited using non‐invasive skin surface electrodes and a transdermal amplitude‐modulated signal (TAMS).

OBJECTIVE

• ? To develop a non‐invasive neuromodulation method targeting the pudendal nerve.

MATERIALS AND METHODS

• ? Bladder overactivity induced by acetic acid (AA) irritation was partially suppressed by electrical stimulation of the pudendal nerve in α‐chloralose anaesthetized cats using a transdermal amplitude‐modulated signal (TAMS).

RESULTS

• ? During cystometrography (CMG), intravesical infusion of 0.25% AA significantly decreased the mean (se ) bladder capacity to 28.8 (5.9)% of the capacity measured during saline infusion.
• ? The TAMS stimulation inhibited AA‐induced bladder overactivity at 5, 7 and 10 Hz, and significantly increased the mean (se ) bladder capacity to 61.8 (9.9)%, 51.3 (14.5)%, 53.6 (14.9)%, respectively, of the control capacity during saline infusion, whereas stimulation at 20–40 Hz had no effect.
• ? Under isovolumetric conditions at a bladder volume ranging between 130 to 160% of the bladder capacity measured during AA infusion, TAMS stimulation at all frequencies (5–40 Hz) significantly suppressed the irritation‐induced rhythmic bladder contractions, reduced the area under the bladder pressure curve, and decreased the frequency of bladder contractions. However, the amplitude of rhythmic bladder contractions was only significantly decreased at stimulation frequencies of 5–20 Hz.
• ? At bladder volumes above the AA control capacity, TAMS stimulation with frequencies of 20–30 Hz had an excitatory effect, resulting in large amplitude (>25 cmH₂O) bladder contractions.

CONCLUSIONS

• ? TAMS stimulation targeting the cat pudendal nerve can inhibit C‐fibre afferent‐mediated bladder overactivity.
• ? Thus, clinical research seems warranted to explore the usefulness of this technology for patients with overactive bladder symptoms.

     

Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radiotherapy - preliminary results

Study Type – Prognostic (case series) Level of Evidence 4 What's known on the subject? and What does the study add? There have been no reports on the application of HDR‐BT in Japan as salvage therapy for recurrence following radiotherapy. Our data showed that salvage HDR‐BT is effective as an option for treatment of local prostate cancer recurrence after radiotherapy. OBJECTIVE

• ? To assess the preliminary clinical results of salvage high‐dose‐rate brachytherapy (HDR‐BT) applied in cases of suspected local recurrence or of residual tumour after radiotherapy.

PATIENTS AND METHODS

• ? The subjects were 11 patients who met the above conditions and underwent salvage HDR‐BT between December 2006 and January 2009. The T stage at the initial treatment was T1c in three patients, T2 in three patients and T3 in five patients.
• ? Ten patients received HDR‐BT ± electron beam radiation therapy and one patient received proton beam irradiation.
• ? Follow‐up after the completion of salvage HDR‐BT lasted 18–41 months (mean 29 months). A dose of 11.0 Gy radiation was delivered twice (22.0 Gy in total), separated by a 6‐h interval, on the day the applicators were inserted.

RESULTS

• ? Seven of the 11 cases remained in a biochemical non‐evidence of disease state.
• ? The prostate‐specific antigen (PSA) level continuously rose after salvage HDR‐BT in three of the four other cases. Hormone administration was initiated in the four cases of PSA recurrence.
• ? No G3 or more severe events occurred, and the incidence of G2 was low during this study period.

CONCLUSION

• ? Of the 11 cases treated with salvage HDR‐BT, PSA levels remained low in seven cases and the incidence of complications was also low. This suggests that salvage HDR‐BT is effective as an option for treatment of local prostate cancer recurrence after radiotherapy.

     

Mechanisms and urodynamic effects of a potent and selective EP4 receptor antagonist,MF191, on cyclophosphamide and prostaglandin E2‐induced bladder overactivity in rats

Study Type – Aetiology (case control) Level of Evidence 3b What's known on the subject? and What does the study add? Recent evidence has suggested that up‐regulation of the prostaglandin E₂ (PGE₂) receptor subtype 4 (EP4) receptor in the bladder is involved in bladder overactivity. The present study found that MF191, a selective EP4 receptor antagonist, may have effects on the bladder urothelium and inflammatory cells and suppress CYP‐ or PGE₂‐induced bladder overactivity. Systemic or intravesical MF191 administration for the treatment of overactive bladder may merit clinical study.

OBJECTIVE

• ? To investigate the mechanisms and urodynamic effects of a potent and selective prostaglandin E₂ (PGE₂) receptor subtype 4 (EP4) antagonist, MF191, on cyclophosphamide (CYP) or PGE₂‐induced bladder overactivity in rats.

MATERIALS AND METHODS

• ? Experimental and control rats were injected with CYP (200 mg/kg i.p.) or saline on day 1. Continuous cystometrogram (CMGs) were performed on day 3.
• ? In group 1, MF191 (vehicle 0.1 and 1 mg/kg) was given i.v. The bladder was then harvested for histology and immunohistochemistry. Some bladders were harvested for analysis of EP4 expression by Western blotting without a CMG study.
• ? In group 2, MF191 (vehicle 10 nM, and 100 nM) was continuously infused into the bladder.
• ? In group 3, bladder overactivity was induced by intravesical instillation of PGE₂ (200 uM) and vehicle or MF191 (1 mg/kg) was given i.v.

RESULTS

• ? CYP induced bladder inflammation, overactivity and EP4 upregulation. The CYP effects were suppressed by MF191 (1 mg/kg i.v.; intercontraction interval [ICI]: 39.4% increase, and reduced inflammatory cells infiltration, and EP4 expression).
• ? Intravesical instillation of MF191 (100 nM) suppressed CYP‐induced bladder overactivity (ICI: 71.8% increase).
• ? PGE₂‐induced bladder overactivity was suppressed by MF191 (ICI: 43.2% increase).
• ? MF191 had no significant effects on other CMG variables or on control rats.

CONCLUSIONS

• ? MF191 might affect the bladder urothelium and inflammatory cells and suppresses CYP‐ or PGE₂‐induced bladder overactivity.
• ? Systemic or intravesical MF191 administration for the treatment of overactive bladder merits clinical study.

     

Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis

Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Hemorrhagic cystitis (HC) is a relatively rare bladder disease with a complex etiology. With the growing number of patients with pelvic radiation therapy, incidence of this disease has risen considerably. Although treatments like hyperbaric oxygen (HBO) had some benefit to improve the symptoms, the optimal treatment of this disease still remains a tough problem. We reported our experience of intravesical hyaluronic acid (HA) and HBO in treating HC and the results seemed interesting. Intravesical HA is easier to do and well tolerated, and it showed a sustained decrease of bladder bleeding, pelvic pain and frequency of voiding for at least 12 months. We suggest it as an alternative and potential way in treating HC.

OBJECTIVE

• ? To compare the efficacy of intravesical hyaluronic acid (HA) instillation and hyperbaric oxygen (HBO) in the treatment of radiation‐induced haemorrhagic cystitis (HC).

PATIENTS AND METHODS

• ? In total 36 patients who underwent radiotherapy for their pelvic malignancies and subsequently suffered from HC were randomly divided into an HA group and an HBO group.
• ? Symptoms of haematuria, frequency of voiding and the visual analogue scale of pelvic pain (range 0–10) were evaluated before and after the treatment with follow‐up of 18 months.

RESULTS

• ? All patients completed this study and no obvious side effects of intravesical HA were recorded.
• ? The improvement rate showed no statistical difference between the two groups at 6, 12 and 18 months after treatment.
• ? Decrease of frequency was significant in both groups 6 months after treatment, but was only significant in the HA group 12 months after therapy.
• ? The improvement in the visual analogue scale remained significant in both groups for 18 months.

CONCLUSIONS

• ? Intravesical instillation of HA was as effective in treating radiation‐induced HC as HBO.
• ? It is well tolerated and resulted in a sustained decrease of bladder bleeding, pelvic pain and frequency of voiding for at least 12 months.

     

Decision curve analysis assessing the clinical benefit of NMP22 in the detection of bladder cancer: secondary analysis of a prospective trial

Study Type – Decision analysis (based on alternative scenarios) Level of Evidence 2b What's known on the subject? and What does the study add? Several studies have shown that abnormal levels of nuclear matrix protein 22 (NMP22) are associated with bladder cancer, and NMP22 has been approved by the FDA as a urinary biomarker for bladder cancer detection and surveillance. However, the benefit of adding NMP22 to the clinical care of patients remains unclear. Decision curve analysis incorporates the consequences of clinical decisions, such as an increased number of unnecessary cystoscopies or missed cancers.

OBJECTIVE

• ? To employ decision curve analysis to determine the impact of nuclear matrix protein 22 (NMP22) on clinical decision making in the detection of bladder cancer using data from a prospective trial.

PATIENTS AND METHODS

• ? The study included 1303 patients at risk for bladder cancer who underwent cystoscopy, urine cytology and measurement of urinary NMP22 levels.
• ? We constructed several prediction models to estimate risk of bladder cancer. The base model was generated using patient characteristics (age, gender, race, smoking and haematuria); cytology and NMP22 were added to the base model to determine effects on predictive accuracy.
• ? Clinical net benefit was calculated by summing the benefits and subtracting the harms and weighting these by the threshold probability at which a patient or clinician would opt for cystoscopy.

RESULTS

• ? In all, 72 patients were found to have bladder cancer (5.5%). In univariate analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 71.3%), followed by age (67.5%) and cytology (64.3%).
• ? In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 8.2% (area under the curve 70.2–78.4%) and of the base model plus cytology by 4.2% (area under the curve 75.9–80.1%).
• ? Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities.

CONCLUSIONS

• ? NMP22 is a strong, independent predictor of bladder cancer.
• ? Addition of NMP22 improves the accuracy of standard predictors by a statistically and clinically significant margin.
• ? Decision curve analysis suggests that integration of NMP22 into clinical decision making helps avoid unnecessary cystoscopies, with minimal increased risk of missing a cancer.

     

Enhanced S100 calcium‐binding protein P expression sensitizes human bladder cancer cells to cisplatin

What’s known on the subject? and What does the study add? So far, several molecules have been reported to be involved in cisplatin resistance. This study revealed that a decreased expression of S100P is implicated in cisplatin resistance. In addition, S100P overexpression rendered bladder cancer cells sensitive to cisplatin.

OBJECTIVE

• ? To investigate the role of S100 calcium‐binding protein P (S100P) in the gain of cis‐diamminedichloroplatinum (II) (cisplatin) resistance in bladder cancer, having previously found, with cDNA microarrays using two pairs of parental (T24, KK47) and their cisplatin‐resistant bladder cancer cell lines (T24/DDP10, KK47/DDP20), that S100P mRNA expression was significantly reduced in cisplatin‐resistant cells.

MATERIALS AND METHODS

• ? S100P mRNA and protein expression levels were investigated by northern and western blot analyses, respectively.
• ? Intracellular S100P localization was examined by immunocytochemistry and immunohistochemistry.
• ? S100P over‐expression, obtained by transfection with S100P expression plasmid, was used to investigate whether or not S100P affected cellular resistance to cisplatin.

RESULTS

• ? S100P mRNA showed increased expression by cisplatin stimulation in parental cell lines.
• ? On the other hand, S100P mRNA and protein expression levels were markedly reduced in cisplatin‐resistant cells.
• ? The over‐expression of S100P in resistant cells resulted in an increased sensitivity to cisplatin.

CONCLUSIONS

• ? In bladder cancer cells, S100P was expressed and localized mainly in the nucleus.
• ? S100P expression was also involved in cisplatin sensitivity.
• ? S100P might thus represent a molecular marker predicting cisplatin sensitivity and a molecular therapeutic target for cisplatin‐based chemotherapy.

     

Overactive bladder syndrome: an underestimated long‐term problem after treatment of patients with localized prostate cancer?

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? In this study we observed courses of micturition symptoms and differentiated degrees of symptoms for each point in time while also considering the impact of bothersomeness. Our data show that not only significantly more patients who have undergone BT suffer from OAB than those who have undergone RP, but also that those affected show significantly higher values for severity of OAB symptoms throughout the whole observation period of 36 months. Our data analysis further shows that variability of OAB symptoms as well as fluctuation of severity of OAB symptoms vary to a significantly higher degree after BT than after RP. Looking only at mean figures at a given point in time clearly underestimates the underlying problem. This fact is not reflected in the literature.

OBJECTIVE

• ? To look at individual courses of postoperative micturition symptoms, especially urgency, in patients treated either with radical prostatectomy (RP) or with brachytherapy (BT).

PATIENTS AND METHODS

• ? In a prospective longitudinal study we investigated individual changes in micturition symptoms before treatment, and 6, 12, 24 and 36 months after treatment.
• ? All patients received the European Organization for the Research and Treatment of Cancer quality‐of‐life questionnaire, QLQ‐C30, and the International Continence Society male questionnaire at each assessment.
• ? We looked at long‐term results as well as changes in time using repeated measures analysis of variance. We further analysed fluctuation of symptoms using sum of changes.

RESULTS

• ? Of the 389 patients treated consecutively in our clinic over the last few years, 99 patients with a mean (sd ) age of 65 (6.3) years had completed all five questionnaires and thus were further analysed. Of these, 66 (66.7%) were treated with RP and 33 (33.3%) with BT.
• ? With the exception of age, no significant difference was found between the treatment groups either in physical functioning or in prevalence and severity of overactive bladder (OAB) symptoms.
• ? Adjusted for age and pretreatment symptoms in analysis of covariance, we found that there were statistically more symptoms of OAB 36 months after BT compared with those patients treated with RP (P < 0.025). Whereas 30% of patients complained about severe symptoms of urgency after BT, only 11% did so after RP.
• ? Changes of severity of OAB symptoms over the course of time (P < 0.007) using analysis of repeated measures as well as variability of OAB symptoms (P < 0.033) using the two‐sided Wilcoxon t‐test were significantly higher in patients treated with BT than in patients treated with RP.

CONCLUSIONS

• ? Independently of age and physical functioning, BT is significantly associated with higher rates of long‐term urgency symptoms, even after 3 years.
• ? Repeated measurements show that OAB symptoms are highly fluctuating and that in patients treated with BT, severity of symptoms as well as variability of symptoms was significantly higher than in those patients treated with RP.
• ? Persistent OAB seems to be an underestimated problem after treatment for localized prostate cancer, especially in patients treated with BT.