To compare the safety and tolerability of tamsulosin 0.4 mg once daily in younger (< 65 years) and older (> or = 65 years) patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO).
In a retrospective analysis of two European double-blind, randomized, placebo-controlled trials, safety was assessed in 574 younger or older patients treated with tamsulosin or placebo for 12 weeks.
The incidence of adverse events, drug-related adverse events, serious adverse events and discontinuations due to adverse events was similar in older and younger tamsulosin-treated patients and was not significantly different from placebo. Although abnormal ejaculation was slightly more common in younger than older men receiving tamsulosin, the difference was not statistically significant from the placebo groups in both age groups. The incidence of adverse events possibly associated with vasodilation in tamsulosin-treated younger and older patients was 8.4 and 4.2%, respectively; these were comparable with the values for placebo-treated patients: 7.5 and 6%, respectively. Baseline systolic blood pressure was higher in older than younger patients, but there were minimal changes in blood pressure or pulse rate in tamsulosin- or placebo-treated patients in either age group.
Tamsulosin is well tolerated and suitable for use in older and younger patients with LUTS suggestive of BPO (symptomatic BPH).
To evaluate the effect of tamsulosin, 0.4 mg once daily, on sexual function in comparison with placebo and alfuzosin, 2.5 mg three times daily, in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO).
Data from 830 patients randomized into three European multicenter studies with similar protocols were analyzed. In two studies, patients were randomized to receive either tamsulosin, 0.4 mg once daily, or placebo, and in the third, patients were randomized to receive either a fixed dose of tamsulosin, 0.4 mg once daily, or alfuzosin, titrated to 2.5 mg three times daily. The studies employed a 2-week placebo run-in period, followed by a 12-week study period. Sexual function was assessed by related adverse events and by a sexual function score determined from a life-style questionnaire.
Abnormal ejaculation occurred significantly more frequently in patients treated with tamsulosin than in those receiving placebo (p = 0.045); however, the incidence of abnormal ejaculation was similar in patients receiving tamsulosin or alfuzosin in the comparative study. Abnormal ejaculation was not perceived as a major problem by the patients since it resulted in few treatment discontinuations (n = 3). It was also reversible on drug withdrawal. There was no difference between tamsulosin and placebo or alfuzosin with regard to the occurrence of decreased libido or impotence. In addition, there was no significant difference in the change in sexual function score between patients treated with tamsulosin and those treated with alfuzosin. Compared with patients receiving placebo, there was, however, a significant improvement in total sexual function score in patients receiving tamsulosin (p = 0.042).
Tamsulosin, 0.4 mg once daily, is well tolerated and has no overall negative impact on sexual function compared with placebo or alfuzosin. Compared with placebo, tamsulosin may even improve sexual function.
Improvements over existing treatment standards in overactive bladder (OAB) may only be possible through the development of drugs acting via non-cholinergic pathways. This is the first clinical study to be reported in full for the use of a potassium channel opener in OAB.
This randomized, double-blind, placebo-controlled phase II study evaluated the efficacy and safety of ZD0947 (25mg/day for 12 weeks) in patients with OAB. The primary endpoint was mean volume voided per micturition per 24 hours. Key secondary endpoints were changes from baseline in mean numbers of micturition episodes (total, voluntary, and incontinent) per 24 hours.
ZD0947 was not superior to placebo for the primary or secondary efficacy variables. The placebo-adjusted magnitude of effect for ZD0947 (approx. 4 mL) was less than the historic data for cholinergic antagonists (approx. 20 mL). Treatment was generally safe and well tolerated.
The data for ZD0947 are disappointing. More studies are needed to advance the identification of novel, non-cholinergic therapies for OAB.
Although benign prostate hyperplasia (BPH) and prostate cancer (PCa) share features such as hormone-dependent growth and response to treatment with antiandrogen therapy, BPH is generally not considered a premalignant lesion.
To determine whether clinical BPH is associated with an increased risk of PCa incidence and mortality.
Using designs with individual participant data from five national registries, we studied the entire Danish male population from 1980 through 2006, a total of 3,009,258 Danish men. We collected PCa diagnoses (n=53,315), information on PCa mortality (n=25,459), and ascertained clinical BPH (not histologically proven BPH) through hospitalization (n=187,591) and/or surgery (n=77,698) from 1980 to 2006 and the use of α-adrenergic receptor antagonists (n=143,365) and/or the use of 5α-reductase inhibitors (5-ARIs) (n=47,465) from 1995 to 2006.
PCa incidence and mortality was assessed for each category of clinical BPH using Kaplan-Meier plots of cumulative incidence and Cox proportional hazard ratios (HRs) adjusted for potential confounders.
For the entire cohort studies, multivariate-adjusted HRs for PCa incidence were 2.22 (95% confidence interval, 2.13-2.31) in men hospitalized and 3.26 (3.03-3.50) in men operated on for clinical BPH versus general population controls. Corresponding HRs for PCa mortality were 2.00 (1.91-2.08) for hospitalization and 7.85 (7.40-8.32) for surgery. For age-matched cohort studies, corresponding HRs for PCa incidence were 3.04 (2.96-3.13) for hospitalization, 2.60 (2.47-2.73) for surgery, 4.49 (4.33-4.65) for α-adrenergic receptor antagonist use, and 2.54 (2.40-2.68) for 5-ARI use. Each category of clinical BPH has limitations, but limitations differ between the categories and therefore are unlikely to explain the results.
In Danish men followed for up to 27 yr, clinical BPH was associated with a two- to three-fold increased risk of PCa incidence and with a two- to eight-fold increased risk of PCa mortality. These data should not be used to infer causality.
Few series comparing the clinical efficacy of retropubic slings versus transobturator slings for the treatment of female stress urinary incontinence (SUI) are available.
To compare clinical efficacy of retropubic tape operations and transobturator suburethral tape operations for the surgical treatment of female SUI.
From January 2003 to December 2005, 611 patients underwent clinical and urodynamic evaluation before surgical treatment for SUI. Patients with advanced urogenital prolapse (pelvic organ prolapse-quantification scale [POP-Q] scale grade >1) were excluded, and 537 patients were included in this study. After 18 mo, 398 women were available for follow-up efficacy evaluation at a tertiary academic center.
All patients underwent either a retropubic sling procedure or a transobturator sling procedure. Patients were randomly allocated into two study groups at a ratio of 1:1.
After 18 mo all enrolled patients were clinically checked for clinical efficacy of both procedures.
Demographic and urodynamic parameters of patients were similar in both groups. No bladder injury occurred in the transobturator sling group (IVS-04), whereas 13 intraoperational bladder perforations (6.5%) occurred in the retropubic sling group (IVS-02) (p<0.001). The tape erosion rate was <2.5% in both groups (p=0.7). After 18 mo, 398 patients (201 in the IVS-02 group and 197 in the IVS-04 group) were evaluated in terms of clinical efficacy of the procedures. We found out that there was no statistically significant difference in clinical efficacy between these two procedures (chi(2)=1.88, p=0.39). In the IVS-02 group, 75.1% of patients (n=151) remained dry (cured), 16.9% of patients (n=34) reported significant improvement, and 8.0% of patients (n=16) were considered as failures. In the IVS-04 group, 74.1% of patients (n=146) remained dry, 14.2% of patients (n=28) reported significant improvement, and 11.7% (n=23) were considered as failures.
Based on an 18-mo follow-up, the efficacies of both techniques are comparable; however, the retropubic route appears to be more efficient in the intrinsic sphincter deficiency (ISD) group.
Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Three prospectively randomized trials demonstrated an advantage for adjuvant radiotherapy (ART) compared with a wait-and-see (WS) policy.
To determine the efficiency of ART after a 10-yr follow-up in the ARO 96-02 study.
After RP, 388 patients with pT3 pN0 prostate cancer (PCa) were randomized to WS or three-dimensional conformal ART with 60Gy. The present analysis focuses on intent-to-treat patients who achieved an undetectable prostate-specific antigen after RP (ITT2 population)-that is, 159 WS plus 148 ART men.
The primary end point of the study was progression-free survival (PFS) (events: biochemical recurrence, clinical recurrence, or death). Outcomes were compared by log-rank test. Cox regression analysis served to identify variables influencing the course of disease.
The median follow-up was 111 mo for ART and 113 mo for WS. At 10 yr, PFS was 56% for ART and 35% for WS (p<0.0001). In pT3b and R1 patients, the rates for WS even dropped to 28% and 27%, respectively. Of all 307 ITT2 patients, 15 died from PCa, and 28 died for other or unknown reasons. Neither metastasis-free survival nor overall survival was significantly improved by ART. However, the study was underpowered for these end points. The worst late sequelae in the ART cohort were one grade 3 and three grade 2 cases of bladder toxicity and two grade 2 cases of rectum toxicity. No grade 4 events occurred.
Compared with WS, ART reduced the risk of (biochemical) progression with a hazard ratio of 0.51 in pT3 PCa. With only one grade 3 case of late toxicity, ART was safe.
Precautionary radiotherapy counteracts relapse after surgery for prostate cancer with specific risk factors.
Gonadotropin-releasing hormone agonists (GnRHa) are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about their potential effects on cardiovascular mortality. We assessed the relationship between duration of GnRHa therapy and cardiovascular mortality in a large randomized trial of men treated with short-term versus longer-term adjuvant goserelin and radiation therapy (RT) for locally advanced prostate cancer.
From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-4, prostate-specific antigen [PSA] <150 ng/ml) received RT and 4 mo of goserelin and then were randomized to no additional therapy (arm 1) or 24 mo adjuvant goserelin (arm 2) in a phase 3 trial (Radiation Therapy Oncology Group [RTOG] 92-02). Cox regression analyses were performed to evaluate the relationship between treatment arm and cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes (DM), race, PSA, Gleason score, and stage.
After median follow-up of 8.1 yr, 185 cardiovascular-related deaths had occurred. No increase in cardiovascular mortality occurred for men receiving a longer duration of goserelin. At 5 yr, cardiovascular mortality for men receiving longer-term adjuvant goserelin was 5.9% versus 4.8% with short-term goserelin (Gray's p=0.16). In multivariate analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR]=1.09; 95% confidence interval [CI], 0.81-1.47; p=0.58; when censoring at time of salvage goserelin, HR=1.02, 95%CI, 0.73-1.43; p=0.9). Traditional cardiac risk factors, including age, prevalent CVD, and DM, were significantly associated with greater cardiovascular mortality.
Longer duration of adjuvant GnRHa therapy does not appear to increase cardiovascular mortality in men with locally advanced prostate cancer.
Long-term prostate cancer (PCa) survivors are at increased risk for comorbidities and physical deconditioning.
To determine the effectiveness of a year-long randomised controlled trial of exercise training in PCa survivors >5 yr postdiagnosis on physical functioning.
Between 2010 and 2011, 100 long-term PCa survivors from Trans-Tasman Radiation Oncology Group 03.04 Randomised Androgen Deprivation and Radiotherapy previously treated with androgen-deprivation therapy and radiation therapy were randomly assigned to 6 mo of supervised exercise followed by 6 mo of a home-based maintenance programme (n=50) or printed educational material about physical activity (n=50) for 12 mo across 13 university-affiliated exercise clinics in Australia and New Zealand.
Supervised resistance and aerobic exercise or printed educational material about physical activity.
The primary end point was a 400-m walk as a measure of cardiovascular fitness. Secondary end points were physical function, patient-reported outcomes, muscle strength, body composition, and biomarkers. Analysis of covariance was used to compare outcomes for groups at 6 and 12 mo adjusted for baseline values.
Participants undergoing supervised exercise showed improvement in cardiorespiratory fitness performance at 6 mo (-19 s [p=0.029]) and 12 mo (-13 s [p=0.028]) and better lower-body physical function across the 12-mo period (p<0.01). Supervised exercise also improved self-reported physical functioning at 6 (p=.006) and 12 mo (p=0.002), appendicular skeletal muscle at 6 mo (p=0.019), and objective measures of muscle strength at 6 and 12 mo (p<0.050). Limitations included the restricted number of participants undertaking body composition assessment, no blinding to group assignment for physical functioning measures, and inclusion of well-functioning individuals.
Supervised exercise training in long-term PCa survivors is more effective than physical activity educational material for increasing cardiorespiratory fitness, physical function, muscle strength, and self-reported physical functioning at 6 mo. Importantly, these benefits were maintained in the long term with a home-based programme with follow-up at 12 mo.
The effect of an exercise intervention on cardiovascular and metabolic risk factors in prostate cancer patients from the RADAR study, ACTRN: ACTRN12609000729224.
Recent publications suggest a benefit from surgical removal of urothelial carcinoma metastases (UCM) for a subgroup of patients.
We report the combined experience and outcome of patients undergoing resection of UCM gained at 15 uro-oncologic centers in Germany.
Retrospective survey of 44 patients with distant UCM of the bladder or upper urinary tract who underwent complete resection of all detectable metastases in 15 different German uro-oncological centers between 1991 and 2008.
Resected metastatic sites were the following: retroperitoneal lymph nodes (56.8%), distant lymph nodes (11.3%), lung (18.2%), bone (4.5%), adrenal gland (2.3%), brain (2.3%), small intestine (2.3%), and skin (2.3%). Systemic chemotherapy was administered in 35 of 44 patients (79.5%) before and/or after UCM surgery.
Overall, cancer-specific and progression-free survival from time of diagnosis and metastasectomy of UCM.
Median survival from initial diagnosis of UCM and subsequent resection was as follows: overall survival, 35 mo and 27 mo; cancer-specific survival, 38 mo and 34 mo; and progression-free survival, 19 mo and 15 mo. Overall 5-yr survival from metastasectomy for the entire cohort was 28%. Seventeen patients were still alive without progression at a median follow-up of 8 mo. Seven patients without disease progression survived for >2 yr and remained free from tumor progression at a median follow-up of 63 mo. No significant prognostic factors could be determined due to the limited patient number.
Long-term cancer control and possible cure can be achieved in a subgroup of patients following surgical removal of UCM. Metastasectomy in patients with disseminated UCM remains investigational and should only be offered to those with limited disease as a combined-modality approach with systemic chemotherapy.
Intraoperative frozen-section analysis allows real-time histologic assessment of surgical margins (SMs) and identification of candidates for nerve-sparing (NS) procedures.
To examine the efficacy and oncologic safety of a systematic neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during NS radical prostatectomy (RP).
From January 2002 to June 2011, 11 069 consecutive RPs were performed at the University Medical Center Hamburg-Eppendorf. Of these, 5392 (49%) were conducted with NeuroSAFE.
Our NeuroSAFE approach included the whole laterorectal circumference of the prostate to determine the SM status of the complete neurovascular tissue-corresponding prostatic surface. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The impact of NeuroSAFE on NS frequency, SM status, and biochemical recurrence (BCR) was analyzed by chi-square test, and by Kaplan-Meier analyses in propensity score-based matched cohorts.
Positive SMs (PSMs) were detected in 1368 (25%) NeuroSAFE RPs, leading to a secondary resection of the ipsilateral neurovascular tissue. Secondary wide resection resulted in conversion to a definitive negative SM (NSM) status in 1180 (86%) patients. In NeuroSAFE RPs, frequency of NS was significantly higher (all stages: 97% vs 81%; pT2: 99% vs 92%; pT3a: 94% vs 72%; pT3b: 88% vs 40%; p<0.0001) and PSM rates were significantly lower (all stages: 15% vs 22%; pT2: 7% vs 12%; pT3a: 21% vs 32%; p<0.0001) than in the matched non-NeuroSAFE RPs. In propensity score-based comparisons, NeuroSAFE had no negative impact on BCR (pT2, p=0.06; pT3a, p=0.17, pT3b, p=0.99), and BCR-free survival of patients with conversion to NSM did not differ significantly from patients with primarily NSM (pT2, p=0.16; pT3, p=0.26). The accuracy of our NeuroSAFE approach was 97% with a false-negative rate of 2.5%. The major limitations of this study are its retrospective nature and relatively short follow-up.
NeuroSAFE enables real-time histologic monitoring of the oncologic safety of a NS procedure. Systematic NeuroSAFE significantly increases NS frequencies and reduces PSMs. Patients with a NeuroSAFE-detected PSM could be converted to a prognostically more favorable NSM status by secondary wide resection.
There is evidence linking metformin to improved prostate cancer (PCa)-related outcomes.
To evaluate treatment with metformin in patients with castration-resistant PCa (CRPC) and the effect of the treatment on progression-free survival (PFS) and PSA doubling time (PSA DT).
Forty-four men with progressive metastatic CRPC from 10 Swiss centers were included in this single-arm phase 2 trial between December 2010 and December 2011.
Patients received metformin 1000mg twice daily until disease progression.
The primary end point was the absence of disease progression at 12 wk. Simon two-stage optimal design was applied. With a 5% significance level and 90% power, 44 patients were required to test PFS at 12 wk ≤15% (H0) compared with ≥35% (H1).
Thirty-six percent of patients were progression-free at 12 wk, 9.1% were progression-free at 24 wk, and in two patients a confirmed ≥50% prostate-specific antigen (PSA) decline was demonstrated. In 23 patients (52.3%) we observed a prolongation of PSA DT after starting metformin. The homeostatic model assessment index fell by 26% from baseline to 12 wk, indicating an improvement in insulin sensitivity. There was a significant change in insulin-like growth factor-1 and insulin-like growth factor binding protein 3 from baseline to 12 wk. Sample size and lack of a control arm are the limitations of this trial; analyses are therefore exploratory.
Treatment with metformin is safe in nondiabetic patients, and it yields objective PSA responses and may induce disease stabilization. The activity of metformin in PCa, along with its low cost, favorable toxicity profile, and positive effect on metabolic parameters, suggests that further investigation of metformin as therapy for patients with PCa is of interest.
In this trial we assessed the use of the diabetes mellitus drug metformin in patients with advanced prostate cancer. We found disease stabilization and prolongation of prostate-specific antigen doubling time in some patients as well as effects on metabolic parameters.
This study is registered with ClinicalTrials.gov with the identifier NCT01243385.
The study was presented at ESMO 2012 (abstract 1460).
1,000 Millin prostatectomies were performed under general anaesthesia and normal conditions of blood pressure (without hypotension) over a period of 6 years. Observations were made as to the blood losses (Davillas and Miliaressis, 1972), the length of hospitalization, the various complications and the death causes in 17 patients (1.7%).
Among 750 patients who underwent surgery because of benign prostatic hyperplasia, 26 (3.5%) were found, before surgery, to have a huge residual urine of over 1,000 ml without classic prostatic symptoms. Dilatation of the upper urinary tract was found in 22 (84.6%) of these 26 patients. After surgery, almost two thirds of the patients remained with the anatomical damage (dilatation) of the upper tract. Before surgery all the patients had elevated serum creatinine. After release of the obstruction 50% of the patients were left with irreversible renal damage (as determined by serum creatinine). Although anatomical changes of the urinary bladder remained in all the patients, a satisfactory clinical recovery with a fairly good detrusor contraction and almost no residual urine was found after surgical removal of the obstruction. Awareness of the entity described here followed by early treatment can prevent progressive renal failure and detrusor decompensation.
Nonadrenergic, noncholinergic (NANC) contraction has been demonstrated in animal urinary bladder. However, the exact nature of the NANC innervation is still unclear. 1,1-Dimethylphenylpiperazinium (DMPP), which generates action potentials in the cell body of the postganglionic neuron and causes neurotransmitter release (both acetylcholine and noradrenaline), was given intravenously (0.1-0.7 mg/kg) to 3-month-old female Wistar rats under anesthesia (n = 20). Intravesical pressure, heart rate and blood pressure of the rats were monitored on Gould polygraph. Monophasic dose-dependent contractile response was observed upon administration of DMPP in 12 of 20 rats. After total adrenergic and cholinergic blockade with atropine, guanethidine, phentolamine and propranolol, the contractile response was reduced, not completely, in the animals. At the dose of 0.7 mg/kg, the contraction was reduced to about 48% of the original response. The study provides in vivo evidence for NANC contraction in the rat urinary bladder, moreover, the neurotransmitter is released from the postganglionic neurons.
1,200 extracorporeal lithotripsies have been performed in 816 patients. 58% of the stones had a diameter of 3-10 mm, 41% measured between 11 and 20 mm and 1% were larger than 20 mm. The patients were all treated on an outpatient basis without either anesthesia or analgesia. The mean time spent at the lithotripsy center was 2 h: the mean treatment time was 46 min, i.e. 3,450 shocks at a frequency of 1.25/s. 530 patients were reviewed after 3 months. Overall, 64% of them were stone free. These results varied between 73% for stones less than 10 mm in diameter and 43% for stones larger than 20 mm in diameter. 69% of the patients presenting with a single stone were stone free at 3 months. The best results were obtained in upper caliceal stones (78%) and the least satisfactory results were obtained in the lower caliceal stones (68%). The complication rate was low: renal colic in 18% of cases, fever in 2% of cases. Altogether, 13 disobstructions were required, namely 12 endoscopic and 1 surgical. 33% of patients were retreated without admission to hospital. Outpatient extracorporeal piezoelectric lithotripsy is indicated for renal pelvic or caliceal stones less than 20 mm in diameter situated in a nonobstructed renal cavity, in a noninfected patient without any particular risk factors. 85% of patients are currently treated at the lithotripsy center on an outpatient basis.
Vitamin D receptors (VDR) have been detected in normal tissues and in a number of cancer types. This study was undertaken to determine the VDR expression status and to elucidate the prognostic significance of VDRs in superficial transitional cell carcinoma (TCC) of the human bladder.
VDR expression was investigated in the tumour tissue blocks which were obtained by transurethral resection from 105 patients with superficial TCC without concomitant carcinoma in situ and in 30 control subjects. Median follow-up of the patients was 40 months. The expression of nuclear VDR was evaluated immunohistochemically using avidin-biotin-peroxidase method and a monoclonal VDR antibody. VDR staining intensity in samples were assessed semi-quantitatively and graded as [-] if VDR was lacking, [+] if <33% of cells were stained, [++] if 33-66% of cells and [+++] if >66% were stained. Staining characteristics were compared with the clinico-pathologic results.
VDRs were detected in 85.7% of the patients with superficial TCC and in 66.6% of the controls (p = 0.02). No correlation was found between VDR expression and pathological stage and grade (p = 0.05 and p = 0.09, respectively). Progression in pathologic stage was significantly higher in VDR[+++] tumours (p = 0.001). Also, disease-free survival was significantly lower and tumour size was significantly greater in VDR [+++] tumours than [-], [+] and [++] ones (p = 0.02, p = 0.008 and 0.007, respectively). No significant difference was found between patient age, sex, tumour multiplicity in terms of VDR expression. Survival was not affected by VDR expression. In multivariate analysis VDR expression was not found to be an independent prognostic factor.
Superficial TCC of the bladder express VDRs. The association of increased VDR expression and higher disease progression may be useful in discriminating less differentiated superficial TCCs with poor outcome.
Evaluation of the incidence of urological abnormalities as revealed by urological examinations of a large number of patients with enuresis.
Patients with the chief complaint of nocturnal enuresis were examined urologically.
The incidence of urological abnormalities was 1.8% of 940 patients on intravenous pyelography (IVP), 7.1% of 695 patients on voiding cystourethrography (VCG) and 11.5% of 487 patients on cystometry (CM). No abnormal findings were observed in 58 patients on renal ultrasonography (US). 92.1% of reflux cases detected by VCG were low grade and only 8.9% of patients with reflux had pyuria. 20.2% of 446 patients who were submitted to all these examinations had some urological abnormality. Only pollakisuria was statistically more frequent in patients with urological abnormalities than in patients without them.
These data suggest that the incidence of urological abnormalities was rather low when compared with the past literature. In particular, IVP was though to be unnecessary.
The author reviews 1,342 cases of renal cysts in adults reported at the 69th Congress of the French Association of Urology. The major clinical features of the disease are described and the reliability in current practice of the various diagnostic procedures are discussed in the light of this large series.
Vascular endothelial growth factor (VEGF)-targeted therapy has become standard treatment for patients with metastatic renal cell cancer (mRCC). Since these therapies can induce tumor necrosis and minimal tumor shrinkage, Response Evaluation Criteria in Solid Tumors (RECIST) may not be optimal for predicting clinical outcome.
To systematically determine the optimal early posttherapy imaging changes (EPTIC) to separate responders and nonresponders at the first posttreatment follow-up computed tomography (CT).
Seventy mRCC patients with 155 target lesions treated with first-line sunitinib, sorafenib, or bevacizumab at academic medical centers underwent contrast-enhanced thoracic and abdominal CT at baseline and first follow-up after therapy initiation (median: 78 d after therapy initiation; range: 31-223 d).
Evaluations were performed according to (1) RECIST 1.0; (2) Choi criteria; (3) tumor shrinkage (TS) of ≥10% decrease in sum of the longest unidimensional diameter (SLD); and (4) 15% or 20% decrease in mean CT tumor density. Correlation with time to treatment failure (TTF) and overall survival (OS) were compared and stratified by response to each of the radiologic criteria.
Eleven patients were considered responders by RECIST 1.0; 49 based on Choi criteria; 31 patients had ≥10% decrease in the SLD; and 36 and 32 patients had ≥15% and ≥20% decrease, respectively, in mean tumor density on CT. Only the threshold of 10% decrease in the SLD was statistically significant in predicting TTF (10.4 vs 5.1 mo; p=0.02) and OS (32.5 vs 15.8 mo; p=0.002). Receiver operating characteristic analysis yielded a 10% decrease in SLD as the optimal size change threshold for responders. The retrospective nature of the study and measurements by a single oncoradiologist are inherent limitations.
In the retrospectively analyzed study population of mRCC patients receiving VEGF-targeted agents, a 10% reduction in the SLD on the first follow-up CT was an optimal early predictor of outcome.
Objectives:
Sacral neuromodulation has become an established method to treat voiding dysfunction. Currently the use of implanted sacral nerve stimulators is becoming more popular worldwide. Magnetic resonance imaging (MRI) is an important diagnostic tool for many medical and neurological disorders. Many radiology centers do not perform MRI examinations on patients with implanted sacral nerve stimulator. The basis for this policy is that potential hazards such as motion, dislocation or torquing of the implanted pulse generator (IPG), heating of the leads, and damage to the IPG may occur, resulting in painful stimulation. In contrast, many studies conducted on MRI at 1.5Tesla in patients with implantable devices have found the examination to be safe if the area to be imaged is out of the isocenter of the MRI scanner and other precautions are taken.
Methods:
Eight MRI examinations at 1.5Tesla were conducted in areas outside the pelvis on six patients with implanted sacral nerve stimulator (InterStim neurostimulator; Medtronic, Inc, Minneapolis, MN, USA). Implanted pulse generators were examined before and after MRI procedures. All patients had their parameters recorded; then the IPGs were put to "nominal" status. Patients were monitored continuously during and after the procedure. After the MRI session, the site of the implanted device was examined and changes were reported. Devices were then re-programmed to their previous setup with the use of a programmer (model 7432; Medtronic, Inc). Voiding diaries were collected after MRI procedures and compared with previous records.
Results and conclusion:
During the MRI session, no patient showed symptoms that required stopping the examination. There was no change in perception of the stimulation after re-programming of the implanted sacral nerve stimulator, according to patients' feedback. Devices were functioning properly, and no change in bladder functions was reported after MRI examinations. Finally, we hope that presenting these cases will encourage performance of more comprehensive studies on implanted sacral nerve stimulators on a larger patient population in the near future.
To evaluate the safety and suitability of sorbitol-mannitol solution (Purisole((R)), Fresenius, Germany) as a fluid for irrigation during electrosurgical resection of prostate (TURP).
120 sequential patients undergoing TURP were studied. Serum electrolytes were measured before and the day after surgery. Time and weight of resection were recorded. Use of blood transfusion was recorded.
There were no adverse effects attributable to the use of the irrigant. There were no technical, electrical or instrument problems. None of the surgeons had any difficulties with clarity of view during resection when bleeding was light. There was no significant change in any of the serum electrolytes between pre-operative and postoperative values. No patient developed significant postoperative hyponatraemia or the 'TUR syndrome'.
Purisole (sorbitol-mannitol) solution is entirely satisfactory as an irrigant for electrosurgical resection and in the present study there were no measurable changes in patients' electrolytes around the time of surgery. What small changes occurred indicate there is an overall mild dehydration effect through the process of surgery, which may be in part attributable to irrigant, but this change was small and does not reach either clinical or statistical significance. Purisole offers theoretical advantages over glycine solution and there are no obvious disadvantages. The authors would thereby recommend it in preference to glycine.
Laparoscopic cryoablation has recently been proposed as a minimally invasive nephron-sparing treatment for selected patients. We report on our experience with a retroperitoneoscopic technique using multiple ultrathin cryoprobes.
Seven patients underwent retroperitoneoscopic renal cryoablation for solid renal masses. Mean tumor size on the CT scan was 2.6 (1.5-3.5) cm. A double freeze-thaw cycle of renal cryoablation was performed under real-time ultrasound monitoring using a total of six 1.5-mm cryoprobes simultaneously.
Cryoablation was technically successful in all patients without any need for conversion. Mean duration of surgery was 161 (130-195) minutes and mean blood loss was 107 (50-250) ml. Perioperative biopsy of the tumor confirmed renal cell carcinoma in four patients and angiomyolipoma in two patients; it was inconclusive in one case. Mean follow-up for 13.6 (4-22) months showed no evidence of residual tumor or recurrence.
Retroperitoneoscopy-assisted cryosurgical ablation using multiple ultrathin 1.5-mm cryoprobes is a minimally invasive treatment that is suitable to treat small renal tumors.
Hospital-acquired urinary tract infections (HUTI) represent a significant impairment in the quality of health care. Incidence in catheterized patients has been estimated at approximately 20%, however few data are available in urologic patients. We report a prospective surveillance program over 6 years in our urologic department and evaluate its evolution.
Population consists of all patients admitted to the urology ward for 48 hours or more over a 6-year period from 1994. Data recorded: age, gender, duration of stay, insertion and removal of catheters, diagnosis of HUTI. Analysis: calculation of incidence, and incidence density for HUTI and for catheter-related HUTI, analysis of trends by chi(2) trend test.
A total of 10,054 consecutive patients were included, 52% were catheterized. The median incidence of catheter-related HUTI in catheterized patients was 13.0%, the incidence density was 25.1 HUTI/1000 patient-days of catheterization. The proportion of HUTI and specific catheter-related HUTI patients decreased, respectively from 8.4% and 14.2% to 6.5% and 12.3% during the study period (p<0.05).
The rate of HUTI was not as high as previously reported, perhaps due to a controlled catheter policy. Surveillance was associated with a significant decrease in infection rates, suggesting a beneficial feedback effect. Evaluation of diagnoses and surgical procedures would ensure an optimal quality control program.
To make qualitative as well as semiquantitative analyses of 10,000 urinary calculi of large city population, a combined crystal-optical X-ray diffractometric method proved to be very useful. This combination goes to complement the advantages of polarization microscopy (with its minimal substance requirements, its proof limits of less than 1%, and its insight into stone texture) with those of X-ray diffraction (with its fast semiquantitative analysis and simple differentiation of all the stone components). About 30% of the calculi were found to have a monomineral composition. The most frequent types of calculi in our examination were: 33.2% whewellite/weddellite, 24.9% whewellite, 13.5% whewellite/weddellite/apatite, 7.0% struvite/apatite, and 3.9% uric acid/uric acid dihydrate.
The percentage of free prostatic-specific antigen (PSA) has been introduced as a tool to avoid unnecessary biopsies in men with normal digital rectal examination (DRE) and serum PSA between 4.1 and 10 ng/ml. In this series we also analyze its utility in men with normal DRE and serum PSA between 10.1 and 20 ng/ml.
A series of 1149 consecutive men with normal DRE and serum PSA between 4.1 and 20 ng/ml submitted for the first ultrasound guided sextant biopsy is analyzed. In 921 (80.2%) the serum PSA was from 4.1 to 10 ng/ml and in 228 (19.8%) from 10.1 to 20 ng/ml. Total and free serum PSA determinations were done by the inmunoradiometric assays Tandem and Tandem free PSA (Hybritech Inc.).
The overall detection rate of prostate cancer was 27.9%. In the group of men which serum PSA ranged from 4.1 to 10 ng/ml the rate of detection was 25.4% and 37.7% when it was between 10.1 and 20 ng/ml. Using 25% or less of percent free PSA as a criterion for performing prostatic biopsy it would have detected 95.3% and 95.4% of the prostate cancers, respectively. The rate of unnecessary avoided biopsies would be 17.5% when serum PSA ranged from 4.1 to 10 ng/ml and 17.6% between 10.1 and 20 ng/ml.
This prospective study demonstrates that the percentage of free PSA seems to have similar utility when serum PSA levels are between 4.1 and 10 ng/ml and between 10.1 and 20 ng/ml, at the time of the first prostatic biopsy indication.
The authors analysed the potential use and limitations of carbonic anhydrase IX (CAIX) antigen as a marker with diagnostic and prognostic value in cases of clear-cell renal cell carcinoma (ccRCC). The study reports that >95% of ccRCCs show high and homogeneous levels of CAIX expression by reverse transcription-polymerase chain reaction and immunohistochemistry. Monoclonal antibody (MAb) G250 has a high affinity for the CAIX antigen. Using MAb G250 in iodine 131-G250 radioimmunoscintigraphy (RIS) and fluorodeoxyglucose F 18 positron emission tomography (PET) can detect primary ccRCC and metastatic sites through the affinity with CAIX antigen. CAIX expression in ccRCC is also presented as a significant and independent adverse predictor of survival. Finally, CAIX has a potential role as a predictor of response to immunotherapy. Seventy-eight percent of renal cell carcinomas(RCCs) responding to interleukin-2 therapy showed high CAIX-expressing primary tumours. Similarly, CAIX expression was associated with a significantly higher treatment response rate in patients with metastatic RCC who received sorafenib.
