Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group.

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1-16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought.

Incidental finding of an angiomyxoma of the urinary bladder: A case report of a rare but aggressive tumour.

Angiomyxoma is a rare mesenchymal tumor arising in the pelvic and perineal regions. Diagnosis of urinary bladder angiomyxoma is difficult, as it lacks typical signs and symptoms, and relies on immunochemistry. We present the case of a 53 year old patient presenting with an incidental finding of bladder tumor during an ultrasound. After a complete transurethral resection was performed, the pathology report led to angiomyxoma diagnosis. After 6 weeks a secondary TURB, along with a CT urogram showed no evidence of residual volume. Transurethral resection seems to be a safe and effective treatment of urinary bladder angiomyxoma.

Diagnosis of Low-Grade Urothelial Neoplasm in the Era of the Second Edition of the Paris System for Reporting Urinary Cytology.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) is considered the gold standard when it comes to diagnostic classifications of urine specimens. Its second edition brought some important changes, including the abolition of the diagnostic category of "low-grade urothelial neoplasm (LGUN)", acknowledging the inability of cytology to reliably discern low-grade urothelial lesions. METHODS: In this retrospective study, we assessed the validity of this change, studying the cytological diagnoses of histologically diagnosed low-grade urothelial carcinomas during a three-year period. Moreover, we correlated the sum of the urinary cytology diagnoses of this period with the histological diagnoses, whenever available. RESULTS: Although all the cytological diagnoses of LGUN were concordant with the histological diagnoses, most low-grade urothelial carcinomas were misdiagnosed cytologically. Subsequently, the positive predictive value (PPV) of urinary cytology for the diagnosis of LGUN was 100%, while the sensitivity was only 21.7%. Following the cyto-histopathological correlation of the sum of the urinary cytology cases, the sensitivity of urinary cytology for the diagnosis of high-grade urothelial carcinoma (HGUC) was demonstrated to be 90.1%, the specificity 70.8%, the positive predictive value (PPV) 60.3%, the negative predictive value (NPV) 93.6% and the overall accuracy 77.2%, while for LGUN, the values were 21.7%, 97.2%, 87.5%, 58.6% and 61.9%, respectively. Risk of high-grade malignancy was 0% for the non-diagnostic (ND), 4.8% for the non-high-grade urothelial carcinoma (NHGUC), 33.3% for the atypical urothelial cells (AUCs), 65% for the suspicious for high-grade urothelial carcinoma (SHGUC), 100% for the HGUC and 12.5% for the LGUN diagnostic categories. CONCLUSIONS: This study validates the incorporation of the LGUN in the NHGUC diagnostic category in the second edition of TPS. Moreover, it proves the ability of urinary cytology to safely diagnose HGUC and stresses the pivotal role of its diagnosis.

Implementation and external validation of Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score for predicting complications in 74 consecutive partial nephrectomies.

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Partial nephrectomy (PN) is the gold standard operation for small renal tumours. The decision for or against a PN has been based mostly on preoperative radiological evaluation of the tumour. Three nephrometry scoring systems have been recently proposed for prediction of postoperative complications of PN (RENAL, C-index and PADUA). We validate externally the accuracy of the PADUA system and suggest for the first time a novel scoring system, based on the original PADUA system, which implements three other significant factors for the postoperative course of a partial. OBJECTIVE: • To externally validate the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification of renal tumours managed by partial nephrectomy (PN). PATIENTS AND METHODS: • Seventy-four consecutive patients in a single academic tertiary institution underwent open PN. • Incidence of 90-day complications was stratified by several clinicopathological variables, such as gender, age of the patient, hospital stay, pathology report, tumour characteristics and positive surgical margins. PADUA scores were given to each case. • The severity of complications was also categorized with the Clavien system. RESULTS: • The optimal threshold of PADUA for the prediction of complications was 8 with a sensitivity equal to 90.9% and a specificity equal to 77.8% (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.73-1.00). • Multivariate analysis revealed that that PADUA is an independent predictor for the risk of complications. • Also, PADUA score ≥ 8 identified a group of patients with almost 20-fold higher risk of complications (hazard ratio [HR]= 19.82; 95% CI, 1.79-28.35; P= 0.015). • Patients with papillary histology had greater risk for complications than those with clear-cell tumours (HR = 4.88; 95% CI, 1.34-17.76; P= 0.016). CONCLUSIONS: • The PADUA score is a simple anatomical system that predicts the risk of postoperative complications. This is the first external validation of this system for open PN from a single centre. • The authors believe that PADUA is an efficient tool, since the only variable of the present study that predicted a higher incidence of complications was the histology type, which is determined after surgery. • However, it should be applied to laparoscopic and robot-assisted series and it could also include the ischaemia time and surgeon experience in the overall scoring to be complete.

(1)H NMR metabonomic analysis in renal cell carcinoma: a possible diagnostic tool.

(1)H NMR based metabonomic approach was applied in order to monitor the alterations of plasma metabolic profile in Renal Cell Carcinoma (RCC) patients and controls. (1)H NMR spectra of plasma samples from 32 RCC patients and 13 controls (patients exhibiting benign urologic disease) were recorded and analyzed using multivariate statistical techniques. Alterations in the levels of LDL/VLDL, NAC, lactate, and choline were observed between RCC patients and controls discriminating these groups in Principal Component Analysis (PCA) plots. Post OSC PLS-DA presented a satisfactory clustering between T1 with T3 RCC patients. Decrease in plasma lipid concentrations in RCC patients was verified using conventional clinical chemistry analysis. The results suggest that combination of (1)H NMR spectroscopy with PCA has potential in cancer diagnosis; however, a limitation of the method to monitor RCC is that major biomarkers revealed (lipoproteins and choline) in this metabolic profile are not unique to RCC but may be the result of the presence of any malignancy.

Quantitative study of mast cells in experimentally induced benign prostatic hyperplasia.

INTRODUCTION: Mast cells are involved in a number of biological responses to exocrine and endocrine stimuli, by releasing growth factors and certain cytokines. The aim of this study was to evaluate their number and distribution in experimentally induced benign prostatic hyperplasia in rats. MATERIALS AND METHODS: Adult Wistar rats (100 days old) were given citral transdermally for 1 month. Morphological characteristics and mast cell concentration were studied in proximal and distal zones after staining with hematoxylin-eosin and Giemsa, respectively. RESULTS: Citral induced mild benign prostatic hyperplasia. Mast cell numbers were increased significantly in both the proximal (2.97 +/- 0.52 vs. 1.4 +/- 0.17, p = 0.004) and distal zone (2.8 +/- 0.68 vs. 1.16 +/- 0.11, p = 0.011). CONCLUSION: Transdermal citral application resulted in a significant increase of mast cell numbers in the stroma of the rat ventral prostate. Furthermore, these mast cells were larger, contained a significant number of intracytoplasmic granules and degranulated. This finding suggests a role for mast cells in the pathogenesis of benign prostatic hyperplasia.

Beta-adrenergic receptor blockade and prostate peptide growth factor expression in the rat.

BACKGROUND AND AIM: In the rat prostate, beta-adrenoreceptor (beta-AR) stimulation does not alter basal prostatic tone but may inhibit alpha1-AR-mediated, field stimulation-induced or receptor-independent contractile responses. The present study was designed to assess the alteration of basic fibroblast growth factor (bFGF) and transforming growth factor-beta (TGFbeta) expression in the rat ventral prostate in response to beta-AR blockade with propranolol. RESULTS: At sacrifice, body weight as well as ventral prostate weight and prostate morphology were not significantly affected by propranolol treatment. Stromal elements and the majority of prostatic epithelial cells in control animals demonstrated positive staining for the anti-bFGF antibody, while positive staining for TGFbeta was seen only in epithelial cells. Propranolol treatment resulted in considerable decrease of bFGF staining intensity in both stromal and epithelial cells, while the immunostaining pattern for TGFbeta was almost abolished. RESULTS AND CONCLUSIONS: The results from this study provide evidence to suggest that prolonged propranolol treatment affects peptide growth expression in the rat ventral prostate as in other tissues, and confirms the notion that autonomic nervous system controls, at least partly, prostate gland functional characteristics. Moreover, it may also affect prostate homeostasis by intervening in stromal-epithelial interaction through alterations in the expression of peptide growth factors without affecting prostate volume.

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate.

PURPOSE: Alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of the alpha1 blocker, terazosin, on the expression of basic fibroblast growth factor (bFGF) in the rat ventral prostate. METHODS: Wistar rats were treated with terazosin (1.2 mg/kg body weight, po, every second day) for 120 days. The expression of bFGF was assessed immuno-histochemically in tissue sections and by Western blotting in whole tissue preparations. RESULTS: Terazosin treatment did not affect prostate weight or histomorphology. In the control group, epithelial and stromal cells demonstrated positive staining for the anti-bFGF antibody. In contrast, the same staining in terazosin-treated specimens was either absent or extremely weak. An analogous difference was observed among the corresponding immunoblots. CONCLUSIONS: These findings implicate the reduction of bFGF expression by terazosin as a potential additional molecular mechanism of its action that may include alterations in peptide growth factor mediated prostate homeostasis.

Androgens and bladder outlet obstruction: a correlation with pressure-flow variables in a preliminary study.

OBJECTIVES: To determine the relationship between androgens, lower urinary tract symptoms (LUTS) and urodynamic variables of bladder outlet obstruction (BOO) in patients with LUTS/benign prostatic hyperplasia (BPH), as androgens are important in the pathogenesis of LUTS. PATIENTS AND METHODS: Twenty-five men with symptomatic BPH were enrolled in the study and had a complete urodynamic investigation, establishing BOO. Age, prostate-specific antigen level, prostate volume and postvoid residual volume were recorded and the International Prostate Symptom Score (IPSS) was estimated. Detrusor pressure at maximum flow (P(det)Q(max)), at urethral closure (P(det)Cl, the pressure at the end of urinary flow) and maximum detrusor pressure (P(detmax)) was recorded, while detrusor overactivity (DO) was noted when present. Blood samples were collected to measure total testosterone (T), and free T (FT) was calculated. Patients were grouped according to FT levels as low (<72 pg/mL) and normal (FT > or =72 pg/mL). RESULTS: Ten patients had a low FT level, with a mean (sd) of 54.3 (16.5) pg/mL, and 15 a normal level of FT, of 90.5 (11) pg/mL. FT was negatively correlated with P(det)Cl, and P(det)Q(max); the mean P(det)Cl and P(det)Q(max) differed significantly between patients with low and normal FT levels. Fourteen patients had DO and they had significantly lower levels of FT than those with no DO. All patients with a FT level of <60 pg/mL had DO, and the presence of instability differed significantly from the rest of the group. CONCLUSIONS: Low T levels in clinical BOO correlated negatively with P(det)Cl and P(det)Q(max), while promoting DO. Androgen seems to have an ameliorating role in lower urinary tract function.

The effectiveness of a scientific symposium to change urologists' attitude towards treatment of LUTS/BPH.

PURPOSE: The use of interactive voting systems in continuing education helps to evaluate the alteration in the audience's views after a presentation. This study was designed to evaluate whether urologists' attitude towards management of benign prostate hyperplasia can be changed, and to estimate objectively the achievement of educational goals by using an interactive voting system. METHODS: The audience attitude was repetitively estimated by responding to questions using wireless keypads. Educational goal achievement was calculated by adding the percentage of those changing their opinion from "wrong" to "right" and that of those insisting on their initial "right" opinion. RESULTS: Giving a "wrong" answer and the probability of opinion change were independent of age and board certification. Being initially on the "wrong" side resulted in a greater probability of opinion change. The educational goals were achieved in 20.8-86.2% of cases. CONCLUSION: Satellite symposia are helpful learning environments. The use of an interactive voting system may help to evaluate objectively the achievement of educational goals.

In vitro biocompatibility between mitomycin-C (MMC) and bacillus Calmette-Guerin (BCG).

BACKGROUND: Mitomycin-C (MMC) and bacillus Calmette-Guerin (BCG) intravesical instillations are widely and effectively used as adjuvant treatment for superficial bladder cancer. In an attempt to improve the efficacy of intravesical therapy, MMC and BCG have also been used in a sequential or an alternating mode. The aim of this study was to assess the in vitro biocompatibility between these agents. MATERIALS AND METHODS: The effect of MMC on BCG clumping tendency was assessed by estimating the number of colony forming units (CFU) of BCG in suspension, during incubation at 37 degrees C for 3 h, with repeated recordings of the suspension optical density (OD). Preparations containing either BCG plus MMC or BCG plus an equivalent amount of sterile water were cultivated using the non-radiometric system BACTEC MGIT 960. The final concentrations of the agents, following transfer of the preparations into the tubes of the system, were 1.25 mg/ml for BCG and 1 mg/ml for MMC. During the cultivation process, the tubes of the system were automatically checked every 60 min for fluorescence emission, which is an indication of mycobacteria growth. A comparative cultivation of the same preparations on Lowenstein-Jensen solid medium was also performed. RESULTS: The OD of the BCG preparation remained almost unaffected for 3 h and was minimally altered by inclusion of MMC. After 34-38 h of cultivation in the BACTEC MGIT 960 system, all 7 cultures of the BCG+sterile water preparations became positive. In contrast, no BCG+MMC specimen became positive after an incubation period of 42 days. Following re-cultivation of the 7 negative BCG+MMC specimens, 6 remained negative, whereas 1 specimen became positive after an incubation period of 22 days. On Löwenstein-Jensen medium, growth of mycobacteria was noted only in the BCG+sterile water specimens and not in the BCG+MMC specimens. CONCLUSION: The results of this study indicate that, although MMC has no apparent effect on BCG tendency to form clumps in suspension, it may inhibit its growth in vitro. However, this does not necessarily compromise BCG anti-tumour activity. As the in vivo interaction of the drugs may be different, the efficacy of the combined BCG+MMC treatment should be defined in clinical trials.

Efficacy of tolterodine in preventing urge incontinence immediately after prostatectomy.

PURPOSE: Urgency and urge incontinence are frequently observed after prostatectomy. Although symptoms ameliorate within a relatively short time, they usually cause significant stress and anxiety to the patient as far as their duration is concerned. Aim of our study was to determine the efficacy of tolterodine in preventing urgency and urge incontinence after catheter removal in patients that underwent prostatectomy for benign prostate hyperplasia. PATIENTS AND METHODS: Twenty-seven patients with moderate/severe lower urinary tract symptoms due to benign prostatic enlargement, scheduled for prostatectomy, were randomised into two groups, Group A (14 pts) received tolterodine 2 mg b.i.d starting the day of surgery, while group B patients received no such treatment. Tolterodine treatment was discontinued 15 days after catheter removal. All patients completed the International Prostatic Symptom Score (IPSS) and the International Continence Society (ICS-BPH) forms the day before surgery, and three times more, one, fifteen and thirty days after catheter removal. RESULTS: Pre-operative total 1PSS and frequency of urgency/urge incontinence as determined by questions 3 and 4 of the ICS-BPH questionnaire were equally distributed between groups. Tolterodine was well tolerated and no adverse effects were reported. Post-operative IPSS and QoL scores did not differ between groups. However, the frequency of urge incontinence both the first day and fifteen days after catheter removal was significantly lower in the tolterodine group (16.6% vs. 69.2%, p=0.004 and 8.3% vs. 38.4%, p=0.039, respectively). CONCLUSION: Tolterodine was well tolerated in all patients and had a beneficial effect regarding the postoperative urge incontinence. Trials of a larger scale could determine which patients would benefit more, especially according to the presence of storage lower urinary tract symptoms prior to surgery.

Novel insights into the mechanism of action of intravesical immunomodulators.

To date, the precise mechanism of intravesical immunomodulators remains unknown. In vitro, interferon alpha (IFN-alpha) acts directly on neoplastic cells and inhibits their proliferation while it induces their differentiation. Urothelium and transitional cell carcinoma (TCC) cells express IFN-alpha receptor, the density of which correlates with lesion grade. IFN-alpha reduces neo-microvascular density in the normal urothelium adjacent to the tumor after transurethial resection (TUR), possibly via inhibition of COX-1. Moreover, IFN-alpha induces the membrane expression of tumor-related antigens and MHC antigens, providing a basis for a cellular immune response. When given intravesically, IFN-alpha may result in local and systemic T cell and NK cell activation. By monitoring nitric oxide (NO) end-products in urine and evaluating inducible nitric oxide synthase (iNOS) expression immunohistochemically, we were able to show that IFN-alpha may induce urothelial iNOS expression with subsequent formation of peroxynitrite, which might contribute to the antineoplastic action of IFN-alpha. Bacillus Calmette-Guerin (BCG) is thought to bind to the bladder wall via interaction between the bacterial antigen 85 complex and fibronectin. Although systemic reactions (evolution of cellular immune response, systemic production of cytokines and oxygen free radicals) have been reported, a likely scenario is that exposure to BCG results in a massive local immune response, characterized by induced expression of cytokines in the urine and in the bladder wall, and by a marked infiltration of the bladder wall by granulocytes and mononuclear cells. BCG-induced changes in tumor cell phenotype render them able to act both as lymphokine-alphactivated killer cell targets and antigen presenting cells. Although BCG may act directly on the proliferation of tumor cells, helper and cytotoxic T cells and, most probably, NK cells are absolutely necessary for any antitumor effects. Tumor cell killing is mediated through FasLigand, perforin and TNF-alpha. In a recent study, we found that BCG up-regulated iNOS expression in normal human urothelium in vivo, suggesting a role for NO in BCG-mediated antitumor activity.

Prognostic significance of metallothionein expression in renal cell carcinoma.

BACKGROUND: Metallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC) and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival. PATIENTS AND METHODS: The immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining) and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival). RESULTS: Positive MT staining was present in 21 cases (49%), being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included) was observed in 31 cases, in a percentage 25-50% of tumor cells in 7 cases, and in a percentage of 50-75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival. CONCLUSIONS: The inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic parameter.

Changes in end products of nitric oxide in urine and induction of nitric oxide synthase expression in urinary bladder during intravesical instillations of IFN-alpha2b.

Interferon-alpha2b (IFN-alpha2b) is being used intravesically for preventing recurrence and progression of superficial transitional cell carcinoma of the bladder. However, its mechanism of action when instilled intravesically is not yet elucidated. We monitored end products of nitric oxide (NO) in urine in 12 bladder cancer patients undergoing intravesical instillations of IFN-alpha2b. Urine end products of NO levels rose gradually after each instillation, reaching a peak value after the third instillation. Although the patients continued their treatment for 5 more weeks, no further alteration was observed. Inducible nitric oxide synthase (iNOS) expression was immunohistochemically evaluated in urinary bladder biopsy specimens before and after IFN-alpha2b instillations. It was shown that IFN-alpha2b induced urothelial iNOS expression, with subsequent oxidative stress. The peroxynitrite (ONOO-) formed from the combination of NO with superoxide (O2-) provides important clues in the role of ONOO- as a causative factor in the antineoplastic action of IFN-alpha2b.

The impact of body mass on management of patients with renal colic.

OBJECTIVE: To study the impact of body mass on diagnosis and initial response to medical treatment in patients presenting with renal colic. PATIENTS AND METHODS: One hundred and sixty-five consecutive patients presenting with symptoms of renal colic have been examined. Patients were divided in 3 groups according to their body mass index: normal-weight (BMI < or = 24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (BMI > or = 30 kg/m2). Diagnosis of renal colic was based on history, clinical examination, presence of hematuria in a urine sample, appearance of a stone on a plain radiograph, and/or presence of hydronephrosis in ultrasonography. In addition, previous history of renal colic, time to seek medical advice and time to pain relief following administration of medications were examined. RESULTS: Mean body mass index did not differ between patients with a history of < or = 1, 1-5 and > or = 5 renal colics (P = 0.65). Prevalence rates of appearance of either lithiasis or hydronephrosis vs normal findings on the Kidney-Ureter-Bladder plain radiograph or ultrasonography were not different between normal-weight, overweight and obese subjects (P = 0.38 and P = 0.90 respectively). The time to seek for medical advice and the response to treatment were not different between the study groups (P = 0.24 and P = 0.53 respectively). CONCLUSION: Body mass does not have any impact on diagnosis, time to seek for medical advice or response to treatment in patients with renal colic.

Clinical efficacy of distigmine bromide in the treatment of patients with underactive detrusor.

PURPOSE: The aim of this study was to assess the clinical efficacy of distigmine bromide, an anticholinesterase agent, deemed to improve detrusor function thereby restoring normal voiding patterns in patients suffering from detrusor underactivity. MATERIALS AND METHODS: A total of 27 patients (11 men and 16 women) with poor detrusor function were included in the study. The diagnosis was established using pressure-flow studies. All patients received distigmine bromide at a dose of 5 mg three times daily for 4 weeks and re-attended for a follow-up urodynamic investigation. The results of baseline pressure-flow studies were compared to those after completion of treatment. RESULTS: Treatment with distigmine bromide resulted in a statistically significant reduction of residual volume and percent residual volume, obviating the need for intermittent self-catheterisation in 11 patients. In addition, maximum flow rate and detrusor pressure at maximum flow increased, although not significantly. The drug was generally well tolerated by the majority of patients. CONCLUSION: Distigmine bromide shows clinical efficacy in patients with poor detrusor function and may therefore be used alternatively in selected cases.

Prognostic significance of cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma treated with first-line sunitinib: a European multiinstitutional study.

INTRODUCTION/BACKGROUND: The aim of this study was to evaluate the prognostic role of CN in patients with mRCC and synchronous metastases treated with the VEGF receptor TKI, sunitinib. PATIENTS AND METHODS: Patients with a diagnosis of metastases before, at the time of, or within 3 months from the diagnosis of renal cell carcinoma (RCC) and first-line treatment with sunitinib were included. Baseline characteristics were correlated with overall survival (OS) according to hazard ratios estimated from univariate Cox proportional hazards models. Significant factors were then included in a multivariate Cox proportional hazards model. RESULTS: One hundred eighty-six patients treated between January 2006 and March 2012 were selected. Thirty-six (19%) had not undergone CN. CN was offered to younger patients with better prognoses. Patients who underwent CN lived significantly longer than patients without CN (median OS, 23.9 [95% confidence interval (CI), 20.8-28.8] vs. 9 [95% CI, 4-16.4] months; P < .001). Multivariate analysis showed that CN had an independent prognostic significance. No specific subgroup benefiting from CN was identified. CONCLUSION: CN was an independent favorable prognostic factor in patients with synchronous metastases from RCC, treated with sunitinib. Information regarding the selection of mRCC patients likely to benefit from CN might be derived by ongoing phase III trials.

Terazosin treatment induces caspase-3 expression in the rat ventral prostate.

BACKGROUND: Quinazoline-based alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of terazosin on the expression of caspase-3 in the rat ventral prostate. METHODS: Fifteen Wistar rats were treated with terazosin (1.2 mg/kg body weight, given orally every second day) for 120 days. Another 15 control animals received the same amount of distilled water. The expression of caspase-3 was assessed immunohistochemically in formalin-fixed, paraffin-embedded tissue sections. RESULTS: Terazosin treatment did not affect prostate weight and histomorphology. In controls caspase-3 was expressed weakly and sporadically. In contrast, strong and weak expression was evident in 67% and 33% of the terazosin-treated specimens, respectively. CONCLUSIONS: These findings implicate the induction of caspase-3 expression by terazosin as a potential molecular mechanism of its apoptotic action on prostate cells.