OBJECTIVE Obesity and diabetes are considered risk factors for Renal Cell Carcinoma (RCC). We aimed to explore whether insulin resistance (IR) plays an independent role in the development of RCC. DESIGN In a hospital-based case-control study, we analyzed serum glucose, insulin, leptin and adiponectin levels among 60 incident RCC patients and 236 age- and gender-matched healthy controls. We assessed insulin resistance according to insulin levels, alone or controlled for diabetes mellitus (DM). An alternative measure of insulin resistance, such as the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index, was also assessed with and without controlling for history of DM. We used logistic regression to estimate odds ratios (ORs) adjusted for possible confounders. RESULTS The positive association of DM and waist to hip ratio as a measure of obesity with RCC was evident in the data set. Insulin levels controlled or not controlled for DM, however, were inversely associated with the risk for RCC; notably, an approximately 40% higher risk was observed in the 1 st tertile when compared with the 2 nd and 3 rd tertile levels of insulin resistance. Similar results were obtained when HOMA-IR was alternatively used. The inverse associations persisted and were even strengthened after controlling for potential confounding factors in multivariate analyses. CONCLUSIONS Our data suggest that insulin resistance may be inversely associated with RCC risk, independently of obesity, DM, lifestyle and hormonal confounding variables. Given the close interconnections among metabolic, inflammatory and immune pathways in RCC causation, it is difficult to infer which process actually initiates a pathologic cascade. The findings should be considered as preliminary data that need to be further confirmed in more appropriate study designs.
Mitropoulos, Dionisios MD, PhD, FEBU; Pappas, Paris MD, PhD; Banias, Constantinos MD; Leonardou, Polytimi MD; Alamanis, Christos MD, PhD, FEBU; Giannopoulos, Aris MD, PhD Author Information
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.
The protein components of urine are useful indicators of renal function and human health in general. Urine samples are easily attainable making them ideal substrates for biomarker research. Analysis of the urine proteome however, has been hindered by the great variability of the urine specimens, and the presence of various proteins in low abundance or modified forms. To alleviate some of these problems urine samples from five different individuals were pooled, concentrated and the proteome. characterized by a combination of preparative electrophoresis and 2-DE, followed by PMF. A total of 778 protein spots corresponding to 141 different gene products were identified. In comparison, 171 spots corresponding to 44 unique proteins were identified in the unfractionated starting material. Among the proteins identified from the preparative electrophoresis were many of low abundance such as proteins involved in signal transduction. Furthermore, the median molecular mass of the identified proteins from the preparative electrophoresis was significantly lower in comparison to the proteins identified from the unfractionated starting material (39886 Da versus 71317 Da, respectively). Concluding, application of this methodology provides a coherent analysis of the urine proteome and contributes to the generation of the urine protein map in health and disease.
Objectives To evaluate prospectively the combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone has produced objective clinical responses in HRPC. Methods Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a somatostatin analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups. Results The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant). Conclusions The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone analog, somatostatin analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.
Transitional cell carcinoma (TCC) of ureteral stump after radical nephrectomy is rare. Following nephrectomy patients with a prior history of bladder cancer must have their ureteral stumps evaluated. Furthermore, the presence of hematuria should alert the urologist to a possible TCC in the ureteral stump. We present a patient who developed TCC of the ureteral stump after radical nephrectomy.
Prostate biopsy is usually performed without anesthesia. We evaluated the patient’s perception of pain/discomfort experienced during the procedure in terms of the type of anesthesia used: periprostatic infiltration with 2% lidocaine, or intrarectal instillation of lidocaine-prilocain cream. A total of 198 patients were divided into three groups: group 1 (control group, n =40) received sonographic gel intrarectally prior to biopsy, group 2 ( n =75) were given intrarectal instillation of lidocaine-prilocain cream, and group 3 ( n =80) received periprostatic anesthesia by injecting 10 ml of 2% lidocaine. Pain after each biopsy was assessed using an 11-point linear visual analog pain scale. The mean pain scores were 5.1 in group 1, 4.8 in group 2, and 2.5 in group 3, resulting in a significant difference between group 3 and both groups 1 and 2, but not between groups 1 and 2. The incidence of biopsy-related adverse events did not differ among groups. Transrectal ultrasonographic guided periprostatic anesthesia is superior to intarectal instillation of lidocaine-prilocain cream.
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.
Gastrin releasing peptide (GRP) is a neuropeptide that has been suggested to play a role in the development of some malignancies. Our aim was: (1) to identify the expression of GRP in cancerous prostate glands, and (2) to correlate its expression to various pathological parameters and to the patient's clinical outcome. Using standard immunohistochemistry, we evaluated GRP expression in both biopsy and radical prostatectomy specimens from 30 patients with prostatic adenocarcinomas. GRP was expressed in 18 radical prostatectomy specimens (60%) and in 15 biopsies (50%). There was an association between positive immunoexpression of GRP, relapse ( P=0.029) and advanced tumor stages (i.e. pT3, pT4) ( P=0.049). In the respective biopsies, GRP immunostatus was similar to that observed in the subsequent radical prostatectomy specimens. GRP immunoexpression may be of some value as a diagnostic and prognostic marker. Patients whose pathology specimens demonstrate GRP immunopositivity should be closely monitored, since they appear to be at higher risk of disease progression and relapse.
The aim of this study was to access the utility of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay for prostatic specific membrane antigen (PSMA) in predicting non-organ confined (NOC) disease in final radical prostatectomy (RP) specimens. Nested RT-PCR for PSMA was performed on the blood of 33 patient candidates for RP, 20 patients with untreated metastatic disease and 20 healthy men. The final pathology report on the 33 RP patients was compared with the RT-PCR results and Partin nomograms. In the RP group, 4/18 patients with confined disease and 9/15 with NOC disease had positive RT-PCR assays. Sensitivity, specificity, positive and negative predictive values for RT-PCR were 60%, 77.7%, 69% and 70%, respectively. The Partin tables for this group of patients showed a sensitivity, specificity, positive and negative predictive values of 75%, 71%, 60% and 83%, respectively. P-values for the Partin tables and the RT-PCR assay were respectively 0.014 and 0.037. RT-PCR of PSMA has an independent predictive value and could help predict NOC disease in clinically localized prostate cancers, but is still less efficient than Partin tables.
The Serenoa repens lipido-sterolic extract (SRLSE, Permixon, Pierre Fabre Medicament, Castres, France) is used to treat benign prostate hyperplasia. We studied the in vivo effect of SRLSE on mast cell accumulation and the histological characteristics of the rat ventral prostate. Adult Wistar rats received either tocopherol or SRLSE (50 and 100 mg/kg body weight, respectively) every second day for 90 days. Histological features were studied in hematoxylin-eosin stained tissue sections while mean mast cell numbers were determined in Giemsa-stained sections. The central region of the ventral prostate in treated animals showed significant changes with acinar epithelium becoming flat or low cuboidal. In the same region, mean mast cell number per optical field in the control, low-dose and high-dose groups were, respectively, 4.7+/-0.7, 3.4+/-1.0 and 2.4+/-0.6, showing a dose-dependent, statistically significant decrease. Administering SRLSE significantly reduces mast cell accumulation and provokes epithelium atrophy within the central area of the rat ventral prostate. These phenomena may participate in the clinical activity of the drug.
Apoptosis is a process which can retard the progress of malignant tumours. In the present study we investigated the immunohistochemical expression of three pro-apoptotic proteins (Bax, Fas receptor and caspase 3 – CPP32) as well as the apoptotic index (TUNEL Index) in 53 urothelial carcinomas of the urinary bladder. We examined all possible relationships between these factors and clinicopathological variables, as well as the patients' disease free survival. All three markers, and in particular the Fas receptor, were detectable in a remarkable proportion of specimens, however, none of the markers examined was associated with any clinicopathological parameter. In multivariate statistical analysis, Bax emerged as an independent predictor of a favourable prognosis. It is noteworthy that none of the pro-apoptotic markers examined was directly linked with the apoptotic rate of the malignant cells.
Congenital seminal vesicle cysts associated with renal agenesis are uncommon, but are currently detected more frequently with the use of sectional imaging procedures. Approximately 200 cases have been reported. The unique feature of our case is the combination of this disorder with an ipsilateral undescended testis. Our patient underwent partial vesiculectomy, in which the cyst was removed and the seminal vesicle remnant with its vas deferens was preserved. A review of the infertile cases and the impact of surgical treatment on fertility are discussed. Features that render partial vesiculectomy applicable and the potential effect of this procedure on fertility are highlighted.