Metabolic syndrome (MetS) and prostate cancer (PCa) are highly prevalent conditions worldwide. Current evidence suggests the emerging hypothesis that MetS could play a role in the development and ...progression of several neoplasms. The aims of this study are to evaluate the impact of MetS and MetS factors on PCa incidence, on the risk of high-grade PCa and to analyze the role of MetS and single MetS components on the development of aggressive PCa features.
A systematic literature search and analysis on PubMed, EMBASE, Cochrane and Academic One File databases until September 2015 was performed by 2 independent reviewers to evaluate the associations between MetS and PCa incidence, and between MetS and high-grade PCa incidence (bioptical Gleason Score⩾8, Prognostic Group 4-5 according to the novel prostate cancer grading system). Also the association between MetS and individual MetS components with pathological Gleason Score⩾8, extra-capsular extension, seminal vesicle invasion, positive surgical margins and biochemical recurrence (defined as two consecutive PSA values ⩾0.2 ng ml
after radical prostatectomy) was evaluated.
24 studies were selected including a total of 132 589 participants of whom 17.35% had MetS. There was a slight association between MetS and PCa incidence (odds ratio (OR)=1.17 (1.00-1.36), P=0.04) and between high-grade PCa and MetS (OR= 1.89 (1.50-2.38), P<0.0001) but the studies were statistically heterogeneous. No association was found between MetS components and PCa risk except for hypertension. MetS was significantly associated with pathologic Gleason Score⩾8 (OR= 1.77 (1.34-2.34); P<0.01), extra-capsular extension (OR=1.13 (1.09-1.18); P<0.01), seminal vesicle invasion (OR=1.09 (1.07-1.12); P<0.01), positive surgical margins (OR=1.67 (1.47-1.91); P<0.01) and biochemical recurrence (OR=1.67 (1.04-2.69); P<0.01).
The presence of MetS is associated with worse oncologic outcomes in men with PCa, in particular with more aggressive tumor features, and biochemical recurrence.
Epidemiological data indicate that lower urinary tract symptoms (LUTS)/BPH can be associated with metabolic syndrome (MetS). Chronic inflammation has been proposed as a candidate mechanism at the ...crossroad between these two clinical entities.Aim of study is to examine the correlation among pre-operatory LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy specimens.
A total of 271 consecutive men treated with simple prostatectomy were retrospectively selected for this study in two tertiary referral centers for LUTS/BPH. Prostate diameters and volume were measured by transrectal ultrasound, LUTS scored by International Prostate Symptom Score (IPSS) and obstruction by uroflowmetry. The International Diabetes Federation and American Heart Association and the National Heart, Lung and Blood Institute was used to define MetS. The inflammatory infiltrate was investigated combining anatomic location, grade and extent of flogosis into the overall inflammatory score (IS); the glandular disruption (GD) was used as a further marker.
Eighty-six (31.7%) men were affected by MetS. Prostatic volume and anterior-posterior (AP) diameter were positively associated to the number of MetS components. Among MetS determinants, only dyslipidaemia (increased serum triglycerides and reduced serum high-density lipoprotein) was associated with an increased risk of having a prostatic volume >60 cm(3) (hazard ratio (HR) = 3.268, P < 0.001). A significant positive correlation between the presence of MetS and the IS was observed. MetS patients presented lower uroflowmetric parameters as compared with those without MetS (Maximum flow rate (Q(max)): 8.6 vs 10.1, P = 0.008 and average flow rate (Q(ave)): 4.6 vs 5.3, P = 0.033, respectively), and higher obstructive urinary symptoms score (P = 0.064). A positive correlation among both IS-GD and IPSS Score was also observed (adjusted r = 0.172, P = 0.008 and adjusted r = 0.128, P = 0.050).
MetS is associated with prostate volume, prostatic AP diameter and intraprostatic IS. The significantly positive association between MetS and prostatic AP diameter could support the observation that MetS patients presented lower uroflowmetric parameters. In conclusion, MetS can be regarded as a new determinant of prostate inflammation and BPH progression.
Recent data have shown that cardiotoxicity represents a potentially important side-effect in patients treated with sunitinib. We reviewed cardiac adverse events in patients with metastatic renal cell ...carcinoma (RCC) who underwent treatment with this agent.
The medical records of 175 patients with metastatic RCC treated with sunitinib at eight Italian institutions were retrospectively reviewed. Alterations in left ventricular ejection fraction (LVEF) and blood pressure were evaluated. Patients with preexisting cardiac risk factors were specifically scrutinized for increased expression of cardiac changes.
Grade 3 hypertension was seen in 17 patients (9.7%); in 12 of these 17, hypertension developed after receiving the third sunitinib cycle. Among these 17 patients, 12 (70.6%) also experienced left ventricular systolic (LVEF) dysfunction; in all, 33 of the 175 patients (18.9%) developed some degree of cardiac abnormality, of which 12 were classified as grade 3 LVEF dysfunction and/or congestive heart failure (CHF) (6.9%). Significant univariate associations for predictors of CHF were history of hypertension (P=0.008), history of coronary heart disease (P=0.0005) and prior treatment with an angiotensin-converting enzyme inhibitor (P=0.04). Multivariate analysis suggested that a history of coronary artery disease odds ratio (OR) 18, 95% confidence interval (CI) 4–160, P=0.005 and hypertension (OR 3, 95% CI 1.5–80, P=0.04) was the only significant independent predictors of CHF.
Patients undergoing sunitinib, especially those with a previous history of hypertension and coronary heart disease, are at increased risk for cardiovascular events and should be monitored for exacerbations of their hypertension and for evidence of LVEF dysfunction during treatment.
Although pediatric malignant extracranial germ-cell tumors (meGCTs) are among the most chemosensitive solid tumors, a group of patients relapse and die of disease. To identify new markers predicting ...clinical outcome, we examined the prognostic relevance of tumor-infiltrating T lymphocytes (TILs) and the expression of PD-1 and PD-L1 in a cohort of pediatric meGCTs by in situ immunohistochemistry. MeGCTs were variously infiltrated by T cell-subtypes according to the tumor subtype, tumor location and age at diagnosis. We distinguished three different phenotypes: i) tumors not infiltrated by T cells (immature teratomas and half of the yolk sac tumors), ii) tumors highly infiltrated by CD8
+
T cells expressing PD-1, which identifies activated tumor-reactive T cells (seminomas and dysgerminomas), iii) tumors highly infiltrated by CD8
+
T cells within an immunosuppressive tumor microenvironment characterized by CD4
+
FOXP3
+
Treg cells and PD-L1-expressing tumor cells (embryonal carcinomas, choriocarcinomas and the remaining yolk sac tumors). Tumor subtypes belonging mixed meGCTs were variously infiltrated, suggesting the coexistence of multiple immune microenvironments either facilitating or precluding the entry of T cells.
These findings support the hypothesis that TILs influence the development of meGCTs and might be of clinical relevance to improve risk stratification and the treatment of pediatric patients.
Aim of the study was to evaluate efficacy and efficiency of 180-watt Green-Light XPS (GL-XPS) laser photoselective vaporization of the prostate (PVP) in patients under 5-Alpha-Reductase Inhibitors ...(5ARI) treatment.
A consecutive series of patients with lower urinary tract symptoms due to benign prostatic enlargement treated by PVP with the GL-XPS were enrolled. Patients were divided in two groups according to the chronic use (>6 months) of 5ARI. These two groups were compared on lasing density (kilojoules per prostate volume), vaporization efficiency (prostate volume per lasing time), vaporization power (kilojoules per lasing time), Prostate Specific Antigen (PSA) reduction from baseline, symptom score change from baseline and uroflowmetry parameters improvement. Follow-up was performed at 3, 6 and 12 months with International Prostate Symptom Score, Uroflowmetry parameters and PSA.
Overall 193 patients were enrolled. Out of them 87/193 (45%) were on 5ARI treatment. No significant differences were recorded between the two groups at baseline. Median age was 68 years old and median prostate volume was 60 ml. In terms of laser efficiency, no statistically significant differences were recorded in terms of lasing time (25 min vs. 24.5 min; p>0.05); energy used (250 kJ vs. 221 kJ; p>0.05), lasing density (6.8 kJ/ml vs. 6.6 kJ/ml, p>0.05), vaporization efficiency (1.4 ml/min vs. 1.3 ml/min, p>0.05) and vaporization power (9.6 kJ/min vs. 9.4 kJ/min; p>0.05). Finally, no significant differences were also recorded postoperatively in the two groups in terms of PSA reduction, improvement in symptom score and uroflowmetry parameters (p>0.05).
Thirty-seven efficacy and efficiency outcomes were not statistically different between the two groups. 5ARI does not reduce the performance and ability of the 180-watt Green-Light XPS laser system.
Smoking, hypertension, abdominal obesity and metabolic abnormalities have been considered individual factors involved in prostate cancer (PCa) pathogenesis. All of these factors are used to define ...the individual cardiovascular risk (CVR). The aim of our study was to evaluate the association between CVR and PCa diagnosis and grade among a consecutive series of men undergoing prostate biopsy.
From 2010 onwards, consecutive patients undergoing 12-core prostate biopsy were enrolled. Body mass index was measured before the biopsy. Blood samples were collected and tested for: PSA, fasting glucose, triglycerides and high-density lipoproteins. Blood pressure was also recorded. Metabolic syndrome was defined according to the Adult Treatment Panel III and CVR according to the European Association of Cardiologist Guidelines. We evaluated the association between CVR and PCa biopsy Gleason score using logistic regression analyses.
Five hundred and eighty-four patients were enrolled. Four hundred and six patients (70%) presented a moderate/high CVR. Two hundred and thirty-seven (40.6%) patients had cancer on biopsy; 157 with moderate/high CVR and 80 with low/no CVR (P=0.11). Out of the 237 patients with PCa, 113 had a Gleason score 6 and 124 a Gleason score ⩾7. Out of them, 92/124 (75%) presented a moderate/high CVR (P=0.004). Moderate/high CVR was not associated with an increased risk of PCa (odds ratio (OR): 0.741, confidence interval (CI): 0.474-1.156; P=0.186) but with an increased risk of Gleason score ⩾7 (OR: 2.154, CI: 1.076-4.314; P=0.030).
In our study, a moderate/high CVR is associated with an increased risk of a high-grade Gleason score when PCa is diagnosed on biopsy. Although these results should be confirmed in multicentre studies, patients with moderate/high CVR should be carefully evaluated for PCa diagnosis.
To investigate the efficacy of tamsulosin in patients with lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) with intravesical prostatic protrusion (IPP). Ultrasound ...measurement of the IPP has been previously described as an effective instrument for the evaluation of benign prostatic obstruction (BPO) and could help in clarifying the role of alpha-blockers in patients with (BPE).
Patients with BPE and LUTS were enrolled in this observational study. Intravesical prostatic protrusion was graded as grade 1 (< 5 ml), 2 (5 < IPP < 10 ml) and 3 (> 10 ml). Patients were treated with tamsulosin for twelve weeks. Evaluation was performed before and at the end of treatment by means of International Prostate Symptom Score (IPSS) and uroflowmetry. Patients were considered responders if a reduction of IPSS > 3 points was reported.
One hundred forty-two patients were enrolled. Twelve patients were excluded because of incomplete data. Fifty patients showed an IPP grade 1 (group A), 52 a grade 2 (group B) and 28 a grade 3 (group C). Treatment success was obtained in 82%, 38,5% and 7,1% of patients respectively; these differences (group A vs B-C and group B vs C) were highly significant. The odd ratio to obtain a treatment success was of 59 and 8.1 in group A and group B respectively, in comparison to group C. After a multivariate regression, the relationship between IPP grade and treatment success remained significant. Improvement of uroflowmetry parameters has been reported in all the groups especially in patients with a low grade IPP (p value = 0,016 group A vs group B; p value = 0,005 group A vs group C). Prostate volume seems not to influence this relationship.
Intravesical prostatic protrusion has found to be significantly and inversely correlated with treatment success in patients with LUTS and BPE under alpha-blockers therapy. Alpha blockers odd ratio of success is 59 times higher in patients with a low grade IPP in comparison to patients with a high grade.
Abstract Background Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently ...evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients. Methods The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index. Results During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%). Conclusion Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5-year-recurrence rate of almost 40%.
Abstract Introduction To evaluate the applicability of a modified Clavien classification system (CCS) in grading postoperative complications of transurethral resection of bladder tumours (TURB). ...Materials and methods A series of patients undergoing monopolar TURB from April 2011 to March 2012 at five Italian centers were enrolled. All complications occurring within the first 30-day postoperative period were prospectively recorded and graded according to the CCS. Results Overall, 275 patients were included. Median age was 71 (63/78) years; median BMI was 28 (25.4/30.8) Kg/m2 , median tumour size was 2 (1–3) cm; median number of tumour lesions was 1 (1–3). Median operative time was 30 (20/45) min. Fifty-seven complications were recorded in 43 patients. Overall postoperative morbidity rate was 16%. Most of the complications were not serious and classified as Clavien type I (42 cases; 74%) or II (8 cases, 14%). Higher grade complications were scarce: CCS IIIa in 1 case (2%) and CCS IIIb in six cases (10%). No TURB related death was reported. Six patients were re-operated due to significant bleeding or clot retention on postoperative days 2–7. On univariate (73.5 ± 38 versus 36.7 ± 21.6 min) and multivariate analysis longer operative time was an independent predictor of complications (OR: 1.06 per min, 95%CI 1.04–1.08, p = 0.001). Conclusions A modified CCS can be used as a standardized tool to objectively define the complications of TURB which confirms to be a safe procedure with a low surgical morbidity. This tool can be used to aid in patient counselling and to facilitate scientific assessment.
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