113 research outputs found

    Management of Biochemical Recurrence after Primary Curative Treatment for Prostate Cancer: A Review

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    How to manage patients with prostate cancer (PCa) with biochemical recurrence (BCR) following primary curative treatment is a controversial issue. Importantly, this prostate-specific antigen (PSA)-only recurrence is a surrogate neither of PCa-specific survival nor of overall survival. Physicians are therefore challenged with preventing or delaying the onset of clinical progression in those deemed at risk, while avoiding over-treating patients whose disease may never progress beyond PSA-only recurrence. Adjuvant therapy for radical prostatectomy (RP) or local radiotherapy (RT) has a role in certain at-risk patients, although it is not recommended in low-risk PCa owing to the significant side-effects associated with RT and androgen deprivation therapy (ADT). The recommendations for salvage therapy differ depending on whether BCR occurs after RP or primary RT, and in either case, definitive evidence regarding the best strategy is lacking. Options for treatment of BCR after RP are RT at least to the prostatic bed, complete or intermittent ADT, or observation; for BCR after RT, salvage RP, cryotherapy, complete or intermittent ADT, brachytherapy, high-intensity focused ultrasound (HIFU), or observation can be considered. Many patient- and cancer-specific factors need to be taken into account when deciding on the best strategy, and optimal management depends on the involvement of a multidisciplinary team, consultation with the patient themselves, and the adoption of an individualised approach. Improvements in imaging techniques may enable earlier detection of metastases, which will hopefully refine future management decisions

    Measuring thermal spread during bipolar cauterizing using an experimental pneumoperitoneum and thermal sensors

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    ObjectiveDuring nerve-sparing robot-assisted radical prostatectomy (RARP) bipolar electrocoagulation is often used but its use is controversial for the possible thermal damage of neurovascular bundles. Aim of the study was to evaluate the spatial-temporal thermal distribution in the tissue and the correlation with the electrosurgery-induced tissue damage in a controlled, CO2-rich environment modelling the laparoscopy conditions..MethodsWe manufactured a sealed plexiglass chamber (SPC) equipped with sensors to reproduce experimentally the environmental conditions of pneumoperitoneum during RARP. We evaluated in 64 pig musculofascial tissues (PMTs) of approximately 3 cm3 √ó 3 cm3 √ó 2 cm3 the spatial-temporal thermal distribution in the tissue and the correlation with the electrosurgery-induced tissue damage in a controlled CO2-rich environment modeling the laparoscopy conditions. Critical heat spread of bipolar cauterizing during surgical procedure was assessed by the employment of a compact thermal camera (C2) with a small core sensor (60 √ó 80 microbolometer array in the range 7‚Äď14 őľm).ResultsBipolar instruments used at 30 W showed a thermal spread area of 18 mm2 when applied for 2 s and 28 mm2 when applied for 4 s. At 60 W, bipolar instruments showed a mean thermal spread and 19 mm2 when applied for 2 s; and 21 mm2 when applied for 4 s. Finally, histopathological analysis showed that thermal damage is distributed predominantly on the surface rather than in depth.ConclusionsThe application of these results is very interesting for the definition of an accurate use of bipolar cautery during nerve-sparing RARP. It demonstrates the feasibility of using miniaturized thermal sensors, thus addressing the potential for next developments regarding the design of thermal endoscopic devices for robotic use

    ERG alterations and mTOR pathway activation in primary prostate carcinomas developing castration-resistance

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    Abstract Introduction One of the most common sites of distant metastasization of prostate cancer is bone, but to date reliable biomarkers able to predict the risk and timing of bone metastasization are still lacking. Patients and methods Surgically resected paraffin embedded samples from 12 primary prostate cancers that developed metachronous bone metastasis at different time points were studied (six cases within 2 years, six cases after 5 years from surgery). A targeted next-generation DNA and RNA sequencing able to assess simultaneously mutations, copy number alterations and fusion events of multiple genes was used. Immunohistochemistry was used to assess mTOR pathway activation. Results Rearrangements of ETS family genes, molecular alterations in PTEN and TP53 genes were detected in 10, 6 and 5 cancers, respectively. Nine samples showed TMPRSS2-ERG fusions, which were associated with increased ERG expression at immunohistochemistry. mTOR pathway activation was documented in 6 patients, with a clear trend of prevalence in late-metastatic patients (p‚ÄČ=‚ÄČ0.08). Conclusions A simultaneous next-generation targeted DNA and RNA sequencing is applicable on routine formalin-fixed paraffin-embedded tissues to assess the multigene molecular asset of individual prostate cancers. This approach, coupled with immunohistochemistry for ERG and mTOR pathway proteins, may help to better characterize prostate cancer molecular features with a potential impact on clinical decisions

    The preoperative serum ratio of total prostate specific antigen (PSA) to free testosterone (FT), PSA/FT index ratio, and prostate cancer. Results in 220 patients undergoing radical prostatectomy

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    Objectives: To evaluate associations of preoperative total prostate specific antigen (PSA) to free testosterone (FT), the PSA/FT index ratio, with features of pathology prostate cancer (PCA) and to investigate its prognostic potential in clustering the PCA population. Patients and methods: After excluding criteria, the records of 220 patients who underwent radical prostatectomy (RP) were retrospectively reviewed. Serum samples of PSA, total testosterone (TT) and FT were collected at 8.00 A.M., one month after biopsies and before RP. The PSA/FT ratio was computed in the population of patients who were clustered in groups according to ranking intervals of the PSA/FT ratio which identified at least 4 clusters which were coded as A, B, C, and D. The independent associations of the PSA/FT index ratio were assessed by statistical methods and a two-sided P < 0.05 was considered to indicate statistical significance. Results: TT correlated to FT which was a significant predictor of PSA in the population of patients who were subsequently clustered, according to increasing interval values of the PSA/FT index ratio, in groups that showed a stronger linear association of FT with PSA. The PSA/FT index ratio significantly associated with pathology features of prostate cancer such as pathology Gleason score (pGS), invasion of the seminal vesicles (pT3b), proportion of positive cores (P+) and proportion of cancer involving the volume of the prostate. In the population of patients, TT, PSA/FT index ratio and P+ independently associated with pGS 65 7 and pT3b; moreover, the odds ratio (OR) of the PSA/FT index ratio resulted 9.11 which was stronger than TT (OR = 1.11) and P+ (OR = 8.84). In the PCA population, TT, PSA/FT index ratio and P+ also independently associated with pT3b PCA; interestingly, the OR of PSA/FT index resulted 54.91 which was stronger than TT (OR = 1.31) and P+ (26.43). Conclusions: Preoperative PSA/FT index ratio is an independent strong factor which directly associates with aggressive features of pathology PCA; moreover, it might express prognostic potential for clustering the patient population in risk classes. Confirmatory studies are required

    High surgeon volume and positive surgical margins can predict the risk of biochemical recurrence after robot-assisted radical prostatectomy

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    Background: The aim of this study was to determine whether any clinical factors are independent predictors of positive surgical margins (PSM), and to assess the association of PSM and biochemical recurrence (BR) after robot-assisted radical prostatectomy (RARP). Methods: The population included cases with negative surgical margins (control group) and patients with PSM (study group). Tumor grade was evaluated according to the International Society of Urologic Pathology (ISUP) system. A logistic regression model assessed the independent association of factors with the risk of PSM. The risk of BR was assessed by Cox\u2019s multivariate proportional hazards. Results: A total of 732 consecutive patients were evaluated. Extend pelvic lymph node dissection (ePLND) was performed in 342 cases (46.7%). Overall, 192 cases (26.3%) had PSM. The risk of PSM was positively associated with the percentage of biopsy positive cores (BPC; odds ratio, OR = 1.012; p = 0.004), extracapsular extension (pT3a; OR=2.702; p < 0.0001), invasion of seminal vesicle (pT3b; OR = 2.889; p < 0.0001), but inversely with body mass index (OR = 0.936; p = 0.021), and high surgeon volume (OR = 0.607; p = 0.006). Independent clinical factors associated with the risk of BR were baseline prostate-specific antigen (PSA; hazard ratio, HR = 1.064; p = 0.004), BPC (HR = 1.015; p = 0.027), ISUP biopsy grade group (BGG) 2/3 (HR = 2.966; p = 0.003), and BGG 4/5 (HR = 3.122; p = 0.022). Pathologic factors associated with the risk of BR were ISUP group 4/5 (HR = 3.257; p = 0.001), pT3b (HR = 2.900; p = 0.003), and PSM (HR = 2.096; p = 0.045). Conclusions: In our cohort, features related to host, tumor, and surgeon volume are associated with the risk of PSM, which is also an independent parameter predicting BR after RARP. The surgical volume of the operating surgeon is an independent factor that decreases the risk of PSM, and, as such, the risk of BR


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    INTRODUCTION AND OBJECTIVES: To determinate bene\ufb01ts of the association of local anaesthetic wounds in\ufb01ltration and US-TAPblock with ropivacaine on postoperative pain, early recovery and hospital stay in patients undergoing robot assisted radical prostatectomy (RARP). METHODS: The study is double-blinded randomized controlled trial. Our hypothesis was that the association of wound in\ufb01ltration and US-TAP block with Ropivacaine would decrease immediate postoperative pain and opioids use. Primary outcomes included postoperative pain and opioids demand during the hospital stay. Secondary outcomes were nausea/vomiting rate, stool passing time, use of pro-kinetics, length of hospital stay and 30-days readmission to the hospital for pain or other US-TAP-block related complications RESULTS: A total of 100 patients who underwent RARP were eligible for the analysis; 57 received the US-TAP block with 20 ml of 0.35% Ropivacaine (US-TAP-block group) and 43 did not receive USTAP block (no-US-TAP group). All the patients received the local wound anaesthetic in\ufb01ltration with 20 ml of 0.35% Ropivacaine. USTAP block group showed a decreased mean NRS (2.7vs1.8; p[0.04) and reduced use of opioid (8 vs 2; p[0.01) in the \ufb01rst 24 h. Moreover, we found a shorter mean LOS (4.7 vs 4.2; p[ 0.04) with a reduced use of pro-kinetics during the hospital stay (31 vs 12; p<0.001). No US-TAP-block related complications to were reported. CONCLUSIONS: Association of anaesthetic wound in\ufb01ltration and US-TAP block with Ropivacaine as part of a multimodal analgesic regimen can be safely offered to patients undergoing RARP and ePLND. It improves the immediate post-operative pain control, reducing opioids administration and is associated to a decreased use of pro-kinetics and shorter hospital stay

    The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer

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    We analyzed the cardiovascular toxicities related to the use of abiraterone and enzalutamide in prostate cancer. We found that these agents are associated with an increased risk of all- and high-grade cardiac toxicity as well as an increased risk of all- and high-grade hypertension. Follow-up for the onset of treatment-related cardiovascular events should be considered in these patients treated with abiraterone and enzalutamide.Introduction: The cardiovascular toxicity related to abiraterone and enzalutamide has been previously studied by our group. In this analysis, we aim to update our previous findings related to abiraterone and enzalutamide, including the new available evidence, both in castration-resistant and hormone-sensitive prostate cancer. Patients and Methods: Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (Cis) were calculated using fixed- or random-effects methods. Results: We included 7 articles in this meta-analysis, covering a total of 8660 patients who were used to evaluate cardiovascular toxicity. The use of new hormonal agents was associated with an increased risk of all-grade (RR, 1.36; 95% CI, 1.13-1.64; P = .001) and high-grade (RR, 1.84; 95% CI, 1.21-2.80; P = .004) cardiac toxicity. The use of new hormonal agents was also associated with an increased risk of all-grade (RR, 1.98; 95% CI, 1.62-2.43; P = .001) and high-grade (RR, 2.26; 95% CI, 1.84-2.77; P = .004) hypertension compared with the controls. Abiraterone was found to significantly increase the risk of both cardiac toxicity and hypertension, whereas enzalutamide significantly increases only the risk of hypertension. No differences were found based on the dose of prednisone used with abiraterone. The major limitation of this study is that data are available only as aggregate, and no single-patient information could be analyzed. Conclusions: Abiraterone and enzalutamide significantly increase the incidence and RR of cardiovascular toxicity in patients affected by metastatic prostate cancer. Follow-up for the onset of treatment-related cardiovascular events should therefore be considered in these patients. (C) 2017 Elsevier Inc. All rights reserved

    LC3B and ph-S6K are both expressed in epithelioid and classic renal angiomyolipoma: a rationale tissue-based evidence for combining use of autophagic and mTOR targeted drugs

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    Background: Targeted drugs to the autophagy processes are emerging in clinical trials. The aim of this work is to assess the magnitude of autophagic expression in renal angiomyolipoma. Methods: Fourteen cases of renal angiomyolipoma were recruited. Anti-LC3B-II and anti-phospho-S6K were detected by Western blot analysis. For immunohistochemical staining, sections were stained with the antibodies LC3B-II and cathepsin-K. LC3B-II was also analyzed by immunofluorescence. We have also carried out electron microscopy analysis on tumor cells. Results: 13 classic and 1 epithelioid renal angiomyolipoma were recruited. The Western-blot LC3B-II analysis shows increasing in protein expression in all cases, however quantitative protein expression ranged from 1 to 15 (mean 5). The autophagosome protein LC3B-I also significantly increased in all tumor extraction. The expression of LC3B-II protein was confirmed in tumoral samples by immunofluorescence. The lysosomal marker cathepsin-K was observed by immunohistochemistry on all tumours. The Western-blot ph-S6K analysis showed significant protein overexpression along all cases after evaluation of the quantitative S6K/Ponceaus ratio. In 6/14 (52%) the expression was high, with a quantitative increase of 653 fold induction in 4 angiomyolipoma compared to normal tissue. At electron microscopy, cancer cells evidenced round or oval electron-dense granules associated with membranes and granules with double membrane. Conclusion: Both autophagic LC3B-II and ph-S6K molecules are over-represented in both epithelioid and classic renal angiomyolipoma and a combined use of inhibitors to the autophagic and mTOR processes may be designed in clinical trials, when enrolling patients affected by tumours in tuberous sclerosis or angiomyolipoma at risk of bledding

    Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors

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    Purpose The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade >= 2).Methods This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients.Results 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naive (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG >= 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS >= 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively.Conclusions Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions.Trial registration The present study was registered at ClinicalTrials.gov number: NCT05078359

    Idiopathic stuttering priapism treated with salbutamol orally: a case report

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    Recurrent ischaemic priapism also known as stuttering priapism is an uncommon form of ischaemic priapism, and its treatment is not yet clearly defined. If left untreated, it may evolve into classic form of acute ischaemic priapism and lead to erectile dysfunction due to fibrosis of corpora cavernosa. Several drugs have been proposed with variable results and only supported with level three or four of evidence. Hormonal therapy such as cyproterone acetate, oestrogen, bicalutamide or Lh-Rh agonist are often effective but can cause side effects such as hypogonadal state and infertility. Other medical options are 5-alpha-reductase and phosphodiesterase-5 inhibitors, ketoconazole, baclofen, digoxin, gabapentin and beta-2-agonist terbutaline. We report the first case of stuttering priapism treated with beta-2-agonist salbutamol
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