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Prostate cancer ranks among the most prevalent tumours globally. While early detection reduces the likelihood of metastasis, managing advanced cases poses challenges in diagnosis and treatment. Current international guidelines support the concurrent use of 99Tc-Bone Scintigraphy and Contrast-Enhanced Chest and Abdomen CT for the staging of metastatic disease and response assessment. However, emerging evidence underscores the superiority of next-generation imaging techniques including PSMA-PET/CT and whole-body MRI (WB-MRI). This review explores the relevant scientific literature on the role of WB-MRI in metastatic prostate cancer. This multiparametric imaging technique, combining the high anatomical resolution of standard MRI sequences with functional sequences such as diffusion-weighted imaging (DWI) and bone marrow relative fat fraction (rFF%) has proved effective in comprehensive patient assessment, evaluating local disease, most of the nodal involvement, bone metastases and their complications, and detecting the increasing visceral metastases in prostate cancer. It does have the advantage of avoiding the injection of contrast medium/radionuclide administration, spares the patient the exposure to ionizing radiation, and lacks the confounder of FLARE described with nuclear medicine techniques. Up-to-date literature regarding the diagnostic capabilities of WB-MRI, though still limited compared to PSMA-PET/CT, strongly supports its widespread incorporation into standard clinical practice, alongside the latest nuclear medicine techniques.
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INTRODUCTION AND METHODS: Myophosphorylase deficiency, also known as McArdle disease or Glycogen Storage Disease type V (GSD-V), is an autosomal recessive metabolic myopathy that results in impaired glycogen breakdown in skeletal muscle. Despite being labelled as a "pure myopathy," cardiac involvement has been reported in some cases, including various cardiac abnormalities such as electrocardiographic changes, coronary artery disease, and cardiomyopathy. Here, we present a unique case of a 72-year-old man with GSD-V and both mitral valvulopathy and coronary artery disease, prompting a systematic review to explore the existing literature on cardiac comorbidities in McArdle disease. RESULTS: Our systematic literature revision identified 7 case reports and 1 retrospective cohort study. The case reports described 7 GSD-V patients, averaging 54.3 years in age, mostly male (85.7%). Coronary artery disease was noted in 57.1% of cases, hypertrophic cardiomyopathy in 28.5%, severe aortic stenosis in 14.3%, and genetic dilated cardiomyopathy in one. In the retrospective cohort study, five out of 14 subjects (36%) had coronary artery disease. DISCUSSION AND CONCLUSION: Despite McArdle disease primarily affecting skeletal muscle, cardiac involvement has been observed, especially coronary artery disease, the frequency of which was moreover found to be higher in McArdle patients than in the background population in a previous study from a European registry. Exaggerated cardiovascular responses during exercise and impaired glycolytic metabolism have been speculated as potential contributors. A comprehensive cardiological screening might be recommended for McArdle disease patients to detect and manage cardiac comorbidities. A multidisciplinary approach is crucial to effectively manage both neurological and cardiac aspects of the disease and improve patient outcomes. Further research is required to establish clearer pathophysiological links between McArdle disease and cardiac manifestations in order to clarify the existing findings.
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Introduction: Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole-mount specimens and PSMA-PET parameters. Methods: We included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated. Results: Forty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen's kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg <20% had a higher concordance in VS and VP (Cohen's kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (p = 0.3) and PSMA-TL (p = 0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (p = 0.04). Higher SUVmax was associated with membranous and combined VP expression (p = 0.008). No difference emerged between patients with PSMA%neg <20% or PSMA%neg >20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (p = 0.5, p = 0.5, and p = 0.9 respectively). Conclusions: We found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg <20% seems to have a better concordance in terms of visual score.
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BACKGROUND: Positron Emission Tomography-Computed Tomography using Prostate-Specific Membrane Antigen (PSMA PET/CT) is notable for its superior sensitivity and specificity in detecting recurrent PCa and is under investigation for its potential in pre-treatment staging. Despite its established efficacy in nodal and metastasis staging in trial setting, its role in primary staging awaits fuller validation due to limited evidence on oncologic outcomes. This systematic review and meta-analysis aims to appraise the diagnostic accuracy of PSMA PET/CT compared to CI for comprehensive PCa staging. METHODS: Medline, Scopus and Web of science databases were searched till March 2023. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. Primary outcomes were specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of PSMA PET/CT for local, nodal and metastatic staging in PCa patients. Due to the unavailability of data, a meta-analysis was feasible only for detection of seminal vesicles invasion (SVI) and LNI. RESULTS: A total of 49 studies, comprising 3876 patients, were included. Of these, 6 investigated accuracy of PSMA PET/CT in detection of SVI. Pooled sensitivity, specificity, PPV and NPV were 42.29% (95%CI: 29.85-55.78%), 87.59% (95%CI: 77.10%-93.67%), 93.39% (95%CI: 74.95%-98.52%) and 86.60% (95%CI: 58.83%-96.69%), respectively. Heterogeneity analysis revealed significant variability for PPV and NPV. 18 studies investigated PSMA PET/CT accuracy in detection of LNI. Aggregate sensitivity, specificity, PPV and NPV were 43.63% (95%CI: 34.19-53.56%), 85.55% (95%CI: 75.95%-91.74%), 67.47% (95%CI: 52.42%-79.6%) and 83.61% (95%CI: 79.19%-87.24%). No significant heterogeneity was found between studies. CONCLUSIONS: The present systematic review and meta-analysis highlights PSMA PET-CT effectiveness in detecting SVI and its good accuracy in LNI compared to CI. Nonetheless, it also reveals a lack of high-quality research on its performance in clinical T staging, extraprostatic extension and distant metastasis evaluation, emphasizing the need for further rigorous studies.
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This study aimed to assess the efficacy of a novel prophylactic scheme of fosfomycin trometamol in patients undergoing elective HoLEP (holmium laser enucleation of the prostate) or TURP (transurethral resection of the prostate) procedures for treating benign prostatic hyperplasia. Patients affected by benign prostatic hyperplasia and undergoing elective HoLEP or TURP procedures during the period February 2022-June 2023 were prospectively enrolled. Two 3 g oral fosfomycin trometamol doses 12 h apart were administered at 8.00 p.m. on day -1 (i.e., the day before HoLEP or TURP procedure) and at 8.00 a.m. on day 0 (i.e., the day of the surgical procedure). The following outcomes were assessed: prevalence of fever occurring in the first 48 h after surgical procedure; prevalence of urological complications occurring after the surgical procedure; prevalence of proven urinary tract infections (UTIs) and/or bloodstream infections (BSIs) at 14 days post-procedure; and prevalence of emergency department admission for UTI-related sepsis at 14 days post-procedure. Univariate analysis comparing patients with and without proven UTI, BSI, or emergency department admission at 14 days post-procedure was carried out. Overall, 96 patients (median age 70 years) undergoing HoLEP (82.3%) or TURP (17.7%) were prospectively included. Median (IQR) time of surgical procedure after the morning fosfomycin dose was 226.5 min (range 88.5-393.75 min). Fever in the post-surgical 48 h occurred in 3/96 patients (3.1%). Prevalence of proven UTI at 14 days was as low as 1.0% (1/96), whereas no patient had proven BSI or UTI-related sepsis requiring emergency department admission at 14 days. Our findings support the contention that a prophylactic scheme based on two doses of fosfomycin trometamol 12 h apart before surgical intervention may represent a valuable strategy for preventing infectious complications in urologic patients undergoing HoLEP or TURP. Larger definitive confirmatory studies are warranted.
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AIM: To evaluate the indication of the endodontic treatment for vital intact teeth with the root apex involved in large radicular cystic lesions of endodontic origin. METHODOLOGY: This prospective cohort study enrolled healthy participants with radicular cysts of endodontic origin and with the root apex of vital intact teeth involved in the bone defect, as determined by cone beam computed tomography (CBCT). Thirty-two sound vital teeth were analysed by thermal (TPT) and electric pulp tests (EPT) before surgery (T0) and 1 week (T1), 2 weeks (T2), 3 months (T3) and 6 months (T4) post-surgery. Student's t-test (p < .05) was used to compare the EPT values at baseline and T4. anova (p < .05) was used to analyse the EPT variations for all maxillary and mandibular teeth. McNemar test (p < .05) was used to compare the results according to variation in EPT values gathering by variation, no variation and no response. RESULTS: At T1, 75 and 65.7% of teeth responded positively whilst 25 and 34.3% did not respond to EPT and TPT, respectively. The variation of the EPT values between T0 and T1 was observed for 50.0% of teeth, whilst no variation was noticed in 25.0% of teeth. At T4, 90.6 and 87.5% of teeth responded positively whilst 9.4 and 12.5% did not respond to EPT and TPT, respectively. At T4, variation of the EPT values between T0 and T4 was observed for 28.1%, whilst no variation was noticed in 62.5% of teeth. There were no statistical differences in EPT results between T0 and T4 (p > .05), but significant differences were observed for EPT values between T1 and T4 (p < .05), and between mandibular and maxillary teeth. The pulp sensibility of maxillary teeth worsened after surgery, before reverting progressively to T0 values, whilst no statistically significant differences were observed for mandibular teeth at the different time points. CONCLUSIONS: These data support the inconsistence of the prophylactic endodontic treatment in healthy vital teeth with apex involvement in large cystic lesions of endodontic origin. Post-surgery follow-up with TPT and EPT is recommended to assess pulp status.
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Cone-Beam Computed Tomography , Radicular Cyst , Humans , Prospective Studies , Female , Male , Adult , Radicular Cyst/diagnostic imaging , Radicular Cyst/surgery , Treatment Outcome , Dental Pulp Test , Root Canal Therapy/methods , Young Adult , Tooth Apex/diagnostic imaging , Middle AgedABSTRACT
AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5â mmHg (P < 0.0001). The number of SBP drops <90 and <100â mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around â¼15â mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13â mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.
Subject(s)
Hypertension , Hypotension , Orthostatic Intolerance , Syncope, Vasovagal , Humans , Antihypertensive Agents/therapeutic use , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Hypertension/drug therapy , Orthostatic Intolerance/diagnosis , Orthostatic Intolerance/drug therapy , Reflex , Syncope, Vasovagal/diagnosis , Syncope, Vasovagal/prevention & control , Proof of Concept StudyABSTRACT
BACKGROUND: The role of local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies on prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) has scarcely been explored. Limited data are available to identify men who would benefit from RP; on the contrary, those more likely to benefit already have systemic disease. OBJECTIVE: We aimed to assess the predictors of prostate-specific antigen (PSA) persistence in surgically managed PCa patients with lymphadenopathies on a PSMA PET/CT scan by integrating clinical, magnetic resonance imaging (MRI), and PSMA PET/CT parameters. DESIGN, SETTING, AND PARTICIPANTS: We identified 519 patients treated with RP and extended lymph node dissection, and who received preoperative PSMA PET between 2017 and 2022 in nine referral centers. Among them, we selected 88 patients with nodal uptake at preoperative PSMA PET (miTxN1M0). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome was PSA persistence, defined as a PSA value of ≥0.1 ng/ml at the first measurement after surgery. Multivariable logistic regression models tested the predictors of PSA persistence. Covariates consisted of biopsy International Society of Urological Pathology (ISUP) grade group, clinical stage at MRI, and number of positive spots at a PET/CT scan. A regression tree analysis stratified patients into risk groups based on preoperative characteristics. RESULTS AND LIMITATIONS: Overall, lymph node invasion (LNI) was detected in 63 patients (72%) and 32 (36%) experienced PSA persistence after RP. At multivariable analyses, having more than two lymph nodal positive findings at PSMA PET, seminal vesicle invasion (SVI) at MRI, and ISUP grade group >3 at biopsy were independent predictors of PSA persistence (all p < 0.05). At the regression tree analysis, patients were stratified in four risk groups according to biopsy ISUP grade, number of positive findings at PET/CT, and clinical stage at MRI. The model depicted good discrimination at internal validation (area under the curve 78%). CONCLUSIONS: One out of three miN1M0 patients showed PSA persistence after surgery. Patients with ISUP grade 2-3, as well as patients with organ-confined disease at MRI and a single or two positive nodal findings at PET are those in whom RP may achieve the best oncological outcomes in the context of a multimodal approach. Conversely, patients with a high ISUP grade and extracapsular extension or SVI or more than two spots at PSMA PET should be considered as potentially affected by systemic disease upfront. PATIENT SUMMARY: Our novel and straightforward risk classification integrates currently available preoperative risk tools and should, therefore, assist physician in preoperative counseling of men candidates for radical treatment for prostate cancer with positive lymph node uptake at prostate-specific membrane antigen positron emission tomography.
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Lymphadenopathy , Prostatic Neoplasms , Male , Humans , Prostate-Specific Antigen , Prostate/diagnostic imaging , Prostate/surgery , Prostate/pathology , Positron Emission Tomography Computed Tomography/methods , Seminal Vesicles/pathology , Lymphatic Metastasis/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Lymph Nodes/pathology , Prostatectomy , Positron-Emission Tomography , Magnetic Resonance Imaging , Lymphadenopathy/pathology , Lymphadenopathy/surgeryABSTRACT
ADHD is a neurodevelopmental disorder largely diffused among children and adolescents. The current method of diagnosis is based on agreed clinical literature such as DSM-5, by identifying and evaluating signs of hyperactivity and inattention. Multiple reviews have assessed that EEG is not sufficiently reliable for the diagnosis of ADHD. Theta-Beta Ratio is now the sole EEG parameter considered for analysis, although it is not robust enough to be utilized as a confirmatory technique for diagnosis. In this setting, new objective approaches for reliably classifying neurotypical and ADHD subjects are required. As a result, we suggest a new methodology based on Functional Data Analysis, a statistical class of methods for dealing with curves and functions. The initial stage in our method is to separate frequency bands from the EEG signal using a wavelet decomposition. We next compute the Power Spectral Densities of each of these bands and represent them as mathematical functions via spline interpolation. Finally, the relevance of the collected features is assessed using the Permutation ANOVA test. Using this method, we can detect different patterns in the PSDs of the groups and identify statistically significant features, confirming prior findings in the literature. We validate the features using classification techniques such as Bagging trees, Random Forest, and AdaBoost. The latter reaches the highest accuracy score of 76.65%, confirming the relevance of the extracted features.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Electroencephalography , Child , Adolescent , Humans , Electroencephalography/methods , Theta Rhythm , Attention Deficit Disorder with Hyperactivity/diagnosis , Beta Rhythm , Data AnalysisABSTRACT
BACKGROUND: The learning curve for robot-assisted radical prostatectomy (RARP) remains controversial, with prior studies showing that, in contrast with evidence on open and laparoscopic radical prostatectomy, biochemical recurrence rates of experienced versus inexperienced surgeons did not differ. OBJECTIVE: To characterize the learning curve for positive surgical margins (PSMs) after RARP. DESIGN, SETTING, AND PARTICIPANTS: We analyzed the data of 13 090 patients with prostate cancer undergoing RARP by one of 74 surgeons from ten institutions in Europe and North America between 2003 and 2022. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable models were used to assess the association between surgeon experience at the time of each patient's operation and PSMs after surgery, with adjustment for preoperative prostate-specific antigen level, grade, stage, and year of surgery. Surgeon experience was coded as the number of robotic radical prostatectomies done by the surgeon before the index patient's operation. RESULTS AND LIMITATIONS: Overall, 2838 (22%) men had PSMs on final pathology. After adjusting for case mix, we found a significant, nonlinear association between surgical experience and probability of PSMs after surgery, with a lower risk of PSMs for greater surgeon experience (p < 0.0001). The probabilities of PSMs for a patient treated by a surgeon with ten, 250, 500, and 2000 prior robotic procedures were 26%, 21%, 18%, and 14%, respectively (absolute risk difference between ten and 2000 procedures: 11%; 95% confidence interval: 9%, 14%). Similar results were found after stratifying patients according to extracapsular extension at final pathology. Results were also unaltered after excluding surgeons who had moved between institutions. CONCLUSIONS: While we characterized the learning curve for PSMs after RARP, the relative contribution of surgical learning to the achievement of optimal outcomes remains controversial. Future investigations should focus on what experienced surgeons do to avoid positive margins and should explore the relationship between learning, margin rate, and biochemical recurrence. Understanding what margins affect recurrence and whether these margins are trainable or a result of other factors may shed light on where to focus future efforts in surgical education. PATIENT SUMMARY: In patients receiving robotic radical prostatectomy for prostate cancer, we characterized the learning curve for positive margins. The risk of surgical margins decreased progressively with increasing experience, and plateaued around the 500th procedure. Understanding what margins affect recurrence and whether these margins are trainable or a result of other factors has implications for surgeons and patients, and it may shed light on where to focus future efforts in surgical education.
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The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43-79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9-3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without "canonical" mutations.
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Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Male , Aged , Kidney Neoplasms/diagnosis , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Kidney/pathology , Mutation , Carcinoma, Renal Cell/pathology , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolismABSTRACT
The Prostate Imaging and Reporting Data System (PI-RADS) has a key role in the management of prostate cancer (PCa). However, the clinical interpretation of PI-RADS 3 score lesions may be challenging and misleading, thus postponing PCa diagnosis to biopsy outcome. Multiparametric magnetic resonance imaging (mpMRI) radiomic analysis may represent a stand-alone noninvasive tool for PCa diagnosis. Hence, this study aims at developing a mpMRI-based radiomic PCa diagnostic model in a cohort of PI-RADS 3 lesions. We enrolled 133 patients with 155 PI-RADS 3 lesions, 84 of which had PCa confirmation by fusion biopsy. Local radiomic features were generated from apparent diffusion coefficient maps, and the four most informative were selected using LASSO, the Wilcoxon rank-sum test (p < 0.001), and support vector machines (SVMs). The selected features where augmented and used to train an SVM classifier, externally validated on a holdout subset. Linear and second-order polynomial kernels were exploited, and their predictive performance compared through receiver operating characteristics (ROC)-related metrics. On the test set, the highest performance, equally for both kernels, was specificity = 76%, sensitivity = 78%, positive predictive value = 80%, and negative predictive value = 74%. Our findings substantially improve radiologist interpretation of PI-RADS 3 lesions and let us advance towards an image-driven PCa diagnosis.
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Multiparametric magnetic resonance imaging (mpMRI) is currently the most effective diagnostic tool for detecting prostate cancer (PCa) and evaluating adenocarcinoma-mimicking lesions of the prostate gland, among which granulomatous prostatitis (GP) represents the most interesting diagnostic challenge. GP consists of a heterogeneous group of chronic inflammatory lesions that can be differentiated into four types: idiopathic, infective, iatrogenic, and associated with systemic granulomatous disease. The incidence of GP is growing due to the increase in endourological surgical interventions and the adoption of intravesical instillation of Bacillus Calmette-Guerin in patients with non-muscle invasive bladder cancer; therefore, the difficulty lies in identifying specific features of GP on mpMRI to avoid the use of transrectal prostate biopsy as much as possible.
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BACKGROUND: Although the therapeutic role of extended pelvic lymph node dissection (ePLND) in patients with prostate cancer (PCa) is still under debate, this procedure is recommended for staging purposes in selected cases. Nomograms for predicting lymph node invasion (LNI) do not account for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, which is characterized by a high negative predictive value for nodal metastases. OBJECTIVE: To externally validate models predicting LNI in patients with miN0M0 PCa at PSMA PET and to develop a novel tool in this setting. DESIGN, SETTING, AND PARTICIPANTS: Overall, 458 patients with miN0M0 disease undergoing radical prostatectomy (RP) and ePLND at 12 centers between 2017 and 2022 were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Available tools were externally validated using calibration plots, the area under the receiver operating characteristic curve (AUC), and decision curve analyses to assess calibration, discrimination, and the net benefit. A novel coefficient-based model was developed, internally validated, and compared with available tools. RESULTS AND LIMITATIONS: Overall, 53 patients (12%) had LNI. The AUC was 69% for the Briganti 2012, 64% for the Briganti 2017, 73% for the Briganti 2019, and 66% for the Memorial Sloan Kettering Cancer Center nomogram. Multiparametric magnetic resonance imaging stage, biopsy grade group 5, the diameter of the index lesion, and the percentage of positive cores at systematic biopsy were independent predictors of LNI (all p ≤ 0.04). Internal cross-validation confirmed a coefficient-based model with AUC of 78%, better calibration, and a higher net benefit in comparison to the other nomograms assessed. Use of a 5% cutoff would have spared 47% ePLND procedures (vs 13% for the Briganti 2019 nomogram) at the cost of missing only 2.1% LNI cases . The lack of central review of imaging and pathology represents the main limitation. CONCLUSIONS: Tools for predicting LNI are associated with suboptimal performance for men with miN0M0 PCa. We propose a novel model for predicting LNI that outperforms available tools in this population. PATIENT SUMMARY: Tools currently used to predict lymph node invasion (LNI) in prostate cancer are not optimal for men with negative node findings on PET (positron emission tomography) scans, leading to a high number of unnecessary extended pelvic lymph node dissection (ePLND) procedures. A novel tool should be used in clinical practice to identify candidates for ePLND to reduce the risk of unnecessary procedures without missing LNI cases.
Subject(s)
Nomograms , Prostatic Neoplasms , Male , Humans , Prostate/pathology , Neoplasm Staging , Lymphatic Metastasis/diagnostic imaging , Lymph Node Excision/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Positron-Emission TomographyABSTRACT
Lymphedema is a chronic progressive disorder that significantly compromises patients' quality of life. In Western countries, it often results from cancer treatment, as in the case of post-radical prostatectomy lymphedema, where it can affect up to 20% of patients, with a significant disease burden. Traditionally, diagnosis, assessment of severity, and management of disease have relied on clinical assessment. In this landscape, physical and conservative treatments, including bandages and lymphatic drainage have shown limited results. Recent advances in imaging technology are revolutionizing the approach to this disorder: magnetic resonance imaging has shown satisfactory results in differential diagnosis, quantitative classification of severity, and most appropriate treatment planning. Further innovations in microsurgical techniques, based on the use of indocyanine green to map lymphatic vessels during surgery, have improved the efficacy of secondary LE treatment and led to the development of new surgical approaches. Physiologic surgical interventions, including lymphovenous anastomosis (LVA) and vascularized lymph node transplant (VLNT), are going to face widespread diffusion. A combined approach to microsurgical treatment provides the best results: LVA is effective in promoting lymphatic drainage, bridging VLNT delayed lymphangiogenic and immunological effects in the lymphatic impairment site. Simultaneous VLNT and LVA are safe and effective for patients with both early and advanced stages of post-prostatectomy LE. A new perspective is now represented by the combination of microsurgical treatments with the positioning of nano fibrillar collagen scaffolds (BioBridgeTM) to favor restoring the lymphatic function, allowing for improved and sustained volume reduction. In this narrative review, we proposed an overview of new strategies for diagnosing and treating post-prostatectomy lymphedema to get the most appropriate and successful patient treatment with an overview of the main artificial intelligence applications in the prevention, diagnosis, and management of lymphedema.
Subject(s)
Lymphatic Vessels , Lymphedema , Male , Humans , Quality of Life , Artificial Intelligence , Lymphedema/diagnosis , Lymphedema/etiology , Lymphedema/therapy , Lymphatic Vessels/pathology , Lymphatic Vessels/surgery , Prostatectomy/adverse effectsABSTRACT
BACKGROUND: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients. METHODS: we performed a retrospective analysis of 113 recurrent PCa after previous radical prostatectomy and salvage therapies with oligorecurrent disease at PSMA-PET (≤3 lesions in N1/M1a-b) in three high-volume European centres. Patients underwent second-line salvage treatments: MDT targeted to PSMA (including surgery and/or radiotherapy), and the conventional approach (observation or Androgen Deprivation Therapy [ADT]). Patients were stratified according to treatments (MDT vs. conventional approach). Patients who underwent MDT were stratified according to stage in PSMA-PET (N1 vs. M1a-b). The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were Metastases-free survival (MFS) and Castration Resistant PCa free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS. Multivariable Cox regression models identified predictors of progression and metastatic disease. RESULTS: Overall, 91 (80%) and 22 (20%) patients were treated with MDT and the conventional approach, respectively. The median follow-up after PSMA-PET was 31 months. Patients who underwent MDT had a similar PFS compared to the conventional approach (p = 0.3). Individuals referred to MDT had significantly higher MFS and CRPC-FS compared to those who were treated with the conventional approach (73.5% and 94.7% vs. 30.5% and 79.5%; all p ≤ 0.001). In patients undergoing MDT, no significant differences were found for PFS and MFS according to N1 vs. M1a-b disease, while CRPC-FS estimates were significantly higher in patients with N1 vs. M1a-b (100% vs. 86.1%; p = 0.02). At multivariable analyses, age (HR = 0.96) and ADT during second line salvage treatment (HR = 0.5) were independent predictors of PFS; MDT (HR 0.27) was the only independent predictor of MFS (all p ≤ 0.04) Conclusion: Patients who underwent second-line PSMA-guided MDT experienced higher MFS and CRPC-FS compared to men who received conventional management.
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Background: To evaluate multiparametric magnetic resonance imaging (mpMRI) parameters, such as TransPA (transverse prostate maximum sectional area), TransCGA (transverse central gland sectional area), TransPZA (transverse peripheral zone sectional area), and TransPAI (TransPZA/TransCGA ratio) in predicting prostate cancer (PCa) in prostate imaging reporting and data system (PI-RADS) 3 lesions. Methods: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), the area under the receiver operating characteristic curve (AUC), and the best cut-off, were calculated. Univariate and multivariate analyses were carried out to evaluate the capability to predict PCa. Results: Out of 120 PI-RADS 3 lesions, 54 (45.0%) were PCa with 34 (28.3%) csPCas. Median TransPA, TransCGA, TransPZA and TransPAI were 15.4cm2, 9.1cm2, 5.5cm2 and 0.57, respectively. At multivariate analysis, location in the transition zone (OR=7.92, 95% CI: 2.70-23.29, P<0.001) and TransPA (OR=0.83, 95% CI: 0.76-0.92, P<0.001) were independent predictors of PCa. The TransPA (OR=0.90, 95% CI: 0.082-0.99, P=0.022) was an independent predictor of csPCa. The best cut-off of TransPA for csPCa was 18 (Sensitivity 88.2%, Specificity 37.2%, PPV 35.7%, NPV 88.9%). The discrimination (AUC) of the multivariate model was 0.627 (95% CI: 0.519-0.734, P<0.031). Conclusions: In PI-RADS 3 lesions, the TransPA could be useful in selecting patients requiring biopsy.
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Background: Current literature does not provide large-scale data regarding clinical outcomes of robot-assisted (RAPN) versus open (OPN) partial nephrectomy. Moreover, data assessing predictors of long-term oncologic outcomes after RAPN are scarce. Objective: To compare perioperative, functional, and oncologic outcomes of RAPN versus OPN, and to investigate the predictors of oncologic outcomes after RAPN. Design setting and participants: This study included 3467 patients treated with OPN (n = 1063) or RAPN (n = 2404) for a single cT1-2N0M0 renal mass from 2004 to 2018 at nine high-volume European, North American, and Asian institutions. Outcome measurements and statistical analysis: The study outcomes were short-term postoperative, functional, and oncologic outcomes. Regression models investigated the effect of surgical approach (open vs Robot assisted) on study outcomes, and interaction tests were used for subgroup analyses. Propensity score matching for demographic and tumor characteristics was used in sensitivity analyses. Multivariable Cox-regression analyses identified predictors of oncologic outcomes after RAPN. Results and limitations: Baseline characteristics were similar between patients receiving RAPN and OPN, with only few differences. After adjusting for confounding, RAPN was associated with lower odds of intraoperative (odds ratio [OR]: 0.39, 95% confidence interval [CI]: 0.22, 0.68) and Clavien-Dindo ≥2 postoperative (OR: 0.29, 95% CI: 0.16, 0.50) complications (both p < 0.05). This association was not affected by comorbidities, tumor dimension, PADUA score, or preoperative renal function (all p > 0.05 on interaction tests). On multivariable analyses, we found no differences between the two techniques with respect to functional and oncologic outcomes (all p > 0.05). Overall, there were 63 and 92 local recurrences and systemic progressions, respectively, with a median follow-up after surgery of 32 mo (interquartile range: 18, 60). Among patients receiving RAPN, we assessed predictors of local recurrence and systemic progression with discrimination accuracy (ie, C-index) that ranged from 0.73 to 0.81. Conclusions: While cancer control and long-term renal function did not differ between RAPN and OPN, we found that the intra- and postoperative morbidity-especially in terms of complications-was lower after RAPN than after OPN. Our predictive models allow surgeons to estimate the risk of adverse oncologic outcomes after RAPN, with relevant implications for preoperative counseling and follow-up after surgery. Patient summary: In this comparative study on robotic versus open partial nephrectomy, functional and oncologic outcomes were similar between the two techniques, with lower morbidity-especially in terms of complications-for robot-assisted surgery. The assessment of prognosticators for patients receiving robot-assisted partial nephrectomy may help in preoperative counseling and provides relevant data to tailor postoperative follow-up.
ABSTRACT
PSMA-PET/CT is a suitable replacement for conventional imaging in the primary staging of PCa. The aim of this retrospective study was to assess the correlation between parameters discovered by PSMA PET/CT in primary staging and either prostate histopathology (pT) findings or PSMA-IHC expression in a cohort of biopsy-proven high-risk PCa candidates for surgery. Clinical information (age, iPSA-value, and grading group) and PSMA-PET/CT parameters (SUVmax, PSMA tumor volume [PSMA-TV], and total lesion [PSMA-TL]) were compared with pT (including histologic pattern, Gleason grade, and lymphovascular invasion [LVI]) and PSMA-IHC features, including visual quantification (VS) with a four-tiered score (0 = negative, 1+ = weak, 2+ = moderate, 3+ = strong), growth pattern (infiltrative vs expansive), and visual pattern (cytoplasmic vs membranous). In total, 44 patients were enrolled, with a median age of 67 (IQR 57-77); the median iPSA was 9.4 ng/dL (IQR 12.5-6.0). One patient (3%) was grading group (GG) 3, 27/44 (61%) were GG4, and 16/44 (36%) were GG5. PSMA-PET/CT detection rate for the presence of primary prostate cancer was 100%. Fused/poorly formed Gleason grade 4 features were predominant (22/44-50%); a cribriform pattern was present in 18/44 (41%) and acinar in 4/44 (9%). We found that lower PSMA-TVs were mostly related to acinar, while higher PSMA-TVs correlated with a higher probability to have a cribriform pattern (p-value 0.04). LVI was present in 21/44(48%) patients. We found that higher PSMA-TV and PSMA-TL are predictive of LVI p-value 0.002 and p-value 0.01, respectively. There was no correlation between PET-parameters and perineural invasion (PNI), probably because this was present in almost all the patients. Moreover, patients with high PSMA-TL values displayed the highest PSMA-IHC expression (VS3+) with a membranous pattern. In conclusion, PSMA-TV and PSMA-TL are predictors of a cribriform pattern and LVI. These conditions are mostly related to higher aggressiveness and worse outcomes.