Search

Objective: To describe the initial experience with PSMA-PET/CT-guided biopsy in European referral centres., Methods: This multicenter observational cohort study was endorsed by the Young Academic Urologist (YAU) Prostate Cancer Group of the EAU and conducted across 6 tertiary-level European centres. PSMA-guided biopsies were carried out in a cognitive/fusion manner for all the recruited patients with or without MRI-guided biopsies and/or standard biopsy (SB). PCa and clinical significant PCa (csPCA) detection rate (DR) at prostate biopsy was assessed. Uni- and multivariable models were employed to identify features related to csPCA., Results: Overall, 72 patients were recruited. The topographic location of the dominant lesion depicted by PSMA PET/CT was significantly associated with the location of csPCa, especially in the biopsy naïve cohort. The DR for PCa and csPCa of PSMA-PET/CT-guided biopsies was significantly higher than SB (0.40 ± 0.43 vs 0.23 ± 0.29, and 0.36 ± 0.44 vs 0.21 ± 0.30, respectively, both P <.05) but did not surpass MRI-guided biopsies (0.40 ± 0.43 vs 0.47 ± 0.44, and 0.36 ± 0.44 vs 0.47 ± 0.34, respectively, both P >.05). PSMA-PET/CT-guided biopsy performed better in the biopsy naïve than in the repeated biopsy setting. A SUVmax cut-off value equal to 4.8 provided the best results for detecting csPCa., Conclusion: Our real-world data illustrate the potentialities of PSMA-PET/CT-guided biopsy in diagnosing PCa. Specifically, in biopsy naïve patients with suspicion of high-risk disease, the use of PSMA-PET/CT-targeted biopsy can be considered. Additionally, in the context of repeated biopsies, a PSMA-PET/CT target biopsy might be advisable over the SB., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the reliability of an age estimation method based on the pulp⁄tooth area ratio by assessing intra- and inter-examiner agreement across five observers at different intervals. Using the same X-ray device and technical parameters, 96 digital periapical X-ray images of upper and lower canines were obtained from 28 deceased people in Central America, whose age at death ranged from 19 to 49 years. Excellent and good agreement of results were achieved, and there were no statistically significant differences. The R2 value for upper teeth (54.0%) was higher than the R2 value for lower teeth (45.7%). The highest intraclass correlation coefficient value was 0.995 (0.993-0.997) and the lowest 0.798 (0.545-0.895). Inter-examiner agreement was high with values of 0.975 (0.965-0.983) and 0.927 (0.879-0.955). This method is adequate for assessing age in missing and unidentified people, including victims of mass disasters., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Urine is a promising biological fluid for prostate cancer (PCa) diagnostics due to its non-invasive collection and wide range of biomarkers. The aim of this study was to assess the role of urinary PSA (uPSA) and urinary Zinc (uZinc) as biomarkers for the diagnosis of PCa in combination with routine parameters of standard of care (SOC - blood PSA, abnormal DRE, age) and MRI in patients candidates for prostate biopsy., Methods: Urine samples after prostatic massages were collected from men with suspected PCa scheduled for prostate biopsy. Quantification of uPSA was performed by ECLIA platform and confirmed by ELISA assay, while uZinc measurement was evaluated by ICP-MS and confirmed by colorimetric in vitro assay. Six multivariate logistic regression analysis were performed to assess diagnostic performance of uPSA and uZinc (urine), SOC and MRI alone, and combination of MRI+SOC, MRI+urine and SOC+MRI+urine. The discriminative power of the logistic models was assessed by calculating the area under the receiver operating characteristic (ROC) curves (AUC)., Results: Two hundred thirty-eight patients were included in the analysis; 145 of them were diagnosed with PCa. Urine test showed a better discrimination of HS from CP, in respect of uPSA and uZinc alone, both for PCa of any grade and Gleason Score ≥7 (4+3) (AUC 0.804 and 0.823 respectively). ROC curve combining SOC+MRI+urine showed an AUC=0.882, that is statistically different from SOC or MRI alone, or MRI+SOC (P=0.0001, P=0.0001, and P=0.008 respectively). PCa risk algorithm designed considering SOC+MRI+urine results in potential reduction of 57% of unnecessary biopsies compared to the current standard parameters., Conclusions: The loss of uPSA and Zinc production and secretion during neoplastic transformation of the prostate could potentially represent a hallmark of PCa. Its combination with age, PSA and DRE, as well as with mpMRI could represent an interesting approach to improve the diagnostic accuracy of PCa.

The aim of this study is to present the first Italian experience with robotic-assisted retrograde intrarenal surgery (rRIRS) using the Ily ® platform. Procedures were performed for renal stones using the Ily ® Robot (STERLAB, Vallauris, France), which is a ureteroscope holder with multiple degrees of freedom that can be controlled remotely through a wireless controller. In March 2023, consecutive patients with indications for rRIRS were included in the study. Demographic variables and stone characteristics were collected, and standard perioperative data were assessed. The one-month stone-free rate (SFR, i.e. no residual fragments) was evaluated using ultrasound. All participating surgeons filled out a Surgeons' Satisfaction Questionnaire (SSQ) based on a Likert-type scale. The questionnaire focused on: 1) ease of use; 2) ergonomics during renal cavity exploration; 3) stability during stone fragmentation. Among the patients, one had bilateral stones, while two had stones on the right side. The mean stone size was 13 mm. The average operative time was 70 minutes and the mean docking time was three minutes. No perioperative complications were recorded, and all patients were discharged on the first postoperative day. The one-month SFR was 100%. The SSQ scores were as follows: 1) ease of use: 4/5; 2) ergonomics: 5/5; 3) stability during stone fragmentation: 5/5. Based on the initial experience, the results indicate the feasibility, safety, and effectiveness of rRIRS. The ergonomic efficiency of the system was highly appreciated by the surgeons. While a cost-effectiveness analysis within clinical trials is necessary, rRIRS shows the potential for a more sustainable future for endoscopists and an improved workplace environment.

Background: Nowadays a tool able to predict the risk of lymph-node invasion (LNI) in patients underwent target biopsy (TB) only before radical prostatectomy (RP) is still lacking. Our aim is to develop a model based on mp-MRI and target biopsy (TB) alone able to predict the risk of LNI., Methods: We retrospectively extracted data of patients with preoperative positive mp-MRI and TB only who underwent RARP with ePLND from April 2014 to March 2020. A logistic regression model was performed to evaluate the impact of pre- and intra-operative factors on the risk of LNI. Model discrimination was assessed using an area under (AUC) the ROC curve. A nomogram, and its calibration plot, to predict the risk of LNI were generated based on the logistic model. A validation of the model was done using a similar cohort., Results: 461 patients were included, of which 52 (11.27) had LNI. After logistic regression analysis and multivariable model DRE, PI-RADS, seminal vesicle invasion, PSA and worst GS at I and II target lesions were significant predictors of LNI. The AUC was 0.74 [0.67-0.81] 95% CI. The calibration plot shows that our model is very close to the ideal one which is in the 95% CI. After the creation of a visual nomogram, the cut-off to discriminate between the risk or not of LNI was set with Youden index at 60 points that correspond to a risk of LNI of 7%. The model applied on a similar cohort shown a LH+ of 2.58 [2.17-2.98] 95% CI., Conclusions: Our nomogram for patients undergoing MRI-TB only takes into account clinical stage, SVI at MRI, biopsy Gleason pattern and PSA and it is able to identify patients with risk of LNI when a score higher than 7% is achieved., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The aim of this paper was to compare safety and functional outcomes of total, hemi and focal ablation by the latest focal high-intensity focused ultrasound (HIFU) device., Methods: This is a prospective study including patients with low to intermediate-risk PCa treated with HIFU by Focal One ® device from 11/2018 to 3/2020. Before the treatment all patients underwent mp-magnetic resonance imaging (MRI) and subsequent MRI/transrectal ultrasound (TRUS) fusion and standard biopsy. Patients were stratified according to the type of ablation: total, hemi- or focal ablation. Functional data (IPSS, Quality of Life [QoL], IIEF-5, maximum flow [Qmax] and post void residual [PVR] at flowmetry) were assessed preoperatively and at 1, 3, 6 and 12 months after treatment. Moreover, the urinary symptoms reported by patients at IPSS questionnaire were divided in "irritative" and "obstructive" and compared., Results: One hundred patients were enrolled. Median prostate volume and lesion diameter were 46 (IQR 25-75) mL and 10 (IQR 6-13) mm. 15, 50 and 35 patients underwent total, hemi- and focal ablation, respectively. No differences were found between them except for operative time (lower in the focal group, P<0.01). Significant lower incidence of irritative symptoms was identified in the focal group compared to the others (P<0.05 at 1 and 3 months of follow-up). No differences were found among the baseline status and the postoperative assessment in terms of obstructive IPSS items, IIEF-5, QoL, Qmax and PVR (all P value>0.05)., Conclusions: Our study suggests that patients' specific HIFU tailoring with the MRI/real-time TRUS Guidance by Focal One ® device is able to minimize the side effects of treatment.

Identification of living undocumented individuals highlights the need for accurate, precise, and reproducible age estimation methods, especially in those cases involving minors. However, when their country of origin is unknown, or it can be only roughly estimated, it is extremely difficult to apply assessment policies, procedures, and practices that are accurate and child-sensitive. The main aim of this research is to optimize the correct classification of adults and minors by establishing new cut-off values for four different continents (Africa, America, Asia, and Europe). For this purpose, a vast sample of 10,701 orthopantomographs (OPTs) from four continents was evaluated. For determination and subsequent validation of the new third molar maturity index (I 3M ) cut-off values by world regions, a cross-validation by holdout method was used and contingency tables (confusion matrices) were generated. The lower third molar maturity indexes, from both left and right side (I 3M L and I 3M R) and the combination of both sides (I 3M L&#95;I 3M R) were calculated. The new cut-off values, that aim to differentiate between a minor and an adult, with more than 74.00% accuracy for all populations were as follows (I 3M L; I 3M R; I 3M L&#95;I 3M R, respectively): Africa = (0.10; 0.10; 0.10), America = (0.10; 0.09; 0.09), Asia = (0.15; 0.17; 0.14), and Europe = (0.09; 0.09; 0.09). The higher sensitivity (Se) was detected for the I 3M L for male African people (91%) and the higher specificity (Sp) of all the parameters (I 3M L; I 3M R; I 3M L&#95;I 3M R) for Europeans both male and female (> 91%). The original cut-off value (0.08) is still useful, especially in discriminating individuals younger than 18 years old which is the goal of the forensic methods used for justice., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In the era of mpMRI guided target fusion biopsy (FB), the role of concomitant standard biopsy (SB) in naïve patients still remains under scrutiny. The aim of this study was to compare the detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy naïve patients with positive mpMRI who underwent FB alone (Arm A) vs FB+SB (Arm B). Secondary objectives were to compare the incidence of complications, the overall PCa DR and the biopsy results with final pathological findings after robotic prostatectomy (RARP)., Methods: This is a single center prospective non-inferiority parallel two arms (1:1) randomized control trial (ISRCTN registry number ISRCTN60263108) which took place at San Luigi Gonzaga University Hospital, Orbassano (Turin, Italy) from 4/2019 to 10/2021. Eligible participants were all adults aged<75 years old, biopsy naïve, with serum PSA<15 ng/mL and positive mpMRI (Pi-Rads V.2>3). FB was performed under ultrasound guidance using the BioJet fusion system; four to six target samples were obtained for each index lesion. SB was performed in accordance with the protocol by Rodríguez-Covarrubias. RARP with total anatomical reconstruction was carried out when indicated. DR of PCa and csPCA (Gleason Score >7) were evaluated. Post-biopsy complications according to Clavien-Dindo were recorded. Concordance between biopsy and RARP pathological findings was evaluated. Fisher's Exact test and Mann-Whitney test were applied; furthermore, Logistic Principal Component Analysis (LogPCA) and Pearson's correlation method, in terms of correlation funnel plots, were performed to explore data in a multivariate way., Results: 201 and 193 patients were enrolled in Arm A and B, respectively. csPCa DR was 60.2% vs. 60.6% in Arm A and B respectively (Δ 0.4%; P=0.93); whilst overall PCa DR was 63.7% vs. 71.0% (Δ 7.3%; P=0.12). However, in a target only setting, the addition of SB homolaterally to the index lesion reaching a non-inferior performance compared to the combined sampling (Δ PCa DR 3%). Although the differences of 7.3% in PCa DR, during RARP were registered similar nerve sparing rate (P=0.89), positive surgical margins (P=0.67) and rate of significant upgrading (P=0.12). LogPCA model showed no distinction between the two cohorts; and Pearson's correlation values turned to be between -0.5 and +0.5. In Arm B, the lesion diameter <10 mm is the only predictive variable of positive SB only for PCa (P=0.04), with an additional value +3% for PCa DR., Conclusions: In biopsy naïve patients, FB alone is not inferior to FB+SB in detecting csPCa (Δ csPCa DR 0.4%). Δ 7.3% in overall PCa DR was registered between the two Arms, however the addition of further standard samples homolaterally to mp-MRI index lesion improved the overall PCa DR of FB only sampling (Δ PCa DR 3%). The omission of SB did not influence the post-surgical outcomes in terms of NS approach, PSMr and upgrading/downgrading.

Purpose: To assess the use of the new Focal-One ® HIFU platform in salvage setting to evaluate the occurrence of postoperative complications., Methods: Patients who underwent salvage HIFU (sHIFU) with Focal-One ® platform were enrolled prospectively (Candiolo cancer institute-FPO IRCCS; registry number: 258/2018). Perioperative and postoperative outcomes (in terms of oncological and functional ones) were recorded during the first year of follow-up. In particular postoperative complications were classified according to Clavien-Dindo system., Results: 20 patients were enrolled. No grade 3 complications were recorded. Referring to grade 2 complications, eight patients reported urgency after 3 months of follow-up, and in 4 cases, a low urinary tract infection occurred. Evaluating the impact of sHIFU on patients' sexual potency, micturition and quality of life, no significant deterioration was recorded during the follow-up as proven using the ANOVA analysis for repeated measurements. Only two patient had a biochemical failure after 12 months of follow-up., Conclusions: The real-time intraoperative guidance with Focal-One ® platform, allows a continuous monitoring and tailoring of the treatment, with a minimization of the adverse events even in a salvage setting., (© 2021. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Age estimation in children is fundamental in both clinical and forensic fields. The aim of this study was to evaluate the accuracy of the Cameriere’s European and Italian formulae for age estimation in Sardinian children and adolescents, a genetically isolated population. A sample of 202 orthopantomograms of healthy Sardinian children and adolescents (100 females and 102 males) aged between 6 and 17 years was retrospectively evaluated. The seven left mandibular teeth were assessed with the Cameriere’s European and Italian formulae. The teeth with closed apex (N0) were counted and, in the teeth with open apex, the distance between the inner sides was calculated. All variables showed a significant and negative correlation with age except N0 and g. Sex (g), the variables s, N0, and the first-order interaction between them, contributed substantially to the age measurement (p < 0.001). Although the value of x5 had a low prediction level, it generated the following multiple linear regression formula, specific for the Sardinian sample: Age = 10.372 + 0.469 g + 0.810 N0 − 1.079 s − 0.398 s ∙ N0 − 0.326 × 5. Only the Sardinian and European formulae allowed to obtain an acceptable interclass agreement (both the lower and upper >0.7). The results showed that the European formula could be accurate for assessing age in this sample of children and adolescents.

Background: In current precision prostate cancer (PCa) surgery era the identification of the best patients candidate for prostate biopsy still remains an open issue. The aim of this study was to evaluate if the prostate target biopsy (TB) outcomes could be predicted by using artificial intelligence approach based on a set of clinical pre-biopsy., Methods: Pre-biopsy characteristics in terms of PSA, PSA density, digital rectal examination (DRE), previous prostate biopsies, number of suspicious lesions at mp-MRI, lesion volume, lesion location, and Pi-Rads score were extracted from our prospectively maintained TB database from March 2014 to December 2019. Our approach is based on Fuzzy logic and associative rules mining, with the aim to predict TB outcomes., Results: A total of 1448 patients were included. Using the Frequent-Pattern growth algorithm we extracted 875 rules and used to build the fuzzy classifier. 963 subjects were classified whereas for the remaining 484 subjects were not classified since no rules matched with their input variables. Analyzing the classified subjects we obtained a specificity of 59.2% and sensitivity of 90.8% with a negative and the positive predictive values of 81.3% and 76.6%, respectively. In particular, focusing on ISUP ≥ 3 PCa, our model is able to correctly predict the biopsy outcomes in 98.1% of the cases., Conclusions: In this study we demonstrated that the possibility to look at several pre-biopsy variables simultaneously with artificial intelligence algorithms can improve the prediction of TB outcomes, outclassing the performance of PSA, its derivates and MRI alone., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The diagnostic accuracy of the I 3M to assess the legal age of 18 years has already been tested in several specific-population samples. The left lower third molar has been extensively used for discriminating between minors and adults. This research aimed to compare the usefulness of lower third molar maturity indexes, from both left and right side (I 3M L and I 3M R), in samples originating from four distinct continents in order to examine possible differences in their accuracy values. For this purpose, a sample of 10,181 orthopantomograms (OPGs), from Europe, Africa, Asia and America, was analysed and previously scored in other studies. The samples included healthy subjects with no systemic disorders with both third molars and clear depicted root apices. Wilcoxon Signed Rank test for left and right asymmetry did not show any significant differences. Data about sensitivity, specificity, predictive values, likelihood ratio and accuracy were pooled together and showed similar results for I 3M L and I 3M R, respectively. In addition, all these quantities were high when only the I 3M R was considered to discriminate between adults and minors. The present referable database was the first to pool third molar measurements using panoramic radiographs of subjects coming from different continents. The results highlighted that both I 3M L and I 3M R are reliable indicators for assessing the legal age of 18 years old in those jurisdictions where this legal threshold has been set as the age of majority., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: Benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) is diagnosed in up to 80% of men during their lifetime. Several novel ultra-minimally invasive surgical treatments (uMISTs) for BPH/benign prostatic obstruction (BPO) have become available over the past 5 yr., Objective: To evaluate the perioperative and functional outcomes of recently introduced uMISTs for BPH/BPO, including Urolift, Rezūm, temporary implantable nitinol device, prostatic artery embolization (PAE), and intraprostatic injection., Evidence Acquisition: A systematic literature search was conducted in December 2020 using Medline (via PubMed), Embase (via Ovid), Scopus, and Web of Science (registered on PROSPERO as CRD42021225014). The search strategy used PICO criteria and article selection was conducted in accordance with the PRISMA guidelines. The risk of bias and the quality of the articles included were assessed. A dedicated data extraction form was used to collect the data of interest. Pooled and cumulative analyses were performed to compare perioperative and functional outcomes between study groups. A random-effects model using the DerSimonian and Laird method was used to evaluate heterogeneity. Stata version 15.0 software was used for all statistical analyses., Evidence Synthesis: The initial electronic search identified 3978 papers, of which 48 ultimately met the inclusion criteria and were included in the analysis. Pooled analysis revealed a uMIST benefit in terms of International Prostate Symptom Score (IPSS; -9.81 points, 95% confidence interval [CI] -11.37 to -8.25 at 1 mo; -13.13 points, 95% CI -14.98 to -11.64 at 12 mo), maximum flow rate (from +3.66 ml/s, 95% CI 2.8-4.5 to +4.14 ml/s, 95% CI 0.72-7.56 at 12 mo), and postvoid residual volume (-10.10 ml, 95% CI -27.90 to 7.71 at 12 mo). No negative impact was observed on scores for the International Index of Erectile Function-5, Male Sexual Health Questionnaire-Ejaculatory Dysfunction bother and function scales (overall postintervention change in pooled median score of 1.88, 95% CI 1.34-2.42 at the start of follow-up; and 1.04, 95% CI 0.28-1.8 after 1 yr), or the IPSS-Quality of Life questionnaire., Conclusions: Novel uMISTs can yield fast and effective relief of LUTS without affecting patient quality of life. Only Rezūm, UroLift, and PAE had a minimal impact on patients' sexual function with respect to baseline, especially regarding preservation of ejaculation., Patient Summary: We reviewed outcomes for recently introduced ultra-minimally invasive surgical treatments for patients with lower urinary tract symptoms caused by benign prostate enlargement or obstruction. The evidence suggests that these novel techniques are beneficial in terms of controlling symptoms while preserving sexual function., Take Home Message: Novel ultra-minimally invasive treatments can yield fast and effective relief of lower urinary tract symptoms without affecting a patient's quality of life., (© 2021 The Author(s).)

Estimation of age of majority has important applications in the forensic daily practice because of the increasing demand for age estimates of unaccompanied minors. Diagnostic accuracy of I 3M to assess legal adult age of 18 years has been already tested in several specific population samples. The aim of this work was to compare the available data about sensitivity and specificity of the third molar maturity index (I 3M ) from five different regional groups' radiographic samples to study possible ethnical difference. For this purpose, a sample of 6157 orthopantomograms (OPGs), coming from 15 countries, was analysed. Data about sensitivity and specificity were pooled using a bivariate modelling approach. The one-way MANOVA analysis was applied to assess the likelihood that sensitivity and specificity of the five regional groups are sampled from the same population. The result of the one-way MANOVA showed that both sensitivity and specificity did not depend from the regional groups. The obtained sensitivity was 84% (95% CI: 82% and 85%), and its specificity was 94% (95% CI: 93% and 95%). Based on these results, the I 3M was a useful statistical tool to identify whether a subject has reached the legal age of 18 years old, regardless of his or her ethnicity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Bayesian approach is being a fundamental tool in forensic and legal field where inferences and decisions are made. In this study, a full Bayesian calibration model was developed to make probabilistic inferences about age estimation in a reference sample of 891 periapical X-rays of upper and lower canines. These teeth belonged to both deceased and living adult subjects, aged between 20 and 86 years, coming from five different countries (Turkey, Italy, Portugal, Japan and Mexico). For this purpose, the narrowing of pulp chamber due to the apposition of secondary dentine was analysed by means of the pulp/tooth area ratio. To determine the agreement of the method, intra- and inter-observer differences for measuring process were calculated by means of the intraclass correlation coefficient (ICC) analysis. Observer error tests showed excellent agreement between observers and between repeated assessments. According to the results of the ANCOVA, neither nationality nor sex was associated to the secondary dentine apposition while it is associated with individual's age. The results of the present study indicated that the concept of probability is intrinsically linked to the assessment of age in a forensic context, and the Bayesian approach could be considered a robust tool to overtake the bias generated by traditional regression models, thus helping the decision-making process in a legal framework.

Background: The serum prostate-specific antigen is the most widespread biomarker for prostate disease. Its low specificity for prostatic malignancies is a matter of concern and the reason why new biomarkers for screening purposes are needed. The correlation between altered production of the main steroids and prostate carcinoma (PCa) occurrence is historically known. The purpose of this study is to evaluate the modifications of a comprehensive urinary endogenous steroidal profile (USP) induced by PCa, by multivariate statistical methods., Methods: A total of 283 Italian subjects were included in the study, 139 controls and 144 PCa-affected patients. The USP, including 17 steroids and five urinary steroidal ratios, was quantitatively evaluated using gas chromatography coupled with single quadrupole mass spectrometry (GC-MS). The data were interpreted using a chemometric, multivariate approach (intrinsically more sensible to alterations with respect to traditional statistics) and a model for the discrimination of cancer-affected profiles was built., Results: Two multivariate classification models were calculated, the former including three steroids with the highest statistical significance (e.g. testosterone, etiocholanolone and 7β-OH-DHEA) and PSA values, the latter considering the three steroids' levels only. Both models yielded high sensitivity and specificity scores near to 70%, resulting significantly higher than PSA alone., Conclusions: Three USP steroids resulted significantly altered in our PCa population. These preliminary results, combined with the simplicity and low-cost of the analysis, open to further investigation of the potential role of this restricted USP in PCa diagnosis.

Background: The aim of this study is to evaluate if multiparametric magnetic resonance (mpMRI)-transrectal ultrasound (TRUS) fusion targeted biopsy (TBx) versus untargeted standard biopsy (SBx) may decrease the rate of pathological upgrading of Gleason Score (GS) 3+4 prostate cancer (PCa) at radical prostatectomy (RP). We also evaluated the impact of percent pattern 4 and cribriform glands at biopsy in the risk of GS 3+4=7 upgrading., Methods: A total of 301 patients with GS 3+4 PCa on biopsy (159 SBx and 142 TBx) who underwent laparoscopic robot-assisted RP were sequentially enrolled. Histological data from RP sections were used as reference standard. The concordance of biopsy with pathological GS, as well as the GS 3+4 upgrading at RP were evaluated in different univariate and multivariate binary logistic regression models, testing age, PSA, fPSA%, tumor volume, PI-RADS, clinical stage, percentage of Gleason pattern 4 (GP) and/or presence of cribriform sub-type at biopsy., Results: Of the 301 biopsies, the median of GP 4 was 16% of the tissue. Minimal GP 4 (≤16%) cancers had a significant lower median volume (1.7 mL) than those with GP4 >16% (2.9 mL), (P<0.001). Pathological GS 3+4 was confirmed for 58.8% and 82.2% for SBx and TBx patients, respectively. The rate of upgraded and downgraded GS on SBx versus TBx was 38.8% vis. 16.7% and 1.8% and 2.1%, respectively. The rate of upgrading was significantly associated with the presence of GP4 >16% versus ≤16% (OR 4.4, 95% CI 1.4-12.0; P=0.021) and with the presence of cribriform sub-type at biopsy specimens (OR 6.2, 95% CI 2.2-18.7; P<0.001)., Conclusions: We demonstrated that TBx technique significantly reduced the risk of GS 3+4 upgrading at RP, compared to SBx one. The rate of upgrading was significantly associated with GP4>16%, mostly when cribriform sub-type was present at biopsy specimens.

The Palatal Rugae are considered a useful human identification marker for both orthodontists and forensic personnel. The principal aim of the present study was to evaluate the stability of palatal rugae with a 3D-3D superimposition procedure following Slow Maxillary Expansion (SME), in order to assess whether they kept their uniqueness and validity for human identification, even after a specific dental treatment. For this purpose, a sample of 27 digital dental models - belonging to growing patients (13 males and 14 females), aged between 8.5 and 15 years, who underwent SME therapy - was retrospectively studied and compared with a control group of 27 untreated subjects - (13 males and 14 females). Digital dental models were obtained pre-treatment and at device removal; both were processed by means of an intraoral scanner. A superimposition procedure was thus performed to reach the minimum point-to-point distance between two models of palatal rugae. Intra- and inter-observer differences were statistically analyzed by paired Wilcoxon test and Intra-class Correlation coefficient (ICC), showing values larger than 0.93. There was no difference in Root-Mean-Square (RMS) values between untreated control subjects and subjects treated with Leaf Expander (p = 0.062). A RMS value of 0.43 was the threshold to distinguish the pooled group ("Untreated" and "Leaf") from any mismatch. According to the obtained results, this study failed to reject the null hypothesis and presented no differences between the RMS values of the Test group and the RMS values of the untreated control group. This work highlighted the usefulness of 3D superimposition procedure for purposes of human identification, in subjects undergoing dental treatment. However, keeping in sight the forensic use of this technique as a helpful probation element in court, further studies should be performed to confirm these findings.

This work aims to assess the validity of the cut-off value (0.08) of the third molar maturity index (I 3M ) for discriminating minors from adults in Sardinian population. A sample of 336 digital panoramic radiographs of healthy Sardinian children and young minors (165 females and 171 males), aged between 15 and 23 years (mean age, 19.35 years in females and 18.80 years in males), was retrospectively evaluated. The left lower third molars were analysed by applying a specific cut-off value of 0.08 determined by Cameriere et al. in 2008. The reliability and reproducibility of the test was also studied: the intra-class correlation coefficients (ICC) were 0.91 (95% CI, 0.89-0.93) and 0.88 (95% CI, 0.86-0.90), for the intra- and inter-observer reliability, respectively. The I 3M gradually decreased as the real age gradually increased in both sexes. According to the pooled results of the diagnostic test, the accuracy (ACC) was 0.86 (95% CI, 0.82-0.89); the proportion of correctly classified subjects (Se = sensitivity) was 0.82 (95% CI: 0.76-0.86); and specificity (Sp = specificity) was 0.95 (95% CI, 0.89-0.97). The positive predictive values (PPV) and the negative predictive values (NPVs) were 0.97 (95% CI, 0.94-0.99) and 0.70 (95% CI, 0.62-0.77). The LR+ and the LR- were 17.12 (95% CI, 7.27 to 40.36) and 0.19 (95% CI, 0.14 to 0.25). In spite of this, significant differences in the early mineralisation of the third molar were found between sexes as well as in the results of the diagnostic test, showing a better sensitivity in males than in females. The results showed that, although the third molar teeth are highly variable in development, and with differences between females and males as compare to other teeth, the I 3M is a reliable method to distinguish between minors and adults even in such a genetic isolate population.

Aim: To evaluate the accuracy of multiparametric magnetic resonance-transrectal ultrasound fusion targeted biopsy (TBx) in the characterization of the index tumor, as confirmed by association with radical prostatectomy (RP) specimens., Patients and Methods: A total of 152 patients with TBx-confirmed prostate cancer (PCa) underwent robot-assisted RP. Stained whole-mount histological sections were used as the reference standard. All lesions with a volume >0.5 ml and/or pathological Gleason score (GS) >6 were defined as clinically significant PCa. The index lesion was defined as the largest tumor focus within the prostate gland., Results: The pathological index tumours included: 147 lesions (96.7%) with a volume >0.5 ml and five (3.3%) with a volume ≤0.5 ml, but with a pathological GS ≥7; 135 (88.8%) were located in the peripheral zone. TBx accuracy in the detection of the correct site of the index lesion by reference standard was 82.2%. Sensitivity, specificity, positive and negative predictive value were: 82.3%, 50.4%, 82.8% and 49.7%, respectively. The primary/secondary Gleason grade and GS of the 152 index tumors were properly estimated in 130 (85.5%), 115 (75.6%) and 127 (83.6%) cases, respectively. The concordance of TBx with pathological GS was 83.6%. The rate of up-grading and down-grading of TBx Gleason sum was 12.2% and 4.2%, respectively., Conclusion: TBx has a high sensitivity for characterization of index lesions, with a good concordance for topographic and Gleason grading accuracy between biopsy and surgical specimens., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The Briganti updated nomogram (BN) is the most popular predictive model aiming to predict the presence of lymph node invasion (LNI) in patients with prostate cancer (PCa), but it lacks information obtained by preoperative imaging. The primary aim of the study was to evaluate the role of multiparametric prostate magnetic resonance imaging (mp-MRI) in the indication to perform pelvic lymph nodes dissection (PLND) or not in patients with risk of LNI according to BN below 5%., Methods: Since March 2012 and September 2016, 310 patients who underwent a preoperative mp-MRI for staging purpose and subsequent robot-assisted extended PLND (RAEPLND) were retrospectively evaluated. Mp-MRIs were prospectively analyzed by two experienced radiologists. The imaging parameters analyzed were the presence of extracapsular extension (ECE), seminal vesicles invasion (SVI) and predominant Gleason pattern 4 (pG4). All patients underwent RAEPLND by two experienced surgeons with a standardized technique. A dedicated uropathologist performed all pathological analysis. Univariate analysis and multivariate logistic regression analysis were used in order to identify the predictors of LNI in patients with PCa., Results: In the overall population, 57 (18.4%) patients had histologically proven pN1 disease. 48/250 patients (19.2%) with a risk of LNI ≥5% as calculated by the BN were staged pN1 at final histopathological analysis. 9/60 patients (15.0%) with a risk of LNI <5% as calculated by BN, who underwent RAEPLND anyway according to the findings at mp-MRI, were staged pN1 at final histopathological analysis. At multivariate logistic regression analysis, all the three mp-MRI parameters were significant independent predictors of LNI after RAEPLND., Conclusions: The role of mp-MRI seemed to be crucial in patients with a risk of LNI <5% as calculated by the BN. The presence of ECE, SVI, or pG4 at mp-MRI was found to be an independent predictor of LNI by itself.

This study provides regression equations for estimation of age of infants from the dimensions of their developing deciduous teeth. The sample comprises 97 individuals of known sex and age (62 boys, 35 girls), aged between 2 days and 1,081 days. The age-estimation equations were obtained for the sexes combined, as well as for each sex separately, thus including "sex" as an independent variable. The values of the correlations and determination coefficients obtained for each regression equation indicate good fits for most of the equations obtained. The "sex" factor was statistically significant when included as an independent variable in seven of the regression equations. However, the "sex" factor provided an advantage for age estimation in only three of the equations, compared to those that did not include "sex" as a factor. These data suggest that the ages of infants can be accurately estimated from measurements of their developing deciduous teeth., (© 2017 American Academy of Forensic Sciences.)

Background: The literature is lacking randomised controlled trials comparing robot-assisted (RARP) and laparoscopic (LRP) radical prostatectomy, especially for follow-up >1 yr., Objective: To report 5-yr outcomes for our previously published prospective randomised study comparing RARP and LRP., Design, Setting, and Participants: From January 2010 to January 2011, 120 patients with organ-confined prostate cancer were enrolled and randomly assigned to RARP or LRP., Intervention: A single surgeon performed all interventions using the same transperitoneal anterograde technique., Outcome Measurements and Statistical Analysis: Continence, potency, and serum prostate-specific antigen were assessed postoperatively at 1, 3, 6, and 12 mo, and then every 6 mo until 60 mo. At the end of the follow-up period, patients were administered questions 1 and 46 of the Expanded Prostate Cancer Index Composite questionnaire to assess their satisfaction with the intervention and general health status. A generalised estimating equations model was used to compare time series data for functional results, and Kaplan-Meier and Cox models were used to analyse oncologic outcomes., Results and Limitations: The probability of achieving continence (odds ratio [OR] 2.47, p<0.021) and potency (OR 2.35, p<0.028) over time was more than doubled for the RARP compared to the LRP group. There was no difference between the two approaches in terms of patient survival. Pathologic Gleason score, positive surgical margins, and pT stage were associated with significantly higher biochemical recurrence in Cox multivariate models. Patient satisfaction with the intervention and their general health status was significantly higher in the RARP group., Conclusions: Throughout the 5-yr follow-up, RARP yielded better functional results compared to LRP, without compromising oncologic outcomes., Patient Summary: In this report we looked at 5-yr outcomes for a study comparing robot-assisted radical prostatectomy (RARP) and laparascopic radical prostatectomy for the treatment of prostate cancer. We found that continence and potency are better among patients treated with RARP, while oncologic results are comparable., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Analysis of the frontal sinus is an important tool in personal identification. Cone beam-computed tomography (CBCT) is also progressively replacing conventional radiography and multi-slice computed tomography (MSCT) in human identification. The aim of this study is to develop a reproducible technique and measurements from 3D reconstructions obtained with CBCT, for use in human identification. CBCT from 150 patients (91 female, 59 male), aged between 15 and 78 years, was analysed with the specific software program MIMICS 11.11 (Materialise N.V., Leuven, Belgium). Corresponding 3D volumes were generated and maximal dimensions along 3 directions (x, y, z), X M, Y M, Z M (in mm), total volume area (in mm(3)), V t, and total surface (in mm(2)), S t, were calculated. Correlation analysis showed that sinus surfaces were strongly correlated with their volume (r = 0.976). Frontal sinuses were separate in 21 subjects (14 %), fused in 67 (44.6 %) and found on only one side (unilateral) in 9 (6 %). A Prominent Middle of Fused Sinus (PMS) was found in 53 subjects (35.3 %). The intra- (0.963-0.999) and inter-observer variability (0.973-0.999) showed a great agreement and a substantial homogeneity of evaluation.

Objective: Extended pelvic lymph nodes dissection (EPLND) allows the removal of a higher number of lymph nodes than limited PLND. The aims of this study were to describe our robot-assisted EPLND (RAEPLND) technique with related complications, and to report the number of lymph nodes removed and the rate of lymph nodal metastasis., Materials and Methods: 153 patients underwent RAEPLND prior to robot-assisted radical prostatectomy (RARP). Indications were defined according to Briganti nomogram, to predict risk of lymph-nodal metastasis. Lymphatic packages covering the distal tract of the common iliac artery, the medial portion of the external iliac artery, the external iliac vein and the internal iliac vessels, together with the obturator and the presacral lymphatic packages were removed on both sides., Results: Median preoperative PSA was 7.5 ng/mL (IQR 5.5-11.5). Median operative time was 150 min (135-170). Median RAEPLND alone operative time was 38 min (32.75-41.25); for right and left side, 18 (15-29) and 20 min (15.75-30) (p=0.567). Median number of lymph nodes retrieved per patient was 25 (19.25-30); 13 (11-16) and 11 (8-15) for right and left side. In 19 patients (12.41%) metastasis was found at the level of pelvic lymph nodes. Median number of positive lymph nodes was 1 (1-4.6) per patient. Complications occurred in 11 patients (7.3%)., Conclusions: the number of lymph nodes removed was comparable to published data about open series, allowing the increase of detection rate of lymph nodal metastasis for minimally invasive approach without compromising complications' rate if performing the procedure following reported technique.

Background: To evaluate pathological patterns of prostate biopsy in men with changes in risk class by prostate cancer gene 3 (PCA3) score and with elevated serum prostate-specific antigen (PSA) or positive digital rectal examination (DRE), undergoing a repeat biopsy., Patients and Methods: A total of 108 males of two Italian Institutions who had undergone at least two PCA3 score assessments with changed PCA3 risk class were selected. Comparison of PCA3 score in patients with negative re-biopsy [normal parenchyma, benign prostatic hyperplasia (BPH), chronic prostatitis, high-grade prostate intraepithelial neoplasia (HG-PIN), atypical small acinar prostate (ASAP)] or positive re-biopsy was performed., Results: The up- and down-grading rates for PCA3 score were 71.3% (n=77) and 28.7% (n=31), respectively. Among the 77 up-graded patients, the median change in PCA3 score was 24 (range=4-69), while among the 31 down-graded ones, the median change was 17 (2 to 55). The PCA3 score in 24 out of 29 (82.7%) patients with prostate cancer (PCa) was up-graded. No association was found for correlation of PCA3 score change with age >65 years (p=0.975), family history of prostate cancer (p=0.796), positive DRE (p=0.179), use of 5-alpha-reductase inhibitors (p=0.793) and BPH/prostatitis/HG-PIN/ASAP diagnosis (p=0.428)., Conclusion: PCA3 score can be considered a marker that is stable over time in most cases; notably, up to 20% of patients have a clinically relevant change of risk class. The rate of PCa was higher in patients whose PCA3 score was up-graded, even if no robust cut-off for PCA3 score fluctuation was identified., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE)., Patients and Methods: in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals)., Results: The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97)., Conclusion: The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The methodology used to identify individuals in forensic anthropology requires a minimum degree of precision and accuracy and should be based on identified and representative samples. Achievement of these objectives in infant skeletons is hampered by the scarcity of appropriate samples. The dental age estimation methods of Liversidge et al. (Am J Phys Anthropol 90: 307-313, 1993) and Deutsch et al. (Growth 49: 207-17, 1985) were applied to the Granada osteological collection of identified infants (Granada, Spain) in order to evaluate its applicability in a Mediterranean population. Significant differences were found between the estimated and real ages in both cases. Based on the measurements obtained in 140 fetuses and infants, new regression formulas were developed to estimate age from the metric study on deciduous teeth. Independent functions are provided for each deciduous maxillary and mandibular tooth in each sex, along with the margin of error (95% confidence interval). These formulas appear to offer one of the best methods available for estimating the age of Mediterranean infants in forensic anthropology settings.

Aim: To evaluate the relationship between Prostate cancer gene 3 (PCA3) score and prostate cancer as assessed by Gleason Score (GS) and pathological stage in a series of Italian patients, with elevated Prostate specific antigen (PSA) undergoing radical prostatectomy (RP)., Patients and Methods: A total of 222 patients underwent RP for clinically localized prostate cancer; total PSA, free-PSA (%fPSA) and PCA3 score were collected and the possible associations among PCA3 and histological grade/pathological stage at biopsy and RP were investigated., Results: Median PCA3 scores by GS at radical prostatectomy were 51 vs. 67 (GS <7 vs. GS ≥ 7, p=0.007), while scores at the biopsy were 56 vs. 67 (GS <7 vs. GS ≥ 7, p=0.007), and in pT2 vs. pT3 patients they were 54 vs. 80 (p=0.001). Positive digital rectal examination (DRE) (odds ratio (OR)=5.47, p=0.026), pT3 pathological stage (OR=3.68, p=0.006) and PCA3 ≥ 35 (OR=2.04, p=0.030) were the main risk factors for the presence of an aggressive disease (GS ≥ 7 at RP)., Conclusion: PCA3 score could play an interesting role in predicting significant disease: positive DRE (OR=5.47, p=0.026), pT3 pathological stage (OR=3.68, p=0.006) and PCA3 ≥ 35 (OR=2.04, p=0.030) were the main independent risk factors for GS ≥ 7 at RP.

Objective: To determine an optimal prostate cancer gene 3 (PCA3) cutoff in predicting prostate cancer in Italian patients undergoing first or repeat biopsy., Study Design: In this observational multicenter study 1246 men with elevated prostate specific antigen (PSA) and negative digital rectal examination, with prostate biopsy after PCA3 assessment, were divided into two groups submitted to PCA3 testing before or after previous negative biopsies. Ideal PCA3 cutoff was identified using area under the curve of the receiver operating characteristic analysis. Various cutoff values were used to determine the best predictive score. Univariate and multivariate logistic regression models compared age, PSA, free-PSA, and PCA3 score to predict prostate cancer., Results: PCA3 cutoff 39-50 had the highest accuracy in the repeat biopsy group in which cutoff of 39 could have avoided 51.9% negative repeat biopsies, eventually missing 7.8% of cancers (all low risk); cutoff of 50 would have prevented 56.5% of negative repeat biopsies, missing 29 tumors (10.3%), 5 potentially aggressive. The PCA3 test performed poorly in the first biopsy group., Conclusion: We confirm the usefulness of PCA3 in Italian men with a previous negative biopsy. We achieved the best performance at a cutoff of 39. PCA3 did not perform better than PSA in non-biopsy-selected men.

Background: Preclinical studies have highlighted the activity of lenalidomide in mantle cell lymphoma and its anti-proliferative synergy with dexamethasone., Design and Methods: In this prospective, multicenter, phase II study, patients with relapsed/refractory mantle cell lymphoma who were not eligible for, or had relapsed after, intensive treatments received lenalidomide 25 mg/day (days 1-21 of each 28-day cycle) and dexamethasone (40 mg/day on days 1, 8, 15, and 22) for up to 12 months., Results: The primary end-points, overall and complete response rates, were achieved by 17 of 33 (52%; 95% confidence interval [CI], 35-68%) and 8 of 33 patients (24%; 95% CI, 13-41%), respectively, by the end of treatment. Fifteen patients (45%) discontinued treatment prematurely, 13 due to lack of response. The median progression-free and overall survival were 12 months (95% CI, 5-19 months) and 20 months (95% CI, 12 months to not estimable), respectively. Treatment resulted in a significant increase in microvessel density (P=0.033) and non-significant increases in macrophage and natural killer cell counts, while serum levels of neoangiogenic factors did not change significantly. Grade 3/4 adverse events were neutropenia (53%), leukopenia (25%), thrombocytopenia (22%), infections (12%), and febrile neutropenia (12%)., Conclusions: These results confirm a favorable safety and activity profile of lenalidomide in relapsed/refractory mantle cell lymphoma. The contribution of dexamethasone in achieving these results is unclear because of its possible detrimental effect on the immune activation generated by lenalidomide and a higher risk of developing infectious complications. (clinicaltrials.gov identifier: NCT00786851).

The disease management is the collection of the processes aimed to control the health care and improving the quality at same time reducing the overall cost of the procedures. Our system, Health-Mining, is a Decision Support System with the objective of controlling the adequacy of hospitalization and therapies, determining the effective use of standard guidelines and eventually identifying better ones emerged from the medical practice (Evidence Based Medicine). In realizing the system, we have the aim of creation of a path to admissions- appropriateness criteria construction, valid at an international level. A main goal of the project is rule extraction and the identification of the rules adequate in term of efficacy, quality and cost reduction, especially in the view of fast changing technologies and medicines. We tested Health-Mining in a real test case for an Italian Region, Regione Veneto, on the installation of pacemaker and ICD.

An integrated information flexible system is proposed in this paper for indoor medical applications. The system is intended to provide clinicians with a portable device enabling to discover and recognize patients and easily access their electronic record in a fast and secure way for consultation or updating. Moreover the developed solution allows communication with medical equipments for wireless monitoring of patients biosignals. Requirements for such a system are therefore high flexibility and mobility, as well as fast and secure wireless communication. These features were achieved combining the use of Bluetooth technology with a Personal Digital Assistant, which was provided with a multilayer software architecture to allow easy access to Hospital database and to communicate with external medical devices. A prototype was also realized and the testing phase has indicated good performances on both patient discovery and wireless monitoring.