The prognostic role of next-generation imaging-driven upstaging in newly diagnosed prostate cancer patients.

PURPOSE: Phase III evidence showed that next-generation imaging (NGI), such as prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), provides higher diagnostic accuracy than bone scan and contrast-enhanced computed tomography (conventional imaging, CI) in the primary staging of intermediate-to-high-risk prostate cancer (PCa) patients. However, due to the lack of outcome data, the introduction of NGI in routine clinical practice is still debated. Analysing the oncological outcome of patients upstaged by NGI (though managed according to CI) might shed light on this issue, supporting the design of randomised trials comparing the effects of treatments delivered based on NGI vs. CI. METHODS: We prospectively enrolled a cohort of 100 biopsy-proven intermediate-to-high-risk PCa patients staged with CI and PSMA PET/CT (though managed according to the CI stage), to assess the frequency of the stage migration phenomenon. Stage migration was then assessed as biochemical recurrence-free survival (bRFS) predictor. RESULTS: Three patients were lost at follow-up after imaging. PSMA PET/CT upstaged 26.8% of patients compared to CI, while it downstaged 6.1% of patients. Notably, 50% of patients excluded from surgery due to the presence of bone metastases at CI would have been treated with radical-intent approaches if PSMA PET/CT had guided the treatment choice. After a median follow-up of 6 months of surgically treated patients, 22/83 (26.5%) had biochemical recurrence (BCR). PSMA PET/CT-driven upstaging determined a significant risk increase for BCR (HR:3.41, 95%CI:1.21-9.56, p = 0.019). Including stage migration in a univariable and multivariable model identified PSMA PET/CT-upstaging as an independent predictor of bRFS. CONCLUSIONS: In conclusion, implementing NGI for staging purposes improves the prediction of bRFS. Although phase III evidence is still needed, this advancement suggests that NGI may better identify patients who would benefit from local treatments than those who may achieve better oncological outcomes through systemic treatment.

Development and validation of a clinical decision support system based on PSA, microRNAs, and MRI for the detection of prostate cancer.

OBJECTIVES: The aims of this study are to develop and validate a clinical decision support system based on demographics, prostate-specific antigen (PSA), microRNA (miRNA), and MRI for the detection of prostate cancer (PCa) and clinical significant (cs) PCa, and to assess if this system performs better compared to MRI alone. METHODS: This retrospective, multicenter, observational study included 222 patients (mean age 66, range 46-75 years) who underwent prostate MRI, miRNA (let-7a-5p and miR-103a-3p) assessment, and biopsy. Monoparametric and multiparametric models including age, PSA, miRNA, and MRI outcome were trained on 65% of the data and then validated on the remaining 35% to predict both PCa (any Gleason grade [GG]) and csPCa (GG ≥ 2 vs GG = 1/negative). Accuracy, sensitivity, specificity, positive and negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated. RESULTS: MRI outcome was the best predictor in the monoparametric model for both detection of PCa, with sensitivity of 90% (95%CI 73-98%) and NPV of 93% (95%CI 82-98%), and for csPCa identification, with sensitivity of 91% (95%CI 72-99%) and NPV of 95% (95%CI 84-99%). Sensitivity and NPV of PSA + miRNA for the detection of csPCa were not statistically different from the other models including MRI alone. CONCLUSION: MRI stand-alone yielded the best prediction models for both PCa and csPCa detection in biopsy-naïve patients. The use of miRNAs let-7a-5p and miR-103a-3p did not improve classification performances compared to MRI stand-alone results. CLINICAL RELEVANCE STATEMENT: The use of miRNA (let-7a-5p and miR-103a-3p), PSA, and MRI in a clinical decision support system (CDSS) does not improve MRI stand-alone performance in the detection of PCa and csPCa. KEY POINTS: • Clinical decision support systems including MRI improve the detection of both prostate cancer and clinically significant prostate cancer with respect to PSA test and/or microRNA. • The use of miRNAs let-7a-5p and miR-103a-3p did not significantly improve MRI stand-alone performance. • Results of this study were in line with previous works on MRI and microRNA.

Third molar maturity index (I3M) assessment according to different geographical zones: a large multi-ethnic study sample.

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 (I3M) 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 (I3ML and I3MR) and the combination of both sides (I3ML_I3MR) 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 (I3ML; I3MR; I3ML_I3MR, 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 I3ML for male African people (91%) and the higher specificity (Sp) of all the parameters (I3ML; I3MR; I3ML_I3MR) 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.

Biomaterials for Regenerative Medicine in Italy: Brief State of the Art of the Principal Research Centers.

Regenerative medicine is the branch of medicine that effectively uses stem cell therapy and tissue engineering strategies to guide the healing or replacement of damaged tissues or organs. A crucial element is undoubtedly the biomaterial that guides biological events to restore tissue continuity. The polymers, natural or synthetic, find wide application thanks to their great adaptability. In fact, they can be used as principal components, coatings or vehicles to functionalize several biomaterials. There are many leading centers for the research and development of biomaterials in Italy. The aim of this review is to provide an overview of the current state of the art on polymer research for regenerative medicine purposes. The last five years of scientific production of the main Italian research centers has been screened to analyze the current advancement in tissue engineering in order to highlight inputs for the development of novel biomaterials and strategies.

Implementing telemedicine for the management of benign urologic conditions: a single centre experience in Italy.

PURPOSE: To assess the use of telemedicine with phone-call visits as a practical tool to follow-up with patients affected by urological benign diseases, whose clinic visits had been cancelled during the acute phase of the COVID-19 pandemic. METHODS: Patients were contacted via phone-call and a specific questionnaire was administered to evaluate the health status of these patients and to identify those who needed an "in-person" ambulatory visit due to the worsening of their condition. Secondarily, the patients' perception of a potential shift towards a "telemedicine" approach to the management of their condition and to indirectly evaluate their desire to return to "in-person" clinic visits. RESULTS: 607 were contacted by phone-call. 87.5% (531/607) of the cases showed stability of the symptoms so no clinic in-person or emergency visits were needed. 81.5% (495/607) of patients were more concerned about the risk of contagion than their urological condition. The median score for phone visit comprehensibility and ease of communication of exams was 5/5; whilst patients' perception of phone visits' usefulness was scored 4/5. 53% (322/607) of the interviewees didn't own the basic supports required to be able to perform a real telemedicine consult according to the required standards. CONCLUSION: Telemedicine approach limits the number of unnecessary accesses to medical facilities and represents an important tool for the limitation of the risk of transmission of infectious diseases, such as COVID-19. However, infrastructures, health workers and patients should reach out to a computerization process to allow a wider diffusion of more advanced forms of telemedicine, such as televisit.

Study of the ethnicity's influence on the third molar maturity index (I3M) for estimating age of majority in living juveniles and young adults.

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 I3M 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 (I3M) 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 I3M 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.

Assessment of bullet holes through the analysis of mushroom-shaped morphology in synthetic fibres: analysis of six cases.

Textiles damage analysis is a very valuable tool in forensic investigations. However, to date, very little research has been carried out to understand the impact of bullet causing damages to clothing. According to the review of the most recent scientific papers, the frictional heating and crushing action of a bullet passing through synthetic fibres cause a unique transformation in their ends called mushroom-shaped morphology. In this study, the textile remains of six individuals executed during the first decade of the Chilean military dictatorship period (1973-1990) were analysed. The purpose was to examine their clothing in order to describe the fibre defects in the bullet holes. The fibres were directly observed using two different models of stereomicroscopy (MZ16A and EZ4D, Leica Microsystem Ltd., Wetzlar, Germany) and through a combination of transmitted, oblique and co-axial illumination (with Leica DFC500 Digital Camera), at × 230 and at a resolution of up to 840 Lp/mm. The mushroom-shaped morphology, along with rupturing of yarns, fibrillation or splitting of fibres, was observed in the bullet holes. Although the mushroom-shaped is a useful pattern for bullet hole identification in synthetic fibres, further research needs to be performed for developing a sounder interpretational framework of this type of forensic evidence.

A full Bayesian calibration model for assessing age in adults by means of pulp/tooth area ratio in periapical radiography.

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.

Comparison of the third molar maturity index (I3M) between left and right lower third molars to assess the age of majority: a multi-ethnic study sample.

The diagnostic accuracy of the I3M 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 (I3ML and I3MR), 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 I3ML and I3MR, respectively. In addition, all these quantities were high when only the I3MR 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 I3ML and I3MR 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.

Total anatomical reconstruction during robot-assisted radical prostatectomy: focus on urinary continence recovery and related complications after 1000 procedures.

OBJECTIVES: To present the functional and oncological outcomes after ≥1 year of follow-up, following an experience of >1000 robot-assisted radical prostatectomies (RARPs) with our standardised total anatomical reconstruction (TAR) technique. To evaluate which factors influence postoperative continence recovery in order to obtain a nomogram to predict the risk of postoperative urinary incontinence (UI). PATIENTS AND METHODS: The enrolment phase began in June 2013 and ended in May 2017. Patients were prospectively included in the study with the following inclusion criteria: (i) localised prostate cancer (clinical stages cT1-3, cN0, cM0); (ii) indication for RP; and (iii) preoperative multiparametric prostate magnetic resonance imaging. All patients underwent RARP with the TAR technique done at the end of the demolitive phase. The continence rates were assessed at 24 h, and 1, 4, 12, 24 and 48 weeks after catheter removal. Patients were defined as continent if they answered 'zero pad' or 'one safety pad' per day. A logistic regression model was used to evaluate the potential impact of some pre- and intraoperative factors on postoperative urinary continence recovery. Model discrimination was assessed using an area under (AUC) the receiver operating characteristic (ROC) curve. A nomogram to predict the risk of postoperative UI after RARP with the TAR technique was generated based on the logistic model. RESULTS: In all, 1008 patients were enrolled in our study. At 24 h, and 1, 4, 12, 24 and 48 weeks after catheter removal, 621 (61.61%), 594 (58.93%), 803 (79.66%), 912 (90.48%), 950 (94.25%) and 956 (94.84%) patients were continent, respectively. In the logistic regression model, the variables analysed had a higher impact on continence recovery at 4 and 12 weeks. At 4 weeks, the postoperative odds of urinary continence recovery increased with the absence of diabetes [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.41-5.41] and D'Amico low vs high risk (OR 2.01, 95% CI 1.01-3.99). At 12 weeks, urinary continence increased with the absence of diabetes (OR 3.01, 95% CI 1.23-7.35), D'Amico low vs high risk (OR 4.04, 95% CI 1.56-10.47), and D'Amico intermediate vs high risk (OR 3.33, 95% CI 1.66-6.70). ROC curves were drawn and an AUC value of 61.9% (95% CI 57.49-66.36) at 4 weeks and 63.8% (95% CI 58.03-69.65) at 12 weeks were computed. Based on these parameters, two nomograms (at 4 and 12 weeks postoperatively) were generated. CONCLUSION: The TAR technique conferred excellent results in the early recovery of urinary continence. Two nomograms were created, to predict preoperatively the postoperative odds of urinary continence recovery at 4 and 12 weeks after RARP by integrating the presence of diabetes and D'Amico risk classification.

Use of chitosan membranes after nerve-sparing radical prostatectomy improves early recovery of sexual potency: results of a comparative study.

OBJECTIVES: To evaluate the 1-year efficacy of chitosan membrane (ChiMe) application on the neurovascular bundles (NVBs) after nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) in potency recovery rate. To compare the results with those of a contemporary cohort of patients who did not benefit from chitosan use. PATIENTS AND METHODS: Patients in the ChiMe group were enrolled at our institution from July 2015 to September 2016 in a preliminary phase II study. All of them underwent NS-RARP with ChiMe applied on the NVBs and were followed over time to complete a 1-year follow-up. The control group was composed of patients who underwent NS-RARP at our institution without the application of ChiMe from January 2015. The patients were further classified into two groups based on the amount of nerves spared: Group A, comprised patients who underwent a monolateral or bilateral full NS; Group B, comprised patients in which a full NS was not performed. The demographics, peri- and postoperative data, and complications were recorded and compared. Potency recovery was recorded for Group A vs Group B in both the ChiMe and the control groups. RESULTS: In all, 136 patients were enrolled in the ChiMe group and 334 patients in the control group. There were no differences between groups in terms of baseline variables. Based on the amount of nerves preserved, 183 patients were included in Group A and 287 in Group B. Odds ratios at different time points showed that the only two factors influencing potency recovery were the amount of nerves preserved (Group A vs Group B) and the application or not of ChiMe on the NVBs spared. Comparing the ChiMe vs control groups at different time points, we found a statistically significant improvement in the potency recovery rate in the ChiMe group at 1 month (36.76% vs 25.88%; P = 0.02) and 2 months (52.2% vs 39.22%; P = 0.01) after surgery, showing a favourable trend at every time point of the entire follow-up period, even if not significant after the second postoperative month. In Group A, the log-rank test showed a statistically significant difference between the ChiMe vs control groups (P = 0.02), in particular at 1 and 2 months after surgery (P = 0.02 and P = 0.01, respectively). CONCLUSION: The application of ChiMe on the NVBs resulted in a higher potency recovery rate at 1 and 2 months after a bilateral or monolateral full NS-RARP. A trend of a higher and shorter potency recovery rate showed it to be favourable to use ChiMe, even in the cohort of patients who did not undergo a full NS procedure.

Hydrocephalus of King Charles II of Spain, the Bewitched King.

King of the Spanish Habsburg dynasty and sovereign of the overseas Spanish Empire, Charles II of Spain, was physically disabled, disfigured, mentally retarded, and he proved impotent. He is known in history as El Hechizado (the Bewitched) because both him and the people believed that his mental and physical incapacity were due to a "witchcraft act." Although several authors speculated about different diseases, most of them genetic such as pituitary hormone deficiency, distal renal tubular acidosis, Klinefelter syndrome, fragile X syndrome, or male XX hermaphroditism, the hypothesis of hydrocephalus was not taken into account. We don't have clear elements to hypothesize a certain etiology of Charles II' hydrocephalus; however, we think the herpetic infection he suffered of after his birth should not be ignored.

3-Year follow-up of temporary implantable nitinol device implantation for the treatment of benign prostatic obstruction.

OBJECTIVES: To report 3-year follow-up results of the first implantations with a temporary implantable nitinol device (TIND® ; Medi-Tate Ltd., Or Akiva, Israel) for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 32 patients with LUTS were enrolled in this prospective study. The study was approved by the local Ethics Committee. Inclusion criteria were: age >50 years, International Prostate Symptom Score (IPSS) ≥10, peak urinary flow (Qmax ) <12 mL/s, and prostate volume <60 mL. The TIND was implanted within the bladder neck and the prostatic urethra under light sedation, and removed 5 days later in an outpatient setting. Demographics, perioperative results, complications (according to Clavien-Dindo classification), functional results, and quality of life (QoL) were evaluated. Follow-up assessments were made at 3 and 6 weeks, and 3, 6, 12, 24 and 36 months after the implantation. The Student's t-test, one-way analysis of variance and Kruskal-Wallis tests were used for statistical analyses. RESULTS: At baseline, the mean (standard deviation, sd) patient age was 69.4 (8.2) years, prostate volume was 29.5 (7.4) mL, and Qmax was 7.6 (2.2) mL/s. The median (interquartile range, IQR) IPSS was 19 (14-23) and the QoL score was 3 (3-4). All the implantations were successful, with a mean total operative time of 5.8 min. No intraoperative complications were recorded. The change from baseline in IPSS, QoL score and Qmax was significant at every follow-up time point. After 36 months of follow-up, a 41% rise in Qmax was achieved (mean 10.1 mL/s), the median (IQR) IPSS was 12 (6-24) and the IPSS QoL was 2 (1-4). Four early complications (12.5%) were recorded, including one case of urinary retention (3.1%), one case of transient incontinence due to device displacement (3.1%), and two cases of infection (6.2%). No further complications were recorded during the 36-month follow-up. CONCLUSIONS: The extended follow-up period corroborated our previous findings and suggests that TIND implantation is safe, effective and well-tolerated, for at least 36 months after treatment.

Is the third molar maturity index (I3M) useful for a genetic isolate population? Study of a Sardinian sample of children and young adults.

This work aims to assess the validity of the cut-off value (0.08) of the third molar maturity index (I3M) 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 I3M 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 I3M is a reliable method to distinguish between minors and adults even in such a genetic isolate population.

Multiparametric Magnetic Resonance/Ultrasound Fusion Prostate Biopsy: Number and Spatial Distribution of Cores for Better Index Tumor Detection and Characterization.

PURPOSE: We evaluated the minimum core number for better index tumor detection to determine the best core site as well as biopsy Gleason score heterogeneity in the same index lesion. The aim was to optimize the highest Gleason score detection. MATERIALS AND METHODS: A total of 327 patients with negative digital rectal examination underwent magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy for elevated/rising prostate specific antigen and/or 1 or more detectable lesions on multiparametric magnetic resonance imaging after a previous negative standard biopsy. Depending on the diameter of each index lesion (8 or less, or greater than 8 mm) 4 or 6 cores, respectively, were taken according to a well determined sequence. RESULTS: Of the patients 166 (50.7%) had prostate cancer, including 79 (47.6%) with an 8 mm or less index lesion and 87 (52.4%) with a greater than 8 mm index lesion. Of patients with an index tumor 8 mm or less 7 (8.9%) had 1, 31 (39.2%) had 2, 27 (34.2%) had 3 and 14 (17.7%) had 4 positive cores. Similarly, of patients with a lesion greater than 8 mm 8 (9.2%) had 1, 30 (34.5%) had 2, 13 (14.9%) had 3, 14 (16.1%) had 4, 12 (13.8%) had 5 and 10 (11.5%) had 6 positive cores. The major prevalence of positive cores was observed in the center of the target. Gleason score heterogeneity was found in 12.6% of those with an 8 mm or less target vs 26.4% with a target greater than 8 mm. In the center of the target there was a slight prevalence of Gleason pattern 4 or greater, or a lesser pattern. CONCLUSIONS: Approaching magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy with a single core might be inadequate. Rather, taking 2 cores in the center of the index lesion may provide more accurate cancer detection and optimize the chances of finding the highest Gleason pattern.

In-parallel comparative evaluation between multiparametric magnetic resonance imaging, prostate cancer antigen 3 and the prostate health index in predicting pathologically confirmed significant prostate cancer in men eligible for active surveillance.

OBJECTIVE: To assess the performance capabilities of multiparametric magnetic resonance imaging (mpMRI), the prostate health index (PHI) and prostate cancer antigen 3 (PCA3) in predicting the presence of pathologically confirmed significant prostate cancer (PCSPCa), according to the European Randomized Study of Screening Prostate Cancer definition, in a single cohort of patients who underwent radical prostatectomy (RP) but who were eligible for active surveillance (AS). MATERIALS AND METHODS: An observational retrospective study was performed in 120 patients with prostate cancer (PCa), treated with robot-assisted RP but eligible for AS according to Prostate Cancer Research International: Active Surveillance criteria. Blood and urine specimens were collected before initial prostate biopsy for PHI and PCA3 measurements, respectively. In addition, all patients underwent mpMRI, preoperatively and 6-8 weeks after biopsy, with a 1.5T scanner using a four-to-five-channel phase array coil combined with an endorectal coin. mpMRI images were assessed and diagrams showing the prostate sextants were used to designate regions of abnormality within the prostate. Prostate findings were assigned to one of five categories according to Prostate Imaging-Reporting and Data System guidelines (PI-RADS) and considered positive for PCa if final PI-RADS score was >3 and negative if ≤3. RESULTS: Pathologically confirmed reclassification was observed in 55 patients (45.8%). mpMRI showed good specificity and negative predictive value (0.61 and 0.73, respectively) for excluding PCSPCa compared with the PHI and PCA3. On multivariate analyses and after 1 000 bootstrapping resampling, the inclusion of both mpMRI and the PHI significantly increased the accuracy of the base model in predicting PCSPCa. For the prediction of PCSPCa, in particular, the base model had an area under the curve (AUC) of 0.71 which significantly increased by 4% with the addition of the PHI (AUC = 0.75; P < 0.01) and by 7% with the addition of mpMRI (AUC = 0.78; P < 0.01). Decision-curve analysis showed that the multivariable model with mpMRI had the highest net benefit. CONCLUSION: In a single cohort of patients who underwent RP but who were eligible for AS, mpMRI and, to a lesser extent, the PHI, had an important role in discriminating the presence of PCSPCa; both measures could therefore be useful in the selection and monitoring of patients undergoing AS.

High prostate cancer gene 3 (PCA3) scores are associated with elevated Prostate Imaging Reporting and Data System (PI-RADS) grade and biopsy Gleason score, at magnetic resonance imaging/ultrasonography fusion software-based targeted prostate biopsy after a previous negative standard biopsy.

OBJECTIVE: To determine the association among prostate cancer gene 3 (PCA3) score, Prostate Imaging Reporting and Data System (PI-RADS) grade and Gleason score, in a cohort of patients with elevated prostate-specific antigen (PSA), undergoing magnetic resonance imaging/ultrasonography fusion software-based targeted prostate biopsy (TBx) after a previous negative randomised 'standard' biopsy (SBx). PATIENTS AND METHODS: In all, 282 patients who underwent TBx after previous negative SBx and a PCA3 urine assay, were enrolled. The associations between PCA3 score/PI-RADS and PCA3 score/Gleason score were investigated by K-means clustering, a receiver operating characteristic analysis and binary logistic regression. RESULTS: The PCA3 score difference for the negative vs positive TBx cohorts was highly statistically significant. A 1-unit increase in the PCA3 score was associated to a 2.4% increased risk of having a positive TBx result. A PCA3 score of >80 and a PI-RADS grade of ≥4 were independent predictors of a positive TBx. The association between the PCA3 score and PI-RADS grade was statistically significant (the median PCA3 score for PI-RADS grade groups 3, 4, and 5 was 58, 104, and 146, respectively; P = 0.006). A similar pattern was detected for the relationship between the PCA3 score and Gleason score; an increasing PCA3 score was associated with a worsening Gleason score (median PCA3 score equal to 62, 105, 132, 153, 203, and 322 for Gleason Score 3+4, 4+3, 4+4, 4+5, 5+4, and 5+5, respectively; P < 0.001). CONCLUSION: TBx improved PCA3 score diagnostic and prognostic performance for prostate cancer. The PCA3 score was directly associated both with biopsy Gleason score and PI-RADS grade: notably, in the 'indeterminate' PI-RADS grade 3 subgroup.

Multiparametric magnetic resonance imaging and active surveillance: How to better select insignificant prostate cancer?

OBJECTIVES: To evaluate the role of multiparametric magnetic resonance imaging in improving the predictive accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria for active surveillance in prostate cancer. METHODS: A retrospective study was carried out with 126 prostate cancer patients treated with robot-assisted radical prostatectomy, but eligible for active surveillance according to the Prostate Cancer Research International: Active Surveillance criteria; 63 patients were also eligible according to the Epstein criteria. All patients underwent preoperative multiparametric magnetic resonance imaging, after at least 6 weeks from biopsy. The images from the multiparametric magnetic resonance imaging were assessed, and diagrams showing prostate sextants were used to designate regions of abnormalities within the prostate. Findings in the prostate were assigned to one of five categories according the Prostate Imaging-Reporting and Data System guidelines (v1.0), and considered positive for prostate cancer if the final Prostate Imaging-Reporting and Data System guidelines were >3 and negative if ≤3. Multivariate logistic regression analysis was carried out to evaluate the gain in accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria when added to multiparametric magnetic resonance imaging. Decision curve analysis was carried out to identify the net benefit of each model. RESULTS: The inclusion of multiparametric magnetic resonance imaging to the Epstein criteria and the Prostate Cancer Research International: Active Surveillance multivariate model significantly increased their accuracy in predicting pathologically-confirmed insignificant prostate cancer by 7% and 5%, respectively. At the decision curve analysis evaluation, the model including the Prostate Cancer Research International: Active Surveillance criteria and multiparametric magnetic resonance imaging improved the clinical risk prediction over the other models. CONCLUSIONS: The present findings suggest that multiparametric magnetic resonance imaging is able to increase the predictive accuracy of Prostate Cancer Research International: Active Surveillance and Epstein criteria to identify prostate cancer patients eligible for active surveillance.

Reliability of frontal sinus by cone beam-computed tomography (CBCT) for individual identification.

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.

Robot-Assisted Extended Pelvic Lymph Nodes Dissection for Prostate Cancer: Personal Surgical Technique and Outcomes.

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.