Design of a magnetic resonance imaging-based screening program for early diagnosis of prostate cancer: preliminary results of a randomized controlled trial-Prostate Cancer Secondary Screening in Sapienza (PROSA).

OBJECTIVES: The main objective is to propose an MRI-based screening protocol, investigating the role of MRI without the injection of contrast media (bi-parametric MRI, bpMRI) as a secondary prevention test for prostate cancer (PCa) early diagnosis, comparing MRI with the prostate specific antigen (PSA) test. For this reason, preliminary results of Prostate Cancer Secondary Screening in Sapienza (PROSA) are presented, to investigate the efficiency of an MRI-based screening protocol. PROSA is a prospective, randomized, single-center study. To date, 351 men have been enrolled and blindly randomized into two different arms: (A) Men underwent a bpMRI regardless of their PSA values (175); (B) Men followed as per clinical practice: those with increased PSA (61) were referred to bpMRI, while those with normal PSA (112) were not. Men who screened positive on MRI were directed to MR-directed targeted biopsy. On arm A, 4 clinically significant PCa have been detected, while none was found on arm B (p = 0.046). To evaluate the efficiency of the screening protocol, we calculated the experimental event rate (EER, 3.6%), control event rate (CER, 1.2%.), absolute risk reduction (ARR, 2.5%), and number needed to treat (NNT, 40.3). PROSA represents an interesting experience in the field of imaging-based PCa screening. The preliminary data from this trial highlight the promising role of non-contrast MRI as a screening tool for early detection of PCa. Further data will finally validate the most appropriate screening program. CLINICAL RELEVANCE STATEMENT: PROSA depicts an interesting experience in the field of research focused on imaging-based prostate cancer screening. Its preliminary data highlight the promising role of non-contrast MRI as a screening tool for early detection of PCa. KEY POINTS: • Promotion of an MRI-based screening protocol, investigating the role of non-contrast MRI as a secondary prevention test for prostate cancer early diagnosis, comparing MRI with PSA test. • Prostate Cancer Secondary Screening in Sapienza (PROSA) represents an interesting experience in the field of research focused on imaging-based prostate cancer screening; its preliminary results indicate that it is possible to use non-contrast MRI as a screening tool for early detection of PCa. • This new approach to PCa screening could facilitate the early diagnosis of clinically significant prostate cancer while reducing the number of unnecessary prostate biopsies and the detection of clinically insignificant prostate cancer.

MR-Neurography of the facial nerve in parotid tumors: intra-parotid nerve visualization and surgical correlation.

PURPOSE: One of the most severe complications in surgery of parotid tumors is facial palsy. Imaging of the intra-parotid facial nerve is challenging due to small dimensions. Our aim was to assess, in patients with parotid tumors, the ability of high-resolution 3D double-echo steady-state sequence with water excitation (DE3D-WE) (1) to visualize the extracranial facial nerve and its tracts, (2) to evaluate their relationship to the parotid lesion and (3) to compare MRI and surgical findings. METHODS: A retrospective study was conducted including all patients with parotid tumors, who underwent MRI from April 2022 to December 2023. Two radiologists independently reviewed DE3D-WE images, assessing quality of visualization of the facial nerve bilaterally and localizing the nerve's divisions in relation to the tumor. MRI data were compared with surgical findings. RESULTS: Forty consecutive patients were included (M:F = 22:18; mean age 56.3 ± 17.4 years). DE3D-WE could excellently visualize the nerve main trunk and the temporofacial division in all cases. The cervicofacial branch was visible in 99% of cases and visibility was good. Distal divisions were displayed in 34% of cases with a higher visibility on the tumor side (p < 0.05). Interrater agreement was high (weighted kappa 0.94 ± 0.01 [95% CI 0.92-0.97]). Compared to surgery accuracy of MRI in localizing the nerve was 100% for the main trunk, 96% for the temporofacial and 89% for the cervicofacial branches. CONCLUSIONS: Facial nerve MR-neurography represents a reliable tool. DE3D-WE can play an important role in surgical planning of patients with parotid tumors, reducing the risk of nerve injury.

The learning curve in bladder MRI using VI-RADS assessment score during an interactive dedicated training program.

OBJECTIVE: The purpose of the study was to evaluate the effect of an interactive training program on the learning curve of radiology residents for bladder MRI interpretation using the VI-RADS score. METHODS: Three radiology residents with minimal experience in bladder MRI served as readers. They blindly evaluated 200 studies divided into 4 subsets of 50 cases over a 3-month period. After 2 months, the first subset was reassessed, resulting in a total of 250 evaluations. An interactive training program was provided and included educational lessons and case-based practice. The learning curve was constructed by plotting mean agreement as the ratio of correct evaluations per batch. Inter-reader agreement and diagnostic performance analysis were performed with kappa statistics and ROC analysis. RESULTS: As for the VI-RADS scoring agreement, the kappa differences between pre-training and post-training evaluation of the same group of cases were 0.555 to 0.852 for reader 1, 0.522 to 0.695 for reader 2, and 0.481 to 0.794 for reader 3. Using VI-RADS ≥ 3 as cut-off for muscle invasion, sensitivity ranged from 84 to 89% and specificity from 91 to 94%, while the AUCs from 0.89 (95% CI:0.84, 0.94) to 0.90 (95% CI:0.86, 0.95). Mean evaluation time decreased from 5.21 ± 1.12 to 3.52 ± 0.69 min in subsets 1 and 5. Mean grade of confidence improved from 3.31 ± 0.93 to 4.21 ± 0.69, in subsets 1 and 5. CONCLUSION: An interactive dedicated education program on bladder MRI and the VI-RADS score led to a significant increase in readers' diagnostic performance over time, with a general improvement observed after 100-150 cases. KEY POINTS: • After the first educational lesson and 100 cases were interpreted, the concordance on VI-RADS scoring between the residents and the experienced radiologist was significantly higher. • An increase in the grade of confidence was experienced after 100 cases. • We found a decrease in the evaluation time after 150 cases.

The use of MRI in urothelial carcinoma.

PURPOSE OF REVIEW: To conduct a nonsystematic review of the existing literature to investigate the role of Magnetic Resonance Imaging (MRI) in urothelial carcinomas (UCs). RECENT FINDINGS: Imaging is becoming progressively more crucial in local and distant staging of UCs, especially in cases of bladder cancer (BCa). The primary objective of imaging in patients with BCa is to detect lesions and distinguish T1 from T2 stages, since the treatment varies significantly. SUMMARY: The applicability of MRI in the management of UCs has been investigated, particularly focusing on the new evidence on multiparametric MRI (mpMRI) of the bladder and Vesical Imaging-Reporting And Data System score for the description of BCa and discussing the possible utility of MRI for upper tract urothelial carcinomas . Imaging modalities, in particular CT and MRI, are essential tools for the local and distant staging of UCs. MpMRI of the bladder and VI-RADS score accurately define the risk of muscle invasiveness, promoting tailored therapeutic planning. Moreover, mpMRI has also been included in patients' follow-up and in the assessment of response to systematic therapy. MRI utility and possible application in upper tract urothelial carcinomas cases are yet to be discovered.

Mortality in Italian veterans deployed in Bosnia-Herzegovina and Kosovo.

BACKGROUND AND AIMS: The possible increase of cancer risk in military personnel deployed in Balkans during and after the 1992-1999 wars, mainly related to the depleted uranium, was addressed by several studies on European veterans of those war theatres. This article reports on the results of the mortality study on the Italian cohort of Bosnia and Kosovo veterans (Balkan cohort). METHODS: Mortality rates for the Balkan cohort (71 144 persons) were compared with those of the Italian general population as well as to those of a comparable and unselected control cohort of not deployed military personnel (114 269 persons). Ascertainment of vital status during the period 1995-2008 of all the persons in the two cohorts has been carried out through deterministic record linkage with the national death records database, from information provided by the respective Armed Force General Staff, and through the civil registry offices of the veterans' residence or birth municipalities. RESULTS: The Balkan cohort experienced a mortality rates lower than both the general population (SMR = 0.56; 95% CI 0.51-0.62) and the control group (SMR = 0.88; 95% CI 0.79-0.97). Cancer mortality in the deployed cohort group was half of that from the general population mortality rates (SMR = 0.50; 95% CI 0.40-0.62) and slightly lower if compared with the control group cancer mortality rates (SMR = 0.95; 95% CI 0.77-1.18). CONCLUSION: Balkan veteran cohort did not show any increase in general mortality or in cancer mortality.

Seeing is Believing: State of the Art Imaging of Bladder Cancer.

Imaging plays an important role in bladder cancer (BCa) diagnostic work-up. Ultrasound achieves an intermediate sensitivity in detecting urinary tract alterations and is considered a suboptimal imaging technique in diagnosis of BCa. CT urography accurately detects BCa in patients presenting with hematuria Multiparametric MRI achieves a very high rate of BCa detection and helps with accurate staging of patients; however, this modality is still not widely supported by international guidelines. The main applications of MRI are local tumor staging and differentiation between non-muscle-invasive BCa and muscle-invasive BCa. These applications led to development of Vesical Imaging-Reporting and Data System (VI-RADS) scoring system. The VI-RADS scoring system was developed in the setting of post-resection of primary bladder tumor and instillation of intravesical Bacillus Calmette-Guerin therapy; however validation of this system in the post-treatment setting showed promising results. The high risk of BCa recurrence leads to its application in the assessment of response to therapy and for disease surveillance after treatment. MRI is rapidly becoming a leading imaging modality in BCa diagnostic workup, assessment of response to therapies and for longitudinal surveillance, and plays an important role in BCa surgical and radiation therapy treatment planning.

Predictive role of node-rads score in patients with prostate cancer candidates for radical prostatectomy with extended lymph node dissection: comparative analysis with validated nomograms.

BACKGROUND AND OBJECTIVES: The Reporting and Data System (RADS) have been used in the attempts to standardize the results of oncological scans in different scenarios, such as lymph nodes, adding configuration criteria to size determination. We analyze the predictive value of preoperative Node-RADS determination at imaging for pelvic lymph node (PLN) involvement in cases of prostate cancer (PC) considered for radical prostatectomy (RP) with extended lymph node dissection (eLND) and we compare it with validate predictive nomograms (MSKCC, Briganti and Gandaglia). METHODS: 150 patients with a histological diagnosis of PC (high risk or intermediate with an estimated risk for pN+ higher than 5% using the Briganti or 7% using the Gandaglia nomogram) submitted for RP with an ePLND from 2018 and 2021 were retrospectively examined. Node-RADS determination was performed in all cases using the preoperative magnetic resonance (MR), performed by a radiologist blinded for pathologic results and compared with the MSKCC, Briganti 2012, Gandaglia 2017 and Gandaglia 2019 nomograms. RESULTS: PLN involvement at final pathology (pN+) was found in 36/150 (24.0%) of cases and the mean percentage of positive LNs in pN+ cases was 15.90 ± 13.40. The mean number of PLNs removed at RP was similar (p = 0.188) between pN0 (23.9 ± 8.0) and pN+ (25.3 ± 8.0) cases. Considering a Node RADS 4-5 positive and a Node RADS 1-2 negative, the PPV was 100% and the NPV was 79.6%. A Node RADS score 4-5 showed a lower sensitivity (0.167 versus 0.972, 1.000, 0.971, 0.960 respectively), a higher specificity (1.000 versus 0.079, 0.096, 0.138, 0.186 respectively) and a similar AUC (0.583 versus 0.591, 0.581, 0.574, 0.597 respectively) when compared to MSKCC, Briganti 2012, Gandaglia 2017 and Gandaglia 2019 nomograms. CONCLUSIONS: Our evaluation suggests that Node RADS score, combining configuration criteria to size determination could improve specificity in terms of pathologic PLN prediction but a very low sensitivity has been also described.

A method to estimate mortality trends when death certificates are imprecisely coded: an application to cervical cancer in Italy.

Systematic analysis of mortality trends of cervix and corpus uteri cancers is difficult in Italy, as in many other countries, because of the poor specification of uterine cancer subsites in official death statistics. The aim of this article is to propose a method for the analysis of uterine cancers mortality based on high quality incidence and prevalence data from population-based cancer registries. The method assumes that the excess mortality of cancer patients, compared to death rates expected in the general population, is attributable to the specific cancer. The method is applied to estimate mortality trends for cancers of cervix, corpus and uterus as whole, during the period 1987-1999, in an area covered by 8 Italian cancer registries. Official mortality rates for the 2 subsites were about 60% lower than excess mortality rates, due to the very high proportion of deaths attributed to not specified subsite. Age adjusted cervical cancer excess mortality rates decreased from 3.7 to 2.7 x 100,000 women. Excess mortality for corpus uteri cancer remained approximately stable between 3 and 3.3 x 100,000 women in the period 1990-1999. The results support the efficacy of organized screening in reducing cervical cancer mortality. The same method can be used to assess mortality rates for every cancer entity identifiable in cancer registries data, not otherwise available from official death records.

Cluster analysis of mortality and malformations in the Provinces of Naples and Caserta (Campania Region).

The possible adverse health effects associated with the residence in the neighbourhood of toxic dump sites have been the object of many epidemiological studies in the last two decades;some of these reported increases of various health outcomes. The present study reports the cluster analysis of mortality and malformations at municipality level, standardized by socioeconomic deprivation index, in an area of the Campania Region characterized by a widespread illegal practice of dumping toxic and urban waste. Clusters have been observed with significant excess of mortality by lung, liver, gastric, kidney and bladder cancers and of prevalence of total malformations and malformations of limb, cardiovascular and urogenital system. The clusters are concentrated in a sub-area where most of the illegal practice of dumping toxic waste has taken place

[Review of epidemiological studies of cancer risk among Gulf War and Balkans veterans]. / Rassegna degli studi epidemiologici sul rischio di tumori tra i militari della Guerra del Golfo e delle missioni nei Balcani.

OBJECTIVE: Analysis of the available epidemiological evidence on cancer risk among Gulf war and Balkans veterans. DESIGN AND SETTING: Eligible for the review were all studies published in peer-reviewed journals indexed in MedLine by the end of 2007. The review includes twelve studies published between 1996 and 2006 All of them are retrospective cohort studies focused on different outcomes: mortality, hospitalizations or cancer incidence. The study populations are from US, UK, Sweden, Denmark and Italy. The description ofthe studies reviewed focusses on their main features (design, study population, health outcomes and ascertainment procedures, analytical methods). RESULTS: Results are summarized by cancer site: all cancers, neoplasms that may be a target of exposure to depleted uranium (lung cancer, leukemias, kidney cancer, bone cancer), and other neoplasms (lymphomas, brain cancer, and cancer of the testis) relatively frequent among young adults. The overall incidence of cancers is not increased in the cohort studies of Gulf war and Balkans veterans published to date, nor there is consistent evidence of excess risks of neoplasms possibly related to exposure to depleted uranium. However, in the Danish cohort of Balkans veterans an increased risk ofbone cancer has been observed, but the excess disappeared when a 1-year latency was considered. An increased brain cancer risk in relation to exposure to nerve-gas agents has been observed. Sporadic excesses of Hodgkin lymphoma and testicular cancer in deployed veterans have been reported. CONCLUSION: None of the studies reviewed could obiectively assess exposures to depleted uranium or to other potentially carcinogenic agents experienced in the theaters. The study cohorts are young and the follow-up periods are probably too short to capture excesses of long latency outcomes. The update of the follow-up of the cohorts and studies of other cohorts with a better assessment of exposure to depleted uranium and to other potentially relevant risk factors are warranted.

[Neonatal mortality in campania region: analysis of causes of death by current data]. / Mortalità neonatale in Campania: analisi delle cause di morte attraverso l'uso di dati correnti.

OBJECTIVE: to analyze neonatal mortality by cause using the P-Perinatal classification system of the Italian National Institute of Statistics (ISTAT). DESIGN: comparisons by birth cohort (1991-2001 vs 1981-1990). Estimates of the rate ratio (RR) and 95% confidence intervals (CI). The 56 ISTAT causes of perinatal death were regrouped into 7 categories. SETTING: the study was carried out in the Campania region, which has the largest number of births in southern Italy and high neonatal mortality. The analysis covered 1627641 live births and 12865 neonatal deaths. RESULTS: neonatal mortality declined significantly over time (RR= 0.58; 95% CI 0.56-0.60). The decrease was greater for early (first 6 days of lfe) (RR=0.54; 95% CI 0.51-0.56) than for late neonatal mortality (6th to 29th day of life) (RR=0.75; 95% CI 0.69-0.81). Rates declined for all causes, but RR were particularly low for prematurity (RR=0.24; 95% CI 0.22-0.28), pre-partum hypoxia (RR=0.28; 95% CI 0.22-0.35), intra-partum hypoxia (RR=0.42; 95% CI 0.38-0.47). More limited declines were observed for congenital anomalies (RR=-0.67; 95% CI 0.61-0.72) and for RDS (Respiratory Distress Syndrome) (RR=0.82; 95% CI 0.77-0.87). Declines inpre- and intra-partum hypoxia and for other causes were observed in both early and late neonatal mortality. Mortality due to congenital abnormalities declined more in the early neonatal period (RR=0.59; 95% CI 0.53-0.65) than in the late neonatal period (RR=0.86; 95% CI 0.75-0.99). RDS, which was the leading cause of death in both periods, was the only cause for which there was an increase in late neonatal mortality (RR= 1.21; 95% CI 1.05-1.40). CONCLUSION: Available current data allow to describe different determinants of neonatal mortality by causes of death. Currently, improvement of RDS care is necessary in order to reduce high neonatal mortality.

Cancer mortality in an area of Campania (Italy) characterized by multiple toxic dumping sites.

Several recent studies have documented that a widespread practice of dumping toxic wastes has taken place for many years in the Provinces of Naples and Caserta. Extensive programs of environmental monitoring are currently ongoing in the area. In this frame, the Department of Civil Defence of the Italian Government has appointed an ad hoc study group in order to assess the health status of the population resident in the area of interest. The first investigation performed by the study group has been a geographic study on cancer mortality and occurrence of malformations in 196 municipalities constituting the two Provinces. The study detected an area located in the southeastern part of the Province of Caserta and in the northwestern part of the Province of Naples, where cancer mortality and congenital malformations show significantly increased rates with respect to expected figures derived from the regional population. The area highlighted by the study is, in general terms, overlapping with the area where most illegal dumping of toxic wastes took place. It is now recommended that mortality studies be extended to take into account other health outcomes, to search for correlations with environmental exposures, and consider possible confounding factors.

Congenital heart disease in live-born children: incidence, distribution, and yearly changes in the Campania Region.

OBJECTIVES: Congenital heart disease (CHD), the most common cardiac malformation in the fetal and neonatal period, represents a heterogeneous group of defects with little known cause. The aim of this study was to investigate the incidence rate (IR) of CHD without spontaneous resolution in the first year of life, the age at diagnosis, the most common type of CHD, and the IR changes in severe and nonsevere CHD during the study period. METHODS: From January 1997 to December 2002, 4559 live births with CHD (diagnosed until December 2004) were enrolled in the Campania Region. Number of live-born children by month was derived from national registries. RESULTS: About 70% of CHD patients were diagnosed within the first year of life. The overall mean regional IR of CHD was 11.1 (confidence interval 10.8-11.4) patients per 1000 live-born children. The overall mean IR of CHD was significantly different in the five provinces of the Campania Region, but the annual IR remained stable in each of them throughout the study period. The relative risk in live-born children and residents in the areas with an elevated IR of CHD was higher for nonsevere CHD, but of low significance for severe CHD. At least one-third of CHD patients had atrial septal defects. CONCLUSIONS: We described the highest IR of CHD from one of the largest samples used up to now for this purpose (410 181 live-born children), but we think that this value could be higher (poor surveillance in some areas). Moreover, this study increases the awareness that CHD patients with a few symptoms are frequently underdiagnosed in areas with inadequate health services and that by an improved availability of pediatric echocardiographic assesments seem warranted. Eight years of surveillance and an increasing attention of both pediatricians and cardiologists to mild CHD in some provinces allowed us to demonstrate that, despite previous reports, the most common CHD in our region was atrial septal defect.

Familial recurrence of congenital heart disease in patients with ostium secundum atrial septal defect.

AIMS: Ostium secundum atrial septal defect (osASD) is one of the most common cardiac malformations. Few data are available on the familial recurrence of congenital heart disease (CHD), in particular, in a large group of patients with isolated osASD. The aim is to investigate the familial recurrence of CHD in up to third-degree relatives from a large sample of consecutively enrolled patients with osASD, taking into account the influence of degree of relatedness (as number of relatives). METHODS AND RESULTS: From January 1998 to December 2002, we enrolled 583 patients with osASD and 408 healthy subjects, referred to our tertiary centre. We hypothesized that a positive family history required at least one relative with CHD to constitute a risk factor. In this model of analysis, the null hypothesis is a similar familial history between cases and controls. Among 583 patients with osASD, 109 (19%) had at least one relative with CHD. Among the 408 healthy subjects studied, only 23 (6%) had a family history of CHD. A familial recurrence of CHD was demonstrated in 72 of 312 (23%) patients with isolated osASD and in 37 of 271 (13.6%) patients with non-isolated osASD. Familial recurrence of isolated osASD was demonstrated in 22 of 312 patients (7%) with an isolated osASD and only in six of 271 patients (2.2%) with non-isolated osASD. The familial recurrence risk of isolated osASD in patients with isolated osASD was higher in sibs, especially in sisters (33.3%). CONCLUSION: This study underscores the role of genetic factors in the determination of CHD, particularly osASD. Our results could represent the basis for further studies to calculate a 'value of family history' to adapt the familial recurrence to the real size of each family group. In this way, we could select families with a 'tendency' to develop CHD, particularly osASD. In these families, we could analyse the genetic pattern to establish abnormalities and the bases of CHD.