OBJECTIVES:Early-onset prostate cancer is becoming increasingly prevalent, and MRI-first strategies are gaining interest as a potential screening tool. However, MRI characteristics of the prostate in younger men remain underexplored. This study aimed to characterize prostate MRI features in a young, asymptomatic male cohort undergoing contrast-free biparametric MRI for prostate cancer screening, to determine the detection rate of clinically significant prostate cancer, and to identify clinical and imaging predictors of clinically significant disease. METHODS:A total of 659 prostate MRIs were acquired; after excluding men who declined biopsy, 641 participants formed the final cohort. Peripheral-zone signal patterns on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps were assessed by two blinded radiologists. PI-RADS scores were assigned independently. Men with PI-RADS ≥ 4 were offered targeted MRI-TRUS fusion biopsy (PI-RADS 3 in case of PSAD ≥ 0.16). Multivariable logistic regression was performed to identify independent predictors of csPCa. RESULTS:Median PSA 1.02 ng/mL (IQR 0.58-2.03) and PSA density (PSAD) 0.03 ng/mL/mL (IQR 0.02-0.05). The most common peripheral-zone appearance was heterogeneous T2 hypointensity (74.7%), homogeneous DWI hyperintensity (59.4%), and homogeneous ADC hypointensity (66.1%). PI-RADS distribution was: 0.5% PI-RADS 1, 81.1% PI-RADS 2, 14.2% PI-RADS 3, 3.6% PI-RADS 4, and 0.6% PI-RADS 5. Forty-one men (6.4%) underwent biopsy, yielding 5 ciPCa, 23 csPCa, and 13 negative results, corresponding to csPCa in 3.6% of the entire cohort. In multivariable analysis, PSAD ≥ 0.15 ng/mL/mL, PI-RADS 4-5, and family history were independently associated with csPCa (all p < 0.01). CONCLUSIONS:Contrast-free bpMRI effectively characterizes prostate morphology in younger men and identifies csPCa at an early stage. PSAD, PI-RADS category, and family history significantly enhance risk stratification, supporting the integration of bpMRI-based approaches into future MRI-first screening strategies for younger, asymptomatic populations.

The journal retracts the article titled "Neutral Sphingomyelinase Modulation in the Protective/Preventive Role of rMnSOD from Radiation-Induced Damage in the Brain" [...].

Sarcopenia has already been widely investigated as a potential indicator of negative outcomes in oncology patients. Our aim was to evaluate the potential predictive role of sarcopenia assessed using an Artificial Intelligence-powered software in response to neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). In this single-centre retrospective study, we enrolled patients diagnosed with non-metastatic MIBC who underwent NAC and had available pre-treatment mpMRI of the bladder and baseline CT scan. The follow-up MRI assessment was performed using the NacVI-RADS algorithm to evaluate response to systematic therapy. AI-based software automatically calculated the skeletal muscle index (SMI) from CT images at the L3 vertebral level. Multivariate logistic regression analysis was performed to assess independent predictors of response to NAC, and a receiver operating characteristic (ROC) analysis was subsequently conducted to provide an additional level of statistical validation. Fifty-five patients were included (mean age: 67.2 years). Sarcopenia was identified in 36.4

Multiparametric MRI of the bladder is highly accurate in the detection and local staging of bladder cancer. The Vesical Imaging Reporting and Data System (VI-RADS) scoring system has improved the diagnostic accuracy, reproducibility, and interpretability of bladder MRI in the assessment of the invasion of the muscularis propria. There are several technical details concerning bladder MRI that need to be strictly applied to obtain the highest possible diagnostic potential from the MRI. In addition, image evaluation, accurate interpretation, and reporting need to be standardized to optimize diagnostic accuracy and interreader agreement. This review describes the patient population for bladder MRI and discusses, with a practical approach, the correct acquisition protocol for optimal image quality using VI-RADS with reporting tips, pitfalls, and challenges for its clinical application. This review also discusses the latest evidence, clinical implications, current controversies, and future challenges, including gaps in knowledge, of the VI-RADS scoring system.

BACKGROUND AND OBJECTIVE:Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) has limited accuracy, and it is linked to overdiagnosis. The PROSA trial aimed to evaluate whether a contrast-free biparametric magnetic resonance imaging (bpMRI)-first screening strategy improves the detection of clinically significant PCa (csPCa) as the primary outcome. The secondary outcomes included overall PCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective. METHODS:This single-center, randomized controlled trial enrolled 816 asymptomatic men aged 49-69 yr (≥40 yr with a PCa family history). Participants were randomized into two arms: arm A underwent bpMRI regardless of the PSA levels; arm B received bpMRI only if PSA ≥3 ng/ml (or 2.5 ng/ml with a family history). Men with Prostate Imaging Reporting and Data System score ≥3 were directed to a targeted biopsy. Imaging and pathology assessors were blinded; csPCa is defined as International Society of Urological Pathology grade group ≥2. The primary outcomes included csPCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective. KEY FINDINGS AND LIMITATIONS:Among 759 randomized men, biopsy and csPCa detection rates were higher in arm A (10.8% and 4.6%, respectively) than in arm B (5.2% and 1.8%, respectively), with a relative risk of 2.6 (95% confidence interval 1.1-6.1; p = 0.05) for the csPCa detection rate. Benefit-harm metrics favored the MRI-first strategy, showing higher grade selectivity (1.89 vs 1.75), biopsy efficiency (0.74 vs 0.54), and biopsy avoidance (23.1 vs 11.9). No serious adverse event was recorded. The MRI-first strategy yielded an incremental cost-effectiveness ratio of €2201.75 per csPCa case detected. Limitations include single-round design and short follow-up. CONCLUSIONS AND CLINICAL IMPLICATIONS:In this randomized screening trial, a contrast-free MRI-first pathway improved csPCa detection, enhanced benefit-harm metrics, and showed favorable cost effectiveness.

BACKGROUND:Radical prostatectomy (RP) is recommended in case of localized or locally advanced prostate cancer (PCa), but it can lead to side effects, including urinary incontinence (UI) and erectile dysfunction (ED). Magnetic resonance imaging (MRI) is recommended for PCa diagnosis and staging, but it can also improve preoperative risk-stratification. PURPOSE:This nonsystematic review aims to provide an overview on factors involved in RP side effects, highlighting anatomical and pathological aspects that could be included in a structured report. EVIDENCE SYNTHESIS:Considering UI evaluation, MR can investigate membranous urethra length (MUL), prostate volume, the urethral sphincter complex, and the presence of prostate median lobe. Longer MUL measurement based on MRI is linked to a higher likelihood of achieving continence restoration. For ED assessment, MRI and diffusion tensor imaging identify the neurovascular bundle and they can aid in surgery planning. Finally, MRI can precisely describe extra-prostatic extension, prostate apex characteristics and lymph-node involvement, providing valuable preoperative information for PCa treatment. CONCLUSIONS:Anatomical principals structures involved in RP side effects can be assessed with MR. A standardized MR report detailing these structures could assist urologists in planning optimal and tailored surgical techniques, reducing complications, and improving patients' care.

The primary aim was to determine the performance of neoadjuvant chemotherapy VI-RADS (nacVI-RADS) in predicting response to systemic therapy in patients with MIBC and to evaluate its inter-reader agreement. Prospective study, including patients with non-metastatic muscle-invasive bladder cancer (MIBC) who underwent neoadjuvant chemotherapy before radical cystectomy (RC). Patients underwent pre- and post-treatment MRI. Radiological response was evaluated by two experienced radiologists using nacVI-RADS scoring system. Reference standard was defined using histopathological findings. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were calculated to assess nacVI-RADS performance for each reader. Inter-reader agreement was determined with Cohen’s k statistics. Fifty-five patients with non-metastatic MIBC, 46 males (84

Purpose: The aim of the study was to determine the impact of using a semi-automatic commercially available AIassisted software (Quantib (R) Prostate) on inter-reader agreement in PI-RADS scoring at different PI-QUAL ratings and grades of reader confidence and on reporting times among novice readers in multiparametric prostate MRI. Methods: A prospective observational study, with a final cohort of 200 patients undergoing mpMRI scans, was performed at our institution. An expert fellowship-trained urogenital radiologist interpreted all 200 scans based on PI-RADS v2.1. The scans were divided into four equal batches of 50 patients. Four independent readers evaluated each batch with and without the use of AI-assisted software, blinded to expert and individual reports. Dedicated training sessions were held before and after each batch. Image quality rated according to PI-QUAL and reporting times were recorded. Readers' confidence was also evaluated. A final evaluation of the first batch was conducted at the end of the study to assess for any changes in performance. Results: The overall kappa coefficient differences in PI-RADS scoring agreement without and with Quantib (R) were 0.673 to 0.736 for Reader 1, 0.628 to 0.483 for Reader 2, 0.603 to 0.292 for Reader 3 and 0.586 to 0.613 for Reader 4. Using PI-RADS >= 4 as cut-off for biopsy, the AUCs with AI ranged from 0.799 (95 % CI: 0.743, 0.856) to 0.820 (95 % CI: 0.765, 0.874). Inter-reader agreements at different PI-QUAL scores were higher with the use of Quantib, particularly for readers 1 and 4, with Kappa coefficient values showing moderate to slight agreement. Conclusion: Quantib (R) Prostate could potentially be useful in improving inter-reader agreement among less experienced to completely novice readers if used as a supplement to PACS.

Background: Current cross-sectional imaging modalities exhibit heterogenous diagnostic performances for the detection of a lymph node invasion (LNI) in bladder cancer (BCa) patients. Recently, the Node-RADS score was introduced to provide a standardized comprehensive evaluation of LNI, based on a five-item Likert scale accounting for both size and configuration criteria. In the current study, we hypothesized that the Node-RADS score accurately predicts the LNI and tested its diagnostic performance. Methods: We retrospectively reviewed BCa patients treated with radical cystectomy (RC) and bilateral extended pelvic lymph node dissection, from January 2019 to June 2022. Patients receiving preoperative systemic chemotherapy were excluded. A logistic regression analysis tested the correlation between the Node-RADS score and LNI both at patient and lymph-node level. The ROC curves and the AUC depicted the overall diagnostic performance. In addition, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for different cut-off values (>1, >2, >3, >4). Results: Overall, data from 49 patients were collected. Node-RADS assigned on CT scans images, was found to independently predict the LNI after an adjusted multivariable regression analysis, both at the patient (OR 3.36, 95%CI 1.68–9.40, p = 0.004) and lymph node (OR 5.18, 95%CI 3.39–8.64, p < 0.001) levels. Node-RADS exhibited an AUC of 0.87 and 0.91 at the patient and lymph node levels, respectively. With increasing Node-RADS cut-off values, the specificity and PPV increased from 57.1 to 97.1% and from 48.3 to 83.3%, respectively. Conversely, the sensitivity and NPV decreased from 100 to 35.7% and from 100 to 79.1%, respectively. Similar trends were recorded at the lymph node level. Potentially, Node-RADS > 2 could be considered as the best cut-off value due to balanced values at both the patient (77.1 and 78.6%, respectively) and lymph node levels (82.4 and 93.4%, respectively). Conclusions: The current study lays the foundation for the introduction of Node-RADS for the regional lymph-node evaluation in BCa patients. Interestingly, the Node-RADS score exhibited a moderate-to-high overall accuracy for the identification of LNI, with the possibility of setting different cut-off values according to specific clinical scenarios. However, these results need to be validated on larger cohorts before drawing definitive conclusions.

Background: Sarcopenia is a well know prognostic factor in oncology, influencing patients’ quality of life and survival. We aimed to investigate the role of sarcopenia, assessed by a Computed Tomography (CT)-based artificial intelligence (AI)-powered-software, as a predictor of objective clinical benefit in advanced urothelial tumors and its correlations with oncological outcomes. Methods: We retrospectively searched patients with advanced urothelial tumors, treated with systemic platinum-based chemotherapy and an available total body CT, performed before and after therapy. An AI-powered software was applied to CT to obtain the Skeletal Muscle Index (SMI-L3), derived from the area of the psoas, long spine, and abdominal muscles, at the level of L3 on CT axial images. Logistic and Cox-regression modeling was implemented to explore the association of sarcopenic status and anthropometric features to the clinical benefit rate and survival endpoints. Results: 97 patients were included, 66 with bladder cancer and 31 with upper-tract urothelial carcinoma. Clinical benefit outcomes showed a linear positive association with all the observed body composition variables variations. The chances of not experiencing disease progression were positively associated with ∆_SMI-L3, ∆_psoas, and ∆_long spine muscle when they ranged from ~10–20% up to ~45–55%. Greater survival chances were matched by patients achieving a wider ∆_SMI-L3, ∆_abdominal and ∆_long spine muscle. Conclusions: A CT-based AI-powered software body composition and sarcopenia analysis provide prognostic assessments for objective clinical benefits and oncological outcomes.

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.

Circular RNAs (circRNAs) are a new class of “non-coding RNAs” that originate from non-sequential back-splicing of exons and/or introns of precursor messenger RNAs (pre-mRNAs). These molecules are generally produced at low levels in a cell-type-specific manner in mammalian tissues, but due to their circular conformation they are unaffected by the cell mRNA decay machinery. circRNAs can sponge multiple microRNAs or RNA-binding proteins and play a crucial role in the regulation of gene expression and protein translation. Many circRNAs have been shown to be aberrantly expressed in several cancer types, and to sustain specific oncogenic processes. Particularly, in virus-associated malignancies such as human papillomavirus (HPV)-associated anogenital carcinoma and oropharyngeal and oral cancers, circRNAs have been shown to be involved in tumorigenesis and cancer progression, as well as in drug resistance, and some are useful diagnostic and prognostic markers. HPV-derived circRNAs, encompassing the HPV E7 oncogene, have been shown to be expressed and to serve as transcript for synthesis of the E7 oncoprotein, thus reinforcing the virus oncogenic activity in HPV-associated cancers. In this review, we summarize research advances in the biogenesis of cell and viral circRNAs, their features and functions in the pathophysiology of HPV-associated tumors, and their importance as diagnostic, prognostic, and therapeutic targets in anogenital and oropharyngeal and oral cancers.

Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells.

Sphingomyelins (SMs) are a class of relevant bioactive molecules that act as key modulators of different cellular processes, such as growth arrest, exosome formation, and the inflammatory response influenced by many environmental conditions, leading to pyroptosis, a form of programmed cell death due to Caspase-1 involvement. To study liver pyroptosis and hepatic SM metabolism via both lysosomal acid SMase (aSMase) and endoplasmic reticulum/nucleus neutral SMase (nSMase) during the exposure of mice to radiation and to ascertain if this process can be modulated by protective molecules, we used an experimental design (previously used by us) to evaluate the effects of both ionizing radiation and a specific protective molecule (rMnSOD) in the brain in collaboration with the Joint Institute for Nuclear Research, Dubna (Russia). As shown by the Caspase-1 immunostaining of the liver sections, the radiation resulted in the loss of the normal cell structure alongside a progressive and dose-dependent increase of the labelling, treatment, and pretreatment with rMnSOD, which had a significant protective effect on the livers. SM metabolic analyses, performed on aSMase and nSMase gene expression, as well as protein content and activity, proved that rMnSOD was able to significantly reduce radiation-induced damage by playing both a protective role via aSMase and a preventive role via nSMase.

Gastric cancer (GC) is a complex disease linked to a series of environmental factors and unhealthy lifestyle habits, and especially to genetic alterations.GC represents the second leading cause of cancer-related deaths worldwide.Its onset is subtle, and the majority of patients are diagnosed once the cancer is already advanced.In recent years, there have been innovations in the management of advanced GC including the introduction of new classifications based on its molecular characteristics.Thanks to new technologies such as next-generation sequencing and microarray, the Cancer Genome Atlas and Asian Cancer Research Group classifications have also paved the way for precision medicine in GC, making it possible to integrate diagnostic and therapeutic methods.Among the objectives of the subdivision of GC into subtypes is to select patients in whom molecular targeted drugs can achieve the best results; many lines of research have been initiated to this end.After phase III clinical trials, trastuzumab, anti-Erb-B2 receptor tyrosine kinase 2 (commonly known as ERBB2) and ramucirumab, anti-vascular endothelial growth factor receptor 2 (commonly known as VEGFR2) monoclonal antibodies, were approved and introduced into first-and second-line therapies for patients with advanced/metastatic GC.However, the heterogeneity of this neoplasia makes the practical application of such approaches difficult.Unfortunately, scientific progress has not been matched by progress in clinical practice in terms of significant improvements in prognosis.Survival continues to be low in contrast to the reduction in deaths from many common cancers such as colorectal, lung, breast, and prostate cancers.Although several target molecules have been identified on which targeted drugs can act and novel products have been introduced into experimental therapeutic WJGO https://www.wjgnet.com

Gastric cancer（GC） is a complex disease linked to a series of environmental factors and unhealthy lifestyle habits, and especially to genetic alterations. GC represents the second leading cause of cancer-related deaths worldwide. Its onset is subtle, and the majority of patients are diagnosed once the cancer is already advanced. In recent years, there have been innovations in the management of advanced GC including the introduction of new classifications based on its molecular characteristics. Thanks to new technologies such as next-generation sequencing and microarray, the Cancer Genome Atlas and Asian Cancer Research Group classifications have also paved the way for precision medicine in GC, making it possible to integrate diagnostic and therapeutic methods. Among the objectives of the subdivision of GC into subtypes is to select patients in whom molecular targeted drugs can achieve the best results; many lines of research have been initiated to this end. After phase III clinical trials, trastuzumab, antiErb-B2 receptor tyrosine kinase 2（commonly known as ERBB2） and ramucirumab, anti-vascular endothelial growth factor receptor 2（commonly known as VEGFR2） monoclonal antibodies, were approved and introduced into first-and second-line therapies for patients with advanced/metastatic GC.However, the heterogeneity of this neoplasia makes the practical application of such approaches difficult. Unfortunately, scientific progress has not been matched by progress in clinical practice in terms of significant improvements in prognosis. Survival continues to be low in contrast to the reduction in deaths from many common cancers such as colorectal, lung, breast, and prostate cancers.Although several target molecules have been identified on which targeted drugs can act and novel products have been introduced into experimental therapeutic protocols, the overall approach to treating advanced stage GC has not substantially changed. Currently, surgical resection with adjuvant or neoadjuvant radiotherapy and chemotherapy are the most effective treatments for this disease.Future research should not underestimate the heterogeneity of GC when developing diagnostic and therapeutic strategies aimed toward improving patient survival.