Search Results (222)

Objective: To evaluate the early oncological outcomes of patients treated with robot-assisted radical prostatectomy for prostate cancer with multiple PIRADS lesions at baseline mpMRI in a tertiary referral center. Methods: Data of consecutive patients undergoing robot-assisted radical prostatectomy between 2020 and 2022 at a high-volume tertiary referral center were prospectively collected. mpMRI data was evaluated by two expert uro-radiologists at our center. All patients received an MRI–ultrasound fusion biopsy. Results: Overall, 286 patients with multiple PIRADS lesions treated with robot-assisted radical prostatectomy at a tertiary referral center were included. Unilateral and bilateral nerve-sparing were achieved in 63 (22.3%) and 124 (43.1%) patients, respectively. Median age was 69 years (IQR: 64–72), while median Charlson Comorbidity Index was 3 (IQR: 2–4). The presence of two PIRADS lesions was found in the 81.8% of cases, while 18.2% presented with three or more. Bilateral lesions were observed in 67.4% of cases. The dominant lesion was PIRADS 4 in 57.3% and PIRADS 5 in 32.3% of cases, with a median diameter of 12 mm (IQR: 10–17). Pathological upstaging to pT3 occurred in 61% of patients. Overall, 9.8% of cases exhibited positive surgical margins (PSMs), most of them single and limited in extent. Postoperative major complications were recorded in 6.3% of patients. At a median follow-up of 18 months (IQR: 6–29), biochemical recurrence (BCR) occurred in 8% of patients. Patients with PIRADS 5 lesions experienced shorter BCR-free survival compared to those with PIRADS 3–4. On multivariable Cox regression, PIRADS 5 independently predicted biochemical recurrence (HR: 2.52; 95% CI: 1.10–5.80; p = 0.029), after adjustment for age, number of lesions, and nerve-sparing status, with the performance of nerve-sparing not associated with an increased risk of recurrence, including in patients with multifocal disease. Conclusions: Nerve-Sparing Robot-Assisted Radical Prostatectomy in patients with multiple PIRADS lesions achieves encouraging short-term oncologic outcomes, with biochemical recurrence-free survival exceeding 84% at 3 years, despite high rates of multifocality and pathological upstaging. Full article

Objective: This study aims to evaluate the additional diagnostic value of systematic (SBx) and perilesional biopsies (PBx) compared with targeted biopsy (TBx) in patients with mpMRI-detected PI-RADS 3-4–5 lesions. Methods: We performed a retrospective analysis of 208 men with PI-RADS ≥ 3 lesions who underwent mpMRI–ultrasound fusion biopsy at a single institution. Clinically significant prostate cancer (csPCa; ISUP ≥ 2) was identified in 155 patients (74.5%), who constituted the study cohort. All patients underwent a standardized biopsy protocol consisting of 3–5 TBx cores, 3 PBx cores sampled within a 10 mm radius of the index lesion, and 10 SBx cores using the KOELIS Trinity^® system. Detection rates of csPCa and ISUP grade upgrading were analyzed and stratified by PI-RADS category. Results: TBx csPCa detection rates increased progressively with PI-RADS score: 39% for PI-RADS 3, 50% for PI-RADS 4, and 60% for PI-RADS 5 lesions. PBx showed a 42.5% detection rate of csPCa in PI-RADS 3 and 58% and 85.3% of csPCa in PI-RADS 4 and 5 respectively, whereas SBx detected 34.5% of csPCa in PI-RADS 3, 46% of csPCa in PI-RADS 4, and 60.5% of csPCa in PI-RADS 5. Despite these detection rates, PBx and SBx rarely provided clinically meaningful upgrading over TBx findings. ISUP grade upgrading occurred in only 7.3% of PBx cases and 1.8% of SBx cases in PI-RADS 5 lesions, with similarly low upgrading rates observed in PI-RADS 3–4 lesions. Conclusions: In patients with high-grade lesions like PI-RADS 4–5, TBx alone identifies the vast majority of csPCa, while SBx and PBx contribute minimal additional diagnostic or grading benefit. These findings support biopsy de-escalation strategies in high-risk mpMRI settings to reduce unnecessary sampling and procedure-related morbidity. On the other hand, in the PI-RADS 3 subgroup, omitting non-targeted sampling (SBx and/or PBx) may lead to underdiagnosis of higher-grade tumors not captured by TBx alone, potentially resulting in substantial changes in therapeutic strategy and, consequently, patient prognosis. Full article

Introduction: Soft tissue sarcomas (STS) exhibit profound molecular heterogeneity. While recurrent gene fusions hold significant diagnostic and therapeutic value—guiding treatment selection and identifying novel molecular targets—our understanding of their broader clinical implications remains limited. Materials and Methods: We performed next-generation sequencing (NGS; FusionPlex Sarcoma v2, Archer™) and bioinformatic analysis (STAR v.2.7, Arriba) on formalin-fixed paraffin-embedded (FFPE) core needle biopsy specimens. The cohort consisted of patients enrolled in a phase II clinical trial (NCT03651375) who received preoperative chemoradiotherapy according to the UNRESARC protocol. Results: The analysed cohort comprised nine adult patients (median age 66 years; range 44–73) diagnosed with undifferentiated pleomorphic sarcoma (UPS; n = 3), malignant peripheral nerve sheath tumour (MPNST; n = 3), myxofibrosarcoma (MFS; n = 2), and leiomyosarcoma (LMS; n = 1), predominantly high-grade (G3; 5/9) and extremity-localised (6/9). Gene fusions were detected in one-third of patients (3/9), exclusively in G3 tumours. Specifically, we identified an SGSH-PRKCA fusion in MFS (thigh), a LINC01133-OGA fusion in MPNST (thorax), and a concurrent JAZF1-MYH7B (chr7:27995037 intronic-chr20:33563203 exon/splice-site, out-of-frame but preserving myosin domains) with a PRKCA-associated intergenic rearrangement (chr1, retaining C1/kinase domains) in UPS (upper back). Notably, the SGSH-PRKCA and JAZF1-MYH7B pairs have not been previously described in the literature for these STS subtypes. Fusion-positive (F1) cases showed stable radiological disease (RECIST 1.1 SD) and EORTC C/D pathological responses with 5–20% residual viable tumour, whereas fusion-negative (F0) cases showed a wider range of radiological and pathological outcomes, including partial response, progression, and stable disease. Conclusions: Our analysis suggests that broad genomic profiling may provide complementary molecular information in diagnostically challenging cases managed at specialised sarcoma centres, particularly when morphology and immunohistochemistry are insufficient. In the present series, however, the detected rearrangements did not alter systemic treatment, and the data do not support claims of prognostic, predictive, or therapeutic actionability. Full article

Introduction: Clinical staging based on digital rectal examination is imprecise, leading to pathological upstaging in patients with prostate cancer (PCa). Accurate preoperative assessment remains a challenge despite the use of multiparametric magnetic resonance imaging (mpMRI) and fusion-guided biopsy. This study aims to identify key predictors of upstaging in preoperative patients. Materials and Methods: A retrospective analysis of 924 patients who underwent radical prostatectomy between July 2012 and January 2025 was performed. Variables included prostate-specific antigen, prostate volume, biopsy type, MRI, body mass index and age. Upstaging was defined as ≥pT3 in patients staged clinically as cT1–2. Optimal cut-offs for continuous variables were defined statistically. Multivariable logistic regression was applied to identify independent predictors of upstaging and minor staging upgrading (MSU)—defined as any upward shift in the pathological T stage relative to the clinical T stage. Model performance was evaluated using the area under the Receiver Operating Characteristic (ROC) curve (AUC). Results: Upstaging occurred in 31.9% and MSU in 50.6% of patients. The mean age was 65 years. Cut-off values for PSA density (PSAD) were 0.29 for upstaging and 0.28 for MSU. In the full-cohort model (AUC = 0.628), PSAD (odds ratio (OR) = 2.55), age (OR = 1.04), and hypertension (HT) (OR = 1.47) were associated with upstaging. In PIRADS-based models, PIRADS 5 and PSAD predicted both upstaging (OR = 1.62 and 6.10, respectively; AUC = 0.664) and MSU (OR = 1.75 and 4.67, respectively; AUC = 0.659). MSU was also associated with HT and a lack of fusion biopsy (AUC = 0.622). Conclusions: PSAD and PIRADS 5 lesions are strong determinants of pathological upstaging and MSU in PCa. These factors should be considered in preoperative risk stratification to improve staging accuracy. Despite advances in imaging and biopsy techniques, upstaging remains a common phenomenon, underlining the need for further refinement of diagnostic protocols. Full article

Extracellular vesicles (EVs) are promising biomarkers for liquid biopsy, but their clinical application is limited by intrinsic heterogeneity and the lack of methods capable of resolving functionally distinct EV subpopulations at the single-vesicle level. Conventional bulk analyses obscure rare but clinically relevant EV subsets, while most single-EV approaches focus on physical properties or surface markers, with limited access to intravesicular functional information. Here, we report a fusion-enabled EV detection strategy at the single-particle level for functional profiling of macrophage-derived EVs. Liposomal probes encapsulating L-arginine, NADPH, and a nitric oxide (NO)-responsive fluorescent dye are engineered to fuse with EV membranes, delivering substrates into the vesicle lumen. In macrophage-derived EVs, inducible nitric oxide synthase (iNOS) catalyzes NO production, activating the fluorescent probe and generating a localized signal within individual vesicles. Signal generation is confined to vesicle-restricted reactions, ensuring specificity and minimizing background. The formation of hybrid vesicles further facilitates optical detection using conventional fluorescence microscopy. Full article

Breast cancer remains the most frequently diagnosed malignancy in women worldwide, accounting for approximately 2.3 million new cases and 670,000 deaths annually. The diagnostic landscape has undergone a paradigm shift over the past two decades, evolving from morphology-based classification toward molecularly informed, precision-guided strategies. Early and accurate diagnosis is fundamental to improving outcomes; advances in imaging technology, including digital breast tomosynthesis (DBT), contrast-enhanced mammography (CEM), and abbreviated magnetic resonance imaging (MRI), have improved sensitivity and specificity in diverse patient populations. Simultaneously, the integration of artificial intelligence (AI) and radiomics into screening workflows offers unprecedented potential for risk stratification and a reduction in false-positives. At the pathological level, multi-gene expression profiling assays such as Oncotype DX, MammaPrint, Prosigna, and EndoPredict have refined prognostic classification and guide adjuvant chemotherapy decisions in early-stage hormone receptor-positive disease. The emergence of liquid biopsy, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal biomarkers provides minimally invasive tools for real-time monitoring of response, residual disease, and the evolution of resistance mechanisms. Precision diagnostics now encompass next-generation sequencing (NGS)-based comprehensive genomic profiling, enabling identification of actionable alterations such as PIK3CA mutations, HER2 amplification, BRCA1/2 pathogenic variants, and NTRK fusions, each linked to approved therapeutic agents. The purpose of this review is to provide a comprehensive synthesis of current and emerging diagnostic modalities in breast cancer—from population-level screening to individualized molecular profiling—and to examine how integrative, multimodal diagnostic platforms are reshaping clinical decision-making in the era of precision medicine. Full article

Background/Objectives: An accurate preoperative assessment of prostate cancer malignancy is crucial for risk stratification and selection of the optimal treatment strategy. This study assessed the concordance of Gleason scores between MRI–TRUS fusion biopsy and radical prostatectomy specimens, and identified clinical and histopathological factors associated with post-procedural Gleason score upgrading. Methods: This retrospective analysis involved patients who underwent transperineal MRI–TRUS fusion biopsy followed by radical prostatectomy from 2020 to 2025. Concordance, upgrading, and downgrading of the Gleason score were assessed by comparing biopsy results with the final histopathological examination. Clinical parameters (age, PSA level, prostate volume, and PSA density) and histopathological features of biopsies (Gleason score and percentage of prostate lobes affected by cancer) were analyzed. Multivariate logistic regression models were stratified by PSA level (<10 ng/mL and >10 ng/mL). Results: Gleason score concordance was found in 53.1% of the 603 patients analyzed, upgrading in 29.9%, and downgrading in 17.1%. Higher Gleason scores on biopsy were independently associated with a lower risk of upgrading in the entire cohort and in both PSA subgroups. Larger tumor extent on biopsy was associated with a lower risk of upgrading, with heterogeneous dependencies between prostate lobes. The other clinical parameters showed no independent association with upgrading. Conclusions: Gleason score upgrading remains common after radical prostatectomy. The risk of this progression is primarily related to the histopathological features of the biopsy rather than to baseline clinical parameters, reflecting the limitations of biopsy as a sampling method and the biological heterogeneity of prostate cancer. Full article

Background: Transperineal magnetic resonance (MRI)/ultrasound (US) fusion-guided prostate biopsy has emerged as a promising alternative to the transrectal approach by improving lesion targeting and reducing infectious complications. However, real-world data addressing factors that influence the detection of clinically significant prostate cancer (csPCa), including imaging characteristics and procedural experience, remain limited. Objective: To evaluate the diagnostic performance, safety profile, and independent predictors of csPCa detection in patients who underwent transperineal MR/US fusion-guided prostate biopsy, with particular emphasis on PIRADS category, prostate-specific antigen (PSA) level, and procedural learning curve. Methods: In this study, patient data were prospectively recorded in a routinely maintained institutional database, while the present analysis was conducted retrospectively. A total of 136 patients with clinical suspicion of prostate cancer—defined as elevated prostate-specific antigen (PSA), abnormal digital rectal examination, or PIRADS ≥3 on multiparametric MRI—underwent transperineal MR/US fusion-guided biopsy between January 2023 and October 2024. Results: Prostate cancer was detected in 45.5% of patients, whereas csPCa was identified in 32.3%. The PIRADS category emerged as the strongest independent predictor of csPCa detection, with PIRADS-5 lesions showing a significantly greater likelihood of csPCa than PIRADS-3 lesions (OR 6.70, p = 0.006). The PSA level was also independently associated with csPCa detection (OR 1.06 per ng/mL increase, p = 0.033). Although csPCa detection rates increased across learning curve groups, procedural experience was not an independent predictor after adjustment. The procedure demonstrated a favorable safety profile, with a low rate of infectious and noninfectious complications despite minimal use of antibiotic prophylaxis. The multivariable model showed moderate explanatory power and acceptable overall classification accuracy. Conclusions: Transperineal MR/US fusion-guided prostate biopsy provides reliable detection of clinically significant prostate cancer with a low complication rate and consistent performance across different stages of institutional experience. The PIRADS category and PSA level remain key determinants of csPCa detection, supporting the integration of MRI-based risk stratification into contemporary prostate cancer diagnostic methods. Full article

Background and Clinical Significance: Plexiform fibromyxoma (PFM) is a rare benign gastric mesenchymal neoplasm characterized by multinodular plexiform growth of bland spindle cells in a myxoid or fibromyxoid stroma. We report a case of the cellular form of PFM with limited myxoid stroma and aberrant KIT expression, resulting in diagnostic difficulty by biopsy. Case Presentation: A 59-year-old woman presented with a slowly enlarging 15 mm gastric antral submucosal tumor. A resected specimen by laparoscopic and endoscopic cooperative surgery revealed spindle cell proliferation forming plexiform nodules with a myxoid background in limited areas. Positive immunoreactivity of a subset of spindle cells for KIT suggested a diagnosis of gastrointestinal stromal tumor (GIST), although DOG1 was negative. In addition, diffuse staining for CD10, smooth muscle actin, and D2-40 was confusing. MALAT1::GLI1 fusion was detected by next-generation sequencing analysis. Consequently, a diagnosis of PFM was established. Conclusions: This case expands the morphologic and immunophenotypic spectrum of PFM and indicates the possible diagnostic utility and biological significance of D2-40 expression. Although molecular confirmation of MALAT1::GLI1 fusion is definitive for the diagnosis of PFM, the findings of the present case may aid diagnosis in challenging cases that mimic GIST. Full article

Prostate cancer (PCa) remains a major global health challenge, yet conventional diagnostic methods are often limited by suboptimal accuracy and efficiency. Artificial intelligence (AI) has emerged as a rapidly developing technology capable of integrating multi-source data to enhance clinical decision-making. This narrative review synthesizes current evidence regarding AI applications across key diagnostic domains, including medical imaging, digital pathology, liquid biopsy, and multi-omics integration. Findings indicate that AI models for magnetic resonance imaging (MRI) can improve risk stratification and may reduce unnecessary biopsies in some cohorts, particularly when evaluated alongside structured radiology assessment and clinical variables. In digital pathology, deep learning algorithms have shown high agreement with expert genitourinary pathologists for automated Gleason grading in controlled and externally validated settings, with potential to reduce reporting time for high-volume workflows. Additionally, AI-powered liquid biopsy models may support non-invasive risk stratification, particularly for patients with prostate-specific antigen (PSA) levels in the diagnostic gray zone, while multi-omics integration is being investigated to enhance personalized assessment. Despite advances, challenges regarding data heterogeneity, algorithm interpretability, and workflow integration persist. Future research should prioritize multimodal data fusion, explainable AI development, robust calibration and decision-analytic evaluation, and large-scale prospective validation to standardize protocols and fully realize the potential of AI in precision prostate cancer care. Full article

Background/Objectives: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare central nervous system neoplasm characterized by leptomeningeal dissemination and heterogeneous clinical and molecular features. Owing to its rarity, the prognostic relevance of clinical, radiological, and molecular factors remains poorly defined. This systematic review aimed to comprehensively summarize the clinicopathological characteristics, molecular landscape, treatment strategies, and survival outcomes of patients with DLGNT. Methods: A systematic literature search was conducted in PubMed, Embase, Scopus, and Google Scholar to identify published cases of DLGNT. Studies reporting individual patient data were included. Clinical, molecular, treatment, and survival data were pooled. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan–Meier method, with subgroup analyses according to clinical and molecular variables. Results: Seventy-five patients were included. Most patients were pediatric, and spinal leptomeningeal dissemination and hydrocephalus were frequent. BRAF alterations, most commonly KIAA1549::BRAF fusion, were frequently identified, although no molecular marker predicted survival. The median OS was 89 months, and the median PFS was 30 months. Surgical resection was associated with significantly longer OS compared with biopsy only, while a trend toward longer PFS was observed. Survival outcomes did not differ significantly according to age group, BRAF status, chemotherapy, or radiotherapy. Conclusions: DLGNT is a rare and heterogeneous tumor with variable presentation and prolonged survival in selected patients. Although surgical resection may be associated with improved survival, interpretation is limited by selection bias. No single molecular alteration reliably predicts prognosis, highlighting the need for prospective multicenter studies with standardized molecular profiling. Full article

Liver fibrosis (LF) represents a crucial intermediate stage in the pathological progression from chronic liver disease to cirrhosis and hepatocellular carcinoma. Early and accurate diagnosis is of vital importance for the intervention treatment of diseases and the improvement of prognosis. Traditional liver biopsy, long regarded as the diagnostic gold standard, remains associated with several notable limitations such as invasiveness, sampling errors and inter-observer variability. Lately, as artificial intelligence (AI) technology progresses swiftly, radiomics and deep learning (DL) have risen to prominence as non-invasive diagnostic instruments, showing significant potential in the LF diagnostic evaluation. This review summarizes the latest advancements in radiomics and DL for LF diagnosis, staging, prognosis prediction and etiological differentiation. It also analyzes the application value of multimodal imaging modalities, including magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound in this field. Despite ongoing challenges in model generalization and standardization, improved model interpretability, technological integration and multimodal fusion, the continuous advancement of radiomics and DL technologies holds promise for AI-driven imaging analysis strategies. These approaches aim to integrate multiple clinical monitoring methods, overcome obstacles in the early LF diagnosis and treatment and provide new perspectives for precision medicine of this disease. Full article

Ampullary carcinoma (AC) is a rare gastrointestinal malignancy with dual intestinal and pancreatobiliary differentiation, complicating diagnosis, staging, and treatment. This review synthesizes current epidemiology, pathology, and multi-omic data to outline a pragmatic care pathway: lineage-first at presentation, mutation-fast at progression. Histology remains the primary classifier: the intestinal subtype generally aligns with colorectal regimens, whereas pancreatobiliary and mixed subtypes favor pancreaticobiliary therapy. In selected fit patients, modified FOLFIRINOX may address mixed phenotypes. Next-generation sequencing adds precision by identifying therapeutically relevant alterations, including ERBB2/HER2 amplifications, MSI-high/dMMR, BRAF V600E, and rare NTRK or RET fusions, while KRAS mutations are enriched in pancreatobiliary tumors. We recommend early application of a rapid-core panel (KRAS/BRAF, MSI/dMMR, ERBB2/HER2, RNA-based fusions) to capture high-impact targets, followed by comprehensive profiling at first progression. Liquid biopsy, plasma circulating tumor DNA (ctDNA), or bile-derived DNA may complement tissue and help identify the dominant lineage. Research priorities include ampulla-enriched umbrella trials, explicit AC subcohorts in tissue-agnostic studies, and ctDNA-informed endpoints. This lineage-first, mutation-fast paradigm supports precision care and evidence generation in AC. Full article

Objectives: To develop a prediction model able to accurately predict which patients will harbor higher risk prostate cancer in the systematic biopsy template compared to the targeted biopsy during MRI/US fusion biopsy. Methods: We included patients who underwent fusion biopsy. Clinical and radiographic variables were collected from patients’ records. The outcome of the model was higher risk prostate cancer in the systematic compared with targeted biopsies. An extreme gradient boosting model was trained and tested. We evaluated variable importance and clinical benefit. Results: Five hundred and twenty-nine patients were included. Eighty-two (15.5%) patients had higher risk prostate cancer in the systematic biopsies. The area under the ROC curve and negative predictive value were 0.82 and 0.92, respectively. The four most important features for outcome prediction were prostate volume, PSAD, patient’s age, and PSA. The decision curve showed increased clinical benefit of our model at threshold probabilities of 0–0.5. Limitations include the retrospective design of the study and the lack of external validation of the model. Conclusions: We developed a prediction model able to accurately predict which patients must undergo systematic and targeted biopsy. This prediction model has the potential to help in the decision whether to perform SB and thus may lower the adverse event rate while keeping a high detection rate. Full article

Background and Clinical Significance: Acute promyelocytic leukemia (APL) is a rapidly progressive subtype of acute myeloid leukemia defined by PML::RARA fusion and characterized by life-threatening coagulopathy. Because the disease typically follows an aggressive course, immediate treatment is essential once APL is suspected. This case report describes an atypical de novo presentation marked by indolent progression rather than the expected aggressive trajectory. Case Presentation: A 37-year-old female exhibited gradually declining white blood cell and neutrophil counts over the course of a year, followed by unexplained pancytopenia with severe neutropenia (0.1 × 10⁹/L). Evaluation for nutritional deficiencies and autoimmune disease was unrevealing aside from a positive ANA without clinical features of autoimmunity. Bone-marrow biopsy demonstrated morphologic and flow cytometric findings suggestive of APL, low-level t(15;17), PML::RARA fusion, and concomitant TP53 loss and ETV6 mutation. Despite the indolent clinical presentation and low disease burden, the molecular and cytogenetic findings confirmed the diagnosis of classical APL with TP53 loss and ETV6 mutation. Induction therapy with all-trans-retinoic acid and arsenic trioxide resulted in hematologic remission. Conclusions: This case highlights an unusually indolent form of de novo APL not previously documented in the literature, expanding the recognized clinical spectrum of the disease. The findings emphasize the importance of still considering severe diagnoses, such as APL, when presentations deviate from classical patterns. Atypical clinical trajectories should prompt careful assessment of marrow morphology and immunophenotypic features. Continued characterization of such cases may refine diagnostic criteria and direct individualized approaches to therapy. Full article