Search Results (364)

Aims: Prostate cancer (PCa) presents ongoing challenges in differentiating aggressive from indolent disease using traditional biomarkers such as prostate-specific antigen (PSA). The Phosphatase and Tensin Homolog (PTEN), a key tumour suppressor involved in cellular growth regulation, is emerging as a promising biomarker for risk stratification. This meta-analysis aims to evaluate the prognostic significance of PTEN loss in PCa, particularly its relationship with Gleason grade groups (GG), as defined by the ISUP system, and clinical outcomes. Methods: A systematic review and meta-analysis of 16 studies encompassing 11,375 patients was conducted in accordance with PRISMA guidance. Studies included evaluated PTEN loss, stratified by hemizygous and homozygous deletions, and its association with GG and clinical endpoints such as biochemical recurrence and lethal progression. Pooled odds ratios (ORs) and hazard ratios (HRs) were calculated using a random-effects model. Results: PTEN loss was significantly associated with tumour aggressiveness. Compared to GG1 tumours, the odds of PTEN loss were markedly increased in Gleason GG 2 and 3(OR: 2.78, 95% CI: 1.95–3.61) and GG ≥ 4 (OR: 6.35, 95% CI: 5.37–7.33). Homozygous PTEN deletions were more strongly associated with high-grade tumours than hemizygous deletions. Clinically, PTEN loss was predictive of adverse outcomes, including increased risk of biochemical recurrence (HR: 1.78, 95% CI: 1.31–2.25) and lethal progression (HR: 2.57, 95% CI: 1.12–3.95). Conclusion: PTEN loss correlates with higher GG and poorer clinical outcomes in PCa. Incorporating PTEN assessment into clinical decision making could improve risk stratification, guiding early intervention strategies and identifying patients suitable for active surveillance. Full article

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, often diagnosed at an advanced stage due to its asymptomatic progression. The high recurrence rate and development of platinum-based chemotherapy resistance contribute to its poor prognosis. Despite advancements in molecular profiling, predictive biomarkers for chemotherapy response and recurrence risk remain limited. In this study, we developed OvarianTag™, a biomarker panel integrating apoptosis and necroptosis pathways, to predict chemotherapy benefit and disease progression in EOC patients. This observational study was conducted in two phases. In the first phase, 45 patients were recruited, and RNA was extracted from fresh ovarian tissues (normal, benign, and malignant). qRT-PCR was performed to assess the relative expression of genes involved in apoptosis and necroptosis-regulated cell death pathways. Machine learning algorithms were applied to identify the relevant prognostic markers, leading to the development of OvarianTag™. In the second phase, 55 additional EOC patients were included, and their formalin-fixed, paraffin-embedded (FFPE) tumor samples were analyzed using qRT-PCR. The classifier algorithm incorporated hierarchical clustering to stratify patients based on gene expression profiles. Significant differences in TNFRSF10C/TRAIL-R3, TNFRSF10B/TRAIL-R2, and CASP8 expression levels were observed between patient groups. CASP8 downregulation was strongly correlated with platinum resistance and a poor prognosis. Decision tree models achieved 83.3% accuracy in predicting platinum response and 79.2% accuracy in recurrence risk stratification. The OvarianTag™ classifier demonstrated high sensitivity and specificity in identifying high-risk patients, supporting its potential as a prognostic tool. The OvarianTag™ panel provides a novel approach for risk stratification in EOC, integrating apoptosis and necroptosis pathways to refine chemotherapy response prediction and recurrence risk assessment. This molecular assay has the potential to guide personalized treatment strategies, enhancing clinical decision-making and improving patient outcomes. Further validation in independent cohorts is warranted to establish its clinical utility. Full article

Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Despite advances in diagnosis and treatment, recurrence and mortality remain significant concerns. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has shown prognostic value in several malignancies, but its utility in EC remains underexplored. Objective: To evaluate the prognostic significance of the preoperative NLR in patients with endometrial cancer undergoing primary surgical treatment. Methods: We conducted a retrospective cohort study including 398 patients with histologically confirmed endometrial adenocarcinoma surgically treated at a tertiary cancer center. Preoperative complete blood counts were used to calculate NLR, and a cutoff value of 2.27 was determined through Receiver Operating Characteristic (ROC) analysis. Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards modeling. Results: Patients with NLR ≥ 2.27 had significantly reduced median overall survival (OS) compared to those with NLR < 2.27 (72.3 vs. 92.8 months, p = 0.008). In multivariate analysis, elevated NLR remained an independent predictor of poorer OS (HR = 1.87; 95% CI: 1.156–3.017; p = 0.011), alongside age ≥ 64 years, lymphovascular space invasion (LVSI), lymph node involvement, and distant metastases. ROC analysis yielded an Area Under the Curve (AUC) of 0.646 for NLR. Notably, vaginal brachytherapy was associated with improved survival (HR = 0.53; p = 0.026), while other adjuvant therapies were not independently significant. Conclusions: Preoperative NLR is an accessible, independent prognostic biomarker in endometrial cancer and may serve as a surrogate indicator of tumor-promoting inflammation and immune dysregulation. Its integration into preoperative assessment could enhance risk stratification and guide personalized treatment strategies. However, findings should be interpreted in light of the study’s retrospective design, single-center setting, and lack of molecular classification data. Prospective validation is warranted to confirm its clinical utility. Full article

Background/Objectives: Sepsis is a severe medical condition characterized by a dysregulated host response to infection, with potentially fatal outcomes, requiring early diagnosis and rapid intervention. The limitations of traditional sepsis identification methods, as well as the complexity of clinical data generated in intensive care, have driven increased interest in applying artificial intelligence in this field. The aim of this narrative review article is to analyze how artificial intelligence is being used in the diagnosis and prognosis of sepsis, to present the most relevant current models and algorithms, and to discuss the challenges and opportunities related to integrating these technologies into clinical practice. Methods: We conducted a structured literature search for this narrative review, covering studies published between 2016 and 2024 in databases such as PubMed/Medline, Scopus, Web of Science, IEEE Xplore, and Google Scholar. The review covered models based on machine learning (ML), deep neural networks (DNNs), Recurrent Neural Networks (RNNs), and clinical alert systems implemented in hospitals. The clinical data sources used, algorithms applied, system architectures, and performance outcomes are presented. Results: Numerous artificial intelligence models demonstrated superior performance compared to conventional clinical scores (qSOFA, SIRS), achieving AUC values above 0.90 in predicting sepsis and mortality. Systems such as Targeted Real-Time Early Warning System (TREWS) and InSight have been clinically validated and have significantly reduced the time to treatment initiation. However, challenges remain, such as a lack of model transparency, algorithmic bias, difficulties integrating into clinical workflows, and the absence of external validation in multicenter settings. Conclusions: Artificial intelligence has the potential to transform sepsis management through early diagnosis, risk stratification, and personalized treatment. A responsible, multidisciplinary approach is necessary, including rigorous clinical validation, enhanced interpretability, and training of healthcare personnel to effectively integrate these technologies into everyday practice. Full article

Urothelial carcinoma in situ (UCIS) is a high-grade non-muscle-invasive neoplasm with significant clinical implications due to its potential for progression to muscle-invasive disease. Accurate diagnosis and risk stratification are crucial for appropriate management, particularly given the variability in response to intravesical Bacillus Calmette-Guérin (BCG) therapy. While the diagnosis of UCIS primarily relies on morphological criteria, immunohistochemical (IHC) markers serve as valuable ancillary tools, particularly in challenging cases. Markers such as CK20, CD44, p53, and Ki-67 have been extensively studied, though none demonstrate complete sensitivity or specificity. Additionally, molecular classification has identified luminal and basal subtypes, with potential prognostic and therapeutic implications. Recent studies have also explored predictive biomarkers for BCG response, including PD-L1, whose expression correlates with recurrence and potential responsiveness to immune checkpoint inhibitors. Emerging targeted therapies, such as enfortumab vedotin, have shown promise, with nectin-4 overexpression observed in most UCIS cases. Despite these advancements, challenges remain, including interobserver variability in morphological assessment, heterogeneous IHC methodologies, and the need for standardized molecular testing. This review highlights the current understanding of diagnostic, prognostic, and predictive tissue biomarkers in UCIS, underscoring the potential role of molecular profiling in guiding personalized treatment strategies. Future research should focus on refining biomarker-driven classification systems to improve risk stratification and therapeutic decision-making in UCIS patients. Full article

Background: Despite clinical and pathological risk tools, predicting outcomes in non-muscle-invasive bladder cancer (NMIBC), particularly high-grade (HG) cases, remains challenging due to its unpredictable recurrence and progression. There is an urgent need for molecular biomarkers to enhance risk stratification and guide treatment. Methods: We assessed the prognostic potential of eight miRNAs (miR-9, miR-143, miR-182, miR-205, miR-27a, miR-369, let-7c, and let-7g) in a cohort of ninety patients with primary bladder cancer. Expression data were retrieved from our previously published studies. Kaplan–Meier’s and Cox’s regression analyses were used to evaluate the associations with overall survival (OS), metastasis-free survival (MFS), and clinical outcomes. Principal component analysis (PCA) was performed to identify informative miRNA combinations. Target gene prediction, pathway enrichment (DAVID), and drug–gene interaction mapping (DGIdb) were conducted in silico. Results: A high expression of let-7g and miR-9 was significantly associated with better OS in HG NMIBC and MIBC, respectively (p = 0.013 and p = 0.000). MiR-9 downregulation correlated with metastasis in MIBC (p = 0.018). Among all combinations, miR-205 and miR-27a best predicted intermediate-risk NMIBC progression and recurrence (r² = 0.982, p = 0.000). A functional analysis revealed that these miRNAs regulate key cancer-related pathways (MAPK, mTOR, and p53) through genes such as TP53, PTEN, and CDKN1A. Drug interaction mapping identified nine target genes (e.g., DAPK1, ATR, and MTR) associated with eight FDA-approved bladder cancer therapies, including cisplatin and gemcitabine. Conclusions: Let-7g, miR-9, miR-143, miR-182, and miR-205 emerged as promising biomarkers for outcome prediction in NMIBC. Their integration into liquid biopsy platforms could support non-invasive monitoring and personalized treatment strategies. These findings warrant validation in larger, prospective studies and through functional assays. Full article

Next-generation sequencing has overturned the dogma of biliary sterility, revealing low-biomass microbiota along the gut–biliary axis with metabolic and immunologic effects. This review synthesizes evidence on composition, function, and routes of colonization across benign and malignant disease. In cholelithiasis, Proteobacteria- and Firmicutes-rich consortia provide β-glucuronidase, phospholipase A₂, and bile salt hydrolase, driving bile supersaturation, nucleation, and recurrence. In primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis, intestinal dysbiosis and disturbed bile acid pools modulate pattern recognition receptors and bile acid signaling (FXR, TGR5), promote Th17 skewing, and injure cholangiocytes; bile frequently shows Enterococcus expansion linked to taurolithocholic acid. Distinct oncobiomes characterize cholangiocarcinoma subtypes; colibactin-positive Escherichia coli and intratumoral Gammaproteobacteria contribute to DNA damage and chemoresistance. In hepatocellular carcinoma, intratumoral microbial signatures correlate with tumor biology and prognosis. We critically appraise key methodological constraints—sampling route and post-sphincterotomy contamination, antibiotic prophylaxis, low biomass, and heterogeneous analytical pipelines—and outline a translational agenda: validated microbial/metabolomic biomarkers from bile, tissue, and stent biofilms; targeted modulation with selective antibiotics, engineered probiotics, fecal microbiota transplantation, and bile acid receptor modulators. Standardized protocols and spatial, multi-omic prospective studies are required to enable risk stratification and microbiota-informed therapeutics. Full article

Perioperative/neoadjuvant chemo-immunotherapy is a standard treatment for patients with resectable non-small cell lung cancer (NSCLC). However, several key clinical questions remain unresolved, including the monitoring of tumor response during neoadjuvant treatment, detection of residual disease after neoadjuvant treatment or after surgery, stratification of recurrence risk, and earlier detection of disease recurrence. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker to address these challenges. Data from several recent clinical trials of perioperative/neoadjuvant chemo-immunotherapy demonstrated that ctDNA clearance before surgery was associated with higher rates of major pathological response. Additionally, landmark ctDNA positivity after surgery identified patients at high risk of disease recurrence, and longitudinal ctDNA monitoring enabled earlier detection of recurrence compared with radiographic surveillance. Several ongoing trials are incorporating ctDNA as a biomarker to guide treatment decisions, including optimizing the duration of neoadjuvant therapy, evaluating the need for surgery, and tailoring adjuvant strategies. These trials, together with further development of ctDNA detection technologies, will clarify the role of ctDNA analysis in refining perioperative treatment strategies and may ultimately enable individualized care in patients with resectable NSCLC. In this review, we discuss the current research data on ctDNA analysis in NSCLC in this era of perioperative chemo-immunotherapy. Full article

Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, the risks associated with re-irradiation, and recent changes in the WHO classification of CNS tumors highlight the need for more personalized and strategic treatment approaches. This systematic review evaluates the safety, efficacy, and clinical considerations for use of SRS for recurrent meningiomas. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted using the PubMed, Scopus, and Web of Science databases for studies reporting outcomes of SRS in recurrent, pathologically confirmed intracranial meningiomas. Studies were excluded if they were commentaries, reviews, case reports with fewer than three cases, or had inaccessible full text. The quality and risk of bias of the included studies were assessed using the modified Newcastle-Ottawa Scale. Data on patient and tumor characteristics, SRS treatment parameters, clinical outcomes, adverse effects, and statistical analysis results were extracted. Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II meningiomas demonstrated more variable outcomes, with 3-year PFS ranging from 23% to 100%. Grade III tumors had consistently poorer outcomes, with reported 1-year and 2-year PFS rates as low as 0% and 46%, respectively. SRS performed after surgery alone was associated with superior outcomes, with local control rates of 79% to 100% and 5-year PFS ranging from 40.4% to 91%. In contrast, tumors previously treated with radiotherapy, with or without surgery, showed substantially poorer outcomes, with 3- to 5-year PFS ranging from 26% to 41% and local control rates as low as 31%. Among patients with prior radiotherapy, outcomes were particularly poor in Grade II and III recurrent tumors. Toxicity rates ranged from 3.7% to 37%, and were generally higher for patients with prior radiation. Predictors of worse PFS included prior radiation, older age, and Grade III histology. Conclusions: SRS may represent a reasonable salvage option for carefully selected patients with recurrent meningioma, particularly following surgery alone. Outcomes were notably worse in high-grade recurrent meningiomas following prior radiotherapy, emphasizing the prognostic significance of both histological grade and treatment history. Notably, the lack of molecular and genetic data in most existing studies represents a key limitation in the current literature. Future prospective studies incorporating molecular profiling may improve risk stratification and support more personalized treatment strategies. Full article

Background and Objectives: Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide and, beyond its oncogenic potential, may impair reproductive health in both sexes. This review examines HPV’s effects on male and female fertility, obstetric outcomes, vertical transmission, and fertility-sparing management in oncology. Materials and Methods: A systematic search of PubMed, Embase, and Scopus was conducted using terms related to HPV and reproduction. Additional search terms included those related to therapeutic vaccines, antivirals, and genotype prevalence. English-language human studies reporting clinical reproductive outcomes were included. Thirty-seven studies met the inclusion criteria. Two reviewers independently screened and assessed study quality using a simplified GRADE framework. Results: In men, seminal HPV infection correlates with reduced progressive motility (SMD ≈ −0.85), abnormal morphology, and increased DNA fragmentation. In women, high-risk HPV doubles the odds of infertility (OR ≈ 2.3) and is associated with endometrial involvement. High first-trimester viral load predicts vertical transmission (aOR 6.4), which is also increased by vaginal delivery (RR 1.8) and is linked to PROM (OR 1.8) and preterm birth (OR 1.8). Modeling suggests that nine-valent vaccination plus 5-year HPV-based screening could reduce CIN2+ by up to 80% and excisional treatments by >75%. Fertility-sparing surgery in early cervical cancer yields a <4% recurrence and up to 68% live birth rates. Conclusions: This review uniquely synthesizes reproductive and oncologic impacts of HPV and emphasizes risk stratification, multidisciplinary prevention, and fertility preservation. Integration of HPV DNA quantification, personalized care, and vaccine-based strategies offers a path toward optimized outcomes in both sexes. Full article

Head and neck cancer (HNC) is the seventh most common cancer worldwide, with rising incidence particularly in oropharyngeal cancer subsites. Despite well-known risk factors, such as tobacco and alcohol consumption as well as human papillomavirus (HPV) infection, most HNCs are diagnosed at an advanced stage, resulting in poor prognosis. Early detection and screening are critical, especially in high-risk populations. Nevertheless, there is a lack of guidelines for a stratified HNC screening. A systematic literature review was conducted following PRISMA guidelines, using PubMed and ScienceDirect databases up to 30 June 2025. Search terms included “screening”, “early diagnosis”, and specific HNC subsites. A total of 199 records were screened, and 160 studies were included based on relevance and scientific rigor. The review concentrates on contemporary screening modalities, stratification of high-risk cohorts, emerging technologies, and cost-effectiveness evidence. Visual inspection and panendoscopy remain the standard tools for HNC screening, but have limited effectiveness and cost-efficiency. Opportunistic screening in high-risk individuals, especially in regions with high HNC prevalence, has shown benefits. Liquid biopsy techniques targeting HPV- and Epstein-Barr virus-related HNC demonstrate high sensitivity for early detection and recurrence monitoring. Novel imaging technologies like narrow-band imaging and Raman spectroscopy show promising diagnostic accuracy but require further validation. Most broad-based screening programs lack cost-effectiveness, while targeted strategies in high-risk groups appear more viable. Screening for HNC should be stratified by individual risk profiles and regional disease prevalence. Emerging technologies, particularly liquid and optical biopsy techniques, offer transformative potential. Future screening strategies must integrate technological advances into tailored, evidence-based protocols to improve early detection and patient outcomes in HNC. Full article

Background: Non-variceal upper gastrointestinal bleeding (NVUGIB) remains a critical medical–surgical emergency associated with significant morbidity, mortality, and healthcare burden worldwide. Despite advances in diagnostic and therapeutic modalities, NVUGIB continues to pose complex clinical challenges, particularly in resource-limited settings. Methods: This retrospective observational study analyzed 364 consecutive adult patients diagnosed with NVUGIB and hospitalized at the First Surgical Clinic of the County Emergency Clinical Hospital Craiova between January 2009 and December 2014. Inclusion criteria required a confirmed diagnosis based on clinical presentation, laboratory findings, and upper gastrointestinal endoscopy (UGIE). Demographic variables, etiology, comorbidities, drug-induced triggers, laboratory parameters, onset-to-admission and onset-to-surgery intervals, endoscopic findings, therapeutic interventions (medical, endoscopic, surgical), rebleeding rates, and mortality were recorded and analyzed. Results were descriptively compared with historical data from the national and international literature. Due to the retrospective and aggregate nature of the data, survival analysis (Kaplan–Meier) was not applicable. Results: Peptic ulcers, erosive gastritis, Mallory–Weiss syndrome, and gastric neoplasms were the predominant etiologies. NSAID use, oral anticoagulation, and alcohol consumption emerged as major risk factors. Endoscopic hemostasis was achieved in the majority of cases; surgical intervention was required in 11.5% of patients, mainly for refractory or recurrent bleeding. The overall mortality rate was 10.9%, consistent with historical benchmarks. Comparative analysis revealed trends in etiology and management reflecting evolving clinical practice standards. Conclusions: NVUGIB remains a significant clinical challenge with persistent mortality and rebleeding risks. This cohort highlights the need for timely diagnosis, risk stratification, and an evidence-based therapeutic strategy integrating modern endoscopic and surgical options. An updated diagnostic and management algorithm is proposed to guide practical decision-making and optimize outcomes in similar tertiary care settings. Full article

Multiple myeloma (MM) is a malignant plasma cell disorder that evolves from precursor conditions including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Understanding the biological continuum and the molecular drivers of disease progression is crucial for early diagnosis and risk-adapted therapy. Recent advances in next-generation sequencing have identified recurrent mutations in the RAS/MAPK, TP53, and MYC pathways, along with epigenetic alterations that contribute to clonal evolution and therapeutic resistance. Novel diagnostic tools including minimal residual disease (MRD) assessment, gene expression profiling, and advanced imaging have improved risk stratification. Therapeutically, the integration of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has dramatically improved patient outcomes. In parallel, emerging immunotherapies such as CAR-T cells, bispecific T-cell engagers, and antibody–drug conjugates are expanding treatment options, especially in relapsed or refractory settings. Future directions aim to personalize treatment using genomics, target the tumor microenvironment, and leverage synthetic lethality and epigenetic vulnerabilities. This review highlights the evolving landscape of plasma cell disorders from molecular pathogenesis to cutting-edge therapeutic innovations, emphasizing the need for precision medicine approaches to improve survival and quality of life for patients with MM and its precursors. Full article

Background: Perioperative factors significantly impact oncologic outcomes after radical cystectomy (RC) for bladder cancer. This study aimed to identify key perioperative predictors for overall (OS) and progression-free survival (PFS) and to develop a prognostic nomogram for the identification of high-risk patients adapted to the clinical routines and standard of care of our country. Methods: We retrospectively analyzed 121 patients undergoing RC (2014–2024). Data on patient demographics, comorbidities, tumor pathology, neoadjuvant treatments, extensive intraoperative factors, and postoperative events were assessed using COX models. A prognostic nomogram for 3-year OS was constructed. Results: Median follow-up was 44.33 months. Significant predictors for worse OS included lymphovascular invasion (LVI) (HR 2.22), higher T stage (HR 8.75), N+ status (HR 1.10), and intraoperative complications (HR 3.04). Similar predictors were noted for PFS. The developed nomogram incorporated T-, N-stages, sex, grade, intraoperative complications and early (12 months) recurrence, and was able to significantly identify patients with a higher mortality risk (p < 0.001) with a C-index of 0.74. Conclusions: Our nomogram for mortality prediction of BC patients offers a promising tool for individualized risk stratification. Further studies are required for its external validation. Full article

Objectives: Hepatocellular carcinoma (HCC) remains a major indication for liver transplantation (LT), but accurate pretransplant risk stratification is critical to improve long-term outcomes. Traditional morphometric criteria such as tumor size and number are limited in predicting recurrence and survival. The HALP (hemoglobin, albumin, lymphocyte, platelet), gamma-glutamyl transpeptidase to platelet ratio (GPR), and FIB-4 indices are emerging systemic inflammatory and nutritional biomarkers that may provide additional prognostic value in HCC patients undergoing LT. Materials and Methods: This retrospective, two-center cohort study included 200 patients who underwent LT for HCC between 2012 and 2023. Preoperative HALP, GPR, and FIB-4 scores were calculated, and their associations with overall survival (OS) and recurrence-free survival (RFS) were assessed using ROC analyses and Cox proportional hazard models. Cut-off values were determined for each biomarker, and survival outcomes were analyzed using Kaplan–Meier methods. Results: A low HALP score (≤0.39) was independently associated with reduced OS but not with RFS. Conversely, low GPR (≤0.45) and FIB-4 (≤3.1) values were significantly associated with both poor OS and higher recurrence risk. Tumor size, number of lesions, and microvascular invasion also independently predicted poor outcomes. Multivariate analysis confirmed HALP, GPR, and FIB-4 as significant preoperative predictors of prognosis in this population. Conclusions: HALP, GPR, and FIB-4 are readily available, cost-effective indices that provide significant prognostic information in HCC patients undergoing LT. Their integration with morphometric criteria may improve pretransplant risk stratification and support individualized clinical decision-making. Full article