Search Results (172)

For over three decades, Proton Pump Inhibitors (PPIs) have served as the established primary therapy for acid-suppressive therapy; however, their clinical utility is frequently compromised by their slow onset of action, meal-time dependency, and metabolic variability driven by CYP2C19 polymorphisms. Potassium-competitive acid blockers (P-CABs) represent a definitive pharmacological shift, offering rapid, reversible, and genotype-independent inhibition of the H⁺/K⁺-ATPase. This review outlines the emergence of South Korea as a global epicenter for P-CAB innovation, predicated upon a strategic partnership between a high domestic burden of Helicobacter pylori infection and a rising incidence of refractory gastroesophageal reflux disease (GERD). We analyze the clinical and structural developments of indigenous Korean agents, specifically tegoprazan and fexuprazan, the latter of which features an optimized 9-h elimination half-life engineered to mitigate nocturnal acid breakthrough. A critical evaluation of recent clinical evidence is provided, including the most recent 2024 prospective Phase III data, which demonstrate that 14-day P-CAB-based triple therapy achieves significantly improved eradication rates in high-clarithromycin-resistance environments. Furthermore, we explore the emerging 2025 trend toward personalized, on-demand maintenance therapy and address critical long-term safety considerations, including the duration-dependent risk of metachronous gastric cancer identified in recent multicenter longitudinal studies. Ultimately, the South Korean clinical framework is providing the foundational evidence for a global transition toward P-CAB-centered treatment algorithms, redefining the standards of care in modern gastroenterology. Full article

Background: Postoperative complications after staging surgery for endometrial cancer often occur after discharge, and 30-day unplanned readmission is an important post-discharge outcome. Existing models lack same-day usability at discharge and sufficient validation, limiting discharge-time risk stratification and transitional care planning. This study aimed to develop and validate a discharge-time risk prediction model based on administrative data for 30-day unplanned hospital readmission among patients undergoing staging surgery for endometrial cancer. Methods: This retrospective cohort study was conducted in accordance with the TRIPOD reporting guidelines. We constructed a nationally representative adult cohort using the Healthcare Cost and Utilization Project Nationwide Readmissions Database (HCUP-NRD) from 2016 to 2022, including index hospitalizations discharged between January and November to ensure complete 30-day follow-up. Variables available at discharge (demographics, payer/income, presentation, inpatient course, discharge disposition, hospital characteristics, Elixhauser index) were included; age and length of stay were modeled with restricted cubic splines. Complex survey-weighted multivariable logistic regression was used for model development with 1000 bootstrap internal validations. Temporal validation within the NRD was performed using 2020–2021 and 2022 data. Decision curve analysis, subgroup, and sensitivity analyses were conducted. Results: A total of 89,627 hospitalizations were included; development and validation cohorts had balanced baselines. Internal validation showed moderate discrimination (AUC 0.719) and good calibration (Brier 0.045; intercept 0.014; slope 0.955). Discharge to home health or institutional care, non-elective or emergency admission, and a higher Elixhauser readmission index (a measure of comorbidity burden) were associated with increased risk. Age and length of stay showed nonlinear associations. Temporal validation yielded a similar performance (AUC 0.708–0.713; Brier 0.043–0.046), and decision curves indicated positive net clinical benefit. Conclusions: The model demonstrated stable discrimination and maintained good calibration after temporal validation and recalibration. It represents a candidate discharge-time decision-support tool, based on administrative data, for identifying patients at higher risk of 30-day unplanned readmission, and may support nurse-led transitional care planning. External validation and local recalibration are required before application in other healthcare settings. Full article

Respiratory medicine is transitioning from symptom-driven, standardized care to a more precise, patient-specific approach guided by molecular profiling. This evolution is being enabled by advances in liquid biopsy, multiomics, and artificial intelligence (AI) analytics. Fractional exhaled nitric oxide (FeNO) and blood eosinophils, the two commonly used markers in asthma, are now being joined by more precise airway markers such as galectin-10, which could aid clinicians in making more informed decisions for biological treatments. In chronic obstructive pulmonary disease (COPD) similar progress is underway, with treatment now emphasizing inflammation endotypes, especially eosinophilic patterns, to direct therapeutic choices. Alongside these developments, routine blood-based ratios (e.g., platelet-to-lymphocyte and neutrophil-to-lymphocyte) are being explored as predictors of exacerbation risk, and forced oscillation testing (FOT) is proving useful for picking up early disease shifts. In more severe conditions, biomarkers are linked to an early and better prognosis, enabling timely intervention. Markers like Matrix metalloproteinase-7 (MMP-7) and CC chemokine ligand 18 (CCL18) have proven to be reliable indicators of mortality and disease progression in idiopathic pulmonary fibrosis. Meanwhile, in lung cancer, liquid biopsies, especially those measuring circulating tumor DNA and micro-RNA (miRNA) panels, are enhancing screening accuracy while helping to cut down on the high false-positive rates seen with low-dose computerised tomography (CT). Other respiratory conditions such as bronchiectasis, pulmonary embolism, pneumonia, and acute respiratory distress syndrome (ARDS) are also benefiting from biomarker advances. At the same time there is a growing push to standardize how these biomarkers are measured. AI-based clinical decision support systems are also playing an increasingly important role in the translation of all these complicated data into actionable clinical insights. Together these developments pave the way for improved respiratory care that is precise and responsive to individual patient needs. Full article

Radioguided surgery has become a key component of contemporary breast cancer care, supporting less invasive approaches while maintaining oncologic safety. This narrative review summarizes current practice and recent developments in radioguided breast and axillary surgery, from established molecular imaging workflows to emerging three-dimensional and intraoperative technologies. Modern breast cancer management is increasingly shaped by tumor biology and the widespread use of neoadjuvant systemic therapy, which is transforming surgical decision-making and driving a shift toward personalized, patient-tailored pathways. In this context, radioguided techniques help maintain procedural accuracy despite therapy-induced changes in breast and nodal anatomy, enabling reliable lesion localization and targeted management of the axilla. We discuss sentinel lymph node strategies and de-escalation concepts, including targeted axillary dissection (TAD) after neoadjuvant therapy using marked nodes and selective removal approaches. We also review localization methods, including radioactive seed–based techniques, and the expanding role of molecular imaging–guided surgery to support intraoperative decision-making. Particular attention is paid to technologies aimed at improving surgical precision and margin assessment, including portable/freehand SPECT concepts and intraoperative PET/CT-based specimen imaging for immediate evaluation of excised tissue. Finally, we highlight how artificial intelligence and digital tools may enable workflow optimization, navigation, image interpretation, and decision support, accelerating the transition toward individualized treatment. Overall, integrating molecular information with real-time 3D guidance can help tailor breast and axillary management to each patient while reducing morbidity. Full article

A critical gap in current efficiency in melanoma patient treatment is the lack of a fully integrated, functional understanding of tumor evolution over time. Recent advances have fundamentally reshaped our understanding of melanoma biology, while increasing clinical complexity has highlighted the need for more comprehensive and biologically informed clinical decision-support frameworks. We propose the implementation of a multimodal disease profiling framework as a core clinical decision-support asset, enhancing treatment optimization across the full disease course in melanoma patients. By integrating proteogenomics, AI-driven digital image analysis, and structured longitudinal clinical metadata, multimodal disease profiling could provide a comprehensive and dynamically evolving view of each patient’s disease. Proteogenomics reveals tumor signaling activity, protein complex dynamics, and emerging therapeutic vulnerabilities that may drive progression and resistance. In parallel, AI-enabled digital pathology analysis characterizes tumor morphology, clonal heterogeneity, and immune context, capturing spatial and functional changes associated with metastatic transition. When combined with longitudinal clinical data, these layers enable patient-specific models tracking tumor evolution, metastasis, and treatment exposure. Leveraging one of the largest melanoma biobank and database resources at the European Cancer Moonshot Center in Lund, our strategy directly addresses the recurrent transition from primary tumors to metastatic disease. This strategy positions multimodal disease profiling as a critical enabler of precision melanoma care by providing biologically grounded, evidence-based decision support, facilitating rapid and structured case assessment through multimodal insights, enabling prediction of treatment response, resistance, and disease trajectory, and supporting adaptive, evidence-informed therapeutic decision-making. Full article

Despite extensive progress in breast cancer biomarker research, only a limited proportion of candidate biomarkers successfully transition from early discovery to clinically validated tools for targeted early detection. This article examines the key translational barriers that impede this progression across the biomarker development continuum. Five major gaps are identified: (i) discovery-to-clinical relevance, (ii) methodological and analytical validation, (iii) regulatory and administrative complexity, (iv) translational performance and real-world integration, and (v) equity and deployment challenges. Collectively, these gaps highlight limitations not only in scientific and methodological rigor but also in validation frameworks, regulatory alignment, implementation feasibility, and healthcare system equity. This article emphasizes that successful biomarker translation requires more than analytical validity. Finally, it requires a supportive ecosystem that enables effective breast cancer early detection strategies and improves population-level outcomes in breast cancer care. Full article

Lung cancer is one of the most common cancers worldwide, with non-small-cell lung cancer (NSCLC) being the most prevalent type. While surgical resection followed by adjuvant platinum-based chemotherapy has been the standard for curative-intent therapy for clinical stage II NSCLC since 2005, disappointing 5-year survival prompted the exploration of newer systemic therapies. In recent years, several landmark trials increasingly support the use of immunotherapy and molecular targeted treatments. The evidence for neoadjuvant chemoimmunotherapy is exciting, but the transition from a surgery-first approach to a new standard of care carries important challenges, including increased surgical attrition, intraoperative technical difficulty, and delays in care. This article provides a comprehensive review of the optimal treatments and emerging therapies for resectable stage II NSCLC. By systematically analyzing recent advances and challenges in NSCLC treatment strategies, we aim to highlight a paradigm shift toward a more molecularly guided, individualized treatment sequence in stage II NSCLC care, with the goal of maximizing each patient’s curative potential. Full article

Cutaneous melanoma is an aggressive skin cancer. While laser therapy is established for non-melanoma skin cancers, its role in melanoma remains controversial and largely unsupported by robust clinical evidence. The gold standard for melanoma management remains surgical excision, as it allows for definitive histopathological diagnosis, Breslow thickness measurement, and surgical margin assessment, which are essential for accurate staging. This narrative review analyzed preclinical and clinical studies evaluating various laser modalities, including Nd:YAG, CO₂, pulsed dye, photodynamic therapy (PDT) and photothermal therapy (PTT), for efficacy, recurrence rates, and limitations in cutaneous melanoma management. Nd:YAG laser (1064 nm) showed potential for local control in thin stage I melanomas, reporting a low local recurrence rate of 0–0.7% and favorable 5-year survival in small, non-randomized cohorts. CO₂ laser (10,600 nm) provides effective palliation and local control for in-transit or unresectable metastases, but local recurrence is highly variable, reaching up to 46.7%. Photodynamic therapy showed variable efficacy, although Chlorin e6 achieved complete local regression in a small series of metastases. A critical limitation of laser therapy is the irreversible destruction of tissue, which precludes these vital assessments. Therefore, laser treatment should be cautiously reserved for cases where standard surgery is not feasible, acknowledging that it may interfere with the evaluation of curative outcomes and accurate staging. Laser therapy is a valuable minimally invasive adjunct for local control in selected patients who are poor surgical candidates or require palliative care. Routine use is restricted by the lack of randomized controlled trials. Future studies should prioritize combination strategies with systemic or immunotherapeutic approaches to enhance overall outcomes. Full article

Background: Outpatient palliative care effectively alleviates symptom burden in advanced cancer patients, yet data from Central–Eastern Europe remain scarce. This retrospective study examined changes in revised Edmonton Symptom Assessment Scale (ESAS) scores from initial outpatient palliative consultation to first follow-up in Hungarian cancer patients, assessing clinically meaningful improvement and inter-symptom associations. Methods: Revised ESAS scores from 119 patients attending an outpatient palliative care clinic (2017–2020) were analyzed using paired baseline and first follow-up assessments (7–30 days). Symptom changes (Time 2–Time 1) were evaluated using Wilcoxon signed-rank tests. Clinically meaningful improvement was assessed with minimal clinically important difference thresholds (0.5× baseline SD). Sankey diagrams visualized symptom transitions, and multivariable linear regression examined inter-symptom associations. Results: Baseline pain was highest (mean 6.29, median 7), followed by fatigue, sleep disorder, and impaired well-being. At follow-up, significant reductions were observed in pain (mean 4.52, p = 0.001), nausea, dyspnea, constipation, sleep disorder, depression, and anxiety (all p < 0.05). Sankey diagrams showed shifts from severe to mild/moderate pain (50% to 24%) and constipation. Clinically meaningful improvement occurred in pain, nausea, and constipation, with 59–65% achieving ≥1-point pain reduction. Regression analyses showed that pain reduction was associated with concurrent improvements in sleep disorder (β = 0.31), depression (β = 0.20), fatigue (β = 0.20), and anxiety (β = 0.14), while dyspnea reduction was associated with concurrent improvements in depression (β = 0.22) and anxiety (β = 0.14). Conclusions: Outpatient palliative care in Hungarian cancer patients resulted in clinically meaningful symptom reductions, particularly pain and dyspnea. Improvements in these core symptoms were associated with concurrent improvements in other symptom domains, underscoring the clinical relevance of inter-symptom associations and supporting early, integrated outpatient palliative care and symptom cluster-based management. Full article

Background/Objectives: Patient satisfaction and supportive care are key quality indicators in certified Head and Neck Cancer Centers (HNCC). We assessed patient-reported experiences across diagnostic staging and surgical treatment pathways, focusing on discharge management and supportive service integration. Materials and Methods: In this prospective cross-sectional study, 84 inpatients were surveyed at the time of hospital discharge after diagnostic tumor staging (n = 45) or surgical treatment (n = 39) at a German tertiary HNCC. Phase-specific standardized questionnaires with five-point Likert scales were analyzed using Pearson’s chi-square and Fisher’s exact tests. Associations of sex and treatment intensity with satisfaction and supportive care utilization were explored descriptively and in an exploratory manner. Results: Overall ratings were high across both cohorts for admission processes, inpatient organization and medical and nursing care, with no statistically significant between-group differences (p > 0.05). Information regarding diagnostic and perioperative procedures was rated very positively in both groups. Discharge-related items were generally favorable. However, patients who underwent surgery reported greater uncertainty and lower reported utilization of formal discharge management. This difference did not reach statistical significance (p = 0.0559) and should therefore be interpreted as a non-significant trend toward less positive evaluation compared with diagnostic patients. Supportive services were rated predominantly good to very good by users (>95% positive ratings). Utilization differed by treatment intensity: Speech therapy was more frequent in operative patients (p < 0.001) and social work counseling was offered and utilized more often in patients undergoing extensive surgery (p = 0.042 and p = 0.027, respectively). Overall dissatisfaction was strongly associated with perceived deficiencies in information on diagnostic procedures and tumor-related counseling (both p < 0.001), whereas waiting time for surgery was not associated with negative overall ratings. Conclusions: Patient satisfaction was consistently high across diagnostic and surgical pathways. Adequate, transparent and repeated information, particularly on diagnostics and tumor counseling, was strongly associated with higher overall satisfaction, whereas objective timing metrics were not associated with negative ratings. Discharge management may represent a sensitive transition point, particularly after extensive surgery and may therefore be a relevant target for further optimization and proactive integration of supportive care services. Sex-specific findings were limited and should be interpreted cautiously due to small subgroup sizes. Full article

Prostate cancer (PCa) remains one of the most prevalent urological malignancies worldwide, with early and accurate diagnosis being critical for improving patient outcomes. Traditional screening approaches, such as digital rectal examination and prostate-specific antigen (PSA) testing, have long served as frontline tools; however, their limited specificity and sensitivity contribute to high rates of false positives, unnecessary biopsies, and overtreatment. Recent UK guidelines and international consensus increasingly question the role of PSA-based population screening, advocating for risk-stratified pathways and multiparametric MRI as first-line investigations. In parallel, advances in molecular biology have identified promising cancer-specific biomarkers, such as prostate cancer antigen 3 (PCA3) and transmembrane protease serine 2 (TMPRSS2:ERG), that outperform PSAs in terms of specificity and prognostic value. These developments have catalysed innovation in biosensor technologies, enabling rapid, cost-effective, and non-invasive detection of single and multiplex biomarkers in urine and serum. Electrochemical and optical affinity-based biosensors offer transformative potential for the development of personalised point-of-care platforms and diagnostics, reducing the reliance on invasive procedures and improving clinical decision-making. The latter can be augmented with artificial intelligence (AI) tools. This review critically examines the limitations of PSAs, synthesises evidence on novel biomarkers and imaging-led strategies, and evaluates the design, performance, and translational challenges of biosensor-based assays. Furthermore, it outlines future directions, including standardisation, large-scale clinical validation, and integration of multiplex biosensors with AI for precision diagnostics. By bridging molecular insights with engineering innovations, these approaches promise to redefine PCa screening and enable accurate, patient-centred care. Full article

Background: Esophagectomy remains the definitive curative treatment for esophageal cancer but is historically burdened by significant procedure-related morbidity. Anastomotic leakage (AL) is still the “Achilles’ heel” of esophageal surgery, serving as a primary benchmark for surgical quality due to its profound impact on patient recovery, healthcare costs, and long-term oncological outcomes. While surgical expertise and perioperative care have matured, reported AL rates remain persistently high. This necessitates a shift in focus from purely technical modifications toward integrated, data-driven preventive strategies. Purpose: Five years after our initial review, this update synthesizes the rapid evolution in AL prevention. We evaluate the transition from empirical surgical pragmatism to evidence-based protocols, integrating recent breakthroughs in real-time perfusion monitoring, prophylactic endoluminal technologies, and multidisciplinary patient optimization. This work provides a contemporary “roadmap” for navigating the complexities of esophageal reconstruction. Conclusions: The prevention of AL has evolved into a multimodal “bundle” that begins well before the index operation. This review highlights the critical shift toward quantitative perfusion assessment via indocyanine green fluorescence angiography, which is increasingly replacing subjective visual inspection as the standard for anastomotic site selection. We discuss the emerging role of gastric ischemic preconditioning as a biological strategy to enhance conduit vascularity, alongside the paradigm of proactive management using preemptive endoluminal vacuum therapy to mitigate septic sequelae in high-risk cases. Furthermore, we examine technical refinements in conduit construction and conditioning—focusing on the ‘tension-perfusion’ relationship—and the essential role of structured prehabilitation within enhanced recovery after surgery frameworks. While the quality of evidence remains heterogeneous, the move toward standardized reporting and objective monitoring marks a new era of precision in esophageal surgery. Full article

Prostate cancer, particularly metastatic castration-resistant prostate cancer (mCRPC), presents therapeutic challenges rooted in adaptive lineage plasticity and neuroendocrine transdifferentiation. Conventional genome-based models fail to account for the divergent clinical trajectories observed among tumors that share identical driver mutations. This limitation requires reconceptualizing cancer as a dynamic system in which tumor cells can execute context-dependent molecular programs governed by epigenetic and transcriptional network remodeling. This review critically evaluates three convergent technological pillars reshaping prostate cancer research and clinical care. First, conditional reprogramming (CR) enables the rapid generation of patient-derived models that preserve genomic fidelity, intratumoral heterogeneity, and reversible phenotypic plasticity without genetic manipulation. Second, single-cell and spatial multi-omics approaches have clarified the cellular trajectories underlying luminal-to-neuroendocrine transdifferentiation, identifying a therapeutically actionable intermediate state. They have revealed the hierarchical transcription factor network (FOXA2–NKX2-1–p300/CBP) which orchestrates chromatin remodeling during this lethal transition. Third, physics-informed machine learning and digital twin architectures aim to move beyond correlative risk prediction toward mechanistically sound forecasting of tumor evolution, treatment response, and resistance emergence. We address unresolved challenges in prospective clinical validation, spatial heterogeneity capture, regulatory pathways for functional diagnostics, and the imperative for causal, as opposed to associative, inference from perturbational datasets. The integration of these three domains through closed-loop experimental–computational feedback cycles represents a paradigm shift from reactive to anticipatory precision oncology. Full article

Triple-negative breast cancer (TNBC) is associated with a high risk of brain metastases (BMs). Although systemic therapies have improved extracranial disease control, the central nervous system (CNS) remains less accessible to numerous agents. As a result, this limited drug penetration makes brain metastases (BMs) remain common in TNBC, which are a leading cause of serious symptoms. This review summarizes recent key advances in triple-negative breast cancer brain metastases (TNBC-BMs), including epidemiology, prognostic stratification, biological mechanisms of CNS tropism and treatment resistance, and evolving management strategies. We discuss potential mechanisms of brain colonization, including the FOXC1-CXCR4 axis, ST6GALNAC5-related interactions with the blood–brain barrier (BBB), and the bidirectional crosstalk between metastatic cells and the brain microenvironment, particularly astrocytes and microglia. Furthermore, we evaluate the evolving clinical management, emphasizing the transition from whole-brain radiotherapy (WBRT) toward more selective local approaches such as stereotactic radiotherapy (SRS) and hippocampal sparing techniques. Concurrently, we examine the integration of CNS active systemic therapy across specific molecular subsets. This review systematically distinguishes standard-of-care interventions from investigational strategies, ultimately underscoring critical evidence gaps within the TNBC-BM landscape. Full article

Background: T-cell-engaging bispecific antibodies (TCEs) have transformed haematological malignancy treatment (blinatumomab > 40% complete remission), yet solid tumour efficacy remains limited (<15% response rates) due to antigen heterogeneity, immunosuppressive microenvironments, and T-cell dysfunction. Systematic molecular engineering, biomarker-driven patient selection, and rational tumour microenvironment modulation are now collectively transforming TCEs from experimental agents into an adaptable platform therapy for solid tumours. Methods: Review of 55 phase I–III trials of CD3-based TCEs in solid tumours, including tarlatamab (DLL3-targeted, small-cell lung cancer) and xaluritamig (STEAP1-targeted, prostate cancer). Analysis of next-generation engineering strategies and resistance mechanisms via genomic and immunohistochemical data. Result: Response rates now approach ~40% in selected settings, marking an inflection point. In extensive-stage small-cell lung cancer, tarlatamab achieved ~40% responses with definitive survival benefit (phase III HR 0.60, 95% CI 0.47–0.77; p < 0.001; median OS 13.6 months). In metastatic castration-resistant prostate cancer, xaluritamig produced ~41% responses in heavily pretreated patients. Step-up dosing reduced severe cytokine release syndrome to <1% (as low as 0.6% with teclistamab), enabling outpatient administration. Neurological adverse events require monitoring but are less frequent than with cellular therapies. Together these results mark a decisive transition from proof-of-concept to clinically validated platform therapy. Discussion: Three resistance mechanisms limit durability: (i) antigen heterogeneity (28–60% of progressors develop antigen-negative subclones); (ii) immunosuppressive microenvironments (stromal barriers, myeloid-derived suppressor cells, hypoxia); (iii) T-cell exhaustion (PD-1/TIM-3/LAG-3 co-expression). Conclusions: Next-generation TCE platforms integrating conditional activation, cytokine payloads, and checkpoint modulation—deployed with biomarker-guided selection and TME-modulating combinations—represent a transformative therapeutic strategy. With tarlatamab’s phase III survival benefit establishing clinical proof-of-concept, and pivotal trials underway for xaluritamig and next-generation agents, TCEs are positioned to become standard-of-care platform therapies in biomarker-defined solid tumours by 2028–2030. Full article