Search Results (806)

The management of resectable pancreatic ductal adenocarcinoma (R-PDAC) and borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) remains a topic of active debate. Although neoadjuvant therapy (NAT) has shown clinical benefits in BR-PDAC, especially in increasing resectability and achieving higher rates of margin-negative (R0) resections, its role in R-PDAC is less clearly defined. Additionally, the role of immunotherapy in PDAC is still being explored, with ongoing trials investigating new combinations to overcome the tumor’s immune-resistant microenvironment. This article provides a comprehensive narrative review of the current evidence comparing NAT with upfront surgery in pancreatic cancer management, focusing on randomized controlled trials and meta-analyses that assess outcomes in R-PDAC and BR-PDAC. The review aims to determine whether NAT offers a significant survival advantage over traditional post-operative strategies and to clarify which clinical scenarios may benefit most from NAT. The literature was identified through a systematic search of PubMed, Scopus, and Google Scholar databases up to March 2025. Article selection adhered to the PRISMA guidelines. Our review of existing evidence supports NAT as the standard of care for BR-PDAC. Meanwhile, management of R-PDAC should be tailored individually, guided by risk stratification that considers both clinical parameters and molecular features. Immunotherapy and targeted therapies are still in early research phases, and their further integration as NAT remains controversial. Full article

Adolescence represents a critical period of neurodevelopment during which brain-derived neurotrophic factor (BDNF) plays a fundamental role in neuronal survival and synaptic plasticity. While exercise-BDNF relationships are well-documented in adults, evidence in adolescents remains limited and inconsistent. This systematic review examined the effects of exercise modalities on circulating BDNF concentrations in adolescent populations. A systematic search was conducted following PRISMA guidelines across multiple databases (FECYT, PubMed, SPORTDiscus, ProQuest Central, SCOPUS, Cochrane Library) through June 2025. Inclusion criteria comprised adolescents, exercise interventions, BDNF outcomes, and randomized controlled trial design. Methodological quality was assessed using the PEDro scale. From 130 initially identified articles, 8 randomized controlled trials were included, with 4 rated as excellent and the other 4 as good quality. Exercise modalities included aerobic, resistance, concurrent, high-intensity interval training, Taekwondo, and whole-body vibration, with durations ranging 6–24 weeks. Four studies demonstrated statistically significant BDNF increases following exercise interventions, four showed no significant changes, and one reported transient reduction. Positive outcomes occurred primarily with vigorous-intensity protocols implemented for a minimum of six weeks. Meta-analysis was not feasible due to high heterogeneity in populations, interventions, and control conditions. Moreover, variation in post-exercise sampling timing further limited comparability of BDNF results. Future research should standardize protocols and examine longer interventions to clarify exercise-BDNF relationships in adolescents. Full article

Background: Immune checkpoint inhibitors (ICIs) have limited efficacy in proficient mismatch repair (pMMR) and microsatellite stability (MSS) metastatic colorectal cancer (mCRC). Inhibition of vascular endothelial growth factor (VEGF) or cytotoxic chemotherapy can boost immunogenicity and has the potential to upregulate ICI efficacy. Methods: A comprehensive electronic literature search was conducted up to April 2025 to identify randomized controlled trials comparing cytotoxic chemotherapy plus bevacizumab with or without ICI. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), objective response rate (ORR), and severe adverse events (AEs: grade 3 or more). A meta-analysis was performed using random-effects models to calculate hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Results: Four studies involving 986 patients (With-ICI group, n = 651; Without-ICI group, n = 335) were included. The meta-analysis demonstrated a significant improvement in PFS in the With-ICI group compared with the Without-ICI group, with an HR of 0.82 (95% CI: 0.70–0.96, p = 0.01) without statistical heterogeneity. No significant improvements were observed between the With- and Without-ICI groups in OS and ORR meta-analyses, but the With-ICI group had a favorable trend in OS. A significant increase in serious AEs was not observed in the With-ICI group. Conclusions: This meta-analysis suggests a potential benefit of adding ICIs to chemotherapy plus bevacizumab in pMMR mCRC; however, the evidence remains preliminary and hypothesis-generating, warranting further investigation in biomarker-driven trials and clarification of long-term outcomes. Full article

Background: The advances in cancer diagnosis and treatment have significantly improved survival rates in pediatric patients, with five-year survival now exceeding 80% in many high-income countries. However, these life-saving therapies often carry long-term consequences, including impaired fertility. The reproductive health of childhood cancer survivors has emerged as a key issue in survivorship care. Objective: This narrative review aims to examine the gonadotoxic effects of cancer treatments on pediatric patients, evaluate fertility preservation strategies in both males and females, and provide guidance on the long-term monitoring of reproductive function post treatment. Methods: A comprehensive literature review was conducted using PubMed, including randomized trials, cohort studies, and clinical guidelines published up to March 2024. The keywords focused on pediatric oncology, fertility, and reproductive endocrinology. Studies were selected based on relevance to treatment-related gonadotoxicity, fertility preservation options, and follow-up care. Results: Radiotherapy and alkylating agents pose the highest risk to fertility. Postpubertal patients have access to standardized preservation techniques, while prepubertal options remain experimental. Long-term effects include premature ovarian insufficiency, azoospermia, hypogonadism, and uterine dysfunction. The psychosocial impacts, especially in female survivors, are profound and often overlooked. Conclusions: Fertility preservation should be discussed at diagnosis and integrated into treatment planning in pediatric patients with cancer. While options for postpubertal patients are established, more research is needed to validate safe and effective strategies for younger populations. A multidisciplinary approach and long-term surveillance are essential for safeguarding future reproductive potential in childhood cancer survivors. Full article

Objective: Craniopharyngioma recurrence risk studies comparing gross total resection (GTR) vs. subtotal resection (STR) with radiotherapy (XRT) provide inconclusive or contradictory results. This may be an effect of the small group sizes and diversity in the approaches used. Currently, the endoscopic endonasal approach (EEA) is preferred in craniopharyngioma management. Here, we aimed to perform a meta-analysis comparing recurrence risk after GTR vs. STR plus XRT in patients treated with the EEA regimen. Methods: We performed a systematic literature search of original English language papers on craniopharyngioma management published in the PubMed, Web of Science, and Scopus databases up to 18 October 2023. Eleven articles included data on recurrence rate after EEA: GTR vs. STR with XRT. We extracted the year of publication, number of patients, surgical approach, extent of resection, and follow-up duration. We used meta-analysis for the odds ratio (OR) in fixed and random effects models and Egger’s and Begg’s tests to assess heterogeneity and publication bias. Follow-up duration and time to recurrence were additionally included in Kaplan–Meier curves with log-rank test analysis. Results: We observed a lower recurrence rate in patients after GTR (10%) as compared to STR with XRT (30%), OR = 0.299, p < 0.001. To increase data reliability, we limited our analysis to studies with at least five patients in each subgroup and also observed lower recurrence in patients after GTR (12%) as compared to STR with XRT (27%), OR = 0.376, p = 0.011. Survival analysis confirmed significant differences in recurrence-free survival percentages between these groups (p = 0.008). Conclusions: To date, this is the largest meta-analysis evaluating the recurrence risk in patients undergoing EEA for craniopharyngioma resection, comparing outcomes between those treated with GTR and those treated with STR plus XRT. The results suggest that GTR significantly reduces recurrence risk. Full article

Background: Intracerebral hemorrhage (ICH) is a severe form of stroke associated with high morbidity and mortality. While neurosurgical evacuation may offer theoretical benefits, its impact on survival and hospital course remains debated. We aimed to compare the outcomes of surgical versus conservative management in patients with lobar, capsulo-lenticular, and thalamic ICH and to identify factors influencing mortality and the surgical decision. Methods: This single-center, retrospective cohort study included adult patients admitted to the County Clinical Emergency Hospital of Sibiu (2017–2023) with spontaneous supratentorial ICH confirmed via CT (deepest affected structure determining lobar, capsulo-lenticular, or thalamic location). We collected data on demographics, clinical presentation (Glasgow Coma Scale [GCS], anticoagulant use), hematoma characteristics (volume, extension), treatment modality (surgical vs. conservative), and in-hospital outcomes (mortality, length of stay). Statistical analyses included t-tests, χ², correlation tests, and logistic regression to identify independent predictors of mortality and surgery. Results: A total of 445 patients were analyzed: 144 lobar, 150 capsulo-lenticular, and 151 thalamic. Surgical intervention was more common in patients with larger volumes and lower GCS. Overall, in-hospital mortality varied by location, reaching 13% in the lobar group, 20.7% in the capsulo-lenticular group, and 35.1% in the thalamic group. Within each location, surgical intervention did not significantly reduce overall in-hospital mortality despite the more severe baseline presentation in surgical patients. In lobar ICH specifically, no clear survival advantage emerged, although surgery may still benefit those most severely compromised. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower mortality (39.4% vs. 61.5%). In patients with large lobar ICH, surgical intervention was associated with mortality rates similar to those seen in less severe, conservatively managed cohorts. Multivariable adjustment confirmed GCS and hematoma volume as independent mortality predictors; age and volume predicted the likelihood of surgical intervention. Conclusions: Despite targeting more severe cases, neurosurgical evacuation did not uniformly lower in-hospital mortality. In lobar ICH, surgical patients with larger hematomas (~48 mL) and lower GCS (~11.6) had mortality rates (~13%) comparable to less severe, conservative cohorts, indicating that surgical intervention was associated with similar mortality rates despite higher baseline risk. However, these findings do not establish a causal survival benefit and should be interpreted in the context of non-randomized patient selection. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower observed mortality (39.4% vs. 61.5%). Thalamic ICH remained most lethal, highlighting the difficulty of deep-brain bleeds and frequent ventricular extension. Across locations, hematoma volume and GCS were the primary outcome predictors, indicating the need for timely intervention, better patient selection, and possibly minimally invasive approaches. Future prospective multicenter research is necessary to refine surgical indications and validate these findings. To our knowledge, this investigation represents the largest and most contemporary single-center cohort study of supratentorial intracerebral hemorrhage conducted in Romania. Full article

Colorectal surgery has undergone significant advances over the past few decades, driven by the evolution of minimally invasive techniques, particularly laparoscopy and robotics. While laparoscopy is widely recognized for its short-term benefits and oncological safety, the increasing adoption of robot-assisted surgery (RAS) has generated considerable debate regarding its clinical benefits, economic implications, and overall impact on patient outcomes. This narrative review synthesizes the existing evidence, highlighting the clinical and economic aspects of RAS in colorectal surgery, while exploring areas for future research. The findings suggest that RAS offers potential technical advantages, including increased precision, three-dimensional visualization, and improved ergonomics, particularly in anatomically complex scenarios such as low rectal resections. Still, its superiority over laparoscopy remains inconclusive and current evidence is mixed. For colon cancer, meta-analyses and analyses of large cohorts suggest lower conversion rates and faster recovery with RAS, although data are mostly retrospective and lack long-term oncological endpoints. In rectal cancer, emerging evidence from randomized controlled trials demonstrates improved short-term outcomes. Additionally, the recently published three-year results of the REAL trial are the first to demonstrate enhanced oncological outcomes following RAS. However, findings remain inconsistent due to methodological heterogeneity, the absence of patient stratification, and limited data on long-term survival and cost-effectiveness. The available evidence indicates that RAS may offer advantages in selected patient populations, particularly for anatomically complex procedures. Yet, its overall utility remains uncertain. Future studies should emphasize high-quality randomized trials, stratified subgroup analyses, and standardized economic evaluations to better define the role of RAS in colorectal surgery. Full article

Background: Androgen deprivation therapy (ADT) is a primary treatment for prostate cancer (PCa) that effectively reduces androgen levels to suppress tumor progression. However, growing evidence suggests potential cognitive side effects, raising concerns about the long-term neurological consequences of this treatment. Objective: This scoping review aims to synthesize the existing evidence linking ADT to cognitive changes in men with PCa, identifying the key cognitive domains affected and outlining gaps in the existing literature. Methods: A systematic literature search was conducted according to the PRISMA-ScR guidelines in CINAHL, PubMed, Scopus, and Web of Science. Studies investigating cognitive function in ADT-treated PCa patients were included, covering randomized controlled trials (RCTs) and cohort, case–control, and cross-sectional studies. The extracted data included the study design, evaluated cognitive characteristics, measurement tools, and overall findings. Results: A total of 22 studies met the inclusion and exclusion criteria. Cognitive assessments varied across studies. While some studies reported cognitive impairments in ADT-treated patients—particularly in working, verbal, and visual memory and executive function—others found no significant effects. The variability in prostate cancer staging, epidemiological study designs, and treatment regimens; the exclusion of comorbid conditions; and the differences in assessment tools, sample sizes, and study durations hinder definitive conclusions about the cognitive effects of ADT. Conclusions: This scoping review highlights the heterogeneous and often contradictory evidence regarding ADT-associated cognitive dysfunction. While certain cognitive domains may be affected, methodological inconsistencies limit robust conclusions. Standardized cognitive assessments and longer longitudinal studies are required to clarify ADT’s role in cognitive decline. As the PCa survival rate increases with extended ADT use, integrating routine cognitive monitoring into clinical practice should be considered for PCa patients. Full article

For patients diagnosed with a malignancy at high risk of developing peritoneal metastases, the concept of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged. The aim of the present study is to assess the role of prophylactic HIPEC in gastric cancer patients at high risk of PC, based on the currently available data in the literature. In total, 14 RCTs and 16 non-RCTs were identified and included in the present review, with 1383 patients included in the RCTs (627 of whom underwent HIPEC) and 1647 patients included in the non-RCTs (with 609 undergoing HIPEC). Prophylactic HIPEC appears to be useful and effective in treating patients with high-risk gastric cancer, improving both overall and disease-free survival. The heterogeneity of data regarding treatment protocols and complication rates suggests that further research is necessary to develop optimal therapeutic approaches and personalized treatment options; in particular, large-scale randomized control trials are needed in order to elucidate the potential benefits associated with the use of prophylactic HIPEC. Full article

Estimating heterogeneous treatment effects (HTEs) across multiple correlated outcomes poses significant challenges due to complex dependency structures and diverse data types. In this study, we propose a novel deep learning framework integrating empirical copula transformations with a CNN-LSTM (Convolutional Neural Networks and Long Short-Term Memory networks) architecture to capture nonlinear dependencies and temporal dynamics in multivariate treatment effect estimation. The empirical copula transformation, a rank-based nonparametric approach, preprocesses input covariates to better represent the underlying joint distributions before modeling. We compare this method with a baseline CNN-LSTM model lacking copula preprocessing and a nonparametric tree-based approach, the Causal Forest, grounded in generalized random forests for HTE estimation. Our framework accommodates continuous, count, and censored survival outcomes simultaneously through a multitask learning setup with customized loss functions, including Cox partial likelihood for survival data. We evaluate model performance under varying treatment perturbation rates via extensive simulation studies, demonstrating that the Empirical Copula CNN-LSTM achieves superior accuracy and robustness in average treatment effect (ATE) and conditional average treatment effect (CATE) estimation. These results highlight the potential of copula-based deep learning models for causal inference in complex multivariate settings, offering valuable insights for personalized treatment strategies. Full article

Background/Objectives: Clostridioides difficile infection (CDI) is a major cause of infectious diarrhea in the inpatient and community setting. Real-world data outside the strict environment of randomized controlled trials (RCTs) are needed to improve the quality of evidence. The aim of this study was to compare different clinical outcomes of CDI patients treated with fidaxomicin with those treated with vancomycin using a representative patient population in the United States of America (USA). Methods: Comprehensive real-world data were analyzed for this retrospective observational study, provided by the TriNetX database, an international research network with electronic health records from multiple USA healthcare providers. This includes in- and outpatients treated with fidaxomicin (FDX) or vancomycin (VAN) for CDI between 01/2013 and 12/2023. The following cohorts were compared: (i) patients treated with fidaxomicin within 10 days following CDI diagnosis (FDX group) vs. (ii) patients treated with vancomycin within 10 days following CDI diagnosis (VAN group). Outcomes analysis between the two cohorts was performed after propensity score matching and included event risk and Kaplan–Meier survival analyses for the following concomitant diseases/events occurring during an observational period of 12 months following CDI diagnosis: death, sepsis, candidiasis, infections caused by vancomycin-resistant enterococci, inflammatory bowel disease, cardiovascular disease, psychological disease, central line-associated blood stream infection, surgical site infection, and ventilator-associated pneumonia. Results: Following propensity score matching, 2170 patients were included in the FDX group and VAN groups, respectively. The event risk analysis demonstrated improved outcomes of patients treated with FDX compared to VAN in 6 out of the 10 events that were analyzed. The highest risk ratio (RR) and odds ratio (OR) were found for sepsis (RR: 3.409; OR: 3.635), candidiasis (RR: 2.347; OR: 2.431), and death (RR: 1.710; OR: 1.811). The Kaplan–Meier survival analysis showed an overall survival rate until the end of the 12-month observational period of 87.06% in the FDX group and 78.49% in the VAN group (log-rank p < 0.001). Conclusions: Our comparative event risk analysis demonstrated improved outcomes for patients treated with FDX compared to VAN in most of the observed events and underlines the results of previously conducted RCTs, highlighting the beneficial role of FDX compared to VAN. Further big data analyses from other industrialized countries are needed for comparison with our observations. Full article

Background: Advanced and recurrent vulvar squamous cell carcinoma (VSCC) presents a major therapeutic challenge with limited treatment options and poor outcomes. Immune checkpoint inhibitors (ICIs) have shown efficacy in other HPV-associated malignancies, but their role in VSCC remains poorly defined due to the rarity of the disease and limited clinical trial data. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines and registered in PROSPERO (CRD420251067565). A comprehensive literature search identified prospective clinical trials evaluating ICIs in patients with advanced, unresectable, recurrent, or metastatic VSCC. The primary outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Risk of bias was assessed using the MINORS tool. Meta-analyses were performed using random-effects models, with subgroup analyses based on PD-L1 status and treatment regimens (monotherapy vs. combination therapy). Results: Six non-randomized single-arm trials involving 181 patients were included. The pooled ORR was 21%, with higher response rates observed in combination therapy (46%) compared to monotherapy (11%), though not statistically significant. Median PFS and OS were 2.2 months and 6.4 months, respectively. ORRs were similar between PD-L1-positive and PD-L1-negative subgroups. A safety analysis showed treatment-related adverse events (AEs) in 73% of patients and grade ≥ 3 AEs in 23%. The incidence of treatment-related death was 3%. Conclusions: ICIs demonstrate modest but durable efficacy and an acceptable safety profile in advanced VSCC. The current evidence supports their use in selected patients. However, response variability and the lack of reliable predictive biomarkers, such as PD-L1 or HPV status, underscore the need for biomarker-driven clinical trials and improved patient selection strategies. Full article

Background and Objectives: Gastric cancer treatment of partial or complete gastrectomy includes lymph nodes dissection (D2) to remove microscopic lymph node metastases adjacent to the tumor. A more extensive approach, an extended dissection (D2plus) has recently been employed, which includes resection of the lymph nodes in the pancreatic and periportal areas. However, despite its potential benefits of longer survival for patients diagnosed with advanced cancer, there are increased risks due to surgical complications. The current study aims to examine the balance between clinical benefit and higher risks of the extended dissection approach versus standard dissection. Materials and Methods: This retrospective analysis of gastric cancer patients treated in Bnai-Zion medical center examined the survival rates, oncological outcomes, and complication rates according to medical records data files. Results: The D2plus group experienced increased postoperative complications rate (56% vs. 20.6% D2 group p = 0.005) with mean survival time, shorter than the D2 standard approach (2.07 years vs. 3.44 years p = 0.01). A higher number of lymph nodes was removed on average in the D2plus group (29.4 ± 11.2), but without statistical significance in comparison to the D2 group (22.6 ± 8.9, p = 0.013). D2plus patients had reduced disease recurrence rates (20% vs. 32.4% in D2 group p = 0.29). Weight loss of D2plus patients was noted for higher rates than the D2 group (40% vs. 17.6% p = 0.056. Conclusions: Our study provides preliminary insights into the comparison between D2 and D2plus dissection in a single-center Western cohort. However, significant baseline differences between groups, particularly age, gender, and histopathological characteristics, limit definitive conclusions. The findings should be interpreted as hypothesis-generating rather than practice-changing. Larger, prospective, multicenter studies with propensity score matching or randomized design are needed to definitively establish the optimal surgical approach for different patient subgroups. Full article

Polatuzumab vedotin (PoV) is a novel antibody-drug conjugate that targets CD79B for the treatment of Non-Hodgkin Lymphoma (NHL). This meta-analysis aimed to evaluate the efficacy and safety of PoV in patients with NHL. A systematic review and meta-analysis of clinical trials evaluating PoV in NHL were conducted. The primary outcomes were complete response (CR) rates, progression-free survival (PFS), and overall survival (OS). Safety outcomes were also assessed. Random-effects models were used for the pooled analyses. Thirteen studies with 1533 patients with NHL were included. PoV significantly improved CR rates compared to control treatments (OR 1.50, 95% CI 1.01–2.21, p = 0.04) and PFS (MD 4.17 months, 95% CI 2.18–6.15, p < 0.0001). OS was not significantly different (OR 0.97, 95% CI 0.47–2.01, p = 0.93). Adverse events were more common with PoV (RR 1.38, 95% CI 0.98–1.94, p < 0.0001). PoV improves CR rates and PFS in patients with NHL, particularly those with relapsed/refractory disease, but is associated with increased adverse events. Further research is needed on long-term survival outcomes and optimal patient selection. PoV appears to be a promising targeted therapy option for NHL, which warrants further investigation. Full article

Background: Refractory ventricular fibrillation (RVF) is a life-threatening condition characterized by the persistence of ventricular fibrillation despite multiple defibrillation attempts. It represents a critical challenge in out-of-hospital cardiac arrest management, with poor survival outcomes and limited guidance from current resuscitation guidelines. In recent years, alternative defibrillation strategies (ADSs), including dual sequential external defibrillation (DSED) and vector change defibrillation (VCD), have emerged as potential interventions to improve defibrillation success and patient outcomes. However, their clinical utility remains debated due to heterogeneous evidence and limited high-quality data. Methods: This narrative review explores the current landscape of ADSs in patients with RVF. MEDLINE, Google Scholar, the World Health Organization, LitCovid NLM, EMBASE, CINAHL Plus, and the Cochrane Library were examined from their inception to April 2025. Results: The available literature is dominated by retrospective studies and case series, with only one randomized controlled trial (DOSE-VF). This trial demonstrated improved survival to hospital discharge with ADSs compared to standard defibrillation. DSED was associated with higher rates of return of spontaneous circulation and favorable neurological outcomes. However, subsequent meta-analyses have produced inconsistent results, largely due to the heterogeneity of the included studies. The absence of sex-, gender-, and ethnicity-specific analyses further limits the generalizability of the findings. In addition, practical barriers, such as equipment availability, pose significant challenges to implementation. Conclusions: ADSs represent a promising yet still-evolving approach to the management of RVF, with DSED showing the most consistent signal of benefit. Further high-quality research is required to enhance generalizability and generate more definitive, high-level evidence. Full article