Search Results (9,210)

Introduction: The NF-κB signaling pathway is a key regulator of oncogenic processes; however, its systemic role in meningiomas remains poorly understood. The aim of this pilot study was to evaluate the expression of genes encoding NF-κB isoforms and IKK complex subunits in peripheral blood mononuclear cells (PBMCs) of patients with meningiomas prior to tumor resection. Methods: The study included 31 patients with meningiomas (WHO grades G1-G3) and 18 healthy volunteers. PBMCs were isolated using density gradient centrifugation, and total RNA was extracted. mRNA expression levels of NFKB1, NFKB2, RELA, RELB, c-REL, CHUK, IKBKB, and IKBKG were quantified by real-time PCR, with GAPDH used as the reference gene. Results: In patients with meningiomas, significantly lower expression of NFKB1 and higher expression of RELA, CHUK, and IKBKB were observed compared with the control group. NFKB1 expression was significantly higher in patients with higher tumor grades (WHO G2/G3) than in those with grade G1 tumors. Moreover, male patients exhibited higher expression levels of c-REL, CHUK, and IKBKB than female patients. Strong positive correlations were observed between components of the canonical NF-κB pathway. Discussion: The results may indicate systemic dysregulation of the NF-κB pathway in immune cells of patients with meningiomas, potentially characterized by activation of the canonical pathway and a shift toward p65/p65 homodimer formation. These alterations could reflect mechanisms associated with immunosuppression. NFKB1 expression may warrant further investigation as a candidate peripheral biomarker of tumor aggressiveness, while the observed sexual dimorphism in gene expression might suggest that sex could represent a relevant factor, requiring confirmation in prospective studies. Full article

Context: Prosthetic rehabilitation of acquired maxillary defects with Maxillary Resection Prostheses (MRPs) remains biomechanically challenging, particularly in partially edentulous patients, where conventional clasp-retained designs often yield suboptimal retention, stability, and functional outcomes. Research Gap: The integration of telescopic crown systems with semi-precision attachments incorporating a rotational latching mechanism has not been previously described as a unified approach to optimise load distribution and prosthesis stability in maxillary defect rehabilitation. Objective: To describe and clinically evaluate a novel prosthetic design combining telescopic crowns and a semi-precision rotational latching attachment to enhance retention, stability, and functional performance of MRPs. Methodology: A 31-year-old patient with a unilateral maxillary defect following partial maxillectomy presented with an unstable interim prosthesis and impaired speech and mastication. A definitive MRP was designed using telescopic crowns on the remaining dentition to establish a controlled path of insertion and improved axial load transfer. A semi-precision attachment with a key–keyway rotational latching mechanism was incorporated into the secondary framework to engage specific undercuts while minimising lateral forces on abutment teeth. A provisional prosthesis was used for 3 months to evaluate base extension, phonetics, and functional parameters before fabrication of the definitive prosthesis. Results: Serial follow-up at 1, 3, and 6 months demonstrate consistent prosthesis stability, precise seating, and favourable retention. Marked improvements were observed in speech intelligibility, masticatory efficiency, and patient-reported comfort. Conclusions: This combined prosthetic strategy represents a novel and biomechanically optimised approach for the rehabilitation of partially edentulous maxillary defects, with promising clinical and functional outcomes. Full article

Background: Pancreatic neuroendocrine tumors (pNETs) represent a heterogeneous group of neoplasms characterized by variable biological behavior and clinical outcomes. Multiple therapeutic strategies have been investigated, including surgery, targeted therapies, peptide receptor radionuclide therapy, and systemic treatments. The present study aimed to summarize survival-related outcomes reported across studies investigating the management of pNETs. Methods: A systematic review of the literature was conducted including studies reporting clinical outcomes in patients with pancreatic neuroendocrine tumors. A total of 27 studies were included in the qualitative analysis. Survival-related outcomes, such as progression-free survival (PFS), recurrence-free survival (RFS), and recurrence rates, were extracted. Studies reporting quantitative survival values were included in the meta-analytical component. A random-effects model was applied, and a forest plot was generated to summarize the reported outcomes. Results: Reported survival outcomes varied substantially across studies. Median PFS values ranged from approximately 5.6 to 86.5 months, while several surgical series reported 5-year overall survival rates exceeding 90%. Recurrence rates following surgical resection ranged from approximately 12% to 26% in some cohorts. The pooled estimate derived from the meta-analytical model was 32.22 (95% CI: 15.65–48.80). Conclusions: The analysis summarizes survival-related outcomes reported in studies investigating pancreatic neuroendocrine tumors and provides a quantitative overview of the reported progression-related endpoints across the analyzed literature. Full article

Implantation of a femoral stem in total hip arthroplasty alters physiological load transfer within the proximal femur. Short-stem designs aim to preserve bone stock and maintain proximal load sharing, yet the influence of femoral neck resection height and its interaction with femoral morphology on primary stability remain insufficiently understood. This in vitro biomechanical study investigated these effects using 33 human femora classified as Dorr B or C. In a paired design, a cemented calcar-guided short stem was implanted with either a low (standard) or +5 mm higher femoral neck resection. Specimens underwent cyclic fatigue loading to assess reversible and irreversible micromotion and interface strain, followed by ultimate compression to quantify global fixation strength. Primary stability was assessed by reversible and irreversible translation of the prosthetic head center of rotation and by cortical interface strain measurements using digital image correlation. Overall fixation strength and irreversible deformation remained comparable across resection heights and Dorr types. In contrast, resection height and femoral morphology influenced reversible micromotion and interface strain, with higher resection reducing reversible micromotion, particularly in Dorr C femora and shifting lateral interface strain toward compression. These findings suggest that surgical technique and femoral morphology mainly affect local, reversible bone–cement–implant mechanics rather than global fixation strength. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with limited therapeutic options, a high mortality rate, and poor overall survival, necessitating the development of new therapeutic and diagnostic strategies. This study investigated the potential of plasma-derived small extracellular vesicles (sEVs) as a source of molecular biomarkers associated with the treatment response. Methods: Plasma samples were obtained from patients with locally advanced and borderline resectable PDAC at baseline and following neoadjuvant chemotherapy, either FOLFIRINOX (5-FU [fluorouracil], leucovorin, oxaliplatin, and irinotecan) or GEM-ABRAX ( gemcitabine plus nab-paclitaxel), followed by stereotactic body radiation therapy (SBRT). sEVs were isolated from plasma at baseline, after neoadjuvant chemotherapy, and following SBRT, and were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), nano-flow cytometry, and real-time PCR (RT-PCR). Results: The isolated sEVs exhibited an average size of <200 nm, expressed canonical exosome markers (CD63 and CD9), and exhibited pancreatic cancer (PanC)-associated markers, including cholecystokinin A receptor (CCK-AR) and carbohydrate antigen 19-9 (CA19-9). The sEV cargo included several PanC-associated microRNAs (miRNAs). Notably, the expression profiles of these miRNAs demonstrated interpatient variability, though a subset of miRNAs showed statistically significant changes following treatment. Conclusions: These findings support the feasibility of sEV isolation and molecular profiling from patient plasma and warrant further investigation as a potential source of biomarkers in pancreatic cancer. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, particularly in metastatic disease where surgical resection is traditionally not recommended. However, the concept of oligometastatic disease—characterized by limited metastatic spread with a presumed more favorable oncological prognosis—has prompted reconsideration of metastasis-directed therapies, including surgery, in carefully selected patients. Methods: A selective literature review was conducted using PubMed to identify studies reporting surgical treatment for oligometastatic PDAC, including synchronous or metachronous metastases. Studies were included if they reported outcomes after resection of the primary tumor and/or metastatic lesions in patients with limited metastatic burden. Results were presented in a narrative way. Results: Retrospective studies suggest that surgical resection of the primary tumor and metastases may be feasible, safe and associated with prolonged survival in selected patients with oligometastatic PDAC. Favorable prognostic factors across studies include response to systemic chemotherapy prior to resection, low tumor marker levels, limited number of metastases, and the possibility of achieving complete macroscopic resection. Patients with isolated pulmonary metastases appear to have particularly favorable outcomes. However, existing evidence is derived exclusively from retrospective analyses and is subject to considerable selection bias. Conclusions: Current evidence indicates that surgery for oligometastatic PDAC may benefit highly selected patients within a multimodal treatment strategy. The results of ongoing prospective and randomized clinical trials are expected to clarify the role of surgery in this setting. Until these results become available, treatment decisions should be individualized and made within multidisciplinary tumor boards. Full article

Background/Objectives: Liposarcoma represents a heterogeneous group of mesenchymal malignancies with distinct molecular profiles and clinical behaviors. While localized disease is managed with surgical resection, advanced or metastatic liposarcoma poses a significant therapeutic challenge due to limited response to traditional cytotoxic chemotherapy. This review summarizes current evidence-based systemic therapies and highlights recent advances in subtype-driven treatment strategies. Methods: We review key clinical trials supporting the use of anthracycline regimens, trabectedin, eribulin, and nuclear export inhibition with selinexor, as well as emerging targeted approaches directed at MDM2 and CDK4 amplification. In addition, we discuss the evolving role of immunotherapy, including checkpoint inhibitors and engineered T-cell receptor therapies targeting cancer–testis antigens. Results: Integrating molecular biology with therapeutic development, we emphasize the importance of histologic and genomic classification in guiding treatment selection and clinical trial design. Conclusion: Continued progress in biomarker-driven strategies and rational combination therapies is expected to further refine personalized treatment approaches and improve outcomes for patients with advanced liposarcoma. Full article

Background and Clinical Significance: Cutaneous paraneoplastic phenomena are infrequently characterised in colorectal cancer (CRC), and chronic pruriginous inflammatory eruptions in particular have received limited attention. In older adults, persistent treatment-resistant dermatoses of unclear aetiology may represent overlooked extraintestinal diagnostic clues to occult malignancy, including potentially curable CRC. Faecal immunochemical testing (FIT) for occult bleeding is a low-cost, non-invasive tool whose role outside conventional alarm-symptom triage remains underexplored. Case presentation: A 72-year-old woman presented for outpatient evaluation with several months of pruriginous, pustular, and crusted symmetric eruption involving the dorsal aspects of the limbs, refractory to standard dermatologic treatment, and without gastrointestinal symptoms. A non-invasive systemic stool-based work-up demonstrated detectable faecal haemoglobin (iFOBT), mildly elevated faecal calprotectin (51.6 mg/kg, ULN 50 mg/kg), markedly elevated faecal alpha-1-antitrypsin (631 µg/mL; 2.3× ULN), and predominance of Escherichia coli on stool culture. Colonoscopy revealed a locally advanced rectal adenocarcinoma; staging classified the lesion as cT3N1M0. The patient received long-course neoadjuvant chemoradiotherapy (50 Gy, concurrent capecitabine) followed by low anterior resection with total mesorectal excision and pathological complete response (ypT0N0, R0), and adjuvant capecitabine. The cutaneous eruption resolved progressively in parallel with antineoplastic therapy without specific dermatologic intervention. The patient remains in remission at over 36 months. Conclusions: Persistent, unexplained, treatment-resistant pruriginous/pustular cutaneous eruptions may, in selected patients, coincide with an underlying malignancy, including colorectal cancer, and should prompt careful individualised clinical assessment, including review of age-appropriate colorectal cancer screening status. This single case raises the hypothesis that quantitative faecal immunochemical testing (FIT) may be prospectively evaluated as a low-cost, non-invasive triage tool in carefully selected patients aged ≥50 years with persistent dermatoses of unclear aetiology, even in the absence of gastrointestinal symptoms. Positive FIT results should be managed according to established local colorectal referral pathways. NICE diagnostics guidance DG56 supports FIT use in symptomatic adults with suspected lower gastrointestinal pathology; however, any extension of FIT to extraintestinal presentations remains investigational and requires formal validation through prospective studies assessing diagnostic yield, cost-effectiveness, and stage distribution. Full article

IDH-wildtype glioblastoma remains the most aggressive primary brain tumor, with a median overall survival (OS) of 14–16 months despite maximal treatment. A small subset of patients, however, survive beyond 30 months, suggesting distinct underlying biological features. The aim of this pilot study was to explore whether selected molecular alterations detectable by FISH show differing distribution patterns between patients with prolonged and poor survival in IDH-wildtype glioblastoma. We retrospectively analyzed 20 patients with newly diagnosed primary IDH-wildtype glioblastoma who underwent gross-total resection followed by standard radiotherapy and temozolomide treatment between 2016 and 2022. Patients were categorized into two predefined groups according to survival outcomes: long-term survivors (OS > 30 months) and short-term survivors (OS < 10 months). Fluorescence in situ hybridization (FISH) was used to evaluate alterations in ATRX, BRAF, and PIK3CA. MGMT promoter methylation, EGFR amplification, and TERT promoter mutation status were obtained from routine diagnostic reports. Because survival groups were intentionally pre-selected as extreme phenotypes, time-to-event analysis was not appropriate. Therefore, statistical comparisons were performed using Fisher’s exact test and multivariable logistic regression with long-term versus short-term survival as a binary outcome. Short-term survivors had a significantly higher median age (57.5 vs. 46.5 years, p = 0.043) and a higher rate of EGFR amplification (100% vs. 50%, p = 0.033). Strikingly, combined BRAF and PIK3CA alterations (predominantly polysomy) were detected in 8 out of 10 (80%) long-term survivors, compared to 0 out of 10 (0%) short-term survivors (p = 0.0007). In multivariable logistic regression adjusted for age and MGMT promoter methylation, BRAF/PIK3CA alteration remained strongly associated with long-term survival, though the effect size was mathematically inflated due to perfect separation (0 events in Group B). BRAF and PIK3CA copy number alterations were observed exclusively in long-term survivors in this small exploratory cohort, suggesting a possible association with prolonged survival. However, given the limited sample size, the selection of extreme survival groups, and the predominance of chromosomal polysomy detected by FISH, these findings should be interpreted as hypothesis-generating only. Further validation in larger cohorts using high-resolution genomic methods is warranted. Full article

Background: Soft-tissue sarcomas (STSs) are rare and heterogeneous malignancies with generally poor and unpredictable prognosis. Tertiary lymphoid structures (TLSs) have been identified as favorable prognostic indicators in several cancer types, yet their role in STS remains poorly defined. This study investigates the prognostic relevance of TLS presence, maturity, location and density in resected STSs. Methods: We retrospectively analyzed 219 cases of primary STS surgically resected at the Bergonié Institute (France) between 1990 and 2020. TLSs were assessed for presence, spatial distribution, semi-quantitative density and degree of maturity using CD20 and CD23 immunohistochemistry, categorizing tumors as fully mature TLS-positive (fmTLS⁺) or -negative (fmTLS⁻). RNA sequencing was performed on 126 formalin-fixed paraffin-embedded samples to characterize immune microenvironment profiles. Survival outcomes—including overall survival (OS), time to locoregional progression (TTLRP), and time to distant progression (TTDP)—were analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Results: The presence of fmTLS was significantly associated with improved 5-year OS (p = 0.012) and cause-specific survival (p = 0.006). Unexpectedly, fmTLS⁺ tumors showed a higher rate of local recurrence (22.9% vs. 8.1%, p = 0.002). On multivariate analysis, high-density fmTLS⁺ tumors conferred a 2.68-fold increased risk of locoregional progression (95% CI: 1.28–5.59, p = 0.009). Transcriptomic profiling confirmed a significant correlation between fmTLS⁺ status and a high-immune phenotype (Φ = 0.30, p < 0.001). Conclusions: STSs with fmTLS are associated with improved OS but increased risk of local recurrence. These findings support fmTLS as a dual prognostic biomarker and highlight the need for tailored surveillance and adjuvant strategies in fmTLS⁺ patients. Full article

Background: Desmoplastic fibroma (DF) is a rare, benign, but locally aggressive intraosseous tumor with a predilection for the mandible in pediatric patients. Owing to its low incidence, evidence guiding management remains limited. Objective: To provide a comprehensive review of the clinical presentation, radiographic features, treatment strategies, and outcomes of pediatric DF of the jaws. Methods: A comprehensive literature review was conducted using PubMed/MEDLINE, Embase, Cochrane Library, and IEEE Xplore to identify relevant studies published between 2000 and 2026. Given the rarity of this entity, a broad search strategy was applied. Eligible studies were analyzed to extract data on patient demographics, clinical features, imaging findings, treatment modalities, and outcomes. Results: A total of 32 studies comprising 45 pediatric cases were identified. The mandible was involved in 86.7% of cases. The most common presentation was painless swelling or facial asymmetry (68.9%). Wide or segmental resection was the primary treatment in 68.9% of cases. Recurrence data were available for 75.6% of cases, with an overall recurrence rate of 2.9%, occurring following incomplete resection. Conclusions: Pediatric DF of the jaws is a rare but locally aggressive tumor requiring accurate diagnosis and individualized surgical management. Complete resection with clear margins appears to provide the most reliable outcomes. However, interpretation of outcomes is limited by the predominance of case reports, heterogeneous reporting, and incomplete follow-up. Future multicenter studies and standardized reporting are needed to better define optimal management strategies. 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

Background/Objectives: Colorectal cancer (CRC) represents a major public health problem in Mexico and is among the malignancies with the highest morbidity and mortality. Alterations in TP53 are frequent molecular events in tumors with chromosomal instability; however, information on TP53 variants in the Mexican population, particularly in exons 4-8, remains limited. Exons 4-8 comprise the main coding region of the p53 DNA-binding domain; therefore, this study aimed to identify TP53 variants in these regions and evaluate p53 protein expression by immunohistochemistry in sporadic CRC. Methods: Tumor samples from 142 patients who underwent surgical resection without neoadjuvant treatment were analyzed. DNA was extracted from tumor tissue. TP53 exons 4-8 were amplified by polymerase chain reaction (PCR), and variants were identified by Sanger sequencing. p53 immunohistochemistry was performed in 40 tumors and 36 adjacent tissues, and nuclear expression was assessed using the Immunoreactivity Score. Results: Forty-three heterozygous variants were identified in 106/142 patients, representing 75% of the cohort. Thirty-one patients carried oncogenic variants, mainly clustered within the DNA-binding domain and involving hotspot residues such as Arg175, Tyr220, Gly245, Arg248, Arg273, and Arg282. Nuclear p53 expression was observed in 9/40 tumors, whereas all adjacent tissues were negative. Conclusions: TP53 alterations in exons 4-8 are frequent and heterogeneous in this Mexican cohort. Integrating mutational profiling with p53 immunohistochemistry provides complementary information for the biological interpretation of these tumors, including variants of translational interest. Full article

Background and Objectives: Positron emission tomography with 18F-FDG (PET-CT) provides a quantitative measure of tumor metabolic activity through the maximum standardized uptake value (SUVmax) of lung tumors—a measure of metabolic activity that may have prognostic value in non-small cell lung cancer (NSCLC). This study evaluated whether preoperative tumor SUVmax predicts outcomes in resected NSCLC. Materials and Methods: This single-center retrospective study included 209 consecutive patients with resected NSCLC who had preoperative FDG PET-CT. SUVmax of the primary tumor was recorded, and patients were stratified into low- and high-SUVmax groups to evaluate survival outcomes. Results: Median age was 62 years and 77% were male. Histologic subtypes were adenocarcinoma (44%), squamous carcinoma (43%), and others (13%), with stage I–III distribution of 39.7%, 33.5%, and 26.8%, respectively. SUVmax demonstrated moderate discrimination for mortality (AUC = 0.652), with an optimal cutoff of 11.14. Patients with SUVmax ≥ 11.14 had significantly worse OS and DFS. However, on multivariate analysis, SUVmax was not an independent predictor of outcomes, while extracapsular invasion (OS) and adjuvant chemotherapy (DFS) remained significant. Conclusions: In this cohort of resected NSCLC, high preoperative SUVmax (≥11.14) was associated with more advanced tumor stage and worse OS/DFS but was not an independent prognostic factor after accounting for other variables. Tumor invasiveness and use of adjuvant therapy were stronger outcome predictors. Preoperative SUVmax may help identify high-risk patients when considered alongside established clinicopathologic factors. Full article

Background: Spleen-preserving (SP) distal pancreatectomy (DP) with splenic vessel resection (SVR) (Warsaw procedure, WP) is an option for the treatment of tumors with low malignant potential. The reverse blood flow through the short gastric arteries (SGA) explains the preservation of the spleen after SVR, but leaves the source of the blood supply to the SGAs hidden. The types of blood supply to the spleen after WP and their incidence have not been previously described, nor has the significance of these types for locally advanced pancreatic head cancer (LAPHC) surgery been determined. Aim: To determine the main types of spleen blood supply after WP, and to assess the feasibility and safety of splenic artery (SA) rotation for the organ-preserving surgery of LAPHC. Methods: Retrospective analyses of demographic and perioperative data, including CT scans, overall (OS) and progression-free (PFS) survival after 71 SP DP SVR and 41 SP SVR pancreaticoduodenectomies (PD) and total pancreatectomies (TP) for LAPHC (2007–2025). Results: In 134 SP procedures, SA was resected in 115 cases (71DP, 9 TP, 3 central, and 32 PD). Indications for surgery were MCN (41), IPMN (14), CSA (3), NEN (25), SPPN (8), PHDAC (40), sarcoma (1), autoimmune (1), and calculous chronic pancreatitis (1). There were no deaths or ischemia-related splenectomies. Morbidity—31% (n23); Dindo–Clavien (D-C) > 3b-2.8%; POPF-grade B-n7 (10.6%); splenic infarctions on CT after SVR-n18 (23%), one symptomatic. CT revealed three types of arterial blood supply to the spleen after SPDP SVR: left gastric artery (LGA) type (n50, 70, 5%), gastro-epyploic arcade (GEA) type (n9, 12, 5%), and an intermediate type (n12, 17%). Spleen- and pancreas tail-preserving SVR pancreatectomies for LAPHC (n41) were accompanied by rotation of the SA to substitute resected SMA (n19) and CHA (n15) for 26 Whipples and 8TPs. There were no ischemic complications. D-C > 3–19.5%. Median OS and PFS for PDAC were 35 and 21 months for 29.5 months median follow-up. Conclusions: Despite the preservation of blood flow through all potential sources of splenic blood supply following resection of the splenic artery, the main collaterals supplying the spleen after WP are LGA branches (~90%). This knowledge, with strict adherence to the developed criteria, allows for the safe preservation of the spleen, pancreatic tail, and stomach during pancreatectomies with SA resection, including its rotation for the substitution of the SMA and CHA in LAPHC. Full article