Search Results (365)

Background: Gallbladder carcinoma (GBC) represents one of the most aggressive malignancies of the hepatobiliary system, evolving along a continuum from chronic inflammation to preneoplastic lesions and invasive cancer. This progression is frequently associated with gallstones and chronic cholecystitis and shares common pathogenic mechanisms with systemic inflammatory and metabolic disorders. Despite its relatively low incidence, GBC is characterized by poor prognosis, largely due to late-stage diagnosis and limited understanding of its molecular underpinnings. Methods: We conducted an observational study including 60 adult patients with radiologically suspected gallbladder cancer (GBC). Patients with disseminated disease, ongoing oncologic treatment, or synchronous malignancies were excluded. Fasting venous blood samples were collected to evaluate tumor markers and biochemical parameters, including carcinoembryonic antigen (CEA) and carbohydrate antigen CA 19-9. Surgical specimens were analyzed histopathologically and staged according to the European Society for Medical Oncology TNM classification system. Statistical analysis was performed using SPSS software (version 26.0), with appropriate parametric or non-parametric tests applied based on data distribution, and a p-value < 0.05 considered statistically significant. Results: Based on histological findings, patients were stratified into benign gallbladder disease (GBD) and GBC groups. CA 19-9 demonstrated higher mean serum levels with lower variability compared to CEA, suggesting superior sensitivity and diagnostic stability for gallbladder adenocarcinoma. In contrast, CEA levels exhibited greater fluctuation, limiting its reliability as a standalone biomarker. Importantly, the combined use of CA 19-9 and CEA improved diagnostic accuracy, supporting a multimarker approach for better clinical stratification. Our findings highlight the diagnostic value of CA 19-9 as a robust biomarker in GBC and support the integration of combined biomarker panels. Beyond tumor markers, the study identified a strong interplay between systemic inflammation and metabolic comorbidities, with obesity and hypertension significantly associated with chronic gallbladder pathology, and diabetes mellitus contributing to increased risk of acute inflammatory episodes. Elevated inflammatory markers, leukocytosis, and cholestatic enzyme alterations further supported the presence of a systemic inflammatory milieu. Multivariate analysis revealed that C-reactive protein (CRP), as a marker of systemic inflammation, was significantly influenced by a combination of clinical and biochemical variables, including age, hemoglobin, hypertension, amylase, CA 19-9, and CEA, explaining over 50% of its variability and up to 85% in advanced fibrotic changes. Additionally, platelet counts were significantly reduced in adenocarcinoma and correlated specifically with CA 19-9 levels, suggesting a potential link between tumor burden, inflammation, and platelet dynamics. Conclusions: Therefore, the observed associations between chronic inflammation, metabolic dysregulation, and tumor marker expression suggest a potential link between gallbladder carcinogenesis and systemic cardiometabolic pathways, opening new perspectives for early detection and targeted therapeutic strategies. Full article

Background and Objectives: Neoadjuvant chemoradiotherapy is a key component of the treatment strategy for locally advanced rectal cancer (LARC), both through its direct impact on oncological prognosis and by increasing the likelihood of sphincter-preserving surgery. Oncological prognosis improves dramatically following a complete pathological response to neoadjuvant therapy. Identifying predictors of response to neoadjuvant therapy has been a challenge over the past two decades, and these factors have not been fully identified. This study aimed to analyze the clinical, biological, and therapeutic factors associated with tumor response following neoadjuvant therapy in patients with locally advanced rectal cancer, with the aim of identifying independent predictors of the absence of a complete pathological response and optimizing personalized treatment strategies. Materials and Methods: This retrospective study included a cohort of 122 patients (81 men and 41 women), with a mean age of 63.5 years, diagnosed with locally advanced rectal cancer at two centers with expertise in colorectal surgery between January 2018 and December 2023. Patients received neoadjuvant treatment in two regimens: long-course chemoradiotherapy with oral radiosensitizing chemotherapy (82 patients) and total neoadjuvant therapy consisting of chemoradiotherapy followed by consolidation chemotherapy (40 patients). A series of clinical, biological, and therapeutic variables was analyzed for their association with pathological responses. Results: According to the Ryan score, the overall complete response rate following neoadjuvant therapy was 17.2%. pCR was observed more frequently in patients treated with total neoadjuvant therapy than in those treated with standard chemoradiotherapy. Elevated pre-treatment CEA levels were independently associated with a higher risk of unfavorable tumor response. The radiation dose and interval between completion of radiotherapy and surgery were significantly associated with tumor regression. Conclusions: These results underscore the importance of personalizing neoadjuvant therapy to improve cancer prognosis. Furthermore, optimizing tumor regression could lead to the potential expansion of sphincter-preserving resection techniques, which would have a direct and significant impact on the quality of life of these patients. Full article

Background/Objectives: Carcinoembryonic antigen (CEA) is widely used in colon cancer management; however, its diagnostic and prognostic accuracy is limited by biological variability, as well as false-positive or false-negative results. Radiomics provides quantitative descriptors of tumor heterogeneity and offers objective assessment of tumor characteristics. This study aimed to evaluate the potential of computed tomography (CT)-based radiomic features to distinguish between CEA-positive and CEA-negative colon cancer patients. Methods: In this retrospective study, 150 patients with histopathologically confirmed colon cancer were screened, and 109 were eligible after image-quality assessment (53 CEA-positive, 56 CEA-negative). A total of 107 radiomic features were extracted from preoperative contrast-enhanced CT images. After z-score normalization, feature robustness was assessed using intra- and inter-observer agreement. Correlation-based feature selection (|ρ| ≥ 0.7) was applied. Five machine-learning classifiers—Support Vector Machine (SVM), Decision Tree, Ensemble, k-Nearest Neighbor (k-NN), and Neural Network (NN)—were trained using stratified 5-fold cross-validation. Performance was evaluated using accuracy, recall, specificity, F1-score, and ROC-AUC. Results: The best performance was obtained with 41 selected features. The k-NN classifier achieved the highest accuracy (77.4 ± 2%) and ROC-AUC (0.8523 ± 0.013), while SVM and NN achieved the highest recall (83.0 ± 0.3). These models showed balanced and robust performance in distinguishing CEA-positive from CEA-negative patients. Conclusions: CT-based radiomic analysis combined with machine learning—particularly k-NN, SVM, and neural network classifiers—showed promising performance in differentiating colon cancer patients according to serum CEA status. Radiomic features may provide imaging-based information associated with serum biomarkers such as CEA, potentially enhancing tumor characterization and supporting more personalized decision-making. Full article

Invasive candidiasis is a fungal infection characterized by a high mortality rate. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family receptors play a crucial role in regulating innate responses of both leukocytes and epithelia. Human CEACAM3, CEACAM5 and CEACAM6 receptors recognize Candida albicans and are expressed in transgenic CEABAC10 mice. In a murine C. albicans infection model, CEABAC10 mice exhibited a shortened survival period attributed to an early cytokine storm, an exacerbated acute phase response, and heightened systemic inflammation compared to their wild-type littermates. The livers and kidneys of CEABAC10 mice displayed intensified purulent necrotizing inflammation, accompanied by increased infiltration of neutrophils and macrophages. Our in vivo and in vitro data indicated that the expression of CEACAM6 on monocytes of CEABAC10 mice caused the elevated cytokine levels and the subsequent exacerbation of the acute phase response upon C. albicans infection, resulting in decreased survival. Full article

Bladder cancer (BC) is one of the most common urinary tract malignancies. In recent years, increasing attention has been paid to the role of pyroptosis—an inflammatory form of programmed cell death—in cancer development. Gasdermin B (GSDM B), a member of the gasdermin protein family, is involved in the regulation of inflammatory processes and the immune response, and its expression may be associated with cancer development and progression. The aim of the study was to assess GSDM B concentrations in the serum of patients with bladder cancer and to determine its potential diagnostic value in comparison with the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). This study included patients with bladder cancer hospitalized at the Department of Urology, Medical University of Białystok, and a healthy control group. GSDM B concentrations were determined by Enzyme-Linked Immunosorbent Assay (ELISA), while CEA and CA19-9 concentrations were determined by chemiluminescent microparticle immunoassay (CMIA). Concentrations in the serum of patients with bladder cancer were significantly higher than in the control group. A positive correlation was found between GSDM B and CEA and CA19-9 concentrations, as well as the age of the subjects. Receiver-operating characteristic (ROC) analysis demonstrated moderate but significant diagnostic value of GSDM B in differentiating patients with BC from healthy controls. No significant differences in GSDM B concentrations were observed between low- and high-grade tumors. These findings suggest that GSDM B may serve as a potential diagnostic marker for bladder cancer, particularly when used as part of a multimarker panel. Full article

Introduction: Liver transplantation has re-emerged as a potential therapeutic option for patients with unresectable colorectal liver metastases after failure of standard treatments. This systematic review and meta-analysis evaluated survival outcomes, recurrence patterns, and prognostic factors associated with this approach. Materials and Methods: A systematic review was conducted according to PRISMA 2020 guidelines and registered in PROSPERO. Electronic databases were searched for studies published between November 2015 and November 2025, that assessed liver transplantation in the context of unresectable colorectal liver metastases. Random-effect meta-analyses were conducted to estimate the pooled overall survival, disease-free survival and recurrence rates. Heterogeneity was assessed using I² statistics. Results: Twenty-three studies involving patients with unresectable liver-only colorectal metastases were included. Pooled overall survival after liver transplantation was 96.6% at 1 year (95% CI 93.9–99.4; I² = 44.3%), 73.4% at 3 years (95% CI 62.9–83.9; I² = 95.4%), and 49.4% at 5 years (95% CI 35.4–63.3; I² = 90.5%). Ten-year overall survival was approximately 27%. The pooled recurrence rate was 63.5% (95% CI 52.5–76.8), and the type of recurrence was mainly extrahepatic, most commonly pulmonary. Disease-free survival was 64.1% (95% CI 47.5–80.7) with substantial heterogeneity (I² = 95.6%). Biological risk factors, including carcinoembryonic antigen levels, metabolic tumor volume, and composite risk scores, consistently influenced survival outcomes. Conclusions: In highly selected patients with unresectable colorectal liver metastases, liver transplantation is associated with favorable long-term survival despite frequent recurrence. Outcomes appear to be primarily driven by tumor biology rather than tumor burden, supporting the cautious use within specialized centers under structured selection protocols. Full article

Background and Objectives: Serum carcinoembryonic antigen (CEA) is a widely used biomarker in non-small cell lung cancer (NSCLC). However, its association with oncogenic driver alterations and prognostic significance across molecular subtypes in metastatic disease remains insufficiently defined. Materials and Methods: This retrospective multicenter study included 332 patients with metastatic NSCLC harboring oncogenic alterations (EGFR, ALK, ROS1, KRAS, and others) from eight oncology centers in Türkiye. Baseline serum CEA levels measured at metastatic diagnosis were analyzed on the natural logarithmic scale. Associations between CEA levels, molecular subtypes, clinical features, and overall survival (OS) were evaluated using generalized linear models and Cox proportional hazards regression. Results: Baseline CEA levels differed significantly across molecular subtypes (p = 0.001), with EGFR-mutant tumors showing the highest median levels. Multivariable analysis identified driver alteration, histology, and metastatic burden as independent determinants of baseline CEA. Higher baseline CEA and metastatic site count were independently associated with increased mortality risk (HR 1.151 and 1.279 per unit increase, respectively; p < 0.001), while female sex was protective (HR 0.626; p = 0.004). KRAS mutations were associated with poorer survival compared with EGFR (HR 2.370; p < 0.001). Kaplan–Meier analyses showed a consistent trend toward longer OS in patients with CEA < 5 ng/mL, with significance only in the rare alteration subgroup. Conclusions: Baseline CEA may reflect underlying tumor biology across molecular subtypes and are associated with survival outcomes in metastatic NSCLC. However, given the variability across subgroups and modest effect sizes, these findings should be interpreted with caution. Prospective studies evaluating longitudinal CEA dynamics are warranted. Full article

Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer in women, and metastasis is the leading cause of BC-related death. Circulating tumor cells (CTCs) are a prerequisite for metastasis. This study examined the diagnostic and prognostic value of CTCs for assessing metastatic risk and recurrence in BC. Methods: The Chiline CATCH^® Circulating Target Cell Enrichment System, an automated negative selection platform, was used to enrich and enumerate CTCs from the peripheral blood of patients with BC. Epithelial cell adhesion molecule (EpCAM) and cell-surface Vimentin (CSV) were used as markers for CTC identification. Results: CSV⁺ CTC counts, but not EpCAM⁺ CTC counts, were increased in patients with BC at higher metastatic risk. A cut-off of >4.5 CSV⁺-CTCs/2 mL blood yielded a sensitivity of 0.56 and specificity of 0.92 for identifying patients at high metastatic risk. CSV⁺-CTCs outperformed conventional serum tumor markers, including cancer antigen 15-3 (CA 15-3), cancer antigen 125 (CA 125), and carcinoembryonic antigen (CEA), in identifying patients with high metastatic risk, and their combined use further improved risk stratification. An elevated CSV⁺-CTC count (≥5 cells/2 mL blood) was significantly associated with worse progression-free survival in patients with BC. Conclusions: These findings suggest that CSV⁺-CTCs may serve as a biomarker for metastatic risk stratification and recurrence monitoring in BC when measured using an automated negative selection platform. Full article

Urachal carcinoma is a rare and aggressive malignancy for which standardized management remains limited, particularly in patients with locally advanced and node-positive disease. We report the case of a 34-year-old woman with urachal adenocarcinoma involving the bladder dome and radiographically suspicious pelvic lymph nodes who underwent robot-assisted partial cystectomy with urachal resection and extended bilateral pelvic lymph node dissection. Because there was no clinical, radiologic, or intraoperative evidence of umbilical involvement, the umbilicus was preserved after preoperative counseling and intraoperative confirmation of a negative proximal margin. Final pathology demonstrated a 4.5 cm enteric-type urachal adenocarcinoma, pT3a pN2 (2/17), with lymphovascular invasion, perineural invasion, and negative surgical margins. Immunohistochemistry and DNA- and RNA-based next-generation sequencing showed microsatellite stability, mismatch-repair proficiency, low tumor mutational burden, and no actionable genomic alteration. Given the absence of an established adjuvant standard, the multidisciplinary tumor board selected adjuvant FOLFOX as a non-standard postoperative strategy based on the overall clinicopathologic context. The patient remained continent, experienced no postoperative complications or treatment-limiting toxicity, and showed normalization of carcinoembryonic antigen and carbohydrate antigen 19-9 levels. This case provides a carefully contextualized example of transparent surgical reasoning and restrained multidisciplinary management in a rare malignancy with limited prospective evidence. Full article

Background: Regorafenib is a standard late-line treatment for refractory metastatic colorectal cancer (mCRC), yet clinical outcomes remain heterogeneous. Identifying accessible biomarkers to predict therapeutic benefit is crucial for balancing efficacy and toxicity. This study evaluated the prognostic value of early dynamic changes in carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA-19-9). Methods: We conducted a retrospective real-world analysis of 61 heavily pretreated mCRC patients receiving regorafenib. Tumor markers were assessed at baseline and after the third cycle (approximately 12 weeks). Systematic threshold optimization using Cox proportional hazards regression and Akaike Information Criterion (AIC) was performed to identify optimal percentage change cutpoints for predicting survival. Results: The optimal thresholds for defining unfavorable marker increases were +14.6% for CEA and +23.5% for CA-19-9. Patients with CEA changes below the cutoff demonstrated significantly superior progression-free survival (PFS) (median 6.1 vs. 4.0 months, p = 0.012) and overall survival (OS) (11.05 vs. 6.0 months, p = 0.035). CA-19-9 changes below the cutoff were associated with improved PFS (p = 0.022) but did not reach statistical significance for OS (p = 0.23). In multivariable analysis, neither marker retained independent significance, likely due to collinearity. Conclusions: Early dynamics of routine tumor markers are prognostic in regorafenib-treated mCRC. specifically, a CEA increase of <14.6% significantly predicts improved survival outcomes. These findings support the utility of serial marker monitoring in real-world practice, though prospective validation is warranted. Full article

Erlotinib (ER) and gefitinib (GB) are frequently prescribed for patients with advanced lung adenocarcinoma (ADC). Although both ER and GB significantly extend median survival, several patients experience early disease relapse due to treatment resistance. This study aimed to identify common genes associated with acquired resistance to ER or GB. This integrative analysis of transcriptomic data identified differentially expressed genes by comparing sensitive PC-9 cells with ER-resistant (PC-9/ER) or GB-resistant (PC-9/GB) cell lines. A Venn diagram was used to identify common genes. Candidate genes were confirmed in our generated drug-resistant cell lines. After six months, the PC-9/ER and PC-9/GB cell lines exhibited 40.7-fold and 109.2-fold increases in resistance to ER and GB, respectively. Flow cytometric analysis demonstrated that both resistant cell lines were resistant to cell cycle arrest and apoptosis induced by ER or GB. Through integrated analysis, we found that two genes, KRT13 and CEACAM5, were up-regulated in both the PC-9/ER and PC-9/GB cell lines. The expression patterns of these two genes did not align with the transcriptome, with only CEACAM5 exhibiting consistent gene and protein expressions. Our findings indicate that CEACAM5 serves as a biomarker for predicting the response of patients to ER and GB treatments. Full article

Background/Objectives: Vitamin D deficiency and malnutrition may lead to poor outcomes in colorectal cancer (CRC) patients. This study aims to perform an integrative analysis of serum vitamin D, nutritional status, anthropometric parameters and biochemical profiles in advanced CRC patients. Methods: The study included 58 advanced CRC patients. Serum vitamin D levels were measured by a chemiluminescence immunoassay. Nutritional status was evaluated with the Mini Nutritional Assessment (MNA). Body composition profiles were assessed using a bioelectrical impedance analyzer, and handgrip strength was measured with a handgrip dynamometer. Biochemical and clinical parameters were retrieved from an electronic database. Correlation, regression and receiver operating characteristic (ROC) analyses were performed. Results: Abnormal nutritional status and vitamin D deficiency were diagnosed in 55.17% and 50.00% of patients, respectively. Sarcopenia was diagnosed in 29.31%. Serum vitamin D concentrations were negatively correlated with absolute neutrophil counts (ANC). MNA scores showed significant negative correlations with ANC, platelet count, alkaline phosphatase and carcinoembryonic antigen. In multivariable regression models, albumin remained statistically associated with both serum vitamin D levels (β 7.049; 95% CI: 1.686–12.413; p = 0.011) and MNA score (β 6.951; 95% CI: 4.623–9.278; p < 0.001). Furthermore, albumin showed exploratory performance in ROC analyses for malnutrition and vitamin D deficiency (AUC^ROC 0.814 and 0.725, respectively), which should be interpreted cautiously given potential overlap with MNA-defined nutritional status and the limited sample size. Conclusions: Vitamin D deficiency, malnutrition and systemic inflammation commonly co-occur and are closely interrelated in patients with advanced CRC. A comprehensive assessment of nutritional status in a CRC supportive care setting is recommended. Full article

Field-effect transistor (FET) biosensors using graphene have become one of the most promising biosensing platforms for the early diagnosis of diseases with features such as high sensitivity, label-free detection and application compatibility with point-of-care systems. Herein, we critically discuss recent advances in graphene FET (GFET) biosensor development toward clinically relevant biomarkers associated with representative diseases including cancer, neurodegenerative disease, infectious disease, and inflammatory conditions. Recent progress was reviewed to evaluate GFET architectures, surface functionalization methods, and detection quality. The biomarkers explored were clusterin in Alzheimer’s disease, thrombin in coagulopathy, estrogen receptor α (ER-α) in breast cancer, Carcinoembryonic antigen in lung cancer, microRNAs for malignant tumors, exosomes derived from HepG2 for the hepatocellular carcinoma (HCC) cell line, interleukin-6 (IL-6) for chronic obstructive pulmonary disease (COPD), Polyclonal antibodies and antigens (P24) for HIV and prostate-specific antigen for prostate cancer. The developed devices demonstrate ultralow detection limits at femtomolar to attomolar concentrations with the aid of designed antibodies, aptamers and nanomaterials. Herein, this review presents the sensing mechanisms and biomedical application of various GFET platforms, focusing on their emerging potential as next-generation platforms for rapid, non-invasive and point-of-care diagnostics. Full article

Background: Finding dependable prognostic biomarkers for metastatic colorectal cancer (mCRC) is crucial. The albumin-to-carcinoembryonic antigen (CEA) ratio (ACR), a measure of nutritional-inflammatory status and tumor load, has emerged as a promising prognostic indicator. This study assessed ACR’s prognostic value of ACR in patients with mCRC. Methods: This retrospective study included 125 patients with mCRC followed at our institution between July 2010 and March 2022. ROC curve analysis was used to determine the optimal cutoff values for ACR, prognostic nutritional index (PNI), lymphocyte-to-monocyte ratio (LMR), and CEA. Kaplan–Meier and Cox regression analyses were used to evaluate progression-free survival (PFS) and overall survival (OS). Results: PFS and OS were 13.3 and 26.0 months, respectively. Patients with an ACR ≥ 4.24 experienced significantly longer PFS (16.8 vs. 11.0 months; p = 0.001) and OS (32.0 vs. 22.3 months; p < 0.001) compared with those with ACR < 4.24. In univariable analyses, ACR was significantly associated with both PFS and OS, whereas PNI, LMR, and CEA were associated with OS only. In multivariable Cox regression models ACR showed a significant association with both PFS (HR 0.413; 95% CI: 0.265–0.643; p < 0.001) and OS (HR 0.341; 95% CI: 0.210–0.551; p < 0.001), while maintenance therapy was significantly associated with PFS only and ECOG performance status, LMR and PNI with OS only. Conclusions: ACR appears to be a cost-effective biomarker that is associated with PFS and OS in mCRC. These findings suggest that ACR may have potential value for prognostic assessment and risk stratification in patients with mCRC. Full article

The availability of biobanked tissues represents an important resource for translational research; however, functional investigations are generally limited to freshly collected samples. To address this limitation, we developed an innovative strategy to restore functional properties of frozen biopsies by microtransplanting patient-derived membrane proteins into Xenopus laevis oocytes. This study aimed to recover and characterize the physiological properties of human colon cancer cell membranes and to investigate the role of neurotransmitter-related signaling and ion currents in cancer. Membrane incorporation was assessed by immunohistochemical detection of tumor-specific markers, including carcinoembryonic antigen, together with confocal microscopy and ultrastructural analyses. Functional viability was evaluated using two-electrode voltage clamp recordings to assess endogenous calcium-activated chloride currents and responses to selected neurotransmitters. The successful incorporation of colon cancer membranes was confirmed by specific immunoreactivity and ultrastructural features consistent with cancer cell architecture. Although no functional responses to the tested neurotransmitters were detected, oocytes microinjected with cancer membranes showed a marked reduction or complete suppression in endogenous calcium-activated chloride currents. These findings demonstrate that membrane microtransplantation into Xenopus oocytes is a reliable translational approach to functionally investigate cancer cell membranes from frozen biopsies, and suggest that altered chloride channel activity may represent a baseline for new studies to investigate new potential therapeutic targets for colon cancer. Full article