Search Results (240)

Background/Objectives: Colorectal cancer (CRC) frequently metastasizes to the peritoneum, significantly worsening patient prognosis. While serum tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are routinely measured, their diagnostic or prognostic role in peritoneal fluid remains unclear. This study aimed to assess the relationship between CEA and CA 19-9 levels in both serum and peritoneal fluid, and the clinical stage of CRC, particularly focusing on the presence of peritoneal metastases and positive cytology. Methods: We retrospectively analyzed data from 89 patients with histologically confirmed CRC who underwent surgery between 2020 and 2023. All patients had preoperative assessment of CEA and CA 19-9 levels in serum and peritoneal fluid, along with cytological examination of peritoneal fluid samples. Patients were categorized based on the presence or absence of macroscopic peritoneal metastases and cytology results. Results: Elevated levels of CEA and CA 19-9 in peritoneal fluid were significantly associated with the presence of peritoneal metastases. A positive cytological finding also correlated with higher marker concentrations. Conclusions: CEA and CA 19-9 levels in peritoneal fluid strongly correlate with peritoneal dissemination in CRC. These markers may serve as additional predictive factors, aiding in early detection of peritoneal spread and improved risk stratification. Their assessment may be useful in guiding intraoperative and postoperative decision-making. Full article

Medullary thyroid carcinoma (MTC) is a rare (~2–5% of all thyroid cancers) neuroendocrine thyroid malignancy originating from parafollicular C-cells of the thyroid gland with variable biological behavior and potential for early metastasis. Diagnosis, staging, and surveillance are heavily reliant on circulating biomarkers. We aimed to provide a comprehensive overview of circulating biomarkers in the management of MTC and propose an integrated, evidence-based algorithm to guide clinical decision-making using both established and emerging biomarkers. This is a narrative review on the evolving landscape of biomarker-driven management in MTC with emphasis on analytical advancements, clinical applications, and the prognostic implications of individual and combined biomarkers. Calcitonin remains the cornerstone biomarker for MTC, and new generation immunoassays have addressed several pre-analytical and analytical challenges such as pre-analytical degradation, inter-assay variability, and biological confounders. Procalcitonin (ProCT) has emerged as a stable and less interference-prone alternative or adjunct to calcitonin, which is particularly useful in cases with indeterminate calcitonin levels. Carcinoembryonic antigen (CEA) remains a useful complementary biomarker often correlating with aggressive behavior, advanced disease, and distant metastases. Kinetic evaluation (doubling times) of calcitonin and CEA offers independent prognostic information values and those < 6 months are associated with poor survival, whereas those > 2 years suggest favorable outcomes. Newer biomarkers such as pro-gastrin-releasing peptide (ProGRP) and carbohydrate antigen 19-9 (CA19-9) show potential in monitoring advanced disease and response to therapy. Their role is still under investigation but appears promising, particularly when used in conjunction with calcitonin and CEA. Our work advances a comprehensive and clinically pragmatic framework for the management of MTC by integrating established and emerging biomarkers with evidence-based algorithms, offering greater diagnostic precision, more reliable prognostic stratification, and improved personalization of follow-up and treatment strategies. Full article

Background: The pro-tumorigenic role of a disintegrin and metalloprotease 15 (ADAM15) is supported by its modified expression in primary tumors and ability to promote tumor growth in colorectal cancer (CRC). Cancer cell-derived ADAM15 promotes the progression of this malignancy by modulating the tumor microenvironment. However, according to our knowledge, this study is the first to assess serum ADAM15 concentrations in CRC patients in comparison to classical tumor markers—carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9)—and a marker of the inflammatory process, C-reactive protein (CRP). The aim was to evaluate whether circulating serum ADAM15 might be a candidate biomarker for CRC diagnosis and progression. Methods: The study included 110 CRC patients and 54 healthy volunteers. Serum concentrations of ADAM15, CEA, and CA19-9 were measured using immunoenzyme assays, while CRP levels were assessed by the turbidimetric method. Diagnostic characteristics of all tested proteins were calculated. Results: Serum ADAM15 and classical tumor marker (CEA and CA19) levels were higher in CRC patients than in healthy subjects. However, a significant difference was observed only for CEA (p < 0.001). ADAM15 concentrations were significantly higher in CRC patients with distant metastases compared to those without metastases (p = 0.043). The highest diagnostic sensitivity (89%) was achieved by combined analysis of ADAM15 and CRP levels. Conclusions: These findings suggest a significant role of ADAM15 in CRC pathogenesis, indicating the usefulness of this protein in the prediction of distant metastases. Measurement of serum ADAM15, especially in combination with classical tumor markers (CEA) and inflammation markers (CRP), may improve the diagnosis of patients with CRC. Full article

Objective: Tumor progression is regulated by systemic immune status, nutritional metabolism, and the inflammatory microenvironment. This study aims to investigate inflammatory–nutritional biomarkers associated with metachronous liver metastasis (MLM) in colorectal cancer (CRC) and develop a machine learning model for accurate prediction. Methods: This study enrolled 680 patients with CRC who underwent curative resection, randomly allocated into a training set (n = 477) and a validation set (n = 203) in a 7:3 ratio. Feature selection was performed using Boruta and Lasso algorithms, identifying nine core prognostic factors through variable intersection. Seven machine learning (ML) models were constructed using the training set, with the optimal predictive model selected based on comprehensive evaluation metrics. An interactive visualization tool was developed to interpret the dynamic impact of key features on individual predictions. The partial dependence plots (PDPs) revealed a potential dose–response relationship between inflammatory–nutritional markers and MLM risk. Results: Among 680 patients with CRC, the cumulative incidence of MLM at 6 months postoperatively was 39.1%. Multimodal feature selection identified nine key predictors, including the N stage, vascular invasion, carcinoembryonic antigen (CEA), systemic immune–inflammation index (SII), albumin–bilirubin index (ALBI), differentiation grade, prognostic nutritional index (PNI), fatty liver, and T stage. The gradient boosting machine (GBM) demonstrated the best overall performance (AUROC: 0.916, sensitivity: 0.772, specificity: 0.871). The generalized additive model (GAM)-fitted SHAP analysis established, for the first time, risk thresholds for four continuous variables (CEA > 8.14 μg/L, PNI < 44.46, SII > 856.36, ALBI > −2.67), confirming their significant association with MLM development. Conclusions: This study developed a GBM model incorporating inflammatory-nutritional biomarkers and clinical features to accurately predict MLM in colorectal cancer. Integrated with dynamic visualization tools, the model enables real-time risk stratification via a freely accessible web calculator, guiding individualized surveillance planning and optimizing clinical decision-making for precision postoperative care. Full article

Background and Aim: Colorectal cancer remains a leading cause of cancer-related mortality, with growing interest in nanotechnology-driven immunotherapeutics. Gold nanoparticles (AuNPs) offer a promising platform due to their biocompatibility, functional versatility, and immunomodulatory potential. Carcinoembryonic antigens (CEAs), highly expressed in colorectal tumors, provide an ideal target for antigen-specific immune activation. The aim of this study is to evaluate the immunogenicity, biodistribution, and therapeutic efficacy of a CEA-functionalized gold nanoparticle (CEA-AuNP) construct in a mouse model of colorectal cancer following oral administration via a customized capsular delivery system. Methods: A 30-day oral administration study was performed in BALB/c mice (n = 30), who received increasing doses of CEA-AuNPs (5–50 mg/kg/day). Histological, hyperspectral imaging, and ELISA-based cytokine analyses were conducted to assess organ integrity, nanoparticle accumulation, and immune modulation. Results: CEA-AuNPs demonstrated a favorable safety profile and dose-dependent accumulation in reticuloendothelial tissues, particularly the spleen and liver. Cytokine profiling revealed enhanced IL-10 responses in the spleen, indicating anti-inflammatory immune modulation, with localized pro-inflammatory signals observed in hepatic tissue at higher doses. No signs of systemic toxicity or significant off-target effects were detected. Conclusions: The oral administration of CEA-AuNPs in healthy mice induced tissue-specific immune responses and exhibited a dose-dependent biodistribution pattern. These results support the further development of CEA-AuNPs as a nanovaccine platform for colorectal cancer immunoprophylaxis. Full article

Gastric cancer remains a significant global health burden, with curative treatment relying on surgical resection, typically total or subtotal gastrectomy. However, the procedure frequently triggers acute metabolic and nutritional disturbances that may impact recovery. Objective: This prospective study aimed to investigate whether the type of gastrectomy (total vs. subtotal) influences early postoperative biochemical and hematological alterations, with particular attention to nutritional impact. Methods: A cohort of 295 patients (123 female, 172 male) who underwent gastrectomy for gastric cancer at the Institute of Oncology Iași (2023–2024) was evaluated. Laboratory parameters, including hemoglobin, hematocrit, lymphocyte and platelet counts, serum albumin, total protein, sodium, potassium, creatinine, and urea, were analyzed preoperatively and on postoperative day 14 using standard clinical methods. Results: Anemia was observed in over 90% of patients, irrespective of sex or procedure type. Electrolyte imbalances (notably hyponatremia and hypokalemia) and indicators of nutritional deficit (hypoalbuminemia, low creatinine) were highly prevalent, with a greater frequency among female patients. Total gastrectomy was associated with more severe biochemical and nutritional alterations compared to subtotal procedures. Conclusions: Total gastrectomy significantly exacerbates early postoperative metabolic and nutritional derangements. These findings reinforce the need for proactive, personalized postoperative nutritional and electrolyte management strategies to support recovery and reduce complication risks. Full article

Rectal cancer management necessitates a rigorous multidisciplinary strategy, emphasizing precise staging and detailed risk stratification to inform optimal therapeutic decision-making. Obtaining an accurate histological diagnosis before initiating treatment is essential. Comprehensive staging integrates clinical evaluation, thorough medical history analysis, assessment of carcinoembryonic antigen (CEA) levels, and computed tomography (CT) imaging of the abdomen and thorax. High-resolution pelvic magnetic resonance imaging (MRI), utilizing dedicated rectal protocols, is critical for identifying recurrence risks and delineating precise anatomical relationships. Endoscopic ultrasound further refines staging accuracy by determining the tumor infiltration depth in early-stage cancers, while preoperative colonoscopy effectively identifies synchronous colorectal lesions. In early-stage rectal cancers (T1–T2, N0, and M0), radical surgical resection remains the standard of care, although transanal local excision can be selectively indicated for certain T1N0 tumors. In contrast, locally advanced rectal cancers (T3, T4, and N+) characterized by microsatellite stability or proficient mismatch repair are optimally managed with total neoadjuvant therapy (TNT), which combines chemoradiotherapy with oxaliplatin-based systemic chemotherapy. Additionally, tumors exhibiting high microsatellite instability or mismatch repair deficiency respond favorably to immune checkpoint inhibitors (ICIs). The evaluation of tumor response following neoadjuvant therapy, utilizing MRI and endoscopic assessments, facilitates individualized treatment planning, including non-operative approaches for patients with confirmed complete clinical responses who comply with rigorous follow-up. Recent advancements in molecular characterization, targeted therapies, and immunotherapy highlight a significant evolution towards personalized medicine. The effective integration of these innovations requires enhanced interdisciplinary collaboration to improve patient prognosis and quality of life. Full article

Background and aim. Gold nanoparticles (AuNPs) offer promising potential as nanocarriers in vaccine development due to their biocompatibility, tunable surface properties and capacity to enhance antigen presentation. This study aimed to evaluate the in vitro cytocompatibility, cellular uptake and antigen processing of carcinoembryonic antigen (CEA)-functionalized AuNPs as a nanovaccine candidate. Materials and Methods. AuNPs were synthesized by citrate reduction and subsequently functionalized with CEA through physical adsorption. Nanoparticle size, morphology, and surface charge were characterized using UV–Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Cytocompatibility was assessed via MTT assay on RAW 264.7 murine macrophages. Cellular uptake and antigen processing were evaluated using hyperspectral dark-field microscopy and fluorescence microscopy with proteasomal pathway markers. Results. The synthesized AuNPs displayed a uniform spherical morphology with a mean hydrodynamic diameter of ~50 nm and a stable zeta potential. CEA conjugation slightly altered the surface charge and spectral profile. MTT assays confirmed good cytocompatibility across tested concentrations. Hyperspectral and confocal microscopy revealed the efficient uptake of CEA-AuNPs by RAW 264.7 cells and colocalization with lysosomal compartments, suggesting successful antigen processing. Conclusions. The in vitro data support the safety and biological interaction of CEA-functionalized AuNPs with macrophages. These findings highlight their potential as a nanovaccine delivery platform and warrant further in vivo evaluation to assess immunogenicity and protective efficacy. Full article

Pulmonary metastasectomy for colorectal cancer represents a key component in modern oncological surgery, balancing precision resection with systemic disease management. Despite ongoing debate initiated by randomized trials, the surgical removal of lung metastases continues to offer significant survival benefits in well-selected patients. This review synthesizes the evolving landscape of pulmonary metastasectomy, integrating classical prognostic indicators, such as the disease-free interval (DFI) and carcinoembryonic antigen (CEA) levels, with emerging molecular insights including KRAS and BRAF mutations. The relationship between surgical radicality, systemic therapies, and personalized genetic profiling is redefining patient selection and optimizing outcomes. By dissecting recent evidence and ongoing controversies, we clarify the complex decision-making required to navigate this complex clinical terrain. Ultimately, the synergy of multidisciplinary care and precision surgery holds the promise of durable disease control and extended survival in colorectal cancer patients with lung metastases. Full article

Circulating tumor cells (CTCs) are multifaceted biomarkers with significant potential for precision oncology, offering opportunities to refine diagnoses and personalize treatments across various cancer types, including colorectal and breast cancer. CTC assays serve as reliable prognostic indicators, even during chemotherapy and/or molecularly targeted therapies. Notably, CTCs exhibit heterogeneity that gradually develops during carcinogenesis and becomes more pronounced in advanced disease stages. These intra- and intertumoral heterogeneities pose challenges, particularly when drug-resistant clones emerge following therapy. The dynamic behavior of CTCs provides valuable insights into treatment response and prognosis. Extensive efforts have led to the development of technologies for effective CTC isolation, accelerating their clinical implementation. While both CTC and circulating tumor DNA (ctDNA) tests offer prognostic value, they reflect different aspects of tumor biology: CTC counts indicate tumor progression, while ctDNA levels correlate with tumor burden. The combined analysis is expected to yield complementary insights. CTC tests are feasible in general hospitals and may serve as tumor markers comparable to, or even superior to, conventional markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) for colorectal cancer, and CA15-3 for breast cancer. Early incorporation of CTC tests into routine blood panels appears to be a rational and promising approach. Full article

Pancreatic cystic lesions (PCLs) are increasingly identified via computerized tomography (CT) and magnetic resonance (MR), with a prevalence of 2–45%. Distinguishing mucinous PCLs (M-PCLs), which include intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) that can progress to pancreatic ductal adenocarcinoma, from non-mucinous PCLs (NM-PCLs) is essential. Carcinoembryonic antigen (CEA) remains widely used but often demonstrates limited sensitivity and specificity. In contrast, endoscopic ultrasound-guided measurement of intracystic glucose more accurately differentiates PCL subtypes, as tumor-related metabolic changes lower cyst fluid glucose in mucinous lesions. Numerous prospective and retrospective studies suggest a glucose cut-off between 30 and 50 mg/dL, yielding a sensitivity of 88–95% and specificity of 76–91%, frequently outperforming CEA. Additional benefits include immediate point-of-care assessment via standard glucometers and minimal interference from blood contamination. DNA-based biomarkers, including KRAS and GNAS mutations, enhance specificity (up to 99%) but exhibit moderate sensitivity (61–71%) and necessitate specialized, expensive platforms. Molecular analyses can be crucial in high-risk lesions, yet their uptake is constrained by technical challenges. In practice, combining glucose assessment with targeted molecular assays refines risk stratification and informs the choice between surgical resection or active surveillance. Future investigations should establish standardized glucose thresholds, improve the cost-effectiveness of genetic testing, and integrate advanced biomarkers into routine protocols. Ultimately, these strategies aim to optimize patient management, limit unnecessary interventions for benign lesions, and ensure timely therapy for lesions at risk of malignant transformation. Full article

Sex steroid hormones and systemic iron metabolism are emerging as modulators of colorectal cancer (CRC) development and progression. However, information linking systemic factors to tumor characteristics and epithelial–mesenchymal transition (EMT) is limited, particularly in a sex-specific context. We measured serum levels of sex hormones [testosterone, estradiol, progesterone, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Carcinoembryonic antigen (CEA)] and iron-related biomarkers (iron, transferrin, ferritin, % transferrin saturation, ceruloplasmin, and the ceruloplasmin/transferrin ratio) in 82 CRC patients and 31 healthy controls. EMT-related proteins [mediator of ErbB2-driven cell motility 1 (MEMO1), E-cadherin, fibronectin, vimentin, and vinculin] were quantified by Western blotting in tumor and adjacent normal mucosa. Non-parametric tests and Spearman correlations were applied, stratified by sex and corrected for age and anemia where appropriate. Progesterone levels were significantly lower in male CRC patients (median 0.17 ng/mL vs. 0.20 ng/mL, p = 0.04) and higher in female patients (0.17 ng/mL vs. 0.10 ng/mL, p = 0.0077) compared with controls. The iron-related biomarkers indicated a pattern of iron deficiency, including in non-anemic patients, with reduced % transferrin saturation (p < 0.01) and an elevated ceruloplasmin/transferrin ratio (p = 0.02). Correlations were found between iron status, tumor stage, and hormonal levels. Progesterone correlated with EMT protein expression in healthy mucosa (e.g., fibronectin in females: ρ = 0.567, p = 0.014; vimentin in males: ρ = −0.446, p = 0.007), but not in tumor tissue. In the healthy mucosa of male patients, ceruloplasmin/transferrin correlated with MEMO1 (ρ = 0.419, p = 0.04), vinculin (ρ = 0.299, p = 0.041), and vimentin (ρ = 0.394, p = 0.07); transferrin levels inversely correlated with MEMO1 expression (ρ = −0.392, p = 0.032), and vimentin showed a positive correlation with serum iron (ρ = 0.350, p = 0.043). Furthermore, fibronectin expression inversely correlated with iron in the sole tumor tissue of female patients (ρ = −0.366, p = 0.040). These findings support the role of sex hormones and iron metabolism in CRC biology, suggesting that EMT might be accompanied by altered iron uptake and redox remodeling, which can enhance cellular motility and the metastatic potential. Full article

Background: The role and underlying mechanisms of synaptophysin-like-1 (SYPL1), a neuroendocrine-associated protein, in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study aims to assess the diagnostic potential of SYPL1 as a serum biomarker for both resectable PDAC (rPDAC) and metastatic PDAC (mPDAC) located at the head of the pancreas. Additionally, the SYPL1 levels were monitored in PDAC patients who underwent surgical resection, with follow-up measurements taken 6 months postoperatively. Method: We analyzed serum SYPL1 in healthy controls (n = 67), rPDAC patients (n = 39), mPDAC patients (n = 22), and rPDAC patients (6-month postoperative) (n = 20) (due to factors such as relocation or death, 20 patients were included instead of 39 patients) by ELISA. Results: The SYPL-1 levels showed significant differences across the groups (controls: 7.43 ± 3.32, PC: 15.89 ± 2.00, mPDAC: 20.01 ± 4.03, p < 0.001). Both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were significantly greater in cancer groups compared to the healthy group. In patients who underwent surgical resection, the SYPL-1 levels showed a significant decrease 6 months after surgery (p < 0.001). Strong correlations were observed between tumor markers, with CA19-9 showing a positive correlation with CEA in both rPDAC (r = 0.550, p < 0.001) and mPDAC (r = 0.623, p = 0.002), while SYPL-1 demonstrated a negative correlation with CEA (r = −0.530, p = 0.009) in mPDAC. Receiver operating characteristic (ROC) analysis revealed excellent diagnostic performance for SYPL-1 in distinguishing both rPDAC (AUC = 0.965) and mPDAC (AUC = 0.985) from healthy controls, achieving superior accuracy compared to conventional markers CEA and CA19-9. Conclusions: Serum SYPL-1 emerges as a promising biomarker for the diagnosis and monitoring of rPDAC and mPDAC. Its significantly elevated levels in cancer groups, coupled with its marked decrease following surgical resection, suggest that SYPL-1 could play a critical role in both initial diagnosis and post-treatment surveillance. The strong correlations observed between SYPL-1, CEA, and CA19-9 further support its potential utility in a multi-marker panel. Notably, SYPL-1 demonstrated superior diagnostic accuracy compared to conventional markers, with high AUC values indicating its excellent ability to distinguish rPDAC and mPDAC from healthy controls. These findings highlight the need for further investigation to validate SYPL-1 as a reliable, non-invasive biomarker that could enhance early detection, prognosis, and treatment monitoring in rPDAC. Full article

Identifying prognostic markers in colorectal cancer (CRC) is crucial for improving treatment outcomes. Although carcinoembryonic antigen (CEA) is recommended in the guidelines of the National Comprehensive Cancer Network, its sensitivity and specificity are inconsistent, limiting its utility in patients with normal CEA levels. Circulating tumor cells (CTCs), including those expressing CD133—a cancer stem cell marker involved in tumor progression and therapy resistance—are associated with metastasis and survival outcomes. This study evaluated the prognostic significance of CD133-positive CTCs, and their combined effect with CEA, in patients with CRC. Peripheral blood samples from 195 patients with CRC (stages I–IV) were analyzed. CTCs were isolated using OncoQuick tubes and CD133 mRNA expression was detected by reverse transcription polymerase chain reaction. In clinicopathological analysis, CD133-positive CTCs were detected in 27.2% of cases, correlating with serosal invasion (p = 0.016). Multivariate Cox analysis showed that CD133-positive CTCs were associated with worse disease-specific survival (p = 0.001). Patients with CD133-positive CTCs and CEA ≥ 5 ng/mL (high CEA) had a significantly poorer prognosis (p < 0.001), whereas those with CD133-negative CTCs and CEA < 5 ng/mL (low CEA) had a better prognosis (p = 0.039). CD133 expression in CTCs, especially in combination with CEA, may serve as a valuable prognostic marker in CRC. Full article

This study explores the change in inflammatory markers over the course of neoadjuvant chemoradiation and adjuvant chemotherapy for LARC and assesses the association with clinicopathological factors at pre-specified time-points. We examined the trends of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), carcinoembryonic antigen (CEA), fibrinogen, and albumin through multilevel modelling of 29 prospective LARC patients across six time-points: before neoadjuvant chemoradiation (T1), week 3 of chemoradiation (T2), post-chemoradiation (T3), post-surgery (T4), midpoint of adjuvant chemotherapy (T5), and chemotherapy completion (T6). Variables collected included ethnic background, body mass index (BMI), smoking status, and pathological responses graded by Ryan tumour regression grade and pathological tumour and nodal status. NLR and PLR demonstrated an increasing trend during chemoradiation. Median CEA was highest at baseline and lowest at T4. The highest median values for NLR, PLR, CRP, and fibrinogen were at T4. Smokers demonstrated a trend towards a higher NLR compared to non-smokers. NLR was significantly higher in Caucasians compared to Asians at T2. Patients with pathological node-negative status had a higher NLR at T5 and T6 and a higher PLR at T1, T3, T5 and T6. Overall, inflammatory indices change dynamically throughout treatment and vary with clinicopathological factors. Full article