Search Results (581)

Organoids are self-organizing multicellular structures generated in vitro that recapitulate the micro-architecture and function of an organ. They are commonly derived from stem cells but can also emerge from pieces of proliferative tissues. Organoid technology has opened novel ways to model development and disease, but it is not without challenges. Computational models of organoids have been established to elucidate organoid growth and facilitate the optimization of organoid cultures. This article is a systematic review of in silico organoid models constructed at single-cell or subcellular resolution. PubMed, Scopus, and Web of Science were searched for original papers published in peer-reviewed journals before 26 September 2025, yielding 439 records after deduplication. Two independent reviewers screened their titles and abstracts, retrieved 84 papers for full-text scrutiny, and identified 32 papers that met the inclusion criteria. They were grouped by organoid type: 12 intestinal, 1 airway, 2 pancreas, 3 neural, 1 kidney, 1 inner cell mass, 9 tumor, and 3 generic. The analysis of these works revealed that computer simulations guided experimental work. Parsimonious computational models provided insights into diverse organoid behaviors, such as the rotation of airway organoids, size oscillations of pancreatic organoids, epithelial patterning of neural tube organoids, or nephron segment formation in kidney organoids. Generally, a deep understanding was achieved through combined in silico and in vitro investigations (e.g., optic cup morphogenesis). Recent research trends suggest that next-generation computational models of organoids may emerge from a more detailed understanding of the complex regulatory circuits that govern stem cell fate, and machine-learning-based, high-throughput imaging of organoids. Full article

Gestational diabetes mellitus (GDM) causes adverse effects on both mothers and offspring. This study investigated the effects of a polyherbal formulation combining Pandanus amaryllifolius root and Tectona grandis leaf extracts on maternal and fetal outcomes in streptozotocin (STZ)-induced GDM rats, compared with metformin. Pregnant rats were assigned to a non-diabetic reference group and diabetic groups, including an untreated diabetic group (negative control), a metformin-treated group (positive control), and diabetic groups treated with low, medium, or high doses of the pandan–teak formulation from gestation day 7 to 21. Medium and high doses significantly increased maternal body weight and pancreatic mass index (p < 0.05) without altering maternal glycemia or insulin levels. Fetal weight increased at medium and high doses, whereas crown–rump length increased only at the high dose. Placental index and fetal glucose levels decreased in a dose-dependent manner (p < 0.05), with no significant change in implantation loss. These findings suggest that the pandan–teak formulation may exert complementary actions that support placental–fetal glucose regulation and fetal growth while maintaining maternal glycemic stability, indicating its potential as a plant-based adjunct approach for gestational diabetes focused on fetal protection. Full article

Background/objectives: Metabolic abnormalities, independent of excess weight, may contribute to cancer risk even among individuals of normal weight, though their role remains unclear. This study sought to ascertain if metabolically unhealthy normal-weight (MUNW) individuals, generally characterized by a normal body mass index alongside the presence of metabolic abnormalities, have higher cancer risk than metabolically healthy peers, to analyze variations in risk across obesity-related cancer types, and to examine which single specific metabolic components can predict cancer independently in normal-weight individuals. Methods: Two authors systematically searched the PubMed, EMBASE, and Web of Science databases for longitudinal studies, published from inception to July 2025, that included normal-weight adults, classified participants by metabolic health status, and reported incident cancer outcomes in metabolically unhealthy versus healthy normal-weight groups. Hazard ratio (HR) estimates were extracted from each study and were pooled using random-effects inverse-variance model with empirical Bayes variance estimator. Results: Thirty-five studies involving 18,210,858 participants (56.0% females, mean age = 53.8 years) were included. A total of 280,828 new cancer cases were diagnosed during follow-up (mean = 10.6 years). In comparison with metabolically healthy normal-weight individuals, MUNW individuals had a 20% higher risk of cancer (HR = 1.20, 95% confidence interval [CI]: 1.13–1.28). Increased risks were observed for gastric cancer (HR = 1.40, 95% CI: 1.04–1.87), pancreatic cancer (HR = 1.37, 95% CI: 1.21–1.54), and colorectal cancer (HR = 1.34, 95% CI: 1.14–1.57), which were the cancer types showing statistically significant associations in subgroup analyses. Normal-weight participants presenting specific metabolic factors like central adiposity or glucose metabolism abnormalities had a 20% (HR = 1.20, 95% CI: 1.13–1.37) and 23% (HR = 1.23, 95% CI: 1.06–1.41) increased cancer risk, respectively. Conclusions: MUNW individuals are at higher risk of cancer, with specific metabolic abnormalities, particularly central adiposity and impaired glucose regulation, emerging as the factors most strongly associated with increased risk in normal-weight individuals. Routine metabolic screening and detailed phenotyping are crucial to identify these risks. Full article

Background/Objectives: Pancreatic cancer is among the most aggressive malignancies, with poor survival rates. Emerging evidence suggests that body composition, including skeletal muscle mass and adiposity distribution, plays a crucial role in predicting patient outcomes. However, its impact on survival in pancreatic cancer remains incompletely understood. The aim of this systematic review was to assess the correlation between body composition parameters and survival outcomes in pancreatic cancer patients, focusing on overall survival. Methods: A comprehensive literature search was conducted, including three main components: pancreatic cancer, body composition, and survival outcomes. Results: 23 studies were included in this review. The findings indicate that body composition can serve as a predictor of survival in pancreatic cancer patients, with 21 studies reporting a significant correlation. The most frequently observed predictor, with 11 studies reporting, was not a baseline parameter but rather changes in parameters over time during treatment. However, discrepancies remain regarding the extent of predictive power and the relative importance of individual components. Conclusions: Specific body composition parameters hold potential as prognostic indicators of survival in pancreatic cancer patients. However, further research is necessary to establish consistent patterns and to clarify which parameters are most predictive and under what conditions. Full article

Background and Objectives: Pancreatoduodenectomy (PD) is the primary treatment for patients with resectable, non-metastatic pancreatic adenocarcinoma and periampullary tumors. Although surgical methods and perioperative management have improved, the procedure still carries a high risk of complications, with postoperative pancreatic fistula (POPF) being the most significant. This study focuses on identifying current risk factors for POPF after PD in a single HPB center. Materials and Methods: We retrospectively analyzed prospectively collected data from patients undergoing PD in our department between October 2018 and April 2024. Data included demographics, comorbidities, lifestyle factors, preoperative tests (bilirubin, CA19-9, HbA1c), intraoperative variables (pancreatic texture, duct diameter), and postoperative outcomes. POPF was classified using the International Study Group of Pancreatic Surgery (ISGPS) criteria. Univariate and multivariate logistic regression analyses were performed. Results: A total of 118 patients underwent PD (82 males, 36 females; mean age 67 (45–85) years; mean body mass index (BMI) 26.6 kg/m²). POPF occurred in 37 patients (31%), with 27 Grade B (23%) and 10 Grade C (9%). The 30- and 90-day mortality rates were 5% and 12.7%, respectively. Univariate analysis showed associations between POPF and soft pancreas (p = 0.018), c-reactive protein (CRP) on postoperative day (POD) 5 (p = 0.004), and serum amylase on POD 0 (p = 0.008). Diabetes mellitus was associated with a lower incidence of POPF (p = 0.014). Multivariate analysis confirmed CRP on POD 5 (OR 1.007, p = 0.025) and DM (OR 0.254, p = 0.015), as independent factors. ROC analysis identified POD 0 amylase >113.5 U/L (AUC 0.717) and POD 5 CRP >125.3 mg/dL (AUC 0.669) as predictive values. Conclusions: POPF remains an important complication after PD. CRP > 126 mg/dL on POD 5 was associated with POPF and may serve as an adjunctive signal to guide further assessment, including imaging. The observed inverse association with diabetes mellitus is hypothesis-generating and should be interpreted cautiously, considering potential confounding and the influence of center volume, surgeon heterogeneity, and institutional protocols. Full article

Background and Objectives: Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies worldwide. Early identification of high-risk patients is essential to improve outcomes. Computed tomography (CT)-derived muscle mass indices, such as the psoas muscle index (PMI) and paravertebral muscle index (PvMI), have recently emerged as potential prognostic markers reflecting both nutritional and inflammatory status. This study aimed to investigate the relationship between CT-derived PMI and PvMI with disease severity, complications, and intensive care unit (ICU) requirement in patients with acute pancreatitis, and to evaluate their prognostic value across age- and sex-specific subgroups. Materials and Methods: This retrospective study included 179 patients hospitalized with AP between January 2023 and February 2025. The psoas muscle area (PMA) and paravertebral muscle area (PvMA) were measured at the L3 vertebral level on CT scans and normalized to height squared to calculate the PMI and PvMI levels. Additionally, patients were classified as having low or normal PMA and PvMA levels based on cutoff values from the existing literature. Clinical, biochemical, and outcome data—including disease severity, complications, and ICU requirement—were analyzed. Subgroup analyses were performed by sex and age (≥65 years). Logistic regression and ROC analyses were used to identify independent predictors and optimal cutoff values. Results: Overall, complications developed in 39.7% of patients, and ICU admission was required in 11.2%. The PMI levels were significantly correlated with albumin, hemoglobin, and inflammatory marker levels. In women, the PMI was independently associated with complicated AP (adjusted OR = 0.655, p = 0.018). In patients ≥65 years, the PvMI level was independently associated with ICU requirement (adjusted OR = 0.780, p = 0.047). The ROC analysis identified PMI ≤ 4.04 cm²/m² as the optimal cutoff for predicting complicated AP (AUC = 0.641, p = 0.049), and PvMI ≤ 18.88 cm²/m² for predicting ICU need (AUC = 0.684, p = 0.020), with moderate discrimination. Conclusions: CT-derived muscle indices might be associated with disease severity and adverse outcomes in AP, particularly among older (≥65 years) and female patients. PMI and PvMI may serve as practical prognostic markers to identify high-risk patients early, enabling timely nutritional and supportive interventions. Validation in larger prospective cohorts is warranted. Full article

Background: Pancreatic hamartoma (PH) is an exceptionally rare, benign, mass-forming lesion accounting for less than 1% of all pancreatic tumors. Its rarity and non-neoplastic nature contribute to significant diagnostic challenges, often leading to misclassification as malignant disease. This study presents a case of PH and a systematic review of all reported cases, with emphasis on histopathological and imaging characteristics. Methods: A comprehensive electronic search of PubMed, Scopus, and Web of Science was conducted up to 1 April 2025, to identify eligible case reports and series. Results: We describe a 37-year-old woman with a cystic lesion of the pancreatic tail, ultimately confirmed histologically as a cystic pancreatic hamartoma following distal pancreatectomy with splenectomy, with an uneventful postoperative course. Of 687 screened studies, 51 met the inclusion criteria, comprising 77 cases (68 adults, 9 pediatric). PHs occurred most frequently in males (52.9%), with a mean age of 59.5 ± 12.9 years, and were often asymptomatic (57.4%). The pancreatic head was the most common site (52.9%). On MRI, PHs typically exhibited low T1-weighted and high T2-weighted signal intensity, with no FDG uptake (82%) and moderate or no restriction on DWI, distinguishing them from neuroendocrine tumors (NETs). Histologically, most lesions were solid (64.7%) or solid–cystic (35.3%), with low spindle cell cellularity and absent Langerhans islets. Conclusions: Low T1WI signal and moderate DWI signal are the key features distinguishing PHs from NETs. Incorporating these findings with EUS-FNA and immunohistochemistry can support a provisional diagnosis and help avoid unnecessary radical surgery. Full article

Background: Vitamin D (VD) insufficiency is present in chronic pancreatitis (CP), leading to increased cardiovascular risk, bone complications, impaired quality of life, and increased mortality. This study aimed to determine the prevalence of VD deficiency in patients with CP and to assess its relationship to CP progression and associated cardiovascular complications. Methods: Seventy patients were enrolled and evaluated for pancreatic exocrine insufficiency by fecal elastase-1, CP severity by M-ANNHEIM classification, cardiovascular risk by 10-year risk mortality scores (SCORE and FRS), and for arterial stiffness using pulse wave velocity (PWV) at a. carotis and a. femoralis. Determination of 25-hydroxyvitamin D was performed by an LC-MS/MS method. Resting energy expenditure was calculated using the Harris–Benedict formula. Results: Mean VD levels were 37.86 ± 24.36 nmol/L (range 3.854–99.874 nmol/L); only five patients were in sufficiency status. VD levels correlated significantly with body mass index (BMI) and resting energy expenditure. In patients with severe structural changes, we observed lower VD levels regardless of etiology (p < 0.01). VD levels were lower in patients with pancreatic exocrine insufficiency (PEI), p < 0.05. Patients with mild CP by M-ANNHEIM had lower levels of VD compared to moderate and advanced CP, p < 0.05. At a cut-off of VD 11.95 nmol/L, we verified pancreatic lithiasis with 89.4% sensitivity, 83.3% specificity, and AUC of 0.826 ± 0.113 (95% CI, 0.61–1). VD status worsened with the increase in the 10-year risk mortality by both SCORE and FRS and PWV, p < 0.05. Conclusions: Most of our patients with CP were VD insufficient. Monitoring of nutritional status in patients with CP is mandatory to prevent the development of malnutrition complications and the associated morbidity and mortality. Full article

This review focuses on the molecular pathogenesis of Type 1 diabetes (T1D), specifically on the key autoantigens targeted by the autoimmune response and the clinical implications of their epitope specificity. T1D is characterized by the destruction of insulin-producing pancreatic β-cells. The autoimmune attack is directed against a defined set of autoantigens, primarily insulin, glutamic acid decarboxylase 65, tyrosine phosphatase-like protein, zinc transporter 8, as well as several minor autoantigens. A critical advancement in understanding the disease has been the analysis of epitope specificity, revealing that immunodominant epitopes are conformational and often localized to C-terminal protein regions, exposed during β-cell degradation. The introduction of sensitive multiplex assays for the simultaneous detection of T1D-associated autoantibodies represents a major diagnostic breakthrough. These platforms enable early diagnosis, risk stratification, and the identification of a “therapeutic window” for intervention. At this preclinical stage, antigen-specific immunotherapies aimed at restoring immune tolerance show significant promise. Ultimately, the combination of personalized diagnostic profiles, epitope mapping, and targeted therapies forms the basis for a new T1D management paradigm focused on halting the autoimmune process itself and preserving functional β-cell mass. Full article

Type 1 diabetes mellitus is a major risk factor for both sarcopenia and osteoporosis, primarily due to the body’s inability to utilize glucose as a result of insulin deficiency. Impairments in insulin and glucose signaling can accelerate the decline in muscle and bone health. To investigate this interaction, we examined whether insulin deficiency exacerbates muscle and bone deterioration in Chrebp knockout (KO) mice. Male wild-type (WT) and KO mice, aged 18 weeks, were intraperitoneally treated with 200 mg/kg BW streptozotocin (STZ), which selectively destroys pancreatic beta cells, thereby inducing insulin deficiency. Two weeks after STZ administration, compared with STZ-treated WT mice, STZ-treated KO mice presented significantly greater reductions in body weight and gastrocnemius muscle weight (BW: WT-vehicle vs. WT-STZ; 2.58 [−1.23, 6.39] (p = 0.21); KO-vehicle vs. KO-STZ: 8.03 [5.23, 10.82]; GA muscle: WT vehicle vs. WT STZ: 0.084 [0.047, 0.12], p < 0.0001; KO vehicle vs. KO STZ: 0.084, [0.047, 0.12], p < 0.0001). The decrease in grip strength caused by STZ administration was greater in the KO mice than in the WT mice (mean differences [95% CIs]: WT vehicle—WT STZ, 49.6. [0.9, 98.4], p = 0.046; WT STZ—KO STZ: 71.40 [29.1, 113.7], p = 0.0059; KO vehicle—KO STZ: 84.3 [51.9, 116.8], p = 0.0003). Consistent with these findings, STZ administration reduced IGF-1 expression and increased atrogin mRNA levels, with the highest levels in STZ-treated KO mice. In skeletal muscle, the changes in IGF-1 and Atrogen induced by STZ administration were significantly greater in the KO group than in the WT group (IGF-1: WT vehicle—WT STZ: 0.19 [−0.072, 0.46], p = 0.17; KO vehicle—KO STZ: 0.79 [0.53, 1.06], p < 0.0001; Atrogen: WT vehicle—WT STZ: −2.7 [−3.01, −2.29], p < 0.0001; KO vehicle—KO STZ: −3.35 [−3.71, −2.99], p < 0.0001). The BMD in the Chrebp-deficient group was greater than that in the wild-type group (WT vehicle—KO vehicle: −5.2 [−8.4, −1.9], p = 0.0014); however, the administration of STZ significantly decreased the BMD only in the KO group (WT vehicle—WT STZ: p = 0.45, KO vehicle—KO STZ: 7.2 [3.9, 10.4], p < 0.0001). These results suggest that Chrebp deficiency combined with insulin deficiency aggravates sarcopenia and osteoporosis risk. Therefore, insulin and glucose signals are important for maintaining muscle and bone mass and function. However, further studies are needed to elucidate the mechanisms by which ChREBP deletion and insulin deficiency cause osteosarcopenia. Full article

Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease in which oxidative stress (OS) promotes pancreatic stellate cells activation and fibrosis. Ranunculus repens L. (R. repens) has been used in Algerian traditional medicine to treat conditions like hepatitis and diabetes. Galectins are β-galactoside-binding lectins implicated in several pathological processes, including inflammation. This study aimed to analyse the chemical composition and evaluate the protective effects of R. repens methanol extract (RRME) in an experimental CP model, as well as in cultured pancreatic cells. CP was induced by intraperitoneal injections of L-arginine in rats. The pancreas was examined histopathologically, using hematoxylin and eosin, and picrosirius red staining. OS markers were assessed in pancreatic homogenates, and RT-qPCR analysis was performed to evaluate the expression of fibrosis markers, proinflammatory cytokines, and galectins 4 and 9. The extract was characterized by Ultra-performance liquid chromatography mass spectrometry, and its antioxidant and antiapoptotic activities were evaluated in vitro using H₂O₂-induced intracellular reactive oxygen species (ROS) generation and paclitaxel-induced apoptosis in pancreatic cell lines. The results showed that treatment with RRME improved relative pancreatic weight and lowered serum lipase activities. It mitigated oxidative stress in pancreatic tissues and reduced fibrosis levels. Inflammation was attenuated, as indicated by decreased interleukin-6, tumor necrosis factor alpha, and leukocyte infiltration. Moreover, RRME down-regulated galectins 4 and 9. Finally, RRME attenuated ROS generation and apoptosis in vitro. These findings suggested that RRME may have therapeutic potential against CP by modulating OS and fibrosis. Full article

Background and Methods: Using a nanoparticle-based enrichment (Proteonano) methodology on human plasma samples, we achieved a substantial increase in identified proteins from ~700 to >5000 proteins compared to neat plasma digest. In a small-scale pilot test, we applied this methodology to a small cohort of plasma samples from pancreatic cancer (PC) patients with different disease stages: (I) primary tumor and (II) metastases, and compared them with healthy controls. Most identified proteins are within the Human Plasma Proteome Project (HPPP) database, and more than 300 proteins are on the list of FDA-approved drug targets. Results: We observed a large and significant increase in ribosomal proteins in the plasma of patients with metastatic PC. ADH1C and ADH1B, both members of the alcohol dehydrogenase family, were particularly upregulated in patients with liver metastasis. Fifteen other predicted secreted and/or cell surface–associated proteins with known cancer associations are also significantly altered and would otherwise go undetected in neat, digested plasma. Conclusions: The significant increase in proteome depth allows a strong foundation for future large-scale experimental and comparative analysis. Lastly, similar conclusions could be reached from comparing different mass spectrometers (Orbitrap Astral and Orbitrap Ascend) and columns (depth and throughput) setups on the same dataset, although the depth approach on the newer Orbitrap Astral instrumentations can reveal additional insights in the plasma proteome. Full article

Background/Objectives: The diagnostic management of obstructive pancreatobiliary pathologies often leads to unnecessary invasive procedures and the overuse of costly imaging due to inherent diagnostic uncertainties. This dilemma highlights the need for a refined triaging strategy. This study aimed to compare the diagnostic competence and triage potential of Transabdominal Ultrasonography (TAUS)—a cost-effective, first-line method—with the efficacy of the invasive method, Endoscopic Ultrasonography (EUS). Our objective was to identify specific TAUS findings that could render EUS redundant or serve as a clinical guide for referral to EUS. Methods: This prospective study included patients evaluated for suspected pancreatobiliary lesions (December 2024–September 2025). Final diagnoses (gold standard) were established using pathology, tumor board decisions, other imaging, or ≥6 months clinical follow-up. TAUS was performed by one operator blinded to clinical data. EUS was immediately performed by a different operator, blinded to TAUS results and all other clinical data. Data were grouped into normal findings, solid masses, cystic lesions, chronic pancreatitis, distal cholangiocarcinoma/ampullary tumors, and choledocholithiasis. Results: A total of 204 patients were included. TAUS sensitivity (76.5%) was significantly lower than EUS (94.6%) (p < 0.001), but both showed high specificity (TAUS: 82.9%; EUS: 88.24%). TAUS performance varied greatly by lesion type: high for solid lesions (81.8%) and chronic pancreatitis (88.9%), but markedly lower for distal common bile duct lesions/ampullary tumors (57.1%; p = 0.006). In univariate analysis, BMI (p < 0.001), lesion size (p = 0.002), MPD dilation (p = 0.001), and localization (p < 0.001) were associated with TAUS success. Lesion size (OR = 1.049, p = 0.029) was the independent predictor in the multivariate analysis. TAUS detected common bile duct dilation in obstructive cases at a high rate (95.9%) but had statistically significantly lower success in reaching a definitive diagnosis (63.3%; p < 0.001). Conclusions: While TAUS lacks the overall sensitivity of EUS, its robust detection performance for solid lesions and chronic pancreatitis suggests that it can reduce the need for further investigation in selected cases. The TAUS detection success, associated with factors like BMI and lesion size, combined with its high rate of common bile duct dilation detection, establishes a reliable triage guideline for referring patients to advanced diagnostic procedures, primarily EUS, to confirm the definitive etiology. Full article

Background/Objectives: Pancreatic cancer (PC) remains one of the deadliest malignancies, with challenges that hinder early detection and few actionable molecular targets. In this study, we aimed to identify biomarkers predictive of PC to support its diagnosis and treatment. Methods: Proteins from formalin-fixed, paraffin-embedded pooled samples of PC (n = 15; 5 pools) and chronic pancreatitis (n = 10; 5 pools) tissues were analyzed via label-free quantitative proteomics using liquid chromatography-tandem mass spectrometry. Immunohistochemistry (IHC) was performed on PC tissue microarrays to assess S100 calcium-binding protein P (S100P) and cathepsin E (CTSE) expression (IHC evaluable pairs: n = 78 for S100P; n = 82 for CTSE). Transwell invasion assays were conducted to evaluate the effects of these proteins on PC cell invasiveness, and Western blotting was used to validate protein expression and elucidate associated molecular mechanisms. Results: Both S100P and CTSE were overexpressed in PC tissues compared with those in adjacent normal tissues. Elevated S100P expression correlated with poor prognosis, whereas higher CTSE expression predicted favorable outcomes; both served as independent prognostic factors in PC. Functionally, S100P promoted PC cell invasion, whereas CTSE suppressed it. Mechanistically, both proteins appeared to regulate epithelial–mesenchymal transition (EMT) and invasive capacity through activation or inhibition of the phosphoinositide 3-kinase (PI3K)–protein kinase B (AKT) signaling pathway. Conclusions: Elevated expression of S100P and CTSE in PC tissues serves as independent indicators in our model of patient survival. Both proteins regulate EMT and invasion, potentially via the PI3K–AKT pathway, and hold significant promise as prognostic biomarkers and therapeutic targets in PC. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, largely due to late diagnosis and the lack of reliable non-invasive biomarkers. Altered trace element homeostasis has been implicated in tumor biology and systemic inflammation, but comprehensive metallomic profiling in PDAC is still limited. Methods: Using inductively coupled plasma mass spectrometry (ICP-MS), we quantified 20 serum and 15 urinary metals in 71 PDAC patients and 69 matched controls. Statistical analyses included univariate Wilcoxon testing, correlation with systemic inflammatory indices (NLR, MLR, SIRI, AISI, HGB/RDW, PCT), and multivariate chemometric modeling (PCA-LDA). K-means clustering was applied to identify patient subgroups with distinct biochemical signatures. Results: PDAC patients showed significantly elevated urinary antimony, chromium, cadmium, and vanadium, whereas controls exhibited higher serum selenium, zinc, barium, vanadium, and cobalt (all p < 10⁻⁵). The PCA-LDA model achieved 99% classification accuracy (Monte Carlo cross-validation, 1000 iterations), highlighting complementary diagnostic contributions of serum and urinary profiles. Serum selenium was inversely associated with SIRI and NLR, while urinary cobalt correlated positively with NLR. Clustering revealed three PDAC subgroups with different inflammatory and metallomic patterns, suggesting underlying biological heterogeneity. Conclusions: PDAC is characterized by opposite serum-urine metal signatures, indicating altered absorption-excretion dynamics. Selenium depletion may represent a protective biomarker, whereas urinary cobalt excretion reflects systemic inflammation. This integrative ICP-MS–chemometric approach provides a promising diagnostic tool for improving early detection and patient stratification in clinical practice. Full article