Search Results (650)

High-dimensional engineering datasets often combine class imbalance, noisy structures, and limited ground truth, making unsupervised analysis difficult to evaluate reliably. This study quantifies how three properties—partition stability, minority class recovery, and topological interpretability—are traded off across clustering methods, using a capacity-matched 25-seed comparison on a TCGA-derived RNA expression dataset (10,095 samples, 19 cancer types, 13,634 genes). We compare K-means across cluster counts $k\in \{19,\dots ,400\}$, self-organizing maps (SOMs) across lattice sizes from 25 to 625 nodes, consensus K-means, a granularity-matched SOM-Super20 control, and four modern baselines (HDBSCAN, spectral clustering, Gaussian mixtures, and Leiden). At matched prototype budgets, K-means is both more reproducible and substantially better at recovering minority classes than SOMs: at 400 prototypes, K-means achieves pairwise NMI $0.819$ versus $0.621$ for the $20\times 20$ SOM and recovers the smallest cancers 6–$14\times$ more effectively (pancreas effective coverage $0.760$ vs. $0.054$).Crucially, the SOM does not close this gap even when given more prototypes ($0.07$ at 625 nodes), so, under matched capacity, minority recovery is better explained by representational capacity and centroid allocation freedom than by topology preservation. The recovery is not free: increasing k overfragments the partition and lowers the pairwise ARI stability ($0.643\to 0.419$ from $k=20$ to $k=400$), while the NMI remains robust ($\approx 0.82$). The hardest minority, pancreas, is recovered only by high-capacity K-means and by no other method evaluated, including SOMs at any size, consensus K-means, SOM-Super20, HDBSCAN, Gaussian mixtures, spectral clustering, and Leiden. The SOM’s distinct value is therefore not stability or recovery but the interpretable two-dimensional topological visualization that it uniquely provides, including a gradient-organized structure that is reproducible across seeds for kidney (weaker for uterus). No single method optimizes all three properties; the appropriate choice depends on whether a task prioritizes reproducibility, minority recovery, or visual interpretability. Because these conclusions follow from the shape of the data and the allocation behavior of the algorithms rather than from biological semantics, we expect them to transfer to high-dimensional imbalanced engineering data, such as those from fault clustering, condition monitoring, and anomaly detection. Full article

Metabolic syndrome (MetS) is a composite classification defined by heterogeneous combinations of cardiometabolic abnormalities. Several components have been associated with pancreatic cancer (PC), but studies often conflate long-term metabolic exposure, tumor-related prediagnostic metabolic change, and prognosis after diagnosis. This review critically evaluates these three settings. This narrative review searched PubMed, Scopus, and Web of Science through April 2026, prioritizing meta-analyses, prospective cohorts, Mendelian randomization studies, clinical studies, preclinical mechanistic evidence, and guidelines. Evidence was interpreted with attention to reverse causation, residual confounding, outcome definitions, and validation. Meta-analyses report a 25–34% higher PC risk among individuals with MetS, with a stepwise gradient across the number of metabolic components; hyperglycemia showed the strongest association among individual components (RR 1.55, 95% CI 1.42–1.70). However, MetS represents multiple versions of exposure, and the epidemiological and clinical evidence remains predominantly observational. Proposed mechanisms involving insulin signaling, adipokines, oxidative stress, epigenetic regulation, and the microbiome are largely preclinical and are not pancreas-specific. New-onset diabetes, rising HbA1c, and involuntary weight loss may mark occult pancreatic ductal adenocarcinoma, but available risk-enrichment models and biomarkers are insufficiently validated for routine screening. After diagnosis, metabolic status and body-composition measures have been associated with survival and perioperative outcomes, although confounding and cancer-related cachexia complicate interpretation. MetS is consistently associated with PC risk but is neither a single causal exposure nor an established target for PC prevention. MetS alone does not justify pancreatic imaging or biomarker testing. Lifestyle and pharmacologic treatment should follow established cardiometabolic indications; their effects on PC incidence remain unproven. Priorities include component-specific causal studies and prospective validation of risk-enrichment strategies. Full article

Background: Pancreatoblastoma (PB) is an exceptionally rare malignant epithelial neoplasm of the pancreas that recapitulates the developing pancreatic anlage. It is defined histologically by acinar-predominant differentiation with characteristic squamoid nests, and it may also show ductal and endocrine differentiation within the same tumor, features that distinguish it from acinar cell carcinoma and solid pseudopapillary neoplasm but that are readily overlooked. It occurs predominantly in young children, although adult-onset disease is well documented. We provide a population-based characterization of PB across the full age spectrum and benchmark it against pancreatic ductal adenocarcinoma (PDAC). Methods: Cases diagnosed between 2000 and 2021 were identified in the Surveillance, Epidemiology, and End Results (SEER) 17-registry database using site and histology codes. Cancer-specific survival (CSS) was estimated and compared, and Cox proportional hazards regression was used to explore associations with cancer-specific mortality. Results: Thirty-nine cases of PB were identified, compared with 155,924 cases of PDAC. The median age at diagnosis was 17 years (range, under 1 to 78 years); 12.8% (n = 5) were younger than 1 year. Males accounted for 69.2% (n = 27) of cases. The cohort was divided at the conventional pediatric-to-adult threshold of 18 years into a pediatric subgroup (age < 18 years; n = 20) and an adult subgroup (age ≥ 18 years; n = 19). CSS at 1 and 5 years was 95.0% and 83.5% in the pediatric subgroup, versus 67.7% and 24.6% in the adult subgroup (log-rank p < 0.001). Five-year CSS was 44.8% in males and 75.0% in females. In an exploratory multivariable model, older age was associated with higher cancer-specific mortality both as a dichotomous variable (adjusted hazard ratio [HR] for age ≥ 18 years 10.7, 95% confidence interval [CI] 2.4–48.2; p = 0.002) and, in a parallel model, as a continuous variable (adjusted HR 1.4 per 10-year increment, 95% CI 1.1–1.8; p = 0.002), indicating an age–mortality gradient. Male sex showed an association in the same direction that did not reach statistical significance (adjusted HR 3.3, 95% CI 0.96–11.6; p = 0.06). Relative to PDAC, PB was more frequently diagnosed in males and was associated with markedly superior survival (1- and 5-year CSS 81.8% and 54.9%, versus 28.8% and 4.0%). Conclusions: Pancreatoblastoma is predominantly a malignancy of young males and carries a substantially more favorable prognosis than PDAC, but outcomes differ markedly across the age spectrum, with adult-onset disease showing considerably poorer survival. Translationally, these population-level estimates support age-stratified prognostic counseling, argue for the referral of adults to centers experienced in rare pancreatic tumors, and provide a rationale for prospective molecular profiling to determine whether adult and pediatric PBs are biologically distinct and whether Wnt/beta-catenin pathway activation is therapeutically actionable. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive metabolic reprogramming, yet how major metabolic pathways are organized at single-cell resolution, and how this relates to the tumor microenvironment and therapeutic vulnerabilities, remains incompletely understood. We analyzed 32,227 cells from the GSE155698 discovery cohort and 32,627 cells from an independent healthy-pancreas reference (GSE229413; n = 5 donors) and introduce the Metabolic Rheostat Index (MRI), the standard deviation across per-cell glycolysis, OXPHOS, and hypoxia pathway scores. A pseudobulk analysis, hallmark gene-set validation, unified-threshold classification, a GDSC2 drug-sensitivity analysis with robust regression, EPIC tumor-purity-adjusted deconvolution, and a survival analysis of 183 TCGA-PAAD samples were performed. The pseudobulk analysis revealed a monotonic MRI gradient from healthy pancreata (mean = 0.259) to adjacent-normal tissue (0.322) to PDAC tumor tissue (0.352; p = 0.0039, Cohen’s d = 1.437), indicating progressive metabolic polarization during malignant transformation driven predominantly by cancer-associated fibroblasts rather than malignant epithelial cells. The glycolysis–hypoxia correlation was stronger in tumor cells (r = 0.121 vs. 0.019), and ERK/MAPK inhibitors showed the greatest drug sensitivity (r = 0.597, p = 0.0008). The Warburg Index correlated with fibroblast infiltration (partial r = 0.312, p = 1.76 × 10⁻⁵) but was not an independent prognostic marker (HR = 0.78, p = 0.321). These findings indicate that PDAC tissue undergoes progressive, stroma-driven metabolic polarization associated with an immunosuppressive microenvironment, providing a multi-dimensional single-cell framework for future metabolic-targeted therapeutic strategies. Full article

Background/Objectives: This study aimed to analyze the effect of diabetes prevalence on mortality levels from gastrointestinal cancers. Methods: The study utilized mortality data for Türkiye from the World Health Organization (WHO) Mortality Database, covering deaths from stomach, colon and rectum, liver, and pancreas cancers, as well as diabetes prevalence data, between 2009 and 2023. Health expenditure and life expectancy data from the World Bank were used as control variables. Results: Diabetes prevalence was significantly correlated with colon and rectum cancer mortality (r = 0.929; p < 0.01), pancreas cancer mortality (r = 0.978; p < 0.01), life expectancy (r = 0.941; p < 0.01), and health expenditure (r = −0.635; p < 0.01). Correlations of diabetes prevalence with esophagus, stomach, and liver cancer mortality were statistically insignificant (p > 0.05). According to generalized linear model analysis results, there was an effect of diabetes prevalence on colon and rectum cancer mortality (B = 383.108; p < 0.01) and pancreas cancer mortality (B = 330.415; p < 0.01). Effects of diabetes prevalence on esophagus, stomach, and liver cancer mortality were statistically insignificant (p > 0.05). Conclusions: Diabetes prevalence was significantly associated with mortality levels for colon and rectal cancer and pancreatic cancer; however, it did not have a significant effect on mortality levels for esophageal, gastric, and liver cancers. Although there is a close relationship between diabetes and the digestive system, a similar relationship between cancer mortality levels of digestive system organs and diabetes is not valid for every organ. We believe that the effect of diabetes on gastrointestinal cancers has a tissue- or organ-specific mechanism of action rather than a digestive mechanism. Full article

Caloric restriction (CR), defined as a 30–60% decrease in ad libitum food intake without malnutrition, has emerged as one of the most robust non-pharmacological interventions for promoting metabolic health and longevity in various species, including yeast, worms, flies, rodents, and perhaps non-human primates. In addition, CR has been shown to reduce the incidence of age-related disorders (for example, diabetes, cancer, and cardiovascular disorders) in mammals. Among the key organs influenced by CR, the pancreas—particularly the insulin-producing β-cells—plays a central role in maintaining glucose homeostasis and metabolic balance. A growing body of evidence suggests that CR exerts its beneficial effects, at least in part, through the modulation of nutrient-sensing pathways and epigenetic regulators. Sirtuins, a family of NAD⁺-dependent deacetylases and ADP-ribosyltransferases, have gained attention as pivotal molecular mediators of CR. By responding to changes in cellular energy status, sirtuins regulate diverse processes including gene expression, oxidative stress response, mitochondrial function, and autophagy. In the pancreas, sirtuins such as SIRT1, SIRT3, and SIRT6 have been implicated in preserving β-cell function, enhancing insulin secretion, and protecting against metabolic stress and inflammation. This review critically examines current evidence regarding the role of individual sirtuins in mediating the pancreatic response to caloric restriction, with particular emphasis on β-cell physiology, insulin secretion, mitochondrial function, autophagy, oxidative stress, and inflammatory signaling. We further discuss how these molecular mechanisms contribute to systemic metabolic homeostasis and may influence healthy longevity. Importantly, we integrate experimental findings with emerging clinical evidence demonstrating the recovery of β-cell function following dietary energy restriction and identify current controversies, limitations, and key knowledge gaps that should guide future translational research. Collectively, available evidence suggests that sirtuins represent central molecular links between caloric restriction and β-cell adaptation, highlighting their potential as therapeutic targets for preserving pancreatic function and preventing metabolic disease. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognised as a systemic disorder with clinically relevant extrahepatic manifestations. Pancreatic diseases have gained particular attention in this context, as they share key metabolic and inflammatory mechanisms with MASLD and may influence each other’s natural history and clinical outcomes. Beyond shared cardiometabolic risk factors, emerging evidence suggests that MASLD may actively contribute to pancreatic dysfunction and disease progression, supporting a bidirectional liver–pancreas relationship. Recognition of this association is essential to improve risk stratification, diagnostic assessment, and clinical management. This review summarises the current evidence linking MASLD with pancreatic disorders, focusing on acute and chronic pancreatitis, pancreatic cancer, and fatty pancreas. We examine shared pathophysiological pathways and discuss how these interactions may affect disease progression, nutritional status, diagnostic strategies, and therapeutic decision-making. We also address key clinical challenges, including alcohol assessment and MASLD–MetALD misclassification, highlight current knowledge gaps, and provide scenario-specific recommendations. Full article

Extracellular Vesicles (EVs) have been increasingly recognized as mediators of intercellular communication in pancreatic tissues, carrying molecular cargo reflective of their cellular origin; however, their direct isolation from solid tissue remains technically challenging due to the high enzymatic activity, lipid content, and structural fragility of the pancreas. Here, we establish a pancreas-adapted and reproducible workflow for the isolation of EVs directly from human and mouse pancreatic tissues across tumor and non-tumorous contexts. This approach integrates controlled tissue processing, gentle enzymatic-mechanical dissociation, and sequential centrifugation to enable efficient vesicle recovery while preserving structural integrity and minimizing contamination. The isolated EVs exhibited characteristic size distributions, intact morphology, and enrichment of canonical EV markers, accompanied by depletion of intracellular components. Quantitative analyses demonstrated high reproducibility across independent isolations, with a coefficient of variation of less than 6%. Proteomic profiling revealed selective enrichment of vesicle-associated proteins and preservation of molecular differences between tumor and normal pancreatic tissues, indicating that tissue-derived EVs retain disease-associated protein signatures. Together, these results establish a standardized framework for pancreas-derived EV isolation that supports reproducible downstream analyses and facilitates molecular characterization of pancreatic tissues. Full article

Background/Objectives: There is limited data on treatment outcomes under immune checkpoint inhibitor (ICI) administration in solid organ transplant recipients (sOTRs). This study aims to evaluate cancer outcome and allograft rejection risk in sOTRs receiving ICI. Methods: This is a retrospective multicenter study. The data had been collected within the Swiss Transplant Cohort Study (STCS) database. We searched for matching individuals from May 2008 up to the end of 2024. The primary outcomes were treatment response and survival; the secondary outcome was allograft rejection. Additional analyses included associated factors such as tumor, transplant, and treatment characteristics. Results: We identified ten patients, six of whom received a kidney allograft, while the remaining four received a liver, lung, pancreas, or combined kidney–pancreas transplant. Treatment response was achieved in half of the sOTRs, with a complete response (CR) in three and prolonged stable disease (SD) in two patients. CR was achieved in all three patients after only a few infusions. At the time of data analysis, four out of ten patients were still alive. Graft rejection occurred in six out of ten cases, five of which occurred after the first cycle of ICI administration. Conclusions: Data is limited and definitive conclusions from this study cannot be drawn given the limited sample size. However, ICI displays promising effects on cancer outcomes in sOTRs with advanced malignancies. The study’s findings demonstrate an overall response in half of sOTRs, but with graft rejection occurring in a similar number of patients. We propose initiating immunotherapy as early as possible, given the promising results, particularly in patients with kidney transplants. We further suggest that in sOTRs, a few ICI infusions could potentially be a cautious option, pending further evidence. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) has dismal survival, and vascular invasion is strongly associated with dissemination and poor outcomes; however, its molecular basis remains unclear. Methods: Transcriptomic and clinical data from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA-PAAD) cohort were integrated with Genotype-Tissue Expression (GTEx) normal pancreas data. Vascular invasion-associated candidate genes were identified using subgroup-specific differential expression filtering. A three-gene prognostic signature was constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression and validated in an independent PACA-AU cohort. Nucleoporin 35 (NUP35) was functionally evaluated by shRNA knockdown, phenotypic assays, endothelial assays using conditioned medium, and Western blotting of extracellular signal-regulated kinase (ERK)-vascular endothelial growth factor A (VEGFA) signaling. Results: We identified 172 vascular invasion-associated candidate genes and developed a three-gene model comprising NUP35, GMNN, and KLK11. The model stratified TCGA patients into risk groups with significantly different overall survival (OS; log-rank p = 0.014) and good predictive performance, with areas under the receiver operating characteristic curve (AUC) of 0.659, 0.722, and 0.796 for 1-, 3-, and 5-year OS, respectively. Consistent trends were observed in PACA-AU. Risk group transcriptomes were enriched for proliferative and tumor progression programs. Among the signature genes, NUP35 was prioritized because higher NUP35 expression was associated with poorer survival and positively correlated with VEGFA expression. NUP35 knockdown suppressed malignant phenotypes, reduced endothelial migration and tube formation, and decreased phosphorylated ERK and VEGFA without altering total ERK levels. Conclusions: A vascular invasion-related three-gene signature enables prognostic stratification in PDAC. NUP35 is associated with malignant and pro-angiogenic phenotypes and may regulate angiogenic activity partly through ERK-VEGFA signaling, supporting its potential as a prognostic biomarker and candidate therapeutic vulnerability. Full article

Magnetic resonance imaging (MRI) plays an essential role in cancer detection and surveillance, yet complete MRI (C-MRI) protocols are lengthy, resource-intensive, and may limit access within population-level cancer care pathways. Abbreviated MRI (A-MRI) protocols have emerged as a streamlined alternative that may preserve diagnostic performance while reducing examination time, cost, and IV contrast exposure. We conducted a narrative review of studies published between 2015 and 2025 evaluating A-MRI in prostate cancer detection and surveillance, pancreatic cystic lesion surveillance, and hepatocellular carcinoma (HCC) surveillance. Evidence was synthesized qualitatively with emphasis on potential advantages, limitations, guideline positions, and evidence gaps. Across the organ systems assessed, A-MRI may demonstrate diagnostic performance comparable to C-MRI in selected clinical contexts. Biparametric MRI has demonstrated noninferior detection of clinically significant prostate cancer; non-contrast A-MRI may be considered for the surveillance of selected low-risk pancreatic cystic lesions, and A-MRI may offer higher sensitivity than ultrasound for HCC surveillance in patients with suboptimal ultrasound visualization. Heterogeneity in the available literature and limited prospective outcome data remain important limitations. Overall, A-MRI represents a complementary, risk-adapted strategy rather than a universal replacement for C-MRI, and further prospective studies are needed to define optimal patient selection and long-term oncologic benefit. Full article

Background/Objectives: Pancreatic cancer (PC) should be diagnosed in its early stages. Therefore, it is necessary to identify high-risk individuals of PC. Methods: Between 2001 and 2017, 1542 PC cases were diagnosed at two tertial care institutions. Of these, 117 cases had undergone abdominal contrast-enhanced computed tomography (CE-CT) 1–10 years before PC diagnosis and were classified as the PC group. Meanwhile, 43,102 cases underwent abdominal CE-CT for close examination of non-pancreatic diseases in the same period, of which 1170 were randomly selected. Of these, 117 cases were matched to the PC group with the propensity score and designated the non-PC group. Pancreatic volumetry was performed using the 3D image analysis system for abdominal CE-CT in both groups and various measurements were compared. In PC group, CE-CT taken 1–10 years before the onset of PC was analyzed. Results: After propensity score matching, baseline characteristics did not significantly differ between the two groups. The whole pancreatic volume/body surface area (BSA) (p = 0.014), volume of main pancreatic duct (MPD) plus cystic lesion/BSA (p < 0.001), volume of pancreatic parenchyma/BSA (p = 0.002), ratio of cross-sectional areas (p = 0.033), and MPD diameter/BSA (p < 0.001) significantly differed between the two groups. In subgroup analysis of patients without cystic lesions, the whole pancreatic volume/BSA, volume of MPD/BSA, volume of pancreatic parenchyma/BSA, ratio of cross-sectional areas, and MPD diameter/BSA significantly differed between the two groups. Conclusions: Pancreatic volumetry could identify patients at high risk of PC. Full article

The pancreas is an organ with two functions: endocrine and exocrine. The proper functioning of the pancreas depends on many factors. One of these is trace elements—precise control of trace element homeostasis is important for both the endocrine and exocrine parts. This review provides a comprehensive summary of current knowledge regarding the role of trace elements: iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in pancreatic physiology and their influence on the pathogenesis of key diseases of this organ, such as diabetes (DM), acute (AP) and chronic pancreatitis (CP), autoimmune pancreatitis (AIP), and pancreatic cancer (PC). Trace elements, including Fe, Cu, Zn, Se, and Mn, play a fundamental role in maintaining endocrine and exocrine homeostasis, participating in insulin synthesis, stabilizing digestive enzymes, and the functioning of antioxidant systems. It has been demonstrated that disturbances in their concentrations lead to the activation of pathological molecular pathways, including oxidative stress, chronic inflammation, and beta-cell apoptosis. In the context of diabetes, excess Fe promotes ferroptosis, whilst exposure to heavy metals such as Cd, Pb, and Hg induces insulin resistance and pancreatic islet dysfunction. In the course of pancreatitis, elements such as Zn and Se exhibit protective potential by stabilizing tissue barriers, whereas toxic metals impair ion transport, exacerbating fibrotic processes. Furthermore, analysis of available data indicates a significant association between heavy metal accumulation and pancreatic carcinogenesis, driven by DNA damage and oncogene modulation. Understanding pancreatic metallomics opens new prospects for early diagnosis, environmental prevention, and the development of targeted therapeutic strategies that restore the body’s micronutrient balance. Full article

Background: Spleen-preserving (SP) distal pancreatectomy (DP) with splenic vessels 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