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Frontiers in Immunology 2024Immune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune...
BACKGROUND
Immune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune microenvironments and conflicting research findings. Mendelian randomization (MR), this study aims to delineate the causal relationships between immune cells and pancreatic cancer while identifying intermediary factors.
METHODS
The genome-wide association study (GWAS) data on immune cells, pancreatic cancer, and plasma metabolites are derived from public databases. In this investigation, inverse variance weighting (IVW) as the primary analytical approach to investigate the causal relationship between exposure and outcome. Furthermore, this study incorporates MR-Egger, simple mode, weighted median, and weighted mode as supplementary analytical approaches. To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. In conclusion, this study employed mediation analysis to elucidate the potential mediating effects of plasma metabolites.
RESULTS
Our investigation revealed a causal relationship between immune cells and pancreatic cancer, highlighting the pivotal roles of CD11c+ monocytes (odds ratio, OR=1.105; 95% confidence interval, 95%CI: 1.002-1.218; P=0.045), HLA DR+ CD4+ antigen-presenting cells (OR=0.920; 95%CI: 0.873-0.968; P=0.001), and HLA DR+ CD8br T cells (OR=1.058; 95%CI: 1.002-1.117; P=0.041) in pancreatic cancer progression. Further mediation analysis indicated that oxalate (proportion of mediation effect in total effect: -11.6%, 95% CI: -89.7%, 66.6%) and the mannose to trans-4-hydroxyproline ratio (-19.4, 95% CI: -136%, 96.8%) partially mediate the relationship between HLA DR+ CD8br T cells and pancreatic cancer in nature. In addition, our analysis indicates that adrenate (-8.39%, 95% CI: -18.3%, 1.54%) plays a partial mediating role in the association between CD11c+ monocyte and pancreatic cancer, while cortisone (-26.6%, 95% CI: 138%, -84.8%) acts as a partial mediator between HLA DR+ CD4+ AC and pancreatic cancer.
CONCLUSION
This MR investigation provides evidence supporting the causal relationship between immune cell and pancreatic cancer, with plasma metabolites serving as mediators. Identifying immune cell phenotypes with potential causal effects on pancreatic cancer sheds light on its underlying mechanisms and suggests novel therapeutic targets.
Topics: Humans; Pancreatic Neoplasms; Mendelian Randomization Analysis; Genome-Wide Association Study; Monocytes; Risk Factors; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38933268
DOI: 10.3389/fimmu.2024.1402113 -
Viruses Jun 2024Infectious pancreatic necrosis virus (IPNV) causes economic losses with a highly variable mortality rate worldwide, especially in rainbow trout. The virus has a...
Infectious pancreatic necrosis virus (IPNV) causes economic losses with a highly variable mortality rate worldwide, especially in rainbow trout. The virus has a double-stranded bi-partite RNA genome designated segment A and B. New complete genome sequences of nine rainbow trout isolates from Turkey were determined and subjected to phylogenetic analysis, identifying all as genotype 5 (serotype Sp). A time-dependent change in the extended pathogenicity motif of VP2 from P217T221A247 (PTA) to PTE P217T221E247 over a period of 10 years was identified. A wider analysis of 99 IPNV sequences from Turkey and Iran revealed the emergence of the motif PTE from 2007 to 2017, inducing significant morbidity in fry by 2013. In fact, displacement of the PTA motif, by the PTE motif in IPNV isolates appeared to be connected to a production peak of rainbow trout in 2013. An additional CAI analysis provided more evidence, indicating that rainbow trout culture in Turkey has an influence on the evolution of IPNV.
Topics: Animals; Infectious pancreatic necrosis virus; Oncorhynchus mykiss; Birnaviridae Infections; Fish Diseases; Turkey; Phylogeny; Evolution, Molecular; Viral Structural Proteins; Genotype; Genome, Viral; Virulence; Amino Acid Motifs; Aquaculture
PubMed: 38932285
DOI: 10.3390/v16060994 -
Nutrients Jun 2024Preoperative malnutrition is a significant factor in patients with pancreatic tumors undergoing pancreaticoduodenectomy. The aim of this study was to assess the...
BACKGROUND
Preoperative malnutrition is a significant factor in patients with pancreatic tumors undergoing pancreaticoduodenectomy. The aim of this study was to assess the association between preoperative malnutrition and delayed discharge within a ten-day timeframe and potential correlations between preoperative malnutrition and postoperative surgical complications.
METHODS
A retrospective cohort study was conducted, recruiting a final sample of 79 patients with benign or malignant cephalic pancreatic tumors from 2015 to 2022. The risk of malnutrition was assessed using the Malnutrition Universal Screening Tool, while length of hospital stay and relevant clinical data were extracted from clinical documentation.
RESULTS
The preoperative malnutrition risk was high in 21.52% of the sample, moderate in 36.71%, and low in 41.77%. Body mass index (BMI) ( = 0.007) and postoperative surgical complications ( < 0.001) were significantly correlated with delayed discharge. No statistically significant differences were found between levels of malnutrition risk and delayed discharge ( = 0.122), or postoperative surgical complications ( = 0.874).
CONCLUSIONS
Postoperative complications and BMI emerge as significant risk factors. The limited sample size may have compromised the collection of homogeneous and significant data. Future studies should evaluate the implementation of personalized nutritional screening tools, nutritional assessment plans, and the involvement of specialized health professionals.
Topics: Humans; Malnutrition; Retrospective Studies; Male; Female; Pancreatic Neoplasms; Pancreaticoduodenectomy; Middle Aged; Postoperative Complications; Aged; Risk Factors; Nutrition Assessment; Length of Stay; Body Mass Index; Preoperative Period; Nutritional Status; Adult; Patient Discharge; Cohort Studies
PubMed: 38931194
DOI: 10.3390/nu16121839 -
Nutrients Jun 2024This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients...
This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients diagnosed with pancreatic cancer who underwent surgery at the Modena Cancer Center between June 2015 and October 2023. Body composition parameters were obtained from CT scans performed before and after surgery. The percentage of sarcopenic patients at the time of diagnosis of pancreatic cancer is 56.82%. Of the patients who died between the first and second CT evaluated, 58% were sarcopenic, thus confirming the role of sarcopenia on outcome. The study found that all body composition parameters (TAMA, SMI, VFI, and SFI) demonstrated a trend towards reduction between two examinations, indicating an overall depletion in muscle and adipose tissue. We then evaluated the relationships between fat-related parameters (VFI, SFI and VSR) and survival outcomes: overall survival and progression-free survival. Cox univariate regression model show significant parameter related to outcomes was adipose tissue, specifically VFI. The study found that higher VFI levels were associated with greater survival rates. This research holds promise for advancing our understanding of the link between body composition and the prognosis of pancreatic cancer patients.
Topics: Humans; Pancreatic Neoplasms; Body Composition; Male; Female; Aged; Sarcopenia; Middle Aged; Adipose Tissue; Tomography, X-Ray Computed; Prognosis
PubMed: 38931189
DOI: 10.3390/nu16121834 -
Nutrients Jun 2024: Modulator therapies improve weight and body mass index (BMI) in cystic fibrosis (CF) patients. We aimed to compare the nutritional risk index (NRI) in adult CF...
: Modulator therapies improve weight and body mass index (BMI) in cystic fibrosis (CF) patients. We aimed to compare the nutritional risk index (NRI) in adult CF patients receiving modulator (MT) or only non-modulator (conventional) therapies (non-MT). : A single-center prospective cohort study was conducted between June and December 2023. The NRI based on weight gain and albumin was calculated at beginning and end of a 12-week period in both groups. This design was pragmatic, since it was based on individual patient access to MT for 12 weeks. : In total, 107 patients were included [mean (SD) age: 23.85 (4.98) years, 54.7% male, 46.7% MT]. In the MT group, mean (SD) weight (kg) and albumin (g/dL) increased significantly [changes: +3.09 (2.74) and +0.17 (0.37); < 0.001]. In the non-MT group, weight and albumin decreased significantly [changes: -0.99 (1.73) and -0.12 (0.30); < 0.001]. Compared to the MT group, baseline mean (SD) NRI in the non-MT group was significantly higher [100.65 (11.80) vs. 104.10 (10.10); = 0.044]. At the end of the 12 weeks, mean (SD) NRI in the MT group was higher than in the non-MT group [104.18 (10.40) vs. 102.58 (12.39); = 0.145]. In the MT group, the NRI category improved in 22 (44%), and worsened in 3 (6%) patients ( < 0.001). In the non-MT group, the NRI category improved in 2 (3.5%), and worsened in 10 (17.5%) patients ( < 0.001). : This is the first study reporting on a positive effect of MT on NRIs, based on weight gain and albumin. Personalized nutrition and routine follow-up of adults with CF based on NRI is recommended prior to MT initiation.
Topics: Humans; Cystic Fibrosis; Male; Prospective Studies; Female; Adult; Nutritional Status; Young Adult; Body Mass Index; Weight Gain; Nutrition Assessment; Cohort Studies; Serum Albumin; Adolescent; Risk Factors
PubMed: 38931166
DOI: 10.3390/nu16121811 -
Journal of Personalized Medicine Jun 2024An elevated serum β2-microglobulin (β2M) level is indicative of impaired glomerular filtration and prerenal diseases, such as malignant tumors, autoimmune disorders,...
An elevated serum β2-microglobulin (β2M) level is indicative of impaired glomerular filtration and prerenal diseases, such as malignant tumors, autoimmune disorders, and liver diseases. An elevated serum β2M level has been shown to promote metastasis via the induction of epithelial-mesenchymal transition (EMT) in cancer cells. However, the therapeutic potential of targeting β2M remains unclear. Here, we aimed to investigate the efficacy of Filtor, a small polymethyl methacrylate fiber-based β2M removal column, in reducing the β2M level and suppressing cancer cell-induced EMT and metastasis. We assessed the effects of Filtor on the changes in metastasis based on the number of circulating tumor cells (CTCs), which reflects the post-EMT cancer cell population. We performed therapeutic apheresis using Filtor on a male patient with sinonasal neuroendocrine carcinoma, a female patient with a history of colorectal cancer, and another female patient with a history of pancreatic ductal adenocarcinoma. Significantly low serum β2M levels and CTC counts were observed immediately and 4 weeks after treatment compared with those in the pretreatment phase. Moreover, the CTC count immediately after therapeutic intervention was markedly reduced, likely because Filtor had trapped CTCs directly. These findings suggest that therapeutic apheresis with Filtor can prevent cancer metastasis and recurrence by directly removing CTCs.
PubMed: 38929860
DOI: 10.3390/jpm14060640 -
Medicina (Kaunas, Lithuania) Jun 2024: This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography-fine needle aspiration cytology (EUS-FNAC) by... (Comparative Study)
Comparative Study
: This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography-fine needle aspiration cytology (EUS-FNAC) by comparing it with liquid-based preparation (LBP) and conventional smear (CS) in pancreas. : The diagnostic categories (I through VII) were classified according to the World Health Organization Reporting System for Pancreaticobiliary Cytopathology. Ten cytologic features, including nuclear and additional features, were evaluated in 53 cases subjected to EUS-FNAC. Nuclear features comprised irregular nuclear contours, nuclear enlargement, hypochromatic nuclei with parachromatin clearing, and nucleoli. Additional cellular features included isolated atypical cells, mucinous cytoplasm, drunken honeycomb architecture, mitosis, necrotic background, and cellularity. A decision tree analysis was conducted to assess diagnostic efficacy. : The diagnostic concordance rate between LBP and CS was 49.1% (26 out of 53 cases). No significant differences in nuclear features were observed between categories III (atypical), VI (suspicious for malignancy), and VII (malignant). The decision tree analysis of LBP indicated that cases with moderate or high cellularity and mitosis could be considered diagnostic for those exhibiting nuclear atypia. Furthermore, in CS, mitosis, isolated atypical cells, and necrotic background exerted a more significant impact on the diagnosis of EUS-FNAC. : Significant parameters for interpreting EUS-FNAC may differ between LBP and CS. While nuclear atypia did not influence the diagnosis of categories III, VI, and VII, other cytopathologic features, such as cellularity, mitosis, and necrotic background, may present challenges in diagnosing EUS-FNAC.
Topics: Humans; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Male; Female; Middle Aged; Aged; Pancreas; Adult; Pancreatic Neoplasms; Cytodiagnosis; Aged, 80 and over; Cytology
PubMed: 38929547
DOI: 10.3390/medicina60060930 -
Medicina (Kaunas, Lithuania) May 2024: The pancreatic solid pseudopapillary neoplasm (SPN), a rare tumor predominantly affecting young women, has seen an increased incidence due to improved imaging and...
: The pancreatic solid pseudopapillary neoplasm (SPN), a rare tumor predominantly affecting young women, has seen an increased incidence due to improved imaging and epidemiological knowledge. This study aimed to understand the outcomes of different interventions, possible complications, and associated risk factors. : This study retrospectively analyzed 24 patients who underwent pancreatic surgery for SPNs between September 1998 and July 2020. : Surgical intervention, typically required for symptomatic cases or pathological confirmation, yielded favorable outcomes with a 5-year survival rate of up to 97%. Despite challenges in standardizing preoperative evaluation and follow-up protocols, aggressive complete resection showed promising long-term survival and good oncological outcomes. Notably, no significant differences were found between conventional and minimally invasive (MI) surgery in perioperative outcomes. Histopathological correlations were lacking in prognosis and locations. Among the patients, one developed diffuse liver metastases 41 months postoperatively but responded well to chemotherapy and transcatheter arterial chemoembolization, with disease stability observed at 159 postoperative months. Another patient developed nonalcoholic steatohepatitis after surgery and underwent liver transplantation, succumbing to poor medication adherence 115 months after surgery. : These findings underscore the importance of surgical intervention in managing SPNs and suggest the MI approach as a viable option with comparable outcomes to conventional surgery.
Topics: Humans; Female; Pancreatic Neoplasms; Adult; Retrospective Studies; Male; Middle Aged; Treatment Outcome; Pancreatectomy; Young Adult; Carcinoma, Papillary; Adolescent; Aged
PubMed: 38929506
DOI: 10.3390/medicina60060889 -
Medicina (Kaunas, Lithuania) May 2024: The risk of developing glycemic dysregulation up to overt diabetes mellitus (DM) after an episode of acute pancreatitis (AP) is increasingly being analyzed. We aimed...
: The risk of developing glycemic dysregulation up to overt diabetes mellitus (DM) after an episode of acute pancreatitis (AP) is increasingly being analyzed. We aimed to assess the changes in serum glucose levels associated with the first episode of AP, as well as the impact of dysglycemia on outcomes such as the severity of inflammation, the length of hospitalization, mortality, and the persistence of hyperglycemia at follow-up. : All patients experiencing their first episode of AP, who presented to the Emergency Room (ER) between 1 January 2020 and 31 December 2023, were retrospectively included. On-admission serum glucose and peak serum glucose during hospitalization were the biological markers used to assess glucose metabolism impairment, and they were correlated with outcomes of AP. : Our study included 240 patients, 46.67% (112 patients) having a biliary etiology for an AP flare. Patients with COVID-19-associated AP exhibited the highest on-admission and peak serum glucose levels (244.25 mg/dL and 305.5 mg/dL, respectively). A longer hospital stay was noted in patients with peak serum glucose levels of ≥100 mg/dL (9.49 days) compared to normoglycemic patients (6.53 days). Both on-admission and peak glucose levels were associated with elevated CRP levels during hospitalization. A total of 83.78% of patients who received antibiotics exhibited on-admission hyperglycemia, and 72.07% had peak serum glucose levels of ≥100 mg/dL. The presence of hyperglycemia at follow-up was associated with both on-admission and peak serum glucose levels of ≥100 mg/dL, as well as with a longer stay, higher CRP levels, and antibiotic use during index admission. : On-admission hyperglycemia predicts a higher inflammatory response in patients at the first episode of AP, while the presence of hyperglycemia during hospitalization is associated with imaging and biological severity and longer hospitalizations, indicating a more severe disease course. Both on-admission and peak in-hospital hyperglycemia were identified as risk factors for sustained hyperglycemia at follow-up.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Pancreatitis; Blood Glucose; Adult; Length of Stay; Hyperglycemia; COVID-19; Aged; Hospitalization; Severity of Illness Index; Biomarkers
PubMed: 38929473
DOI: 10.3390/medicina60060856 -
Children (Basel, Switzerland) May 2024Pancreatic fluid collections (PFCs) are a well-known complication of pancreatitis. PFCs operative management includes percutaneous, endoscopic or surgical drainage. Even...
Pancreatic fluid collections (PFCs) are a well-known complication of pancreatitis. PFCs operative management includes percutaneous, endoscopic or surgical drainage. Even if in adult patients, endoscopic drainage is a well-established treatment, few data are available in pediatric setting. We report our single-center experience of EUS-guided cystogastrostomy and lumen-apposing metal stent (LAMS) positioning in children with PFCs; this, at the best of our knowledge, has never been reported before. All consecutive children with PFCs between April 2020 and November 2022 were enrolled in this retrospective study. PFCs were preoperatively evaluated with MRI or CT scan. All the procedures were performed under general anesthesia. A LAMS Hot-Axios 10 × 15 mm was placed in all patients. We evaluated technical feasibility and clinical outcomes, including complications and recurrence rates. Follow-up included clinical observation, blood tests and US. EUS-guided cystogastrostomy was performed in 3 children (2 males; median age 13.2 years). Median maximum cyst diameter was 14.7 cm (range 10-22 cm). Technical and clinical success rates were 100%. No intra or post-operative complications occurred. Our experience suggests that this can be considered a safe and feasible treatment of PCFs even in the pediatric population, as long as the procedure is performed by an expert Endoscopist in a pediatric tertiary-level Center.
PubMed: 38929223
DOI: 10.3390/children11060643