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Science (New York, N.Y.) Jun 2024Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC...
Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled with pancreatitis (ptPDAC), antigen-presenting type I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8 T cell activation and elimination of ptPDAC with restoration of life span even upon PDAC rechallenge. Using PDAC antigen-loaded cDC1s as a vaccine, immunotherapy-resistant PDAC was rendered sensitive to iCBT with elimination of tumors. cDC1 vaccination coupled with iCBT identified specific CDR3 sequences in the tumor-infiltrating CD8 T cells with potential therapeutic importance. This study identifies a fundamental difference in the immune microenvironment in PDAC concurrent with, or without, pancreatitis and provides a rationale for combining cDC1 vaccination with iCBT as a potential treatment option.
Topics: Dendritic Cells; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Immunotherapy; Animals; Mice; Humans; Tumor Microenvironment; Cancer Vaccines; Immune Checkpoint Inhibitors; Pancreatitis; CD8-Positive T-Lymphocytes; Mice, Inbred C57BL
PubMed: 38935717
DOI: 10.1126/science.adh4567 -
BJS Open May 2024
Meta-Analysis
Topics: Humans; Pancreatic Neoplasms; Biomarkers, Tumor
PubMed: 38935426
DOI: 10.1093/bjsopen/zrae046 -
BJS Open May 2024Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related...
BACKGROUND
Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related biomarker. The aim of the study was to assess soluble suppression of tumourigenicity 2 elevation after hepatectomy and whether it can predict posthepatectomy liver failure.
METHODS
This was a single-centre retrospective study including all patients who underwent a liver resection between 2015 and 2019. Plasma concentrations of soluble suppression of tumourigenicity 2 were measured before surgery and at postoperative days 1, 2, 5 and 7. Posthepatectomy liver failure was defined according to the International Study Group of Liver Surgery and the morbidity rate was graded according to the Clavien-Dindo classification.
RESULTS
A total of 173 patients were included (75 underwent major and 98 minor resection); plasma levels of soluble suppression of tumourigenicity 2 increased from 43.42 (range 18.69-119.96) pg/ml to 2622.23 (range 1354.18-4178.27) pg/ml on postoperative day 1 (P < 0.001). Postoperative day 1 soluble suppression of tumourigenicity 2 concentration accurately predicted posthepatectomy liver failure ≥ grade B (area under curve = 0.916, P < 0.001) and its outstanding performance was not affected by underlying disease, liver pathological status and extent of resection. The cut-off value, sensitivity, specificity, positive predictive value and negative predictive value of postoperative day 1 soluble suppression of tumourigenicity 2 in predicting posthepatectomy liver failure ≥ grade B were 3700, 92%, 85%, 64% and 97% respectively. Soluble suppression of tumourigenicity 2high patients more frequently experienced posthepatectomy liver failure ≥ grade B (64.3% (n = 36) versus 2.6% (n = 3)) and Clavien-Dindo IIIa higher morbidity rate (23.2% (n = 13) versus 5.1% (n = 6)) compared with soluble suppression of tumourigenicity 2low patients.
CONCLUSIONS
Soluble suppression of tumourigenicity 2 may be a reliable predictor of posthepatectomy liver failure ≥ grade B as early as postoperative day 1 for patients undergoing liver resection. Its role in controlling hepatic injury/regeneration needs further investigation. Registration number: ChiCTR-OOC-15007210 (www.chictr.org.cn/).
Topics: Humans; Male; Female; Hepatectomy; Retrospective Studies; Middle Aged; Liver Failure; Postoperative Complications; Aged; Biomarkers; Adult; Liver Neoplasms; Predictive Value of Tests
PubMed: 38935425
DOI: 10.1093/bjsopen/zrae043 -
Supportive Care in Cancer : Official... Jun 2024Parenteral nutrition (PN) can be an effective treatment to improve the nutritional status of patients with pancreatic cancer, but the effects of PN on quality of life... (Comparative Study)
Comparative Study
Effects of parenteral nutrition + best supportive nutritional care vs. best supportive nutritional care alone on quality of life in patients with pancreatic cancer-a secondary analysis of PANUSCO.
PURPOSE
Parenteral nutrition (PN) can be an effective treatment to improve the nutritional status of patients with pancreatic cancer, but the effects of PN on quality of life (QoL) are still understudied. Therefore, we aimed at investigating whether the best supportive nutritional care (BSNC) in combination with PN at home compared to BSNC alone changed QoL in patients with advanced pancreatic cancer undergoing chemotherapy over a period of 7 weeks.
METHODS
n = 12 patients in the PANUSCO study received nutritional counseling only (control group (CG)) and n = 9 patients were also given supportive PN (intervention group (IG)). The primary endpoint was the change of QoL (EORTC-QLQ-C30 and QLQ-PAN26) over 7 weeks between the groups.
RESULTS
There was a significant worsening in social functioning in IG (p = 0.031) and a significant difference between groups in change of social functioning (p = 0.020). In all other domains of QoL, there was no significant difference between groups. Within groups, there was a significant improvement in the domain weight loss in IG (p = 0.031), showing that patients were less worried about their weight being too low. Furthermore, there was a significant difference in the change of BW over time between groups (p < 0.001) with IG showing an increase (p = 0.004) and CG showing no change (p = 0.578).
CONCLUSION
The administration of PN had in one of five domains negative consequences on QoL. The decision to administer PN should always be made individually and together with the patient, and the impact on QoL should be included in the decision to administer PN.
Topics: Humans; Quality of Life; Pancreatic Neoplasms; Male; Female; Middle Aged; Aged; Parenteral Nutrition; Nutritional Support; Nutritional Status
PubMed: 38935156
DOI: 10.1007/s00520-024-08666-1 -
Chirurgie (Heidelberg, Germany) Jun 2024Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are mainly found in the small intestine and pancreas. The course of the disease in patients is highly variable...
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are mainly found in the small intestine and pancreas. The course of the disease in patients is highly variable and depends on the degree of differentiation (G1-G3) of the neoplasm. The potential for metastasis formation of GEP-NEN is high even with good differentiation (G1). Lymph node metastases and, in many cases, liver metastases are also often found. Less common are bone metastases or peritoneal carcinomas. The treatment of these GEP-NENs is surgical, whenever possible. If an R0 resection with removal of all lymph node and liver metastases is successful, the prognosis of the patients is excellent. Patients with diffuse liver or bone metastases can no longer be cured by surgery alone. The long-term survival of these patients is nowadays possible due to the availability of drugs (e.g., somatostatin analogues, tyrosine kinase inhibitors), peptide receptor radionuclide therapy (PRRT) and liver-directed procedures, with a good quality of life.
PubMed: 38935138
DOI: 10.1007/s00104-024-02117-7 -
Cureus May 2024A serous cystic tumor is a rare entity that has a benign course. Its imaging characteristics, such as the presence of multiple cysts with or without nodular enhancement,...
A serous cystic tumor is a rare entity that has a benign course. Its imaging characteristics, such as the presence of multiple cysts with or without nodular enhancement, can simulate other cystic or solid lesions of the pancreas. Identification of the enhancing scar with punctate calcifications on computed tomography (CT) or magnetic resonance imaging (MRI) may be a distinctive finding suggesting this diagnosis. Neuroendocrine tumors of the pancreas are a different and also rare entity. In images, they have early arterial enhancement. In MRI, they are hyperintense on T2 and hypointense on T1, with avid contrast enhancement. A case of a patient with two focal lesions in the pancreas is presented and the importance of integrating clinical findings, semiology in diagnostic images and, if applicable, the histopathological result for the optimal management of pancreatic tumors is illustrated, highlighting the crucial role of a radiologist in this process.
PubMed: 38933621
DOI: 10.7759/cureus.61159 -
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 -
World Journal of Nuclear Medicine Jun 2024Phyllodes tumor is a rare fibroepithelial neoplasm of the breast. This tumor tends to spread by hematogenous route, with common metastatic sites in the lungs, bones, and...
Phyllodes tumor is a rare fibroepithelial neoplasm of the breast. This tumor tends to spread by hematogenous route, with common metastatic sites in the lungs, bones, and liver. Metastases to the pleura, stomach, pancreas, kidneys, and adrenal gland are rare. We present a case of a 52-year-old lady with malignant phyllodes tumor of breast undergone local tumor resection, followed by solitary lung metastasis with lobectomy, and subsequently diagnosed of multiple new metastatic sites in pleura, stomach, pancreas, kidneys, adrenal gland, and bone detected on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography within 2 years.
PubMed: 38933073
DOI: 10.1055/s-0044-1786519 -
Viruses Jun 2024Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges...
Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges such as cellular resistance mediated by the interferon (IFN) response. Dimethyl fumarate (DMF) is used in the treatment of multiple sclerosis and psoriasis and is recognized for its anti-cancer properties and has been shown to enhance both VSVΔ51 and HSV-1 oncolytic activity. Tepilamide fumarate (TPF) is a DMF analog currently undergoing clinical trials for the treatment of moderate-to-severe plaque psoriasis. The aim of this study was to evaluate the potential of TPF in enhancing the effectiveness of oncolytic viruses. In vitro, TPF treatment rendered 786-0 carcinoma cells more susceptible to VSVΔ51 infection, leading to increased viral replication. It outperformed DMF in both increasing viral infection and increasing the killing of these resistant cancer cells and other cancer cell lines tested. Ex vivo studies demonstrated TPF's selective boosting of oncolytic virus infection in cancer cells without affecting healthy tissues. Effectiveness was notably high in pancreatic and ovarian tumor samples. Our study further indicates that TPF can downregulate the IFN pathway through a similar mechanism to DMF, making resistant cancer cells more vulnerable to viral infection. Furthermore, TPF's impact on gene therapy was assessed, revealing its ability to enhance the transduction efficiency of vectors such as lentivirus, adenovirus type 5, and adeno-associated virus type 2 across various cell lines. This data underscore TPF's potential role in not only oncolytic virotherapy but also in the broader application of gene therapy. Collectively, these findings position TPF as a promising agent in oncolytic virotherapy, warranting further exploration of its therapeutic potential.
Topics: Humans; Oncolytic Virotherapy; Cell Line, Tumor; Oncolytic Viruses; Virus Replication; Fumarates; Neoplasms; Dimethyl Fumarate; Herpesvirus 1, Human
PubMed: 38932212
DOI: 10.3390/v16060920 -
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