A Review on the Research Progress of Inducible Nitric Oxide Synthase in the Pathogenesis of Pancreatic Malignancy

Pancreatic cancer is a common tumor of the digestive system, at present, the pathogenesis is still unclear, but in the current research on the pathogenesis of pancreatic malignant tumors, the research on inducible nitric oxide synthase is particularly extensive. Therefore, this article focuses on the research progress of inducible nitric oxide synthase in the pathogenesis of pancreatic cancer. This is a review.

Research Progress on Inducible Nitric Oxide Synthase in the Pathogenesis of Pancreatic Malignancy

Pancreatic cancer is a common tumor of the digestive system. At present, the pathogenesis is still unclear, but current research on inducible nitric oxide synthase in relation to the pathogenesis of pancreatic malignant tumors is particularly extensive. Therefore, this article focuses on the research progress on inducible nitric oxide synthase in the pathogenesis of pancreatic cancer.

Macrophages-induced IL-18–mediated eosinophilia promotes characteristics of pancreatic malignancy

Reports indicate that accumulated macrophages in the pancreas are responsible for promoting the pathogenesis of chronic pancreatitis (CP). Recently, macrophage-secreted cytokines have been implicated in promoting pancreatic acinar-to-ductal metaplasia (ADM). This study aims to establish the role of accumulated macrophage-activated NLRP3-IL-18-eosinophil mechanistic pathway in promoting several characteristics of pancreatic malignancy in CP. We report that in a murine model of pancreatic cancer (PC), accumulated macrophages are the source of NLRP3-regulated IL-18, which promotes eosinophilic inflammation-mediated accumulation to periductal mucin and collagen, including the formation of ADM, pancreatic intraepithelial neoplasia (PanINs), and intraductal papillary mucinous neoplasm. Most importantly, we show improved malignant characteristics with reduced levels of oncogenes in an anti–IL-18 neutralized and IL-18 gene deficient murine model of CP. Last, human biopsies validated that NLRP3-IL-18–induced eosinophils accumulate near the ducts, showing PanINs formation in PC. Taken together, we present the evidence on the role of IL-18–induced eosinophilia in the development of PC phenotype like ADM, PanINs, and ductal cell differentiation in inflammation-induced CP.

Incidence of pancreatic malignancies in the Russian Federation: a retrospective cohort trial

Background. Pancreatic malignancies pose a challenging medical and social problem. The assessment of oncology care requires an in-depth analysis of morbidity and lethality. At a relatively improved prevalence and lethality in other-locale malignancies, pancreatic cancer remains a disappointing situation. Medical statistics in pancreatic malignancy can be used for the specialty care prediction and implementation of measures to advance diagnostic algorithms and population screening.Objectives. An assessment of the pancreatic malignancy incidence and mortality in the adult population of Russian Federation over a six-year period.Methods. A retrospective descriptive cohort trial included statistical data on morbidity and mortality in pancreatic cancer patients (C 25.0-C 25.9) according to the ICD of 10th edition. A comparison cohort sampled patients with all-locale neoplasms (C00-C96) according to the ICD of 10th edition, excluding nosologies C25.0-C25.9. Information was sourced in the Federal Statistical Abstracts for the period of 2014-2019. Inclusion criteria: the study cohort included pancreatic cancer patients diagnosed at the age of 18 years on, and comparison cohort — malignancy patients diagnosed with at 18 years on. The main study indicator were the pancreatic cancer morbidity and mortality figures in Russia.Results. Pancreatic cancer was shown to co-increase main morbidity figures in 2014-2019 compared to malignant neoplasms of other localities. Other-locale malignancies decreased mortality over the study period, which was not the case with pancreatic cancer. The period exhibits more frequent morphologically verified diagnoses and higher population numbers registered with specialty dispensaries. Registered pancreatic cancer figures are significantly higher in the female population. The proportion of advanced pancreatic malignancies at primary diagnosis exceeds that of early stages.Conclusion. The findings expose a demand for improving the system of early pancreatic cancer detection via intensifying preventive measures to capture the patient’s predisposition and screening techniques for early disease diagnosis. An active outpatient surveillance is prerequisite to an effective population involvement in dispensary screening.

68Ga-FAPI-04 PET/MR is helpful in differential diagnosis of pancreatitis from pancreatic malignancy compared to 18F-FDG PET/CT: a case report

Introduction 68Ga-fibroblast activation protein-specific enzyme inhibitor 04 (FAPI-04) is a radiolabelled molecular agent targeting the inhibitor of fibroblast activation protein (FAP), which is often present in tumor stroma and inflammatory tissue with prominent fibroblast proliferation. FAPI-04 is a promising PET tracer for tumor imaging as well as IgG4-related disease (IgG4-RD). Case description We herein present a case where 68Ga-FAPI PET/MR helped to diagnose IgG4-RD that involved pancreas and bile duct. A 62-year-old patient suffered from diffusive discomfort at middle upper abdomen and presented brown urine. Blood test revealed abnormal liver function and elevated IgG4 (4.830g/L↑). 18F-FDG PET showed enlarged uncinate process and dilated bile duct tree. Mild increase of FDG uptake in uncinate process and head of pancreas indicated possible pancreatic malignancy, but the clinical evidence was not sufficient and histology examination was negative. 68Ga-FAPI PET revealed prominent increased radioactivity distribution in the entire pancreas and bile duct, suggesting IgG4-RD. Conclusion FAPI-04 is not only a good PET imaging tracer for tumors, but also for prominent fibroblast-mediated inflammation. FAPI imaging should be considered when the diagnosis using 18F-FDG imaging is ambiguous. The presented case illustrates that 68Ga-FAPI-04 PET is helpful in improving the differential diagnosis of pancreatitis and pancreatic cancer.