-
World Journal of Gastroenterology Feb 2024Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation... (Review)
Review
Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation and fibrosis. Although AIP is rare, its incidence is increasing and is often misdiagnosed as other pancreatic diseases. AIP is commonly classified into two types. Type 1 AIP (AIP-1) is typically associated with elevated serum immunoglobulin G4 (IgG4) levels and systemic manifestations, while type 2 AIP is typically a more localized form of the disease, and may coexist with other autoimmune disorders, especially inflammatory bowel diseases. Additionally, there is emerging recognition of a third type (type 3 AIP), which refers to immunotherapy-triggered AIP, although this classification is still gaining acceptance in medical literature. The clinical manifestations of AIP mainly include painless jaundice and weight loss. Elevated serum IgG4 levels are particularly characteristic of AIP-1. Diagnosis relies on a combination of clinical, laboratory, radiological, and histological findings, given the similarity of AIP symptoms to other pancreatic disorders. The mainstay of treatment for AIP is steroid therapy, which is effective in most cases. Severe cases might require additional imm-unosuppressive agents. This review aims to summarize the current knowledge of AIP, encompassing its epidemiology, etiology, clinical presentation, diagnosis, and treatment options. We also address the challenges and controversies in diagnosing and treating AIP, such as distinguishing it from pancreatic cancer and managing long-term treatment, highlighting the need for increased awareness and knowledge of this complex disease.
Topics: Humans; Autoimmune Pancreatitis; Autoimmune Diseases; Immunoglobulin G; Diagnosis, Differential; Pancreas
PubMed: 38516247
DOI: 10.3748/wjg.v30.i8.817 -
Gastrointestinal Endoscopy Clinics of... Oct 2023Disconnected pancreatic duct (DPD) is common after acute necrotizing pancreatitis (ANP). Its clinical implications vary according to the course of disease. In the early... (Review)
Review
Disconnected pancreatic duct (DPD) is common after acute necrotizing pancreatitis (ANP). Its clinical implications vary according to the course of disease. In the early phase of ANP, parenchymal necrosis along with disruption of pancreatic duct cause acute necrotic collection that evolves into walled-off necrosis (WON). In the later phase, DPD becomes evident as confirmed by magnetic resonance cholangiopancreatography. Clinical manifestations of DPD can vary from being asymptomatic, recurrent pain, recurrent pancreatic fluid collection (PFC), obstructive pancreatitis, or external pancreatic fistula (EPF). Few patients develop new-onset diabetes. Long-term indwelling plastic stents have been proposed to prevent the recurrent PFC.
Topics: Humans; Pancreas; Cholangiopancreatography, Magnetic Resonance; Bile Duct Diseases; Necrosis; Pancreatic Diseases; Pancreatic Ducts
PubMed: 37709409
DOI: 10.1016/j.giec.2023.04.004 -
Archives of Toxicology Jan 2024Ferroptosis is a newly discovered form of regulatory cell death characterized by excessive iron-dependent lipid peroxidation. In the past decade, significant... (Review)
Review
Ferroptosis is a newly discovered form of regulatory cell death characterized by excessive iron-dependent lipid peroxidation. In the past decade, significant breakthroughs have been made in comprehending the features and regulatory mechanisms of ferroptosis, and it has been confirmed that ferroptosis plays a pivotal role in the pathophysiological processes of various diseases, including tumors, inflammation, neurodegenerative diseases, and infectious diseases. The pancreas, which is the second largest digestive gland in the human body and has both endocrine and exocrine functions, is a vital organ for controlling digestion and metabolism. In recent years, numerous studies have confirmed that ferroptosis is closely related to pancreatic diseases, which is attributed to abnormal iron accumulation, as an essential biochemical feature of ferroptosis, is often present in the pathological processes of various pancreatic exocrine and endocrine diseases and the vulnerability of the pancreas to oxidative stress stimulation and damage. Therefore, comprehending the regulatory mechanism of ferroptosis in pancreatic diseases may provide valuable new insights into treatment strategies. In this review, we first summarize the hallmark features of ferroptosis and then analyze the exact mechanisms by which ferroptosis is precisely regulated at multiple levels and links, including iron metabolism, lipid metabolism, the GPX4-mediated ferroptosis defense system, the GPX4-independent ferroptosis defense system, and the regulation of autophagy on ferroptosis. Finally, we discuss the role of ferroptosis in the occurrence and development of pancreatic diseases and summarize the feasibility and limitations of ferroptosis as a therapeutic target for pancreatic diseases.
Topics: Humans; Ferroptosis; Pancreatic Diseases; Autophagy; Cell Death; Iron
PubMed: 37934210
DOI: 10.1007/s00204-023-03625-x -
Gastrointestinal Endoscopy Clinics of... Jul 2024With the introduction of endoscopic retrograde cholangiopancreatography and linear endoscopic ultrasound, interventional pancreaticobiliary (PB) endoscopy has had an... (Review)
Review
With the introduction of endoscopic retrograde cholangiopancreatography and linear endoscopic ultrasound, interventional pancreaticobiliary (PB) endoscopy has had an enormous impact in the management of pancreatic and biliary diseases. Continuous efforts to improve various devices and techniques have revolutionized these treatment modalities as viable alternatives to surgery. In recent years, trends toward combining endoscopic techniques with other modalities, such as laparoscopic and radiological interventions, for complex PB diseases have emerged using a multidisciplinary approach. Ongoing research and clinical experience will lead to refinements in interventional PB endoscopic techniques and subsequently improve outcomes and reduce complication rates.
Topics: Humans; Cholangiopancreatography, Endoscopic Retrograde; Pancreatic Diseases; Biliary Tract Diseases; Endosonography; History, 20th Century; History, 21st Century; Endoscopy, Digestive System
PubMed: 38796288
DOI: 10.1016/j.giec.2023.12.001 -
Cancer Letters Mar 2024Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous tumor comprising pancreatic cancer cells, fibroblasts, immune cells, vascular epithelial cells, and... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous tumor comprising pancreatic cancer cells, fibroblasts, immune cells, vascular epithelial cells, and other cells in the mesenchymal tissue. PDAC is difficult to treat because of the complexity of the tissue components; therefore, achieving therapeutic effects with a single therapeutic method or target is problematic. Recently, precision therapy has provided new directions and opportunities for treating PDAC using genetic information from an individual's disease to guide treatment. It selects and applies appropriate therapeutic methods for each patient, with an aim to minimize medical damage and costs, while maximizing patient benefits. Molecular targeted therapy is effective in most clinical studies; however, it has been ineffective in large-scale randomized controlled trials of PDAC, mainly because the enrolled populations were not stratified on a molecular basis. Molecular stratification allows the identification of the PDAC population being treated, optimizing therapeutic effect. However, a systematic review of precision therapies for patients with highly heterogeneous PDAC backgrounds has not been conducted. Here, we review the molecular background and current potential therapeutic targets related to PDAC and provide new directions for PDAC precision therapy.
Topics: Humans; Carcinoma, Pancreatic Ductal; Fibroblasts; Pancreatic Neoplasms
PubMed: 38278471
DOI: 10.1016/j.canlet.2024.216636 -
Biomolecules Feb 2024Recent studies have shown that a pro-inflammatory diet and dysbiosis, especially a high level of trimethylamine-N-oxide (TMAO), are associated with various adverse... (Review)
Review
Recent studies have shown that a pro-inflammatory diet and dysbiosis, especially a high level of trimethylamine-N-oxide (TMAO), are associated with various adverse health conditions. Cardiovascular diseases and pancreatic diseases are two major morbidities in the modern world. Through this narrative review, we aimed to summarize the association between a pro-inflammatory diet, gut microbiota, and cardiovascular and pancreatic diseases, along with their underlying mechanisms. Our review revealed that TMAO is associated with the development of cardiovascular diseases by promoting platelet aggregation, atherosclerotic plaque formation, and vascular inflammation. TMAO is also associated with the development of acute pancreatitis. The pro-inflammatory diet is associated with an increased risk of pancreatic cancer and cardiovascular diseases through mechanisms that include increasing TMAO levels, activating the lipopolysaccharides cascade, and the direct pro-inflammatory effect of certain nutrients. Meanwhile, an anti-inflammatory diet decreases the risk of cardiovascular diseases and pancreatic cancer.
Topics: Humans; Gastrointestinal Microbiome; Cardiovascular Diseases; Acute Disease; Pancreatitis; Methylamines; Pancreatic Neoplasms
PubMed: 38397447
DOI: 10.3390/biom14020210 -
International Journal of Molecular... Aug 2023In the oncological area, pancreatic cancer is one of the most lethal diseases, with 5-year survival rising just 10% in high-development countries. This disease is...
In the oncological area, pancreatic cancer is one of the most lethal diseases, with 5-year survival rising just 10% in high-development countries. This disease is genetically characterized by as a driven mutation followed by , , and -associated mutations. In clinical aspects, pancreatic cancer presents unspecific clinical symptoms with the absence of screening and early plasmatic biomarker, being that CA19-9 is the unique plasmatic biomarker having specificity and sensitivity limitations. We analyzed the plasmatic exosome proteomic profile of 23 patients with pancreatic cancer and 10 healthy controls by using Nanoscale liquid chromatography coupled to tandem mass spectrometry (NanoLC-MS/MS). The pancreatic cancer patients were subdivided into IPMN and PDAC. Our findings show 33, 34, and 7 differentially expressed proteins when comparing the IPMN vs. control, PDAC-No treatment vs. control, and PDAC-No treatment vs. IPMN groups, highlighting proteins of the complement system and coagulation, such as C3, APOB, and SERPINA. Additionally, PDAC with no treatment showed 11 differentially expressed proteins when compared to Folfirinox neoadjuvant therapy or Gemcitabine adjuvant therapy. So here, we found plasmatic exosome-derived differentially expressed proteins among cancer patients (IPMN, PDAC) when comparing with healthy controls, which could represent alternative biomarkers for diagnostic and prognostic evaluation, supporting further scientific and clinical studies on pancreatic cancer.
Topics: Humans; Early Detection of Cancer; Prognosis; Pancreatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Exosomes; Pancreatic Intraductal Neoplasms; Proteomics; Tandem Mass Spectrometry; CA-19-9 Antigen
PubMed: 37628784
DOI: 10.3390/ijms241612604 -
Gastroenterology Sep 2023The in-hospital survival of patients suffering from acute pancreatitis (AP) is 95% to 98%. However, there is growing evidence that patients discharged after AP may be at...
BACKGROUND & AIMS
The in-hospital survival of patients suffering from acute pancreatitis (AP) is 95% to 98%. However, there is growing evidence that patients discharged after AP may be at risk of serious morbidity and mortality. Here, we aimed to investigate the risk, causes, and predictors of the most severe consequence of the post-AP period: mortality.
METHODS
A total of 2613 well-characterized patients from 25 centers were included and followed by the Hungarian Pancreatic Study Group between 2012 and 2021. A general and a hospital-based population was used as the control group.
RESULTS
After an AP episode, patients have an approximately threefold higher incidence rate of mortality than the general population (0.0404 vs 0.0130 person-years). First-year mortality after discharge was almost double than in-hospital mortality (5.5% vs 3.5%), with 3.0% occurring in the first 90-day period. Age, comorbidities, and severity were the most significant independent risk factors for death following AP. Furthermore, multivariate analysis identified creatinine, glucose, and pleural fluid on admission as independent risk factors associated with post-discharge mortality. In the first 90-day period, cardiac failure and AP-related sepsis were among the main causes of death following discharge, and cancer-related cachexia and non-AP-related infection were the key causes in the later phase.
CONCLUSION
Almost as many patients in our cohort died in the first 90-day period after discharge as during their hospital stay. Evaluation of cardiovascular status, follow-up of local complications, and cachexia-preventing oncological care should be an essential part of post-AP patient care. Future study protocols in AP must include at least a 90-day follow-up period after discharge.
Topics: Humans; Pancreatitis; Patient Discharge; Acute Disease; Aftercare; Cachexia; Retrospective Studies
PubMed: 37247642
DOI: 10.1053/j.gastro.2023.05.028 -
European Journal of Radiology Nov 2023Pancreatic diseases are difficult to diagnose due to their insidious onset and complex pathophysiological developmental characteristics. In recent years, dual-energy... (Review)
Review
Pancreatic diseases are difficult to diagnose due to their insidious onset and complex pathophysiological developmental characteristics. In recent years, dual-energy computed tomography (DECT) imaging technology has rapidly advanced. DECT can quantitatively extract and analyze medical imaging features and establish a correlation between these features and clinical results. This feature enables the adoption of more modern and accurate clinical diagnosis and treatment strategies for patients with pancreatic diseases so as to achieve the goal of non-invasive, low-cost, and personalized treatment. The purpose of this review is to elaborate on the application of DECT for the diagnosis, biological characterization, and prediction of the survival of patients with pancreatic diseases (including pancreatitis, pancreatic cancer, pancreatic cystic tumor, pancreatic neuroendocrine tumor, and pancreatic injury) and to summarize its current limitations and future research prospects.
Topics: Humans; Tomography, X-Ray Computed; Pancreatic Diseases; Pancreatic Neoplasms; Pancreas; Radiography, Dual-Energy Scanned Projection
PubMed: 37742372
DOI: 10.1016/j.ejrad.2023.111090 -
Science Translational Medicine Nov 2023Pancreatic ductal adenocarcinoma (PDAC) is generally refractory to immune checkpoint blockade, although patients with genetically unstable tumors can show modest...
Pancreatic ductal adenocarcinoma (PDAC) is generally refractory to immune checkpoint blockade, although patients with genetically unstable tumors can show modest therapeutic benefit. We previously demonstrated the presence of tumor-reactive CD8 T cells in PDAC samples. Here, we charted the tumor-infiltrating T cell repertoire in PDAC by combining single-cell transcriptomics with functional testing of T cell receptors (TCRs) for reactivity against autologous tumor cells. On the basis of a comprehensive dataset including 93 tumor-reactive and 65 bystander TCR clonotypes, we delineated a gene signature that effectively distinguishes between these T cell subsets in PDAC, as well as in other tumor indications. This revealed a high frequency of tumor-reactive TCR clonotypes in three genetically unstable samples. In contrast, the T cell repertoire in six genetically stable PDAC tumors was largely dominated by bystander T cells. Nevertheless, multiple tumor-reactive TCRs were successfully identified in each of these samples, thereby providing a perspective for personalized immunotherapy in this treatment-resistant indication.
Topics: Humans; CD8-Positive T-Lymphocytes; Transcriptome; Receptors, Antigen, T-Cell; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal
PubMed: 37967201
DOI: 10.1126/scitranslmed.adh9562