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Gastrointestinal Endoscopy Clinics of... Jul 2024
Topics: Humans; Pancreatic Diseases; Endoscopy, Digestive System; Cholangiopancreatography, Endoscopic Retrograde; Biliary Tract Diseases
PubMed: 38796301
DOI: 10.1016/j.giec.2024.03.001 -
International Journal of Surgery... Dec 2023Diagnosing pancreatic lesions, including chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer, poses a challenge and, as a result, is time-consuming. To... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diagnosing pancreatic lesions, including chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer, poses a challenge and, as a result, is time-consuming. To tackle this issue, artificial intelligence (AI) has been increasingly utilized over the years. AI can analyze large data sets with heightened accuracy, reduce interobserver variability, and can standardize the interpretation of radiologic and histopathologic lesions. Therefore, this study aims to review the use of AI in the detection and differentiation of pancreatic space-occupying lesions and to compare AI-assisted endoscopic ultrasound (EUS) with conventional EUS in terms of their detection capabilities.
METHODS
Literature searches were conducted through PubMed/Medline, SCOPUS, and Embase to identify studies eligible for inclusion. Original articles, including observational studies, randomized control trials, systematic reviews, meta-analyses, and case series specifically focused on AI-assisted EUS in adults, were included. Data were extracted and pooled, and a meta-analysis was conducted using Meta-xl. For results exhibiting significant heterogeneity, a random-effects model was employed; otherwise, a fixed-effects model was utilized.
RESULTS
A total of 21 studies were included in the review with four studies pooled for a meta-analysis. A pooled accuracy of 93.6% (CI 90.4-96.8%) was found using the random-effects model on four studies that showed significant heterogeneity ( P <0.05) in the Cochrane's Q test. Further, a pooled sensitivity of 93.9% (CI 92.4-95.3%) was found using a fixed-effects model on seven studies that showed no significant heterogeneity in the Cochrane's Q test. When it came to pooled specificity, a fixed-effects model was utilized in six studies that showed no significant heterogeneity in the Cochrane's Q test and determined as 93.1% (CI 90.7-95.4%). The pooled positive predictive value which was done using the random-effects model on six studies that showed significant heterogeneity was 91.6% (CI 87.3-95.8%). The pooled negative predictive value which was done using the random-effects model on six studies that showed significant heterogeneity was 93.6% (CI 90.4-96.8%).
CONCLUSION
AI-assisted EUS shows a high degree of accuracy in the detection and differentiation of pancreatic space-occupying lesions over conventional EUS. Its application may promote prompt and accurate diagnosis of pancreatic pathologies.
Topics: Adult; Humans; Artificial Intelligence; Sensitivity and Specificity; Pancreas; Endosonography; Pancreatic Neoplasms
PubMed: 37800594
DOI: 10.1097/JS9.0000000000000717 -
Advanced Science (Weinheim,... Mar 2024Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows...
Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Extracellular Vesicles; Glypicans; Pancreatic Neoplasms; Prognosis; RNA, Messenger
PubMed: 38204202
DOI: 10.1002/advs.202306373 -
Abdominal Radiology (New York) May 2024To review the congenital anomalies of the pancreas with their main clinical manifestations and key imaging findings on CT and MRI. (Review)
Review
OBJECTIVE
To review the congenital anomalies of the pancreas with their main clinical manifestations and key imaging findings on CT and MRI.
BACKGROUND AND CLINICAL SIGNIFICANCE
Anomalies of pancreatic development are frequent and generally asymptomatic, but can mimic and predispose individuals to pancreatic or peripancreatic pathologies, such as pancreatitis or malignancy. Their correct diagnosis may help avoid unnecessary further investigations and procedures, or establish adequate treatment when they manifest clinically. Differentiating pancreatic congenital anomalies from their main radiological mimics constitutes a challenge for the radiologist and requires familiarity with key imaging findings.
CONCLUSION
The imaging findings of CT and MRI are essential for the correct diagnosis of congenital pancreatic anomalies.
Topics: Humans; Pancreas; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Diagnosis, Differential; Pancreatic Diseases
PubMed: 38478039
DOI: 10.1007/s00261-024-04229-4 -
Apoptosis : An International Journal on... Apr 2024Pyroptosis, as a type of inflammatory programmed cell death, has been studied in inflammatory diseases and numerous cancers but its role in pancreatic ductal...
BACKGROUND
Pyroptosis, as a type of inflammatory programmed cell death, has been studied in inflammatory diseases and numerous cancers but its role in pancreatic ductal adenocarcinoma (PDAC) remains further exploration.
METHODS
A TCGA-PDAC cohort was enrolled for bioinformatics analysis to investigate the effect of pyroptosis on the prognosis and drug sensitivity of patients. PA-TU-8988T and CFPAC-1 cells were selected for investigating the role of GSDMC in PDAC.
RESULTS
A distinct classification pattern of PDAC mediated by 21 pyroptosis-related genes (PRGs) was identified. It was suggested that higher pyroptosis activity was associated with poor prognosis of patients and higher tumor proliferation rates. We further established a prognostic model based on three PRGs (GSDMC, CASP4 and NLRP1) and the TCGA-PDAC cohort was classified into low and high-risk subgroups. It is noteworthy that the high-risk group showed significantly higher tumor proliferation rates and was proved to be highly correlated with oxaliplatin resistance. Further experiments suggested that overexpression of GSDMC promoted the proliferation and oxaliplatin resistance of PA-TU-8988T cells in vitro and vivo, while downregulation of GSDMC showed opposite effects in CFPAC-1 cells. Finally, we found that the activation of pentose phosphate pathway (PPP) was the mechanism by which GSDMC overexpression promoted the proliferation and oxaliplatin resistance of pancreatic cancer cells.
CONCLUSIONS
In this study, we found that higher pyroptosis activity is associated with worse prognosis and oxaliplatin resistance of PDAC patients. In addition, as a core effector of pyroptosis, GSDMC promoted proliferation and oxaliplatin resistance of pancreatic cancer cells, which will provide new therapeutic target for PDAC patients.
Topics: Humans; Pancreatic Neoplasms; Oxaliplatin; Pyroptosis; Adenocarcinoma; Apoptosis; Cell Line, Tumor; Cell Proliferation; Carcinoma, Pancreatic Ductal; Gasdermins; Biomarkers, Tumor
PubMed: 37848674
DOI: 10.1007/s10495-023-01901-w -
Cancer Research Sep 2023The therapeutic options for treating pancreatic ductal adenocarcinoma (PDAC) are limited, and resistance to gemcitabine, a cornerstone of PDAC chemotherapy regimens,...
UNLABELLED
The therapeutic options for treating pancreatic ductal adenocarcinoma (PDAC) are limited, and resistance to gemcitabine, a cornerstone of PDAC chemotherapy regimens, remains a major challenge. N6-methyladenosine (m6A) is a prevalent modification in mRNA that has been linked to diverse biological processes in human diseases. Herein, by characterizing the global m6A profile in a panel of gemcitabine-sensitive and gemcitabine-insensitive PDAC cells, we identified a key role for elevated m6A modification of the master G0-G1 regulator FZR1 in regulating gemcitabine sensitivity. Targeting FZR1 m6A modification augmented the response to gemcitabine treatment in gemcitabine-resistant PDAC cells both in vitro and in vivo. Mechanistically, GEMIN5 was identified as a novel m6A mediator that specifically bound to m6A-modified FZR1 and recruited the eIF3 translation initiation complex to accelerate FZR1 translation. FZR1 upregulation maintained the G0-G1 quiescent state and suppressed gemcitabine sensitivity in PDAC cells. Clinical analysis further demonstrated that both high levels of FZR1 m6A modification and FZR1 protein corresponded to poor response to gemcitabine. These findings reveal the critical function of m6A modification in regulating gemcitabine sensitivity in PDAC and identify the FZR1-GEMIN5 axis as a potential target to enhance gemcitabine response.
SIGNIFICANCE
Increased FZR1 translation induced by m6A modification engenders a gemcitabine-resistant phenotype by inducing a quiescent state and confers a targetable vulnerability to improve treatment response in PDAC.
Topics: Humans; Carcinoma, Pancreatic Ductal; Cdh1 Proteins; Cell Line, Tumor; Gemcitabine; Pancreatic Neoplasms; RNA, Messenger
PubMed: 37326469
DOI: 10.1158/0008-5472.CAN-22-3346 -
Current Research in Translational... Mar 2024The incidence of pancreatic diseases has been continuously rising in recent years. Thus, research on pancreatic regeneration is becoming more popular. Chronic... (Review)
Review
The incidence of pancreatic diseases has been continuously rising in recent years. Thus, research on pancreatic regeneration is becoming more popular. Chronic hyperglycemia is detrimental to pancreatic β-cells, leading to impairment of insulin secretion which is the main hallmark of pancreatic diseases. Obtaining plenty of functional pancreatic β-cells is the most crucial aspect when studying pancreatic biology and treating diabetes. According to the International Diabetes Federation, diabetes has become a global epidemic, with about 3 million people suffering from diabetes worldwide. Hyperglycemia can lead to many dangerous diseases, including amputation, blindness, neuropathy, stroke, and cardiovascular and kidney diseases. Insulin is widely used in the treatment of diabetes; however, innovative approaches are needed in the academic and preclinical stages. A new approach aims at synthesizing patient-specific functional pancreatic β-cells. The present article focuses on how cells from different tissues can be transformed into pancreatic β-cells.
Topics: Humans; Cell Lineage; Cell Differentiation; Diabetes Mellitus; Hyperglycemia; Pancreatic Diseases
PubMed: 38246021
DOI: 10.1016/j.retram.2023.103412 -
Journal of Ethnopharmacology Jan 2024Acute pancreatitis (AP) is an acute inflammatory condition of pancreas with high morbidity and mortality, which has no effective medical treatment. Chaiqin chengqi...
ETHNOPHARMACOLOGICAL RELEVANCE
Acute pancreatitis (AP) is an acute inflammatory condition of pancreas with high morbidity and mortality, which has no effective medical treatment. Chaiqin chengqi decoction (CQCQD) has been clinically used for AP for many years in China. However, the underlying mechanisms are still unknown.
AIM OF THE STUDY
To investigate the mechanism of CQCQD on gasdermin D (GSDMD) -mediated pyroptosis in AP.
MATERIALS AND METHODS
In this study, network pharmacology was used to screen the potential mechanism of CQCQD protecting against AP and then we focused to investigate the mechanism of CQCQD on GSDMD mediated pyroptosis. Mouse models of AP were conducted by caerulein and L-arginine. In order to clarify the mechanism of CQCQD, two kinds of GSDMD gene knockout mice (Gsdmd and Pdx1Gsdmd) were applied. And the potential interaction between the main components of CQCQD and GSDMD was explored by molecular docking.
RESULTS
In the caerulein-induced AP model, CQCQD ameliorated pancreatic pathological injury, attenuated systemic inflammation and serum enzymatic levers. Moreover, network pharmacology analysis showed GSDMD mediated pyroptosis was one of the core targets of CQCQD protecting against AP. Additionally, CQCQD appreciably decreased the levels of pyroptosis-related proteins N-terminal GSDMD, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3, and cleaved Caspase-1. Furthermore, the protective effect of CQCQD was neutralized in Gsdmd and Pdx1Gsdmd mice in caerulein-induced AP. In addition, we found that CQCQD protects pancreatic tissue from damage and pancreatitis-associated lung injury in the L-arginine-induced mouse model. Moreover, all of the main components of CQCQD possessed binding activity with GSDMD by molecular docking. Seventeen components bound with the human GSDMD Cys191 successfully, which is important for GSDMD pore formation. Among the components, rhein possessed the highest binding activity.
CONCLUSION
CQCQD could reduce pancreatic necrosis and inflammatory response via inhibiting GSDMD-mediated pyroptosis in acinar cells of AP. Rhein may be the key active ingredient of CQCQD in suppressing pyroptosis.
Topics: Mice; Humans; Animals; Pancreatitis; Gasdermins; Pyroptosis; Acute Disease; Ceruletide; Molecular Docking Simulation; NLR Family, Pyrin Domain-Containing 3 Protein
PubMed: 37480969
DOI: 10.1016/j.jep.2023.116920 -
Gastrointestinal Endoscopy Clinics of... Oct 2023Stone clearance with extracorporeal shock wave lithotripsy is a safe and effective procedure for large pancreatic calculi not extractable by the standard endoscopic... (Review)
Review
Stone clearance with extracorporeal shock wave lithotripsy is a safe and effective procedure for large pancreatic calculi not extractable by the standard endoscopic retrograde cholangiopancreatography techniques. In properly selected patients, this minimally invasive approach should be offered as the first line of therapy instead of surgery. Complete stone clearance can be achieved in three-fourths with long-term pain relief in two-thirds of patients. Re-intervention is required in less than half of the patients. Future studies should compare the extracorporeal approach with intraductal lithotripsy using the pancreatoscope.
Topics: Humans; Pancreatic Diseases; Cholangiopancreatography, Endoscopic Retrograde; Endoscopes, Gastrointestinal; Lithotripsy; Pancreatic Ducts
PubMed: 37709412
DOI: 10.1016/j.giec.2023.04.006 -
Frontiers in Endocrinology 2023Some articles suggest that using HbA1c alone for diabetes diagnosis is inappropriate. It requires considerable researches to explore the efficacy of HbA1c for diagnosing...
BACKGROUND
Some articles suggest that using HbA1c alone for diabetes diagnosis is inappropriate. It requires considerable researches to explore the efficacy of HbA1c for diagnosing hyperglycemia in patients with pancreatic disease.
METHODS
This study analyzed 732 patients, comprising of 331 without pancreatic disease and 401 patients diagnosed with pancreatic diseases. All participants underwent the HbA1c assay and oral glucose tolerance test. Kappa coefficients were calculated to assess agreement between the HbA1c and glucose criteria. The receiver operating characteristic curve (ROC) was used to calculate the optimal HbA1c value. DeLong test was analyzed to compared the aera under curves (AUCs).
RESULTS
There were 203 (61.3%) patients with NGT, 78 (23.6%) with prediabetes, and 50 (15.1%) with diabetes in patients without pancreatic diseases. In patients with pancreatic disease, 106 participants were diagnosed with NGT (36.4%), 125 with prediabetes (31.2%), and 130 with diabetes (32.4%). Patients with pancreatic disease exhibited elevated levels of bilirubin, transaminase enzymes, aspartate transaminase, high density lipoprotein cholesterol and total bile acid. The sensitivity and specificity of the HbA1c (6.5%) for diagnosing pancreatic diabetes were 60.8% (95% CI 52.3, 69.3) and 92.6% (95% CI 89.5, 95.7). In prediabetes, the sensitivity and specificity of HbA1c (5.7%) is 53.2% (44.3, 62.0) and 59.6 (51.5, 67.6). The optimal HbA1c value for diagnosing diabetes was 6.0% (AUC = 0.876, 95% CI 0.839, 0.906), with the sensitivity of 83.8% and the specificity of 76.8%. The optimal HbA1c value for the diagnosis of prediabetes was 5.8% (AUC = 0.617, 95% CI: 0.556, 0.675), with the corresponding sensitivity and specificity of 48.0% and 72.6% respectively. The combined tests (HbA1c, 6.0% or FPG, 7.0mmol/L) presented the sensitivity of 85.7% (95% CI 79.1, 91.3)and the specificity of 92.6% (95% CI 87.6, 97.3) in pancreatic diabetes.
CONCLUSION
From our results, the recommended HbA1c by ADA criterion may not be sufficiently sensitive to diagnose hyperglycemia in pancreatic disease. The optimal value of 5.8% and 6.0% improved the accuracy for diagnosing prediabetes and diabetes and should be considered to be applied. Besides, we advocate the combination of HbA1c and FPG test for the diagnosis of diabetes in patients with pancreatic diseases.
Topics: Humans; Prediabetic State; Glycated Hemoglobin; Blood Glucose; Diabetes Mellitus; Hyperglycemia; Pancreatic Diseases
PubMed: 37484959
DOI: 10.3389/fendo.2023.1208187