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Cancer Prevention Research... Nov 2023Protein advanced glycation end products (AGE) formed by nonenzymatic glycation can disrupt the normal structure and function of proteins, and stimulate the receptor for... (Review)
Review
Protein advanced glycation end products (AGE) formed by nonenzymatic glycation can disrupt the normal structure and function of proteins, and stimulate the receptor for AGEs (RAGE), triggering intricate mechanisms that are etiologically related to various chronic diseases, including pancreatic cancer. Many common risk factors of pancreatic cancer are the major sources for the formation of protein AGEs and glycative stress in the human body. Abnormal accumulation of protein AGEs can impair the cellular proteome and promote AGE-RAGE driven pro-inflammatory signaling cascades, leading to increased oxidative stress, protease resistance, protein dysregulation, transcription activity of STAT, NF-κB, and AP-1, aberrant status in ubiquitin-proteasome system and autophagy, as well as other molecular events that are susceptible for the carcinogenic transformation towards the development of neoplasms. Here, we review studies to highlight our understanding in the orchestrated molecular events in bridging the impaired proteome, dysregulated functional networks, and cancer hallmarks initiated upon protein AGE formation and accumulation in pancreatic cancer.
Topics: Humans; Glycation End Products, Advanced; Receptor for Advanced Glycation End Products; Proteome; Pancreatic Neoplasms
PubMed: 37578815
DOI: 10.1158/1940-6207.CAPR-23-0162 -
Annals of Surgery Nov 2023The aim of this study is to define and assess Ideal Outcome in the national or multicenter registries of North America, Germany, the Netherlands, and Sweden.
OBJECTIVE
The aim of this study is to define and assess Ideal Outcome in the national or multicenter registries of North America, Germany, the Netherlands, and Sweden.
BACKGROUND
Assessing outcomes after pancreatoduodenectomy among centers and countries requires a broad evaluation that cannot be captured by a single parameter. Previously, 2 composite outcome measures (textbook outcome and optimal pancreatic surgery) for pancreatoduodenectomy have been described from Europe and the United States. These composites were harmonized into ideal outcome (IO).
METHODS
This analysis is a transatlantic retrospective study (2018-2020) of patients after pancreatoduodenectomy within the registries from North America, Germany, The Netherlands, and Sweden. After 3 consensus meetings, IO for pancreatoduodenectomy was defined as the absence of all 6 parameters: (1) in-hospital mortality, (2) severe complications-Clavien-Dindo ≥3, (3) postoperative pancreatic fistula-International Study Group of Pancreatic Surgery (ISGPS) grade B/C, (4) reoperation, (5) hospital stay >75th percentile, and (6) readmission. Outcomes were evaluated using relative largest difference (RLD) and absolute largest difference (ALD), and multivariate regression models.
RESULTS
Overall, 21,036 patients after pancreatoduodenectomy were included, of whom 11,194 (54%) reached IO. The rate of IO varied between 55% in North America, 53% in Germany, 52% in The Netherlands, and 54% in Sweden (RLD: 1.1, ALD: 3%, P <0.001). Individual components varied with an ALD of 2% length of stay, 4% for in-hospital mortality, 12% severe complications, 10% postoperative pancreatic fistula, 11% reoperation, and 9% readmission. Age, sex, absence of chronic obstructive pulmonary disease, body mass index, performance status, American Society of Anesthesiologists (ASA) score, biliary drainage, absence of vascular resection, and histologic diagnosis were associated with IO. In the subgroup of patients with pancreatic adenocarcinoma, country, and neoadjuvant chemotherapy also was associated with improved IO.
CONCLUSIONS
The newly developed composite outcome measure "Ideal Outcome" can be used for auditing and comparing outcomes after pancreatoduodenectomy. The observed differences can be used to guide collaborative initiatives to further improve the outcomes of pancreatic surgery.
Topics: Humans; Pancreaticoduodenectomy; Pancreatic Fistula; Retrospective Studies; Pancreatic Neoplasms; Adenocarcinoma; Outcome Assessment, Health Care; Postoperative Complications
PubMed: 37476990
DOI: 10.1097/SLA.0000000000006037 -
Journal of Crohn's & Colitis Nov 2023Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and...
BACKGROUND
Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported.
METHODS
An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD.
RESULTS
We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ± 16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred.
CONCLUSIONS
In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.
Topics: Male; Humans; Young Adult; Adult; Middle Aged; Female; Autoimmune Pancreatitis; Pancreatitis; Retrospective Studies; Autoimmune Diseases; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease
PubMed: 37283545
DOI: 10.1093/ecco-jcc/jjad097 -
Canadian Association of Radiologists... Aug 2023Pancreatic cystic lesions (PCLs) are both common and often incidental. These encompass a range of pathologies with varying degrees of concern for malignancy. Although... (Review)
Review
Pancreatic cystic lesions (PCLs) are both common and often incidental. These encompass a range of pathologies with varying degrees of concern for malignancy. Although establishing a diagnosis is helpful for determining malignant potential, many PCLs are either too small to characterize or demonstrate nonspecific morphologic features. The most salient modalities involved in diagnosis and surveillance are magnetic resonance imaging, multidetector computerized tomography, and endoscopic ultrasound. Fine needle aspiration has a role in conjunction with molecular markers as a diagnostic tool, particularly for identifying malignant lesions. Although several major consensus guidelines exist internationally, there remains uncertainty in establishing the strength of the association between all PCLs and pancreatic adenocarcinoma, and in showing a benefit from extended periods of imaging surveillance. No consensus exists between the major guidelines, particularly regarding surveillance duration, frequency, or endpoints. This review paper discusses PCL subtypes, diagnosis, and compares the major consensus guidelines with considerations for local adaptability along with questions regarding current and future priorities for research.
Topics: Humans; Pancreatic Neoplasms; Pancreatic Cyst; Adenocarcinoma; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Pancreas
PubMed: 36220377
DOI: 10.1177/08465371221130524 -
Biomedicine & Pharmacotherapy =... Dec 2023Pancreatic cancer, including pancreatic ductal adenocarcinomas (PDACs), is a malignant tumor with characteristics of tumor-stroma interactions. Patients often have a... (Review)
Review
Pancreatic cancer, including pancreatic ductal adenocarcinomas (PDACs), is a malignant tumor with characteristics of tumor-stroma interactions. Patients often have a poor prognosis and a poor long-term survival rate. In recent years, rapidly-developing single-cell sequencing techniques have been used to analyze cell populations at a single-cell resolution, so that it is now possible to have a more in-depth and clearer understanding of the genetic composition of pancreatic cancer. In this review, we provide an overview of the current single-cell sequencing techniques and their applications in the exploration of intratumoral heterogeneity, the tumor microenvironment, therapy resistance, and novel treatments. Our hope is to provide new insight into the potential of precision therapy, which will perhaps one day lead to significant advances in PDAC treatment.
Topics: Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Tumor Microenvironment
PubMed: 37837881
DOI: 10.1016/j.biopha.2023.115664 -
Surgery Today Dec 2023Although reports suggest that the pancreatic volume decreases after gastrectomy for gastric cancer, the relationship between the pancreatic volume and secretory function...
PURPOSE
Although reports suggest that the pancreatic volume decreases after gastrectomy for gastric cancer, the relationship between the pancreatic volume and secretory function after gastrectomy remains unclear. In this study, we examined the relationship between the pancreatic volume and exocrine and endocrine functions after total gastrectomy.
METHODS
The pancreatic volumes of 18 distal gastrectomy and 15 total gastrectomy patients were retrospectively measured using computed tomography volumetry up to 5 years postoperatively. Ten low anterior resection patients were selected as controls. In addition, the pancreatic volume and exocrine function evaluated by fecal elastase and the insulin secretory function evaluated by glucagon tolerance testing were prospectively examined before and one year after surgery in nine cases of total gastrectomy.
RESULTS
After low anterior resection, the pancreatic volume did not change, but after distal and total gastrectomy, the pancreatic volume decreased continuously until the fifth year. After total gastrectomy, fecal elastase decreased significantly from 865.8 μg/g to 603.2 μg/g in the first year (p = 0.0316), and the insulin secretion capacity also decreased significantly from 3.83 ng/mL to 2.26 ng/mL (p = 0.0019).
CONCLUSIONS
The pancreatic volume decreases continuously after gastrectomy for gastric cancer, and the pancreatic exocrine and endocrine functions decrease along with pancreatic atrophy after total gastrectomy.
Topics: Humans; Atrophy; Gastrectomy; Pancreatic Diseases; Pancreatic Elastase; Retrospective Studies; Stomach Neoplasms
PubMed: 37084095
DOI: 10.1007/s00595-023-02685-x -
Pharmacological Research Aug 2023Pancreatic cancer (PC) is a serious gastrointestinal tract disease for which the 5-year survival rate is less than 10%, even in developed countries such as the USA. The...
Pancreatic cancer (PC) is a serious gastrointestinal tract disease for which the 5-year survival rate is less than 10%, even in developed countries such as the USA. The genomic profile alterations and dysregulated biological mechanisms commonly occur in PC. Macroautophagy/autophagy is a cell death process that is maintained at a basal level in physiological conditions, whereas its level often changes during tumorigenesis. The function of autophagy in human cancers is dual and can be oncogenic and onco-suppressor. Autophagy is a potent controller of tumorigenesis in PC. The supportive autophagy in PC escalates the growth rate of PC cells and its suppression can mediate cell death. Autophagy also determines the metastasis of PC cells, and it can control the EMT in affecting migration. Moreover, starvation and hypoxia can stimulate glycolysis, and glycolysis induction can be mediated by autophagy in enhancing tumorigenesis in PC. Furthermore, protective autophagy stimulates drug resistance and gemcitabine resistance in PC cells, and its inhibition can enhance radiosensitivity. Autophagy can degrade MHC-I to mediate immune evasion and also regulates polarization of macrophages in the tumor microenvironment. Modulation of autophagy activity is provided by silibinin, ursolic acid, chrysin and huaier in the treatment of PC. Non-coding RNAs are also controllers of autophagy in PC and its inhibition can improve therapy response in patients. Moreover, mitophagy shows dysregulation in PC, which can enhance the proliferation of PC cells. Therefore, a bioinformatics analysis demonstrates the dysregulation of autophagy-related proteins and genes in PC as biomarkers.
Topics: Humans; Cell Line, Tumor; Pancreatic Neoplasms; Autophagy; Carcinogenesis; Tumor Microenvironment
PubMed: 37336429
DOI: 10.1016/j.phrs.2023.106822 -
Cell Reports. Medicine Feb 2024In a Mendelian randomization and prospective cohort study, intra-pancreatic fat increases the risk of pancreatic cancer. This provides persuasive human evidence of...
In a Mendelian randomization and prospective cohort study, intra-pancreatic fat increases the risk of pancreatic cancer. This provides persuasive human evidence of causal relation between lipids and cancer in the pancreas, which confirms a prediction of the PANDORA hypothesis.
Topics: Humans; Prospective Studies; Pancreas; Pancreatic Neoplasms; Lipids
PubMed: 38382463
DOI: 10.1016/j.xcrm.2024.101428 -
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