scholarly journals The Screening and Early Detection of Pancreatic Cancer: Who, When, and How?

2020 ◽  
Vol 25 (2) ◽  
pp. 65-71
Author(s):  
Jae Hyuck Chang
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
General Population ◽  
Early Detection ◽  
Imaging Modality ◽  
Ductal Adenocarcinoma ◽  
Average Risk ◽  
Cystic Lesions ◽  
Low Prevalence ◽  
New Onset

More than 80% of patients with pancreatic ductal adenocarcinoma (PDA) present with symptomatic, surgically unresectable disease. If a “stage shift” from the current 20% resectable proportion to greater by early detection can be achieved, it will unequivocally lead to improved survival in this otherwise dismal disease. Although the goal of early detection of PDA is laudable, the relatively low prevalence PDA renders general population screening infeasible. To avoid the perils of overdiagnosis and to focus early detection efforts on individuals deemed to be at higher-than-average risk, we need to define those subsets of individuals, such as familial kindred and patients with precursor cystic lesions, chronic pancreatitis, and new-onset diabetes. The next step is to determine when and how often to conduct surveillance in the atrisk individuals and the modalities (biomarkers and imaging) that will be used in the surveillance and diagnostic settings, respectively. Nonetheless, vast challenges still remain in terms of validated blood-based biomarkers, imaging modality, and when and how often the surveillance.

scholarly journals Screening of Pancreatic Cancer for Early Diagnosis

2021 ◽  
Vol 96 (2) ◽  
pp. 110-115
Author(s):  
Jae Hyuck Chang
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
General Population ◽  
Early Detection ◽  
Early Diagnosis ◽  
Average Risk ◽  
Cystic Lesions ◽  
Diagnostic Modalities ◽  
Low Prevalence ◽  
New Onset

Over 80% of patients with pancreatic ductal adenocarcinomas (PDAs) present with symptomatic, surgically unresectable disease. If a “stage shift” from the current 20% proportion of resectability to early detection could be achieved, this would greatly improve the survival of patients with this generally dismal disease. Although the goal of early detection is laudable, the relatively low prevalence of PDA renders general population screening unfeasible. To avoid the perils of overdiagnosis and to focus early detection efforts on individuals deemed to be at higher-than-average risk, we need to define such subsets of individuals, such as kindred of existing patients and those with precursor cystic lesions, chronic pancreatitis, and new-onset diabetes. The next step is to determine when and how often to monitor at-risk individuals and the diagnostic modalities that will be employed in the surveillance. Enormous challenges remain in terms of validated blood-based biomarkers, imaging modalities, and when and how often surveillance.

Development of Pancreatic Cancer: Targets for Early Detection and Treatment

2016 ◽  
Vol 34 (5) ◽  
pp. 525-531 ◽  
Author(s):  
Markus M. Lerch ◽  
Julia Mayerle ◽  
Ujjwal Mahajan ◽  
Matthias Sendler ◽  
F. Ulrich Weiss ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Tyrosine Kinases ◽  
Histone Deacetylases ◽  
Hedgehog Signaling ◽  
Pharmaceutical Preparations ◽  
Chemotherapeutic Agents ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools

Background: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death worldwide and compared to other malignancies its share in cancer mortality is expected to rise further. This is due to a lack of sensitive diagnostic tools that would permit earlier detection in a potentially curable stage and the very slow progress in finding effective drug treatments for pancreatic cancer. Key Messages: Aside from genetic predispositions and environmental agents, chronic pancreatitis is by far the greatest risk factor for PDAC. It also shares several etiological factors with pancreatic cancer and represents its most challenging differential diagnosis. Biomarkers that can distinguish between chronic pancreatitis and PDAC may therefore be suitable for the latter's early detection. Moreover, targeting the natural history of chronic pancreatitis would be one approach to prevent PDAC. Targeting tumor-cell signaling directly by interfering with receptor tyrosine kinases has shown some efficacy, although the results in clinical trials were less encouraging than for other cancers. Other compounds developed have targeted the formation of extracellular matrix around the tumor, the proteolytic activity in the tumor environment, histone deacetylases, hedgehog signaling and heat shock proteins, but none has yet found its way into routine patient care. Attempts to individualize treatment according to the tumor's somatic mutation profile are novel but so far impractical. Conclusions: Progress in the treatment of pancreatic cancer has been exceedingly slow and mostly dependent on improved pharmaceutical preparations or combinations of established chemotherapeutic agents. The promise of major breakthroughs implied in targeting tumor signal transduction events has so far not materialized.

scholarly journals Advances in Early Detection of Pancreatic Cancer

2019 ◽  
Author(s):  
Atsushi Kanno ◽  
Atsushi Masamune ◽  
Keiji Hanada ◽  
Masataka Kikuyama ◽  
Masayuki Kitano
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Early Diagnosis ◽  
Clinicopathological Features ◽  
Ductal Adenocarcinoma ◽  
Study Group ◽  
Intraductal Papillary Mucinous Neoplasms ◽  
Mucinous Neoplasms

Early detection of pancreatic ductal adenocarcinoma (PDAC) requires further examination after selecting cases with risk factors for the condition, such as family history, hereditary pancreatic carcinoma syndrome, intraductal papillary mucinous neoplasms, or chronic pancreatitis. The Japan Study Group on the Early Detection of Pancreatic Cancer has investigated and clarified the clinicopathological features for the early diagnosis of PDAC. Further approaches for the early diagnosis of PDAC are warranted.

scholarly journals New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e037267
Author(s):  
Dóra Illés ◽  
Emese Ivány ◽  
Gábor Holzinger ◽  
Klára Kosár ◽  
M Gordian Adam ◽  
...  
Keyword(s):  
High Risk ◽  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Symptoms ◽  
Risk Group ◽  
High Risk Group ◽  
Ductal Adenocarcinoma ◽  
Onset Diabetes ◽  
Dismal Prognosis ◽  
New Onset

IntroductionPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. The proposed screening programme may allow the detection of PDAC in the early, operable stage. Diagnosing more patients in the curable stage might decrease the morbidity and mortality rates of PDAC and additionally reduce the burden of the healthcare.Methods and analysisThis is a prospective, multicentre observational cohort study. Patients ≥60 years old diagnosed with new-onset (≤6 months) diabetes will be included. Exclusion criteria are (1) Continuous alcohol abuse; (2) Chronic pancreatitis; (3) Previous pancreas operation/pancreatectomy; (4) Pregnancy; (5) Present malignant disease and (6) Type 1 DM. Follow-up visits are scheduled every 6 months for up to 36 months. Data collection is based on questionnaires. Clinical symptoms, body weight and fasting blood will be collected at each, carbohydrate antigen 19–9 and blood to biobank at every second visit. The blood samples will be processed to plasma and analysed with mass spectrometry (MS)-based metabolomics. The metabolomic data will be used for biomarker validation for early detection of PDAC in the high-risk group patients with new-onset diabetes. Patients with worrisome features will undergo MRI or endoscopic ultrasound investigation, and surgical referral depending on the radiological findings. One of the secondary end points is the incidence of PDAC in patients with newly diagnosed DM.Ethics and disseminationThe study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (41085-6/2019). We plan to disseminate the results to several members of the healthcare system includining medical doctors, dietitians, nurses, patients and so on. We plan to publish the results in a peer-reviewed high-quality journal for professionals. In addition, we also plan to publish it for lay readers in order to maximalise the dissemination and benefits of this trial.Trial registration numberClinicalTrials.gov NCT04164602

scholarly journals A Circulating Exosome RNA Signature Is a Potential Diagnostic Marker for Pancreatic Cancer, a Systematic Study

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2565
Author(s):  
Yixing Wu ◽  
Hongmei Zeng ◽  
Qing Yu ◽  
Huatian Huang ◽  
Beatrice Fervers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Validation Dataset ◽  
Healthy Controls ◽  
Rna Seq ◽  
Healthy Individuals ◽  
Kras Mutations ◽  
Significant Difference ◽  
Rna Signature

Several exosome proteins, miRNAs and KRAS mutations have been investigated in the hope of carrying out the early detection of pancreatic cancer with high sensitivity and specificity, but they have proven to be insufficient. Exosome RNAs, however, have not been extensively evaluated in the diagnosis of pancreatic cancer. The purpose of this study was to investigate the potential of circulating exosome RNAs in pancreatic cancer detection. By retrieving RNA-seq data from publicly accessed databases, differential expression and random-effects meta-analyses were performed. The results showed that pancreatic cancer had a distinct circulating exosome RNA signature in healthy individuals, and that the top 10 candidate exosome RNAs could distinguish patients from healthy individuals with an area under the curve (AUC) of 1.0. Three (HIST2H2AA3, LUZP6 and HLA-DRA) of the 10 genes in exosomes had similar differential patterns to those in tumor tissues based on RNA-seq data. In the validation dataset, the levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis (AUC = 0.815) and healthy controls (AUC = 0.8558), whereas a slight difference existed between chronic pancreatitis and healthy controls (AUC = 0.586). Of the three genes, the level of HIST2H2AA3 was positively associated with KRAS status. However, there was no significant difference in the levels of the three genes across the disease stages (stages I–IV). These findings indicate that circulating exosome RNAs have a potential early detection value in pancreatic cancer, and that a distinct exosome RNA signature exists in distinguishing pancreatic cancer from healthy individuals.

scholarly journals Role of Cardiac Magnetic Resonance in Detecting Biventricular Apical Hypertrophic Cardiomyopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Nathan Zaher ◽  
Hammam Shereef ◽  
Rashid Al Hussain ◽  
John Dawdy ◽  
Diane Levine ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Hypertrophic Cardiomyopathy ◽  
Magnetic Resonance ◽  
General Population ◽  
Right Ventricular ◽  
Imaging Modality ◽  
Transthoracic Echocardiogram ◽  
Apical Hypertrophic Cardiomyopathy ◽  
Low Prevalence

Apical Hypertrophic Cardiomyopathy (ApHCM) is a rare variant of hypertrophic cardiomyopathy with a low prevalence in the general population. ApHCM with right ventricular involvement (BiApHCM) is largely unreported and may not be detected with conventional transthoracic echocardiogram (TTE) alone. Cardiac Magnetic Resonance (CMR) has been demonstrated to be a proficient imaging modality to diagnose BiApHCM. We present a case of BiApHCM that was diagnosed with TTE and further characterized by CMR. This imaging modality may be utilized more in the future to help diagnose and detect the prevalence of BiApHCM.

scholarly journals Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis

EBioMedicine ◽  
2022 ◽  
Vol 75 ◽  
pp. 103797
Author(s):  
Neus Martínez-Bosch ◽  
Helena Cristóbal ◽  
Mar Iglesias ◽  
Meritxell Gironella ◽  
Luis Barranco ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Blood Marker

Paraneoplastic β Cell Dedifferentiation in Nondiabetic Patients with Pancreatic Cancer

2019 ◽  
Vol 105 (4) ◽  
pp. e1489-e1503 ◽  
Author(s):  
Yichen Wang ◽  
Qicheng Ni ◽  
Jiajun Sun ◽  
Min Xu ◽  
Jing Xie ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Endocrine Cells ◽  
Fasting Blood Glucose ◽  
Ductal Adenocarcinoma ◽  
Benign Tumors ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Glucose Transporter 2 ◽  
Onset Diabetes ◽  
New Onset

Abstract Context Beta-cell dedifferentiation was recently proposed as a mechanism of β-cell dysfunction, but whether it can be a trigger of β-cell failure preceding hyperglycemia in humans is uncertain. Pancreatic cancer can cause new-onset diabetes, yet the underlying mechanism is unknown. Objective To investigate whether β-cell dedifferentiation is present in nondiabetic pancreatic ductal adenocarcinoma (PDAC) patients, we examined pancreatic islets from 15 nondiabetic patients with benign tumors (control) and 15 nondiabetic PDAC patients. Design We calculated the number of hormone-negative endocrine cells and evaluated important markers of β-cell dedifferentiation and function in the paraneoplastic islets. We assessed tumor-related inflammatory changes under the pancreatic cancer microenvironment and their influence on β-cell identity. Results We found nearly 10% of nonhormone expressing endocrine cells in nondiabetic PDAC subjects. The PDAC islets were dysfunctional, evidenced by low expression of Glucose transporter 2 (GLUT2) and Urocortin3 (UCN3), and concomitant upregulation of Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3) expression and proinsulin accumulation. Pancreatic cancer caused paraneoplastic inflammation with enhanced tissue fibrosis, monocytes/macrophages infiltration, and elevated inflammatory cytokines. Moreover, we detected β-cell dedifferentiation and defects in GSIS in islets exposed to PANC-1 (a cell line established from a pancreatic carcinoma of ductal origin from a 56-year-old Caucasian male)-conditioned medium. In a larger cohort, we showed high prevalence of new-onset diabetes in PDAC subjects, and fasting blood glucose (FBG) was found to be an additional useful parameter for early diagnosis of PDAC. Conclusions Our data provide a rationale for β-cell dedifferentiation in the pathogenesis of pancreatic cancer–associated diabetes. We propose that β-cell dedifferentiation can be a trigger for β-cell failure in humans, before hyperglycemia occurs.

scholarly journals Microbial Dysbiosis and polyamine metabolism as predictive markers for early detection of pancreatic cancer

2018 ◽  
Author(s):  
Roberto Mendez ◽  
Kousik Kesh ◽  
Nivedita Arora ◽  
Leá Di Martino ◽  
Florencia McAllister ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Rate ◽  
Early Detection ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Ductal Adenocarcinoma ◽  
Metabolic Reconstruction ◽  
Microbiome Analysis ◽  
Early Stages ◽  
Kpc Mice

AbstractPurposeThe lack of tools for early detection of pancreatic ductal adenocarcinoma (PDAC) is directly correlated to the abysmal survival rate in patients. In addition to several potential detection tools under active investigation, we tested the gut microbiome and its metabolic complement as one of the earliest detection tools that could be useful in patients at high-risk for PDAC.Experimental DesignA combination of 16s pyrosequencing and whole-genome sequencing of gut microbiota was used in a spontaneous genetically engineered PDAC murine model (KRASG12DTP53R172HPdxCre or KPC). Metabolic reconstruction of microbiome was done using the HUmanN2 pipeline. Serum polyamine levels were measured from murine and patient samples using standard methods.ResultsResults showed a progressive Proteobacterial and Firmicutes dominance in gut microbiota in early stages of PDAC development. Upon in silico reconstruction of active metabolic pathways within the altered microbial flora, polyamine and nucleotide biosynthetic pathways were significantly elevated. These metabolic products are known to be actively assimilated by the host and eventually utilized by rapidly dividing cells for proliferation validating their importance in the context of tumorigenesis. In KPC mice, as well as PDAC patients, we show significantly elevated serum polyamine concentration. Therefore, at the early stages of tumorigenesis, the gut microbial composition changes in a way to release metabolites that foster host tumorigenesis, thereby fulfilling the ‘vicious cycle hypothesis’ of the role of the microbiome in health and disease states.ConclusionsOur results provide a potential, precise, non-invasive tool for early detection of PDAC, which will result in improved outcomes.SynopsisGut microbiota changes during early stages of pancreatic ductal adenocarcinoma (PDAC) progression and contributes towards host polyamine pool. Both changes can be used as an early predictive marker for PDAC.Translational RelevancePancreatic carcinogenesis progresses through pre-cancerous PanIN lesions to invasive cancer. Even though these morphological changes are histologically distinct, imaging techniques are not able to distinguish the pre-invasive PanINs from normal pancreas, making detection of a tumor at a precancerous stage impossible. Thus, majority of cases (85–90%) present with advanced pancreatic cancer at the time of diagnosis. This contributes to the dismal survival rate in this disease. Our study of gut microbiome analysis on KPC mice during tumor progression followed by metabolic reconstruction and experimental validation in human samples indicate that gut-microbiome analysis along with an analysis of the microbial metabolites can be developed as potential biomarkers for detection of PDAC at early stages when histological changes are not yet grossly apparent.

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