Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection

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.

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

The Korean Journal of Pancreas and Biliary Tract ◽

10.15279/kpba.2020.25.2.65 ◽

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.

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Development of Pancreatic Cancer: Targets for Early Detection and Treatment

Digestive Diseases ◽

10.1159/000445233 ◽

2016 ◽

Vol 34 (5) ◽

pp. 525-531 ◽

Cited By ~ 3

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.

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Screening of Pancreatic Cancer for Early Diagnosis

Korean Journal of Medicine ◽

10.3904/kjm.2021.96.2.110 ◽

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.

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Early detection of pancreatic cancer in patients with chronic pancreatitis: diagnostic utility of a K-ras point mutation in the pancreatic juice

The American Journal of Gastroenterology ◽

10.1111/j.1572-0241.2001.03608.x ◽

2001 ◽

Vol 96 (3) ◽

pp. 700-704 ◽

Cited By ~ 27

Author(s):

Pierre-Edouard Queneau ◽

Gerard-Louis Adessi ◽

Pascal Thibault ◽

Denis Cleau ◽

Bruno Heyd ◽

...

Keyword(s):

Pancreatic Cancer ◽

Chronic Pancreatitis ◽

Early Detection ◽

Point Mutation ◽

Pancreatic Juice ◽

Diagnostic Utility

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Advances in Early Detection of Pancreatic Cancer

10.20944/preprints201901.0133.v1 ◽

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.

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