Sweet Predictions Speak Volumes for Early Detection of Pancreatic Cancer

Søreide, Kjetil

doi:10.1053/j.gastro.2018.06.054

Cited by 14 publications

(13 citation statements)

References 19 publications

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“…A French study suggested that branch duct IPMN in men with recent onset diabetes should be considered for resection, as the incidence of malignancy and high-grade dysplasia was higher in this group[27]. This is in line with the evolving evidence that developing fasting blood glucose intolerance is associated with risk of pancreatic malignancy[28,29]. New onset diabetes associated with an IPMN is also a clear indication for resection in healthy individuals when following the European guidelines as it is a “relative indication” that should lead to resection in patients without comorbidities (Table 1).…”

Section: Ipmns Of Main Duct Branch Duct and Mixed Typementioning

confidence: 56%

Observation or resection of pancreatic intraductal papillary mucinous neoplasm: An ongoing tug of war

Aunan¹,

Jamieson²,

Søreide³

2019

WJGO

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An increasing number of patients are being referred to pancreatic centres around the world due to often incidentally discovered cystic neoplasms of the pancreas. The evaluation and management of pancreatic cystic neoplasms is a controversial topic and with existing guidelines based on a lack of strong evidence there is discordance between centres and guidelines with regard to when to offer surgery and when to favour surveillance. The frequency, duration and modality of surveillance is also controversial as this is resource-consuming and must be balanced against the perceived benefits and risks involved. While there is consensus that the risk of malignancy should be balanced against the life-expectancy and comorbidities, the indications for surgery and surveillance strategies vary among the guidelines. Thus, the tug of war between surveillance or resection continues. Here we discuss the recommendations from guidelines with further accumulating data and emerging reports on intraductal papillary mucinous neoplasm in the literature.

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Section: Ipmns Of Main Duct Branch Duct and Mixed Typementioning

confidence: 56%

Observation or resection of pancreatic intraductal papillary mucinous neoplasm: An ongoing tug of war

Aunan¹,

Jamieson²,

Søreide³

2019

WJGO

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“…CTCs circulating tumour cells, cfDNA cell-free DNA, miRNA microRNA, PanIN pancreatic intraepithelial neoplasia, PDAC pancreatic adenocarcinoma. (Reprinted from K. Søreide [16], Copyright (2018), with permission from Elsevier)…”

Section: Methodsmentioning

confidence: 99%

“…In addition, the poor vessel density within the tumour partly explains both the hypoxic environment (lack of nutrients) and the poor response to most types of chemotherapy. The aggressive nature and early metastatic potential of PDAC sets in with an aggressive perineural growth pattern culminating by early invasion and metastasis, even when cancers are still considered small in size (<2 cm) [16,27,28]. Hence, PDACs have a bad biology even in the very early stages and for rather small tumours [29].…”

Section: A Background Of Bad Behaviour In Tumour Biologymentioning

confidence: 99%

“…1). For the rest of the population, the risk factors are generic-smoking, obesity and aging are strongly related to risk of PDAC-and too general to allow for screening of particular persons at risk [16]. Thus, great interest exists in investigating biological factors and novel technologies that can facilitate an earlier diagnosis or be predictive or prognostic for patients with PDAC.…”

Section: Introductionmentioning

confidence: 99%

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Molecular biology in pancreatic ductal adenocarcinoma: implications for future diagnostics and therapy

et al. 2019

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Background Novel technology has enabled researchers to better characterize pancreatic cancers at the molecular level. We wanted to explore some of the emerging discoveries, such as molecular subclassification, use of liquid biopsy and use of organoids in cancer assessment. Methods A literature review with a search specific to the topic, with recent reviews in major journals and a focus on the last 5 years (until December 2018), was done. Results Pancreatic ductal adenocarcinoma (PDAC) may now be classified into clinical subgroups based on the predominant genomic profiles, but consensus on one classification system is lacking. Several subtypes have been suggested, including categories such as basal-like, stroma-activated, desmoplastic, pure classical and immune classical types. Further refinement may translate into clinically meaningful groups for therapeutic or prognostic purposes. Liquid

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“…2 However, pancreatic cancer demonstrates features of aggressive biology; early invasiveness even in smaller tumors with frequent perineural infiltration and a strong desmoplastic stromal response, rendering tumors resistant to most forms of therapy. 3,4 In a large population-based study of patients with pancreatic cancer, investigators identified a subgroup of patients with small cancers (<0.5 cm) at diagnosis, of which almost one third (31%) already had metastasis at the time of diagnosis. 5 The propensity to metastasize into the liver is believed to start early and likely involve the tumor stroma, with exosomes or vesicles secreted into the circulation, creating docks for circulating tumor cells to settle into so-called premetastatic niches in the liver.…”

Section: Introductionmentioning

confidence: 99%

Is There a Trojan Horse to Aggressive Pancreatic Cancer Biology? A Review of the Trypsin-PAR2 Axis to Proliferation, Early Invasion, and Metastasis

Søreide

Roalsø

Aunan

2020

Journal of Pancreatic Cancer

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Purpose: Pancreatic cancer is one of the most lethal of solid tumors and is associated with aggressive cancer biology. The purpose is to review the role of trypsin and effect on molecular and cellular processes potentially explaining the aggressive biology in pancreatic cancer. Methods: A narrative literature review of studies investigating trypsin and its effect on protease systems in cancer, with special reference to pancreatic cancer biology. Results: Proteases, such as trypsin, provides a significant advantage to developing tumors through the ability to remodel the extracellular matrix, promote cell invasion and migration, and facilitate angiogenesis. Trypsin is a digestive enzyme produced by the exocrine pancreas that is also related to mechanisms of proliferation, invasion and metastasis. Several of these mechanisms may be co-regulated or influenced by activation of proteinaseactivated receptor 2 (PAR-2). The current role in pancreatic cancer is not clear but emerging data suggest several potential mechanisms. Trypsin may act as a Trojan horse in the pancreatic gland, facilitating several molecular pathways from the onset, which leads to rapid progression of the disease. Pancreatic cancer cell lines containing PAR-2 proliferate upon exposure to trypsin, whereas cancer cell lines not containing PAR-2 fail to proliferate upon trypsin expression. Several mechanisms of action include a proinflammatory environment, signals inducing proliferation and migration, and direct and indirect evidence for mechanisms promoting invasion and metastasis. Novel techniques (such as organoid models) and increased understanding of mechanisms (such as the microbiome) may yield improved understanding into the role of trypsin in pancreatic carcinogenesis. Conclusion: Trypsin is naturally present in the pancreatic gland and may experience pathological activation intracellularly and in the neoplastic environment, which speeds up molecular mechanisms of proliferation, invasion, and metastasis. Further investigation of these processes will provide important insights into how pancreatic cancer evolves, and suggest new ways for treatment.

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Sweet Predictions Speak Volumes for Early Detection of Pancreatic Cancer

Cited by 14 publications

References 19 publications

Observation or resection of pancreatic intraductal papillary mucinous neoplasm: An ongoing tug of war

Observation or resection of pancreatic intraductal papillary mucinous neoplasm: An ongoing tug of war

Molecular biology in pancreatic ductal adenocarcinoma: implications for future diagnostics and therapy

Is There a Trojan Horse to Aggressive Pancreatic Cancer Biology? A Review of the Trypsin-PAR2 Axis to Proliferation, Early Invasion, and Metastasis

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