Early detection of pancreatic cancer

Pereira, Stephen P.; Oldfield, Lucy; Ney, Alexander; Hart, Phil A.; Keane, M. G.; Pandol, Stephen J.; Li, Debiao; Greenhalf, William; Jeon, Christie Y.; Koay, Eugene J.; Almario, Christopher V.; Halloran, Christopher; Lennon, Anne Marie; Costello, Eithne

doi:10.1016/s2468-1253(19)30416-9

Cited by 338 publications

(344 citation statements)

References 120 publications

(141 reference statements)

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“…A previous review investigating the role of pepsinogens in early detection of gastric cancers reported that they had only moderate capacity to detect gastric cancer [173]. Another review on early pancreatic cancer detection highlighted that no single biomarker has yet translated to clinical use and suggested the use of 'robust panels of biomarkers' [9]. This review confirms that more research is required before we have sufficient evidence about biomarkers for upper GI cancers to warrant their adoption into clinical practice.…”

Section: Discussionsupporting

confidence: 57%

Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review

et al. 2020

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Introduction Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations. Methods We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted on types of biomarkers, populations and outcomes. Heterogeneity prevented pooling of outcomes. Results We identified 149 eligible studies, involving 22,264 cancer cases and 49,474 controls. A total of 431 biomarkers were identified (183 microRNAs and other RNAs, 79 autoantibodies and other immunological markers, 119 other proteins, 36 metabolic markers, 6 circulating tumour DNA and 8 other). Over half ( n = 231) were reported in pancreatic cancer studies. Only 35 biomarkers had been investigated in at least two studies, with reported outcomes for that individual marker for the same tumour type. Apolipoproteins (apoAII-AT and apoAII-ATQ), and pepsinogens (PGI and PGII) were the most promising biomarkers for pancreatic and gastric cancer, respectively. Conclusion Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended. Electronic Supplementary Material The online version of this article (10.1007/s12325-020-01571-z) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 57%

Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review

et al. 2020

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“…Pancreatic cancer is one of the most dangerous solid cancers (Kamisawa et al 2016;Pereira et al 2020). The American Cancer Society estimates that 57,600 individuals (30,400 men and 27,200 women) will be diagnosed with pancreatic cancer, and pancreatic cancer will cause approximately 47,050 deaths (24,640 men and 22,410 women) in 2020 (https://www.cancer.org/cancer/pancreatic-cancer/ about/key-statistics.html, accessed on May 11, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Early diagnosis is essential in improving the prognosis of pancreatic cancer, but it is challenging (Singhi et al 2019;Vasen et al 2019;Pereira et al 2020). The Pancreatic Cancer Registry in Japan revealed that the 5-year survival rates of patients with the Union for International Cancer Control stage 0 (high-grade pancreatic intraepithelial neoplasia [PanIN]/ carcinoma in situ [CIS]), stage IA (tumor size < 2 cm with no lymph node metastasis and no distant metastasis), and stage IB (tumor size > 2 cm but no more than 4 cm, with no lymph node metastasis and no distant metastasis) were 85.8%, 68.7%, and 59.7%, respectively, but accounted for only 1.7%, 4.1%, and 6.3%, respectively, in all registered patients (Egawa et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Focal Parenchymal Atrophy and Fat Replacement Are Clues for Early Diagnosis of Pancreatic Cancer with Abnormalities of the Main Pancreatic Duct

Miura

Kaneda

Kikuta

et al. 2020

Tohoku J. Exp. Med.

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Pancreatic cancer is one of the most dangerous solid tumors, but its early diagnosis is difficult. The abnormality of the main pancreatic duct (MPD), such as a single localized stricture and upstream dilatation, might be useful in the early detection of pancreatic cancer. However, these findings are often observed in benign inflammatory cases. This study aimed to clarify whether early pancreatic cancer presenting MPD abnormalities has characteristic features different from those of benign cases. This is a single-center, retrospective study. We analyzed 20 patients who underwent pancreatectomy presenting with a single, localized MPD stricture without identifiable masses on imaging: 10 patients with pancreatic ductal adenocarcinoma (cancer group; 6 with stage 0 and 4 with stage I) and 10 patients with benign strictures (benign group; 8 with inflammation and 2 with low-grade pancreatic intraepithelial neoplasms). Pancreatectomy was performed in these benign cases because high-grade intraepithelial neoplasm was suspected. Although the proportion of patients with diabetes mellitus tended to be higher in the cancer group (6/10) than that in the benign group (1/10) (P = 0.058), other clinical characteristics were not different between the groups. Preoperative cytological malignancies were detected in four patients in the cancer group (4/10) but not in the benign group (P = 0.09). Focal parenchymal atrophy and fat replacement were more frequently detected on computed tomography in the cancer group (7/10) than in the benign group (1/10) (P = 0.02). In conclusion, focal parenchymal atrophy and fat replacement may provide clues for the early diagnosis of pancreatic cancer.

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“…Pancreatic cancer continues to have a poor 5-year survival rate despite its rising incidence [20,21]. By 2030, it is estimated to become the second leading cause of cancer related deaths [5].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of KLK8 Predicts Poor Prognosis in Pancreatic Cancer

Hua

Liu

et al. 2020

Preprint

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Background: Pancreatic ductal adenocarcinoma (PDAC) is a growing cause of cancer-related mortality worldwide. Kallikrein-related peptidase 8 (KLK8) has potential clinical values in many cancers. However, the clinicopathological significances of KLK8 in PDAC remain unknown. Methods: The relationship of KLK8 to clinicopathological features of PDAC was investigated based on public databases. KLK8 expression was examined in human PDAC tissues. Cell proliferation and apoptosis were evaluated in KLK8-overexpressed human pancreatic cancer cell lines Mia-paca-2 and Panc-1. The related signaling pathways of KLK8 involved in pancreatic cancer progression were analyzed by gene set enrichment analysis (GSEA) and further verified in in vitro studies. Results: KLK8 was up-regulated in tumor tissues in the TCGA-PAAD cohort, and was an independent prognostic factor for both overall survival and disease-free survival of PDAC. KLK8 mRNA and protein expressions were increased in PDAC tissues compared with para-cancerous pancreas. KLK8 overexpression exerted pro-proliferation and anti-apoptotic functions in Mia-paca-2 and Panc-1 cells. GSEA analysis showed that KLK8 was positively associated with PI3K-Akt-mTOR and Notch pathways. KLK8-induced pro-proliferation and anti-apoptotic effects in Mia-paca-2 and Panc-1 cells were attenuated by inhibitors for PI3K, Akt, and mTOR, but not by inhibitor for Notch.Conclusion: KLK8 overexpression exerts pro-proliferation and anti-apoptotic functions in pancreatic cancer cells via PI3K/Akt/mTOR pathway. Upregulated KLK8 in PDAC predicts poor prognosis and may be a potential therapeutic target for PDAC.

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Early detection of pancreatic cancer

Cited by 338 publications

References 120 publications

Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review

Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review

Focal Parenchymal Atrophy and Fat Replacement Are Clues for Early Diagnosis of Pancreatic Cancer with Abnormalities of the Main Pancreatic Duct

Upregulation of KLK8 Predicts Poor Prognosis in Pancreatic Cancer

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