Screening for Early Pancreatic Neoplasia in High-Risk Individuals: A Prospective Controlled Study

Canto, Marcia I.

doi:10.1016/j.cgh.2006.04.003

Cited by 128 publications

(250 citation statements)

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“…This differentiation is essential in the management of high-risk individuals who show suspicious changes within the pancreas in endoscopic ultrasound (EUS) or other imaging studies. Because many high-risk individuals show pancreatitis-like changes within the pancreas, differentiation between these irregularities and high-grade PanINs and PDAC is important (12,32). In the future, these lesions can be evaluated by in vivo CFL using targeted probes to improve diagnostic accuracy.…”

Section: Discussionmentioning

confidence: 99%

“…To date, several conditions associated with familial PDAC have been described and groups of individuals at low, moderate, or high risk for developing the disease have been defined (9,10). Although clinical trials are currently testing screening protocols for the high-risk group, aimed at detecting curable precursors of PDAC such as intraductal papillary mucinous neoplasia, pancreatic intraepithelial neoplasia (PanIN), and early-stage PDAC (10)(11)(12), the results of these trials show that early lesions are often missed. Furthermore, false positive findings can lead to overtreatment of a significant fraction of the screened population (12).…”

mentioning

confidence: 99%

“…Although clinical trials are currently testing screening protocols for the high-risk group, aimed at detecting curable precursors of PDAC such as intraductal papillary mucinous neoplasia, pancreatic intraepithelial neoplasia (PanIN), and early-stage PDAC (10)(11)(12), the results of these trials show that early lesions are often missed. Furthermore, false positive findings can lead to overtreatment of a significant fraction of the screened population (12). These findings show that better diagnostic tools for the detection of preneoplastic lesions and early-stage PDAC are urgently needed.…”

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confidence: 99%

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In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging

Eser

Messer²,

Eser³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor patient outcome often resulting from late diagnosis in advanced stages. To date methods to diagnose early-stage PDAC are limited and in vivo detection of pancreatic intraepithelial neoplasia (PanIN), a preinvasive precursor of PDAC, is impossible. Using a cathepsin-activatable near-infrared probe in combination with flexible confocal fluorescence lasermicroscopy (CFL) in a genetically defined mouse model of PDAC we were able to detect and grade murine PanIN lesions in real time in vivo. Our diagnostic approach is highly sensitive and specific and proved superior to clinically established fluorescein-enhanced imaging. Translation of this endoscopic technique into the clinic should tremendously improve detection of pancreatic neoplasia, thus reforming management of patients at risk for PDAC. is one of the deadliest human malignancies, with an extremely poor 5-y survival rate below 5% (1). Because patients generally present with symptoms relating to late stages of the disease, diagnosis of resectable PDAC is achieved in less than 15% of cases (1). However, investigators have reported that diagnosis and resection of early-stage PDAC (<2 cm in size) can result in a 4-y survival rate of up to 78% (2-5). These data suggest that early detection of PDAC can improve patient outcome. In addition, it has been shown that resection of PDAC combined with adjuvant chemotherapy can improve 5-y survival rates to 25%. Thus, increasing the chance of resection will lead to improved survival.Of the more than 33,000 new cases of PDAC diagnosed in the United States every year, ∼10% occur in families with a high prevalence of PDAC and are thus referred to as familial (6, 7). In a cohort study of twins, it was proposed that inherited factors may be responsible for up to 36% of pancreatic cancers, suggesting that the incidence of familial pancreatic cancer may be even higher than presently assumed (8). To date, several conditions associated with familial PDAC have been described and groups of individuals at low, moderate, or high risk for developing the disease have been defined (9, 10). Although clinical trials are currently testing screening protocols for the high-risk group, aimed at detecting curable precursors of PDAC such as intraductal papillary mucinous neoplasia, pancreatic intraepithelial neoplasia (PanIN), and early-stage PDAC (10-12), the results of these trials show that early lesions are often missed. Furthermore, false positive findings can lead to overtreatment of a significant fraction of the screened population (12). These findings show that better diagnostic tools for the detection of preneoplastic lesions and early-stage PDAC are urgently needed. Recent data demonstrate that preinvasive precursors progress slowly over many years to decades to invasive pancreatic cancer (13). The parental pancreatic cancer founder clone then requires more than 5 y to acquire the capacity to metastasize (13). Thus, there is a time frame of several years for the diagnosi...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging

Eser

Messer²,

Eser³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…The diagnostic yield of screening was 10 %. Eight patients had confirmed pancreatic neoplasms as determined after surgery and using EUS-guided fine-needle aspiration (EUS-FNA) [26]. In the CAPS 3 study, researchers screened 216 adult asymptomatic high-risk individuals for PC at five American academic medical centers using CT, MRI, and EUS.…”

Section: Screening Programs For High-risk Individualsmentioning

confidence: 99%

Diagnostic strategies for early pancreatic cancer

et al. 2014

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“…PanIN 3 is the stage when the lesion is ready to invade and therefore considered the target lesion for early detection and curative treatments. [3,4] Intraductal papillary mucinous neoplasm (IPMN) is another precursor of PC. IPMN are pancreatic lesions that develop from the malignant transformation of the cells lining the pancreatic ducts and are characterized by mucin production, cystic dilation of the pancreatic ducts and intraductal papillary growth.…”

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confidence: 99%