Early Detection of Pancreatic Cancer: Opportunities and Challenges

Published on May 1, 2019in Gastroenterology17.373
· DOI :10.1053/J.GASTRO.2019.01.259
Aatur D. Singhi41
Estimated H-index: 41
(University of Pittsburgh),
Eugene J. Koay34
Estimated H-index: 34
(University of Texas MD Anderson Cancer Center)
+ 1 AuthorsAnirban Maitra136
Estimated H-index: 136
(University of Texas MD Anderson Cancer Center)
Sources
Abstract
Most patients with pancreatic ductal adenocarcinoma (PDAC) present with symptomatic, surgically unresectable disease. Although the goal of early detection of PDAC is laudable and likely to result in significant improvement in overall survival, the relatively low prevalence of PDAC renders general population screening infeasible. The challenges of early detection include identification of at-risk individuals in the general population who would benefit from longitudinal surveillance programs and appropriate biomarker and imaging-based modalities used for PDAC surveillance in such cohorts. In recent years, various subgroups at higher-than-average risk for PDAC have been identified, including those with familial risk due to germline mutations, a history of pancreatitis, patients with mucinous pancreatic cysts, and elderly patients with new-onset diabetes. The last 2 categories are discussed at length in terms of the opportunities and challenges they present for PDAC early detection. We also discuss current and emerging imaging modalities that are critical to identifying early, potentially curable PDAC in high-risk cohorts on surveillance.
Download
📖 Papers frequently viewed together
2,893 Citations
66 Citations
413 Citations
References194
Newest
#1Laura D. Wood (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 57
#2Matthew B. Yurgelun (Harvard University)H-Index: 23
Last. Michael G. Goggins (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 7
view all 3 authors...
In the previous decade, comprehensive genomic analyses have yielded important insights about the genetic alterations that underlie pancreatic tumorigenesis. Whole-exome and whole-genome sequencing of pancreatic ductal adenocarcinomas have confirmed the critical driver genes altered in the majority of pancreatic cancers, as well as identified numerous less frequently altered driver genes, and have delineated cancer subgroups with unique biological and clinical features. It is now appreciated that...
21 CitationsSource
#1Zohar Levi (TAU: Tel Aviv University)H-Index: 28
#2Yakir Rottenberg (HUJI: Hebrew University of Jerusalem)H-Index: 11
Last. Jeremy D. Kark (HUJI: Hebrew University of Jerusalem)H-Index: 23
view all 11 authors...
BACKGROUND: There is growing concern regarding the impact of adolescent obesity on adult health. The objective of this study was to evaluate the association between body mass index (BMI) in late adolescence and the incidence of pancreatic cancer during adulthood. METHODS: The authors analyzed a cohort of 1087,358 Israeli Jewish men and 707,212 Jewish women who underwent a compulsory physical examination between ages 16 and 19 years from 1967 to 2002. Pancreatic cancer incidence through December ...
12 CitationsSource
#1Eugene J. Koay (University of Texas MD Anderson Cancer Center)H-Index: 7
#1Eugene J. Koay (University of Texas MD Anderson Cancer Center)H-Index: 34
Last. Jason B. Fleming (University of Texas MD Anderson Cancer Center)H-Index: 69
view all 38 authors...
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with variable presentations and natural histories of disease. We hypothesized that different morphologic characteristics of PDAC tumors on diagnostic computed tomography (CT) scans would reflect their underlying biology. Experimental Design: We developed a quantitative method to categorize the PDAC morphology on pretherapy CT scans from multiple datasets of patients with resectable and metastatic disease and correlated t...
31 CitationsSource
#1Aatur D. Singhi (University of Pittsburgh)H-Index: 41
#2Kevin McGrath (University of Pittsburgh)H-Index: 36
Last. Marina N. Nikiforova (University of Pittsburgh)H-Index: 13
view all 21 authors...
Objective DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS / GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53 / PIK3CA / PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing. Design Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopi...
115 CitationsSource
#1Anirban Maitra (University of Texas MD Anderson Cancer Center)H-Index: 136
#2Ayush Sharma (Mayo Clinic)H-Index: 11
Last. Suresh T. Chari (Mayo Clinic)H-Index: 103
view all 15 authors...
AbstractThe National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases initiated the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) in 2015 (the CPDPC's origin, structure, governance, and research objectives are desc
26 CitationsSource
#1Matthew Kulzer (University of Pittsburgh)H-Index: 3
#2Aatur D. Singhi (University of Pittsburgh)H-Index: 41
Last. Anil K. Dasyam (University of Pittsburgh)H-Index: 16
view all 9 authors...
Cystic neoplasms in the pancreas are encountered frequently on imaging, often detected incidentally during evaluation for other conditions. They can have a variety of clinical and imaging presentations, and similarly, wide-ranging prognostic and treatment implications. In the majority, imaging helps in diagnosis of pancreatic cystic neoplasms (PCNs) and guides management decisions. But, a significant minority of the PCNs remain indeterminate. There have been multiple recent advances in biomarker...
8 CitationsSource
#1Marta Sandini (University of Milano-Bicocca)H-Index: 15
#2Manuel Patino (Harvard University)H-Index: 11
Last. Carlos Fernandez-del Castillo (Harvard University)H-Index: 101
view all 23 authors...
Importance Sarcopenia and sarcopenic obesity have been associated with poor outcomes in unresectable pancreatic cancer (PC). Neoadjuvant treatment (NT) is used increasingly to improve resectability; however, its effects on fat and muscle body composition have not been characterized. Objectives To evaluate whether NT affects muscle mass and adipose tissue in patients with borderline resectable PC (BRPC) and locally advanced PC (LAPC) and determine whether there were potential differences between ...
38 CitationsSource
#1Ayush Sharma (Mayo Clinic)H-Index: 11
#2Harika Kandlakunta (Mayo Clinic)H-Index: 2
Last. Suresh T. Chari (Mayo Clinic)H-Index: 103
view all 7 authors...
Background & Aims Of patients with new-onset diabetes (NOD; based on glycemic status) older than 50 years, approximately 1% are diagnosed with pancreatic cancer (PC) within 3 years. We aimed to develop and validate a model to determine risk of PC in patients with NOD. Methods We retrospectively collected data from 4 independent and nonoverlapping cohorts of patients (N = 1,561) with NOD (based on glycemic status; data collected at date of diagnosis and 12 months previously) in the Rochester Epid...
66 CitationsSource
#1Ijm Levink (EUR: Erasmus University Rotterdam)H-Index: 1
#2Marco J. Bruno (EUR: Erasmus University Rotterdam)H-Index: 23
Last. DL Cahen (EUR: Erasmus University Rotterdam)H-Index: 1
view all 3 authors...
Purpose of review Management of intraductal papillary mucinous neoplasm (IPMN) is currently based on consensus, in the absence of evidence-based guidelines. In recent years, several consensus guidelines have been published, with distinct management strategies. In this review, we will discuss these discrepancies, in order to guide treating physicians in clinical management.
11 CitationsSource
#1Amit Khera (Harvard University)H-Index: 75
#2Mark Chaffin (Broad Institute)H-Index: 26
Last. Sekar KathiresanH-Index: 137
view all 11 authors...
A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation1. Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature2–5, it has not yet been possible to use...
867 CitationsSource
Cited By107
Newest
#1Dana K. AndersenH-Index: 21
#2Suresh T. ChariH-Index: 103
Last. Stephen J. PandolH-Index: 74
view all 7 authors...
Source
#1Placido D (UCPH: University of Copenhagen)
#2Bo Yuan (Harvard University)H-Index: 2
Last. Franz A (Harvard University)
view all 0 authors...
Pancreatic cancer is an aggressive disease that typically presents late with poor patient outcomes. There is a pronounced medical need for early detection of pancreatic cancer, which can be facilitated by identifying high-risk populations. Here we apply artificial intelligence (AI) methods to a large corpus of more than 6 million patient records spanning 40 years with 24,000 pancreatic cancer cases in the Danish National Patient Registry. In contrast to existing methods that do not use temporal ...
Source
Last. I. V. Dodonova (First Pavlov State Medical University of St. Peterburg)
view all 0 authors...
Source
#1Wenjing Song (WHU: Wuhan University)H-Index: 4
#2Xin He (WHU: Wuhan University)H-Index: 5
Last. Jingwei Zhang (WHU: Wuhan University)H-Index: 37
view all 0 authors...
Objective: Pancreatic ductal adenocarcinoma (PDAC) is highly lethal. Although progress has been made in the treatment of PDAC, its prognosis remains unsatisfactory. This study aimed to develop novel prognostic genes related to glycolysis in PDAC and to apply these genes to new risk stratification. Methods: In this study, based on the Cancer Genome Atlas (TCGA) PAAD cohort, the expression level of glycolysis-related gene at mRNA level in PAAD and its relationship with prognosis were analyzed. Non...
Source
#2Ned P Quirke (UCD: University College Dublin)
view all 0 authors...
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and carries a dismal prognosis. Resectable patients are treated predominantly with surgery while borderline resectable patients may receive neoadjuvant treatment (NAT) to downstage their disease prior to possible resection. PDAC tissue is stiffer than healthy pancreas, and tissue stiffness is associated with cancer progression. Another feature of PDAC is increased tissue heterogeneity. We postulate that tumour s...
Source
#1Venkata S. Katabathina (University of Texas at Austin)H-Index: 16
#2Suryakala Buddha (Boston Children's Hospital)
Last. Srinivasa R. PrasadH-Index: 44
view all 0 authors...
A wide spectrum of hereditary syndromes predispose patients to distinct pancreatic abnormalities, including cystic lesions, recurrent pancreatitis, ductal adenocarcinoma, nonductal neoplasms, and parenchymal iron deposition. While pancreatic exocrine insufficiency and recurrent pancreatitis are common manifestations in cystic fibrosis and hereditary pancreatitis, pancreatic cysts are seen in von Hippel-Lindau disease, cystic fibrosis, autosomal dominant polycystic kidney disease, and McCune-Albr...
Source
#1Stefan Markovic (Weizmann Institute of Science)H-Index: 2
#2Tangi RousselH-Index: 5
Last. Lucio Frydman (Weizmann Institute of Science)H-Index: 56
view all 0 authors...
Detecting and mapping metabolism in tissues represents a major step in detecting, characterizing, treating and understanding cancers. Recently introduced deuterium metabolic imaging techniques could offer a noninvasive route for the metabolic imaging of animals and humans, based on using 2 H magnetic resonance spectroscopic imaging (MRSI) to detect the uptake of deuterated glucose and the fate of its metabolic products. In this study, 2 H6,6' -glucose was administered to mice cohorts that had be...
1 CitationsSource
#1Ananya Malhotra (Lond: University of London)H-Index: 3
#2Bernard Rachet (Lond: University of London)H-Index: 51
Last. Laura M. Woods (Lond: University of London)H-Index: 18
view all 5 authors...
BACKGROUND Pancreatic cancer (PC) represents a substantial public health burden. Pancreatic cancer patients have very low survival due to the difficulty of identifying cancers early when the tumour is localised to the site of origin and treatable. Recent progress has been made in identifying biomarkers for PC in the blood and urine, but these cannot be used for population-based screening as this would be prohibitively expensive and potentially harmful. METHODS We conducted a case-control study u...
Source
#1Marco GalloH-Index: 16
Last. Francesco Giorgino (University of Bari)H-Index: 61
view all 19 authors...
Pancreatic cancer (PC) is a common cause of cancer-related death, due to difficulties in detecting early-stage disease, to its aggressive behaviour, and to poor response to systemic therapy. Therefore, developing strategies for early diagnosis of resectable PC is critical for improving survival. Diabetes mellitus is another major public health problem worldwide. Furthermore, diabetes can represent both a risk factor and a consequence of PC: nowadays, the relationship between these two diseases i...
Source
#1Keiran Logan (Ulster University)H-Index: 6
#2Heather Nesbitt (Ulster University)H-Index: 13
Last. John F. Callan (Ulster University)H-Index: 34
view all 9 authors...
Abstract Gemcitabine and nab-paclitaxel (Abraxane®) is a standard of care chemotherapy combination used in the treatment of patients with advanced pancreatic cancer. While the combination has shown a survival benefit when compared to gemcitabine monotherapy, it is associated with significant off-target toxicity. Ultrasound targeted microbubble destruction (UTMD) has emerged as an effective strategy for the site-specific deposition of drug-payloads. However, loading a single microbubble formulati...
Source