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Gastroenterology Mar 2021There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established.
METHODS
CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined.
RESULTS
In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection.
CONCLUSION
CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.
Topics: Aged; CA-19-9 Antigen; Diagnosis, Differential; Early Detection of Cancer; Feasibility Studies; Female; Healthy Volunteers; Humans; Liquid Biopsy; Male; Mass Screening; Middle Aged; Pancreatic Cyst; Pancreatic Neoplasms; Pancreatitis, Chronic; Sensitivity and Specificity; United States
PubMed: 33333055
DOI: 10.1053/j.gastro.2020.11.052 -
Gastroenterology Jan 2023Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been...
Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.
BACKGROUND & AIMS
Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time.
METHODS
The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens.
RESULTS
Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations.
CONCLUSIONS
PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.
Topics: Humans; Retrospective Studies; Cystadenoma, Serous; Prospective Studies; Pancreatic Neoplasms; Pancreatic Cyst; High-Throughput Nucleotide Sequencing; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Genomics; Mitogen-Activated Protein Kinases
PubMed: 36209796
DOI: 10.1053/j.gastro.2022.09.028 -
Gastrointestinal Endoscopy Clinics of... Jul 2023Pancreatic cystic lesions (PCLs) have been diagnosed with increasing frequency likely due to the widespread use of cross-sectional imaging. A precise diagnosis of the... (Review)
Review
Pancreatic cystic lesions (PCLs) have been diagnosed with increasing frequency likely due to the widespread use of cross-sectional imaging. A precise diagnosis of the PCL is important because it helps identify patients in need of surgical resection and those who can undergo surveillance imaging. A combination of clinical and imaging findings as well as cyst fluid markers can help classify PCLs and guide management. This review focuses on endoscopic imaging of PCLs including endoscopic and endosonographic features and fine needle aspiration. We then review the role of adjunct techniques, such as microforceps, contrast-enhanced endoscopic ultrasound, pancreatoscopy, and confocal laser endomicroscopy.
Topics: Humans; Pancreatic Neoplasms; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Pancreatic Cyst; Pancreas; Endosonography
PubMed: 37245937
DOI: 10.1016/j.giec.2023.03.005 -
The Surgical Clinics of North America Jun 2020This article outlines the principles behind the management of pancreatic cystic lesions. We outline what the general surgeon needs to know in managing and triaging these... (Review)
Review
This article outlines the principles behind the management of pancreatic cystic lesions. We outline what the general surgeon needs to know in managing and triaging these patients. It is our feeling that the general surgeon is often the first line of evaluation of these complex patients and a working knowledge of the different types of cysts is critical to safe care of the patient.
Topics: Adult; Aged; Cell Transformation, Neoplastic; Diagnosis, Differential; Early Diagnosis; Endosonography; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pancreas; Pancreatectomy; Pancreatic Cyst; Pancreatic Ducts; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Tomography, X-Ray Computed
PubMed: 32402302
DOI: 10.1016/j.suc.2020.02.006 -
Gastrointestinal Endoscopy Clinics of... Jul 2023Pancreatic cystic neoplasms (PCNs) are increasingly detected because of the widespread use of cross-sectional imaging and overall aging population. While the majority of... (Review)
Review
Pancreatic cystic neoplasms (PCNs) are increasingly detected because of the widespread use of cross-sectional imaging and overall aging population. While the majority of these cysts are benign, some can progress to advanced neoplasia (defined as high-grade dysplasia and invasive cancer). As the only widely accepted treatment for PCNs with advanced neoplasia is surgical resection, accurate preoperative diagnosis, and stratification of malignant potential for deciding about surgery, surveillance or doing nothing remains a clinical challenge. Surveillance strategies for pancreatic cysts (PCNs) combine clinical evaluation and imaging to assess changes in cyst morphology and symptoms that may indicate advanced neoplasia. PCN surveillance heavily relies on various consensus clinical guidelines that focus on high-risk morphology, surgical indications, and surveillance intervals and modalities. This review will focus on current concepts in the surveillance of newly diagnosed PCNs, especially on low-risk presumed intraductal papillary mucinous neoplasms (those without worrisome features and high-risk stigmata), and appraise current clinical surveillance guidelines.
Topics: Humans; Aged; Pancreas; Pancreatic Neoplasms; Pancreatic Cyst; Neoplasms, Cystic, Mucinous, and Serous; Pancreatectomy
PubMed: 37245939
DOI: 10.1016/j.giec.2023.03.010 -
Gastrointestinal Endoscopy Clinics of... Jul 2023Pancreatic cyst fluid analysis can help diagnose pancreatic cyst type and the risk of high-grade dysplasia and cancer. Recent evidence from molecular analysis of cyst... (Review)
Review
Pancreatic cyst fluid analysis can help diagnose pancreatic cyst type and the risk of high-grade dysplasia and cancer. Recent evidence from molecular analysis of cyst fluid has revolutionized the field with multiple markers showing promise in accurate diagnosis and prognostication of pancreatic cysts. The availability of multi-analyte panels has great potential for more accurate prediction of cancer.
Topics: Humans; Pancreatic Neoplasms; Cyst Fluid; Pancreatic Cyst; Biomarkers; Biomarkers, Tumor
PubMed: 37245938
DOI: 10.1016/j.giec.2023.03.006 -
Gastrointestinal Endoscopy Clinics of... Jul 2023The overall prevalence of pancreatic cysts (PCs) is high in the general population. In clinical practice PCs are often incidentally discovered and are classified into... (Review)
Review
The overall prevalence of pancreatic cysts (PCs) is high in the general population. In clinical practice PCs are often incidentally discovered and are classified into benign, premalignant, and malignant lesions according to the World Health Organization. For this reason, in the absence of reliable biomarkers, to date clinical decision-making relies mostly on risk models based on morphological features. The aim of this narrative review is to present the current knowledge regarding PC's morphologic features with related estimated risk of malignancy and discuss available diagnostic tools to minimize clinically relevant diagnostic errors.
Topics: Humans; Pancreatic Neoplasms; Pancreatic Cyst; Biomarkers; Precancerous Conditions
PubMed: 37245940
DOI: 10.1016/j.giec.2023.03.011 -
Gastrointestinal Endoscopy Clinics of... Jul 2023
Topics: Humans; Magnetic Resonance Imaging; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 37245942
DOI: 10.1016/j.giec.2023.04.009 -
Praxis Jun 2022All about the Pancreas Ultrasound has made tremendous progress with the use of contrast media and elastography, particularly in patients with small, solid pancreatic... (Review)
Review
All about the Pancreas Ultrasound has made tremendous progress with the use of contrast media and elastography, particularly in patients with small, solid pancreatic lesions (SPL) <20mm and cystic tumors (CPL) of any size. In the case of solid and cystic pancreatic lesions, the differential diagnosis must first be evaluated after detection in order to define the indications for radical surgery, strategies for preserving the pancreatic parenchyma or simply for control examinations. Contrast-enhanced transcutaneous (TUS, CEUS) and endoscopic (EUS, CE-EUS) ultrasound and elastography facilitate further characterization of SPL and ZPL. Pancreatic ductal adenocarcinomas (PDAC) show hypoenhancement in contrast-enhanced ultrasound. The majority of the important differential diagnoses, on the other hand, are multi-enhancing. PDAC are almost always harder than healthy pancreatic parenchyma. In contrast, elastographically soft SPL are - with very few exceptions - benign. This review provides an overview of the use of modern ultrasound techniques to detect and characterize solid and cystic pancreatic lesions.
Topics: Elasticity Imaging Techniques; Humans; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 35765789
DOI: 10.1024/1661-8157/a003910 -
World Journal of Gastroenterology Jun 2021Cystic pancreatic lesions involve a wide variety of pathological entities that include neoplastic and non-neoplastic lesions. The proper diagnosis, differentiation, and...
Cystic pancreatic lesions involve a wide variety of pathological entities that include neoplastic and non-neoplastic lesions. The proper diagnosis, differentiation, and staging of these cystic lesions are considered a crucial issue in planning further management. There are great challenges for their diagnostic models. In our time, new emerging methods for this diagnosis have been discovered. Endoscopic ultrasonography-guided fine-needle aspiration cytology with chemical and molecular analysis of cyst fluid and EUS-guided fine needle-based confocal laser endomicroscopy, through the needle microforceps biopsy, and single-operator cholangioscopy/pancreatoscopy are promising methods that have been used in the diagnosis of cystic pancreatic lesions. Hereby we discuss the diagnosis of cystic pancreatic lesions and the benefits of various diagnostic models.
Topics: Endoscopic Ultrasound-Guided Fine Needle Aspiration; Endosonography; Humans; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 34135548
DOI: 10.3748/wjg.v27.i21.2664