The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts

BACKGROUND AND AIMS: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. PATIENTS AND METHODS: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. RESULTS: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100 % and 93.2 %), but low sensitivity (48.3 % and 56.3 %) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8 %) and AUC (0.84) significantly compared to KRAS (65.3 % and 0.74) or CEA (65.8 % and 0.74) alone, but only in the clinical cohort (P < 0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73 % vs. 37 %, P = 0.001). The negative predictive value of KRAS mutation was 77.6 % in differentiating non-malignant cysts. CONCLUSIONS: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use

Screening for Pancreatic Adenocarcinoma in BRCA2 Mutation Carriers: Results of a Disease Simulation Model

Background: BRCA2 mutation carriers are at increased risk for multiple cancers including pancreatic adenocarcinoma (PAC). Our goal was to compare the effectiveness of different PAC screening strategies in BRCA2 mutation carriers, from the standpoint of life expectancy. Methods: A previously published Markov model of PAC was updated and extended to incorporate key aspects of BRCA2 mutation carrier status, including competing risks of breast- and ovarian-cancer specific mortality. BRCA2 mutation carriers were modeled and analyzed as the primary cohort for the analysis. Additional higher risk BRCA2 cohorts that were stratified according to the number of first-degree relatives (FDRs) with PAC were also analyzed. For each cohort, one-time screening and annual screening were evaluated, with screening starting at age 50 in both strategies. The primary outcome was net gain in life expectancy (LE) compared to no screening. Sensitivity analysis was performed on key model parameters, including surgical mortality and MRI test performance. Findings: One-time screening at age 50 resulted in a LE gain of 3.9 days for the primary BRCA2 cohort, and a gain of 5.8 days for those with BRCA2 and one FDR. Annual screening resulted in LE loss of 12.9 days for the primary cohort and 1.3 days for BRCA2 carriers with 1 FDR, but resulted in 20.6 days gained for carriers with 2 FDRs and 260 days gained for those with 3 FDRs. For patients with ≥ 3 FDRs, annual screening starting at an earlier age (i.e. 35–40) was optimal. Interpretation Among BRCA2 mutation carriers, aggressive screening regimens may be ineffective unless additional indicators of elevated risk (e.g., 2 or more FDRs) are present. More clinical studies are needed to confirm these findings. Funding American Cancer Society – New England Division – Ellison Foundation Research Scholar Grant (RSG-15-129-01-CPHPS)

Endoscopic Ultrasound and Related Technologies for the Diagnosis and Treatment of Pancreatic Disease - Research Gaps and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic endoscopic ultrasound (EUS). The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed

Diagnosis and management of relapsing pancreatitis associated with cystic neoplasms of the pancreas

One of the most important causes of relapsing pancreatitis is a cystic neoplasm of the pancreas. These low grade malignancies may cause pancreatitis by obstructing or communicating with a pancreatic duct. Patients with relapsing pancreatitis and a focal fluid fluid collection should be investigated for the possibility of a mucinous cystic neoplasm. Cross sectional imaging can provide a diagnosis with the imaging findings of a low attenuation cystic lesion containing mural calcification (CT scanning) or a lobular T2 enhancing lesion (MRCP). Endoscopic ultrasound can provide more detailed imaging with the ability to guide fine needle aspiration of the cyst fluid. Cyst fluid analysis can provide a diagnosis of a mucinous cystic lesion with the combination of cytology (mucinous epithelium), elevated carcinoembryonic antigen (CEA), and the presence of DNA mutations. Management of these patients consists of surgical resection and monitoring in patients not able to withstand surgery

Do Molecular Tests Really Differentiate Malignant Ipmns From Benign?

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Diagnostic and therapeutic endoscopic approaches to intraductal papillary mucinous neoplasm

Pancreatic cystic lesions are increasingly identified on routine imaging. One specific lesion, known as intraductal papillary mucinous neoplasm (IPMN), is a mucinous, pancreatic lesion characterized by papillary cells projecting from the pancreatic ductal epithelium. The finding of mucin extruding from the ampulla is essentially pathognomonic for diagnosing these lesions. IPMNs are of particular interest due to their malignant potential. Lesions range from benign, adenomatous growths to high-grade dysplasia and invasive cancer. These mucinous lesions therefore require immediate attention to determine the probability of malignancy and whether observation or resection is the best management choice. Unresected lesions need long-term surveillance monitoring for malignant transformation. The accurate diagnosis of these lesions is particularly challenging due to the substantial similarities in morphology of pancreatic cystic lesions and limitations in current imaging technologies. Endoscopic evaluation of these lesions provides additional imaging, molecular, and histologic data to aid in the identification of IPMN and to determine treatment course. The aim of this article is to focus on the diagnostic and therapeutic endoscopic approaches to IPMN