A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

The Clinical Utility of Evaluating the Luminal Upper Gastrointestinal Tract During Linear Endoscopic Ultrasonography.

BACKGROUND: The clinical utility of performing esophagogastroduodenoscopy (EGD) before linear endoscopic ultrasonography (L-EUS) to evaluate the luminal upper gastrointestinal (GI) tract is not well established. GOALS: The study was aimed to determine the prevalence of clinically meaningful luminal abnormalities (any luminal finding requiring further evaluation with mucosal biopsy or initiation of treatment) in patients undergoing L-EUS. The study also sought to compare the ability of the gastroscope and the linear echoendoscope in identifying these lesions. STUDY: A prospective, multicenter cohort study enrolled patients undergoing L-EUS for nonluminal indications. All patients underwent EGD followed by L-EUS by 2 different endoscopists. The second endoscopist was blinded to the results of the initial EGD. The identification of clinically meaningful luminal lesions and quality of endoscopic visualization of the upper GI tract were measured. RESULTS: In the cohort of 175 patients, 52 (29.7%) patients had clinically meaningful luminal findings seen in the upper GI tract. There was no significant difference in the number of clinically meaningful lesions identified on EGD and L-EUS (25.1% vs. 22.9%, P=0.39). No significant difference was found in the miss rate of clinically meaningful lesions between the 2 modalities (EGD: 4.5% vs. EUS: 6.9%, P=0.39). CONCLUSIONS: A substantial minority of patients undergoing L-EUS for nonluminal indications will have clinically meaningful luminal findings. The endoscopic evaluation of the luminal upper GI tract can be adequately achieved using the linear echoendoscope.