Citations 2
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
Wald, Abigail I. , Spagnolo, Daniel M. , Grupillo, Maria, Lai, Yi-Tak, O’Broin-Lennon, Anne Marie, Park, Walter G. , Pfau, Patrick , Kubiliun, Nisa , Easler, Jeffrey J. , Dam, Aamir, Mok, Shaffer , Wallace, Michael B. , Kumbhari, Vivek , Marsh, Wallis, Thakkar, Shyam , Fairley, Kimberly, Bhat, Yasser M., Nasr, John , Khalid, Asif , Fasanella, Kenneth, Chennat, Jennifer, Singh, Harkirat , Sarkaria, Savreet, Slivka, Adam, Gabbert, Charles, Sawas, Tarek , Tielleman, Thomas , Vanderveldt, Hendrikus Dutch, Tavakkoli, Anna , Smith, Katelyn, Hruban, Ralph H. , Paniccia, Alessandro , Zureikat, Amer H., Lee, Kenneth K. , Ongchin, Melanie , Zeh, Herbert J. , Minter, Rebecca M., He, Jin , Wallace, Michael B , Nikiforova, Marina N. , Melan, Melissa A. , Brand, Randall E. , McGrath, Kevin , Polanco, Patricio Marcelo , DeWitt, John M. , Boone, Brian A. , Afghani, Elham , Ramrakhiani, Sanjay , Skef, Wasseem , Thiruvengadam, Nikhil Ravi , Das, Rohit Kumar , Smith, Lynette M. , Bell, Phoenix , Nikiforov, Yuri E. , Singhi, Aatur Dilip
Annals of Surgery | May 22, 2023 | Volume: 278 | Issue: 4 | Pages: e789-e797
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.
Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections
Noel, Pawan, Patel, Krutika , Durgampudi, Chandra, Trivedi, Ram N., Oliveira, Cristiane de , Pannala, Rahul , Lee, Kenneth , Chennat, Jennifer, Slivka, Adam, Khalid, Asif , DeLany, James P. , Cline, Rachel, Acharya, Chathur , Jaligama, Deepthi, Murad, Faris, Yadav, Dhiraj , Navina, Sarah, Singh, Vijay , de Oliveira, Cristiane, Singh, Vijay P, Crowell, Michael D. , Brand, Randall E. , Papachristou, Georgios I. , Whitcomb, David C. , Singh, Vijay P
Gut | December 10, 2014 | Volume: 65 | Issue: 1 | Pages: 100-111
Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.