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

被引：18

作者：

Nikiforova, Marina N. ^{[1
]}

Wald, Abigail I. ^{[1
]}

Spagnolo, Daniel M. ^{[1
]}

Melan, Melissa A. ^{[1
]}

Grupillo, Maria ^{[1
]}

Lai, Yi-Tak ^{[1
]}

Brand, Randall E. ^{[2
]}

O'Broin-Lennon, Anne Marie ^{[3
]}

Mcgrath, Kevin ^{[2
]}

Park, Walter G. ^{[4
]}

Pfau, Patrick R. ^{[5
]}

Polanco, Patricio M. ^{[6
]}

Kubiliun, Nisa ^{[7
]}

Dewitt, John ^{[8
]}

Easler, Jeffrey J. ^{[8
]}

Dam, Aamir ^{[9
]}

Mok, Shaffer R. ^{[9
]}

Wallace, Michael B. ^{[10
,11
]}

Kumbhari, Vivek ^{[10
]}

Boone, Brian A. ^{[12
]}

Marsh, Wallis ^{[12
]}

Thakkar, Shyam ^{[13
]}

Fairley, Kimberly J. ^{[13
]}

Afghani, Elham ^{[3
]}

Bhat, Yasser ^{[14
]}

Ramrakhiani, Sanjay ^{[14
]}

Nasr, John ^{[15
]}

Skef, Wasseem ^{[16
]}

Thiruvengadam, Nikhil R. ^{[16
]}

Khalid, Asif ^{[2
]}

Fasanella, Kenneth ^{[2
]}

Chennat, Jennifer ^{[2
]}

Das, Rohit ^{[2
]}

Singh, Harkirat ^{[2
]}

Sarkaria, Savreet ^{[2
]}

Slivka, Adam ^{[2
]}

Gabbert, Charles ^{[2
]}

Sawas, Tarek ^{[7
]}

Tielleman, Thomas ^{[7
]}

Vanderveldt, Hendrikus Dutch ^{[7
]}

Tavakkoli, Anna ^{[7
]}

Smith, Lynette M. ^{[17
]}

Smith, Katelyn ^{[1
]}

Bell, Phoenix D. ^{[1
]}

Hruban, Ralph H. ^{[18
]}

Paniccia, Alessandro ^{[19
]}

Zureikat, Amer ^{[19
]}

Lee, Kenneth K. ^{[19
]}

Ongchin, Melanie ^{[19
]}

Zeh, Herbert ^{[20
]}

机构：

[1] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15260 USA

[2] Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA

[3] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Med, Baltimore, MD USA

[4] Stanford Univ, Dept Med, Stanford, CA USA

[5] Univ Wisconsin, Dept Med, Madison, WI USA

[6] Univ Texas Southwestern Med Ctr, Dept Surg, Dallas, TX USA

[7] Univ Texas Southwestern Med Ctr, Dept Internal Med, Dallas, TX USA

[8] Indiana Univ, Hlth Med Ctr, Dept Gastroenterol & Hepatol, Indianapolis, IN USA

[9] H Lee Moffitt Canc Ctr & Res Inst, Dept Gastrointestinal Oncol, Tampa, FL USA

[10] Mayo Clin, Dept Med, Div Gastroenterol & Hepatol, Jacksonville, FL USA

[11] Sheikh Shakhbout Med City, Abu Dhabi, U Arab Emirates

[12] West Virginia Univ, Hlth Sci Ctr, Dept Surg, Morgantown, WV USA

[13] West Virginia Univ, Dept Med, Sect Gastroenterol & Hepatol, Hlth Sci Ctr, Morgantown, WV USA

[14] Palo Alto Med Fdn PAMF, Dept Gastroenterol, Mountain View, CA USA

[15] West Virginia Univ, Hlth Sci Ctr, Dept Med, Morgantown, WV USA

[16] Loma Linda Univ, Med Ctr, Dept Med, Div Gastroenterol Hepatol, Loma Linda, CA USA

[17] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE USA

[18] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD USA

[19] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA

[20] Univ Texas Southwestern, Dept Clin Sci, Surg, Dallas, TX USA

[21] Univ Wisconsin, Dept Surg, Madison, WI USA

[22] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA

来源：

ANNALS OF SURGERY | 2023年 / 278卷 / 04期

关键词：

intraductal oncocytic papillary neoplasm; intraductal papillary mucinous neoplasm; mucinous cystic neoplasm; pancreatic ductal adenocarcinoma; pancreatic neuroendocrine tumor; serous cystadenoma; pseudocyst; FUKUOKA GUIDELINES; DIAGNOSIS; MANAGEMENT; EXPERIENCE; NEOPLASMS;

D O I：

10.1097/SLA.0000000000005904

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

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.

引用

页码：E789 / E797

页数：9

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