A multimodality test to guide the management of patients with a pancreatic cyst

Molecular and clinical markers outperform current clinical and imaging criteria for the diagnosis and management of patients with pancreatic cysts. Pancreatic prognostication Early, accurate detection of pancreatic cancer is a high priority. However, not all pancreatic cysts develop into cancer and they can be difficult to triage, leading to both missed diagnoses and unnecessary surgeries. Springer, Masica, and Dal Molin et al. developed a machine-learning method that integrates high-dimensional clinical, imaging, and molecular data to diagnose and determine the likely best course of action for patients with pancreatic cysts: discharge and no follow-up, discharge and routine monitoring, or surgery. The test, tuned to avoid discharging patients with potential malignancies, outperformed the current standard of care in managing patients in all groups, demonstrating its potential for both clinicians and patients. Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.

[1]  F. Real,et al.  European evidence-based guidelines on pancreatic cystic neoplasms , 2018 .

[2]  B. Enestvedt,et al.  ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts , 2018, The American Journal of Gastroenterology.

[3]  K. Kinzler,et al.  Detection of aneuploidy in patients with cancer through amplification of long interspersed nucleotide elements (LINEs) , 2018, Proceedings of the National Academy of Sciences.

[4]  Jin‐Young Jang,et al.  of the pancreas , 2017 .

[5]  M. Radovich,et al.  Pancreatic Cyst Fluid Vascular Endothelial Growth Factor A and Carcinoembryonic Antigen: A Highly Accurate Test for the Diagnosis of Serous Cystic Neoplasm. , 2017, Journal of the American College of Surgeons.

[6]  M. Makary,et al.  Patients with a resected pancreatic mucinous cystic neoplasm have a better prognosis than patients with an intraductal papillary mucinous neoplasm: A large single institution series. , 2017, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.].

[7]  Young Joon Ahn,et al.  A novel approach for selecting combination clinical markers of pathology applied to a large retrospective cohort of surgically resected pancreatic cysts , 2017, J. Am. Medical Informatics Assoc..

[8]  S. Chari,et al.  Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis , 2016, Gut.

[9]  A. Iafrate,et al.  Impact of next-generation sequencing on the clinical diagnosis of pancreatic cysts. , 2016, Gastrointestinal endoscopy.

[10]  A. Krasinskas,et al.  A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas , 2015, The American journal of surgical pathology.

[11]  Jin-Young Jang,et al.  A combination of molecular markers and clinical features improve the classification of pancreatic cysts. , 2015, Gastroenterology.

[12]  K. Lillemoe,et al.  Effects of Comorbidities on Outcomes of Patients With Intraductal Papillary Mucinous Neoplasms. , 2015, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[13]  Robert A. Moran,et al.  Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas) , 2015, Gut.

[14]  P. Moayyedi,et al.  American gastroenterological association technical review on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. , 2015, Gastroenterology.

[15]  K. Kinzler,et al.  Complement c5a receptor facilitates cancer metastasis by altering T-cell responses in the metastatic niche. , 2014, Cancer research.

[16]  Susan Hutfless,et al.  Role of a Multidisciplinary Clinic in the Management of Patients with Pancreatic Cysts: A Single-Center Cohort Study , 2014, Annals of Surgical Oncology.

[17]  Narasimhan P. Agaram,et al.  Vascular endothelial growth factor, a novel and highly accurate pancreatic fluid biomarker for serous pancreatic cysts. , 2014, Journal of the American College of Surgeons.

[18]  Elliot K Fishman,et al.  A Systematic Review of Solid-Pseudopapillary Neoplasms: Are These Rare Lesions? , 2014, Pancreas.

[19]  K. Lillemoe,et al.  Branch Duct Intraductal Papillary Mucinous Neoplasms: Does Cyst Size Change the Tip of the Scale? A Critical Analysis of the Revised International Consensus Guidelines in a Large Single-Institutional Series , 2013, Annals of surgery.

[20]  H. Friess,et al.  European experts consensus statement on cystic tumours of the pancreas. , 2013, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[21]  R. Karchin,et al.  Collections of simultaneously altered genes as biomarkers of cancer cell drug response. , 2013, Cancer research.

[22]  K. Kinzler,et al.  Evaluation of DNA from the Papanicolaou Test to Detect Ovarian and Endometrial Cancers , 2013, Science Translational Medicine.

[23]  N. Valsangkar,et al.  851 resected cystic tumors of the pancreas: a 33-year experience at the Massachusetts General Hospital. , 2012, Surgery.

[24]  K. Kinzler,et al.  FAST-SeqS: A Simple and Efficient Method for the Detection of Aneuploidy by Massively Parallel Sequencing , 2012, PloS one.

[25]  Richard S. Kwon,et al.  Comparison of surgical and endoscopic sample collection for pancreatic cyst fluid biomarker identification. , 2012, Journal of proteome research.

[26]  Masao Tanaka,et al.  Multicenter Study of Serous Cystic Neoplasm of the Japan Pancreas Society , 2012, Pancreas.

[27]  D. Gouma,et al.  Impact of nationwide centralization of pancreaticoduodenectomy on hospital mortality , 2012, The British journal of surgery.

[28]  A. Maitra,et al.  Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways , 2011, Proceedings of the National Academy of Sciences.

[29]  R. Karchin,et al.  Correlation of somatic mutation and expression identifies genes important in human glioblastoma progression and survival. , 2011, Cancer research.

[30]  P. Fockens,et al.  Endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions provides inadequate material for cytology and laboratory analysis: initial results from a prospective study. , 2011, Endoscopy.

[31]  K. Kinzler,et al.  Detection and quantification of rare mutations with massively parallel sequencing , 2011, Proceedings of the National Academy of Sciences.

[32]  R. Hruban,et al.  Cystic precursors to invasive pancreatic cancer , 2011, Nature Reviews Gastroenterology &Hepatology.

[33]  N. Rofsky,et al.  Prevalence of Incidental Pancreatic Cysts in the Adult Population on MR Imaging , 2010, The American Journal of Gastroenterology.

[34]  F. Bosman,et al.  WHO Classification of Tumours of the Digestive System , 2010 .

[35]  K. Horton,et al.  Prevalence of unsuspected pancreatic cysts on MDCT. , 2008, AJR. American journal of roentgenology.

[36]  G. Klöppel,et al.  Pancreatic ductal adenocarcinomas with cystic features: neither rare nor uniform , 2005, Modern Pathology.

[37]  Elizabeth Lee-Lewandrowski,et al.  Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. , 2004, Gastroenterology.

[38]  Karen A. F. Copeland.  An Introduction to Categorical Data Analysis , 1997 .

[39]  E. Suchman,et al.  The American Soldier: Adjustment During Army Life. , 1949 .

[40]  E. Suchman,et al.  The American soldier: Adjustment during army life. (Studies in social psychology in World War II), Vol. 1 , 1949 .