Pancreas Program - Research

Research and Selected Publications

Acute Pancreatitis

  • Develop and implement clinical decision support tools to increase adherence to accepted clinical best practices, improve clinical outcomes and lower hospitalization costs for patients.
  • Quantify and reduce the risk and severity of acute pancreatitis due to the procedure endoscopic retrograde cholangio-pancreatography (ERCP) through patient selection, pharmacologic therapy, hydration and prophylactic pancreatic duct stenting.
  • Investigate molecular mechanisms of pancreatic injury, healing and/or pancreatic cancer (e.g. ADAM17, Hedgehog signaling) that may translate to future clinical treatment targets

Research Studies (selected publications)

  • Vege SS, DiMagno MJ, Forsmark CE, Martel M, Barkun AN. Initial medical treatment of acute pancreatitis: AGA Institute Technical Review. Gastroenterology 2018;154:1103–1139.
  • Schulman AR, Abougergi MS, Thompson CC. Assessment of the July effect in post-endoscopic retrograde cholangiopancreatography pancreatitis: Nationwide inpatient sample. World J Gastrointest Endosc 2017;9:296-303.
  • Kubiliun NM, Adams MA, Akshintala VS, et al. Evaluation of pharmacologic prevention of pancreatitis after endoscopic retrograde cholangiopancreatography: A systematic review. Clin Gastroenterol Hepatol 2015;13:1231-1239.
  • DiMagno MJ, Wamsteker EJ, Rizk RS, Spaete JP, Gupta S, Sahay T, Costanzo J, Napolitano LM, Hyzy RC, Desmond JS. A combined paging alert and web-based instrument alters clinician behavior and shortens hospital stay. Am J Gastroenterol 2014;109:306-315.
  • DiMagno MJ, Wamsteker EJ, Rai J, Rivera MA, Spaete JP, Elmunzer BJ, Saini SD: Do larger periprocedural fluid volumes reduce the severity of post-ERCP pancreatitis? Pancreas 2014;434:642-647. PMCID: PMC4024358
  • DiMagno MJ, Spaete J, Ballard DD, Wamsteker EJ, Saini SD: Risk models for post-ERCP pancreatitis (PEP). Smoking and chronic liver disease as predictors of protection against PEP. Pancreas 2013;42(6):996-1003. PMCID: PMC3701741
  • Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012;366:1414-22
  • DeBenedet AT, Raghunathan TE, Wing JJ, Wamsteker EJ, DiMagno MJ: Alcohol use and cigarette smoking as risk factors for post-endoscopic retrograde cholangiopancreatography pancreatitis. Clin Gastroenterol Hepatol 2009;7:353-358.

Translational Studies (selected publications)

  • Park MJ, Iyer S, Xue X, Cunha JB, Gu S, Moons D, Pipe SW, Williams JA, Simeone DM, Shah YM, Omary MB. HIF1-alpha regulates acinar cell function and response to injury in mouse pancreas. Gastroenterology 2018;154:1630-1634.e3.
  • Halbrook CJ, Wen HJ, Ruggeri JM, Takeuchi KK, Zhang Y, di Magliano MP, Crawford HC: Mitogen-activated protein kinase kinase activity maintains acinar-to-ductal metaplasia and is required for organ regeneration in pancreatitis. Cell Mol Gastroenterol Hepatol 2017;3:99-118.
  • Chen X, Sans MD, Strahler JR, Karnovsky A, Ernst SA, Michailidis G, Andrews PC, Williams JA. Quantitative organellar proteomics analysis of rough endoplasmic reticulum from normal and acute pancreatitis rat pancreas. J Proteome Res 2010;9:885-896.
  • DiMagno MJ, Lee SH, Owyang C, Zhou SY: Inhibition of acinar apoptosis occurs during acute pancreatitis in the human homologue DeltaF508 cystic fibrosis mouse. Am J Physiol Gastrointest Liver Physiol 2010;299:G400-G412. PMCID: PMC2928535
  • DiMagno MJ, Lee SH, Hao Y, Zhou SY, McKenna BJ, Owyang C: A proinflammatory, antiapoptotic phenotype underlies the susceptibility to acute pancreatitis in cystic fibrosis transmembrane regulator (-/-) mice. Gastroenterology 2005;129:665-681.
  • DiMagno MJ, Williams JA, Hao Y, Ernst SA, Owyang C: Endothelial nitric oxide synthase is protective in the initiation of caerulein-induced acute pancreatitis in mice. Am J Physiol Gastrointest Liver Physiol 2004;287:G80-87.
  • Kubisch C, DiMagno MJ, Tietz AB, Welsh MJ, Ernst SA, Brandt-Nedelev B, Diebold J, Wagner AC, Goke B, Williams JA, Schäfer C. Overexpression of heat shock protein Hsp27 protects against cerulein-induced pancreatitis. Gastroenterology 2004;127:275-286.
  • Sans MD, DiMagno MJ, D'Alecy LG, Williams JA: Caerulein-induced acute pancreatitis inhibits protein synthesis through effects on eIF2B and eIF4F. Am J Physiol Gastrointest Liver Physiol 2003;285:G517-528.

Chronic Pancreatitis

  • Measure and identify specific factors that influence quality of life
  • Characterize pain pattern and identify predictors for reducing abdominal pain in response to medical, endoscopic and surgical interventions
  • Improve the clinical application of endoscopic ultrasonography, direct pancreatic function testing and biomarkers to establishing a firm diagnosis of chronic pancreatitis

Research Studies (selected publications)

  • Lee AA, Baker JRB, Wamsteker EJ, Saad, R, DiMagno MJ. Small intestinal bacterial overgrowth is common in chronic pancreatitis (CP) and associates with diabetes, CP severity, low zinc levels and opiate use. Am J Gastroenterol 2019 Apr 16. 
  • Machicado JD, Amann ST, Anderson MA, et al. Quality of life in chronic pancreatitis is determined by constant pain, disability/unemployment, current smoking, and associated co-morbidities. Am J Gastroenterol 2017;112:633-642
  • Reddy N, Nangia S, DiMagno MJ: The Chronic Pancreatitis International Classification of Diseases, Ninth Revision, Clinical Modification code 577.1 is inaccurate compared with criterion-standard clinical diagnostic scoring systems. Pancreas 2016;45:1276–1281. PMCID: PMC5021551
  • Kwon RS, Young BE, Marsteller WF, et al. Narcotic independence after pancreatic duct stenting predicts narcotic Independence after lateral pancreaticojejunostomy for chronic pancreatitis. Pancreas 2016;45:1126-1130.
  • Lapp RT, Wolf JS, Jr., Faerber GJ, et al. Duct diameter and size of stones predict successful extracorporeal shock wave lithotripsy and endoscopic clearance in patients with chronic pancreatitis and pancreaticolithiasis. Pancreas 2016;45:1208-1211.
  • Wilcox CM, Yadav D, Ye T, et al. Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings. Clin Gastroenterol Hepatol 2015;13:552-560
  • D'Souza SL, Anderson MA, Korsnes SJ, et al. EUS Diagnostic criteria for chronic pancreatitis: A comparison of conventional versus Rosemont Criteria. Dig Dis Sci 2015;60:3782-3787.
  • Law R, Lopez R, Costanzo A, et al. Endoscopic pancreatic function test using combined secretin and cholecystokinin stimulation for the evaluation of chronic pancreatitis. Gastrointest Endosc 2012;75:764-768.
  • Law R, Parsi M, Lopez R, et al. Cigarette smoking is independently associated with chronic pancreatitis. Pancreatology 2010;10:54-59.
  • Owyang C, Scarpello JH, Vinik AI. Correlation between pancreatic enzyme secretion and plasma concentration of human pancreatic polypeptide in health and in chronic pancreatitis. Gastroenterology 1982;83:55-62
  • Kawanishi H, Sell JE, Pollard HM. Combined endoscopic pancreatic fluid collection and retrograde pancreatography in the diagnosis of pancreatic cancer and chronic pancreatitis. Gastrointest Endosc 1975;22:82-85.

Translational Studies (selected publications)

  • Elenbaas JS, Bragazzi Cunha J, Azuero-Dajud R, Nelson B, Oral EA, Williams JA, Stewart CL, Omary MB: Lamin A/C maintains exocrine pancreas homeostasis by regulating stability of RB and activity of E2F. Gastroenterology 2018;154:1625-1629.e8.

Autoimmune Pancreatis

  • Determine the most effective medical treatment
  • Identify prognostic markers to disease progression and risk for cancer

Research Studies (selected publications)

  • Bi Y, Hart PA, Law R, et al. Obstructive jaundice in autoimmune pancreatitis can be safely treated with corticosteroids alone without biliary stenting. Pancreatology 2016;16:391-396.
  • Ngwa T, Law R, Hart P, et al. Serum IgG4 elevation in pancreatic cancer: diagnostic and prognostic significance and association with autoimmune pancreatitis. Pancreas 2015;44:557-560.
  • Hart PA, Law RJ, Dierkhising RA, et al. Risk of cancer in autoimmune pancreatitis: a case-control study and review of the literature. Pancreas 2014;43:417-421.
  • Yurci A, Stevens T, Shah SN, et al. Evolution in the diagnosis and treatment of autoimmune pancreatitis: experience from a single tertiary care center. Int J Clin Exp Pathol 2013;6:1317-1326.

Hereditary Pancreatitis

  • Determine cancer risk in hereditary pancreatitis and other familial pancreatic cancer conditions
  • Develop a patient registry and establish a prospective protocol
  • Identify biomarkers for early diagnosis of pancreatic cancer in this high-risk population

Research Studies (selected publications)

  • Roberts NJ, Norris AL, Petersen GM, Bondy ML, Brand R, Gallinger S, Kurtz RC, Olson SH, Rustgi AK, Schwartz AG, Stoffel E, et al. Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer. Cancer Discov 2016;6:166-175.
  • Kastrinos F, Mukherjee B, Tayob N, Wang F, Sparr J, Raymond VM, Bandipalliam P, Stoffel EM, Gruber SB, Syngal S. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009;302:1790-1795.

Exocrine Pancreatic Insufficiency

  • Determine the effectiveness of pancreatic enzyme replacement therapy and important cofactors necessary for correcting exocrine pancreatic insufficiency
  • Investigate the utility of direct pancreatic function testing in chronic pancreatitis.
  • Understand regulation of pancreatic digestive function in health and disease mediated by calcium, insulin, nitric oxide and neural signaling.
  • Explore dietary approaches to pancreatic regeneration to achieve an adequate supply of pancreatic digestive enzymes

Research Studies (selected publications)

  • Law R, Lopez R, Costanzo A, et al. Endoscopic pancreatic function test using combined secretin and cholecystokinin stimulation for the evaluation of chronic pancreatitis. Gastrointest Endosc 2012;75:764-768.
  • Taylor JR, Gardner TB, Waljee AK, DiMagno MJ, Schoenfeld PS: Systematic review: efficacy and safety of pancreatic enzyme supplements for exocrine pancreatic insufficiency. Aliment Pharmacol Ther 2010;31:57-72.
  • Waljee AK, DiMagno MJ, Wu BU, Schoenfeld PS, Conwell DL: Systematic review: pancreatic enzyme treatment of malabsorption associated with chronic pancreatitis. Aliment Pharmacol Ther 2009;29:235-246. PMCID: PMC3462488
  • Reddy RC, Hao Y, Lee SH, Gangireddy SR, Owyang C, DiMagno MJ: Pioglitazone reverses insulin resistance and impaired CCK-stimulated pancreatic secretion in eNOS(-/-) mice: therapy for exocrine pancreatic disorders? Am J Physiol Gastrointest Liver Physiol 2007;293:G112-G120.
  • DiMagno MJ, Hao Y, Tsunoda Y, Williams JA, Owyang C: Secretagogue stimulated pancreatic secretion is differentially regulated by constitutive NOS isoforms in mice. Am J Physiol Gastrointest Liver Physiol 2004;286:G428-G436.
  • Owyang C, Louie DS, Tatum D. Feedback regulation of pancreatic enzyme secretion. Suppression of cholecystokinin release by trypsin. J Clin Invest 1986;77:2042-2047.
  • Owyang C, May D, Louie DS. Trypsin suppression of pancreatic enzyme secretion. Differential effect on cholecystokinin release and the enteropancreatic reflex. Gastroenterology 1986;91:637-643.
  • Pollard HM, Miller L, Brewer WA. The external secretion of the pancreas and diabetes mellitus. Am J Dig Dis 1943;10:20-23.

Cystic Fibrosis

  • Clarify mechanisms for pancreatitis associated with cystic fibrosis transmembrane regulator (CFTR) mutations
  • Recognize the impact of CFTR genotype on pancreatic digestive function

Research Studies (selected publications)

  • LaRusch J, Jung J, General IJ, Lewis MD, Park HW, Brand RE, Gelrud A, Anderson MA, Banks PA, Conwell D, et al.: Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis. PLoS Genet 2014;10:e1004376.
  • DiMagno MJ, DiMagno EP: Pancreas divisum does not cause pancreatitis, but associates with CFTR mutations. Am J Gastroenterol 2012;107:318-320.

Translational Studies (selected publications)

  • Radtke AL, Anderson KL, Davis MJ, DiMagno MJ, Swanson JA, O'Riordan MX: Listeria monocytogenes exploits cystic fibrosis transmembrane conductance regulator (CFTR) to escape the phagosome. Proc Natl Acad Sci U S A 2011;108:1633-1638. PMCID: PMC3029685
  • DiMagno MJ, Lee SH, Owyang C, Zhou SY: Inhibition of acinar apoptosis occurs during acute pancreatitis in the human homologue DeltaF508 cystic fibrosis mouse. Am J Physiol Gastrointest Liver Physiol 2010;299:G400-412. PMCID: PMC2928535
  • DiMagno MJ, Lee SH, Hao Y, Zhou SY, McKenna BJ, Owyang C: A proinflammatory, antiapoptotic phenotype underlies the susceptibility to acute pancreatitis in cystic fibrosis transmembrane regulator (-/-) mice. Gastroenterology 2005;129:665-681.

Pancreatic Cysts

  • Delineate the natural history of pancreatic cysts
  • Identify risk factors for malignant pancreatic cysts
  • Identify imaging and biomarker predictors for evolution of cystic tumors to cancer.
  • Develop a clinical decision tool for patients and clinicians

Research Studies (selected publications)

  • Scheiman JM, Hwang JH, Moayyedi P. American Gastroenterological Association technical review on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015;148:824-848.e22.
  • Partyka K, McDonald M, Maupin KA, Brand R, Kwon R, Simeone DM, Allen P, Haab BB: Comparison of surgical and endoscopic sample collection for pancreatic cyst fluid biomarker identification. J Proteome Res 2012;11:2904-2911.
  • Pausawasdi N, Heidt D, Kwon R, Simeone D, Scheiman J: Long-term follow-up of patients with incidentally discovered pancreatic cystic neoplasms evaluated by endoscopic ultrasound. Surgery 2010;147:13-20.
  • Lee CJ, Scheiman J, Anderson MA, Hines OJ, Reber HA, Farrell J, Kochman ML, Foley PJ, Drebin J, Oh YS, et al. Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report. J Gastrointest Surg 2008;12:234-242.

Pancreatic and Ampullary Cancer

Discriminate benign from malignant pancreatic disease using biomarkers and optical imaging

  • Predict pancreatic cancer outcomes based on clinical risk factors (smoking, alcohol,  diabetes)
  • Determine the differential impact of stent type on treatment of malignant biliary obstruction
  • Define and test new metabolic drug targets in pancreatic cancer
  • Understand how signaling pathways predispose to early steps in pancreatic carcinogenesis (e.g. acinar to duct metaplasia, epithelial to mesenchymal transition)
  • Investigate how signaling pathways promote tumor survival, growth and invasion (e.g. involving Usp9x, NRF2 and Hedgehog).

Research Studies (selected publications)

  • Wilson RH, Chandra M, Scheiman JM, et al. Tissue Classification Using Optical Spectroscopy Accurately Differentiates Cancer and Chronic Pancreatitis. Pancreas 2017;46:244-51.Ngwa T, Law R, Hart P, et al. Serum IgG4 elevation in pancreatic cancer: diagnostic and prognostic significance and association with autoimmune pancreatitis. Pancreas 2015;44:557-560
  • Hart PA, Law RJ, Frank RD, et al. Impact of diabetes mellitus on clinical outcomes in patients undergoing surgical resection for pancreatic cancer: a retrospective, cohort study. Am J Gastroenterol 2014;109:1484-1492.
  • Nie S, Yin H, Tan Z, et al. Quantitative analysis of single amino acid variant peptides associated with pancreatic cancer in serum by an isobaric labeling quantitative method. J Proteome Res 2014;13:6058-6066.
  • Hart PA, Law RJ, Dierkhising RA, et al. Risk of cancer in autoimmune pancreatitis: a case-control study and review of the literature. Pancreas 2014;43:417-421.
  • Anderson MA, Zolotarevsky E, Cooper KL, et al. Alcohol and tobacco lower the age of presentation in sporadic pancreatic cancer in a dose-dependent manner: a multicenter study. The American journal of gastroenterology 2012;107:1730-1739.
  • Adams MA, Anderson MA, Myles JD, Khalatbari S, Scheiman JM. Self-expanding metal stents (SEMS) provide superior outcomes compared to plastic stents for pancreatic cancer patients undergoing neoadjuvant therapy. J Gastrointest Oncol 2012;3:309-313.
  • Kawanishi H, Sell JE, Pollard HM. Combined endoscopic pancreatic fluid collection and retrograde pancreatography in the diagnosis of pancreatic cancer and chronic pancreatitis. Gastrointest Endosc 1975;22:82-85.

Translational Studies (selected publications)

  • Halbrook CJ, Pasca di Magliano M, Lyssiotis CA: Tumor Crosstalk networks promote growth and support immune evasion in pancreatic cancer. Am J Physiol Gastrointest Liver Physiol 2018  doi: 10.1152/ajpgi.00416.2017. [Epub ahead of print].
  • Pal A, Dziubinski M, Di Magliano MP, Simeone DM, Owens S, Thomas D, Peterson L, Potu H, Talpaz M, Donato NJ: Usp9x Promotes Survival in Human Pancreatic Cancer and Its Inhibition Suppresses Pancreatic Ductal Adenocarcinoma In Vivo Tumor Growth. Neoplasia 2018, 20:152-164.
  • Chio IIC, Jafarnejad SM, Ponz-Sarvise M, Park Y, Rivera K, Palm W, Wilson J, Sangar V, Hao Y, Ohlund D, et al.: NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer. Cell 2016, 166:963-976.
  • Song Y, Washington MK, Crawford HC: Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer. Cancer Res 2010, 70:2115-2125.
  • Crawford HC, Scoggins CR, Washington MK, Matrisian LM, Leach SD: Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas. J Clin Invest 2002, 109:1437-1444.

Neuroendocrine Tumors

  • Determine the accuracy and cost effectiveness of endoscopic ultrasonography for diagnosing pancreatic neuroendocrine tumors.
  • Investigate the natural history of asymptomatic sporadic and syndromic pancreatic neuroendocrine tumors

Research Studies (selected publications)

  • D'Souza S L, Elmunzer BJ, Scheiman JM: Long-term follow-up of asymptomatic pancreatic neuroendocrine tumors in multiple endocrine neoplasia type I syndrome. J Clin Gastroenterol 2014, 48:458-461
  • Wamsteker EJ, Gauger PG, Thompson NW, Scheiman JM: EUS detection of pancreatic endocrine tumors in asymptomatic patients with type 1 multiple endocrine neoplasia. Gastrointest Endosc 2003, 58:531-535.
  • Gauger PG, Scheiman JM, Wamsteker EJ, Richards ML, Doherty GM, Thompson NW: Role of endoscopic ultrasonography in screening and treatment of pancreatic endocrine tumours in asymptomatic patients with multiple endocrine neoplasia type 1. Br J Surg 2003, 90:748-754.
  • Anderson MA, Carpenter S, Thompson NW, Nostrant TT, Elta GH, Scheiman JM: Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas. Am J Gastroenterol 2000, 95:2271-2277.
  • Bansal R, Tierney W, Carpenter S, Thompson N, Scheiman JM: Cost effectiveness of EUS for preoperative localization of pancreatic endocrine tumors. Gastrointest Endosc 1999;49:19-25.
  • Bansal R, Kochman ML, Bude R, Nostrant TT, Elta GH, Thompson NW, Scheiman JM: Localization of neuroendocrine tumors utilizing linear-array endoscopic ultrasonography. Gastrointest Endosc 1995;42:76-79
  • Thompson NW, Czako PF, Fritts LL, Bude R, Bansal R, Nostrant TT, Scheiman JM: Role of endoscopic ultrasonography in the localization of insulinomas and gastrinomas. Surgery 1994;116:1131-1138.

Publications – PubMed Links