TY - JOUR
T1 - Low serum trypsinogen levels in chronic pancreatitis
T2 - Correlation with parenchymal loss, exocrine pancreatic insufficiency, and diabetes but not CT-based cambridge severity scores for fibrosis
AU - for the North American Pancreatic Study Group (NAPS2)
AU - Zhan, Wei
AU - Akshintala, Venkata
AU - Greer, Phil J.
AU - Greer, Julia B.
AU - Alkaade, Samer
AU - Anderson, Michelle A.
AU - Muniraj, Thiruvengadam
AU - Papachristou, Georgios I.
AU - Sandhu, Bimaljit S.
AU - Slivka, Adam
AU - Wilcox, C. Mel
AU - Bellin, Melena D.
AU - Singh, Vikesh K.
AU - Yadav, Dhiraj
AU - Brand, Randall E.
AU - Whitcomb, David C.
N1 - Funding Information:
This research was partly supported by the China Scholarship Council (WZ), NIH DK061451 (D.C.W.), DK077906 (D.Y.), U01 DK108306 (D.C.W. and D.Y.), and UL1TR000005 . The authors recognize the outstanding laboratory coordination and testing by Kimberly Stello, Danielle Dwyer and Nicole L. Komara. An abstract of the initial analysis was presented at the American Pancreatic Association annual meeting, November 2015.
Publisher Copyright:
© 2020
PY - 2020/10
Y1 - 2020/10
N2 - Background: Chronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas affecting acinar cells, duct cells, islet cells and inflammatory cells including fibrosis-producing stellate cells. Serum trypsinogen is a biomarkers of acinar cell function. Aim: To define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP. Methods: Serum samples from previously ascertained and well phenotyped case and control subjects from the North American Pancreatitis Study II (NAPS2) were used to measure serum trypsinogen levels in a commercial laboratory. Control samples were used to define normal ranges and compared with levels in CP patients with defined features. Results: A final cohort of 279 CP patients and 262 controls from the NAPS2 studies were evaluated. In controls trypsinogen had a mean of 34.96 ng/ml and SD = 11.99. Cut-off values for low trypsinogen ranged from <20 to 10 ng/ml and very low trypsinogen at <10 ng/ml. Compared to controls, CP was associated with very low trypsinogen levels (p < 0.0001). Within CP, very low trypsinogen levels correlated with parenchymal loss (pancreatic surgery [p < 0.05]; atrophy with calcifications, [p < 0.001]), EPI (p < 0.01, trend p < 0.001) and diabetes (trend p < 0.01) but not CT-based criteria for fibrosis (pancreatic duct dilation, irregularity, strictures). Conclusions: Very low serum trypsinogen levels correlate with measures of acinar cell loss including surgical resection, atrophic-calcific CP, diabetes and functional symptoms EPI but not duct morphology criteria. Serum trypsinogen levels correlate with decreased acinar cell function and therefore have biomarker utility clinical management.
AB - Background: Chronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas affecting acinar cells, duct cells, islet cells and inflammatory cells including fibrosis-producing stellate cells. Serum trypsinogen is a biomarkers of acinar cell function. Aim: To define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP. Methods: Serum samples from previously ascertained and well phenotyped case and control subjects from the North American Pancreatitis Study II (NAPS2) were used to measure serum trypsinogen levels in a commercial laboratory. Control samples were used to define normal ranges and compared with levels in CP patients with defined features. Results: A final cohort of 279 CP patients and 262 controls from the NAPS2 studies were evaluated. In controls trypsinogen had a mean of 34.96 ng/ml and SD = 11.99. Cut-off values for low trypsinogen ranged from <20 to 10 ng/ml and very low trypsinogen at <10 ng/ml. Compared to controls, CP was associated with very low trypsinogen levels (p < 0.0001). Within CP, very low trypsinogen levels correlated with parenchymal loss (pancreatic surgery [p < 0.05]; atrophy with calcifications, [p < 0.001]), EPI (p < 0.01, trend p < 0.001) and diabetes (trend p < 0.01) but not CT-based criteria for fibrosis (pancreatic duct dilation, irregularity, strictures). Conclusions: Very low serum trypsinogen levels correlate with measures of acinar cell loss including surgical resection, atrophic-calcific CP, diabetes and functional symptoms EPI but not duct morphology criteria. Serum trypsinogen levels correlate with decreased acinar cell function and therefore have biomarker utility clinical management.
KW - Malnutrition
KW - Pancreatic acinar cell
KW - Pancreatic beta cell
KW - Pancreatic stellate cell
KW - Pathologic calcification
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U2 - 10.1016/j.pan.2020.08.025
DO - 10.1016/j.pan.2020.08.025
M3 - Article
C2 - 32967795
AN - SCOPUS:85091206227
VL - 20
SP - 1368
EP - 1378
JO - Pancreatology
JF - Pancreatology
SN - 1424-3903
IS - 7
ER -