Biomarkers of Chronic Pancreatitis: A systematic literature review.

Hanno Steen, Darwin L Conwell, Mark Topazian, Jo Ann S Rinaudo, Jose Serrano, Liang Li, Savi Appana, Santhi Swaroop Vege, Natasha Kanwar, Vincent Anani, Zobeida Cruz-Monserrate, Stephen Pandol, Richard T Waldron, Dhiraj Yadav, David C Whitcomb, Christopher Forsmark, Phil A Hart, Valentina Pita, Kristyn Gumpper

Journal: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2021;21(2):323-333

PMID: 33558189

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Abstract

BACKGROUND

Chronic pancreatitis (CP) does not have diagnostic or prognostic biomarkers. CP is the end stage of a progressive inflammatory syndrome that is diagnosed at late stages by morphologic features. To diagnose earlier stages of the disease, a new mechanistic definition was established based on identifying underlying pathogenic processes and biomarker evidence of disease activity and stage. Although multiple risk factors are known, the corresponding biomarkers needed to make a highly accurate diagnosis of earlier disease stages have not been established. The goal of this study is to systematically analyze the literature to identify the most likely candidates for development into biomarkers of CP.

METHODS

We conducted a systematic review of candidate analytes from easily accessible biological fluids and identified 67 studies that compared CP to nonpancreatic-disease controls. We then ranked candidate biomarkers for sensitivity and specificity by area under the receiver operator curves (AUROCs).

RESULTS

Five biomarkers had a large effect size (an AUROC > 0.96), whereas 30 biomarkers had a moderate effect size (an AUROC between 0.96 and 0.83) for distinguishing CP cases from controls or other diseases. However, the studies reviewed had marked variability in design, enrollment criteria, and biospecimen sample handling and collection.

CONCLUSIONS

Several biomarkers have the potential for evaluation in prospective cohort studies and should be correlated with risk factors, clinical features, imaging studies and outcomes. The Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreas Cancer provides recommendations for avoiding design biases and heterogeneity in sample collection and handling in future studies.

Address: Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA; The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: [email protected].; Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA; The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.; Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA.; University of Florida, Gainesville, FL, USA.; University of Pittsburgh, Pittsburgh, PA, USA.; Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Pathology, Boston Children's Hospital, Boston, MA, USA; Departments of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.; The Mayo Clinic, Rochester, MN, USA.; The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Division of Digestive Diseases and Nutrition, National Institutes of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.; Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.

DOI: 10.1016/j.pan.2021.01.006

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MeSH Terms: Biomarkers, Humans, Pancreatitis, Chronic