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; The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Pancreatology. 2021 Mar;21(2):323-333. doi: 10.1016/j.pan.2021.01.006. Epub 2021 Jan 22.
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.
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).
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.
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.
慢性胰腺炎(CP)目前尚无诊断或预后的生物标志物。CP 是一种进行性炎症综合征的终末期表现,其形态学特征在晚期才能确诊。为了更早地诊断这种疾病,人们基于潜在的发病机制、疾病活动和分期的生物标志物证据,建立了一种新的机械性定义。尽管已知有多种危险因素,但仍缺乏用于高度准确诊断早期疾病阶段的相应生物标志物。本研究旨在系统地分析文献,以确定最有可能发展为 CP 生物标志物的候选物。
我们对来自易获取的生物体液的候选分析物进行了系统的文献回顾,并确定了 67 项将 CP 与非胰腺疾病对照组进行比较的研究。然后,我们根据接收者操作特征曲线(AUROCs)下的面积来对候选生物标志物的敏感性和特异性进行排名。
有 5 种生物标志物的效应量较大(AUROC>0.96),而 30 种生物标志物的效应量中等(AUROC 在 0.96 到 0.83 之间),可用于区分 CP 病例与对照组或其他疾病。然而,所回顾的研究在设计、入组标准以及生物样本处理和采集方面存在显著差异。
有几种生物标志物具有在前瞻性队列研究中进行评估的潜力,并且应该与危险因素、临床特征、影像学研究和结局相关联。慢性胰腺炎、糖尿病和胰腺癌症研究联合会(Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreas Cancer)提出了一些建议,以避免在未来的研究中出现设计偏差和样本采集与处理的异质性。