Culp, Stacey

INTRODUCTION: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations. METHODS: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight. RESULTS: Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471). DISCUSSION: Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.

Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65–75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

Drivers of the inflammatory response in acute pancreatitis remain incompletely understood. Unsaturated fatty acids, specifically palmitoleic, appear to have an association with more severe acute pancreatitis. This finding presents a new clinical understanding of fatty acid toxicity and highlights a potential future target for treatment in severe acute pancreatitis.