Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Abstract

Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5–9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.

The tumor‐to‐liver ratio of the standardized uptake value is a useful FDG‐PET/CT parameter for predicting malignant intraductal papillary mucinous neoplasm of the pancreas

“…In the Fukuoka guideline 2017, an increased serum CA 19‐9 level is one of the “worrisome features” suggesting malignancy. The sensitivity of both CA19‐9 and CEA for IPMA degeneration is reported to be high, around 90%, but their specificity is not high, around 40% and 6.1%, respectively 16 . In the present study, both CA19‐9 and CEA were not significantly suggestive of malignancy in univariate analysis, which may be due to the small number of cases in the present study and the low specificity.…”

“…The sensitivity of both CA19-9 and CEA for IPMA degeneration is reported to be high, around 90%, but their specificity is not high, around 40% and 6.1%, respectively. 16 In the present study, both CA19-9 and CEA were not significantly suggestive of malignancy in univariate analysis, which may be due to the small number of cases in the present Abbreviations: BMI, body mass index; CAR, CRP-albumin ratio; HGD, high grade dysplasia; HRS, high risk stigmata; IPMA, intraductal papillary mucinous adenoma; IPMC, intraductal papillary mucinous carcinoma; NLR, neutrophil-to-lymphocyte ratio; SUVmax, maximum standardized uptake value; TBR, tumor-to-blood pool ratio of the SUV; TLR, tumor-to-liver ratio of the SUV.…”

Insight of pancreatic cancer: recommendations for improving its therapeutic efficacy in the next decade

“…[8] Recent studies have identified several predictive markers obtained from non/mini-invasive methods have a promising role in screening for IPMNs, such as CA19-9, CEA, circulating microvesicles, MUC5AC, and several long noncoding RNA (lncRNAs). [13][14][15] The rise of machine learning, which is the interplay between artificial intelligence and large datasets, generates a more accurate model of pancreatic cancer's genesis and development, which can analyze large-scale data from different settings and combine them into explorations for pancreatic cancer's etiology. [16] Rech et al used the lncRNA myeloid regulator Morrbid and unbiased random forest machine learning to build unique, contextual signatures for each therapeutic component, revealing multiple cellular mechanisms during treatment.…”

“…[8] Recent studies have identified several predictive markers obtained from non/mini-invasive methods have a promising role in screening for IPMNs, such as CA19-9, CEA, circulating microvesicles, MUC5AC, and several long noncoding RNA (lncRNAs). [13-15]…”

Translational, Precision, and Personalized Medicine in Gastroenterology

“…However, duodenocephalopancreatectomy is not a simple procedure and is associated with significant mortality and morbidity rates, as well as a marked reduction in quality of life. For this reason, it is essential to identify the risk factors associated with cancer in order to only perform this procedure in individuals at highest risk [ 9 ]. Outside of oncology, two other major chapters have sparked a revolution in gastroenterology in recent decades: biological drugs and the interaction of the microbiota in inflammatory bowel disease.…”