Proper attention to signs and symptoms, especially cholestasis, may help identify patients with pancreatic cancer at an earlier stage. Results also provide a current picture of the semiology of pancreatic cancer which could be of use in studies on the potential of proteomic tests in the early detection of this neoplasm.
Purpose
Non-invasive biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are currently not available. Here, we aimed to identify a set of urine proteins able to distinguish patients with early stage PDAC from healthy individuals (H).
Experimental design
Proteomes of 18 urine samples from healthy controls, chronic pancreatitis and PDAC patients (six/group) were assayed using GeLC/MS/MS analysis. The selected biomarkers were subsequently validated using ELISA assays using multiple logistic regression applied to a training dataset in a multicentre cohort comprising 488 urine samples.
Results
LYVE-1, REG1A and TFF1 were selected as candidate biomarkers. When comparing PDAC (n=192) to healthy (n=87) urines, the resulting areas under the receiver operating characteristic curves (AUCs) of the panel were 0.89 (95%CI 0.84-0.94) in the training (70% of the data), and 0.92 (95%CI 0.86-0.98) in the validation (30% of the data) datasets. When comparing PDAC stage I-II (n=71) to healthy urines, the panel achieved AUCs of 0.90 (95%CI 0.84-0.96) and 0.93 (95%CI 0.84-1.00) in the training and validation datasets, respectively. In PDAC stage I-II and healthy samples with matching plasma CA19.9 the panel achieved a higher AUC of 0.97 (95%CI 0.94-0.99) than CA19.9 (AUC=0.88, 95%CI 0.81-0.95, p=0.005). Adding plasma CA19.9 to the panel increased the AUC from 0.97 (95%CI 0.94-0.99) to 0.99 (95%CI 0.97-1.00, p=0.04) but did not improve the comparison of stage I-IIA PDAC (n=17) to healthy urine.
Conclusion
We have established a novel, three-protein biomarker panel that is able to detect patients with early stage pancreatic cancer in urine specimens.
Background and aims
Knowledge on the etiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a metal previously associated with an increased risk of EPC. We evaluated the association between concentrations of trace elements in toenails and EPC risk.
Methods
The study included 118 EPC cases and 399 hospital controls from Eastern Spain. Levels of twelve trace elements were determined in toenail samples by inductively coupled plasma - mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders, were calculated using logistic regression.
Results
Significantly increased risks of EPC were observed among subjects whose concentrations of cadmium (OR=3.58, 95%CI 1.86–6·88; Ptrend=5×10−6), arsenic (OR=2.02, 95%CI 1.08–3.78; Ptrend=0.009), and lead (OR=6.26, 95%CI 2.71–14.47; Ptrend=3×10−5) were in the highest quartile. High concentrations of selenium (OR=0.05, 95%CI 0.02–0.15; Ptrend=8×10−11) and nickel (OR=0.27, 95%CI 0.12–0.59; Ptrend=2×10−4) were inversely associated with risk of EPC.
Conclusion
We report novel associations of lead, nickel, and selenium toenail concentrations with pancreas cancer risk. Furthermore, results confirm previous associations with cadmium and arsenic. These novel findings, if replicated in independent studies, would point to an important role of trace elements in pancreatic carcinogenesis.
Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.
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