Protein biomarkers in pancreatic juice and serum for identification of pancreatic cancer.

BACKGROUND AND AIMS: To date, surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) has not lived up to expectations, as identification of curable stages through imaging remains challenging. Biomarkers are therefore needed. Pancreatic juice (PJ) may be a promising source, because it is in direct contact with the ductal epithelial lining from which PDAC arises. We aimed to develop a panel of biomarkers from serum and PJ to detect PDAC for future surveillance purposes. METHODS: All patients who underwent PJ collection on secretin stimulation at the Erasmus MC were included. Both PJ and serum were evaluated. Protein levels were determined by the Lowry assay. Potential biomarkers (interleukin-8, interferon-γ, neutrophil gelatinase-associated lipocalin [NGAL], mucin 5, subtype AC [MUC5AC], mucin 2, phospholipase A2 group IB) were selected based on previously reported outcomes and assessed with enzyme-linked immunosorbent assay. Serum carbohydrate antigen 19-9 (CA19-9) values were determined by electrochemiluminescence immunoassay. RESULTS: This study included 59 cases and 126 surveilled control subjects (who underwent PJ collection), of whom 71 had a hereditary predisposition (35 genetic, 36 familial) and 55 had (suspected neoplastic) pancreatic cysts. CA19-9 values were available for 53 cases and 48 control subjects. Serum CA19-9, as well as PJ interleukin-8, NGAL and MUC5AC, were associated with PDAC independent of age, gender, and presence of diabetes mellitus. Serum CA19-9 had a significantly higher area under the curve (AUC; .86; 95% confidence interval [CI], .79-.94) than individual PJ markers (AUC, .62-.70). A combination of PJ markers and serum CA19-9 (panel 2: sensitivity 42% [95% CI, 29-57] and specificity 96% [95% CI, 86-100]) did not improve diagnostic performance compared with CA19-9 alone (sensitivity 70% [95% CI, 56-82] and specificity 85% [95% CI, 72-94]). CONCLUSIONS: High levels of serum CA19-9 and PJ-derived proteins are associated with PDAC. Prospective surveillance studies including individuals at risk of developing PDAC are required to validate these findings.

Extracellular vesicle-derived microRNAs in pancreatic juice as biomarkers for detection of pancreatic ductal adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in an advanced stage, with minimal likelihood of long-term survival. Only a small subset of patients are diagnosed with early (T1) disease. Early detection is challenging due to the late onset of symptoms and limited visibility of sub-centimeter cancers on imaging. A novel approach is to support the clinical diagnosis with molecular markers. MicroRNA derived from extracellular vehicles (EVs) in blood has shown promise as a potential biomarker for pancreatic neoplasia, but microRNA derived from pancreatic juice (PJ) may be a more sensitive biomarker, given that is in close contact with ductal cells from which PDAC arises. This study aims to evaluate and compare the performance of PJ- and serum-derived EV-miRNA for the detection of PDAC. METHODS: PJ was collected from the duodenum during EUS after secretin stimulation from 54 patients with PDAC and 118 non-malignant controls. Serum was available for a subset of these individuals. MiR-16, miR-21, miR-25, miR-155 and miR-210 derived from EVs isolated from PJ and serum were analyzed by qPCR, and serum CA19-9 levels were determined by electrochemiluminescence immunoassay. For statistical analysis, either a Mann-Whitney U test or a Wilcoxon Signed Rank test was performed. ROC curves and AUC were used to assess the sensitivity and specificity of miR expression for PDAC detection. RESULTS: Expression of EV-miR-21, EV-miR-25 and EV-miR-16 were increased in cases vs controls in PJ, while only EV-miR-210 was increased in serum. The potential to detect PC was good for a combination of PJ EV-miR-21, EV-miR-25, EV-miR-16 and serum miR-210, CA-19-9, with an area under the curve of 0.91, a specificity of 84.2% and a sensitivity of 81.5%. CONCLUSION: Detection of miRNA from EVs in PJ is feasible. A combined panel of PJ EV-miR-21, EV-miR-25, EV-miR-16, and serum EV-miR-210 and CA19-9 distinguishes cases with PDAC from controls undergoing surveillance with a specificity of 81.5% and sensitivity of 84.2%.

Timing of Ureteric Stent Removal and Occurrence of Urological Complications after Kidney Transplantation: A Systematic Review and Meta-Analysis.

Implanting a ureteric stent during ureteroneocystostomy reduces the risk of leakage and ureteral stenosis after kidney transplantation (KTx), but it may also predispose to urinary tract infections (UTIs). The aim of this study is to determine the optimal timing for ureteric stent removal after KTx. Searches were performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL, Web of Science, and Google Scholar (until November 2017). For this systematic review, all aspects of the Cochrane Handbook for Interventional Systematic Reviews were followed and it was written based on the PRISMA-statement. Articles discussing JJ-stents (double-J stents) and their time of removal in relation to outcomes, UTIs, urinary leakage, ureteral stenosis or reintervention were included. One-thousand-and-forty-three articles were identified, of which fourteen articles (three randomised controlled trials, nine retrospective cohort studies, and two prospective cohort studies) were included (describing in total n = 3612 patients). Meta-analysis using random effect models showed a significant reduction of UTIs when stents were removed earlier than three weeks (OR 0.49, CI 95%, 0.33 to 0.75, p = 0.0009). Regarding incidence of urinary leakage, there was no significant difference between early (<3 weeks) and late stent removal (>3 weeks) (OR 0.60, CI 95%, 0.29 to 1.23, p = 0.16). Based on our results, earlier stent removal (<3 weeks) was associated with a decreased incidence of UTIs and did not show a higher incidence of urinary leakage compared to later removal (>3 weeks). We recommend that the routine removal of ureteric stents implanted during KTx should be performed around three weeks post-operatively.