Exosomes as prognostic biomarkers in pancreatic ductal adenocarcinoma-a systematic review and meta-analysis.

Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive vs negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR = 2.81, CI:1.31-6,00, I2 = 88.7%, P < 0.001), and progression (UHR = 3.33, CI: 2.33-4.77, I2 = 0, P = 0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR = 5.55, CI: 3.24-9.49, I2 = 0, P = 0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR = 2.51, CI: 0.55-11.43, I2 = 90.3%, P < 0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR = 4.08, CI: 2.16-7.69, I2 = 46.9%, P = 0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use.

Prognostic role of cell-free DNA biomarkers in pancreatic adenocarcinoma: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.

Reliability and clinical applicability of a novel tear film imaging tool.

PURPOSE: The aim of our research was to investigate the reliability and clinical applicability of a modern tear film imaging tool by comparing the inter- and intragrader difference. The further goal was to compare the non-invasive tear break-up time (NIBUT) measured with the LacryDiag® device with traditional tear film break-up time (TBUT). METHODS: Comprehensive ophthalmological examination was performed, including LacryDiag® (Quantel Medical, France) (lower tear meniscus height measuring (LTMH), superior and inferior eyelid meibography (MeibS MeibI), interferometry (INT), NIBUT), slit lamp examination, and TBUT. Two independent, well-trained graders selected and analyzed the LTMH, MeibI, MeibS, and INT. The second grader reanalyzed the data 1 month later. Intra- and inter-examiner reliabilities were evaluated using intraclass correlation coefficients (ICC), while for categorical variable, Cohen's kappa statistics were provided. The Bland-Altman plot was used for visualization of the agreement between measurements. RESULTS: Fifty healthy volunteers were examined. For LTMH both the inter- and intragrader variabilities were excellent. Between two graders, the ICC of MeibI was poor; however, between two graders, the ICC of MeibS was good, and the intragrader variability in MeibI and MeibS was excellent. For the INT, both intra- and intergrading were in fair and moderate agreement, although the intragrader agreement was higher. Comparing the NIBUT and TBUT, the agreement was slight. CONCLUSION: Based on our results, examination of a patient during follow-up should be performed by the same examiner, because of the slight agreement. The LacryDiag® is a non-invasive, easy-to-use device, which can examine the tear film and save the recordings for easier follow-up.

Development of disturbance of consciousness is associated with increased severity in acute pancreatitis.

BACKGROUND: Disturbance of consciousness (DOC) may develop in acute pancreatitis (AP). In clinical practice, it is known that DOC may worsen the patient's condition, but we have no exact data on how DOC affects the outcome of AP. METHODS: From the Hungarian Pancreatic Study Groups' AP registry, 1220 prospectively collected cases were analyzed, which contained exact data on DOC, included patients with confusion, delirium, convulsion, and alcohol withdrawal, answering a post hoc defined research question. Patients were separated to Non-DOC and DOC, whereas DOC was further divided into non-alcohol related DOC (Non-ALC DOC) and ALC DOC groups. For statistical analysis, independent sample t-test, Mann-Whitney, Chi-squared, or Fisher exact test were used. RESULTS: From the 1220 patients, 47 (3.9%) developed DOC, 23 (48.9%) cases were ALC DOC vs. 24 (51.1%) Non-ALC DOC. Analysis between the DOC and Non-DOC groups showed a higher incidence of severe AP (19.2% vs. 5.3%, p < 0.001), higher mortality (14.9% vs. 1.7%, p < 0.001), and a longer length of hospitalization (LOH) (Me = 11; IQR: 8-17 days vs. Me = 9; IQR: 6-13 days, p = 0.049) respectively. Patients with ALC DOC developed more frequently moderate AP vs. Non-ALC DOC (43.5% vs. 12.5%), while the incidence of severe AP was higher in Non-ALC vs. ALC DOC group (33.3% vs. 4.4%) (p < 0.001). LOH showed a tendency to be longer in Non-ALC DOC compared to ALC DOC, respectively (Me:13; IQR:7-20 days vs. Me:9.5; IQR:8-15.5 days, p = 0.119). CONCLUSION: DOC during AP is associated with a higher rate of moderate and severe AP and increases the risk of mortality.