MiR-200b categorizes patients into pancreas cystic lesion subgroups with different malignant potential.

Extracellular vesicles (EV) carry their cargo in a membrane protected form, however, their value in early diagnostics is not well known. Although pancreatic cysts are heterogeneous, they can be clustered into the larger groups of pseudocysts (PC), and serous and mucinous pancreatic cystic neoplasms (S-PCN and M-PCN, respectively). In contrast to PCs and S-PCNs, M-PCNs may progress to malignant pancreatic cancers. Since current diagnostic tools do not meet the criteria of high sensitivity and specificity, novel methods are urgently needed to differentiate M-PCNs from other cysts. We show that cyst fluid is a rich source of EVs that are positive and negative for the EV markers CD63 and CD81, respectively. Whereas we found no difference in the EV number when comparing M-PCN with other pancreatic cysts, our EV-based biomarker identification showed that EVs from M-PCNs had a higher level of miR-200b. We also prove that not only EV-derived, but also total cyst fluid miR-200b discriminates patients with M-PCN from other pancreatic cysts with a higher sensitivity and specificity compared to other diagnostic methods, providing the possibility for clinical applications. Our results show that measuring miR-200b in cyst fluid-derived EVs or from cyst fluid may be clinically important in categorizing patients.

Quantitative Software Analysis of Endoscopic Ultrasound Images of Pancreatic Cystic Lesions.

Endoscopic ultrasonography (EUS) is the most accurate imaging modality for the evaluation of different types of pancreatic cystic lesions. Our aim was to analyze EUS images of pancreatic cystic lesions using an image processing software. We specified the echogenicity of the lesions by measuring the gray value of pixels inside the selected areas. The images were divided into groups (serous cystic neoplasm /SCN/, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms /Non-SCN/ and Pseudocyst) according to the pathology results of the lesions. Overall, 170 images were processed by the software: 81 in Non-SCN, 30 in SCN and 59 in Pseudocyst group. The mean gray value of the entire lesion in the Non-SCN group was significantly higher than in the SCN group (27.8 vs. 18.8; p < 0.0005). The area ratio in the SCN, Non-SCN and Pseudocyst groups was 57%, 39% and 61%, respectively; significantly lower in the Non-SCN group than in the SCN or Pseudocyst groups (p < 0.0005 and p < 0.0005, respectively). The lesion density was also significantly higher in the Non-SCN group compared to the SCN or Pseudocyst groups (4186.6/mm2 vs. 2833.8/mm2 vs. 2981.6/mm2; p < 0.0005 and p < 0.0005, respectively). The EUS image analysis process may have the potential to be a diagnostic tool for the evaluation and differentiation of pancreatic cystic lesions.

Preoperative Serum Carbohydrate Antigen 19-9 Levels Cannot Predict the Surgical Resectability of Pancreatic Cancer: A Meta-Analysis.

Background and Aims: Pancreatic ductal adenocarcinoma has one of the worst prognosis of all malignancies. This investigated the relationship between the preoperative serum carbohydrate antigen 19-9 and surgical resectability. Methods: A systematic search was performed in three databases (MEDLINE, EMBASE, and Web of Science) to compare the surgical resectability of pancreatic ductal adenocarcinoma in patients with high and low preoperative serum carbohydrate antigen 19-9 values. The receiving operating characteristic curves were constructed and the weighted mean differences for preoperative serum carbohydrate antigen 19-9 levels of resectable and unresectable groups of patients were calculated. The PROSPERO registration number is CRD42019132522. Results: Results showed that there was a significant difference in resectability between the low and high carbohydrate antigen 19-9 groups. Six out of the eight studies utilised receiver operating characteristic curves in order to find the cut-off preoperative carbohydrate antigen 19-9 levels marking unresectability. The overall result from the pooled area under curve values from the receiver operating characteristic curves was 0.794 (CI: 0.694-0.893), showing that the preoperative carbohydrate antigen 19-9 level is a "fair" marker of resectability. The result of the pooled weighted mean differences was 964 U/ml (p < 0.001) showing that there is a significant carbohydrate antigen 19-9 difference between the resectable and unresectable groups. Based on the results of the I-squared test, the result was 87.4%, accounting for "considerable" heterogeneity within the population. Conclusion: Carbohydrate antigen 19-9 is not a reliable marker of unresectability, it should not be used on its own in surgical decision-making.

Estimation of Phase Ratio in Bulk, Textured TWIP/TRIP Steels from Pole Figures.

The volume fraction of austenite (γ), ε martensite and α' martensite is of key importance in the research of TWIP/TRIP steels. When mechanical loading is involved, the crystallographic texture also develops, which complicates X-ray diffraction-based phase ratio determination. The problem is more pronounced when only a couple, or only one Bragg-reflection can be measured. A solution for such cases is to determine the ratio of the phases based on the pole distribution function of a selected Bragg-reflection of the present phases. In this manuscript, this method is reconsidered for and applied to non-transmittable bulk specimens for the first time in the reflection mode of XRD pole figure measurements. First, the method was applied to a series of γ-α' powder mixtures. The results were compared to those obtained by the Rietveld method. Afterwards, the technique was applied to strongly textured, bulk TWIP/TRIP steel specimens which were tensile tested at different temperatures. It was shown that the results of the presented method were close to those of the Rietveld technique in the case of powder mixtures. The results of the tensile-tested steels revealed that the α' content increases with decreasing test temperatures, and the variation of the α' ratio correlates very well with the ultimate tensile strength versus the temperature, confirming the contribution of the α' content to the strength of TWIP/TRIP steels.

Sarcopenia as an independent predictor of the surgical outcomes of patients with inflammatory bowel disease: a meta-analysis.

Patients with inflammatory bowel disease (IBD) are at risk of sarcopenia, which is associated with poor clinical outcomes. We conducted this study to assess whether sarcopenia predicts the need for surgery and postoperative complications in patients with IBD. We performed a systematic search of four electronic databases, last updated in March, 2019. Data from studies comparing rates of surgery and postoperative complications in sarcopenic IBD patients versus non-sarcopenic IBD patients were pooled with the random-effects models. We calculated the odds ratios (OR) with a 95% confidence interval (CI). Ten studies with a collective total of 885 IBD patients were included in our meta-analysis. Although the analysis of raw data did not reveal significant differences between the two groups with respect to the rate of surgery and postoperative complications (OR = 1.826; 95% CI 0.913-3.654; p = 0.089 and OR = 3.265; 95% CI 0.575-18.557; p = 0.182, respectively), the analysis of adjusted data identified sarcopenia as an independent predictor for both of the undesirable outcomes (OR = 2.655; 95% CI 1.121-6.336; p = 0.027 and OR = 6.097; 95% CI 1.756-21.175; p = 0.004, respectively). Thus, early detection of sarcopenia in patients with IBD is important to prevent undesirable outcomes.

Detection and proteomic characterization of extracellular vesicles in human pancreatic juice.

AIMS: The prognosis of patients with pancreatic cancer has remained virtually unchanged with a high mortality rate compared to other types of cancers. An earlier detection would provide a time window of opportunity for treatment and prevention of deaths. In the present study we investigated extracellular vesicle (EV)-associated potential biomarkers for pancreatic cancer by directly assessing EV size-based subpopulations in pancreatic juice samples of patients with chronic pancreatitis or pancreatic cancer. In addition, we also studied blood plasma and pancreatic cancer cell line-derived EVs. METHODS: Comparative proteomic analysis was performed of 102 EV preparations from human pancreatic juices, blood, and pancreatic cancer cell lines Capan-1 and MIA PaCa-2. EV preparations were also characterized by electron microscopy, tunable resistive pulse sensing, and flow cytometry. RESULTS: Here we describe the presence of EVs in human pancreatic juice samples. Pancreatic juice EV-associated proteins that we identified as possible candidate markers for pancreatic cancer included mucins, such as MUC1, MUC4, MUC5AC, MUC6 and MUC16, CFTR, and MDR1 proteins. These candidate biomarkers could also be detected by flow cytometry in EVs found in pancreatic juice and those secreted by pancreatic cancer cell lines. CONCLUSIONS: Together our data show that detection and characterization of EVs directly in pancreatic juice is feasible and may prove to be a valuable source of potential biomarkers of pancreatic cancer.