A novel microfluidic-based assay to determine high-risk pancreatic cysts for surgery utilizing pancreatic cyst fluid: an international multicenter study

225 Background: Pancreatic cysts are a group of lesions with malignant potential. Currently, there are no consistently reliable biomarkers or imaging modalities to accurately predict biologic behavior of these cysts. We tested the hypothesis that tumor-derived exosomes (better conserved than free miRNA) can be acquired endoscopically from pancreatic cyst fluid and may allow for improved distinction between benign, premalignant and malignant cysts. Methods: Exosomes were isolated and characterised by differential and buoyant centrifugation from pancreatic cyst fluid obtained from 30 patients with pseudocysts (PS), serous cystic (SC), mucinous cysts (MC), intraductal papillary mucinous neoplasms (IPMN), pancreatitis (PA), and pancreatic cancer (PC) , confirmed with imaging and histology. An Illumina TruSeq Small RNA kit was used to construct a small RNA library, and the libraries were sequenced using the Illumina NextSeq 500 platform. The resulting sequencing FASTQ files were analyzed using miRDeep2 to identify both known and novel miRNAs. Results: Four significant miRNAs which are shared between six of the analyses, specifically hsa-miR-199b-3p, hsa-miR-199a-2-3p, hsa-miR-199a-1-3p and hsa-let-7i-5p were identified. MiRNA hsa-miR-27a-3p was significant and shared between five of the analyses. A total of 15, 12 and 2 significant miRNAs were shared between four, three and two of the analyses, respectively. Importantly, there were a total of 10 significant miRNAs which were unique to each analysis, with the exception of IPMN vs Pseudocyst, and Pancreatic cancer vs Pancreatitis. Specifically these unique miRNAs for each analysis are: hsa-miR-92a-2-3p (Pancreatitis vs Pseudocyst); hsa-miR-92a-1-3p (Serous vs Pseudocyst); hsa-miR-30e-5p (Pancreatic cancer vs Serous), hsa-miR-30b-5p (IPMN vs Pancreatic cancer); and hsa-miR-23b-3p, hsa-miR-99b-5p, hsa-miR-222-3p, hsa-miR-31-5p, hsa-miR-151a-5p, hsa-miR-221-3p (Pancreatic cancer vs. Pseudocyst). Conclusions: Exosomal miRNAs in pancreatic fluid may be used as a biomarker to differentiate between various cyst types and pancreatic cancer. A larger cohort with miRNA quantification and is needed to further validate these findings .

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Pancreatic cyst fluid glucose: rapid, inexpensive, and accurate diagnosis of mucinous pancreatic cysts

Surgery ◽

10.1016/j.surg.2017.09.051 ◽

2018 ◽

Vol 163 (3) ◽

pp. 600-605 ◽

Cited By ~ 19

Author(s):

Rosalie A. Carr ◽

Michele T. Yip-Schneider ◽

Rachel E. Simpson ◽

Scott Dolejs ◽

Justine G. Schneider ◽

...

Keyword(s):

Pancreatic Cyst ◽

Accurate Diagnosis ◽

Cyst Fluid ◽

Pancreatic Cysts ◽

Pancreatic Cyst Fluid

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PANCREATIC CYST FLUID CEA AND AMYLASE IN THE DIFFERENTIAL DIAGNOSIS OF PANCREATIC CYSTS

Pancreas ◽

10.1097/01.mpa.0000297765.97702.c3 ◽

2007 ◽

Vol 35 (4) ◽

pp. 421

Author(s):

M. Pelaez-Luna ◽

M. Ranjan ◽

J. E. Clain ◽

M. J. Levy ◽

E. Rajan ◽

...

Keyword(s):

Differential Diagnosis ◽

Pancreatic Cyst ◽

Cyst Fluid ◽

Pancreatic Cysts ◽

Pancreatic Cyst Fluid

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Mo1200 Detection of Intraductal Papillary Mucinous Neoplasm (IPMN) With a High Risk of Malignant Transformation From Pancreatic Cyst Fluid Aspirates by the DAS-1 Monoclonal Antibody

Gastroenterology ◽

10.1016/s0016-5085(12)62380-4 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-620

Author(s):

Koushik K. Das ◽

Xin Geng ◽

Hong Xiao ◽

Carlos Fernandez-del Castillo ◽

David G. Forcione ◽

...

Keyword(s):

Monoclonal Antibody ◽

High Risk ◽

Malignant Transformation ◽

Intraductal Papillary Mucinous Neoplasm ◽

Pancreatic Cyst ◽

Cyst Fluid ◽

Mucinous Neoplasm ◽

Pancreatic Cyst Fluid

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Validation of the Canadian syncope risk score in a large prospective international multicenter study

European Heart Journal ◽

10.1093/ehjci/ehaa946.0701 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Zimmermann ◽

J Du Fay De Lavallaz ◽

D Florez ◽

V Widmer ◽

M Freese ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Multicenter Study ◽

Validation Cohort ◽

Risk Group ◽

High Risk Group ◽

Funding Source ◽

International Multicenter Study ◽

International Multicenter ◽

Very High

Abstract Background Management and risk stratification of patients with syncope in the emergency department (ED) is often challenging. In an effort to support ED physicians in disposition decisions, the Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes. Methods The CSRS was developed in a Canadian multicenter study and contains nine predictors: predisposition to vasovagal syncope, heart disease, systolic pressure <90 or >180mmHg in the ED, troponin level >99th percentile, abnormal QRS axis, QRS duration >130ms, QTc interval >480ms and an ED diagnosis of vasovagal or cardiac syncope. Patients can achieve a CSRS score between −3 and +11 points. We validated the CSRS in a large prospective international multicenter study recruiting patients 40 years or older presenting to the ED with a syncopal event within the last 12 hours. Recruitment centers contained smaller provincial hospitals, as well as big University Hospitals in eight countries on three continents. Primary outcome measure were 30-day serious arrhythmic and non-arrhythmic adverse events, as defined by the authors of the original score. Results 1581 patients were eligible for this analysis. The population in this validation cohort was older (mean age 68 vs 54 years) and had a considerably higher rate of serious outcomes compared to the derivation cohort (n=186 (11.8%) vs n=147 (3.6%)). The area under the receiver operating characteristic curve (AUC) for the CSRS was 0.88 (95% confidence interval (CI) 0.86–0.91) and significantly higher compared to the validated OESIL score (AUC 0.75, 95% CI 0.71–0.78, p<0.001). Calibration curve analysis showed an underestimation of risk in patients with a low CSRS and an overestimation in patients with a high CSRS. The rate of observed serious outcomes within 30d increased from 0.8% in the very low risk group (CSRS equal to or below −2) to 48% in the (very) high risk group (CSRS equal to or above 4, Hazard ratio 79.4, 95% CI 11.1–570.9). A Kaplan-Meier plot was used to visualize rates of serious outcomes in three different risk groups (Figure). Conclusion This is the first validation of the Canadian Syncope Risk Score in a large international syncope cohort. The prognostic discrimination of the CSRS for 30-day serious outcomes was very good in our validation cohort and comparable to that of the Canadian derivation study. Despite suboptimal calibration, prognostic analysis showed a high rate of serious outcomes in the CSRS (very) high risk group and a low rate of serious outcomes in the very low risk group. Allowing the clinical judgement of the ED physician in the form of suspected syncope etiology to be a part of the score seems to largely contribute to the high performance of the CSRS. Additional validation studies might be needed to further increase the accuracy of the CSRS in different patient populations with a different incidence of outcomes in settings outside of Canada. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation; Swiss Heart Foundation

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