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Molecular analysis of cyst fluids improves the diagnostic accuracy of pre-operative assessment of pancreatic cystic lesions.

ABSTRACT: Pancreatic cystic lesions (PCL) are increasingly diagnosed. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) cytology is often used for diagnostic confirmation but can be inconclusive. In this study, the role of molecular analyses in the pre-operative diagnostics of PCL is evaluated. Targeted Next Generation Sequencing (NGS) applied on cytology smears was retrospectively evaluated in a cohort of 37 resected PCL. Usefulness of NGS on fresh cyst fluids was tested in a prospective cohort of patients with newly diagnosed PCL (n = 71). In the retrospective cohort, cytology plus NGS displayed higher sensitivity (94.1% vs. 87.1%) and specificity (100% vs. 50%) than cytology alone for the detection of mucinous neoplasms. In the prospective cohort, sensitivity and specificity of conventional cytology alone were 54.2% and 100% for the detection of mucinous neoplasia and 50.0% and 100% for the detection of high-grade dysplasia, respectively. Adding NGS, all lesions which underwent histopathologic verification (12/71, 17%) could be classified without false positive or false negative results regarding the detection of mucinous neoplasm so far. NGS analysis of cfDNA in PCL fluids is feasible and can increase diagnostic accuracy in the detection of mucinous neoplasms compared to cytology alone. However, algorithms for the detection of high-risk lesions need further improvement.

SUBMITTER: Haeberle L

PROVIDER: S-EPMC7858638 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Molecular analysis of cyst fluids improves the diagnostic accuracy of pre-operative assessment of pancreatic cystic lesions.

Haeberle Lena L Schramm Martin M Goering Wolfgang W Frohn Lisa L Driescher Caroline C Hartwig Werner W Preissinger-Heinzel Hubert-Karl HK Beyna Torsten T Neuhaus Horst H Fuchs Katharina K Keitel-Anselmino Verena V Knoefel Wolfram Trudo WT Esposito Irene I

Scientific reports 20210203 1

Pancreatic cystic lesions (PCL) are increasingly diagnosed. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) cytology is often used for diagnostic confirmation but can be inconclusive. In this study, the role of molecular analyses in the pre-operative diagnostics of PCL is evaluated. Targeted Next Generation Sequencing (NGS) applied on cytology smears was retrospectively evaluated in a cohort of 37 resected PCL. Usefulness of NGS on fresh cyst fluids was tested in a prospective cohort of p ...[more]

PMID: 33536452

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Project description:Pancreatic cyst fluids (PCFs) enriched in tumour-derived proteins are considered a potential source of new biomarkers. This study aimed to determine compositional and quantitative differences between the degradome and proteome of PCFs aspirated from different types of pancreatic cyst lesions (PCLs). 91 patients who underwent endoscopic ultrasound-fine needle aspiration under routine clinical diagnosis of PCLs were enrolled. Four cysts were malignant (CAs), and 87 were nonmalignant and consisted of 18 intraductal papillary mucinous neoplasms (IPMNs), 14 mucinous cystic neoplasms (MCNs), nine serous cystic neoplasms (SCNs), 29 pseudocysts (PCs), and 17 unclassified. Profiles of the <5 kDa fraction, the degradome, and the trypsin-digested proteome were analysed using an LTQ-Orbitrap Elite mass spectrometer coupled with a nanoACQUITY LC system. Qualitative analyses identified 796 and 366 proteins in degradome and proteome, respectively, and 689 (77%) and 285 (78%) of them were present in the Plasma Proteome Database. Gene Ontology analysis showed a significant overrepresentation of peptidases and peptidases inhibitors in both datasets. In the degradome fraction, quantitative values were obtained for 6996 peptides originating from 657 proteins. Of these, 2287 peptides were unique to a single type, and 515 peptides, derived from 126 proteins, were shared across cyst types. 32 peptides originating from 12 proteins had differential (adjusted p-value ≤0.05, FC ≥1.5) abundance in at least one of the five cysts types. In proteome, relative expression was measured for 330 proteins. Of them, 33 proteins had significantly (adjusted p-value ≤0.05, FC ≥1.5) altered abundance in at least one of the studied groups and 19 proteins appeared to be unique to a given cyst type. PCFs are dominated by blood proteins and proteolytic enzymes. Although differences in PCF peptide composition and abundance could aid classification of PCLs, the unpredictable inherent PCF proteolytic activity may limit the practical applications of PCF protein profiling.

Project description:Background and study aims Given variable diagnostic yield of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) for pancreatic cystic lesions (PCLs), a through-the-needle (TTN) microforceps biopsy device passed through a 19-gauge FNA needle has been devised to improve tissue sampling. This was a systematic review and meta-analysis to evaluate the feasibility, diagnostic yield, and safety of EUS-guided TTN microforceps biopsy for diagnosis of PCLs. Methods Individualized searches were developed in accordance with PRISMA and MOOSE guidelines. This was a cumulative meta-analysis performed by calculating pooled proportions with rates estimated using random effects models. Measured outcomes included pooled technical success, diagnostic yield, accuracy, and procedure-associated adverse events (AEs) as well as comparison to conventional FNA. Results Eleven studies (n = 518 patients; mean age 64.13 ± 5.83 years; 58.19 % female) were included. Mean PCL size was 33.39 ± 3.72 mm with the pancreatic head/uncinate (35.50 %) being the most common location. A mean of 2.47 ± 0.92 forceps passes were performed with a mean of 2.79 ± 0.81 microbiopsies obtained per lesion. Pooled technical success was 97.12 % (95 % CI, 93.73-98.71; I 2 = 34.49) with a diagnostic yield of 79.60 % (95 % CI, 72.62-85.16; I 2 = 56.00), and accuracy of 82.76 % [(95 % CI, 77.80-86.80; I 2 = 0.00). The pooled serious adverse event rate was 1.08 % (95 % CI, 0.43-2.69; I 2 = 0.00). Compared to conventional FNA, TTN microforceps biopsy resulted in significant improvement in diagnostic yield [OR 4.79 (95 % CI: 1.52-15.06; P = 0.007)] and diagnostic accuracy [OR 8.69 (95 % CI, 1.12-67.12; P = 0.038)], respectively. Conclusions EUS-guided TTN microforceps biopsy appears to be safe and effective for diagnosis of PCLs with improvement in diagnostic yield and accuracy when compared to FNA alone.

Dataset Information

Molecular analysis of cyst fluids improves the diagnostic accuracy of pre-operative assessment of pancreatic cystic lesions.

Publications

Molecular analysis of cyst fluids improves the diagnostic accuracy of pre-operative assessment of pancreatic cystic lesions.

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