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Differentiation of main duct-IPMN from chronic pancreatitis by EUS and duct fluid cfDNA Next Generation Sequencing: a feasibility study

ABSTRACT: Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main duct (MD)-Intraductal Papillary Mucinous Neoplasm (IPMN) and chronic pancreatitis (CP). Distinction of both conditions might be difficult if imaging alone is used as a diagnostic tool. Cell-free DNA in MPD fluid obtained by Endoscopic Ultrasound (EUS)-guided fine needle aspiration (FNA) might help to distinguish MD-IPMN from CP. Methods: All patients with a dilated MPD ≥ 5 mm in EUS were prospectively analysed in this single centre study. EUS-guided pancreatic duct fluid aspiration was performed when MD-IPMN or CP was suspected in patients fit for surgery. Fourteen hot spot regions of known oncogenes or tumor suppressor genes (AKT1, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS, PIK3CA, SMAD4, TP53, APC) were analysed by deep targeted NGS. Results were correlated to histopathology of tumor biopsy and/or clinical long-term follow-up. Results: 115 patients with a mean MPD diameter of 9.8 mm (range 5.0-22.7) were identified of whom 21/115 (18.3%) were eligible for duct fluid analysis. All 9 patients with histologically proven MD-IPMN showed one or more KRAS/GNAS-mutations in pancreatic duct fluid whereas all 7 patients with CP were KRAS/GNAS wild type. TP53- as well as FBXW7-mutations were found in both conditions. No definitive histopathological diagnosis or follow-up diagnosis could be made in 5 patients. MPD diameter was significantly larger in MD-IPMN (11.7 mm (7.0-22.7); n=9) than in patients with CP (8.1 mm (5.0-14.5); n=31): p = 0.0112. Conclusions: Highly sensitive KRAS/GNAS-testing in aspirated MPD fluid obtained by EUS-guided FNA supports distinction of MD-IPMN from CP. MPD diameter was significantly larger in MD-IPMN than in CP. Trial Registration: NCT03820531 from 25/01/2019.

ORGANISM(S): Homo sapiens (human)

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PROVIDER: S-BSST965 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:PurposeThe application of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains poorly characterized. Here, we retrospectively analyzed data from patients with TBM who had taken both mNGS and conventional tests including culture of Mycobacterium tuberculosis (MTB), polymerase chain reaction (PCR) and acid-fast bacillus (AFB) stain, and the sensitivity and specificity of these methods were compared.MethodsWe retrospectively recruited TBM patients admitted to the hospital between December 2015 and October 2018. The first collection of cerebrospinal fluid (CSF) samples underwent both mNGS and conventional tests. In addition, patients with bacterial/cryptococcal meningitis or viral meningoencephalitis were mNGS positive controls, and a patient with auto-immune encephalitis was an mNGS negative control.ResultsTwenty three TBM patients were classified as 12 definite and 11 clinical diagnoses, which were based on clinical manifestations, pathogen evidence, CSF parameters, brain imaging, and treatment response. The mNGS method identified sequences of Mycobacterium tuberculosis complex (MBTC) from 18 samples (18/23, 78.26%). In patients with definite TBM, the sensitivity of mNGS, AFB, PCR, and culture to detect MTB in the first CSF samples were 66.67, 33.33, 25, and 8.33%, respectively. The specificity of each method was 100%. Among the four negative mNGS cases (4/23, 17.39%), three turned out positive by repeated AFB stain. The agreement of mNGS with the total of conventional methods was 44.44% (8/18). Combination of mNGS and conventional methods increased the detection rate to 95.65%. One patient was diagnosed as complex of TBM and cryptococcal meningitis, in which AFB stain and cryptococcal antigen enzyme immunoassay were positive and the DNA of Cryptococcus neoformans was detected by mNGS.ConclusionOur study indicates that mNGS is an alternative method to detect the presence of mycobacterial DNA in CSF samples from patients with TBM and deserves to be applied as a front-line CSF test.

Project description:Central nervous system (CNS) complications can occur in 9%-15% of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical manifestations of the CNS complications are non-specific, with most of them being disturbances of consciousness, convulsions, headaches, fever, and epilepsy, making it difficult to infer the cause of the complications based on clinical manifestations. We retrospectively analyzed the sensitivity and feasibility of metagenomic next generation sequencing (mNGS) in the diagnosis of CNS infections after allo-HSCT. Lumbar punctures were performed on 20 patients with CNS symptoms after receiving alternative donor HSCT(AD-HSCT) at the Affiliated Cancer Hospital of Zhengzhou University from February 2019 to December 2020, and their cerebrospinal fluid (CSF) was collected. The mNGS technique was used to detect pathogens in the CSF. Routine CSF testing, biochemical analyses, G experiments, GM experiments, ink staining, acid-fast staining, and bacterial cultures were carried out, and quantitative PCR (qPCR) tests were used to detect cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKPyV), and human alphaherpesvirus (HHV). A total of 29 tests were performed with 21 of them being positive. Of the five negative patients, three were diagnosed with a posterior reversible encephalopathy syndrome, one as having transplantation-associated thrombotic microangiopathy, and one with transient seizure caused by hypertension. Fifteen patients tested positive, of which four had single infections and eleven had mixed infections. Five cases of fungal infections, six cases of bacterial infections, and 13 cases of viral infections were detected. Among the 13 cases of viral infections, ten cases were CMV(HHV-5); three were BKPyV; two were Torque teno virus (TTV); Two were HHV-1,two were EBV(HHV4), and one each of HpyV5 and HHV-6B. Thirteen patients tested positive for virus while the qPCR detection method of 6 identical specimens were below the minimum detection limit(<1×103 U/ml). The mNGS technique is highly sensitive, and it can be used to diagnose CNS infections after allo-HSCT.

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Differentiation of main duct-IPMN from chronic pancreatitis by EUS and duct fluid cfDNA Next Generation Sequencing: a feasibility study

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