RESUMEN
Currently available serum biomarkers for pancreatobiliary cancers lack sensitivity and specificity and ultimate diagnosis still requires invasive procedures for histological confirmation. The detection of tumor-specific genetic aberrations with utilization of cell free DNA (cfDNA) is a less invasive approach than traditional tissue biopsies; however, it has not been implemented into clinical routine. In this study, we investigated bile as a liquid biopsy source in pancreatobiliary cancers and compared its potential as cell-free DNA source to plasma. Blood (n = 37) and bile (n = 21) samples were collected from patients affected by pancreatic ductal adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (CCA) or with non-malignant biliary obstructions (blood n = 16; bile n = 21). Panel-based next generation sequencing (NGS) and digital droplet PCR (ddPCR) were applied for tumor mutation profiling. NGS results from matched tumor tissues (n = 29) served as comparison. Sequencing of cfDNA from bile resulted in detection of 96.2% of the pathogenic tumor mutations found in matched tissue samples. On the other hand, only 31.6% of pathogenic tumor mutations found in tissue could be detected in plasma. In a direct comparison, only half of the mutations detected in bile cfDNA were concordantly detected in plasma from the same patients. Panel NGS and ddPCR displayed comparable sensitivity. In conclusion, bile is a suitable source of cfDNA for the diagnosis of pancreatobiliary cancer and performs more reliably than plasma. Although primary diagnosis still requires histologic confirmation, bile-derived cfDNA could offer an alternative if tissue sampling is not feasible and might allow less invasive disease monitoring.
RESUMEN
OBJECTIVE: The purpose of this study was to assess the feasibility of MDCT colonography in an ultra-low-dose technique in the detection of endoluminal colonic lesions compared with high-resolution video colonoscopy. SUBJECTS AND METHODS: After standard bowel cleansing, 137 patients (77 men, 60 women; mean [+/- SD] age, 57.1 +/- 11.3 years) underwent high-resolution video colonoscopy within 2 hr after ultra-low-dose MDCT colonography had been performed. Ultra-low-dose MDCT colonography was performed with patients in the supine position only using 10 mAs (effective weighted CT dose index, 0.94 mGy). After mathematic noise reduction by nonlinear gaussian filter chains, using dedicated software (ECCET), images were analyzed by two blinded observers in simultaneously displayed interactive 2D and 3D modes. Findings of ultra-low-dose MDCT colonography were compared with the results obtained with high-resolution video colonoscopy. RESULTS: Calculated effective doses were 0.7 and 1.2 mSv for men and women, respectively. Ultra-low-dose MDCT colonography detected 84 (62%) of 135 lesions: 11 (78.6%) of 14 large polyps (> 10 mm), 12 (85.7%) of 14 medium polyps (9.9-5 mm), and 61 (57%) of 107 small polyps (< 5 mm). On a patient-by-patient basis, an overall sensitivity of 70.3% with a specificity of 80.8% was calculated. False-positive findings were seen mostly for small lesions (eight medium and 29 small lesions). Two of the three false-negative lesions were retrospectively detected in contrast-enhanced cleansing fluid; one was a flat lipoma not detectable on ultra-low-dose MDCT colonography. CONCLUSION: Despite an effective dose of approximately 1 mSv, MDCT colonography using an ultra-low-dose technique performs as well as MDCT colonography with a standard dose, according to published data. After mathematic noise reduction, 82% of polyps larger than 5 mm can be detected.