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Genomic profiling of tumors is available, but whether the small fragment obtained via endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is sufficient for these examinations is unknown. Here we investigated whether EUS-FNB specimens are suitable for genomic profiling to identify oncogenic and drug-matched mutations. We constructed a pancreatobiliary cancer panel for targeted panel sequencing that covered 60 significantly mutated genes and compared the results with those of whole-exome sequencing (WES). In total, 20 and 53 formalin-fixed paraffin-embedded tissues obtained via surgery and EUS-FNB were analyzed, respectively. First, we examined the DNA quality and genomic profiles of 20 paired samples from 20 malignant lesions obtained via surgery and EUS-FNB. We then tested 33 samples obtained via EUS-FNB from 24 malignant and 9 benign lesions for the discrimination of malignancy. Finally, we explored drug-matched mutations from EUS-FNB specimens. Although the DNA quantity obtained via surgery was higher than that obtained via EUS-FNB (P = 0.017), the DNA quality and mean depth were equivalent (P = 0.441 and P = 0.251). Panel sequencing of EUS-FNB specimens identified more oncogenic mutations than WES (90 % vs. 50 %). Furthermore, the number of oncogenic mutations did not differ between EUS-FNB and surgically resected specimens. Genomic profiling of EUS-FNB specimens enabled the discrimination of malignancy with 98 % accuracy. Of 44 malignant lesions, drug-matched alterations were identified in 14 % (6/44) of malignant lesions. EUS-FNB specimens can be widely utilized for diagnostic purposes, discrimination of malignancy, and detection of drug-matched mutations for the treatment of pancreatic cancer. • Genomic analysis of FFPE tissue obtained via EUS-FNB revealed oncogenic mutations in almost all patients with PC. • Genomic profiles of EUS-FNB specimens could better discriminate malignancies than conventional histological diagnosis. • Actionable mutations were detected in around 90 % of patients with PC. • EUS-FNB specimens have great potential for revealing the genomic profile of primary tumors in the era of precision medicine. [ABSTRACT FROM AUTHOR]

It is not clear whether archived cytological specimens (ACSs) obtained with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with rapid onsite evaluation (ROSE) can be used for genomic profiling of tumors. We used ACSs to perform genomic analysis of specimens to identify oncogenic and druggable mutations. A panel of 60 significantly mutated genes specific to pancreatobiliary cancer was created and used for genomic analysis of 113 specimens of 44 formalin-fixed paraffin-embedded (FFPE) tissues and 69 ACSs obtained by EUS-FNA with ROSE were included. The quantity and quality of DNA extracted from FFPE tissues and ACSs were compared. We also compared DNA from spray and touch ACSs. Next, genomic profiles were compared. We also evaluated detection of target gene mutations in each specimen. The amount of DNA in FFPE tissues was greater than in ACSs (P = 0.014), but the quality of DNA was comparable (P = 0.378). There was no quantitative or qualitative difference between spray and touch ACSs (P = 0.154 and P = 0.734, respectively). Oncogenic mutations were shared at 82 % in FFPE tissues and ACSs and 82 % in spray and touch ACSs. The sensitivity of genomic analysis in ACSs was 97 % (67 of 69), which was comparable to that of cytology (62 of 69, 90 %; P = 0.165), and was significantly higher than that of histology (32/44, 73 %; P < 0.001). Drug-matched mutations were identified in five of the 44 lesions (11 %). Genomic analysis of ACSs is useful in the prognosis of pancreatic cancer because detection of driver mutations is similar to detection in FFPE tissues. • Genomic analysis of ACS obtained via EUS-FNA with ROSE revealed oncogenic mutations in almost all patients with PC. • Actionable mutations were detected in over 90 % of patients with PC. • Identified drug-matched mutations included germline BRCA2 , ATM , PALB2 , and TSC2 mutations. • Genomic profiling of ACS can be used to detect driver mutations and to search for targeted drugs. [ABSTRACT FROM AUTHOR]

Background & Aims: We investigated the usefulness of dual-phase F-18 fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) to differentiate benign from malignant intraductal papillary mucinous neoplasms (IPMNs) and to evaluate branch-duct IPMNs. Methods: We used FDG-PET/CT to evaluate IPMNs in 48 consecutive patients who underwent surgical resection from May 2004 to March 2012. IPMNs were classified as benign (n = 16) or malignant (n = 32) on the basis of histology analysis. The ability of FDG-PET/CT to identify branch-duct IPMNs was compared with that of the International Consensus Guidelines. Results: The maximum standardized uptake value (SUVmax) was higher for early-phase malignant IPMNs than that for benign IPMNs (3.5 ± 2.2 vs 1.5 ± 0.4, P < .001). When the SUVmax cutoff value was set at 2.0, early-phase malignant IPMNs were identified with 88% sensitivity, specificity, and accuracy. The retention index values for malignant and benign IPMNs were 19.6 ± 17.8 and −2.6 ± 12.9, respectively. When the SUVmax cutoff was set to 2.0 and the retention index value to −10.0, early-phase malignant IPMNs were identified with 88% sensitivity, 94% specificity, and 90% accuracy. In identification of branch-duct IPMNs, when the SUVmax cutoff was set to 2.0, the sensitivity, specificity, and accuracy values were 79%, 92%, and 84%, respectively. By using a maximum main pancreatic duct diameter ≥7 mm, the Guidelines identified branch-duct IPMNs with greater specificity than FDG-PET/CT. The Guidelines criteria of maximum cyst size ≥30 mm and the presence of intramural nodules identified branch-duct IPMNs with almost equal sensitivity to FDG-PET/CT. Conclusions: Dual-phase FDG-PET/CT is useful for preoperative identification of malignant IPMN and for evaluating branch-duct IPMN. [ABSTRACT FROM AUTHOR]

• The number of mutations per patient was significantly higher using the molecular barcoding (MB) panel than using the non-MB panel. • Tumor-derived mutations were detected more frequently using the MB panel than the non-MB panel. • Drug-matched mutations were identified in ERBB2 (3 patients with BTC and 1 patient with PC) and PIK3CA (1 patient with BTC). • Liquid biopsy with MB may have utility in providing genomic information for the prognosis of patients with PBCA. Obtaining sufficient tumor tissue for genomic profiling is challenging in pancreaticobiliary cancer (PBCA). We determined the utility of molecular barcoding (MB) of liquid biopsies (bile, duodenal fluid, and plasma) for highly sensitive genomic diagnosis and detection of druggable mutations for PBCA. Two in-house panels of 60 genes (non-MB panel) and 21 genes using MB (MB panel) were used for the genomic analysis of 112 DNA samples from 20 PBCA patients. We measured the yield of DNA and compared the genomic profiles of liquid samples obtained using the non-MB panel and the MB panel. The utility of the panels in detecting druggable mutations was investigated. A significantly greater amount of DNA was obtained from bile supernatants and precipitates compared to tumor samples (P < 0.001 and P = 0.001, respectively). The number of mutations per patient was significantly higher using the MB panel than using the non-MB panel (2.8 vs. 1.3, P = 0.002). Tumor-derived mutations were detected more frequently using the MB panel than the non-MB panel (P = 0.023). Five drug-matched mutations were detected in liquid samples. Liquid biopsy with MB may have utility in providing genomic information for the prognosis of patients with PBCA. [ABSTRACT FROM AUTHOR]

Background and Aims Histopathologic examination is critical for diagnosing autoimmune pancreatitis (AIP). However, specimens obtained using EUS-guided FNA (EUS-FNA) are not recommended for histopathologic diagnosis because of inadequate sample size volume. We evaluated EUS-FNA efficacy for AIP diagnosis using a 22G needle. Methods Seventy-eight patients exhibiting the imaging characteristics indicative of AIP in the pancreatic parenchyma and pancreatic duct underwent EUS-FNA with a 22G needle at 12 institutions between February 2013 and March 2014. Samples were evaluated for tissue sampling conditions, CD38- and IgG4-positive plasma cell counts, storiform fibrosis (SF), and obliterative phlebitis (OP). Results Tissue specimens containing >10, 5 to 10, and 1 to 4 high-power fields (HPFs) were obtained from 29 (37.2%), 18 (23.1%), and 15 (19.2%) of 78 patients, respectively. The mean ± standard deviation (SD) CD38- and IgG4-positive plasma cell counts were 23.2 ± 18.8/HPF and 5.1 ± 6.7/HPF, respectively. SF was detected in 49 of 78 patients (62.8%) and OP in 38 of 78 patients (48.7%). According to the International Consensus Diagnostic Criteria (ICDC), histopathologic levels corresponded to level 1 in 32, level 2 in 13, and unclassifiable in 17 patients. Hence, 45 of 78 patients (57.7%) could be diagnosed with lymphoplasmacytic sclerosing pancreatitis according to ICDC. Conclusions Pancreatic tissues with at least 1 HPF were obtained by EUS-FNA from approximately 80% of patients, and nearly 60% of patients were diagnosed with ICDC level 2 or higher. Our findings indicate that EUS-FNA with a 22G needle may be useful for the histopathologic diagnosis of AIP. (Clinical trial registration number: UMIN000010097.) [ABSTRACT FROM AUTHOR]

Abstract: Gene silencing due to aberrant DNA methylation plays an important role in carcinogenesis. Previous microarray analysis demonstrated that 14 genes, including hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI2/PB) gene, showed particularly high inductions after 5-aza-2′deoxycytidine (5Aza-dC) treatment in multiple hepatoma cell lines. In the present study, we studied all of these genes except for the HAI2/PB gene and examined DNA methylation status and levels of acetylated histones using bisulphite genomic sequencing and the chromatin immunoprecipitation (ChIP) assay, respectively. Aberrant methylation in primary hepatoma tissues was also examined using methylation-specific polymerase chain reaction (MSP). Genes for E-cadherin, collagen type I alpha 2 (COL1A2), insulin-like growth factor binding protein 2 (IGFBP2), connective tissue growth factor (CTGF) and fibronectin 1 exhibited aberrant methylation in several hepatoma cell lines. The ChIP assay showed that DNA methylation and deacetylation of histones generally coexist except for fibronectin 1. In further studies of 24 primary hepatoma tissues, methylation signals for COL1A2, IGFBP2, CTGF and fibronectin 1 were detected in 13, 18, 4 and 10 patients, respectively. In conclusion, aberrant methylation of COL1A2, IGFBP2, CTGF and fibronectin 1 genes were detected in hepatoma cell lines. We also demonstrated that the methylation of 5′CpG islands and histone deacetylation generally coexisted in the regulation of gene expression except for fibronectin 1. The results of MSP in hepatoma tissues suggested that some of these genes might be involved in the development or progression of hepatoma. [Copyright &y& Elsevier]