Objective Pancreatic cysts are commonly detected in patients undergoing pancreatic imaging. Better approaches are needed to characterize these lesions. In this study we evaluated the utility of detecting mutant DNA in secretin-stimulated pancreatic juice. Design Secretin-stimulated pancreatic juice was collected from the duodenum of 291 subjects enrolled in Cancer of the Pancreas Screening trials at 5 US academic medical centers. The study population included subjects with a familial predisposition to pancreatic cancer who underwent pancreatic screening, and disease controls with normal pancreata, chronic pancreatitis, sporadic IPMN, or other neoplasms. Somatic GNAS mutations (reported prevalence; ~66% of IPMNs) were measured using high-resolution digital melt-curve analysis and pyrosequencing. Results GNAS mutations were detected in secretin-stimulated pancreatic juice samples of 50 of 78 familial and sporadic cases with IPMN(s) (64.1%), 15 of 33 (45.5%) with only diminutive cysts (<5mm), but none of 57 disease controls. GNAS mutations were also detected in 5 of 123 screened subjects without a pancreatic cyst. Among 97 subjects who had serial pancreatic evaluations, GNAS mutations detected in baseline juice samples predicted subsequent emergence or increasing size of pancreatic cysts. Conclusion Duodenal collections of secretin-stimulated pancreatic juice from patients with IPMNs have a similar prevalence of mutant GNAS to primary IPMNs, indicating these samples are an excellent source of mutant DNA from the pancreas. The detection of GNAS mutations before an IPMN is visible suggests that pancreatic juice analysis has potential to help in the risk stratification and surveillance of patients undergoing pancreatic screening.

Background & Aims Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated wither mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer. Methods We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls. Results TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2/22), 17.8% of PanIN-2 (8/45), 38.1% of high-grade IPMNs (8/21), 47.6% of PanIN-3(10/21), and 75% of invasive pancreatic adenocarcinomas (15/20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29/43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52−0.80) and 4/8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions. Conclusion We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dyplasia. clinicaltrials.gov (NCT00438906, NCT00714701)

In 1978, the first case of hepatitis E was identified as non-A, non-B hepatitis. Hepatitis E virus (HEV) infection is believed to be one of the common causes of enterically transmitted acute hepatitis in developing countries and is rare in developed countries, except in patients with a history of travel. However, an increasing number of chronic HEV infection cases have recently been reported in developed countries. In these countries, immunosuppressed patients with HEV infection, such as organ transplant recipients, human immunodeficiency virus (HIV)-infected patients or patients with haematological malignancies, could develop chronic hepatitis E (CHE) infection. Approximately 60% of HEV infections in immunocompromised patients after solid organ transplantation evolve to CHE without antiviral treatment. Clinical manifestations of CHE are often nonspecific symptoms. Many patients with CHE infection are asymptomatic, but some have jaundice, fatigue, abdominal pain, fever and asthenia. Several extrahepatic manifestations have also been reported. Although chronic HEV infection can result in progressive severe liver failure and cirrhosis, diagnosis is often controversial because of the lack of specific diagnostic criteria. Many CHE cases are diagnosed by HEV RNA-positive serum or stool for >6 months. Immunosuppressive drugs, interferon-alpha and ribavirin have been used for treatment. Diagnostic reverse-transcription polymerase chain reaction is useful for estimating treatment efficacy. Preventive measures for HEV infection have been discussed, while systematic guidelines have not yet been reported.

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