The benefit of pancreatic cancer surveillance in carriers of germline BRCA1/2 pathogenic variants.

BACKGROUND: Surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) is recommended. This study aimed to determine the prevalence and outcomes of PDAC and its precursor lesions in BRCA1/2 pathogenic variants (PVs) carriers undergoing pancreatic surveillance. METHODS: A retrospective multicenter cohort study of pancreatic surveillance outcomes in Israeli BRCA1/2 carriers preferably with a family history of PDAC. RESULTS: A total of 180 asymptomatic carriers participated in the screening programs, including 57 (31.7%) with BRCA1 PVs, 121 (67.2%) with BRCA2 PVs, and 12 (6.6%) with PVs in BRCA1/2 and other genes, for a median follow-up period of 4 years. Ninety-one individuals (50.5%) fulfilled the International Cancer of the Pancreas Screening (CAPS) criteria for surveillance whereas 116 (64.4%) fulfilled the American College of Gastroenterology (ACG) criteria. There were four cases of adenocarcinoma and four cases of grade 1-neuroendocrine tumor (G1-NET). All were BRCA2 carriers, and two had no family history of PDAC. Three cancer patients were at resectable stages (IA, IIA, IIB) whereas one had a stage IIIB tumor. Of the G1-NET cases, one had surgery and the others were only followed. Success rate for detection of confined pancreatic carcinoma was thus 1.6% (three of 180) in the whole cohort, 1.6% (two of 116) among individuals who fulfilled ACG criteria and 2.2% (two of 91) in those fulfilling CAPS criteria for surveillance. CONCLUSIONS: Despite the low detection rate of PDAC and its' high-risk neoplastic precursor lesions among BRCA1/2 carriers undergoing pancreatic surveillance, 75% of cancer cases were detected at a resectable stage.

Telomere shortening in liver transplant recipients is not influenced by underlying disease or metabolic derangements.

BACKGROUND: Telomeres are non-coding regions of DNA that cap the ends of chromosomes. Their length is considered a marker of human replicative senescence and premature aging. Given the high association of liver transplantation with the metabolic syndrome, we hypothesized that liver transplant recipients may exhibit premature and accelerated aging. MATERIAL AND METHODS: Telomere length in peripheral blood lymphocytes was measured by polymerase chain reaction in 62 consecutive liver-transplant recipients and 59 healthy control subjects aged 20-76 years. Clinical and laboratory parameters were collected from the medical files. RESULTS: The liver transplant recipients were significantly older than the control subjects (p=0.012), with significantly higher rates of obesity (BMI >30 kg/m(2)), dyslipidemia, hypertension, diabetes, and fatty liver. Mean telomere length was significantly shorter in the transplant group (0.59±0.6 vs. 1.91±1.78 in the controls, p<0.0001). Within the transplant group, there was no significant association between mean telomere length and underlying liver disease or presence of the metabolic syndrome or its constituents. On multivariate analysis, telomere length was negatively associated with patient age (p=0.0001), male sex (p=0.04), acute rejection (p=0.005), and fatty liver (p=0.009), and was positively associated with time from transplantation (p=0.006). CONCLUSIONS: Liver transplantation is associated with shortened telomere length in peripheral blood lymphocytes, suggesting accelerated senescence.

Survey of acceptance of the 2007 American Heart Association guidelines for the prevention of infective endocarditis: a pilot study.

OBJECTIVE: To evaluate the acceptance rate of the 2007 American Heart Association (AHA) prophylactic protocol by the patients for whom the need for prophylaxis for infective endocarditis was downgraded. METHOD AND MATERIALS: A survey among patients was conducted. Patients were included if they had to receive antibiotic prophylaxis prior to dental treatment according to the 1997 AHA protocol and did not require antibiotic prophylaxis prior to dental treatment according to the 2007 AHA guidelines. The perception of the patients and their physicians to the change was analyzed. Possible contributing parameters were assessed. RESULTS: The slight decrease in the rate of acceptance with an increase in time since the AHA publication demonstrated by the logistic regression (odds ratio, 0.93; 95% CI, 0.79 to 1.10) was not statistically significant (P=.41). Parameters related to lower patient acceptance rates were invasiveness of dental treatment and the type of dental setting (P=.046 and .001, respectively). Parameters that were found not to affect the patient acceptance rate were the severity of cardiac condition and a durable history of dental treatments in the same institute (P=.06 and .26, respectively). CONCLUSIONS: Sixteen months after publication of the 2007 AHA guidelines, the acceptance rate of the protocol is moderate to high. Reasons for this partial acceptance are discussed.