Ataxia telangiectasia (AT) is a recessive syndrome, including cerebellar degeneration, immunologic defects and cancer predisposition, attributed to mutations in the recently isolated ATM (ataxia telangiectasia, mutated) gene. AT is diagnosed in 1/40,000 to 1/100,000 live births, with carriers calculated to comprise approximately 1% of the population. Studies of AT families have suggested that female relatives presumed to be carriers have a 5 to 8-fold increased risk for developing breast cancer, raising the possibility that germline ATM mutations may account for approximately 5% of all breast cancer cases. The increased risk for breast cancer reported for AT family members has been most evident among younger women, leading to an age-specific relative risk model predicting that 8% of breast cancer in women under age 40 arises in AT carriers, compared with 2% of cases between 40-59 years. To test this hypothesis, we undertook a germ-line mutational analysis of the ATM gene in a population of women with early onset of breast cancer, using a protein truncation (PTT) assay to detect chain-terminating mutations, which account for 90% of mutations identified in children with AT. We detected a heterozygous ATM mutation in 2/202 (1%) controls, consistent with the frequency of AT carriers predicted from epidemiologic studies. ATM mutations were present in only 2/401 (0.5%) women with early onset of breast cancer (P = 0.6). We conclude that heterozygous ATM mutations do not confer genetic predisposition to early onset of breast cancer.

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Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related death in the USA. Prognosis is best when the disease is detected early; however, nearly two-thirds of newly diagnosed cases of CRC have lymph node involvement or metastatic disease. For years, 5-fluorouracil (FU)-based regimens represented the only viable treatment option for patients with metastatic CRC. However, in recent years several newer agents have been added to the treatment arsenal for this disease. These agents include oxaliplatin, irinotecan and newer monoclonal antibodies targeting the epidermal growth factor receptor (cetuximab and panitumumab) and VEGF (bevacizumab). This review aims to discuss current systemic and targeted therapies for metastatic colon cancer with a focus on mechanism of action, indications, toxicity and efficacy.

Analysis of the number of tumors per individual and the family history of cancer in our cohort suggests that genetic factors may contribute to development of secondary neoplasms in a subset of Hodgkin's disease survivors. Mutational analysis, however, does not support a significant role for heterozygous truncating ATM mutations. Future studies evaluating other genes involved in DNA damage response pathways are warranted.

AIMTo examine whether high-flow nasal oxygen (HFNO) availability influences the use of general anesthesia (GA) in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) and associated outcomes.METHODSIn this retrospective study, patients were stratified into 3 eras between October 1, 2013 and June 30, 2014 based on HFNO availability for deep sedation at the time of their endoscopy. During the first and last 3-mo eras (era 1 and 3), no HFNO was available, whereas it was an option during the second 3-mo era (era 2). The primary outcome was the percent utilization of GA vs deep sedation in each period. Secondary outcomes included oxygen saturation nadir during sedation between periods, as well as procedure duration, and anesthesia-only time between periods and for GA vs sedation cases respectively.RESULTSDuring the study period 238 ERCP or EUS cases were identified for analysis. Statistical testing was employed and a P < 0.050 was significant unless the Bonferroni correction for multiple comparisons was used. General anesthesia use was significantly lower in era 2 compared to era 1 with the same trend between era 2 and 3 (P = 0.012 and 0.045 respectively). The oxygen saturation nadir during sedation was significantly higher in era 2 compared to era 3 (P < 0.001) but not between eras 1 and 2 (P = 0.028) or 1 and 3 (P = 0.069). The procedure time within each era was significantly longer under GA compared to deep sedation (P ≤ 0.007) as was the anesthesia-only time (P ≤ 0.001).CONCLUSIONHigh-flow nasal oxygen availability was associated with decreased GA utilization and improved oxygenation for ERCP and EUS during sedation.

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We present a case of a 76-year-old man with right upper quadrant abdominal pain and weight loss, who was found to have an intraductal papillary neoplasm of the bile duct (IPNB) of the pancreaticobiliary subtype, deemed curatively resectable. The patient declined surgery and opted for endoscopic therapy. He underwent two sessions of endoscopic retrograde cholangiopancreatography (ERCP)-guided radiofrequency ablation (RFA). Ten months later, no evidence of recurrence was identified on repeat ERCP. To our knowledge, this is the first reported case of successful use of RFA as a primary treatment modality for resectable IPNB.

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