Background-Inadequate follow-up of abnormal fecal occult blood test (FOBT) results occurs in several types of practice settings. Our institution implemented multifaceted quality improvement (QI) activities in 2004-2005 to improve follow-up of FOBT positive results. Activities addressed pre-colonoscopy referral processes and system-level factors such as electronic communication and provider education and feedback. We evaluated their effects on timeliness and appropriateness of positive FOBT follow-up and identified factors that affect colonoscopy performance.

Itraconazole, an FDA-approved antifungal, has anti-tumor activity against a variety of cancers.We sought to determine the effects of itraconazole on esophageal cancer and elucidate its mechanism of action. Itraconazole inhibited cell proliferation and induced G1-phase cell cycle arrest in esophageal squamous cell carcinoma and adenocarcinoma cell lines. Using an unbiased kinase array, we found that itraconazole downregulated protein kinase AKT phosphorylation in OE33 esophageal adenocarcinoma cells. Itraconazole also decreased phosphorylation of downstream ribosomal protein S6, transcriptional expression of the upstream receptor tyrosine kinase HER2, and phosphorylation of upstream PI3K in esophageal cancer cells. Lapatinib, a tyrosine kinase inhibitor that targets HER2, and siRNA-mediated knockdown of HER2 similarly suppressed cancer cell growth in vitro. Itraconazole significantly inhibited growth of OE33derived flank xenografts in mice with detectable levels of itraconazole and its primary metabolite, hydroxyitraconazole, in esophagi and tumors. HER2 total protein and phosphorylation of AKT and S6 proteins were decreased in xenografts from itraconazole-treated mice compared to xenografts from placebo-treated mice. In an early phase I clinical trial (NCT02749513) in esophageal cancer patients, itraconazole decreased HER2 total protein expression and phosphorylation of AKT and S6 proteins in tumors. These data demonstrate that itraconazole has potent anti-tumor properties in esophageal cancer, partially through blockade of HER2/AKT signaling.

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