10 The Stem Cell-Targeting Drug Salinomycin Inhibits Proliferation of Normal, Benign Hyperplastic, and Transformed Interstitial Cells of Cajal and Their Stem Cells (ICC-SC) by Increasing the Expression of Cell Cycle Restriction Checkpoint Regulators

Abstract

the index colonoscopy to the first of the following: 10 years follow-up; performance of another colonoscopy without CRC; termination of membership; diagnosis of CRC; or January 31, 2011. CRCs occurring within 6 months after the index colonoscopy were excluded. Analyses used multi-level Cox proportional hazards models with clustering on physician. Potential predictors of subsequent CRC risk included physician ADR, exam type, and patient sex, age, race/ethnicity, family history of CRC, and Charlson comorbidity score. Hazard ratios (HR) for subsequent CRC risk were calculated separately by patient sex and both sexes combined, and by distal and proximal CRC location (both sexes combined). Results: We identified 316,334 colonoscopy exams and 716 subsequent post-colonoscopy CRC cases for the analyses. Patients (both sexes combined) whose colonoscopies were performed by endoscopists with lower ADRs were more likely to be diagnosed with subsequent CRC than patients whose endoscopists had a higher ADR. The adjusted HRs (and CIs) for ADR quartiles of ,20.3%, 20.3%-25.2%, and 25.3%-32.0%, as compared to ≥32.1%, were 1.74 (1.36, 2.24), 1.52 (1.14, 2.04), and 1.31 (1.00, 1.73), respectively (Table). The relationships between ADR and subsequent CRC risk by proximal and distal location were similar (Table). Finally, the linear relationship between ADR and CRC risk did not vary by patient sex. Conclusions: Physician ADR is an independent predictor of subsequent CRC risk following a negative colonoscopy, the relationship does not vary by patient sex, and the relationships were similar for proximal and distal cancers. The use of ADR as a quality measure of colonoscopy’s ability to prevent subsequent cancers appears warranted; cancer risk increases linearly with decreasing physician ADR and there was no clear threshold above which there was no further improvement.