Colorectal mucosa is targeted by toxic agents, which can initiate or promote colon cancer. The mechanism of damage might be a focal irritation with loss of normal epithelial cell barrier function. Genetic alterations in tumors may also affect host inflammatory response. The aim of this study was to define the extent of inflammation in colorectal mucosa, along colorectal carcinogenesis, and in microsatellite stable and unstable colorectal carcinomas. We collected 103 samples of normal colorectal mucosa from 65 patients (35 with colorectal cancer or adenoma, 8 with inflammatory bowel diseases, and 22 controls with normal colonoscopy). We also examined 24 aberrant crypt foci, 14 hyperplastic polyps, 16 adenomas, and 67 samples of colorectal carcinoma. Immunohistochemistry was used to count myeloperoxidase (MPO)-positive cells (neutrophils and monocytes) in Â100
Purpose Evidence-based guidelines inform treatment decisions for patients for whom germline genetic information is available. Our real-time tumor sequencing program, which makes precision treatment decisions for patients with cancer, produces matched germline information, providing a unique opportunity to efficiently implement pharmacogenetics and benefit patients. Methods The germline genetic database from the Michigan Oncology Sequencing (MI-Oncoseq) program was searched for 21 clinically actionable polymorphisms in five cancer-relevant genes: TPMT, DPYD, CYP2C19, CYP3A5, and UGT1A1. Residual germline DNA was sent to an external Clinical Laboratory Improvement Amendments–approved laboratory for confirmatory genotyping. The medical records of MI-Oncoseq patients with actionable phenotypes were searched for receipt of relevant drugs and to determine whether having genetic information at the time of treatment would have led to a treatment recommendation. Results All nine variants in TPMT, DPYD, and CYP2C19 that were detected in MI-Oncoseq were confirmed by external genotyping. Genotype determinations could not be made for CYP3A5*3, UGT1A1*28, or UGT1A1*80. On the basis of retrospective assessment of 115 adult and pediatric patient records, 4.3% (n = 5) had a potentially clinically actionable phenotype for TPMT, DPYD, or CYP2C19 and received a relevant medication. After accounting for differences in adult and pediatric recommendations, three of these patients could have received a treatment recommendation at the time of prescribing. Conclusion Germline genotype determinations for TPMT, DPYD, and CYP2C19 can be used to make evidence-based treatment recommendations in MI-Oncoseq patients. Although the proportion of patients for whom recommendations can be made is small, this added value to MI-Oncoseq and patient care comes at no additional genotyping cost. Pharmacogenetic assessment should be integrated into tumor sequencing programs that genotype matched germline DNA; however, the complexity and additional cost of implementing pharmacogenetics remain challenging.
Implementation of a CPG and process improvements significantly reduced median TTA administration. Total patient arrivals per hour as a proxy of ED crowding did not affect TTA administration. Our data suggest that positive improvements in clinical care can be successful despite fluctuations in ED patient volume.
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