Parvathi A. Myer

There are more than 70 distinct sarcomas, and this diversity complicates the development of precision-based therapeutics for these cancers. Prospective comprehensive genomic profiling could overcome this challenge by providing insight into sarcomas' molecular drivers. Through targeted panel sequencing of 7494 sarcomas representing 44 histologies, we identify highly recurrent and type-specific alterations that aid in diagnosis and treatment decisions. Sequencing could lead to refinement or reassignment of 10.5% of diagnoses. Nearly one-third of patients (31.7%) harbor potentially actionable alterations, including a significant proportion (2.6%) with kinase gene rearrangements; 3.9% have a tumor mutational burden ≥10 mut/Mb. We describe low frequencies of microsatellite instability (<0.3%) and a high degree of genome-wide loss of heterozygosity (15%) across sarcomas, which are not readily explained by homologous recombination deficiency (observed in 2.5% of cases). In a clinically annotated subset of 118 patients, we validate actionable genetic events as therapeutic targets. Collectively, our findings reveal the genetic landscape of human sarcomas, which may inform future development of therapeutics and improve clinical outcomes for patients with these rare cancers.

OBJECTIVES: Gastrointestinal (GI) emergencies may cause substantial morbidity. Our aims were to characterize the national clinical and economic burden of GI visits to emergency departments (EDs) in the United States. METHODS: We performed an observational cross-sectional study using the 2007 Nationwide Emergency Department Sample, the largest US all-payer ED database, to identify the leading causes for ED visits due to GI diseases and their associated charges, stratified by age and sex. Logistic regression was used to analyze predictors of hospitalization after an ED visit. RESULTS: Of the 122 million ED visits in 2007, 15 million (12%) had a primary GI diagnosis. The leading primary GI diagnoses were abdominal pain (4.7 million visits), nausea and vomiting (1.6 million visits), and functional disorders of the digestive system (0.7 million visits). The leading diagnoses differed by age group. The fraction of ED visits resulting in hospitalization was 21.6% for primary GI diagnoses vs. 14.7% for non-GI visits. Women had more ED visits with a primary GI diagnosis than men (58.5 (95% CI 56.0-60.9) vs. 41.6 (95% CI 39.8-43.3) per 1000 persons), but lower rates of subsequent hospitalization (20.0% (95% CI 19.4-20.7%) vs. 24.0% (95% CI 23.3-24.6%)). There were no differences in hospitalization rates between sexes after adjustment by age, primary GI diagnosis, and Charlson Comorbidity Score. The total charges for ED visits with a primary GI diagnosis in 2007 were $27.9 billion. CONCLUSIONS: GI illnesses account for substantial clinical and economic burdens on US emergency medical services.

OBJECTIVES: Heritable and environmental factors may contribute to differences in colorectal cancer (CRC) incidence across populations. We capitalized on the resources of the California Cancer Registry (CCR) and California's diverse Asian population to perform a cohort study exploring the relationships between CRC incidence, nativity, and neighborhood-level factors across Asian subgroups. METHODS: We identified CRC cases in the CCR from 1990 to 2004 and calculated age-adjusted CRC incidence rates for non-Hispanic Whites and US-born vs. foreign-born Asian ethnic subgroups, stratified by neighborhood socioeconomic status (SES) and "ethnic enclave." Trends were studied with joinpoint analysis. RESULTS: CRC incidence was lowest among foreign-born South Asians (22.0/100,000; 95% confidence interval (CI): 19.7-24.5/100,000) and highest among foreign-born Japanese (74.6/100,000; 95% CI: 70.1-79.2/100,000). Women in all Asian subgroups except Japanese, and men in all Asian subgroups except Japanese and US-born Chinese, had lower CRC incidence than non-Hispanic Whites. Among Chinese men and Filipino women and men, CRC incidence was lower among foreign-born than US-born persons; the opposite was observed for Japanese women and men. Among non-Hispanic Whites, but not most Asian subgroups, CRC incidence decreased over time. CRC incidence was inversely associated with neighborhood SES among non-Hispanic Whites, and level of ethnic enclave among Asians. CONCLUSIONS: CRC incidence rates differ substantially across Asian subgroups in California. The significant associations between CRC incidence and nativity and residence in an ethnic enclave suggest a substantial effect of acquired environmental factors. The absence of declines in CRC incidence rates among most Asians during our study period may point to disparities in screening compared with Whites.