Analysis of the Genetic Characteristics and Metastatic Pathways of G1 and G2 Colorectal Neuroendocrine Neoplasms.

Objective: G1 and G2 colorectal neuroendocrine neoplasms (NENs) are a group of rare and indolent diseases. We aimed to delineate their genetic characteristics and explore their metastatic mechanisms. Methods: We used next-generation sequencing technology for targeted sequencing for 54 patients with G1 and G2 colorectal NENs. We delineated their genetic features and compared the genetic characteristics between metastatic NENs and nonmetastatic NENs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was utilized to explore their abnormal pathways and study their potential metastatic mechanisms. Results: We collected 23 metastatic NENs and 31 nonmetastatic NENs. In the whole cohort, the common mutated genes were NCOR2, BRD4, MDC1, ARID1A, AXIN2, etc. The common copy number variations (CNVs) included amplification of HIST1H3D, amplification of HIST1H3E, and loss of PTEN. The KEGG enrichment analysis revealed that PI3K-Akt, MAPK, and Rap1 were the major abnormal pathways. There were significantly different genetic features between metastatic NENs and nonmetastatic NENs. The metastatic NENs shared only 47 (22.5%) mutated genes and 6 (13.3%) CNVs with nonmetastatic NENs. NCOR2, BRD4, CDKN1B, CYP3A5, and EIF1AX were the commonly mutated genes in metastatic NENs, while NCOR2, MDC1, AXIN2, PIK3C2G, and PTPRT were the commonly mutated genes in nonmetastatic NENs. Metastatic NENs presented a significantly higher proportion of abnormal pathways of cell senescence (56.5% vs 25.8%, P = .022) and lysine degradation (43.5% vs 16.1%, P = .027) than nonmetastatic NENs. Conclusion: G1 and G2 colorectal NENs are a group of heterogeneous diseases that might obtain an increased invasive ability through aberrant cell senescence and lysine degradation pathways.

Using a National Representative Sample to Evaluate the Integrity of the 30-Day Surgical Mortality Metric.

The 30-day surgical mortality metric is endorsed by the National Quality Forum for value-based purchasing purposes. However, its integrity has been questioned, as there is documented evidence of hospital manipulation of this measure, by way of inappropriate palliative care designation and changes in patient selection. To determine if there is evidence of potential manipulation, we retrospectively analyzed 1,725,291 surgical admissions from 158 United States hospitals participating in the National Inpatient Sample from 2010 to 2011. As a way of evaluating unnecessary life-prolonging measures, we determined that a significant increase in mortality rate after post-operative day 30 (day 31-35) would indicate manipulation. We compared the post-operative mortality rates for each hospital between Post-Operative Day 26-30 and Post-Operative Day 31-35 using Wilcoxon signed-rank tests. After application of the Bonferroni correction, the results showed that none of the hospitals had a statistically significant increase in mortality after post-operative day 30. This analysis fails to impugn the integrity of this measure, as we did not identify any evidence of potential manipulation of the 30-day surgical mortality metric.