RESUMO
BACKGROUND: The presence of somatic mutations in the KRAS gene has been identified as a reliable strong negative predictor for the response to targeting the epidermal growth factor receptor (EGFR), in patients with metastatic colorectal cancer and the use of anti-EGFR monoclonal antibodies such as Cetuximab and Panitumumab is now restricted to patients with no detectable KRAS mutations. Between 30 and 40 % of colorectal cancers contain a mutated KRAS oncogene. The aim of this study was to evaluate concordance between three methods to analyze KRAS mutational status in regard to clinical testing. METHODS: We analyzed KRAS mutations in codons 12 and 13 of exon 2 in one hundred formalin-fixed paraffin-embedded (FFPE) colorectal cancer samples by three different methods: Direct Sequencing and two commercial kits on allele-specific oligonucleotide hybridization (KRAS StripAssay, Vienna Lab.) and Amplification Refractory Mutation System/Scorpions (ARMS/S; TheraScreen KRAS Mutation kit DxS) based on q-PCR. RESULTS: We have found similar frequencies of KRAS mutations by TheraScreen and Strip-Assay (44 and 48 %), with a κ value of 0.90, indicating almost perfect agreement between methods. The frequency by direct sequencing was much lower (26 %) and the κ values were 0.67 (compared to TheraScreen) and 0.57 (compared to Strip-Assay) indicating low sensitivity. CONCLUSIONS: On analyzing KRAS mutation in FFPE tumor samples, direct sequencing sensitivity is too low to be used in a clinical setting. Choosing between ARMS/S; TheraScreen KRAS Mutation kit DxS and KRAS StripAssay, Vienna Lab, will depend on laboratory facilities and expertise (AU)
Assuntos
Humanos , Neoplasias Colorretais/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Códon , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Mutação , Receptores ErbB/genética , Análise de Sequência de Proteína , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
BACKGROUND: The Joint Commission on the Accreditation of Healthcare Organizations reports that communication breakdowns are responsible for 85% of sentinel events in hospitals. Patients in surgical ICUs are the most vulnerable to communication errors. Fellows and residents are an integral part of the surgical ICU team, but little is known about resident-fellow communication and its impact on surgical ICU patient outcomes. The objective of this study is to describe resident-fellow patient care communication patterns in the surgical ICU and correlate established communication patterns with short-term outcomes. STUDY DESIGN: A prospective observational trial was conducted for 136 consecutive surgical ICU days. We evaluated resident-fellow communication of four cardiorespiratory events: hypotension, new arrhythmias, tachypnea, and desaturation. We prospectively defined three short-term outcomes: improved, not improved, and worse. An intervention was attempted to improve communication. RESULTS: Three hundred twelve events were collected (166 observational and 146 interventional). PGY3 residents covered approximately 60% of days in both phases. PGY3 residents were responsible for 73% of communication errors in the observational phase and 59% of communication errors in the interventional phase. Communication errors were more likely in the late shift (p < 0.0001). The late shift was responsible for 77% of all communication errors. Communication errors resulted in worse short-term outcomes for cardiorespiratory events (p < 0.0002). Effective communication was a significant predictor of improved short-term outcomes (p < 0.0003). The intervention decreased communication errors in the late shift by 10% (p < 0.052). CONCLUSIONS: Communication errors occurred more frequently during the late shift. These communication errors were associated with worsened short-term outcomes. Improved communication in the surgical ICU is a fruitful target to improve clinical outcomes.
