RESUMEN
Screening of postmortem blood and urine samples is used to identify compounds that may have contributed to an individual's death. Toxicologically significant compounds detected by the screen are then quantitated in blood to determine their likely effect upon death. In most laboratories, this is a two-step process. This study compares an established two-step screening and quantitative processes, utilizing a gas chromatography-mass spectrometry (GC-MS) screen followed by quantitation by GC-MS or high-performance liquid chromatography with diode array detection (HPLC-DAD), with a novel method utilizing liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The LC-HRMS assay is able to screen postmortem blood and urine samples and simultaneously measure the concentration of toxicologically significant compounds in postmortem blood. Screening results of 200 postmortem blood samples and 103 postmortem urine samples by LC-HRMS and GC-MS showed that LC-HRMS detected key compounds in 125% more instances and there was a 60% increase in the number of compounds detected. Quantitative values generated using the LC-HRMS assay were within ±10% of values obtained using the established methods by GC-MS or HPLC-DAD. A retrospective analysis of turnaround times pre- and post-adoption of LC-HRMS showed a decrease for all of the compounds in the analysis, including a 43% reduction for free morphine and codeine, a 50% reduction for amphetamine and a 37% reduction for cocaine. Combining screening and quantitation reduced staffing requirements by 2 days for opiate quantitation and 1 day for most other analytes. The adoption of LC-HRMS also significantly reduced sample volume requirements. These results demonstrate that the adoption of LC-HRMS for simultaneous screening and quantitation delivered significant benefits in comparison to the two-step procedure.
Asunto(s)
Estudios Retrospectivos , Espectrometría de Masas , Cromatografía Liquida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Cromatografía Líquida de Alta PresiónRESUMEN
OBJECTIVES: Examine the cause of local recurrence (LR) and patient survival (S) following abdominoperineal resection (APR) and anterior resection (AR) for rectal carcinoma and the effect of introduction of total mesorectal excision (TME) on APR. METHODS: A total of 608 patients underwent surgery for rectal cancer in Leeds from 1986 to 1997. CRM status and follow-up data of local recurrence and patient survival were available for 561 patients, of whom 190 underwent APR (32.4%) and 371 AR (63.3%). Also, a retrospective study of pathologic images of 93 specimens of rectal carcinoma. RESULTS: Patients undergoing APR had a higher LR and lower survival (LR, 22.3% versus 13.5%, P = 0.002; S, 52.3% versus 65.8%, P = 0.003) than AR. LR free rates were lower in the APR group and cancer specific survival was lowered (LR, 66% versus 77%, log rank P = 0.03; S, 48% versus 59%, log rank P = 0.02). Morphometry: total area of surgically removed tissue outside the muscularis propria was smaller in APR specimens (n = 27) than AR specimens (n = 66) (P < 0.0001). Linear dimensions of transverse slices of tissue containing tumor, median posterior, and lateral measurements were smaller (P < 0.05) in the APR than the AR group. APR specimens with histologically positive CRM (n = 11) had a smaller area of tissue outside the muscularis propria (P = 0.04) compared with the CRM-negative APR specimens (n = 16). Incidence of CRM involvement in the APR group (41%) was higher than in the AR group (12%) (P = 0.006) in the 1997 to 2000 cohort. Similar results (36% and 22%) were found in the 1986 to 1997 cohort (P = 0.002). CONCLUSIONS: Patients treated by APR have a higher rate of CRM involvement, a higher LR, and poorer prognosis than AR. The frequency of CRM involvement for APR has not diminished with TME. CRM involvement in the APR specimens is related to the removal of less tissue at the level of the tumor in an APR. Where possible, a more radical operation should be considered for all low rectal cancer tumors.