Expression of E6AP and PML predicts for prostate cancer progression and cancer-specific death.

BACKGROUND: The promyelocytic leukemia (PML) tumor suppressor plays an important role in the response to a variety of cellular stressors and its expression is downregulated or lost in a range of human tumors. We have previously shown that the E3 ligase E6-associated protein (E6AP) is an important regulator of PML protein stability but the relationship and clinical impact of PML and E6AP expression in prostatic carcinoma is unknown. METHODS: E6AP and PML expression was assessed in tissue microarrays from a phase I discovery cohort of 170 patients treated by radical prostatectomy for localized prostate cancer (PC). Correlation analysis was carried out between PML and E6AP expression and clinicopathological variates including PSA as a surrogate of disease recurrence. The results were confirmed in a phase II validation cohort of 318 patients with associated clinical recurrence and survival data. RESULTS: Survival analysis of the phase I cohort revealed that patients whose tumors showed reduced PML and high E6AP expression had reduced time to PSA relapse (P = 0.012). This was confirmed in the phase II validation cohort where the expression profile of high E6AP/low PML was significantly associated with reduced time to PSA relapse (P < 0.001), clinical relapse (P = 0.016) and PC-specific death (P = 0.014). In multivariate analysis, this expression profile was an independent prognostic indicator of PSA relapse and clinical relapse independent of clinicopathologic factors predicting recurrence. CONCLUSION: This study identifies E6AP and PML as potential prognostic markers in localized prostate carcinoma and supports a role for E6AP in driving the downregulation or loss of PML expression in prostate carcinomas.

Cost of endovascular versus open surgical repair of abdominal aortic aneurysms.

BACKGROUND: Endovascular repair of abdominal aortic aneurysms (AAA) is a new minimally invasive method of aneurysm exclusion that has been adopted with increasing enthusiasm, and with acceptable clinical results. It is important, however, to assess new health-care technologies in terms of their economic as well as their clinical impact. The aim of the present study was to compare the total treatment costs for endovascular (EVR) and open surgical repair (OSR) for AAA. METHODS: A retrospective review of patient hospital and outpatient records for 62 patients undergoing either EVR (n = 31) or OSR (n = 31) was carried out between June 1996 and October 1999. Resource utilization was determined by a combination of patient clinical and financial accounting data. Costs were determined for preoperative assessment, inpatient hospital stay, cost of readmissions and follow up, and predicted lifetime follow-up costs. RESULTS: The two groups were well matched, with no significant difference with respect to age, gender, maximum aneurysm diameter or comorbid factors. Endovascular treatment resulted in a shorter intensive care unit (ICU) and hospital stay (mean: 0.07 vs 2.9 days, P < 0.001; mean: 6.0 vs 13.4 days, P < 0.001; respectively) and fewer postoperative complications (P = 0.003). The cost of hospitalization was less for EVR ($7614 vs $15092, P < 0.001), but this was offset by the more costly vascular prosthesis ($10284 vs $686). Costs were higher for the EVR group for preoperative assessment ($2328 vs $1540, P < 0.001) and follow up ($1284 vs $70, P < 0.001). Lifelong follow up could be expected to cost an additional $4120 per patient after EVR. Total lifetime treatment costs including costs associated with readmission for procedure-related complications were higher for EVR ($26909 vs $17650). CONCLUSION: Treatment costs for endovascular repair are higher than conventional surgical repair due to the cost of the vascular prosthesis and the greater requirement for radiological imaging studies.