Preoperative White Blood Cell Count in Patients with Abdominal Aortic Aneurysms and Its Relation to Survival following Surgery.

BACKGROUND: The aim of the present study was to explore whether preoperative white blood cell (WBC) count may predict 30-day mortality and long-term survival following surgery for abdominal aortic aneurysm (AAA). Secondarily, we wanted to assess the potential sex differences in WBC in these patients. METHODS: The study was carried out as a retrospective cohort study. Patients undergoing surgery for intact and ruptured AAA (rAAA) at our institution consecutively in the time period 1994-2007 were included. Patients were either treated with open aneurysm repair or with endovascular aneurysm repair. Data were collected from the patients' medical records, including laboratory reports for WBC count prior to surgery. Mortality and long-term survival were extracted from The Patient Administrative System. RESULTS: A total of 988 patients were included, 712 (72%) patients were treated for intact AAA and 276 (28%) underwent surgery for rAAA. Patients with WBC ≥11 ×109/L had a 8.7-fold higher risk of 30-day mortality undergoing surgery for intact AAA compared to patients with WBC <11 ×109/L (95% confidence interval [CI]: 3.2-23.3, P < 0.001). Patients with a high WBC tended to have inferior long-term survival. However, when excluding 30-day mortality, no statistically significant difference was found (hazard ratio, 1.4; 95% CI: 0.9-2.0, P = 0.121). No association between WBC count and 30-day mortality or long-term survival was observed among patients treated for rAAA. We could not identify any sex differences in WBC, neither in intact AAA nor in rAAA. We were not able identify any association between WBC and specific causes of death. CONCLUSIONS: This study suggests that patients with WBC count ≥11 ×109/L prior to surgery for intact AAA have a higher 30-day mortality compared to patients with WBC <11 ×109/L. We could not identify any substantial difference in long-term survival when excluding 30-day mortality. We did not observe any association between preoperative WBC count and case fatality or long-term survival in patients undergoing surgery for rAAA. No sex differences in WBC were found.

Amplification of TOP2A and HER-2 genes in breast cancers occurring in patients harbouring BRCA1 germline mutations.

BRCA1 associated tumours are found to express an oestrogen receptor negative "basal epithelial-like" phenotype. In contrast to ER negative tumours in general, such tumours rarely harbour amplification of the HER-2 gene. However, little is known about TOP2A gene amplification status in BRCA1-associated tumours. Such information may be of importance to therapy, as amplification of TOP2A has been associated with dose-dependent sensitivity to anthracycline therapy in breast cancer. We examined 40 breast carcinomas from BRCA1 mutation carriers and 40 sporadic breast carcinomas matched for age, tumour diameter and histological grade for HER-2 and TOP2A amplification status using fluorescence in situ hybridisation (FISH). Co-amplification of TOP2A and HER-2 was found in four of the mutation carriers and in three of the controls. While six tumours in the control group harboured HER-2 amplifications with normal TOP2A, this occurred in three of the BRCA1 associated tumours only. In contrast, three of the BRCA1-associated tumours but none of the controls harboured TOP2A amplification despite normal HER-2 status. Our findings have potential therapeutic implications. HER-2 assessment is routinely used to select breast cancer patients for trastuzumab but also dose-intensive anthracycline therapy. Our data suggest that BRCA1-associated breast cancers also need to be tested for TOP2A amplification.

Sensitivity of MRI versus conventional screening in the diagnosis of BRCA-associated breast cancer in a national prospective series.

We wanted to compare the sensitivities of breast magnetic resonance imaging (MRI) and the conventional screening programme consisting of mammography (XRM) +/- ultrasound for early diagnosis of breast cancer in BRCA1/2 mutation carriers. BRCA1/2 mutation carriers were examined prospectively by both breast MRI and XRM +/- ultrasound. Eight hundred and sixty-seven MRI examinations were carried out in 445 BRCA1 and 46 BRCA2 mutation carriers. A total of 25 cancers were observed, five (20%) as interval cancers. At the time of diagnosis, sensitivity to detect cancer was 19/22=86% for MRI and 12/24=50% for XRM. Twenty-one were examined by both methods at the time of diagnosis. In the19 BRCA1 mutation carriers among them, MRI had a sensitivity of 1/3(33%) to diagnose DCIS and 15/16 (94%) among the invasive cancers. For XRM the sensitivities were 1/3(33%) for DCIS, 3/7(42%) for pT1b, 3/6(50%) for pT1c, and 3/3/100%) for pT2. In the two BRCA2 mutation carriers, both were demonstrated by breast MRI, neither was detected by XRM. Breast MRI had increased sensitivity compared to XRM to diagnose all cancers staged less than pT2.

Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer.

PURPOSE: To evaluate potential detrimental effects of exemestane on bone and lipid metabolism. PATIENTS AND METHODS: Postmenopausal women with early breast cancer were randomly assigned to exemestane 25 mg daily or placebo for 2 years in a double-blind setting. Primary objective was to evaluate the effect of exemestane on bone mineral density. Secondary objectives were effects on bone biomarkers, plasma lipids, coagulation factors, and homocysteine. Planned size was 128 patients. RESULTS: One hundred forty-seven patients were enrolled. All patients completed their 24-month visit except for those discontinuing treatment at an earlier stage. The mean annual rate of bone mineral density loss was 2.17% v 1.84% in the lumbar spine (P = .568) and 2.72% v 1.48% in the femoral neck (P = .024) in the exemestane and placebo arm, respectively. The mean change in T-score after 2 years was -0.21 for exemestane and -0.11 on placebo in the hip, and -0.30 and -0.21, respectively, in the lumbar spine. Exemestane significantly increased serum level and urinary excretion of bone resorption, but also bone formation markers. Except for a modest reduction in high-density lipoprotein cholesterol (P < .001) and apolipoprotein A1 (P = .004), exemestane had no major effect on lipid profile, homocysteine levels, or coagulation parameters. CONCLUSION: Exemestane modestly enhanced bone loss from the femoral neck without significant influence on lumbar bone loss. Except for a 6% to 9% drop in plasma high-density lipoprotein cholesterol, no major effects on serum lipids, coagulation factors, or homocysteine were recorded. Bone mineral density should be assessed according to the US Preventive Services Task Force guidelines.