Publications

BACKGROUND

Although magnetic resonance imaging (MRI) is a useful imaging modality for invasive cancer, its role in preoperative surgical planning for ductal carcinoma in situ (DCIS) has not been established. We sought to determine whether preoperative MRI affects surgical treatment and outcomes in women with pure DCIS.

PATIENTS AND METHODS

We reviewed consecutive records of women diagnosed with pure DCIS on core biopsy between 2000 and 2007. Patient characteristics, surgical planning, and outcomes were compared between patients with and without preoperative MRI. Multivariable regression was performed to determine which covariates were independently associated with mastectomy or sentinel lymph node biopsy (SLNB).

RESULTS

Of 149 women diagnosed with DCIS, 38 underwent preoperative MRI. On univariate analysis, patients undergoing MRI were younger (50 years vs. 59 years; P < .001) and had larger DCIS size on final pathology (1.6 cm vs. 1.0 cm; P = .007) than those without MRI. Mastectomy and SLNB rates were significantly higher in the preoperative MRI group (45% vs. 14%, P < .001; and 47% vs. 23%, P = .004, respectively). However, there were no differences in number of re-excisions, margin status, and margin size between the two groups. On multivariate analysis, preoperative MRI and age were independently associated with mastectomy (OR, 3.16, P = .018; OR, 0.95, P = .031, respectively), while multifocality, size, and family history were not significant predictors.

CONCLUSION

We found a strong association between preoperative MRI and mastectomy in women undergoing treatment for DCIS. Additional studies are needed to examine the increased rates of mastectomy as a possible consequence of preoperative MRI for DCIS.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes cardiomyocyte survival and contributes to ischemic preconditioning. S1P lyase (SPL) is a stress-activated enzyme responsible for irreversible S1P catabolism. We hypothesized that SPL contributes to oxidative stress by depleting S1P pools available for cardioprotective signaling. Accordingly, we evaluated SPL inhibition as a strategy for reducing cardiac ischemia-reperfusion (I/R) injury. We measured SPL expression and enzyme activity in murine hearts. Basal SPL activity was low in wild-type cardiac tissue but was activated in response to 50 min of ischemia (n = 5, P < 0.01). Hearts of heterozygous SPL knockout mice exhibited reduced SPL activity, elevated S1P levels, smaller infarct size, and increased functional recovery after I/R compared with littermate controls (n = 5, P < 0.01). The small molecule tetrahydroxybutylimidazole (THI) is a Federal Drug Administration-approved food additive that inhibits SPL. When given overnight at 25 mg/l in drinking water, THI raised S1P levels and reduced SPL activity (n = 5, P < 0.01). THI reduced infarct size and enhanced hemodynamic recovery in response to 50 min of ischemia and to 40 min of reperfusion in ex vivo hearts (n = 7, P < .01). These data correlated with an increase in MAP kinase-interacting serine/threonine kinase 1, eukaryotic translation initiation factor 4E, and ribosomal protein S6 phosphorylation levels after I/R, suggesting that SPL inhibition enhances protein translation. Pretreatment with an S1P₁ and S1P₃ receptor antagonist partially reversed the effects of THI. These results reveal, for the first time, that SPL is an ischemia-induced enzyme that can be targeted as a novel strategy for preventing cardiac I/R injury.

Lipodystrophy is commonly reported in Africa after antiretroviral therapy (ART) is initiated, but few studies have objectively measured changes in body composition. Body composition was determined in 76 HIV-infected participants from Mbarara, Uganda after starting a thymidine-analog regimen, and annual change was determined using repeated measures analysis. We measured skinfolds (tricep, thigh, subscapular, and abdomen), circumferences (arm, hip, thigh, waist), and total lean and fat mass (using bioelectric impedance analysis). A cross-sectional sample of 49 HIV-uninfected participants was studied for comparison. At baseline, most body composition measures were lower in HIV-infected than uninfected participants, but waist circumference was similar. After 12 months on ART, there was little difference in body composition measures between HIV-infected and uninfected participants; median waist circumference appeared higher in HIV-infected participants (79 vs. 75 cm; p = 0.090). Among HIV-infected participants, increases were observed in total lean and fat mass, circumference, and skinfold measures; only the increase in tricep skinfold did not reach statistical significance (+1.05 mm; 95% confidence interval: -0.24, 2.34; p = 0.11). Regional anthropometry in peripheral and central body sites increased over 12 months after ART initiation in HIV-infected persons from southwestern Uganda, suggesting a restoration to health. Gains in the tricep skinfold, a reliable marker of subcutaneous fat, appeared blunted, which could indicate an inhibitory effect of zidovudine on peripheral subcutaneous fat recovery.