Arthur S. Patchefsky

Cerium oxide nanoparticles are potent antioxidants, based on their ability to either donate or receive electrons as they alternate between the +3 and +4 valence states. The dual oxidation state of ceria has made it an ideal catalyst in industrial applications, and more recently, nanoceria's efficacy in neutralizing biologically generated free radicals has been explored in biological applications. Here, we report the in vivo characteristics of custom-synthesized cerium oxide nanoparticles (CeNPs) in an animal model of immunological and free-radical mediated oxidative injury leading to neurodegenerative disease. The CeNPs are 2.9 nm in diameter, monodispersed and have a -23.5 mV zeta potential when stabilized with citrate/EDTA. This stabilizer coating resists being 'washed' off in physiological salt solutions, and the CeNPs remain monodispersed for long durations in high ionic strength saline. The plasma half-life of the CeNPs is ∼4.0 h, far longer than previously described, stabilized ceria nanoparticles. When administered intravenously to mice, the CeNPs were well tolerated and taken up by the liver and spleen much less than previous nanoceria formulations. The CeNPs were also able to penetrate the brain, reduce reactive oxygen species levels, and alleviate clinical symptoms and motor deficits in mice with a murine model of multiple sclerosis. Thus, CeNPs may be useful in mitigating tissue damage arising from free radical accumulation in biological systems.

Fifty-one women (29 to 75 years of age) with 55 cancers (ductal carcinoma in situ [DCIS] or ductal carcinoma in situ with microinvasion [DCISM] were studied by comparing biopsy specimens with mastectomy specimens. Presentation, histologic type, nuclear grade, microscopic duct counts, multicentricity, and microinvasion were correlated. Forty-seven percent of the cancers (26 of 55) were detected by mammography, 18% (ten of 55) were incidental to benign disease, and 35% (19 of 55) were palpable or exhibited nipple abnormality. Incidental tumors were all DCIS, averaged seven ducts, and showed no residual tumor during mastectomy. Mammographic lesions averaged 117 ducts (31% [eight of 26] were DCISM and 42% [11 of 26] were multicentric). Most comedocarcinomas that showed a high incidence of microinvasion were in this group. Clinical lesions averaged 110 ducts (42% [eight of 19] were DCISM and 68% [13 of 19] were multicentric). Three had nodal metastases. Mammographic and clinical tumors in the quantitative range of the incidental group (50 ducts) showed significant differences from it for all variables studied. Histologic and quantitative study of these tumors is necessary to best guide treatment. Incidental tumors, however, may only need observation.

BACKGROUND: Mammography has led to earlier detection of subclinical ductal carcinoma in situ (DCIS) of the breast either as nonpalpable calcifications or as an incidental finding in a biopsy performed for another reason. Many women in whom DCIS was detected early may not be destined to have an invasive carcinoma. How should subclinical DCIS be treated if that is the case? What is the role of excision and surveillance only as an alternative to mastectomy or irradiation? METHODS: All patients with DCIS detected as nonpalpable calcifications or as an incidental finding were eligible for this study. Diagnosis was confirmed, and the histologic subtype was determined. Results of postbiopsy mammography confirmed excision of calcifications; wide local reexcision and assessment of margins was also performed in most patients. The maximum diameter of calcifications considered suitable for this treatment was 25 mm. RESULTS: Between 1978 and 1990, 70 women (72 breasts) were entered into this study (mean follow-up time, 49 months; median follow-up time, 47 months). Of this group, 66% were detected as calcifications and 33% were detected as incidental findings. The recurrence rate was 15.3%. All but one of the patients who experienced a recurrence had the comedo type of DCIS as the initial lesion. Each of the recurrences was of the comedo type. All but one recurrence was at the same site as the primary lesion. None of the patients with DCIS as an incidental finding experienced a recurrence. CONCLUSIONS: Excision and surveillance is a reasonable alternative to mastectomy or irradiation for selected women with DCIS that presents as nonpalpable calcifications or as an incidental finding.

Adenomyoepitheliomas of the breast have been considered to have limited metastatic potential; axillary node metastasis has been reported, but there has been no report of distant metastasis. We report six cases, including two malignant adenomyoepitheliomas, one of which metastasized to the lung and brain. Patient age ranged from 26 to 63 years (mean 46). Primary tumors were solitary and measured 0.9-3.5 cm (mean 1.7). Five of six tumors presented as palpable masses. Two patients treated by local resection have no evidence of disease at 5 and 18 months' follow-up. Two patients treated by local resection had recurrences, one at 48 the other at 60 months. The fifth patient had a spindle-cell type adenomyoepithelioma diagnosed as malignant because of high mitotic rate and cytologic atypicality of the myoepithelial component. This patient was treated by mastectomy and has no evidence of disease at 18 months. The sixth patient, initially treated by local excision, had six local recurrences over 52 months treated by reexcisions, mastectomies, and radiation. A lung metastasis was resected at 54 months and brain metastases were identified at 60 months with death occurring at 64 months. Both malignant adenomyoepitheliomas had high mitotic rates [11-14/10 high-power fields (HPF)] diffusely throughout the tumors and foci of cytologically malignant cells. The malignant adenomyoepithelioma that metastasized had an infiltrative growth pattern that increased with successive local recurrences. The four other tumors had only isolated areas of mitotic activity (maximum 1-9/10 HPF) and minimal cytologic atypia. Immunohistochemistry performed on five of six cases confirmed dual epithelial/myoepithelial cell populations in all tumors examined, including the metastasis. Electron microscopic examination of the malignant adenomyoepithelioma that metastasized also confirmed dual epithelial/myoepithelial cell populations in a local recurrence and the lung metastasis. We conclude that there is a spectrum of behavior for breast adenomyoepitheliomas with potential for local recurrence and, rarely, distant metastasis.