BACKGROUND Minimally invasive surgery was adopted as an alternative to laparotomy (open surgery) for radical hysterectomy in patients with early-stage cervical cancer before high-quality evidence regarding its effect on survival was available. We sought to determine the effect of minimally invasive surgery on all-cause mortality among women undergoing radical hysterectomy for cervical cancer. METHODS We performed a cohort study involving women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer during the 2010–2013 period at Commission on Cancer–accredited hospitals in the United States. The study used inverse probability of treatment propensity-score weighting. We also conducted an interrupted time-series analysis involving women who underwent radical hysterectomy for cervical cancer during the 2000–2010 period, using the Surveillance, Epidemiology, and End Results program database. RESULTS In the primary analysis, 1225 of 2461 women (49.8%) underwent minimally invasive surgery. Women treated with minimally invasive surgery were more often white, privately insured, and from ZIP Codes with higher socioeconomic status, had smaller, lower-grade tumors, and were more likely to have received a diagnosis later in the study period than women who underwent open surgery. Over a median follow-up of 45 months, the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery (hazard ratio, 1.65; 95% confidence interval [CI], 1.22 to 2.22; P = 0.002 by the log-rank test). Before the adoption of minimally invasive radical hysterectomy (i.e., in the 2000–2006 period), the 4-year relative survival rate among women who underwent radical hysterectomy for cervical cancer remained stable (annual percentage change, 0.3%; 95% CI, −0.1 to 0.6). The adoption of minimally invasive surgery coincided with a decline in the 4-year relative survival rate of 0.8% (95% CI, 0.3 to 1.4) per year after 2006 (P = 0.01 for change of trend). CONCLUSIONS In an epidemiologic study, minimally invasive radical hysterectomy was associated with shorter overall survival than open surgery among women with stage IA2 or IB1 cervical carcinoma. (Funded by the National Cancer Institute and others.)
Treatment with RT was associated with longer LRFS, DFS, and OS in patients with early-stage breast cancer and detectable CTCs. These results are hypothesis generating; a prospective trial evaluating CTC-based management for RT after breast-conserving surgery in women with early-stage breast cancer is warranted.
Time-resolved electron paramagnetic resonance (TREPR) spectroscopy was used to study melanin free radicals in human retinal pigment epithelium (RPE) cells and tyrosine-derived synthetic melanin. TREPR signal traces from RPE cells reveal in vivo light-induced melanin free radical photochemistry in more detail than previously known. Electron spin polarization reflecting a non-Boltzmann population within the energy levels of the spin system is observed in RPE cells as the result of the triplet state photoproduction and subsequent disappearance of free radicals in the melanin polymer. In a set of RPE cells cultured from individual sources, differences in optical absorption, continuous wave EPR spectra, and TREPR signals were correlated with apoptosis assays performed by flow cytometry. Continuous wave EPR spectra of RPE cells and TREPR of acidified synthetic melanin suggest that increased melanin aggregation provides an increase in photoprotection in the RPE cells that are relatively less susceptible to blue light-induced apoptosis.continuous wave EPR ͉ electron spin polarization ͉ time-resolved EPR I n the eye, retinal pigment epithelium (RPE) is a monolayer of cuboidal cells between the photoreceptors and choriocapillaris of the eye and is specialized to uptake, phagocytize, and recycle the outer segment of photoreceptors and retinaldehyde, the chromophore of rhodopsin (1). RPE cell death plays a major role in the pathogenesis of age-related macular degeneration, the leading cause of blindness in the population Ͼ60 years of age in the developed world (2). Possible reasons given for the degeneration of RPE cells are their exposure to high oxidative stress and damaging irradiation (2-6).The pigment melanin, found in RPE cells, is a heterogeneous polymer consisting of various monomers believed to be oxidation products of dopa (dihydroxyphenylalinine) derived from tyrosine (7). Melanin contains intrinsic, indolesemiquinone-like doublet-state radicals (8, 9). Extrinsic indolesemiquinone-like radicals are reversibly photogenerated under visible or UV irradiation (9). RPE melanin serves a photoprotective role by absorbing radiation and scavenging free radicals and reactive oxygen species (ROS) (8-11). Evidence also exists for a phototoxic role for melanin in RPE cells, especially in aged cells, including measurable ROS photoproduction (8,(12)(13)(14)(15)(16)(17)(18). Electron paramagnetic resonance (EPR) spectroscopy enables a sensitive and nondestructive analysis and differentiation of natural melanin (9,19,20). The photophysical, redox, and aggregation properties of melanin as well as its ability to bind metals, proteins, and drugs have stimulated numerous studies in chemical, physical, and medical research (8, 9). The diversity and interrelations of its properties and the lack of chemical structures have hampered a clear understanding of the roles of melanin in RPE cells (8,9). Nanosecond time-resolved (TR) EPR studies have not been reported despite the relevance of TREPR to the study of melanin photochemistry (9). El...
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