Margin width is not predictive of residual disease on re-excision in breast conserving therapy.

BACKGROUND: There is lack of consensus regarding re-excision in breast-conserving therapy (BCT) and close margins. We hypothesize that margin width does not predict residual disease. METHODS: The cancer registry was queried from 2003 to 2008 for patients with BCT who underwent re-excision for <2-mm margins. Factors associated with additional disease were evaluated. RESULTS: One thousand eight hundred forty-three patients underwent BCT. Our re-excision rate was 42%. Clinicopathologic factors from 228 patients were analyzed. One hundred five patients (46%) had additional disease; of those, 58% had BCT and 42% mastectomy. One hundred twenty-three (54%) had no additional disease; of those 82% had BCT and 18% mastectomy. Of the 66 patients who underwent mastectomy, 44 (67%) had residual disease; of the 161 who had BCT, 61 (38%) had residual disease (P < 0.01). On univariate analysis, margin width did not correlate with residual disease. Multifocality, non-invasive histology, increasing number of close margins, and higher grade predicted additional disease (P < 0.05). On multivariate analysis, only number of close margins remained significant. CONCLUSIONS: Margin width does not predict additional disease. This challenges the practice of using this to select re-excision candidates. Our data suggest that tumor behavior and extent of disease, defined by volume of residual disease and invasiveness of histology, play a more significant role.

3,3'-diindolylmethane and paclitaxel act synergistically to promote apoptosis in HER2/Neu human breast cancer cells.

BACKGROUND: HER2/neu positive breast tumors are difficult to treat. About 25 to 30% of invasive breast tumors overexpress the HER2/neu oncogene. These tumors are aggressive and become resistant to chemotherapeutic drugs. 3'3'-diindolylmethane (DIM), the active metabolite of indole-3-carbinol, a naturally occurring compound found in cruciferous vegetables, has been found to have anti-cancer properties in both humans and animals. DIM has been shown to induce cell cycle arrest and apoptosis in animal breast cancer models. Because HER2/neu overexpression confers resistance to paclitaxel, and DIM has anti-tumor effects, we hypothesized that DIM will enhance the cytotoxic effects of paclitaxel, a common taxane drug, on human Her2/neu breast cancer cells by potentiating its effect on cell cycle and stimulating apoptosis. METHODS: The MDA-MB-435eB1 human Her2/neu breast cancer cells were treated with varying concentrations of DIM and paclitaxel. The cells were analyzed at different time points (24, 48, and 72 h). Proliferation was measured by a commercial cell proliferation assay (Promega Procheck Assay). Cell-cycle analysis and apoptosis were determined by flow cytometry. Western blot analysis was performed on to determine the effect of DIM and/or paclitaxel on the proteins involved in apoptosis, and epidermal growth factor-induced activation of HER2/neu and ERK1/2 signaling proteins. RESULTS: Both DIM and paclitaxel exhibited time and concentration dependent inhibition of cell proliferation. TUNEL assay indicated that the combination also increased the number of apoptotic cells more than either agent alone. The presence of cleaved poly (ADP-Ribose) polymerase (PARP) significantly increased in the combination treatment, whereas Bcl-2 is decreased. DIM alone decreased the activation of the Her2/neu receptor; the combination decreased the activation of ERK1/ERK2. CONCLUSIONS: DIM in combination with paclitaxel synergistically inhibits growth of Her2/neu human breast cancer cells through G2M phase cell-cycle arrest and induction of apoptosis/necrosis. The Her2/neu receptor and its downstream signaling protein ERK1/2 appear to be involved in DIM's affect on cell growth and differentiation, whereas apoptosis appears to be mediated through the mitochondrial pathway (Bcl-2/PARP). It appears DIM, a naturally occurring, nontoxic compound, may be a beneficial addition to a traditional (taxane-based) chemotherapy regimen.

The first sutureless, laser-welded, end-to-end bowel anastomosis.

The use of laser energy to weld together tissue offers great promise in the expanding field of laser surgery. The published results of laser welding intestinal tissue have, to date, been limited to the successful laser closures of small enterotomies. This is the first report of using laser energy alone to create an end-to-end small bowel anastomosis. A biocompatible, water-soluble, intraluminal stent was employed during the laser welding of this sutureless, stapleless ileal anastomosis in a rabbit model. Excellent recovery and healing were observed. The rapidity, ease, and potential for full precision automation of laser welding mandates further research.