Extreme oncoplasty is a breast conserving operation, using oncoplastic techniques, in a patient who, in most physicians' opinions, requires a mastectomy. These are generally large, greater than 5 cm multifocal or multicentric tumors. Many will have positive lymph nodes. Most will require radiation therapy, even if treated with mastectomy. Sixty-six consecutive patients with multifocal, multicentric, or locally advanced tumors that spanned more than 50 mm were studied (extreme cases). All patients underwent excision and oncoplastic reconstruction using a standard or split wise pattern reduction and immediate contralateral surgery for symmetry. All received postexcisional standard whole breast radiation therapy with a boost to the tumor bed. The extreme cases were compared with 245 consecutive patients with unifocal or multifocal tumors that spanned 50 mm or less (standard cases). All extreme patients were advised to have a mastectomy; all sought a breast conserving second opinion. Diagnostic evaluation included digital mammography, ultrasound, MRI, and PET-CT (if invasive). Standard cases did extremely well. No ink on tumor was achieved 96% of the time among 245 patients. The median tumor size was 21 mm (mean 23 mm). Margins equal or greater than 1 mm were achieved in 88.6% of patients. Seventeen (6.9%) standard patients underwent re-excision to achieve wider margins and only one patient (0.4%) was converted to mastectomy. With 24 months of median follow-up, three patients (1.2%) experienced local recurrence. For extreme cases, no ink on tumor was achieved 83.3% of the time, which is comparable to published positive margin rates after standard lumpectomy. The median tumor size was 62 mm (mean 77 mm). Margins equal or greater than 1 mm were achieved in 54.5% of patients. Six (9.1%) extreme patients underwent re-excision to achieve wider margins and four patients (6.1%) were converted to mastectomy. With a follow-up of 24 months, one patient (1.5%) experienced a local recurrence. Extreme oncoplasty is a promising new concept. It allows successful breast conservation in selected patients with greater than 5 cm multifocal/multicentric tumors. It may be useful in patients with locally advanced tumors following neo-adjuvant chemotherapy. From a quality of life point of view, it is a better option than the combination of mastectomy, reconstruction, and radiation therapy. Long-term data on recurrence and survival are not available, using this approach. Based on historical data, it is expected the local recurrence will be somewhat higher but that there will be little or no impact on survival.

Nitric oxide (NO) regulates flow and permeability. ACh and platelet-activating factor (PAF) lead to endothelial NO synthase (eNOS) phosphorylation and NO release. While ACh causes only vasodilation, PAF induces vasoconstriction and hyperpermeability. The key differential signaling mechanisms for discriminating between vasodilation and hyperpermeability are unknown. We tested the hypothesis that differential translocation may serve as a regulatory mechanism of eNOS to determine specific vascular responses. We used ECV-304 cells permanently transfected with eNOS-green fluorescent protein (ECVeNOS-GFP) and demonstrated that the agonists activate eNOS and reproduce their characteristic endothelial permeability effects in these cells. We evaluated eNOS localization by lipid raft analysis and immunofluorescence microscopy. After PAF and ACh, eNOS moves away from caveolae. eNOS distributes both in the plasma membrane and Golgi in control cells. ACh (10(-5) M, 10(-4) M) translocated eNOS preferentially to the trans-Golgi network (TGN) and PAF (10(-7) M) preferentially to the cytosol. We suggest that PAF-induced eNOS translocation preferentially to cytosol reflects a differential signaling mechanism related to changes in permeability, whereas ACh-induced eNOS translocation to the TGN is related to vasodilation.

Oncoplastic surgery combines plastic surgical techniques with sound surgical oncologic principles. The goal is to completely excise the cancer, with wide surgical margins while maintaining or improving cosmesis. For large, poorly defined, or unfavorably situated tumors, standard lumpectomies may lead to unacceptable cosmetic results in addition to close or involved resection margins. Similar problems may occur for smaller tumors in small breasts. Integration of the two surgical disciplines avoids or minimizes poor cosmetic results after wide excision. It increases the number of women who can be treated with breast-conserving surgery by allowing larger breast excisions with more acceptable cosmetic results. Oncoplastic surgery requires a multidisciplinary approach and thorough preoperative planning. It is absolutely necessary to enlist the cooperation and coordination of surgical oncology, plastic surgery, radiology, pathology, medical oncology, and radiation oncology. Oncoplastic surgery requires a philosophy that the appearance of the breast after tumor excision is important.