Tumor-to-Nipple Distance as a Predictor of Nipple Involvement: Expanding the Inclusion Criteria for Nipple-Sparing Mastectomy.

BACKGROUND: A tumor-to-nipple distance of greater than 2 cm has traditionally been considered a criterion for nipple-sparing mastectomy. This study evaluates whether magnetic resonance imaging and sonographic measurements of tumor-to-nipple distance accurately reflect the risk of nipple involvement by disease. METHODS: All nipple-sparing mastectomy cases with implant-based reconstruction performed by the senior author between July 2006 and December 2014 were retrospectively reviewed. Therapeutic cases with preoperative magnetic resonance imaging or sonography were included. RESULTS: One hundred ninety-five cases were included. Preoperative imaging consisted of sonography (n = 169), magnetic resonance imaging (n = 152), or both (n = 126). With sonography, nipple involvement did not differ between nipple-sparing mastectomy candidates and noncandidates using a tumor-to-nipple distance cutoff of 2 cm (10.7 percent versus 10.6 percent; p = 0.988) or 1 cm (9.3 percent versus 15.0 percent; p = 0.307). With magnetic resonance imaging, nipple involvement did not differ between candidates and noncandidates using a cutoff of 2 cm (11.6 percent versus 12.5 percent; p = 0.881) or 1 cm (11.4 percent versus 13.8 percent; p = 0.718). When sonography and magnetic resonance imaging findings were both available and concordant, nipple involvement still did not differ between candidates and noncandidates using a cutoff of 2 cm (8.8 percent versus 11.8 percent; p = 0.711) or 1 cm (7.6 percent versus 14.3 percent; p = 0.535). CONCLUSION: A tumor-to-nipple distance as small as 1 cm, as measured by sonography or magnetic resonance imaging, should not be considered a contraindication to nipple-sparing mastectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Nipple Resection and Reconstruction After Attempted Nipple-Sparing Mastectomy.

BACKGROUND: Occult nipple malignancy is detected in 0% to 58% of attempted nipple-sparing mastectomies (NSM), prompting excision of the nipple. We report our experience with nipple resection following attempted NSM and our outcomes with subsequent nipple reconstruction. METHODS: An institutional review board-approved retrospective review was performed of attempted NSM cases with immediate implant-based reconstruction from July 2006 to April 2015. Patients who underwent nipple excision were identified. Indications for excision, pathology reports, and reconstructive outcomes were reviewed. RESULTS: Five hundred sixty-eight NSMs were performed in 330 patients. Thirty-four (6%) cases underwent nipple excision, 53% for positive frozen sections, 29% for positive permanent sections, 3% for clinical suspicion, and 15% either at patient request or for symmetry. All of the cases with positive frozen sections had disease on permanent section and 56% had residual disease in the resection specimen. Of the cases with positive permanent sections, frozen sections were negative in 50%, suspicious or atypical in 30%, and not sent in 20% of cases. Thirty percent had residual disease in the resection specimen. Frozen section sensitivity was 64% (or 75% if suspicious and atypical findings are included). There were no false-positive results on frozen section. Sixty-eight percent of cases have undergone nipple reconstruction by CV flap (57%), skate flap (39%), or nipple-sharing technique (4%). The aesthetic result after reconstruction was excellent in 83% of cases. CONCLUSIONS: Our findings support the benefit of intraoperative subareolar frozen section for detection of occult disease. When nipple excision is required, patients can still achieve an excellent aesthetic result with reconstruction.

Obesity paradox, obesity orthodox, and the metabolic syndrome: An approach to unity.

Obesity and the accompanying metabolic syndrome are strongly associated with heightened morbidity and mortality in older adults. In our review of more than 20 epidemiologic studies of major infectious diseases, including leaders such as tuberculosis, community-acquired pneumonia, and sepsis, obesity was associated with better outcomes. A cause-and-effect relationship between over-nutrition and survival with infection is suggested by results of two preliminary studies of infections in mice, where high fat feeding for 8-10 weeks provided much better outcomes. The better outcomes of infections with obesity are reminiscent of many recent studies of "sterile" non-infectious medical and surgical conditions where outcomes for obese patients are better than for their thinner counterparts --- and given the tag "obesity paradox". Turning to the history of medicine and biological evolution, we hypothesize that the metabolic syndrome has very ancient origins and is part of a lifelong metabolic program. While part of that program (the metabolic syndrome) promotes morbidity and mortality with aging, it helps infants and children as well as adults in their fight against infections and recovery from injuries, key roles in the hundreds of centuries before the public health advances of the 20th century. We conclude with speculation on how understanding the biological elements that protect obese patients with infections or injuries might be applied advantageously to thin patients with the same medical challenges.

The brighter (and evolutionarily older) face of the metabolic syndrome: evidence from Trypanosoma cruzi infection in CD-1 mice.

BACKGROUND: Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection. METHODS: In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. RESULTS: In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 mice was reduced from 55% to 20% by an 8-week pre-feeding of an HFD to induce obesity and metabolic syndrome. The addition of metformin reduced mortality to 3%. CONCLUSIONS: It is an interesting observation that both the high fat diet and the metformin, which are known to differentially attenuate host metabolism, effectively modified mortality in T. cruzi-infected mice. In humans, the metabolic syndrome, as presently construed, produces immune activation and metabolic alterations that promote complications of obesity and diseases of later life, such as myocardial infarction, stroke, diabetes, Alzheimer's disease and cancer. Using an evolutionary approach, we hypothesized that for millions of years, the channeling of host resources into immune defences starting early in life ameliorated the effects of infectious diseases, especially chronic infections, such as tuberculosis and Chagas disease. In economically developed countries in recent times, with control of the common devastating infections, epidemic obesity and lengthening of lifespan, the dwindling benefits of the immune activation in the first half of life have been overshadowed by the explosion of the syndrome's negative effects in later life.