Background-Nipple-sparing mastectomy (NSM) is increasingly performed for invasive breast cancer. Growing evidence supporting NSM's oncologic safety has led to its widespread use and broadened indications. Here we examine indications, complications, and long-term outcomes of therapeutic NSM.Methods-From 2003-2016, women undergoing NSM for invasive cancer or ductal carcinoma in situ (DCIS) were identified from a prospectively maintained database. Patient and disease characteristics were compared by procedure year. Complications were compared by procedure year using generalized mixed effects models accounting for a random surgeon effect. Overall survival and time to recurrence were examined.Results-Of the 467 therapeutic NSMs, 337 (72%) were invasive cancer, 126 (27%) were DCIS, and 4 (1%) were phyllodes tumors. Median age was 45 years (range 24-75); median follow-up among survivors was 39.4 months. 357 (76.4%) cases were performed in 2011 or after. When comparing NSMs performed before and after 2011, there was a significant increase in NSMs performed for invasive tumors (58% vs 77%, p<.001). There was no difference in family history, genetic mutations, smoking status, neoadjuvant chemotherapy, prior radiation, nodal involvement, or tumor subtype. 21 (4.5%) nipple excisions were performed; of which 14 were performed for cancer at the nipple margin. 44 breasts (9.4%) had complications that required re-operation. 15 patients had locoregional recurrence or distant metastasis.Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. https://www.springer.com/aamterms-v1
The schedule showed an interesting activity, taking into account that 27% of patients had received previous treatment for MBC. One week of rest may benefit not only the patient but may also improve tolerability and efficacy of the combination.
Surgery should never be indicated on the basis of positive or negative preoperative localization studies. Intraoperative quick parathyroid hormone measurements seem particularly helpful for cases with equivocal localization studies. The best minimal access approach is still a matter of debate, and options include small central incision, video-assisted parathyroidectomy, minimal lateral open approach, and purely endoscopic access via lateral approach. Radioguided surgery does not seem to have a role in routine cases but may be useful to find adenomas during reintervention on scarred difficult surgical fields.
BackgroundObesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells.Methods/DesignFATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers' predictive performance.DiscussionThe work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies.
Healthy expansion of human adipose tissue requires mesenchymal stem cells (hMSC) able to proliferate and differentiate into mature adipocytes. Hence, characterization of those factors that coordinate hMSC-to-adipocyte transition is of paramount importance to modulate the adipose tissue expansion. It has been previously reported that the adipogenic program of hMSC can be disrupted by upregulating caveolar proteins, and polymerase I and transcript release factor (PTRF) is an integral component of caveolae, highly expressed in adipose tissue. Here, we hypothesized that the role of PTRF in adipocyte functionality might stem from an effect on hMSC. To test this hypothesis, we isolated hMSC from the subcutaneous fat depot. We found an upregulated expression of the PTRF associated with decreased adipogenic potential of hMSC, likely due to the existence of senescent adipocyte precursors. Employing short hairpin RNA-based constructs to stably reduce PTRF, we were able to restore insulin sensitivity and reduced basal lipolysis and leptin levels in human adipocytes with high levels of PTRF. Additionally, we pinpointed the detrimental effect caused by PTRF on the adipose tissue to the existence of senescent adipocyte precursors unable to proliferate and differentiate into adipocytes. This study provides evidence that impaired adipocyte functionality can be corrected, at least partially, by PTRF downregulation and warrants further in vivo research in patients with dysfunctional adipose tissue to prevent metabolic complications.
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