Apoptotic caspases have long been studied for their roles in programmed cell death and tumor suppression. With recent discoveries, however, it is becoming apparent these cell death executioners are involved in additional biological pathways beyond killing cells. In some cases, apoptotic cells secrete growth signals to stimulate proliferation of neighboring cells. This pathway functions to regenerate tissues in multiple organisms, but it also poses problems in tumor resistance to chemo- and radiotherapy. Additionally, it was found that activation of caspases does not irreversibly lead to cell death, contrary to the established paradigm. Sub-lethal activation of caspases is evident in cell differentiation and epigenetic reprogramming. Furthermore, evidence indicates spontaneous, unprovoked activation of caspases in many cancer cells, which plays pivotal roles in maintaining their tumorigenicity and metastasis. These unexpected findings challenge current cancer therapy approaches aimed at activation of the apoptotic pathway. At the same time, the newly discovered functions of caspases suggest new treatment approaches for cancer and other pathological conditions in the future.

Background: Revision procedures address contour irregularities and aesthetic concerns following autologous breast reconstruction. Mental health diagnoses are known to influence patient satisfaction with reconstruction. The authors aimed to identify oncologic, reconstructive, and demographic factors, including mental health diagnoses, associated with the number of revisions after autologous breast reconstruction. Methods: The medical records of all adult women undergoing abdominal free flap–based breast reconstruction at a major academic institution between 2011 and 2016 were reviewed. Multivariate logistic regression was used to identify factors associated with receipt of revisions. Negative binomial regression was used to identify characteristics associated with number of revisions received. Results: Of 272 patients identified, 55.2 percent received one revision, 23.2 percent received two revisions, and 10.3 percent received three or more revisions after autologous breast reconstruction (median, one; range, zero to five). After adjustment on multivariate analysis, anxiety (OR, 4.34; p = 0.016) and bilateral reconstruction (OR, 3.10; p = 0.017) were associated with receipt of any revisions; other oncologic and reconstructive factors including breast cancer stage, receipt of radiation therapy, and type or timing of free flap reconstruction were not associated with revisions. Using univariate negative binomial regression, anxiety (incidence rate ratio, 1.34; p = 0.006), Caucasian race (incidence rate ratio, 1.24; p = 0.02), and bilateral reconstruction (incidence rate ratio, 1.39; p = 0.04) were predictive of increased numbers of revisions received. After stepwise selection on multivariate analysis, anxiety remained the only significant predictor of increased numbers of revisions. Conclusions: Preoperative anxiety significantly influences the number of revisions after autologous breast reconstruction. Further research is necessary to better understand the interplay among mental health, patient preference, and outcomes in breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.