4. Laryngoscope, 127:616-622, 2017.

IMPORTANCE Melanoma is among the most common malignant neoplasms in the United States, with 91 270 cases estimated to be diagnosed in 2018. Since 2012, Mohs micrographic surgery (MMS) has gained popularity in the treatment of melanoma in situ. Although current guidelines for invasive melanoma without nodal metastases recommend surgery with wide margin excision (WME), use of MMS for this disease has increased as well, particularly in early stages. How the survival outcomes after each procedure compare with one another for early-stage invasive melanoma is unknown to date. OBJECTIVE To evaluate overall survival of patients with stage I melanoma defined by the American Joint Committee on Cancer Cancer Staging Manual, 8th edition (AJCC-8) after MMS vs traditional WME. DESIGN, SETTING, AND ANALYSIS This retrospective cohort study includes all patients with AJCC-8 stage I melanoma who underwent MMS or WME in the National Cancer Database with a diagnosis from January 1, 2004, through December 31, 2014. The National Cancer Database includes all reportable cases from Commission on Cancer-accredited facilities and represents approximately 50% of all newly diagnosed melanoma cases in the United States. Data were analyzed from November 13, 2018, through June 9, 2019. EXPOSURES MMS vs WME. MAIN OUTCOMES AND MEASURES Overall survival evaluated using multivariable Cox proportional hazards regression analysis. RESULTS A total of 70 319 eligible patients (52.3% male and 47.7% female; median [SD] age, 57.0 [16.2] years) were identified, including 67 085 treated with WME and 3234 treated with MMS. Multivariable Cox proportional hazards regression survival analysis controlling for clinical and tumor factors revealed that treatment with MMS was associated with a modest improvement in overall survival relative to WME (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97). Propensity score-matched analysis of cohorts of patients treated with MMS vs WME also found modestly improved survival for those treated with MMS (HR, 0.82; 95% CI, 0.68-0.98). Academic facilities were more likely to use MMS than nonacademic facilities (odds ratio, 2.03; 95% CI, 1.88-2.18). CONCLUSIONS AND RELEVANCE These findings suggest that Mohs surgery may provide an alternative approach to traditional WME for appropriately selected cases of AJCC-8 stage I melanoma without compromising patient survival.

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Renal ischemia-reperfusion injury (IRI) is a common cause of renal dysfunction and renal failure. Histone/protein deacetylases (HDACs) regulate gene accessibility and higher order protein structures and may alter cellular responses to a variety of stresses. We investigated whether use of pan- and class-specific HDAC inhibitors (HDACi) could improve IRI tolerance in the kidney. Using a model of unilateral renal IRI, we investigated early renal function after IRI, and calculated fibrosis after IRI using an automated scoring system. We found that pan-HDAC inhibition using trichostatin (TSA) yielded significant renal functional benefit at 24–96 hours (p < 0.001). Treated mice developed significantly less fibrosis at 30 days (p < 0.0004). Class I HDAC inhibition with MS-275 yielded similar effects. Protection from fibrosis formation was also noted in a cold ischemia transplant model (p < 0.008) with a trend toward improved cold ischemic survival in TSA-treated mice. These effects were not accompanied by induction of typical ischemic tolerance pathways or by priming of heat shock protein expression. In fact, heat shock protein 70 deletion or overexpression did not alter renal ischemia tolerance. Micro-RNA 21, known to be enhanced in vitro in renal tubular cells that survive stress, was enhanced by treatment with HDACi, pointing to possible mechanism.

Adjuvant radiotherapy is associated with improved survival for patients with adverse features, regardless of stage. The addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features is not associated with improved outcomes.