Faculty Bibliography

The concept that epinephrine-based local anesthetics cannot be injected in terminal appendages has been perpetuated for decades. The hypothesis that the vasoconstrictive effect of epinephrine will result in finger necrosis has been accepted as fact, often preventing its use in hand surgery. To scientifically challenge this hypothesis, a systematic review of the literature was performed, and a survey of ASPS members reported to highlight the lack of evidence-based opinions. A systematic literature review performed using Medline, Embase, PubMed, and Cochrane databases identified all published studies evaluating use of epinephrine/adrenaline in hand, finger or digit surgery. Each study was independently evaluated by three reviewers for inclusion or exclusion from the systematic review. Additionally, a survey (E-survey link) was distributed to all ASPS members and data were collected over a 5-month period through SurveyMonkey®. A total of 568 articles published prior to December 2012 were identified. After elimination of 151 duplicates, 417 articles remained. Fifty-five articles were selected and full examination of the texts was performed. Forty-five studies matched the selection criteria and were included in the analysis. The ASPS member survey demonstrated a 13 % overall questionnaire response rate (5,299 questionnaires/687 responses). Of all respondents, 37.4 % felt it was unsafe to inject local anesthesia mixed with epinephrine into the fingers/thumb, respectively. Critical literature review validated the safety and efficacy of utilizing epinephrine-based local anesthetics. The author's survey elucidates the pervasive concern of employing epinephrine in hand surgery. Level of Evidence: Not ratable.

Oral mucositis is a significant problem in cancer patients treated with radiation or chemotherapy, often hindering definitive cancer treatment. For patients with oral mucositis, pain is the most distressing symptom, leading to loss of orofacial function and poor quality of life. While oral mucositis has been well-described, its pathophysiology is poorly understood. Oral health professionals treating patients with mucositis have almost no effective therapies to treat or prevent oral mucositis. The purpose of this review is to (1) describe the current preclinical models of oral mucositis and their contribution to the understanding of mucositis pathophysiology, (2) explore preclinical studies on therapies targeting mucositis and discuss the clinical trials that have resulted from these preclinical studies, and (3) describe the proposed pathophysiology of oral mucositis pain and preclinical modeling of oral mucositis pain.

Abstract Preoperative breast pain in women with breast cancer may result from a number of causes. Previous work from our team found that breast pain occurred in 28.2% of women (n = 398) who were about to undergo breast cancer surgery. The occurrence of preoperative breast pain was associated with a number of demographic and clinical characteristics, as well as variation in two cytokine genes. Given that ion channels regulate excitability of sensory neurons, we hypothesized that variations in potassium channel genes would be associated with preoperative breast pain in these patients. Therefore, in this study, we evaluated for associations between single-nucleotide polymorphisms and inferred haplotypes among 10 potassium channel genes and the occurrence of preoperative breast pain in patients scheduled to undergo breast cancer surgery. Multivariable logistic regression analyses were used to identify those genetic variations that were associated with the occurrence of preoperative breast pain while controlling for age and genomic estimates of and self-reported race/ethnicity. Variations in four potassium channel genes: (1) potassium voltage-gated channel, delayed rectifier, subfamily S, member 1 (KCNS1); (2) potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3); (3) KCNJ6; and (4) potassium channel, subfamily K, member 9 (KCNK9) were associated with the occurrence of breast pain. Findings from this study warrant replication in an independent sample of women who report breast pain following one or more breast biopsies.

Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence.

BACKGROUND: Metastasis to the cervical (neck) lymph nodes is one of the most significant clinical factors responsible for death from oral squamous cell carcinoma (SCC). Therefore, the lymph nodes are frequently removed when the tumor is excised (neck dissection), even though the majority of patients will not benefit from the extra surgery. Two subtypes of oral SCC distinguished by the presence of tumor genomic aberrations +3q, -8p, +8q and/or +20 differ in risk for metastasis - high for the 3q8pq20 subtype, harboring one or more of the aberrations and low for the non-3q8pq20 subtype, lacking these alterations. A prior analysis of the literature suggested genes differentially methylated in the two subtypes. Therefore, the goal of this study was to further investigate the methylation status of candidate biomarkers of the non-3q8pq20 subtype, and evaluate their utility for identifying patients at low risk for metastasis. METHODS: Methylation status of genes in a cohort of 52 oral SCC patients with at least five year follow up was determined by pyrosequencing. Gene expression levels were determined by quantitative RT-PCR. Growth following re-expression of HOXA9 in cultured oral SCC cells was assessed by proliferation and colony formation assays. RESULTS: A pilot study evaluating methylation levels of HOXA9, MT1A and HOXA11 promoters in DNA from 12 tumors (six each of the 3q8pq20 and non-3q8pq20 subtypes) revealed that only HOXA9 was differentially methylated. Significant differences in methylation levels of HOXA9 were observed amongst the 52 oral SCCs with respect to genomic subtype and nodal status (p = 0.014, and p = 0.024, respectively, Wilcoxon rank sum test). High levels of HOXA9 methylation and low levels of expression in oral SCC cell lines were observed compared to HaCaT, a non-tumorigenic keratinocyte cell line. Re-expression of HOXA9 in the SCC4 oral cancer cell line resulted in diminished proliferation and colony formation. CONCLUSIONS: HOXA9 methylation is frequent in oral cancers and levels are higher in tumors with greater risk of metastasis. Expression of HOXA9 is low in cells with high levels of methylation and reduced expression appears to confer a growth advantage.

BACKGROUND: Loss of volume after autologous fat transfer to the breast is well documented, and various methods to improve long-term survival of fat grafts have been investigated (including both distant and neighboring harvest sites), but no optimal technique has been identified. OBJECTIVE: The authors compare fat graft survival from 2 anatomical donor sites to determine whether there is an optimal site for fat graft harvesting in breast reconstruction. METHODS: Seventy-three patients (109 breasts) who received fat grafting to reconstructed breasts from 2009 to 2012 were enrolled in this retrospective study and divided into 2 groups: group A had fat harvested from the abdomen and group B from the thighs. Fat grafting was performed using a modified Coleman technique for symmetry. For all patients, 3-dimensional scans were obtained and volumes were analyzed. RESULTs: Forty-six patients (66 breasts) received an average of 101 mL of fat injected from the abdomen, and 27 (43 breasts) received an average of 102 mL from the thighs. Group A had 82% volume retention at 16 days, 63% at 49 days, and 45% at 140 days. Group B had 86% at 16 days, 63% at 49 days, and 46% at 140 days (P > .05). Patients were also stratified by radiation exposure and volume injected; neither affected donor site volume retention (P > .05). CONCLUSIONS: Our data suggest that donor site, regardless of volume injected or tissue radiation, did not affect volume retention in fat grafting. Longer-term studies are needed to assess the stability of the breast after fat grafting.

BACKGROUND: Aesthetic procedures are significant sources of revenue for plastic surgeons. With the popularity of nonsurgical aesthetic procedures, many plastic surgeons question how to best tailor their aesthetic practice. METHODS: Revenue generated from surgical and minimally invasive aesthetic procedures performed in the United States between 2000 and 2011 was calculated from the American Society of Plastic Surgeons' annual reports. Regression analysis was performed against six commonly cited economic indicators. RESULTS: In 2011, revenue from minimally invasive procedures increased from $3.0 billion to $5.7 billion (90 percent growth), whereas revenue from surgical procedures decreased from $6.6 billion to $6.0 billion (10 percent decline). Between 2000 and 2011, minimally invasive procedure market share grew from 30 percent to nearly 50 percent. Linear regression analysis revealed significant correlations between surgical procedure revenue and indicators of macroeconomic climate: Dow Jones Industrial Average (R = 0.72; p < 0.01), Standard & Poor's 500 Index (R = 0.64, p < 0.05), and unemployment rate (R = -0.81; p < 0.001). Minimally invasive procedure revenue was significantly correlated with indicators related to microeconomic decision trends: disposable income per capita (R = 0.93; p < 0.001), real gross domestic product per capita (R = 0.88; p < 0.001), and home price index (R = 0.63; p < 0.05). No economic indicator in this study was found to be significantly correlated with both surgical and minimally invasive revenue. CONCLUSION: Despite economic turbulence, minimally invasive procedures are the most rapidly growing source of revenue and are poised to be the dominant source of revenue in the aesthetic market.

The present study aimed to characterize the mechanical response of beagle sartorius muscle fibers under strain rates that increase logarithmically (0.1mm/min, 1mm/min and 10mm/min), and provide an analysis of the fracture patterns of these tissues via scanning electron microscopy (SEM). Muscle tissue from dogs' sartorius was excised and test specimens were sectioned with a lancet into sections with nominal length, width, and thickness of 7, 2.5 and 0.6mm, respectively. Trimming of the tissue was done so that the loading would be parallel to the direction of the muscle fiber. Samples were immediately tested following excision and failures were observed under the SEM. No statistically significant difference was observed in strength between the 0.1mm/min (2.560+/-0.37MPa) and the 1mm/min (2.702+/-0.55MPa) groups. However, the 10mm/min group (1.545+/-0.50MPa) had a statistically significant lower strength than both the 1mm/min group and the 0.1mm/min group with p<0.01 in both cases. At the 0.1mm/min rate the primary fracture mechanism was that of a shear mode failure of the endomysium with a significant relative motion between fibers. At 1mm/min this continues to be the predominant failure mode. At the 10mm/min strain rate there is a significant change in the fracture pattern relative to other strain rates, where little to no evidence of endomysial shear failure nor of significant motion between fibers was detected.