Faculty Bibliography

Unilateral breast reconstruction poses a special set of challenges to the reconstructive breast surgeon compared to bilateral reconstructions. No studies to date provide an objective comparison between autologous and implant based reconstructions in matching the contralateral breast. This study compares the quantitative postoperative results between unilateral implant and autologous flap reconstructions in matching the native breast in shape, size, and projection using three-dimensional (3D) imaging. Sixty-four patients who underwent unilateral mastectomy with tissue expander (TE)-implant (n = 34) or autologous microvascular free transverse rectus abdominus myocutaneous (TRAM; n = 18) or deep inferior epigastric artery perforator (DIEP; n = 12) flap (n = 30) reconstruction from 2007 to 2010 were analyzed. Key patient demographics and risk factors were collected. Using 3D scans of patients obtained during pre and postoperative visits including over 1 year follow-ups for both groups, 3D models were constructed and analyzed for total breast volume, anterior-posterior projection from the chest wall, and 3D comparison. No significant differences in mean age, body mass index, or total number of reconstructive surgeries were observed between the two groups (TE-implant: 52.2 +/- 10, 23.9 +/- 3.7, 3 +/- 0.9; autologous: 50.7 +/- 9.4, 25.4 +/- 3.9, 2.9 +/- 1.3; p > 0.05). The total volume difference between the reconstructed and contralateral breasts in the TE-implant group was insignificant: 27.1 +/- 22.2 cc, similar to the autologous group: 29.5 +/- 24.7 cc, as was the variance of breast volume from the mean. In both groups, the reconstructed breast had a larger volume. A-P projections were similar between the contralateral and the reconstructed breasts in the TE-implant group: 72.5 +/- 3.21 mm versus 71.7 +/- 3.5 mm (p > 0.05). The autologous reconstructed breast had statistically insignificant but less A-P projection compared to the contralateral breast (81.9 +/- 16.1 mm versus 61.5 +/- 9.5 mm; p > 0.05). Variance of A-P projection from the mean was additionally insignificant between the contralateral and reconstructed breasts. Both groups produced similar asymmetry scores based on global 3D comparison (TE-implant: 2.24 +/- 0.3 mm; autologous: 1.96 +/- 0.2 mm; p > 0.05). Lastly, when the autologous group was further subdivided into TRAM and DIEP cohorts, no significant differences in breast volume, A-P projection or symmetry existed. Using 3D imaging, we demonstrate that both TE-implant and autologous reconstruction can achieve symmetrical surgical results with the same number of operations. This study demonstrates that breast symmetry, while an important consideration in the breast reconstruction algorithm, should not be the sole consideration in a patient' decision to proceed with autologous versus TE-implant reconstruction.

Use of nipple-sparing mastectomy (NSM) for risk-reduction and therapeutic breast cancer resection is growing. The role for intraoperative frozen section of the nipple-areolar complex remains controversial. Records of patients undergoing NSM at our institution from 2006 to 2013 were reviewed. Records from 501 nipple-sparing mastectomies were reviewed (216 therapeutic, 285 prophylactic). Of the 480 breasts with sub-areolar biopsies, 307 had intraoperative frozen sections and 173 were evaluated with permanent paraffin section only. Among the 307 intraoperative frozen sections, 12 biopsies were positive on permanent paraffin section (3.9% or 12/307). Of the 12 positive permanent biopsies, five were false negative and the remaining seven concordant intraoperatively. Sensitivity and specificity of sub-areolar frozen section were 0.58 and 1, respectively. Positive sub-areolar biopsies consisted primarily of ductal carcinoma in situ (62% or 13/21). The nipples or nipple-areolar complex were resected in a separate procedure following mastectomy (10/21), intraoperatively following frozen section results (7/21) or during second-stage breast reconstruction (3/21; 1 additional scheduled). Only 30% (6/20) of resected specimens had abnormal residual pathology. Intraoperative frozen section is highly specific and moderately sensitive for the detection of positive sub-areolar biopsies in NSM. Its use can help guide intraoperative reconstructive planning. The presence of positive sub-areolar biopsies in both contralateral and high-risk prophylactic mastectomy specimens emphasizes the need to perform sub-areolar biopsies in all nipple-sparing mastectomies.

Tumor necrosis factor-alpha (TNF-alpha) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-alpha expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-alpha and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-alphaglo) that could be used to conditionally overexpress TNF-alpha. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-alpha in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-alphaglo mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-alphaglo mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-alphaglo mice, we have shown that TNF-alpha expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain.

Surface topography modifications have become a key strategy for hastening the host-to-implant response to implantable materials. The present study evaluated the effect of three different carefully controlled surface texture patterns achieved through microrobotized blasting (controlled to high, medium and low roughness) relative to a larger scale blasting procedure (control) in early osseointegration in a canine model. Four commercially pure grade 2 titanium alloy implants (one of each surface) were bilaterally placed in the radii of six beagle dogs and allowed end points of 1 and 6 weeks in vivo. Following sacrifice, implants in bone were non-decalcified processed for bone morphologic and histometric (bone-to-implant contact; bone area fraction occupancy) evaluation. Surface topography was characterized by scanning electron microscopy and optical interferometry. Results showed initial osteogenic tissue interaction at one week and new bone in intimate contact with all implant surfaces at 6 weeks. At 1 and 6 weeks in vivo, higher bone-to-implant and bone area fraction occupancy were observed for the high texture pattern microrobotized blasted surface relative to others.

BACKGROUND: Permanent paraffin subareolar biopsy during nipple-sparing mastectomy (NSM) tests for occult cancer at the nipple-areolar complex. Intraoperative subareolar frozen section can provide earlier detection intraoperatively. Cost analysis for intraoperative subareolar frozen section has never been performed. METHODS: NSM cases from 2006-2013 were reviewed. Patient records including financial charges were analyzed. RESULTS: Of 480 subareolar biopsies for NSM from 2006-2013, 21 were abnormal (4.4 %). A total of 307 of the subareolar biopsies included intraoperative frozen section. Of the 307, 12 (3.9 %) were abnormal with 7 of 12 detected on intraoperative frozen section. The median baseline charge for an intraoperative subareolar frozen section was $309 for an estimated total cost of $94,863 in 307 breasts. The median baseline charge for interval operative resection of a nipple-areolar complex following an abnormal subareolar pathology result was $11,021. Intraoperative subareolar biopsy avoided an estimated six return trips to the operating room for savings of $66,126. At our institution, routine use of intraoperative frozen section resulted in an additional $28,737 in healthcare charges or $95 per breast. CONCLUSIONS: We present the first cost analysis to evaluate intraoperative subareolar frozen section in NSM. This practice obviated an estimated six return trips to the operating room. With our institutional frequency of abnormal subareolar pathology, intraoperative frozen sections resulted in a marginal increased charge per mastectomy.

PURPOSE: To compare the removal of torque values of machined implant abutment connections (internal and external) with and without soft tissue entrapment using an in vitro model. MATERIALS AND METHODS: Thirty external- and 30 internal-connection implants were embedded in urethane dimethacrylate. Porcine tissue was prepared and measured to thicknesses of 0.5 and 1.0 mm. Six groups (n = 10) were studied: External- and internal-connection implants with no tissue (control), 0.5, and 1.0 mm of tissue were entrapped at the implant/abutment interface. Abutments were inserted to 20 Ncm for all six groups. Insertion torque values were recorded using a digital torque gauge. All groups were then immersed in 1 M NaOH for 48 hours to dissolve tissue. Subsequent reverse torque measurements were recorded. Mean and standard deviation were determined for each group, and one-way ANOVA and Bonferroni test were used for statistical analysis. RESULTS: All 60 specimens achieved a 20-Ncm insertion torque, despite tissue entrapment. Reverse torque measurements for external connection displayed a statistically significant difference (p < 0.05) between all groups with mean reverse torque values for the control (13.71 +/- 1.4 Ncm), 0.5 mm (7.83 +/- 2.4 Ncm), and 1.0 mm tissue entrapment (2.29 +/- 1.4 Ncm) groups. Some statistically significant differences (p < 0.05) were found between internal-connection groups. In all specimens, tissue did not completely dissolve after 48 hours. CONCLUSIONS: External-connection implants were significantly affected by tissue entrapment; the thicker the tissue, the lower the reverse torque values noted. Internal-connection implants were less affected by tissue entrapment.

BACKGROUND: We present an outcomes analysis of the surgical treatment of Robin sequence including all infants and comorbid conditions treated by tongue-lip adhesion (TLA) or mandibular distraction osteogenesis (MDO). METHODS: A 19-year single-institution, multisurgeon retrospective review of all syndromic and nonsyndromic neonates with Robin sequence treated with TLA (1994-2004) or MDO (2004-2013) was performed. Comorbid conditions were recorded in all patients. Outcomes include incidence of tracheostomy, improvement in obstructive breathing, and surgical complications. Need for repeat distraction and conversion from TLA to MDO were included as secondary end-points. Polysomnography data were recorded preoperatively at 1 month and 1 year as a measure of airway improvement. RESULTS: Seventy-four MDO patients and 15 TLA patients during the study period met inclusion criteria. There was no significant difference in mean age at intervention (32.1 +/- 29.0 vs 35.5 +/- 32.1 days), birth weight (2.9 +/- 0.7 vs 3.2 +/- 0.6 kg), prematurity (23.0 vs 35.7%), or intrauterine growth restriction (31.1 vs 15.4%). Central nervous system anomalies (24.3% vs 0.0%; P < 0.04) and gastrostomy tubes (66.2% vs 33.3%; P < 0.03) were present more frequently in MDO patients versus TLA patients. Rates of other organ system anomalies were similar between the groups. The success rate was significantly higher in the MDO group (90.5% vs 60.0%; P < 0.008). Postoperative tracheostomies occurred in 8.1% of the MDO group and 33.3% of the TLA group (P < 0.02). Preoperative apnea-hyponea index was similar between the two groups (38.3 vs 38.1). The apnea-hyponea index was significantly improved in the MDO group at 1 month (4.0 vs 21.7; P < 0.002) and 1 year (5.7 vs 20.5; P < 0.005). Surgical complications were statistically less in the MDO group (20.3 vs 53.3%; P < 0.02). CONCLUSIONS: In the heterogeneous population of Robin sequence, MDO demonstrates superior outcomes measures at 1 month and 1 year compared to TLA. Fewer complications occurred in the MDO group compared to the TLA.

Ionizing radiation is a common therapeutic modality and following irradiation dermal changes, including fibrosis and atrophy, may lead to permanent changes. We have previously demonstrated that occupancy of A2A receptor (A2AR) stimulates collagen production, so we determined whether blockade or deletion of A2AR could prevent radiation-induced fibrosis. After targeted irradiation (40 Gy) of the skin of wild-type (WT) or A2AR knockout (A2ARKO) mice, the A2AR antagonist ZM241385 was applied daily for 28 d. In irradiated WT mice treated with the A2AR antagonist, there was a marked reduction in collagen content and skin thickness, and ZM241385 treatment reduced the number of myofibroblasts and angiogenesis. After irradiation, there is an increase in loosely packed collagen fibrils, which is significantly diminished by ZM241385. Irradiation also induced an increase in epidermal thickness, prevented by ZM241385, by increasing the number of proliferating keratinocytes. Similarly, in A2ARKO mice, the changes in collagen alignment, skin thickness, myofibroblast content, angiogenesis, and epidermal hyperplasia were markedly reduced following irradiation. Radiation-induced changes in the dermis and epidermis were accompanied by an infiltrate of T cells, which was prevented in both ZM241385-treated and A2ARKO mice. Radiation therapy is administered to a significant number of patients with cancer, and radiation reactions may limit this therapeutic modality. Our findings suggest that topical application of an A2AR antagonist prevents radiation dermatitis and may be useful in the prevention or amelioration of radiation changes in the skin.-Perez-Aso, M., Mediero, A., Low, Y. C., Levine, J., Cronstein, B. N. Adenosine A2A receptor plays an important role in radiation-induced dermal injury.