Faculty Bibliography

Background: Calcium hydroxylapatite (CaHA, Radiesse) is approved by the Food and Drug Administration for treatment of moderate to severe wrinkles and folds, including nasolabial folds (NLF). A pivotal NLF split-face study previously compared the performance of Radiesse to human-based collagen at six months and safety of Radiesse through one year. Objective: The authors assess the long-term safety and effectiveness of Radiesse for the treatment of NLF. Postapproval long-term results now extend to more than three years and are presented here. Methods: This study reports an extension phase of a previously reported one-year premarket study of 117 patients comparing Radiesse to collagen. During the initial study, patients were treated to optimal correction and then followed for 12 months; they were offered retreatment with Radiesse between six and 12 months in both folds to balance asymmetry. Of the 117 original split-face study subjects with moderate to severe NLF, 102 were enrolled in this extended follow-up. During this extension study, treating physicians used the Global Aesthetic Improvement Scale (GAIS) and clinical examination to evaluate subjects at intervals up to 39 months after the last injection of Radiesse. Results: Forty percent of the folds evaluated at least 30 months after the last Radiesse treatment were graded as 'improved' or better on the GAIS. Expectedly, the reported improvement was substantially less at this later time point than had been seen at earlier points in the premarket study, indicating some moderate, sustained improvement in some patients. There were no long-term or delayed-onset adverse events in these 102 patients followed for three years, including no reports of nodules, granulomata, or infections, such as have been reported with certain other dermal fillers. Conclusions: These results demonstrate the long-term safety and effectiveness of Radiesse. Three years after Radiesse injection, no delayed-onset or long-term adverse events were reported. In addition, many patients showed some long-term cosmetic improvement. The durability and safety of Radiesse compare favorably with other injectable fillers

OBJECTIVES/HYPOTHESIS: AlloDerm (LifeCell Corp., Branchburg, NJ) is commonly employed for reconstruction of ablative soft tissue and mucosal defects following surgical resections. Although devoid of growth factors, AlloDerm may serve as an adhesive matrix for binding of growth factors, increasing local angiogenesis, and wound healing. We hypothesized that AlloDerm would enhance angiogenesis and might be altered with autologous blood products to enhance initiation of the angiogenic response. METHODS: We used a human placental vein in a fibrin-thrombin clot-based angiogenesis model. Four groups, human placental vein (HPVM), HPVM with AlloDerm, HPVM with AlloDerm plus platelet-poor plasma, and HPVM with AlloDerm plus platelet-rich plasma were evaluated. Endothelial cell growth was evaluated visually (40x). Hematoxylin and eosin staining and immunofluorescent staining for growth within the AlloDerm matrix were also performed. To assess human umbilical vein endothelial cell (HUVEC) sites of attachment to AlloDerm, we incubated HUVEC cells with AlloDerm for a period of 2 weeks and evaluated attachment with anti-factor VIII immunofluorescence. RESULTS: Angiogenic initiation decreased in the combined placental vein with AlloDerm group (P < .0001 at day 7, 14, 21). Additionally, initiation in the AlloDerm plus platelet-poor plasma group was significantly better than the AlloDerm alone group when placentas 2 and 3 were compared (P < .0001). On hematoxylin and eosin staining and immunofluorescent factor VIII staining, no endothelial growth into the AlloDerm was noted in the samples analyzed. CONCLUSIONS: AlloDerm may be enriched with platelet-poor plasma to stimulate greater initiation and wound healing; however, AlloDerm inhibits angiogenic initiation in this model.

The viability of fat grafts harvested with an established technique after cryopreservation remains unknown. This study was conducted in vitro to evaluate the viability of autologous fat grafts harvested with the Coleman technique and subsequently preserved with our preferred cryopreservation method. Eight adult females were enrolled in this study. In each patient, 10 mL of fat grafts were harvested with the Coleman technique by a single surgeon from the lower abdomen. In group 1, 5 mL of fresh fat grafts were mixed with cryoprotective agents and underwent cryopreservation with controlled slow cooling and fast rewarming. In group 2, 5 mL of fresh fat grafts without cryopreservation from the same patient served as a control. The fat graft samples from both groups were evaluated with trypan blue vital staining, glycerol-3-phophatase dehydrogenase assay, and routine histology. Viable adipocyte counts were found similar in both group 1 and group 2 (3.46 +/- 0.91 vs. 4.12 +/- 1.11 x 10/mL, P = 0.22). However, glycerol-3-phophatase dehydrogenase activity was significantly lower in group 1 compared with group 2 (0.47 +/- 0.09 vs. 0.66 +/- 0.09 u/mL, P < 0.001). Histologically, the normal structure of fragmented fatty tissues was found primarily in both groups. Our results indicate that autologous fat grafts harvested with the Coleman technique and preserved with our preferred cryopreservation method have a normal histology with near the same number of viable adipocytes as compared with the fresh fat grafts. However, those cryopreserved fat grafts appear to have a less optimal level of adipocyte specific enzyme activity compared with the fresh ones and thus may not survive well after they are transplanted without being optimized

BACKGROUND: Facial nerve explorations and microstimulation of distal nerve branches during facial reanimation procedures by the senior author (J.K.T.) have yielded various observations. This prompted the authors to quantify the surgical findings with an anatomical study and a subsequent analysis of the electrophysiologic intraoperative data. The present report details the microanatomical observations. METHODS: Ten fresh cadaveric hemiface dissections (five specimens) were performed. The facial nerve branches were traced distally under the operating microscope and mapped with India ink. A number of nerve branches exited the parotid at approximately 9 +/- 0.85 cm from the facial nerve trunk division, and their distribution was noted. Photographic documentation was obtained. RESULTS: The mean number of nerve branches was 7.70 +/- 1.05 at the anterior parotid border and 13.80 +/- 1.81 distally. Differences in the number and configuration of nerve branches existed even between the two sides of the face. The frontal branch had a mean nerve number of 2.80 +/- 0.63; the zygomatic branch, 4.40 +/- 1.34, the buccal branch, 3.20 +/- 0.78; and the marginal mandibular branch, 2.30 +/- 0.48. In 70 percent of specimens, the buccal branches originated from both upper and lower nerve divisions and interconnected with the marginal mandibular branch in 50 percent of specimens. Distally, connectivity was found between buccal branches and the infraorbital nerve, the marginal mandibular branches, and the mental nerve. A constant lower zygomatic or zygomaticobuccal branch reached the procerus and corrugator supercilii muscles. A twig from the frontal branch reached the corrugator muscle in 60 percent of cases. CONCLUSIONS: Diversity of facial nerve anatomy is recognized and documented. Specific anatomical relationships are clarified and demonstrated as a guiding map

Since 1976, experimental and clinical studies have suggested the superiority of vascularized nerve grafts. In this study, a 27-year experience of the senior author is presented regarding vascularized nerve grafts and fascia for complex upper extremity nerve reconstruction. The factors influencing outcomes as well as a comparison with conventional nerve grafts is presented. Since 1981, 21 vascularized nerve grafts, other than vascularized ulnar nerve, were used for reconstruction of nerve injuries in the upper extremity. Indications were prolonged denervation time, failure of the previously used conventional nerve grafts, and excessive scar in the recipient site. Injury was in the hand/wrist area (n = 5), in the forearm (n = 4), in the elbow (n = 2), in the arm (n = 4), or in the plexus (n = 6). Vascularized sural (n = 9), saphenous (n = 8), superficial radial (n = 3), and peroneal (superficial and deep) nerves were used. The mean follow-up was 31.4 months. Vascularized nerve grafts for upper extremity injuries provided good to excellent sensory return in severely scarred upper extremities in patients in whom conventional nerve grafts had failed. They have also provided relief of causalgia after painful neuroma resection and motor function recovery in selective cases even for above the elbow injuries. Small diameter vascularized nerve grafts should be considered for bridging long nerve gaps in regions of excessive scar or for reconstructions where conventional nerve grafts have failed

Soft-tissue reconstruction of traumatic patella and proximal tibial defects is challenging. Pedicled perforator-based adipocutaneous rotation flaps are a versatile local option as they have axial perfusion and greater freedom of transposition compared with random-pattern flaps, and replace the ideal tissue properties of this anatomic region.Experimental: Anatomic dissections were performed on 15 fresh cadaver legs and location of the dominant perforator measured. Clinical: A retrospective review was conducted at the University of Maryland/R Adams Cowley Shock Trauma Center evaluating patients over a 3-year period.Experimental: Cadaver dissections confirmed a principal perforator at 11.4 +/- 1.6 cm inferior to the patella. This vessel is consistently suitable in length and caliber for large rotation flap design. Clinical: Anterior tibial artery perforator flaps were performed on 4 patients following Gustilo IIIB wounds to the patella and tibial plateau. Two patients had rotation flap reconstructions to salvage failed gastrocnemius muscle flaps. All flaps were successful, however, one patient had overwhelming hardware infection several months later despite successfully healed flap.Local anterior tibial artery perforator flaps based on predictable perforators provide reliable coverage of patella and knee defects, bestowing versatility and flexibility to the reconstructive surgeon's armamentarium.

BACKGROUND: Since 2005, seven facial composite tissue allotransplantations have been performed in five different centers in three countries. Four teams have reported their outcomes in separate publications. The authors sought to review the first four global experiences and compare several factors. This review facilitates discussion of indications and future implications for facial composite tissue allotransplantation. METHODS: A thorough review of five publications by the four transplantation groups was conducted. Additional information gathered from official press releases or surgeon presentations was also included. Summary of data and comparative analysis were performed. RESULTS: Patient selection is of utmost importance; specifically, patient compliance with the immunosuppressive and postoperative regimen. Functional and aesthetic improvement must be achieved by composite tissue allotransplantation reconstruction to justify lifelong immunosuppression; therefore, patients with loss of perioral and/or periorbital structures have priority. Objective measures are required to monitor this functional restoration. The importance of viral mismatch was demonstrated by the severe cytomegalovirus viremia observed in the third facial transplant patient. Finally, the mucosa appears to be a predictor of rejection and is more antigenic than skin. Histopathologic diagnosis of mucosal rejection may allow early treatment and prevention of subsequent diffuse composite tissue allotransplant rejection. CONCLUSIONS: The pioneering teams that ventured into facial composite tissue allotransplantation offered their patients improved aesthetic, functional, and social outcomes not possible with conventional measures in a single procedure. In addition, these innovative facial composite tissue allografts have provided early data on important factors related to patient selection, donor/recipient matching, immunosuppressive protocols, objective measures of functional recovery, and monitoring of acute graft rejection.

It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(-) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms.