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Background: Keloids are an abnormal proliferation of scars that can involve large areas of tissue beyond the original injury site. Hypertrophic scars are similar clinically, but do not exceed the original scar limits. These scarring abnormalities can cause noxious symptoms such as pain, tenderness, itching, and ulcerations. The aim of this review is to discuss current therapies for both types of abnormal scarring, and to determine if guidelines can be provided for excisional treatment with adjuvant therapies versus non-excisional methods., Methods: A systematic literature search was performed through the Web of Science database. The search revolved around keywords such as "keloid," "hypertrophic scars," and "treatment." Articles were reviewed and screened for inclusion and exclusion criteria. The review focuses on an analysis and summarization of randomized control trials regarding keloid or hypertrophic scar treatments., Results: The original searches produced 1161 and 1275 articles for keloid and hypertrophic scars, respectively. In total, 316 duplicates were found. After accounting for 2014-2019 publication time, 655 keloid and 893 hypertrophic scar articles were reviewed. This resulted in 15 articles that pertained to treatment and randomized control trials., Conclusions: Keloids and hypertrophic scars present a clinical challenge. Based on qualitative review of recurrence, neither excision plus adjuvant therapy or nonsurgical treatments can be recommended preferentially at this time. More research is needed to determine if recurrence rate bias exists between the treatment regimens, as excisional treatment plus adjuvant therapy is reserved for refractory scars., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Context: High rates of mortality and chemical dependence occur following the overuse of narcotic medications, and the prescription of these medications has become a central discussion in health care. Efforts to curtail opioid prescribing include Enhanced Recovery After Surgery (ERAS) guidelines, which describe local anesthesia techniques to decrease or eliminate the need for opioids when used in a comprehensive protocol. Here, we review effective perioperative blocks for the decreased use of opioid medications post-breast reconstruction surgery., Evidence Acquisition: A comprehensive review was conducted using keywords narcotics, opioid, surgery, breast reconstruction, pain pump, nerve block, regional anesthesia, and analgesia. Papers that described a local anesthetic option for breast reconstruction for decreasing postoperative narcotic consumption, written in English, were included., Results: A total of 52 papers were included in this review. Local anesthetic options included single-shot nerve blocks, nerve block catheters, and local and regional anesthesia. Most papers reported equal or even superior pain control with decreased nausea and vomiting, length of hospital stay, and other outcomes., Conclusions: Though opioid medications are currently the gold standard medication for pain management following surgery, strategies to decrease the dose or number of opioids prescribed may lead to better patient outcomes. The use of a local anesthetic technique has been shown to reduce narcotic use and improve patients' pain scores after breast reconstruction surgery., Competing Interests: Conflict of Interests: None of the authors have any financial conflicts of interest in any of the products, devices, or drugs mentioned in this article., (Copyright © 2020, Author(s).)

Background:  Venous flow couplers are typically used to monitor free flaps during the postoperative period, with a continuous venous signal available immediately after completion of the anastomosis. Intraoperative loss of the coupler signal is not uncommon and may require adjustments in free flap inset and even flap thickness to get the venous signal to return. The effects of intraoperative coupler signal loss and the role of this technology on flap outcomes have not been evaluated. We hypothesized that the use of intraoperative coupler can be protective of both early and late flap complications by preventing unfavorable flap insets., Patients and Methods:  All patients who underwent free flap breast reconstruction between January 2018 and June 2019 by single microsurgery team were included. Flap inset and inset changes based on flow coupler signal problems were reviewed in the procedure notes. Patient demographics data and clinical outcomes were analyzed with comprehensive chart review., Results:  Forty-four consecutive patients with 69 free flaps were identified. There were no significant differences in patient characteristics or venous coupler size used in venous anastomosis. Although the number of operating room take backs for venous insufficiency was not significantly different between two groups, the free flaps with inset change had significantly higher complications that required later surgical intervention ( p  = 0.0464)., Conclusion:  Surgeons should be aware that intraoperative coupler signal loss can be associated with poor clinical outcomes postoperatively and these flaps may require more perfusion imaging, flap debulking, or even additional venous anastomosis., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background:  More than 85 patients have received over 100 hand/arm transplants and more than 35 patients have received full or partial face transplants at institutions around the world. Given over two decades of experience in the field and in the light of successful outcomes with up to 17 years follow up time, should we still consider vascularized composite allograft (VCA) as a research/clinical investigation? We present the results of a nationwide electronic survey whose intent was to gather institutional bias with regard to this question., Methods:  An 11 question survey that was developed by VCA advisory committee of American Society of Transplantation was sent to all identified Internal Review Board chairs or directors in the United States., Results:  We received a total of 54 responses (25.3%) to the survey. The majority (78%) of responses came from either the chairperson, director, or someone who is administratively responsible for an IRB., Conclusion:  Though certainly not an exhaustive investigation into each institution's preference, we present a representative sampling. The results of which favor VCA as an accepted clinical procedure given the appropriate setting. Further research is needed to fully ascertain practices at each individual institution., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

During reconstructive breast surgery, intraoperative assessment of tissue perfusion has been solely based on subjective clinical judgment. However, in the last decade, intraoperative indocyanine green angiography (ICGA) has become an influential tool to visualize blood flow to the tissue of interest. This angiography technique produces real-time blood flow information to provide an objective assessment of tissue perfusion., Methods: A comprehensive literature search of articles pertaining to ICGA in breast reconstruction surgery was performed. The overall findings of the articles are outlined here by surgical procedure: skin-sparing and nipple-sparing mastectomy, implant-based reconstruction, and autologous reconstruction., Results: Overall, there were 133 articles reviewed, describing the use of ICGA in breast reconstruction surgery. We found that ICGA can provide valuable information that aids in flap design, anastomotic success, and perfusion assessment. We also included example photographs and videos of ICGA use at our institution., Conclusions: ICGA can reduce postoperative tissue loss and aid in intraoperative flap design and inset. Despite the benefits of ICGA, its technical use and interpretation have yet to be standardized, limiting its widespread acceptance., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Patient safety is defined as freedom from accidental or preventable harm produced by medical care. The identification of patient- and procedure-related risk factors enables the surgical team to carry out prophylactic measures to reduce the rate of complications and adverse events.The purpose of this review is to identify the characteristics of patients, practitioners, and microvascular surgical procedures that place patients at risk for preventable harm, and to discuss evidence-based prevention practices that can potentially help to generate a culture of patient safety., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: The application of hematopoietic cell transplantation for induction of immune tolerance has been limited by toxicities associated with conditioning regimens and to graft-versus-host disease (GVHD). Decades of animal studies have culminated into sufficient control of these two problems, making immune tolerance a viable alternative to life-long application of immunosuppressive drugs to prevent allograft rejection., Methods: Studies in mice have paved the way for the application of HCT with limited toxicity in large animal models. Resultant studies in the pig, dog, and ultimately the nonhuman primate have led to appropriate methods for achieving nonmyeloablative irradiation protocols, dose, and timing of post-grafting immunosuppressive drugs, monoclonal antibody therapy, and biologicals for costimulatory molecule blockade. The genetics field has been extensively evaluated in appreciation of the ultimate need to obtain organs from MHC-mismatched unrelated donors., Results: Nonmyeloablative conditioning regimens have been shown to be successful in inducing immune tolerance across all three animal models. Postgrafting immunosuppression is also important in assuring sustained donor hematopoiesis for tolerance. Donor chimerism need not be permanent to establish stable engraftment of donor organs, thereby essentially eliminating the risk of GVHD. Using nonmyeloablative HCT with monoclonal antibody immunosuppression, the kidney has been successfully transplanted in MHC-mismatched nonhuman primates., Conclusions: Nonmyeloablative HCT for the establishment of temporary mixed chimerism has led to the establishment of stable tolerance against solid organ allografts in large animal models. The kidney, considered a tolerogenic organ, has been successfully transplanted in the clinic. Other organs such as heart, lung, and vascularized composite allografts (face and hands), remain distant possibilities. Further study in large animal models will be required to improve tolerance against these organs before success can be attained in the clinic., Competing Interests: Competing Interests The authors have declared that no competing interests exist.

Learning Objectives: After studying this article, the participant should be able to: 1. Understand how to determine nipple-areola complex positioning on the reconstructed breast. 2. Understand the multitude of local flap and distant graft options for nipple-areola complex reconstruction. 3. Draw at least three fundamental nipple-areola complex reconstruction patterns. 4. Understand the forces that are responsible for flattening of the reconstructed papule. 5. Understand the current techniques used in secondary nipple-areola complex reconstructions., Summary: Nipple-areola complex reconstruction and tattooing represent the final two stages of breast reconstruction. Nipple-areola complex reconstruction is typically accomplished with the use of local flaps, local flaps with augmentation grafts, or a combination thereof. Regardless of the technique used, however, all nipple-areola complex reconstructions lose a degree of projection over time. Options for secondary reconstruction include the use of local tissue flaps alone or in combination with acellular biological matrices.

Background: The development of safe and reliable protocols for the transplantation of the face and hands may be accomplished with animal modeling of transplantation of vascularized composite allografts (VCA). Previously, we demonstrated that tolerance to a VCA could be achieved after canine recipients were simultaneously given marrow from a dog leukocyte antigen-identical donor. In the present study, we extend those findings across a dog leukocyte antigen mismatched barrier., Methods: Eight recipient dogs received total body irradiation (4.5 cGy), hematopoietic cell transplantation (HCT), either marrow (n = 4) or granulocyte-colony stimulating factor mobilized peripheral blood stem cells (n = 4), and a VCA transplant from the HCT donor. Post grafting immunosuppression consisted of mycophenolate mofetil (28 days) and cyclosporine (35 days)., Results: In 4 dogs receiving bone marrow, 1 accepted both its marrow transplant and demonstrated long-term tolerance to the donor VCA (>52 weeks). Three dogs rejected both their marrow transplants and VCA at 5 to 7 weeks posttransplant. Dogs receiving mobilized stem cells all accepted their stem cell transplant and became tolerant to the VCA. However, 3 dogs developed graft-versus-host disease, whereas 1 dog rejected its stem cell graft by week 15 but exhibited long-term tolerance toward its VCA (>90 weeks)., Conclusions: The data suggest that simultaneous transplantation of mobilized stem cells and a VCA is feasible and leads to tolerance toward the VCA in a haploidentical setting. However, there is a higher rate of donor stem cell engraftment compared with marrow HCT and an increase in the incidence of graft-versus-host disease.

Ventral hernia repair (VHR) for large abdominal wall defects is challenging. Prior research established that the use of mesh is superior to suture closure alone and that component separation is an effective technique to combat loss of abdominal domain. Studies comparing component separation technique (CST) outcomes utilizing synthetic versus biologic mesh are limited. A retrospective review was conducted of 72 consecutive patients who underwent VHR with CST between 2006 and 2010 at our institution. Surgeon preference and the presence of contamination guided whether synthetic mesh (27 patients) or biologic mesh (45 patients) was used. Mean follow-up interval for all comers was 13.9 months and similar in both groups (P > 0.05). Degree of contamination and severity of premorbid medical conditions were significantly higher in the biologic mesh group, as reflected in the higher Ventral Hernia Working Group (VHWG) score (2.04 versus 2.86). Clinical outcomes, as measured by both minor and major complication rates and recurrence rates, were not significantly different. Minor complication rates were 26% in the synthetic group and 37% in the biologic group and major complication rates 15% in the synthetic group and 22% in the biologic group. There was 1 recurrence (4%) in the synthetic mesh group versus 5 (11%) in the biologic mesh group. Multivariable analysis for major complications revealed no significant difference for either synthetic or biologic mesh while controlling for other variables. Subset analysis of uncontaminated cases revealed recurrence rates of 4% in the synthetic mesh group and 6% in the biologic mesh group. VHR using CST and either synthetic mesh or biologic mesh resulted in low recurrence rates with similar overall complication profiles, despite the higher average VHWG grading score in the biologic mesh group. Our results support the VHWG recommendation for biologic mesh utilization in higher VHWG grade patients. In VHWG grade 2 patients, our clinical outcomes were similar, supporting the use of either type of mesh.

Background: Injury to the face can result in the loss of critical specialized structures (the eyelids, lips, ears and nose). Vascularized composite allotransplantation (VCA) allows the surgeon to replace exactly what has been lost. The success of the clinical face transplants suggests the possibility of transplanting specialized units of the face. In this study we explore the neurovascular anatomy and technical specifics for harvest of a functional composite eyelid subunit flap., Methods: 12 fresh cadaver heads were studied, each yielding two flaps (N = 24). The facial (FA) and superficial temporal arteries (STA) were cannulated and injected with a gelatin/acrylic dye mixture. 6 cadaver heads were evaluated via high-resolution three-dimensional CT scans with contrast., Results: The dye injected into the STA uniformly stained the tissue of the eyelid/periorbital subunit. Injection into the FA resulted in staining of the skin and soft tissues in the medial canthal region and superior eyelid skin in 66% of specimens. CT scan studies confirm our findings with injection into the STA resulting in contrast infiltration of the palpebral arterial arcades in all cases. Injection of the FA resulted in contrast infiltration of the palpebral arterial arcades in 2 of 3 cases., Conclusions: Based this study, a periorbital flap can be based on the STA. Motor innervation of the flap is via the zygomatic and buccal branches of the facial nerve with sensory innervation via the infraorbital, supraorbital and supratrochlear nerves. FA could be used, but its ability to perfuse the entire flap was inconsistent., (Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

This study tested the hypothesis that vascularized composite allografts (VCA) could be accepted in a robust model of hematopoietic chimerism by injecting allogeneic bone marrow cells (BMC) into swine fetuses. Outbred Yorkshire sows and boars were screened to ensure the absence of the major histocompatibility (MHC) allele SLA(cc) of inbred MGH miniature swine and then mated. Bone marrow harvested from an SLA(cc) swine donor was T-cell depleted and injected intravenously into the fetuses between days 50-55 of gestation. After birth, the piglets were studied with flow cytometry to detect donor cells and mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML) assays to assess their response to donor. Donor-matched VCAs from SLA(cc) donors were performed on four chimeric and two nonchimeric swine. The results showed donor cell engraftment and multilineage macrochimerism after the in utero transplantation of adult BMC, and chimeric animals were unresponsive to donor antigens in vitro. Both control VCAs were rejected by 21 days and were alloreactive. Chimeric animals accepted the VCAs and never developed antidonor antibodies or alloreactivity to donor. These results confirm that the intravascular, in utero transplantation of adult BMC leads to donor cell chimerism and donor-specific tolerance of VCAs across a full MHC barrier in this animal model., (© 2014 Steunstichting ESOT.)

Background: Wound complications after perineal and groin obliterative procedures are a significant cause of morbidity, particularly following chemoradiation therapy. Vertical and, increasingly, oblique rectus abdominis myocutaneous flaps have been used to fill potential dead space and bring healthy, vascularized tissue into the defect. The authors compared the complications and outcomes of patients undergoing perineal or groin reconstruction with vertical or oblique rectus abdominis myocutaneous flaps. They hypothesized that the oblique flap offers outcomes similar to those of the vertical flap, without an increased risk of complications., Methods: All patients who underwent immediate reconstruction of perineal, pelvic, or groin defects using vertical (n=49) or oblique rectus abdominis myocutaneous (n=22) flaps over the past 10 years at the University of Washington Medical Center were reviewed retrospectively. Patient, disease, and obliterative procedure characteristics and donor- and recipient-site complications were compared. Statistical analysis was performed using the t test for continuous variables and Fisher's exact test for categorical variables., Results: There were no statistically significant differences in major or minor donor- or recipient-site complication rates, need for augmented fascial closure, need for additional flaps, flap loss, readmission, or reoperation rate between the two groups., Conclusions: Immediate reconstruction of perineal or groin defects with oblique rectus abdominis myocutaneous flaps results in complication rates similar to those with reconstruction using with vertical flaps. Oblique flap reconstruction is a reasonable and safe alternative, providing several distinct advantages over the vertical flap, including greater arc of rotation, thinner skin paddle, less bulk, and limited fascial harvest., Clinical Question/level of Evidence: Therapeutic, III.

Background: We have previously demonstrated that tolerance to a vascularized composite allograft (VCA) can be achieved after the establishment of mixed chimerism. We test the hypothesis that tolerance to a VCA in our dog leukocyte antigen-matched canine model is not dependent on the previous establishment of mixed chimerism and can be induced coincident with hematopoietic cell transplantation (HCT)., Methods: Eight dog leukocyte antigen-matched, minor antigen mismatched dogs received 200 cGy of radiation and a VCA transplant. Four dogs received donor bone marrow at the time of VCA transplantation (group 1), whereas a second group of four dogs did not (group 2). All recipients received a limited course of postgrafting immunosuppression. All dogs that received HCT and VCA were given donor, third-party, and autologous skin grafts., Results: All group 1 recipients were tolerant to their VCA (>62 weeks). Three of the four dogs in group 2 rejected their VCA transplants after the cessation of immunosuppression. Biopsies obtained from the muscle and skin of VCA from group 1 showed few infiltrating cells compared with extensive infiltrates in biopsies of VCA from group 2. Compared with autologous skin and muscle, elevated levels of CD3+ FoxP3+ T-regulatory cells were found in the skin and muscle obtained from the VCA of HCT recipients. All group 1 animals were tolerant to their donor skin graft and promptly rejected the third-party skin grafts., Conclusion: These data demonstrated that donor-specific tolerance to all components of the VCA can be established through simultaneous nonmyeloablative allogeneic HCT and VCA transplantation protocol.

Background: The Cook-Swartz Doppler has long been a trusted tool for close monitoring of blood flow after microvascular reconstruction; however, device implantation requires additional operating time. Synovis Life Technologies, Inc. received FDA approval in 2010 for the Flow Coupler, which combines an end-to-end anastomotic coupler with a removable 20 MHz Doppler, allowing both procedures to be performed simultaneously. However, its short history of widespread use necessitates further evaluation in the clinical setting. The authors studied the Synovis Flow Coupler in comparison to the more well-established Cook-Swartz Doppler for effectiveness and reliability in detection of vascular compromise., Methods: The authors reviewed 220 free flap breast reconstructions in 150 patients over a three-year period in which either the Cook-Swartz Doppler or the Synovis Flow Coupler was implanted to monitor blood flow. Outcomes measured include false-positive or false-negative rates (FPR, FNR); rates of OR take-back and salvage; and flap survival., Results: FPR was 1.0% for the Cook-Swartz Doppler and 1.9% for the Synovis Flow Coupler (p>0.05). FNR was 0.0% for both groups. Take-back rates were 10.1% for the Cook-Swartz, and 4.5% for Synovis (p>0.05). Flap failure rates were 1.8% and 0.9% for the Cook-Swartz and Synovis devices, respectively (p>0.05)., Conclusions: Our study reveals no statistically significant differences in outcomes for free flap breast reconstruction where either the Cook-Swartz Doppler or the Synovis Flow Coupler was used to monitor blood flow to the perforator flap., Level of Evidence: III., (Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Prosthetic reconstruction using human acellular dermis (ADM) is a common practice in breast reconstruction. AlloDerm and FlexHD are two different forms of ADM, each with unique characteristics. No studies have directly compared the postoperative complications of these 2 products., Methods: The outcomes of 547 consecutive implant-based breast reconstructions were reviewed., Results: Reconstruction was performed in 382 consecutive women (547 total breasts), employing mostly immediate reconstruction (81%). Mean follow-up was 6.4 months. Among immediate reconstructions, 165 used AlloDerm and 97 used FlexHD. Complications were similar by univariate analysis. In multivariate analysis, smoking and higher initial implant fill were risk factors for delayed healing. The use of FlexHD, single-stage reconstruction, and smoking were independent risk factors for implant loss., Conclusions: There is no significant difference in the complication rates between AlloDerm and FlexHD in immediate breast reconstruction. Multivariate analysis suggests that FlexHD may be a risk factor for implant loss.

Background: Preoperative knowledge of a patient's individual variations in facial artery anatomy would benefit plastic surgeons for reconstructive planning. The authors evaluated the feasibility of multislice computed tomographic angiography in vascular mapping of the facial artery., Methods: In total, 187 facial arteries in 94 patients without facial tumor or vascular disease were studied. Anatomical variations of the facial artery were classified into four types: type 1, a short course that terminates proximal to the superior labial artery; type 2, an intermediate course that terminates distal to the superior labial artery near the nasolabial fold; type 3, a classic course that extends to the lateral nasal ala beyond the nasolabial fold with an angular branch; and type 4, duplex with dominant lateral angular branch. Facial artery patterns were compared with dominant patterns of the facial-submental artery bifurcation. The extent of the inferior and superior labial artery was evaluated separately., Results: Sixty-four facial artery branches (34 percent) were classified as type 1, 74 (40 percent) as type 2, and 45 (24 percent) as type 3. Type 4 was seen in only four branches (2 percent). The facial artery was dominant in the facial-submental artery bifurcation in 84 percent of type 3 facial arteries. Three-dimensional volume-rendered images allow detailed visualization of the facial artery and its branches and help preoperative mapping., Conclusion: Facial computed tomographic angiography allows detailed visualization of the facial artery and its branches and is a potential noninvasive imaging tool for preoperative vascular mapping for facial reconstructive operations.

Background: CT angiography has become the gold-standard imaging modality prior to DIEP flap breast reconstructions. Recent studies show excellent correlation between CTA and operative perforator location, but not their clinical significance. This study seeks to specifically evaluate the clinical utility of CTA in DIEP free flaps., Methods: Preoperative CT angiography of the deep inferior epigastric system was obtained in 52 sequential DIEP free flaps involving 37 patients with dominant perforators marked by radiologist. Planned and used perforators were documented by the surgeon before and after the operation., Results: A total of 62 out of 76 planned perforators were ultimately used (82%). Of those not used, 71% were abandoned due to inadequacy of preoperative CT. An additional 38 perforators were used that were not part of the initial preoperative plan, 60% of which were added due to inadequacy of the preoperative CT for planning. In total 23/52 flaps (44%) involved intraoperative changes due to features not appreciated on preoperative CT., Conclusion: CTA mapping of perforators prior to DIEP flap surgery increases surgeon confidence and reduces operative time; however, there are still a significant number of changes made based on clinical judgment. This study highlights the importance of surgeon review of CTA images. Caution is warranted in reliance on CTA mapping, and significant perforators should not be sacrificed until the anticipated perforator(s) have been exposed and evaluated., Level of Evidence: Level 3., (Published by Elsevier Ltd.)

Background: Allogeneic hematopoietic cell transplantation provides a reliable method for inducing tolerance toward solid organ grafts. However, this procedure can result in graft-versus-host disease, thereby limiting its application. Here, we test the hypothesis that mixed chimerism can be intentionally reverted to host hematopoiesis without rejection of a kidney graft., Methods: Recipient dogs were given 2-Gy total-body irradiation (TBI) before and a short course of immunosuppression after marrow infusion from dog leukocyte antigen-identical littermates. All dogs achieved stable mixed chimerism. After a mean of 20 weeks, one cohort of dogs received kidney transplants from their respective marrow donors. Subsequently, recipients were reconditioned with 2-Gy TBI and given autologous granulocyte colony-stimulating factor-mobilized leukocytes (recipient leukocyte infusion [RLI]) that had been collected before marrow transplantation., Results: Dogs receiving a second TBI and RLI without a kidney transplant rejected their donor hematopoietic graft within 3 weeks. Dogs that received kidney grafts, followed by a second TBI and RLI, rejected their marrow graft without rejecting their transplanted kidneys for periods greater than 1 year., Conclusion: Mixed chimerism may be clinically reverted to 100% recipient without rejection of a kidney allograft. This finding may have application toward minimizing the risk of graft-versus-host disease in solid organ transplantation patients given hematopoietic cell transplantation from human leukocyte antigen-identical donors.

Background: Infection rates for breast surgery are 3 to 15 percent, higher than average for a clean surgical procedure. Preoperative and postoperative antibiotics have lowered infection rates in other surgical groups, yet there is no consensus on postoperative prophylactic antibiotic use in microsurgical breast reconstruction., Methods: A retrospective review of consecutive patients who underwent autologous breast reconstruction between 2006 and 2009 was performed. Specific risk factors for autologous reconstruction were reviewed, including medical comorbidities, irradiation, and chemotherapy history. Data were collected on type and duration of prophylactic antibiotics. A prospective cohort of patients who received only 24 hours of postoperative antibiotics was identified. The incidence of surgical-site infections was measured using Centers for Disease Control and Prevention criteria., Results: A total of 256 patients with 360 microvascular breast reconstructions who received both preoperative and postoperative prophylactic antibiotics were analyzed. The overall surgical-site infection rate was 17.2 percent (44 of 256 patients). Surgical-site infection was correlated with increased age, tobacco use, and prior radiation. Duration of postoperative antibiotic use did not differ in those patients who developed surgical-site infections (6.2 versus 7.7 days; p = 0.19). Eighty-two patients (32 percent) received only 24 hours of postoperative antibiotics, while 174 (68 percent) received more than 24 hours of antibiotics for a median duration of 10 days. There was no difference in the overall surgical-site infection rate in those who received more than 24 hours of antibiotics (19.5 versus 15.5 percent; p = 0.47)., Conclusion: There was no reduction in the overall surgical-site infection rate among autologous breast reconstruction patients who received postoperative antibiotic prophylaxis for more than 24 hours., Clinical Question/level of Evidence: Therapeutic, III.

Composite tissue allograft (CTA) transplantation, such as the clinical face and hand transplants, has now been performed in multiple centers across the world. The transplants have successfully treated complex injuries that have either failed conventional approaches or where autologous reconstruction could not restore both form and function. CTA transplantation has the potential to improve outcomes over traditional techniques. However, the widespread application of CTA transplantation continues to be limited by the need for chronic immunosuppression. Due to the small numbers of CTA transplants performed, any modification in the immunosuppression used will likely be based from the solid organ literature. The renal transplantation literature has served as the basis for the current selection of CTA drug regimens and in this article we review the evidence in the renal transplant literature for the selection of immunosuppressive regimens. The study then compares the regimens used in both the face and hand transplantation with those regimens currently used for renal transplantation., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Excision of head and neck melanoma is often limited by critical structures, which can lead to incomplete excision with positive pathologic margin and increased local recurrence rate. Complete excision with recommended margins and immediate reconstruction is possible when surgical oncologists and plastic surgeons work collaboratively. Our purpose was to evaluate local recurrence rate after excision and immediate reconstruction. We reviewed 98 consecutive patients treated for primary head and neck cutaneous melanoma at a single institution between 1999 and 2004. We assessed local recurrence rate. A total of 72 patients (73%) were followed for an average of 5.2 ± 1.7 years while 26 patients were excluded due to less than 1 year of follow-up. Adjacent tissue transfer was the most common reconstruction (87%). Local recurrence was reported in 2.8% and distant metastasis in 12.5% of patients. Immediate reconstruction after excision of head and neck melanoma can be safely performed with low local recurrence rate.

Background: Mixed donor-host chimerism, established through hematopoietic cell transplantation (HCT), is a reproducible strategy for the induction of tolerance toward solid organs. Here, we ask whether a nonmyeloablative conditioning regimen establishing mixed donor-host chimerism leads to tolerance of antigenic vascularized composite allografts., Methods: Stable mixed chimerism was established in dogs given a sublethal dose (1-2 Gy) total body irradiation before and a short course of immunosuppression after dog leukocyte antigen-identical marrow transplantation. Vascularized composite allografts from marrow donors were performed after a median of 36 months (range, 4-54 months) after HCT., Results: All marrow recipients maintained mixed donor-host hematopoietic chimerism and accepted vascularized composite allografts for periods ranging between 52 and 90 weeks; in turn, marrow donors rejected vascularized composite allografts from their respective marrow recipients within 18 to 29 days. Biopsies of muscle and skin of vascularized composite allografts from mixed chimeras showed few infiltrating cells compared with extensive infiltrates in biopsies of vascularized composite allografts from marrow donors. Elevated levels of CD3+ FoxP3+ T-regulatory cells were found in skin and muscle of vascularized composite allografts of mixed chimeras compared with normal tissues. In mixed chimeras, increased numbers of T-regulatory cells were found in draining compared with nondraining lymph nodes of vascularized composite allografts., Conclusions: These data suggest that nonmyeloablative HCT may form the basis for future clinical applications of solid organ transplantation and that T-regulatory cells may function toward maintenance of the vascularized composite allograft.

Despite advances in imaging technology, it is unclear whether preoperative MRI diagnosis of osteomyelitis influences surgical management and improves surgical outcome. The purpose of this retrospective study was to determine whether preoperative diagnosis of osteomyelitis by pelvic MRI influenced the surgical management of pressure sores and flap outcomes. The characteristics, pre- and intraoperative management, and surgical outcomes of the most recent flap surgery in 2 groups were compared: 26 patients diagnosed with osteomyelitis by preoperative MRI and 21 patients diagnosed by culture growth from an intraoperative bone specimen postoperatively. Patients with osteomyelitis diagnosed by MRI had 10 ulcer recurrences at the same site (39%) versus 6 (29%) among patients with osteomyelitis diagnosed by bone culture (odds ratio = 2.4, P = 0.22). We found that patients with a diagnostic preoperative MRI did not differ significantly in rates of antibiotic administration, ostectomy, dehiscence, revision, or infection.

Currently, more than 65 hand transplants have been performed with studies demonstrating favorable cosmetic and functional outcomes and cortical reintegration of the transplanted hand. Due to such favorable outcomes, many view hand transplant as a potential gold standard for treatment of a double amputee. However, ethical debate continues regarding risks and benefits of this nonlifesaving procedure. Clinicians, patients, and society must agree on whether hand transplantation is ethical and affordable. If a decision is made to transplant a hand, this must be performed in a dedicated center that facilitates integration of multiple specialists, ethicists, pharmacists, and rehabilitationists., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In flap reconstruction of complex defects the perfusion of the reconstructive flap is critical to the ultimate success of the reconstruction. This is especially true in perforator-based flaps where it can be difficult to assess the adequacy of perfusion in the operating room. However, the ability to definitively determine the degree of flap perfusion is imperative to clinical decision-making. An emerging technology using near-infrared angiography with indocyanine green (ICG) dye may significantly improve the immediacy and accuracy of the assessment of flap perfusion. This article reviews the current state of ICG angiography and its use in clinical practice in plastic surgery. There are 17 case series, including a total of 386 patients, published in the literature using ICG angiography in various plastic surgical procedures. ICG angiography may aid flap design and assessment in the intraoperative/postoperative settings, reduce complications, and ultimately improve outcomes., (© Thieme Medical Publishers.)

Background: Social media is a common term for web-based applications that offer a way to disseminate information to a targeted audience in real time. In the current market, many businesses are utilizing it to communicate with clients. Although the field of plastic surgery is constantly changing in response to innovative technologies introduced into the specialty, the utilization of social media in plastic surgery practices is currently unclear., Objectives: The authors evaluate the current attitudes and practices of aesthetic surgeons to emerging social media technology and compare these to attitudes about more traditional modes of communication., Methods: A 19-question web-based survey was disseminated by e-mail to all board-certified or board-eligible American plastic surgeons (n = 4817). Respondents were asked to answer questions on three topics: (1) their use of social media in their personal and professional lives, (2) their various forms of practice marketing, and (3) their demographic information., Results: There were 1000 responses (20.8%). Results showed that 28.2% of respondents used social media in their practice, while 46.7% used it in their personal life. Most plastic surgeons managed their social media themselves or through a staff member. The majority of respondents who used social media in their practice claimed that their efforts were directed toward patient referrals. The typical plastic surgery practice that used social media was a solo practice in a large city with a focus on cosmetic surgery. Local competition of plastic surgeons did not correlate with social media use. Most plastic surgeons (88%) advertised, but the form of marketing varied. The most common forms included websites, print, and search engine optimization, but other modalities, such as television, radio, and billboards, were still utilized., Conclusions: Social media represents a new avenue that many plastic surgeons are utilizing, although with trepidation. As social media becomes commonplace in society, its role in plastic surgery practice development and communication will become more prominent and defined.

The clinical application of perforator-based flaps for microsurgical breast reconstruction has increased exponentially over the past 10 years. The benefits of the procedure are thought to be that it produces less postoperative pain, lowers abdominal morbidity, and allows for better preservation of muscles at the donor site compared with conventional musculocutaneous flaps. The disadvantages of perforator flaps are that they are more difficult to harvest, which can result in a longer operative time and higher costs. The vascular anatomy of the deep inferior epigastric artery and its perforating branches in the abdominal wall varies greatly not only among individuals but also from one side of the abdomen to the other. Perforator location, number, caliber, and the intramuscular trajectory of the branches all impact the design and harvest of the flap. The creation of a presurgical map of the vessels on the abdomen can facilitate surgical planning and could decrease operating room time, reduce intraoperative complications, and lead to improved outcomes. This article reviews the available techniques for preoperative planning with the currently available imaging modalities: hand-held Doppler, color Doppler (duplex) ultrasound, CT angiography, and MR angiography., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Pressure ulcers are estimated to be present in more than one-third of patients with spinal cord injury. The rate of recurrence after flap surgery over last 50 years has ranged between 3 and 82 percent, with no trend toward improvement. This study seeks to identify and evaluate patient and operative characteristics associated with flap dehiscence and ulcer recurrence., Methods: A retrospective chart review of all patients who underwent pressure ulcer flap coverage between 1993 and 2008 was performed. Thirty-one demographic and operative variables were collected. Multivariate logistic regression with generalized estimating equation was used to evaluate the effect of significant variables. The primary outcome was recurrence of pressure ulcer at the operative site. Secondary outcomes included flap line dehiscence and the need for operative revision., Results: There were 88 recurrences of pressure ulcers after flap surgery (39 percent) of 227 operations performed on 135 patients. Thirty-six flaps (16 percent) had dehiscences necessitating return to the operating room. Hemoglobin A1c less than 6 percent and previous same-site flap failure were associated with both dehiscence and recurrence (odds ratios, 2.15 and 3.84; and odds ratios, 6.51 and 3.27). Younger age and albumin less than 3.5 were associated with early flap failure (odds ratios, 5.95 and 2.45). Ischial wound location correlated with late recurrence (odds ratio, 4.01). Patients with multiple risk factors had operative success rates that approached zero., Conclusions: Confirmation of adequate nutritional status and strict preoperative management of blood glucose may improve operative success rates. The authors propose that operative management should be approached with trepidation, if at all, in young patients with recurrent ischial ulcers.

The feasibility of composite tissue allografts (CTAs) has been demonstrated by the successful transplantation of the hand, abdomen, and face. However, the survival of these transplants depends on immunosuppression. Our laboratory is interested in achieving tolerance to decrease the risks associated with the use of chronic immunosuppression. The purpose of this experiment was to develop a large-animal model for CTA. Four canine flaps were autotransplanted to examine the use of a myocutaneous rectus flap based on the deep inferior epigastric vessels. Five CTA transplants were performed between dog leukocyte antigen (DLA)-identical littermates without posttransplant immunosuppression. The allografts were followed clinically and underwent routine biopsies. The anatomic dissections and autotransplants were all successful and revealed that the flap could be divided into two separate components. Skin was perfused by the superficial epigastric artery. Rectus muscle was perfused by the deep inferior epigastric system. This allowed the allografts to be transplanted as muscle or skin or with both components based on the external iliac artery and veins. The DLA-identical littermates rejected the allografts in 15 to 30 days. This study demonstrated the versatility of the myocutaneous rectus flap for use in canines as CTA models., (Copyright Thieme Medical Publishers.)

There are multiple techniques used to reconstruct the vagina after oncologic extirpation. However, the long-term functional results of vaginal reconstruction are not well appreciated.A review was conducted of all 27 consecutive patients undergoing vaginal reconstruction from 1990 to 2007. A modified Sexual Adjustment Questionnaire was mailed to patients. Also, a review of all published studies of myocutaneous vaginal reconstructions with postoperative sexual function was performed.Patients underwent vertical rectus abdominis myocutaneous flap (18), gracilis (4), pudendal artery fasciocutaneous flaps (3), or rectus and peritoneum flaps (2). Of 27 patients, 14 (52%) had postoperative complications. Of 12 patients, 6 (50%) reported sexual function. This compares with an overall 52.3% return to sexual function reported in 8 studies of myocutaneous vaginal reconstruction.Vaginal reconstruction yielding sexual function remains a challenge to the reconstructive surgeon. Preoperative education of the patient about sexual function is of paramount importance.

Background: To plan abdominal perforator-based microsurgical breast reconstruction, duplex ultrasound is often employed to preoperatively identify the location of abdominal wall perforating vessels. Recently, several groups have published the use of computed tomography angiography for preoperative planning in perforator flap breast reconstruction. The purpose of this study was to compare the accuracy of computed tomography angiography in locating clinically useful abdominal wall perforators with that of duplex ultrasound., Methods: A prospective study was conducted of 22 consecutive patients undergoing 30 abdomen-based microsurgical breast reconstructions using both preoperative computed tomography angiography and duplex ultrasound. Perforator data were obtained with both computed tomography angiography and ultrasound. The two largest perforators were chosen per abdominal side for comparison between studies. In addition, the locations of perforators were confirmed at surgery., Results: Computed tomography angiography preoperatively identified 83 of the largest perforators, while only 55 of these large perforators (66.3 percent) were preoperatively identified on ultrasound. No superficial inferior epigastric arteries were identified by ultrasound. However, in all eight breast reconstructions performed with the superficial inferior epigastric system, the superficial inferior epigastric arteries were identified preoperatively as adequate size for microsurgical transfers, with an average diameter of 1.6 mm., Conclusions: There are many advantages to preoperative computed tomography angiography for planning abdominal perforator-based microsurgical breast reconstruction, including accurate identification of perforating vessels, the underlying branching pattern of the deep inferior epigastric artery, and the presence of the superficial inferior epigastric vessels. This study demonstrates the superiority of computed tomography angiography over duplex ultrasound as a tool for preoperative planning of perforator-based breast reconstruction.

Perforator-based microsurgical reconstruction of the breast has steadily increased since the introduction of the technique in the 1990s. The procedure appears to offer less postoperative pain, lower abdominal morbidity, and better preservation of the rectus muscles than the more conventional flaps. However, the major disadvantage of these flaps that they can be difficult to harvest, resulting in a longer operative times. The challenges in flap dissection are a result of the variability in the vascular anatomy of the deep inferior epigastric artery (DIEA) and its perforating branches through the rectus muscle. The location, number, and caliber of the perforators and the intramuscular trajectory of the DIEA branches vary greatly not only from individual to individual, but from one hemiabdomen to the other. The establishment of a presurgical map of the vessels on the abdomen facilitates surgical planning and may decrease operating room time, reduce intraoperative complications, and possibly improve outcomes. This article reviews the available techniques for preoperative planning with the currently available imaging modalities of handheld Doppler, color Doppler (duplex) ultrasound, computed tomography angiography, and magnetic resonance angiography.

Background: Feasibility of composite tissue allotransplantation (CTA) has been substantiated by transplantations of the hand, abdominal wall, and face. CTA has the potential to reconstruct "like with like," but the risk-to-benefit ratio and clinical indications have yet to be determined. We sought to examine the current attitudes about the emerging field of CTA from those who treat complex facial injuries., Study Design: In 2007, a Web-based blinded survey was sent to both burn and plastic surgeons involved in facial reconstruction. We examined the practice profile with regard to complex facial injuries and asked respondents to assess the level of risk in CTA and indications for facial transplantation. Surgeons were asked to evaluate three clinical cases (two closely mirroring clinical face transplantations) for suitability for treatment with CTA., Results: One hundred sixty-four surgeons responded (54% response rate) and averaged 17.3 years in practice. They saw 12.1 severe facial-injury patients per year. A total of 78.7% agreed that current techniques do not provide adequate reconstruction for severe facial injuries, and 26.2% were in favor of performing CTA on immunosuppression. Acceptable indications for CTA were multiple failed reconstructions (70%), total facial burn (59%), and absence of remote tissue (55%). Ten percent saw no acceptable indication for CTA. The scenarios that mimicked recent transplantations had moderate support in favor of CTA (20.7% for the Chinese patient and 29.3% for the French patient)., Conclusions: This survey demonstrates support for use of CTA to reconstruct complex facial deformities. Surgeons continue to be wary of immunosuppression and chronic rejection, and many want to wait for better immunologic treatment options.

Purpose: Although composite tissue allotransplantation (CTA) is unparalleled in its potential to reconstruct "like with like," the risk-benefit ratio and clinical indications are difficult to determine. We examined current attitudes regarding the emerging field of CTA from those who treat complex hand injuries., Methods: A web-based survey regarding CTA was sent to members of the American Society for Surgery of the Hand, which identified their demographic data and practice profiles. Respondents' support for CTA and their assessment of the level of risk associated with these procedures were addressed. Additional questions focused on the clinical application of CTA with current immunosuppression, ethical issues surrounding CTA, and the indications for hand transplantation. Finally, 2 clinical situations that closely mirrored past hand transplantations were presented, and members evaluated their suitability for allotransplantation., Results: A total of 474 surgeons responded to the survey (22% response rate), who were divided in their opinion of hand transplantation with 24% in favor, 45% against, and 31% undecided. The majority (69%) consider this surgery to be a high-risk endeavor; however, a large percentage (71%) still believe it to be an ethical procedure when performed on properly selected patients. The most accepted indications for hand transplantation were loss of bilateral hands (78%) and amputation of a dominant hand (32%). Only 16% were in favor of performing transplants with the immunosuppression available today. In response to the clinical situation, 66% would offer transplantation to a bilateral hand amputee, whereas only 9% would offer transplantation to a patient with diabetes who had lost his or her dominant hand., Conclusions: This survey demonstrates support for hand allotransplantation as a solution for dominant-hand and bilateral hand amputees. However, surgeons continue to be concerned about the adverse effects of immunosuppression and the risks of acute and chronic rejection, and many want to wait for the development of better immunologic treatment options.

Body mass index (BMI) must be considered when selecting patients suitable for abdomen-based microsurgical breast reconstruction. It is unknown whether BMI or age affects quality or quantity of abdominal wall perforating blood vessels. The purpose of this study was to identify differences in abdominal wall perforating blood vessels among patients with different BMI and age. A retrospective review was conducted of 66 patients undergoing abdomen-based microsurgical breast reconstruction tissue transfer from 2000 to 2006. Median age was 48.6 years (+/- 8.2). Patients were divided into BMI < 25 (28 patients), BMI 25 to 30 (26 patients), or BMI > 30 (12 patients). Perforator size and location was determined by ultrasound data. There was a greater number of perforators in horizontal zone II compared with the remaining zones (P < 0.05, Bonferroni corrected). There were no differences between age or BMI and the number of perforators or average perforator size per patient. A significant positive linear association was found between the average perforator diameter and total number of abdominal wall perforators. We concluded there is no anatomical difference in perforator quality among patients with varying BMIs

A variety of defects of the upper and lower eyelids can be encountered after Mohs surgery. The goals of eyelid reconstruction are to provide structural and functional restoration with an acceptable aesthetic result. A thorough knowledge of the intricate anatomy of the eyelids combined with familiarity of the wide variety of reconstructive options is required to achieve these goals. In this article, we review the anatomy of the eyelids, and we present commonly used techniques for reconstruction of the upper and lower eyelids and the medial and lateral canthal regions after Mohs surgery.

Lockwood's changes in surgical design of the medial thigh lift have improved results and decreased complications but still have the fundamental problem of poor tissue fixation to rigid tissue. To provide increased support to the medial thigh incisions, modifications to this technique have been tried. This article describes the authors' approach to the medial thigh lift in both those patients who have undergone traditional weight loss and the massive weight-loss thigh-lift patient.

Learning Objectives: After studying this article, the participant should be able to: 1. Discuss nomenclature and anatomy associated with reconstruction of the back. 2. Perform preoperative assessment, decision making, and counseling of patients. 3. Describe current surgical planning, including careful analysis of the defect and appropriate selection of tissue to provide coverage while maximizing form and function., Background: The plastic surgeon is called to reconstruct defects in the posterior truck that involve an extensive zone of injury. Simple solutions, such as wide undermining and primary closure, will not result in a stable closed wound. Successful closure of these wounds depends on preoperative evaluation of tissue needs and host defects, and selection of the most appropriate flap to close dead space and provide vascularized tissue to the wound bed., Methods: The authors examined the literature regarding the available treatment options surrounding reconstruction of posterior back wounds. They review the important details surrounding the use of each flap and present select cases from their own experience regarding reconstruction of the back., Results: : The posterior trunk benefits from multiple flaps that can be used in reconstruction of the back. The wound must be evaluated in terms of tissue requirements and host issues, such as infection or previous radiation. Most wounds can be closed in a single stage, after careful flap section based on the wound's needs and anatomic location, with minimal postoperative complications. Early and aggressive treatment of these wounds improves patient outcomes and can reduce the time spent in hospital., Conclusions: Reconstruction of the posterior trunk depends on careful analysis of the tissue defects, host issues, and application of functional anatomy. The majority of wounds can be reconstructed after thorough débridement with a vascularized muscle flap.

Background: The aim was to investigate if intravascular in utero injection of adult bone marrow into swine fetuses could lead to macrochimerism and tolerance to the donor., Methods: Outbred Yorkshire sows and boars screening negative for MHC allele SLA of MGH miniature swine were bred. A laparotomy was performed on the sows at 50 days gestation to expose the uterus. Bone marrow harvested from SLA miniature swine was T-cell depleted and injected intravascularly into seventeen fetuses. Flow cytometry was performed to detect donor cells (chimerism) in the peripheral blood after birth. Mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML) assays were used to assess the response to donor MHC. Previously frozen skin grafts from the bone marrow donor were placed on the offspring from the first litter. Donor-matched renal transplant from SLA donors were performed on chimeric swine, with and without a short 12-day course of cyclosporine, and one nonchimeric littermate., Results: Nine inoculated offspring demonstrated donor cell chimerism in the peripheral blood and lymphohematopoietic tissues. All animals with detectable chimerism within the first three weeks were consistently nonreactive to donor MHC in vitro. Animals challenged with donor skin grafts displayed prolonged graft survival without producing antidonor antibodies. All chimeric animals accepted donor-matched kidney allografts, even one without cyclosporine. The kidney in the nonchimeric littermate rejected by day 21., Conclusions: Transplantation of allogeneic adult bone marrow into immunocompetent fetal recipients resulted in chimerism. In utero inoculation led to operational tolerance to the donor's major histocompatibility antigens and long-term acceptance to organ allografts.

Background: There is currently a great need for an in vitro assay to assess the presence of tolerance following allotransplantation to determine whether immunosuppressive medications can be discontinued. Our laboratory has recently developed an assay involving coculture inhibition of cell-mediated lympholysis that correlates with tolerance to allografts in swine leukocyte antigen (SLA) Class I-mismatched miniature swine. The potential for clinical application of this assay may depend on 2 important factors: (1) whether the assay can be used in the presence of immunosuppression; and (2) whether frozen-stored naive responder cells can be utilized., Methods: Long-term tolerant MGH miniature swine that had accepted SLA Class I-mismatched kidney transplants after a 12-day course of cyclosporine or tacrolimus were studied. Two long-term tolerant and 2 naive control animals were treated with a clinically relevant dose of cyclosporine for 2 weeks (trough level 100 to 400 ng/ml) to simulate the ongoing "chronic" immunosuppression used in human recipients of allografts. Cells from tolerant or naive, recipient-matched animals were stimulated for 6 days with donor or third-party SLA. These primed cells were then cocultured with naive unstimulated recipient major histocompatibility complex (MHC)-matched responders and irradiated stimulators. Responder cells were tested both fresh and frozen., Results: Suppression of cytotoxic responses of naive responder cells was observed in all coculture assays using cells from tolerant animals primed against donor antigen in vitro, but not in assays using similarly primed cells from naive animals. Responder cells from tolerant animals receiving immunosuppression had a suppressive activity similar to that from cells of the same animals not receiving immunosuppression. Similar suppression was also observed in coculture assays using either fresh or frozen naive responder cells., Conclusions: This coculture assay appears to correlate with the presence of tolerance under conditions applicable to the clinical setting. The assay appears to identify peripheral regulatory mechanisms of tolerance in allogeneic transplant recipients, and therefore may provide an approach for determining an appropriate timepoint at which to test withdrawal of immunosuppressive medications.

Background: The antigenicity of skin is a major obstacle to expanding human composite tissue transplantation. For example, multiple rejection episodes of the skin have been noted in clinical hand transplant patients. We have previously demonstrated tolerance to vascularized musculoskeletal allografts in major histocompatibility complex (MHC)-matched miniature swine treated with 12 days of cyclosporine. This regimen did not reproducibly lead to tolerance to subsequent frozen donor skin grafts. However, such skin grafts did not have a primary vascular supply. The aim of this study was to determine if tolerance to limb allografts with a vascularized skin component could be achieved with MHC matching and a 12-day course of immunosuppression., Methods: Hind limb grafts harvested with a 100 cm(2) cutaneous paddle were transplanted heterotopically into six MHC-matched, minor antigen-mismatched miniature swine. All animals received a 12-day course of cyclosporine. One control animal was not immunosuppressed. Grafts were evaluated with biweekly biopsies and tissue viability determined by histologic analysis. To test for sensitization, frozen donor skin grafts were applied to all animals that survived to postoperative day 100., Results: All treated animals (n=6) were tolerant to their musculoskeletal allografts at the time of necropsy (>100 days) regardless of the status of the epidermis. One animal demonstrated tolerance to the skin for more than 180 days. The other five animals demonstrated prolonged survival of the epidermal portion of the graft. The control animal rejected the graft epidermis at 10 days postoperatively. Frozen donor skin grafts demonstrated accelerated rejection (<10 days) in three of the animals and led to simultaneous rejection of both the epidermis of the allograft and the skin graft in the long-term tolerant animal. The rejection of the skin grafts did not break tolerance to the musculoskeletal portion in any of the animals., Conclusions: All animals exhibited indefinite survival of the musculoskeletal portion of their allografts but only prolonged survival of the epidermis. The loss of the graft skin appears to be the result of an isolated immune reaction to the skin, and, in particular, the epidermis. This observation is further substantiated by the accelerated rejection of secondarily placed frozen donor skin grafts.

Background: An important component of a composite tissue limb allograft (CTA) is the vascularized bone marrow and bone marrow stroma, which when transplanted could create immediate marrow space and engraftment. We have previously demonstrated that tolerance to musculoskeletal allografts can be achieved with a 12-day course of cyclosporine without the presence of long-term peripheral donor cell chimerism. The objective of this study was to determine the fate of the donor bone marrow after transplantation of a limb allograft in a miniature swine model., Methods: CTAs from donor swine were heterotopically transplanted into six MHC-matched, minor-antigen-mismatched recipients, and a 12-day course of cyclosporine was given. Previous animals transplanted without cyclosporine rejected their grafts in less than 42 days. A non-MHC-linked marker, pig allelic antigen (PAA), was used to distinguish host and donor cells. Three PAA- animals received PAA+ CTAs, and three PAA+ animals received PAA- CTAs. Bone marrow was harvested from the donor limb grafts and the recipient and analyzed by flow cytometry and histology. Thymus, spleen, and mesenteric lymph nodes were also harvested from the recipient swine and evaluated for the presence of donor cells by flow cytometry., Results: All animals receiving cyclosporine demonstrated permanent tolerance to their allografts. Donor bone marrow cells were present in all grafts at the time of transplantation and during the immediate postoperative period. By 48 weeks, donor cells were no longer detectable within the marrow space of the allograft. In long-term animals host bone marrow cells replaced donor cells in the graft marrow space. No evidence of donor cell engraftment was found in recipient animals., Conclusion: This study demonstrates that in long-term tolerant recipients of musculoskeletal allografts there is no evidence of persistent donor bone marrow cells in the hematopoietic tissues of the graft or the host. Rather, the recipient's bone marrow cells and lymphocytes repopulate the donor marrow space of the graft.

Background: Although transplantation of musculoskeletal allografts in humans is technically feasible, the adverse effects of long-term immunosuppression subject the patient to high risks for correcting a non-life-threatening condition. Achieving immunologic tolerance to musculoskeletal allografts, without the need for chronic immunosuppression, could expand the clinical application of limb tissue allografting. Tolerance to musculoskeletal allografts has been accomplished previously in miniature swine in our laboratory. Although stable, mixed chimerism has been suggested as the mechanism underlying long-term tolerance in a rat limb model, the mechanism of this tolerance induction has not been established. This report explores the possible relationship between hematopoietic chimerism and tolerance to musculoskeletal allografts in swine., Methods: Twelve miniature swine underwent vascularized musculoskeletal allograft transplantation from histocompatibility complex (MHC) matched, minor antigen-mismatched donors. Eight animals received a 12-day coprse of cyclosporine, one of which was excluded due to subtherapeutic levels. Four recipients were not immunosuppressed. Serial biopsies to assess graft viability and flow cytometry to assess chimerism were performed. Donor and third-party skin grafts were placed on recipients with surviving allografts greater than 100 days to validate tolerance., Results: Both groups developed early peripheral chimerism, but this chimerism became undetectable by postoperative day 19 in the cyclosporine group and by day 13 in the control group. Animals receiving cyclosporine developed permanent tolerance to their allografts, whereas those not receiving cyclosporine rejected their allografts in 6-9 weeks. Animals demonstrating tolerance to their bone allografts also demonstrated prolonged donor skin graft survival., Conclusions: Induction of tolerance to musculoskeletal allografts can be achieved in the MHC matched swine. Although hematopoietic chimerism is present in the immediate postoperative period, persistent, long-term chimerism does not seem to be necessary for maintenance of such tolerance.