James E. Zins

Membranous versus endochondral bone: implications for craniofacial reconstruction.

Based on observations in the human suggesting improved membranous bone graft take, an experimental study was undertaken in 15 rabbits and 7 monkeys to evaluate the differences in take between membranous and endochondral bone grafts. Using vital stains, serial cephalograms, direct measurements, and point-counting techniques, the grafts were compared. In both types of experimental animals, membranous bone maintained its volume to a significantly greater extent than endochondral bone when autografted in the craniofacial region. The loss of volume with endochondral grafts was at the end of the experiment more than three times that of membranous grafts in the rabbit (65 percent endochondral loss versus 19.5 percent membranous loss) and more than four times volume loss in the monkey (17.2 percent membranous volume loss versus 88 percent endochondral loss). The uptake of vital stains (tetracycline and alizarin) was greater with membranous bone, and point counting demonstrated more living membranous bone (40.5 percent membranous versus 28.1 percent endochondral) at the end of the experiment. These studies confirm the increased resorption of endochondral bone grafts when compared with membranous grafts and substantiate clinical impressions that cranial donor sites are preferable for craniofacial recipient areas when clinically feasible.

The early revascularization of membranous bone.

The experimental finding that membranous onlay bone grafts maintain volume and viability to a greater extent than do endochondral grafts may be related to the more rapid vascularization of membranous bone. Microangiographic techniques were used to study the rates of vascularization of membranous and endochondral bone grafts in adult white New Zealand rabbits at 1, 3, 7, 14, and 21 days after bone grafting. Vascularization patterns were quantified microscopically using a modified point-counting technique. At 3 days, membranous bone grafts demonstrated vessel ingrowth from both soft tissue and host bone. Little ingrowth was seen in endochondral grafts. By day 7, 2.5 vessels per square were indentified entering membranous grafts, while an average of 0.6 vessels per square were counted for endochondral bone grafts. At day 14, there was an average of greater than 20 vessels per square for membranous grafts versus 1.8 for their endochondral counterparts. At 21 days, the endochondral grafts demonstrated persistent avascular central areas not seen in membranous grafts. Membranous onlay bone grafts in the rabbit are more rapidly vascularized than endochondral grafts. This factor may affect the greater volume maintenance seen in experimental membranous grafts.

Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers

Smoking results in impaired wound healing and poor surgical results. In this retrospective study, we compared outcomes in 155 smokers, 76 ex‐smokers, and 517 nonsmokers who received postmastectomy breast reconstructions during a 10‐year period. Ex‐smokers were defined as those who had quit smoking at least 3 weeks before surgery. Transverse rectus abdominis musculocutaneous (TRAM) flap surgery was performed significantly less often in smokers (24.5 percent) than in ex‐smokers (30.3 percent) or nonsmokers (39.1 percent) (p < 0.001). Tissue expansion followed by implant was performed in 112 smokers (72.3 percent), 50 (65.8 percent) ex‐smokers, and 304 nonsmokers (58.8 percent) (p = 0.002). The overall complication rate in smokers was 39.4 percent, compared with 25 percent in ex‐smokers and 25.9 percent in nonsmokers, which is statistically significant (p = 0.002). Mastectomy flap necrosis developed in 12 smokers (7.7 percent), 2 ex‐smokers (2.6 percent), and 8 nonsmokers (1.5 percent) (p < 0.001). Among patients receiving TRAM flaps, fat necrosis developed in 10 smokers (26.3 percent), 2 ex‐smokers (8.7 percent), and 17 nonsmokers (8.4 percent). Abdominal wall necrosis was more common in smokers (7.9 percent) than in ex‐smokers (4.3 percent) or nonsmokers (1.0 percent). In this large series, tissue expansion was performed more often in smokers than was autogenous reconstruction. Complications were significantly more frequent in smokers. Mastectomy flap necrosis was significantly more frequent in smokers, regardless of the type of reconstruction. Breast reconstruction should be done with caution in smokers. Ex‐smokers had complication rates similar to those of nonsmokers. Smokers undergoing reconstruction should be strongly urged to stop smoking at least 3 weeks before their surgery. (Plast. Reconstr. Surg. 107: 342, 2001.)

A new composite facial and scalp transplantation model in rats

There are limited sources of autogenous tissue available for reconstruction of severe facial and scalp deformities caused by extensive tumor ablation, burns, or trauma. Allografts from cadaveric sources may serve as a reconstructive alternative. However, technical and immunological aspects of harvesting and transplanting face and scalp flaps limit the routine use of such procedures. For evaluation of the feasibility of composite-tissue reconstruction, an experimental model of composite face/scalp flap transplantation in rats was designed. Technical aspects of the model, survival rates, and the complications encountered during development of the model are presented. A total of 64 animals, in three experimental groups, were studied. In group I, the anatomical study group (n = 6), the anatomical features of the face and scalp region in rats were explored. Groups II and III were the transplantation groups. Isograft transplantations were performed between identical Lewis rats (RT11 to RT11), and allografts were transplanted, across major histocompatibility complex barriers, between Lewis-Brown Norway rats (RT1l/n) and Lewis rats (RT11). In group II (the control group, n = 8), transplantation of nonvascularized composite face/scalp isografts and allografts was performed. In group III (the transplantation group, n = 50), vascularized face/scalp isografts (n = 36) and allografts (n = 14) were transplanted. Complications included partial or total flap necrosis, death attributable to food aspiration, and poor general condition. To prevent acute and chronic allograft rejection, cyclosporine A (16 mg/kg per day) therapy was initiated 24 hours after transplantation; the dose was tapered to 2 mg/kg per day within 4 weeks and was maintained at that level thereafter. Long-term survival (>170 days) was achieved, without any signs of rejection, with low-dose (2 mg/kg per day) cyclosporine A therapy. This is the first report documenting successful composite face/scalp flap transplantation in the rat model.

A Review on Bevacizumab and Surgical Wound Healing: An Important Warning to All Surgeons

Bevacizumab (Avastin, Genentech, Inc, San Francisco, CA), a humanized monoclonal antibody against vascular endothelial growth factor, was recently approved for the treatment of metastatic breast cancer. A PubMed and OVID search was performed using keywords: bevacizumab, Avastin, wound healing, VEGF, angiogenesis, and colorectal cancer. Our objective was to review the current literature in regard to bevacizumab and its adverse effects on surgical wound healing. Bevacizumab has been associated with multiple complications in regard to wound healing, such as dehiscence, ecchymosis, surgical site bleeding, and wound infection. Current literature suggests patients should wait at least 6 to 8 weeks (>40 days) after cessation to have surgery (half-life = 20 days). In addition, postoperative reinitiation of bevacizumab must wait ≥28 days to prevent an increased risk of wound healing complications, and the surgical incision should be fully healed. The adverse effects of bevacizumab in regard to wound healing must be considered in all surgical patients.

The roles of revascularization and resorption on endurance of craniofacial onlay bone grafts in the rabbit.

A total of 32 New Zealand white rabbits underwent subperiosteal implantation of fresh autogenous unicortical calvarial and iliac crest grafts on their snouts with microscrew rigid fixation. After 3 and 10 days, vascularity was assessed by latex casting, and osteoclastic activity was determined by histochemical staining for tartrate-resistant acid phosphatase. After 70 days, volumetric analysis and tartrate-resistant acid phosphatase staining were performed on six animals. The calvarial grafts demonstrated greater volume maintenance than the iliac bone (72 percent versus 32 percent, p < 0.025). There were significantly greater osteoclastic activity and revascularization in the cancellous portion of calvarial and iliac crest bone grafts by the 10th day of onlay grafting. Minimal activities were present at the cortical bone. Because calvarial grafts contain more cortical bone, its superior volume maintenance can be understood by the architectural influence on revascularization and resorption.

The world's experience with facial transplantation: What have we learned thus far?

The objective of this review article is to summarize the published details and media citations for all seven face transplants performed to date to point out deficiencies in those reports so as to provide the basis for examining where the field of face transplantation stands, and to act as a stimulus to enhance the quality of future reports and functional outcomes. Overall long-term function of facial alloflaps has been reported satisfactorily in all seven cases. Sensory recovery ranges between 3 and 6 months, and acceptable motor recovery ranges between 9 and 12 months. The risks and benefits of facial composite tissue allotransplantation, which involves mandatory lifelong immunosuppression analogous to kidney transplants, should be deliberated by each institution’s multidisciplinary face transplant team. Face transplantation has been shown thus far to be a viable option in some patients suffering severe facial deficits which are not amenable to modern-day reconstructive technique.

Induction of tolerance in composite-tissue allografts

Background. Transplantation of composite-tissue allograft (CTA) such as the human hand recently became a clinical reality. The high risks associated with the use of lifelong immunosuppression have been the prohibiting factor in the routine use of the CTA transplants. In this article, we present a new approach of inducing long-term, donor-specific tolerance to CTAs without recipient preconditioning and need for chronic immunosuppression. Methods. We have developed a clinically applicable 35-day protocol that induces donor-specific tolerance in a rat hindlimb-transplantation model across major histocompatibility complex (MHC) barrier [Lewis-Brown-Norway (LBN, RT1l/n→F1) to Lewis (LEW, RT1l) by using cyclosporine A (CsA) and a mouse monoclonal antibody against rat &agr;&bgr;-T-cell receptor (TCR) to systemically eliminate alloresponsive cells. Standard skin grafting, flow cytometry (FC), and mixed lymphocyte reaction (MLR) were used to assess efficacy of immunodepletion and confirm donor-specific tolerance and chimerism. Results. Under this protocol long-term tolerance (>720 days) was induced in all (n=5) CTA recipients across the MHC barrier without further need for immunosuppression. Tolerance was confirmed in all limb-allograft recipients by skin grafting in vivo and by MLR in vitro. The animals rejected third-party grafts, indicating immunocompetence. Conclusions. In this CTA model, combined protocol of &agr;&bgr;-TCR monoclonal antibody and CsA resulted in induction of donor-specific tolerance across the MHC barrier without recipient conditioning. We believe that our findings will foster development of new therapeutic strategies and expand clinical applications for composite-tissue transplantation.

Treatment of dermatofibrosarcoma protuberans with Mohs micrographic surgery.

Ten patients with dermatofibrosarcoma protuberans, all of whom had been treated previously by conventional excisional surgery without success, were treated with Mohs micrographic surgery. A team approach utilizing margin control by Mohstrained physicians and reconstruction by surgical specialists was employed. Average follow-up exceeds 3 1/2 years, with no recurrences. Microscopically controlled excision appears to be the treatment of choice for dermatofibrosarcoma protuberans.

Use of calcium-based bone cements in the repair of large, full-thickness cranial defects: a caution.

Background: Calcium-based bone cements have increased in popularity for the correction of craniofacial contour defects. The authors’ experience with them in more than 120 patients has resulted in the establishment of strict criteria for their use. Although the authors’ overall complication rate with these cements has been low, certain patient groups have an unacceptably high complication rate. The authors describe their experience with the repair of large, full-thickness cranial defects using calcium-based bone cements. Methods: The study group comprised 16 patients who underwent correction of large, full-thickness (>25 cm2) skull defects. The surgical technique included reconstruction of the floor of the defect with rigid fixation to the surrounding native bone, interposition of the cement to ideal contour, and closure of the defect. Results: The mean patient age was 35 years (range, 1 to 69 years). The mean defect area was 66.4 cm2 (range, 30 to 150 cm2). Cases were equally divided between BoneSource and Norian CRS. The mean amount of bone cement used was 80 g. Follow-up varied between 1 and 6 years (mean, 3 years). Major complications occurred in eight of 16 patients, with one occurring as late as 6 years postoperatively. Complications occurred throughout the course of review, indicating that they were not caused by a learning curve. Conclusion: Because of the unacceptably high complication rate with the use of calcium-based bone cements in large skull defects, the authors believe that their use is contraindicated and have returned to using autogenous split skull cranial bone reconstruction for these patients.