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PURPOSE To prospectively assess the feasibility, risk profile, and effect on fibrinogen levels of tenecteplase in transcatheter thrombolysis for peripheral arterial and venous occlusive disease. MATERIALS AND METHODS Between March 2001 and January 2002, 18 consecutive patients (14 men, four women) with arterial ( n = 13) or venous ( n = 5) occlusive disease were treated with tenecteplase infusions of 0.25 mg/h. Technical success was defined as restoration of antegrade flow and removal of more than 95% of thrombus. Clinical success was defined in arterial cases as immediate limb salvage and relief of ischemic rest pain and in venous cases as resolution or improvement in extremity pain and swelling. Major bleeding was defined as an intracranial bleeding episode, bleeding that resulted in death, or bleeding that required transfusion, surgery, or cessation of thrombolytic therapy. RESULTS Technical success was achieved in all 18 patients (100%). Clinical success was achieved in 11 of 13 arterial cases (85%) and in four of five (80%) venous cases. The mean duration of thrombolysis treatment was 21.5 hours ± 6.2 (range, 7–35 h), with total tenecteplase doses of 7.1 mg ± 4.3 (range, 1.75–18.75 mg). Major bleeding occurred in one patient (5.5%) because of slow oozing from bilateral femoral groin access sites, which caused a 25% decrease in hematocrit level. There were no deaths, intracranial hemorrhages, remote sites of bleeding, or minor bleeding complications. The serum fibrinogen level dropped to a mean of 77.4% ± 19.2% of baseline. CONCLUSION In this initial study, tenecteplase was shown to be a feasible treatment for peripheral arterial and venous thrombolysis with only moderate effect on fibrinogen levels.

Background Although prolonged composite tissue allograft (CTA) survival is achievable in animals using immunosuppressive drugs, long-term immunosuppression of CTAs in the clinical setting may be unacceptable for most patients. The purpose of this study was to develop a model for reliable CTA tolerance induction in the adult rat across a major MHC mismatch without the need for long-term immunosuppression. Methods Mixed allogeneic chimeras were prepared by using rat strains with strong MHC incompatibility [WF (RT1Au), ACI (RT1Aa)] WF + ACI-->WF, n=23. The bone marrow (BM) of recipient animals was pretreated with low-dose irradiation (500-700 cGy), followed by reconstitution with a mixture of T cell-depleted syngeneic (WF) and allogeneic (ACI) cells. Additionally, the recipient animals received a single dose of anti-lymphocyte serum (10 mg) 5 days before bone marrow transplantation (BMT) and tacrolimus (1 mg/kg/day) from the day before BMT to 10 days post-BMT. Hindlimb transplants were performed 12 months after BMT. Five animals received a limb allograft irradiated (1000 cGy) just before transplantation. Rat chimeras were characterized (percentage of donor cells present within the bloodstream) by flow cytometry at 3 and 12 months after BM reconstitution and after hindlimb transplantation. Results Peripheral blood lymphocyte chimerism (WF/ACI) remained stable >12 months after BM reconstitution in 18/23 animals. Multi-lineage chimerism of both lymphoid and myeloid lineages was present, suggesting that engraftment of the pluripotent rat stem cell had occurred. In animals with donor chimerism >60% (n=18) no sign of limb rejection was present for the duration of the study. All animals with chimerism 60 days in 14/21 rats. Postoperative flow cytometry studies demonstrated stable chimerism in all animals studied (n=10). Five out of five animals with irradiated limb transplants showed no sign of GVHD at >100 days. Conclusions Stable mixed allogeneic chimerism can be achieved in a rat hindlimb model of composite tissue allotransplantation. Hindlimb allografts to mixed allogeneic chimeras exhibit prolonged, rejection-free survival. Partial functional return should be expected. The BM transplanted as part of the hindlimb allograft plays a role in the etiology of GVHD. Manipulating that BM before transplantation may influence the incidence of GVHD. This represents the first reliable rat hindlimb model demonstrating rejection-free CTA survival in an adult animal across a major MHC mismatch without the long-term need for immunosuppressive agents.

Objective To analyze a series of patients treated for recurrent or chronic abdominal wall hernias and determine a treatment protocol for defect reconstruction. Background Data Complex or recurrent abdominal wall defects may be the result of a failed prior attempt at closure, trauma, infection, radiation necrosis, or tumor resection. The use of prosthetic mesh as a fascial substitute or reinforcement has been widely reported. In wounds with unstable soft tissue coverage, however, the use of prosthetic mesh poses an increased risk for extrusion or infection, and vascularized autogenous tissue may be required to achieve herniorrhaphy and stable coverage. Methods Patients undergoing abdominal wall reconstruction for 106 recurrent or complex defects (104 patients) were retrospectively analyzed. For each patient, hernia etiology, size and location, average time present, technique of reconstruction, and postoperative results, including recurrence and complication rates, were reviewed. Patients were divided into two groups based on defect components: Type I defects with intact or stable skin coverage over hernia defect, and Type II defects with unstable or absent skin coverage over hernia defect. The defects were also assigned to one of the following zones based on primary defect location to assist in the selection and evaluation of their treatment: Zone 1A, upper midline; Zone IB, lower midline; Zone 2, upper quadrant; Zone 3, lower quadrant. Results A majority of the defects (68%) were incisional hernias. Of 50 Type I defects, 10 (20%) were repaired directly, 28 (56%) were repaired with mesh only, and 12 (24%) required flap reconstruction. For the 56 Type II defects reconstructed, flaps were used in the majority of patients (n = 48; 80%). The overall complication and recurrence rates for the series were 29% and 8%, respectively. Conclusions For Type I hernias with stable skin coverage, intraperitoneal placement of Prolene mesh is preferred, and has not been associated with visceral complications or failure of hernia repair. For Type II defects, the use of flaps is advisable, with tensor fascia lata representing the flap of choice, particularly in the lower abdomen. Rectus advancement procedures may be used for well-selected midline defects of either type. The concept of tissue expansion to increase both the fascial dimensions of the flap and zones safely reached by flap transposition is introduced. Overall failure is often is due to primary closure under tension, extraperitoneal placement of mesh, flap use for inappropriate zone, or technical error in flap use. With use of the proposed algorithm based on defect analysis and location, abdominal wall reconstruction has been achieved in 92% of patients with complex abdominal defects.

Background: The efficacy of prophylactic mastectomy and oophorectomy in reducing breast and ovarian carcinoma has recently been reported in high-risk women. Because cost has become central to medical decision-making, this study was designed to evaluate currently existing coverage policies for these procedures. Methods: A confidential detailed cross-sectional nationwide survey of 481 edical directors from the American Association of Health Plans, Medicare, and Medicaid was conducted. Results: Of the 150 respondents, 65% (n 5 97) had 100,000 or more enrolled members and 35% (n 5 53) had fewer than 100,000 enrolled members. Only 44% of private plans have specific policies for coverage of prophylactic mastectomy for a strong family history of breast cancer and 38% of plans for a BRCA mutation. Only 20% of total responding plans had a policy for coverage of prophylactic oophorectomy under any clinical circumstance. Governmental carriers were significantly less likely to have any policy for prophylactic surgery (range, 2%–12%) compared with nongovernmental plans (range, 24%–44%; P,.001). No significant regional differences for coverage policies were identified (P.05). Conclusions: Significant variations currently exist for health insurance coverage of prophylactic mastectomy and oophorectomy. As genetic testing becomes widespread, more uniform policies should be established to enable appropriate high-risk candidates equal access and coverage for these procedures.

The management of complex bronchopleural fistula remains a major therapeutic challenge for the thoracic surgeon. Although the incidence of bronchopleural fistula following lung resection has decreased in recent years to 1% to 2%, when it occurs, it is associated with significant morbidity and mortality. Using illustrative cases, the epidemiology and pathophysiology of bronchopleural fistula are reviewed and operative strategies are discussed. Algorithms for the diagnosis and treatment are suggested on the basis of cases described in the literature. The best way to prevent a fistula is to rigorously follow the surgical techniques described, with minimal devascularization of the bronchus and prophylactic coverage of the stump in high-risk patients. Successful management of a fistula is combined with treatment of the associated empyema cavity. Definitive repair should be accomplished expeditiously, minimizing the number of procedures performed. When treatment is protracted, secondary complications are more likely and survival is adversely affected. The first step should be control of active infection and adequate drainage of the hemithorax, followed by timely repair of the bronchopleural fistula when possible and reinforcement of the stump with vascularized tissue. If a residual cavity is present it must also be obliterated with a pedicled muscle flap.

Background Functional restoration following resection or traumatic injury to the mandible depends on the reliability of the bony reconstruction to heal primarily and support endosseous implants. Although vascularized bone flaps (VBF) and nonvascularized bone grafts (NVBG) are both widely used to reconstruct the mandible, indications for each remain ill-defined. The purpose of this study was to compare bone graft/flap healing and success of implant placement in patients reconstructed with VBF versus NVBG. Methods Over the past 10 years, 75 consecutive mandibular reconstructions were performed (26 free bone grafts, 49 vascularized bone flaps). Etiology of the defect, history of irradiation, bone defect size, number of operations, graft/flap success, and dental implant success rates were determined and compared. Bone graft/flap success was defined as complete bony union. Implant success was defined as complete osseointegration. Mean follow-up was 3 years. Results Free flaps were used primarily for malignant disease (78%, 38/49). Bone grafts were used primarily for benign disease (88%, 23/26). History of prior irradiation: 11% (3/26) NVBG versus 45% (22/49) VBF. Length of bony defect (mean): 8.1 cm NVBG versus 9.4 cm VBF. Successful bony union, any size defect: 69% (18/26) NVBG versus 96% (47/49) VBF (p Conclusions Despite the fact that patients reconstructed with VBFs were older, had larger defects, and were treated primarily for malignant disease and therefore had a higher incidence of irradiation to the affected mandible than in patients treated with NVBGs, the incidence of bony union was higher, requiring fewer operations to achieve union, and the implant success rate was significantly greater than for NVBG patients. Results were similar when considering lateral defects only. Based on these results, VBFs are indicated in most cases of mandibular reconstruction; NVBGs are effective for short bone defects (

Purpose: The purpose of this study was to determine the efficacy of vascularized free fibula bone grafts for mandibular salvage reconstruction. Patients and Methods: Seven patients had fibula grafts after failed attempts at mandibular reconstruction. The prior attempts involved 20 operative procedures. Four of the seven patients (57%) had a history of radiation to the affected mandible. Bony defects averaged 10.2 cm (range, 4.5 to 24 cm), and the associated soft tissue defects averaged 6 × 12 cm. Average follow-up was 16 months. Cosmetic (facial symmetry) and functional (speech quality, oral continence, deglutition, donor site morbidity, dental rehabilitation) results were evaluated by questionnaire and clinical examinations. Results: Soft tissue coverage and mandibular restoration were successful in all patients, and flap survival was 100%. Five of the seven patients (70%) achieved good or excellent functional results, and five of seven (70%) achieved good or excellent esthetic results. Complications were minimal, and the average hospital stay was 14 days. Conclusions: When the initial attempt at mandibular reconstruction is unsuccessful, mandibular function and esthetics can be salvaged with reliable vascularized soft tissue and bone flaps. As long as appropriate flap options are considered and the patient is medically stable, successful mandibular reconstruction should be achievable despite the number or cause of prior failed attempts.

As our contributors to this section have pointed out, there are at present two main methods of reconstructing defects of the pharynx and cervical esophagus: free jejunal transfer (FJT) and tubed radial forearm flap. The advantage of the FJT is that it is a tube, thus limiting the enteric suture lines to proximal and distal. The radial forearm flap requires not only the proximal and distal suture lines but a long longitudinal suture line to create the tube. This increase the possibility for fistula formation. The controversy surrounding this case concerns what to do with a remaining mucosal strip after a subtotal laryngectomy. Traditional reconstructive principles would dictate that normal tissue should not be sacrificed, but some would argue that the remaining mucosa should be sacrificed to allow for use of a FJT. The other alternative would be use of a radical forearm skin flap tubed to 270 degrees. At the University of Texas M. D. Anderson Cancer Center, we preferentially use the FJT for almost all defects and would probably have sacrificed the remaining mucosal strip in this particular case. We have used skin flaps to patch pharyngeal defects and prevent stricture in a number of cases. This is usually done however when the remaining pharyngeal mucosa approaches 50% or greater. Although we do not routinely use the tubed radial forearm flap because of the increased rate of fistula formation, there are some definite indications for its use. The first important indication is in patients in whom speech rehabilitation is desired or indicated. The skin flap provides a stiffer resonating chamber for the speech production and does not have the peristalsis or the mucus production associated with the jejunal flap. Another indication for use of radial forearm flap would be when there is a contraindication to celiotomy, ie, patients with hepatic cirrhosis and associated ascites or other abdominal conditions precluding abdominal exploration. In this situation, avoiding an intra-abdominal procedure would limit operative morbidity. In conclusion, one should use whichever procedure obtains a healed wound and re-establishes continuity of the upper gastrointestinal tract. In our hands, retention of the remaining mucosal segment would not be critical in this particular case and in fact would present a hindrance to use of the FJT.

Lymphatic regeneration following unilateral hindlimb autotransplantation was studied in 14 Lewis rats using Technetium-99 radiolabeled sulfur colloid (TC-99) lymphoscintigraphy and compared to the lymphatic pattern exhibited in four unoperated control rats. Control animals demonstrate a reproducible flow of lymph along the deep lymphatic system from the foot, draining into the ipsilateral inguinal nodes, and then up to the para-aortic nodes. Following replantation, lymphatic outflow from the replanted limb begins to occur within 3 to 6 days, reaching normal lymphatic clearance within 12 days. However, the pattern of lymphatic flow is ill-defined, relying on multiple small channels of the superficial lymphatic system. In contrast to controls, at 3 hr post TC-99 injection, lymphatic drainage in replanted rats is via the inguinal and axillary nodal regions bilaterally. This abnormal pattern persisted in the replanted animals for the duration of this study, 160 days. It is evident that lymphatic regeneration in this animal model is associated with a rapid return to normal levels of lymphatic clearance via collateral channels within the subcutaneous tissue. The rapidity with which lymphatic drainage is restored, and its localization within the subcutaneous tissue, can explain why replanted tissues and microvascular free flaps seldom develop lymphedema. In addition, the rat hindlimb replantation model may prove useful for studies of the general mechanisms and specific factors responsible for lymphangiogenesis.

The role of wound debridement and flap coverage in treating pressure sores is clearly established. However, criteria and supportive clinical data for specific flap selection and the sequence of flaps for coverage of the ischium remain ill-defined. From 1979-1995, 114 consecutive patients underwent flap coverage of 139 ischial pressure sores. Preoperative risk factors, prior flap history, defect size, flap success, complication rates, and the length of hospitalization were retrospectively evaluated and compared for 112 flaps in 87 patients. Flap success was defined as a completely healed wound. Average follow-up was 10 months (range: 1 month-9 years). Overall, 83% (93/112) of the flaps healed. In the majority of cases (75%, 84/112), wound debridement and flap reconstruction was achieved in a single stage. However, there were significant differences in the healing rates among the various flaps used. The inferior gluteus maximus island flap and the inferior gluteal thigh flap had the highest success rates, 94% (32/34) and 93% (25/27), respectively, while the V-Y hamstring flap and the tensor fascia lata flap had the poorest healing rates, 58% (7/12) and 50% (6/12), respectively. Flap success was not significantly affected by the age of the patient or the prior number of flaps used and preoperative risk factors were equally distributed across all types of flaps. The overall complication rate was 37% (41/112), most commonly from a slight wound edge dehiscence (n = 16) that healed with local wound care within one month postoperatively. Results of this study show that proper flap selection and the appropriate sequence of flap use significantly improve success rates for ischial pressure sore coverage in both the short- and long-term. Based upon flap reliability (successful healing rates), reusability, and the need to preserve as many future flap options as possible, a rationale for flap selection is presented which can be individualized to any patient.

Modern treatment of complex midfacial defects has evolved over the past 5 years, primarily with the advent of reliable vascularized bone flaps and osseointegrated implants. To determine the effectiveness of these advances, 26 consecutive patients with complex midfacial defects treated from 1991 through 1995 with immediate muscle-flap coverage were evaluated. The etiology of the defect included neoplasm (n = 23) and trauma (n = 3). Seventy-eight percent of the patients received adjuvant radiation therapy. Follow-up ranged from 3 months to 4 years, with a mean of 18 months. Twenty-three patients (88 percent) were reconstructed with a single major procedure. All patients had free-flap reconstruction, and 100 percent of the flaps survived. Late tumor recurrence was seen in 5 of 23 patients (22 percent) and was detected promptly. Aesthetic and functional results were rated good or excellent in 77 and 88 percent of the patients, respectively, as determined by patient questionnaires and physical examinations. Fourteen of 18 patients (78 percent) undergoing partial or complete alveolar ridge resection received dental rehabilitation, 43 percent of whom received osseointegrated implants into either a bone flap or remaining native bone. Osseointegrated implants were inset during the initial reconstruction 50 percent of the time. A treatment algorithm for free-flap selection based on the size of the defect and the bony requirement for reconstruction is presented. Bony restoration is only required in those areas where osseointegrated implants need to be placed. In such cases, the fibula osteocutaneous free flap is the flap of choice. Otherwise, soft-tissue flaps are selected based on wound size. Immediate free-flap coverage provides effective, single-stage treatment, both aesthetically and functionally, for complex midfacial defects.

The purpose of this study was to determine the role of the fibular free flap in reconstructing lateral segmental defects of the mandible. Over the past 5 1/2 years, 17 consecutive patients underwent reconstruction of their lateral mandible with the fibular free flap. Patients included 12 men and 5 women, the mean age was 54 years (range, 29-76 years), and the mean length of the mandibular defect was 6.3 cm (range, 2.5-9 cm). The majority of patients with tumors (54%) were treated for recurrence and 92% received radiation to the operative field. The mean operative time to perform the microsurgery and bone plating was 4 hours. Postoperative morbidity occurred in 3 patients (18%) (plate fracture, malocclusion, orocutaneous fistula). Five patients (29%) required leg donor site skin grafting. Donor site morbidity included a minor cellulitis, a transient neuropraxia, and one case of leg swelling. None required additional surgery for donor complications. Thus far, 71% of the patients have received dental rehabilitation and 35% had osseointegrated implants placed in their bone flap. Eighty-two percent of the patients achieved both good or excellent aesthetic and functional results. Sixteen patients (94%) tolerate at least a soft diet and 65% are on a regular diet. Five patients developed tumor recurrence an average of 9 months postoperatively with a mean survival of 21 months. This study demonstrates that the fibular free flap is highly reliable for reconstructing the lateral mandible in a single stage, with low overall morbidity, and provides for excellent dental and speech rehabilitation. For most patients, the fibular free flap should be considered for lateral mandibular reconstruction even in those patients with a limited life expectancy.

The fibula osteocutaneous free flap is effective for managing most mandibular defects. Debate over several technical aspects of the flap dissection continues to take place in the literature, specifically with regard to skin island viability and donor leg morbidity. In our experience, the fibula flap is harvested based solely on the septal perforators without incorporating portions of the soleus muscle. Flap bulk is minimized whereas donor leg function is maximized. Therefore, the overall dissection can proceed expeditiously, with extreme care necessary only in the deep posterior compartment at the level of the peroneal vessels. Optimal skin island viability can be ensured by harvesting a long segment of skin along the same axis as the underlying fibula to include the maximum number of perforators. This provides enough soft tissue and pedicle length to reconstruct virtually any size defect. Subsequently, a subperiosteal bone dissection to remove unneeded proximal fibula preserves the vascularity of the remaining skin and bone. Adherence to these and other principles outlined in this article should consistently ensure flap success with minimal morbidity.

Refinements in microsurgical techniques, plate fixation, and osseointegration have changed the conceptual approach to midface reconstruction. Free tissue transfer has emerged as the ideal method of reconstructing complex midfacial defects. Single-stage bony restoration of the palate and orbital rim using the folded fibular osteocutaneous free flap is described. The fibular free flap is our first choice for reconstructing complex midfacial defects. The thin, soft, pliable tissue is ideal for intraoral and palatal reconstructions. The bone can be tailored precisely to fit any desired shape, and forms a sturdy support for both orbital and dental prostheses. With a single flap, rapid and reliable restoration of midfacial appearance, orbital support, and palatal function can be achieved.

In both vascular and microvascular surgery, there is a need for a non-thrombogenic, small-caliber, arterial substitute. Clinically, most vessel substitutes with diameters under 4 mm have low patency rates. An arterial conduit made from a biocompatible human acellular dermis may be useful as a small vessel conduit. The purpose of this study was to evaluate and compare the patency rates of a vascular conduit made from rolled human acellular dermal (ACD) matrix and a similar-sized polytetrafluoroethylene (PTFE) tube, using the rat femoral artery interposition model. Twenty-eight days after implantation, 9 or 10 (90 percent) ACD grafts and 5 of 8 (62.5 percent) PTFE grafts were patent. False aneurysms formed in 6 ACD conduits along the longitudinal suture line. The three patent non-aneurysmal ACD conduits developed an endothelial luminal lining. While further studies are needed, acellular dermis appears to be a promising material for use as a vessel substitute.

In microvascular surgery when local recipient vessels are inadequate, vein grafting is required. There are several potential inherent disadvantages of immediate vein grafting, including the development of graft thrombosis or leakage, an increased opportunity for technical errors, and an increased number of anastomoses in series. All of these may contribute to a higher failure rate for composite-tissue transplantation requiring vein grafts. The authors hypothesized that in cases where vein grafting is obviously required, the creation of a temporary, looped, arteriovenous fistula (AVF) would reduce the morbidity of vein grafting, by allowing the detection of thrombosis or technical errors predisposing to thrombosis prior to free-tissue transplantation. Since delaying the division of an AVF for 5 or more days may allow time for healing of the endothelium at the AVF anastomotic site, the hypothesis was that composite-tissue transplantation whose vein grafts were installed as an AVF divided in a delayed manner, might have better patency than those in which vein grafts were installed at the time of reconstruction. This study reviews the results of 16 patients (8 females, 8 males) who underwent 17 microvascular reconstructions using AVFs. Patient courses and outcomes were compared between those undergoing immediate (8 patients) and delayed (7 patients) AVF construction, division, and free-tissue transplantation. There was a low patency rate for AVFs which were divided in a delayed fashion (2 of 7 patients, 29 percent), compared with those which were immediately divided (10 of 10, 100 percent). These results suggest that, in spite of a strong theoretical basis for delayed division of the AVF, delayed harvesting of the AVF is empirically associated with a higher thrombosis rate (p = 0.0048, Fishers exact test).

Despite technical feasibility, composite tissue allotransplantation has not been applied clinically because of immunosuppressive toxicity associated with these highly antigenic allografts. Combination immunosuppression therapy can help overcome this obstacle by allowing lower doses of individual drugs and minimizing toxicity. RS-61443 (mycophenolate mofetil), an effective immunosuppressant that inhibits lymphocyte proliferation, was tested at subtherapeutic doses in combination with cyclosporine (CsA) in a rat hindlimb allotransplantation model with a major antigenic mismatch at the MHC. Five groups were studied: untreated autograft controls (n=4), untreated allograft controls (n=6), allografts receiving low-dose CsA 1.5 mg/kg/day (n=11), allografts receiving low-dose RS-61443 15 mg/kg/day (n=17), and allografts receiving combination low-dose CsA 1.5 mg/kg/day + RS-61443 15 mg/kg/day (n=18). The autograft controls survived indefinitely, while untreated allograft control animals developed severe rejection within 12 days. Subtherapeutic CsA and RS-61443 monotherapy groups developed acute rejection in 64% and 100% of rats, respectively. In contrast, only 11% of rats receiving combination therapy with CsA + RS-61443 at these same subtherapeutic doses developed acute rejection (P < or = 0.0013). Bone marrow toxicity, manifested primarily by anemia and measured objectively by hematocrits, was reduced significantly (P=0.04) in animals receiving low-dose RS-61443 therapy when compared with high-dose controls. These results confirm that subtherapeutic RS-61443 + CsA combination therapy is efficacious in preventing rejection while minimizing toxicity.

Advances in immunosuppression and selective reinnervation may soon make laryngeal transplantation a potential therapy for patients undergoing total laryngectomy. Successful transplantation requires a clear delineation of those vessels necessary to completely revascularize the larynx. Our hypothesis is that the arterial inflow provided by a single superior thyroid artery is sufficient to revascularize the entire larynx. To test this hypothesis, 8 cadavers were studied via either barium latex injection (n = 4) to assess contralateral tissue perfusion or India ink (n = 4), to determine the degree of mucosal perfusion. Following injection via a single superior thyroid artery, all larynges demonstrated either complete, bilateral tissue perfusion evidenced by x-ray visualization of the barium latex injected specimen or bilateral mucosal staining with India ink. We conclude that bilateral perfusion of the entire larynx transplant, including laryngeal and epiglottic mucosa, would occur after revascularization of a single superior thyroid artery. These findings suggest that reliable revascularization of a larynx transplant is technically possible using modern microsurgical techniques.

The purpose of this study was to determine the donor leg morbidity and function after removal of the fibula free flap for mandible reconstruction. In the past 24 months, 29 consecutive patients underwent a total of 30 fibula free flap mandible reconstructions. A muscle-sparing technique was used to harvest the fibula flap, and the proximal 6 cm and distal 8 cm of fibula were left intact. Patients included 20 men and 9 women; their mean age was 58.8 years (range 29 to 82 years); the mean length of fibula removed was 14.5 cm (range 8 to 25 cm); osteocutaneous flaps were used in 27 patients (90 percent); and 16 patients (53 percent) required skin grafts to the donor leg. Donor leg morbidity and function were determined by patient questionnaire, physical examination, and isokinetic testing, with the opposite, unoperated leg serving as a control. Immediate postoperative morbidity occurred in 5 patients (17 percent) (infection, wound separation, or partial graft loss); none required additional surgery for donor complications. Patient questionnaires were completed by all patients at an average of 7.3 months after surgery. Patients were able to ambulate pain-free an average of 5.1 weeks (range 2 to 32 weeks) postoperatively and were all fully able to engage in all daily and recreational activities. Most (21 patients, 72 percent) were free of any donor pain, and the remainder (28 percent) had only occasional mild discomfort. Other complaints included ankle stiffness (41 percent), mild ankle instability (10 percent), and transient peroneal motor (7 percent) or sensory (28 percent) loss, which resolved in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharyngoesophageal reconstruction remains a challenge to the head and neck surgeon. The goals of pharyngoesophageal reconstruction include restoration, with minimal morbidity, of a person's ability to swallow and to speak. Myocutaneous flaps, gastric pull-up, and the jejunal free flap are popular methods of pharyngoesophageal reconstruction; however, none of these modalities is clearly ideal. We have begun utilizing the radial forearm fasciocutaneous free flap for pharyngoesophageal reconstruction. Twelve patients have had reconstruction with this flap with follow-up from 2 to 15 months. Seven defects were circumferential, and five were noncircumferential. Ten patients (83%) have had successful restoration of both swallowing ability and voice. Donor site morbidity was minimal. The leading complication was salivary leak, which was present in eight (67%) patients. Five of the leaks closed with nonsurgical intervention. No cases of flap necrosis occurred. The radial forearm free flap is a thin and pliable flap that closely approximates the tissue consistency of normal pharynx. Successful restoration of a patient's ability to swallow approximates that of enteral flaps and is superior to that of MC flaps. Successful speech restoration is superior to that of enteral and MC flaps. Donor site morbidity is less than that caused by enteral flaps because laparotomy is avoided. Salivary leak is higher than with enteral flaps. Part of this difference is accountable to the high number of secondary and technically challenging reconstructions in this series, and we have taken steps to lower this rate of leakage. These preliminary data show that the radial forearm fasciocutaneous free flap is well suited for pharyngoesophageal reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients undergoing laryngopharyngectomy require the restoration of both deglutition and voice. The tubed radial forearm flap offers the combined advantages of rapid harvest, minimal morbidity, long flap pedicle, extraordinary reliability, and the possibility of customizing the flap to fit virtually any defect. Most importantly, this technique provides superior restoration of speech and deglutition.

Purpose: Large ischemic wounds, particularly with exposed bone or tendons, may not heal even after successful revascularization. We have taken an aggressive approach for limb salvage that uses autogenous vein grafting and simultaneous microvascular free tissue transfer. Methods: In the past year, seven patients (average age 67 years; range 56 to 79) with ischemic disease and distal ulceration underwent revascularization for limb salvage and free tissue transfer. Each had a nonhealing wound (average size 80 cm 2 ), present for 8.6 months (range 2 to 24 months). Simultaneous vein bypass and free tissue transfer was performed in four (57%) of the seven patients. Results: All flaps were initially viable; however, one was lost on day 4 because of hypotension and congestive heart failure. One patient with a successful flap died at 1 month of pneumonia. Minor wound complications were seen in four (57%) of seven patients. Five of the seven patients had the wounds heal completely and are ambulatory at an average follow up of 10 months. Conclusions: Our aggressive approach was successful in preserving limb length and function in 71% of our patients. We perform simultaneous procedures whenever possible to minimize operative and hospitalization times. We believe that this combined approach optimizes the treatment of ischemic limbs with large ulcers. (J VASC SURG 1993;18:648-55.)

Although the fibula osteocutaneous free flap has many advantages when used in mandibular reconstruction, many investigators have found the skin island is not always reliable. We present a technique that enhances skin island reliability by including a maximal number of skin perforators. This method has been used in 10 consecutive osteocutaneous free flaps without any skin loss. This technique also expands the usefulness of the fibula free flap, allowing it to be used for shorter bone defects or in cases when skin coverage is needed at a distance from the bone. In addition, this method provides additional vascularized soft tissue for neck contour restoration and coverage of fixation plates.

An improved technique for gaining access to the inferior gluteal vessels is presented. This method allows rapid isolation of these vessels, preservation of greater pedicle length, and improved access for the performance of microsurgery. The innervation and function of the gluteus maximus is also preserved. We believe the use of this technique makes the inferior gluteal vessels the receptor vessels of choice for microsurgical procedures in the sacral area. An illustrative patient is presented in whom these vessels were used for a combined serratus anterior-latissimus dorsi free muscle flap for sacral wound coverage.

Aeromonas hydrophila infections are a recognized complication of postoperative leech application, and can occur with measurable frequency in populations of patients treated with leeches. We review 11 previously reported leech-related Aeromonas infections and analyze seven unreported cases. These infections range from minor wound complications to extensive tissue loss and sepsis. Often, these infections followed leech application to tissue with questionable arterial perfusion. Onset of clinical infection in these patients ranged from within 24 hours of leech application to 10 days or more after leech application. Late infections may represent bacterial invasion from colonized necrotic tissue. Based on these observations, we recommend that leech applications be restricted to tissue with arterial perfusion to minimize contamination of necrotic tissue. We also recommend that patients treated with leeches receive antibiotics effective against Aeromonas hydrophila before leech application. Patients treated with leeches and discharged with eschars or open wounds might benefit from oral antibiotic therapy until wound closure. These precautions may minimize or eliminate this complication of leech use.

Preliminary reports have indicated that debridement of the bony sequestrum followed by muscle-flap coverage allows successful treatment of chronic osteomyelitis. To determine the long-term effectiveness of this procedure, 34 consecutive patients with chronic osteomyelitis of the distal lower extremity treated with debridement, a 10- to 14-day course of culture-specific antibiotics, and immediate muscle-flap coverage were evaluated. Patients were treated from 1979 through 1984, and long-term (greater than 5 years) follow-up was available for 27 (79 percent). Twenty-three (85 percent) of these patients underwent microvascular muscle transplantation (gracilis or latissimus dorsi), and four underwent local muscle flaps (gastrocnemius or soleus) for immediate wound coverage. Twenty-four patients (89 percent) healed and were without recurrence over long-term (greater than 5 years, mean 7.4 years) follow-up. Of the three with recurrence, two were cured (greater than 5 years follow-up) after additional muscle-flap procedures. Thus the overall success rate was 96 percent, with a minimum 5-year follow-up. Guidelines for muscle-flap selection and treatment techniques in current use are presented. Debridement and immediate muscle-flap coverage provide effective, single-stage treatment of chronic osteomyelitic wounds and allow antibiotics to be restricted to short-term use. Furthermore, muscle flaps covered with skin grafts provide durable coverage while allowing subsequent ancillary procedures (i.e., bone grafts) to be performed under the flaps.

Recent advances in the understanding of the pathophysiology and treatment of osteomyelitis have been discussed. Some of the advances (in either knowledge or technology) that we have found particularly useful include the following: The discovery of additional prognostic factors, which allow more reliable preoperative assessment. The development of the Ilizarov device, which allows bone fixation and later limb lengthening. Confirmation of the effectiveness of single-staged debridement and muscle flap closure. Confirmation that a brief (10 to 14 day) course of antibiotics is as effective as more prolonged therapy. The development of several new free muscle donor sites and a greater appreciation of the need for careful insetting of the muscle. The development of local antibiotic delivery systems, especially continuous antibiotic irrigation catheters. The development of newer oral and intravenous antibiotics that allow outpatient therapy following surgery. The recognition that patients require extended follow-up, and that any recurrences can be successfully treated with a second debridement and muscle flap closure.

Recent published series demonstrate the safety and effectiveness of skin-sparing mastectomy (SSM) with immediate reconstruction for the treatment of early-stage breast carcinoma. Although several reports have retrospectively evaluated outcomes after breast reconstruction for locally advanced disease (stages IIB and III), no study has specifically considered immediate breast reconstruction after SSM for locally advanced disease.From 1996 to 1998, 67 consecutive patients with breast carcinoma underwent SSM with immediate reconstruction and were prospectively observed. From this group of patients, those with locally advanced disease (stage IIB, n = 12; stage III, n = 13) were analyzed separately. Tumor characteristics, adjuvant therapy, type of reconstruction, operative time, complications, hospital stay, and incidence of local recurrence and distant metastasis were noted.Breast reconstruction consisted of a transverse rectus abdominis myocutaneous flap (n = 22) or a latissimus flap plus an implant (n = 4). The median operative time was 5.5 hours; the average hospital stay was 5.2 days. Complications required reoperation in three patients (12%): partial skin flap necrosis in two and partial abdominal skin necrosis in one. Surgery on the opposite breast for symmetry was required in one patient (4%). Postoperative adjuvant therapy was not significantly delayed (median interval, 32 days). With a median length of follow-up of 49.2 months (range, 33-64 months), local recurrence was present in only one patient (4%), with successful local salvage treatment, and distant metastasis was present in four patients (16%).SSM with immediate reconstruction seems safe and effective and has a low morbidity for patients with advanced stages of breast carcinoma. Local recurrence rates and the incidence of distant metastasis are not increased compared with those of patients who have had modified radical mastectomies without reconstruction.

The objective of this study was to evaluate whether an innervated skeletal muscle might augment detrusor function. In four dogs we performed the latissimus dorsi myoplasty, a transfer of the latissimus muscle as an innervated free flap wrapped around the bladder. Stimulation of the latissimus dorsi free flap initially achieved an average bladder pressure of 45.8 +/- 8.41 cm H2O, sufficient for partial evacuation. After 4 months the muscle generated a maximal pressure of 82 cm H2O, resulting in an evacuation of 27.7%. For selected patients, the latissimus dorsi bladder myoplasty may provide an alternative to intermittent catheterization in the future.

OBJECTIVE: To elucidate the causes of cardiovascular hemorrhage associated with mediastinitis and to review recommendations for prevention and treatment. SUMMARY BACKGROUND DATA: Mediastinal debridement with immediate or early coverage using healthy, vascularized tissue has lead to greatly reduced morbidity and mortality for patients with mediastinitis. Myocardial hemorrhage has been anecdotally reported. PATIENTS AND METHODS: Over a 36-month period, 7 patients developed massive cardiovascular bleeding after undergoing debridement for poststernotomy mediastinitis. Causes included puncture or erosion by a sternal edge in three and tearing at the myocardial-sternal interface in four. RESULTS: Five patients survived and remain infection-free at an average of 24 months of follow-up. In these patients, ventricular defects were closed with pledgeted sutures and muscle transposition was used concomitantly to reinforce the repair. This involved a slide of the left pectoralis major muscle and turnover of the right pectoralis in three patients, bilateral sliding in one patient, and bilateral pectoralis and an omental flap in one patient who required additional coverage of the lower mediastinum. CONCLUSIONS: When a patient who has undergone mediastinal debridement shows evidence of significant bleeding, we recommend application of pressure for control of hemorrhage, expeditious return to an operating room with available cardiopulmonary bypass, and immediate muscle coverage with healthy, well-vascularized tissue. Finally, early sternectomy might largely prevent this life-threatening complication.

Objective: To establish a treatment algorithm for the long-term surgical management of pressure sores. Design: Retrospective case series. Setting: University-based teaching hospital. Patients: From March 1979 to July 1995, 280 unselected pressure sore reconstructions (113 ischial, 94 sacral, and 73 trochanteric sores) were performed in 201 patients (130 men and 71 women; age range, 16-90 years; mean, 50 years). Of the patients, 90% had severe spinal cord injuries (paraplegia or quadriplegia). Forty-one percent of the wounds were chronic (present longer than 3 months). Main Outcome Measures: Length of stay, postoperative morbidity and mortality, and flap success (defined as a completely healed wound). Results: Overall, 89% of the flaps healed primarily (ischium, 83% [94/113]; sacrum, 91% [86/94]; trochanter, 93% [68/73]). Three fourths of cases were treated in a single stage (debridement and reconstruction). The inferior gluteus maximus island flap (ischium) (94% [32/34]), the V-Y gluteus maximus advancement flap (sacrum) (97% [36/37]), and the tensor fascia lata flap (trochanter) (95% [42/44]) had the highest success rates. Flap success was not significantly affected by the size of the pressure sore or the number of previous flaps used. Postoperative hospital stays averaged 20 days. The overall complication rate was 28%, most commonly from a slight wound edge dehiscence. Conclusions: Flap selection and the appropriate short-and long-term sequence of flap use significantly improve success rates for pressure sore coverage. Reconstruction can be reliably performed in a single stage with a relatively short hospitalization. Arch Surg. 1997;132:868-873

Objective: To establish a treatment algorithm for reconstructing complex midfacial defects. Design: Retrospective case series. Setting: University-based teaching hospital. Patients: Thirty-one consecutive patients were treated from 1991 through 1995. The 18 males and 13 females were aged 15 to 90 years (mean age, 58 years). The cause of the defect included neoplasm (n=27) and trauma (n=4). Reconstruction consisted of 1 of 4 free flaps: rectus abdominis, radial forearm, fibula, or latissimus dorsi. Aesthetic and functional results were determined by patient questionnaires and physical examinations. Main Outcome Measures: Length of stay, postoperative morbidity and mortality, degree of aesthetic and functional restoration, and detection of tumor recurrence. Results: Twenty-seven (87%) of the 31 patients underwent reconstruction with a single major procedure. All of the flaps survived. Postoperative hospital stays averaged 14 days. Late tumor recurrence occurred in 7 (23%) of the 31 patients and was promptly detected. Aesthetic and functional results were rated good or excellent in 77% (24/31) and 87% (27/31) of patients, respectively. Of the 20 patients who underwent alveolar ridge resection, 16 (80%) received dental rehabilitation, 44% of whom received osseointegrated implants into either a bone flap or remaining native bone. Osseointegrated implants were inset during the initial reconstruction 57% (4/7 patients) of the time. Conclusions: For complex midfacial defects, free-flap transfer can be performed with a high degree of success, restoring both appearance and function in most patients. The only instance in which bone is necessary to reconstruct the midface involves those areas in which osseointegrated implants are needed, ie, alveolar ridge (dental implant) and/or orbit (ocular prosthesis). In such cases, the fibula osteocutaneous free flap is the flap of choice. Otherwise, soft-tissue flaps are selected based on wound size. Arch Surg. 1996;131:960-966

While transplantation of the larynx may eventually be useful in post-laryngectomy reconstruction, three criteria must first be met before human transplants can be attempted: transplant viability must be high, immunosuppression must be safe and effective and functional recovery of the larynx must occur. To study these first two criteria, a total of 11 canine larynx transplants were performed: 3 autografts, 6 orthotopic allografts and 2 heterotopic allografts. The rationale and technical performance of these different transplant procedures are reviewed in detail. Orthotopic transplant recipients received cyclosporin A (CsA) while the heterotopic allograft recipients received RS-61443 and methylprednisolone in addition to CsA. Overall, 9 of 11 of the transplants remained viable. In contrast, all 3 autografted animals developed esophageal-cutaneous fistulas; 2 developed sepsis and were sacrificed on post-operative days (POD) 5 and 28, respectively. The third survived for 91 days and demonstrated a high degree of regeneration in the recurrent and superior laryngeal nerves of the transplant. Orthotopically transplanted dogs also had a high morbidity and perioperative mortality (5 of 6 animals). The single “long-term” survivor was treated with CsA alone, but developed complete transplant rejection on POD 33. The two heterotopic transplant recipients had no perioperative morbidity and the combination of CsA, RS-61443 and methylprednisolone given these latter animals was effective in the longterm prevention of rejection. One of these heterotopic recipients died of sepsis on POD 68 while the other remained alive and well on POD 168. Our present findings show that currently available microsurgical techniques allow experimental canine laryngeal transplantation to be done with significantly high transplant viability rates. In the dog, CsA alone is inadequate for the long-term prevention of transplant rejection while combined therapy with CsA, RS-61443 and methylprednisolone can provide long-term rejection-free larynx transplant survival. The newly developed heterotopic larynx transplant model allows studies of transplant viability, rejection mechanisms and neural regeneration and functional recovery to be performed with minimal animal morbidity and lowered research costs.

Tracheoesophageal voice restoration after laryngectomy is possible with a variety of neopharyngeal reconstructions. We have used the tubed radial forearm free flap for neopharyngeal reconstruction since 1991. Six patients have undergone voice restoration with the Blom-Singer prosthesis and were available for quantitative and qualitative speech analysis. These patients were compared to five laryngectomy patients with standard pharyngeal closures and similar voice restorations. The free flap patients produced similar loudness levels compared to the standards with soft speech (52.06 dB and 47.19 dB, respectively) and loud speech (62.66 dB and 60.91 dB, respectively). The free flap patients demonstrated adequate intelligibility, with fundamental frequencies comparable to standards (124.82 Hz and 135.66 Hz, respectively), although with increased jitter (5.00% versus 1.96%). No differences were statistically significant, but evaluation by trained and naive listeners demonstrated significant differences in voice quality. This quantitative and qualitative analysis of tracheoesophageal speech after radial forearm free flap reconstruction of the neopharynx demonstrates that acceptable voice can be achieved, but with limitations.

For recovery to be deemed adequate, the laryngectomized patient requires restoration of both the ability to swallow and to speak. Immediate results and long-term functional recovery after pharyngoesophageal (PE) reconstruction with the radial forearm free flap were studied in 22 consecutive patients who had undergone primary (n = 3) or secondary (n = 19) reconstructions after total laryngectomy. Circumferential reconstructions were done in 13 patients (mean length 10 cm, range 6 to 16) and patch reconstructions in 9 patients (defect size range 4 × 4 cm to 8 × 7 cm). Flap leakage was evaluated for all patients, and postoperative diet and ability to swallow were evaluated for 16 patients with an intact tongue base. Voice was evaluated for 6 patients with circumferential reconstructions who had later undergone tracheoesophageal puncture with placement of a Blom-Singer voice prosthesis, and the results compared with those of a control group of 5 voice-restored patients who had undergone laryngectomy with primary closure of the pharyngoesophagus. All 22 flaps survived and none of the patients died. Although 7 (32%) reconstructions leaked, all but 1 closed spontaneously. Fourteen (88%) of the patients with an intact tongue base have no dysphagia and are on a regular diet, and 2 remain on an oral liquid diet. Compared with controls, patients with a radial free-flap reconstruction had similar loudness with soft speech (43 dB for controls versus 52 dB for radial patients) and loud speech (61 dB versus 63 dB), comparable fundamental frequencies (136 Hz versus 125 Hz), and increased jitter (2% versus 5%). Speech intelligibility was judged by untrained listeners as excellent for 4 of the patients with radial flaps and good for the other 2. The radial free flap offers the advantages of rapid harvest, high flap reliability, and minimal donor-site and patient morbidity. Leakage rate and deglutition restoration were similar to those of other reconstructions, including the free jejunal flap. Speech rehabilitation in patients secondarily reconstructed with the radial free flap was nearly equivalent to that of total laryngectomy patients who have primary closure of the pharynx and was superior to that reported with other popular PE reconstructions, including the gastric pull-up and the free jejunal flap.

Among arterial anatomic conditions which will adversely affect the harvest of the fibula are 1) significant arteriosclerotic disease within the tibial-peroneal vessels; 2) peroneal arteria magna (PAM), a condition in which only the peroneal artery supplies the foot; and 3) absence of the peroneal artery, either congenitally or as an acquired defect. In each of these anatomic conditions, removal of the peroneal vessels and the fibula free flap will jeopardize either the donor leg, the fibula flap, or both. All patients considered for fibula flaps were evaluated with preoperative leg angiograms. In 28 consecutive patients evaluated with angiography for planned free-fibula flap reconstructions, 23 actually underwent free-fibula harvest. Angiographic abnormalities that altered the operative plan were found in seven (25 percent) patients. Four of the seven patients had vascular examinations prior to surgery with abnormal findings. Three of the seven (11 percent) patients with abnormal arterial anatomy had normal vascular examinations prior to surgery. Thus, if a preoperative angiogram had not routinely been done, the abnormal anatomy would not have been discovered until surgery. This could have resulted in an unusable flap in one patient, and an ischemic or gangrenous foot in two other patients. With this angiographic guidance, there were no vascular complications from harvest of the fibula. The routine use of preoperative bilateral leg angiography is recommended, or an alternative method of vessel imaging, in all patients evaluated for microvascular free-tissue transfer of the fibula.

The treatment of choice for bladder atonia is clean intermittent catheterization. To eliminate the catheter-related morbidity and increase the quality of life for patients with an atonic bladder, the restoration of bladder contractility would be desirable. Based on our hypothesis that skeletal muscle might augment bladder contractility, we designed the present study to examine the ability of the latissimus dorsi muscle in situ to empty a bladder-like reservoir and to regenerate after division and repair of the supplying motor nerve. In 4 dogs, the left latissimus dorsi muscle was dissected, mobilized and wrapped around a bladder substitute (100-ml. silicone reservoir). Stimulation of the thoracodorsal nerve resulted in the evacuation of 63.8 +/- 6.2% of the reservoir's volume and a maximum pressure of 109.5 +/- 18.6 cm. H2O. Four months later, the thoracodorsal nerve supplying motor control to the muscle was transected and microsurgically reanastomosed. Using transcutaneous stimulation, we recorded the pressure generation and resulting evacuation at regular intervals for 8 months (that is, 12 months after the initial surgery). At the end of this period, the pressure was 79.3 +/- 12.1 cm. H2O (72.4% of the initial value), expelling 48.3 +/- 6.7% of total volume. This long-term study demonstrates: (1) the ability of the transposed latissimus dorsi muscle to evacuate a bladder-like reservoir; and (2) the regenerative potential of muscle and nerve after nerve transsection and repair. Use of skeletal muscle, which can be readily stimulated, may serve to facilitate bladder emptying and provide a treatment alternative to intermittent catheterization in the future.

The requirement for effective, minimally toxic immunosuppression remains a major obstacle to performing human composite tissue allotransplantation. The skin component of composite tissue (e.g., limb) allografts is especially antigenic, necessitating toxic immunosuppressant doses to prevent or reverse acute rejection. In previous experiments, RS-61443, an experimental mycophenolic acid ester that inhibits lymphocyte proliferation with minimal toxicity, prevented acute limb allograft rejection in rats for more than 8 months when started on the day of transplantation. In this study, the ability of RS-61443 to reverse established acute rejection was tested in a rat model of hindlimb allotransplantation. Brown-Norway donors and Fischer 344 recipients provided a MHC mismatch for orthotopic midfemur limb transplants that were performed with microsurgical repair of femoral vessels and sciatic nerve. Three groups were studied: untreated allografts (n = 6); allografts receiving RS-61443 at 30 mg/kg/day, started on postoperative day 7 (n = 11); and allografts receiving RS-61443 at 30 mg/kg/day, started on postoperative day 9 (n = 9). Skin and soft tissues were biopsied periodically to assess rejection. Untreated allografts had complete acute rejection within 12-13 days. Animals in both the 7- and 9-day groups developed moderate to severe rejection clinically and histologically before initiation of immunosuppressive therapy. In both groups, RS-61443 was able to reverse rejection completely in all animals from which biopsies were obtained at the time of death at 9-16 weeks after transplantation (P < 0.007). RS-61443 was highly effective as a primary immunosuppressant for reversing established acute rejection in rat hindlimb allografts.

Although technically possible, limb allotransplantation has not been applied clinically. The skin component is especially antigenic, requiring high immunosuppressant doses with an unacceptable toxicity profile. RS-61443, an experimental mycophenolic acid ester that inhibits lymphocyte proliferation without major systemic toxicity, was tested as an immunosuppressant to prevent rejection of rat hindlimb allotransplants. Utilizing Brown-Norway donors and F344 recipients to provide a major mismatch at the MHC, midfemur orthotopic limb transfer was performed with microsurgical repair of femoral vessels and sciatic nerve. Four primary groups were studied: autografts (n = 4); untreated allografts (n = 6); allografts receiving CsA 10 mg/kg for 20 days, then twice per week (n = 6); and allografts receiving RS-61443 30 mg/kg/day (n = 6). Skin and soft tissues were biopsied to assess rejection. Autografts had indefinite limb survival, while untreated allografts had complete acute rejection within 10-12 days. Five of the six CsA rats developed delayed mild-moderate acute rejection within 6 months. In contrast, 5 of the 6 RS-61443 rats had no rejection after at least 32 weeks, while the sixth rat developed only slight rejection on skin biopsy. All animals regained full sensation and partial functional return. RS-61443 is highly effective as a primary immunosuppressant for hindlimb allotransplantation. The disturbing moderate rejection observed in CsA animals, which was absent with RS-61443, may significantly hamper function of transplanted limbs.

• Perineal wounds developing after abdominoperineal resection result in chronic purulent drainage and intermittent episodes of sepsis and are generally unresponsive to conservative medical and surgical treatment. Thirteen consecutive patients (aged 27 to 74 years; mean, 48 years) who underwent debridement and immediate muscle flap closure of these wounds were analyzed to identify risk factors for delayed healing and to evaluate the effectiveness of muscle flap coverage. Three risk factors were identified: preoperative or postoperative radiation therapy, resection for recurrent carcinoma, and inflammatory bowel disease. A total of 19 muscle flaps (11 gracilis, five gluteal thigh, two gluteus maximus, and one rectus abdominis) were used to close these wounds. During an average 3.5-year follow-up, four (31%) minor complications and one (8%) recurrence were noted to occur. Muscle flaps provide safe, effective, single-stage procedures for the closure of chronic perineal wounds. ( Arch Surg. 1990;125:1371-1377)