De novo generation of permanent neovascularized soft tissue appendages by platelet-derived growth factor.

Treatment of wounds with pharmacologic doses of the BB homodimeric form of recombinant PDGF (rPDGF-BB) induces the recruitment, activation, and proliferation of mesenchymal cells, resulting in the deposition of provisional, and subsequently collagen-containing extracellular matrix. In preliminary experiments with an in vitro growth chamber model in the rat consisting of a silicone shell containing a dissected femoral vascular bundle, we found that rPDGF-BB incorporated into a rapidly dissolving collagen type I film induces the generation of a marked, but transient amount of de novo tissue around the femoral vascular bundle. In the present studies, the new tissue generated around the femoral vascular bundle was wrapped with a full thickness syngeneic skin graft to determine if functional support of the graft would lead to sustained maintenance of the underlying generated tissue and create an epithelialized soft tissue appendage. The tissue generated after a single application of rPDGF-BB was skin grafted on the 10th day, exteriorized 20 d later, and observed for an additional month. This led to the formation of soft tissue appendages which demonstrated marked neovascularization, fibroblast migration and proliferation, and increased glycosaminoglycan, fibronectin, and collagen fibril deposition, now leading to preservation of the newly generated tissue. In contrast, minimal new tissue was generated in control-treated vascular bundles or bundles treated with inactive PDGF-BB, and grafting with skin failed to sustain the underlying tissue. Thus, rPDGF-BB coupled with skin grafting induced the formation of functional large soft tissue appendages which are potentially useful clinically to fill tissue defects or to serve as a cell delivery system for transfected genes.

Localization of topically applied TFPI binding sites in an intimectomized microvessel.

Tissue factor pathway inhibitor, TFPI, has been shown to be highly effective as a topically applied antithrombotic in an arterial model of vascular thrombosis. To elucidate the mechanism and site of TFPI action, recombinant TFPI was conjugated to 30 nm diameter gold particles and used to localize the sites of TFPI binding in a traumatized microvessel by transmission electron microscopy. The model, the central artery of the rabbit ear, was transected, denuded of endothelial lining (intimectomized), and re-anastomosed. Prior to the restoration of blood flow, TFPI-gold or unconjugated gold particles in solution were applied by irrigation to the intimectomized vessel lumen. After 10 min of blood flow, the artery was harvested for electron microscopy. TFPI-gold binding was localized to the fine strands of fibrin that lined the lumen of the intimectomized section of the artery. Little or no binding was found on platelets, exposed smooth muscle, cell membrane fragments, or uninjured vessel segments. The TFPI-gold binding could be competed with native TFPI. TFPI-gold was inhibitory, although less potent than native TFPI, in a prothrombin time assay. Unconjugated gold exhibited very little binding in the vascular model. Hence, the TFPI-gold conjugate behaved like native TFPI. Our observations have identified the fibrin complex as an in vivo binding site for TFPI and suggest that this is an in vivo site of action for TFPI as a topical antithrombotic agent.

Closure of complex abdominal wall defects with bilateral rectus femoris flaps with fascial extensions.

Large full-thickness abdominal wall defects present a difficult reconstructive problem. Synthetic mesh has significant drawbacks and should be used only as a temporizing measure. Ideally abdominal wall defects should be resurfaced with well-vascularized autologous fascia and skin. A variety of myofascial, myocutaneous, and myofasciocutaneous flaps have been described. This report describes two cases of near-total abdominal wall reconstruction using bilateral rectus femoris myocutaneous flaps with fasciocutaneous extensions of superficial thigh fascia and skin. In both cases the rectus femoris flaps and fascial extensions healed, and the patients went on to full recovery. In one patient the skin over the fascial extension did not survive and had to be debrided and the underlying vascularized fascia resurfaced with a skin graft. The extended rectus femoris flap is a reliable and versatile flap that leaves negligible functional deficits. The fascial extensions are reliable and well perfused and should be included in the reconstruction of larger abdominal wall defects. The skin overlying the fascial extensions is less reliable, and selective use is recommended.

Tissue generation with growth factors.

BACKGROUND: An in vivo experimental model was introduced to determine whether the mitogenic effect of recombinant platelet-derived growth factor (rPDGF) could be used to generate potentially useful tissue. METHODS: In Lewis rats, the extended femoral arteriovenous bundle was placed within silicone chambers containing collagen disks. The disks could deliver their content of rPDGF-BB (125 to 131 micrograms/disk) either as a rapid pulse or as a slow release. The time course of tissue generation was determined by harvesting the specimens at various postoperative days. The effect of continuous versus pulsed delivery was determined at 30 days. Analysis of the generated tissue was performed by use of histomorphometry. RESULTS: Pulsed delivery of rPDGF-BB induced the formation of a substantial amount of tissue that peaked at 10 to 15 days (145.9 +/- 13.8 vs 35.0 +/- 6.8 mm3, p < 0.0001); however, the generated tissue completely subsided by day 30. Sustained delivery of rPDGF-BB caused continuous growth of the tissue and was more effective than pulsed delivery. CONCLUSIONS: In an experimental model that approximates an in vivo tissue culture system, rPDGF-BB can induce a tenfold increase in tissue within the chamber. However, that tissue is labile and its survival necessitates continuous rPDGF-BB delivery. To become useful for reconstructive purposes, means to stabilize this new tissue growth are needed.

Local irrigation with tissue factor pathway inhibitor inhibits intimal hyperplasia induced by arterial interventions.

OBJECTIVE: To evaluate the capacity of local irrigation with tissue factor pathway inhibitor (TFPI) to inhibit vessels from neointimal lesion formation following intimectomy or balloon angioplasty. DESIGN: The common carotid arteries in New Zealand white rabbits were subjected to either intimectomy or balloon angioplasty. INTERVENTION: Before restoring blood flow, the lumina of the vessels were irrigated with 1 mL of Dulbecco phosphate-buffered saline either with TFPI (100 micrograms/mL [TFPI group, n = 10]) or without TFPI (control group, n = 10). MAIN OUTCOME MEASURES: The area of neointimal formation and the ratio of the intimal to medial areas (I/M) were determined from elastin-stained sections. RESULTS: The area of neointima and the I/M ratio were not significantly different at 2 weeks postoperatively. However, at 4 weeks, TFPI-treated vessels demonstrated a significant reduction in the neointimal lesion and the I/M ratio compared with those of controls, following both angioplasty and intimectomy. Transmission electron microscopy showed a lack of platelet aggregation and thrombus formation at the intimal surface in the TFPI-treated vessels. CONCLUSIONS: Local irrigation with TFPI at the time of arterial interventional therapy inhibits intimal hyperplasia following either balloon angioplasty or intimectomy. We hypothesize that TFPI binds to the injured vessel surface and inhibits the cascade of thrombotic events that promote intimal hyperplasia.

Treatment of avascular ulcers with cytokine-induced tissue generation and skin grafting.

BACKGROUND: Recombinant platelet-derived growth factor (rPDGF-BB) stimulates migration and proliferation of fibroblasts and smooth muscle cells and induces the rapid development of granulation tissue. This study investigated the use of rPDGF-BB and skin grafting to heal avascular ulcers using a rabbit model. We further investigated the effect of a hyaluronic acid carrier and a vascular pedicle on rPDGF-induced tissue generation in this model. METHODS: Large avascular ulcers were created on both ears of New Zealand white rabbits. One ulcer was treated with topical rPDGF-BB, the other with control buffer. After 5 or 7 days, the amount of granulation tissue migration from the wound margin was measured, and the wounds were skin grafted. In another group of ulcers, rPDGF-BB treatment was combined with a hyaluronic acid disk or an intact central axial ear artery and vein. RESULTS: Whereas control wounds generated 1.00 +/- 0.27 mm and 1.75 +/- 0.25 mm of granulated tissue migration from the wound margin by days 5 and 7, respectively, rPDGF-BB treatment increased the amount of granulation tissue migration to 1.88 +/- 0.23 mm and 3.00 +/- 0.86 mm by days 5 and 7 after treatment, respectively (P <0.05 at both time points). Hyaluronic acid disks stimulated 2.50 +/- 0.22 mm of granulation tissue migration by day 7 in controls; when rPDGF-BB was added to the carrier, the migration increased to 4.50 +/- 0.29 mm from the wound margin (P<0.05). Granulation tissue migration was further increased with an intact vascular pedicle: 5.75 +/- 0.48 mm in controls versus 7.75 +/- 0.25 mm with rPDGF-BB treatment (P<0.01). Skin grafts applied to the treated ulcers failed to survive in all groups except those with intact vascular pedicles. CONCLUSIONS. This study demonstrates that rPDGF-BB can increase the amount of granulation tissue generated over an avascular wound. This tissue generation is enhanced by both a hyaluronic acid carrier and a vascular pedicle. A vascular pedicle was required for skin graft survival. This study supports the role of hyaluronic acid in rPDGF-BB induced tissue generation and the requirement of a direct blood supply for functional cytokine-induced tissue generation.

Morbid obesity. Second gastric operations for poor weight loss.

This is a report of a clinical investigation of weight gain occurring after initial good weight loss following an operation performed to treat morbid obesity. The reasons for weight gain or poor weight loss after the first operation, the indications for a second operation, and the effectiveness and complications of four different "second" operations were examined. Thirty-five patients who were weight loss failures, a subgroup of 556 patients upon whom one of five bariatric operations had been performed, provided the clinical material for this investigation. The findings indicate that technical and nontechnical patient factors are responsible for the failure of the initial bariatric operation. The most effective second operation to treat weight loss failures was gastric bypass with Roux-en-Y gastrojejunostomy (GBRY). More difficult to perform than when done as the first bariatric operation, GBRY when done as a second operation is associated with a higher complication rate.

Free flap surgery. The second decade.

After 2 decades of increasing expertise, microvascular free tissue transfer has gradually evolved from being a procedure of last resort to become a first choice reconstructive procedure. Improved success rates, reduced operative time, and patient morbidity have widened the indications for the procedure. This has profoundly affected our reconstructive principles and, in many instances, reversed some well-established dogmas of wound care, cancer resectability, and salvage of multilated parts. As the constraints of tissue survival decrease, more attention can be given to the artistry and functional restoration.

Avoiding free flap failure.

To obtain up-to-date statistics on free flap success rates, a survey of 644 consecutive free flaps performed by nine expert microsurgeons was conducted in 1991. Analysis of the failures shed light on the current problem areas. Because operative experience is the most important factor related to improved success rates, a questionnaire aimed at probing the experts for the lessons learned as their success rates improved was sent to 12 expert microsurgeons. From this source of data, and from the author's experience, a breakdown of the causes of free flap failure is given.

Digital reconstruction with island flaps.

Better understanding of the vascular anatomy of the hand and of flap perfusion allows the hand surgeon to perform single-stage reconstruction of digital defects through a multitude of island flap transfers. The usefulness of more than 20 separate island flaps is discussed, and the technique of flap transfer is presented for each.

Free flap coverage of the hand.

Microvascular free tissue transfer has been a major advancement in the treatment of soft-tissue defects of the hand. Free tissue transfers have expanded our options and have altered our approach to hand defects. It is no longer satisfactory to cover hand wounds with unsightly, bulky flaps of tissue. Microsurgical free tissue transfers have given us the tools for more refinement in hand soft-tissue reconstruction and have changed the standards for a successful outcome.

Principles of flap prefabrication.

Clinical flap prefabrication can be classified according to the basic technique of plastic surgery used for the prefabrication. There are currently three methods: (1) delay or expansion; (2) grafting; and (3) vascular induction by staged transfer. Illustrative cases are given to point out the advantages and indications for each method. A fourth, still experimental, method is based on cell biology advances that are looming on the horizon and may have revolutionary future clinical applications.

Refinements in hand coverage with microvascular free flaps.

The specialized tissue requirements or dorsal and palmar skin are analyzed and options for full-thickness replacement outlined in detail. Thoughtful and accurate preoperative planning is the key to success. Dorsal coverage with a variety of pedicled and free fasciocutaneous flaps are quite satisfactory. Palmar coverage is more difficult and the need for sensation more critical. Free vascularized temporoparietal fascial flaps covered with full-thickness skin grafts are currently the treatment of choice for most complex wounds.

Reconstruction of the hand with forearm island flaps.

From all of the flaps reviewed, it is important to know how to select the most suitable choice in each case. Aside from the technical expertise of the surgeon, the indication depends on the size and the location of the substance loss. For large defects in any location, the radial forearm flap remains the most reliable and safest choice. For children and women, the authors prefer distant pedicled transfers or free flaps to minimize cosmetic donor site morbidity. For small or medium defects that cannot be managed by a local transposition flap, the indication is based on the location of the wound. Palmar defects, if proximal and ulnar, may be covered using the dorsal ulnar flap, with little morbidity in the donor area. The anterior interosseous flap seems a better choice whenever vascularized tendon, nerve, or bone are needed also. For the first web space and neighboring radial defects, the posterior interosseous flap provides a reasonable alternative. Dorsal defects of the hand can be reconstructed with a posterior interosseous flap, provided there is no suspicion of injury to the anastomotic dorsal system of the wrist. The anterior interosseous flap is a good choice for composite osteocutaneous transfers. For complex composite defects, the ulnar artery forearm flap distally based may be indicated for reconstructive problems requiring vascularized flexor tendons. The anterior interosseous flap is able to provide excellent quality vascularized bone. Indications depend above all on the surgeon's experience and on the different schools. As always, the better flap is that which is performed by the surgeon who has mastered the particular surgical technique. In conclusion, this article is devoted to an update on forearm flaps and illustrates the innovative strength of this specialty. It also points out that, through in depth knowledge of the anatomy, flaps may be raised from many anatomic regions of a limb without disturbing the main vascular axis of that extremity. Minimizing the donor site morbidity while maximizing the quality of the reconstruction is the primary concern when indications are established for reconstructive hand surgery, which is where one of the authors' main research efforts resides.

Advances in total phalloplasty and urethroplasty with microvascular free flaps.

This article focuses on the lateral arm free flap as the option that comes closest to meeting the diverse aesthetic and functional goals of phalloplasty. The authors introduce a new technique for incorporating a prefabricated neourethra within the lateral arm to permit the coexistence of an erectile prosthesis alongside a fully vascularized urethra that extends to the distal tip. The unrecognized value of the radial forearm free flap for urethroplasty is also discussed and a case of reconstruction following urethral loss is presented. Also described is how the prefabricated urethra technique may be useful for repairing severe hypospadias defects.

Monitoring of free flaps with surface-temperature recordings: is it reliable?

Surface-temperature recording (STR) is one of the oldest and simplest methods of postoperative monitoring of free flaps. Its usefulness, however, remains poorly documented, and its problems, not well understood. To assess its value, we reviewed our series of 600 consecutive free flaps where surface-temperature recording was the main method of monitoring used and a detailed temperature record was kept. Seventy flaps suffered a postoperative microvascular compromise necessitating a surgical reexploration. Of these, 62 charts were satisfactory for review and were matched with 62 charts from similar but uncomplicated flaps. The derived value C delta T, which represents the change in temperature difference (delta T) between flap and control sites over a specified time period, was calculated at each time point. Of 10,000 derivations, only once did C delta T greater than 1.8 degrees C fail to identify a microvascular thrombosis, and 17 times a false alarm was given. Therefore, when properly applied and interpreted, the sensitivity of surface-temperature recording is 98 percent, and its predictive value is 75 percent, making it a simple, inexpensive, and highly reliable technique of free-flap monitoring. The thermodynamics behind surface-temperature recording is reviewed, pointing out the pitfalls that have to be avoided in order to improve the reliability of this technique.

The lateral arm/proximal forearm flap.

The classic lateral arm flap is constrained by limited skin availability, thick subcutaneous tissue, a short vascular pedicle, and inconsistent sensory innervation. We report modifications of the lateral arm flap which increase its skin availability, provide thin sensate skin, and extend the overall reach of the flap. The vascular anatomy of the lateral arm/proximal forearm flap was studied in 10 fresh anatomic specimens. The posterior radial collateral artery communicated with a rich vascular plexus that extended well into the proximal forearm. This plexus is also fed by communicating branches from the radial recurrent artery. Fifteen lateral arm/proximal forearm flaps have been utilized for various upper and lower extremity reconstructions and three penile constructions. All flaps survived, and there was primary healing of all wounds. Three are presented which demonstrate the versatility of the lateral arm/proximal forearm flap.

Free flaps as flow-through vascular conduits for simultaneous coverage and revascularization of the hand or digit.

In complex extremity injuries, which include volar skin loss and ischemic digits, simultaneous coverage and revascularization are required. In this series of 12 patients, free-tissue transfers were utilized to provide both soft tissue coverage and a flow-through arterial conduit for revascularization. Eleven cases involved the hand or digits, and one case involved the great toe. Six cases were performed for acute ischemia associated with traumatic soft-tissue loss. The remaining six flaps were utilized to lengthen contracted vascular pedicles and provide vascularized soft-tissue coverage during reconstruction of severe hand and foot contractures. Nine temporoparietal fascia free flaps were used for hand or digit revascularization. Two fillet flaps were created, one from a nonreplantable foot and another from an isolated index amputation. The distal end of the axial artery of the flap was anastomosed to a digital artery to restore circulation. Fascial flaps were covered with full-thickness skin grafts. Primary wound healing was achieved in all patients. There were no flap losses or other complications. All the distal parts were revascularized adequately by the axial arteries of the flaps, and functional recovery was good. In this technique, the flap satisfied the need for both coverage and revascularization. Vein grafts were not needed. This series further describes the utility of flow-through flaps in the revascularization of digits.

Prefabrication of composite free flaps through staged microvascular transfer: an experimental and clinical study.

The feasibility of prefabricating free flaps by inducing, through the process of staged reconstruction, an arteriovenous bundle and its surrounding fascia to perfuse a selected block of tissue was investigated experimentally and clinically. Sixteen rat knee joints were wrapped with their ipsilateral superficial inferior epigastric (SIE) fascia. In 8 joints, the composite flaps were resected en bloc and were immediately replaced orthotopically pedicled upon the superficial inferior epigastric vessels. In the remaining joints, the resection and orthotopic transfer were performed 2 weeks later. Only the joints in the latter group, which benefited from the staging period, were found to be perfused. The long finger proximal interphalangeal joint of a child was reconstructed by the staged microvascular transfer of his second toe proximal interphalangeal joint. At the first stage, a temporalis fascia flap was wrapped around the toe proximal interphalangeal joint and revascularized to the dorsalis pedis vessels. Six weeks later, the joint and its temporalis fascia envelope were dissected, and the "prefabricated" joint flap was transferred to the hand and revascularized to the wrist vessels. Bony union progressed uneventfully with excellent recovery of the range of motion. We conclude that regardless of the indigenous vascular anatomy, an unlimited array of composite free flaps can be constructed and transferred based on induced large vascular pedicles.

Nonsurgical breast enlargement using an external soft-tissue expansion system.

Less than 1 percent of the women interested in having larger breasts elect to have surgical augmentation mammaplasty with insertion of breast implants. The purpose of this report is to describe and test the efficacy of a nonsurgical method for breast enlargement that is based on the ability of tissues to grow when subjected to controlled distractive mechanical forces. Seventeen healthy women (aged 18 to 40 years) who were motivated to achieve breast enlargement were enrolled in a single-group study. The participants were asked to wear a brassiere-like system that applies a 20-mmHg vacuum distraction force to each breast for 10 to 12 hours/day over a 10-week period. Breast size was measured by three separate methods at regular intervals during and after treatment. Breast tissue water density and architecture were visualized before and after treatment by magnetic resonance imaging scans obtained in the same phase of the menstrual cycle. Twelve subjects completed the study; five withdrawals occurred due to protocol noncompliance. Breast size increased in all women over the 10-week treatment course and peaked at week 10 (final treatment); the average increase per woman was 98 +/- 67 percent over starting size. Partial recoil was seen in the first week after terminating treatment, with no significant further size reduction after up to 30 weeks of follow-up. The stable long-term increase in breast size was 55 percent (range, 15 to 115 percent). Magnetic resonance images showed no edema and confirmed the proportionate enlargement of both adipose and fibroglandular tissue components. A statistically significant decrease in body weight occurred during the course of the study, and scores on the self-esteem questionnaire improved significantly. All participants were very pleased with the outcome and reported that the device was comfortable to wear. No adverse events were recorded during the use of the device or after treatment. We conclude that true breast enlargement can be achieved with the daily use of an appropriately designed external expansion system. This nonsurgical and noninvasive alternative for breast enlargement is effective and well tolerated.