Galip Agaoglu

A cadaver study in preparation for facial allograft transplantation in humans Part II. Mock facial transplantation

Background: The authors have performed mock facial transplantation by harvesting total facial-scalp flaps from donors and transferring them to recipient cadavers. Methods: A total of 10 fresh human cadavers were dissected. In the donor, the authors have measured the time of facial-scalp flap harvesting, and the length of the arterial and venous pedicles and sensory nerves that were included in the facial flaps. In the recipient, the authors have evaluated the time of facial skin harvest as a monobloc full-thickness graft, the anchoring regions for the inset of the donor facial flaps, and the time sequences for the vascular pedicle anastomoses and nerve coaptations. Results: In the donor cadaver, the mean harvesting time of the total facial-scalp flap harvest was 235.62 ± 21.94 minutes. The mean length of the supraorbital, infraorbital, mental, and great auricular nerves was 1.5 ± 0.15, 2.46 ± 0.25, 3.02 ± 0.31, and 6.11 ± 0.42 cm, respectively. The mean length of the external carotid artery, the facial vein, and external jugular vein was 5 ± 0.32, 3.15 ± 0.32, and 5.78 ± 0.5 cm, respectively. In the recipient cadaver, the mean harvesting time of facial skin as a monobloc full-thickness graft was 47.5 ± 3.53 minutes. The mean time for the preparation of the arterial and venous pedicles and sensory nerves for the future anastomoses and coaptation was 30 ± 0 minutes. The mean time for facial flap anchoring was 22.5 ± 3.53 minutes. The total mean time of facial mock transplantation without vessels and nerve repair was 320 ± 7.07 minutes (5 hours 20 minutes). Conclusion: Based on anatomical dissections in this cadaver study, the authors have estimated the time and sequence of facial flap harvest and inset to mimic the clinical scenario of the facial transplantation procedure.

New surgical approach in facial transplantation extends survival of allograft recipients

We have previously developed a composite total face–scalp allotransplantation model based on bilateral common carotid arteries (CCA) and external jugular veins. To decrease the mortality rates, different modifications of arterial anastomoses in the facial allograft recipients are presented. Eighteen full face–scalp allograft transplantations were performed across major histocompatibility (MHC) barriers between ACI (RT1a) donors and Lewis (RT11) recipients. Bilateral CCA and bilateral external carotid arteries of the recipients were used as recipient vessels to vascularize the flap in 5 and 4 transplants, respectively. In 9 transplants, unilateral CCA of the recipients were used to vascularize the face/scalp flap. All the animals received CsA 16 mg/kg/d Sc, which was tapered over 4 weeks to 2 mg/kg/d. In transplants utilizing bilateral CCA, the survival rate of the animals was very short. Transplants in which unilateral CCA were used yielded 100% survivals over 200 days posttransplant. These modifications of arterial anastomoses have significantly improved survival of facial allograft recipients.

Hematopoietic Stem Cell Engraftment and Seeding Permits Multi‐Lymphoid Chimerism in Vascularized Bone Marrow Transplants

Vascularized bone marrow transplantation (VBMT) across a MHC barrier under a 7‐day αβ‐TCR mAb and CsA protocol facilitated multiple hematolymphoid chimerism via trafficking of the immature (CD90) bone marrow cells (BMC) between donor and recipient compartments. Early engraftment of donor BMC [BN(RT1n)] into the recipient BM compartment [LEW(RT1l)] was achieved at 1 week posttransplant and this was associated with active hematopoiesis within allografted bone and correlated with high chimerism in the hematolymphoid organs. Two‐way trafficking between donor and recipient BM compartments was confirmed by the presence of recipient MHC class I cells (RT1l) within the allografted bone up to 3 weeks posttransplant. At 10 weeks posttransplant, decline of BMC viability in allografted bone corresponded with bone fibrosis and lack of hematopoiesis. In contrast, active hematopoiesis was present in the recipient bone as evidenced by the presence of donor‐specific immature (CD90/RT1n) cells, which correlated with chimerism maintenance. Clonogenic activity of donor‐origin cells (RT1n) engrafted into the host BM compartment was confirmed by colony‐forming units (CFU) assay. These results confirm that hematolymphoid chimerism is developed early post‐VBMT by T‐cell lineage and despite allografted bone fibrosis chimerism maintenance is supported by B‐cell linage and active hematopoiesis of donor‐origin cells in the host BM compartment.

Clinical outcome of peripheral nerve decompression in diabetic and nondiabetic peripheral neuropathy.

Surgical decompression of peripheral nerves in patients with diabetes was reported to restore sensation and improve function. In this study, a retrospective review of 12 diabetic and 20 nondiabetic patients with lower-extremity peripheral neuropathy who underwent surgical decompression was performed. Clinical evaluation by Tinel test, muscle power examination, and 2-point discrimination were performed preoperatively, at 6 months, and between 9 and 15 months postdecompression. Clinical outcomes were classified into excellent, good, or fair based on improvement in symptoms and return of function. Thirty-two patients underwent 36 surgeries, in which 99 lower-extremity nerves were decompressed. There was a statistically significant improvement in muscle function (P < 0.001) and 2-point discrimination for the small toe (P = 0.008) and big toe (P = 0.038). At a mean of 7.7 months, 90% of patients showed significant improvement in pain and function. It is concluded that surgical decompression was associated with significant improvement in clinical outcome in patients with diabetic and idiopathic neuropathy with evidence of superimposed compression.

Applications of bilateral vascularized femoral bone marrow transplantation for chimerism induction across the major histocompatibility (MHC) barrier Part II

Bilateral vascularized bone marrow transplant (VBMT) model was designed to induce chimerism across the major histocompatibility (MHC) barrier under combined αβ T-cell receptor monoclonal antibody and cyclosporine A (αβ-TCRmAb/CsA) protocol. Seventeen transplants were performed between BN(RT1n) donors and Lewis(RTIl) recipients. Group I, isograft controls; Group II, allografts rejection controls; Group III, allografts under 7-day protocol of αβ-TCRmAb/CsA. Donor bilateral femoral bones were bilaterally anastomosed to the abdominal aorta and inferior vena cava of recipient. At day 7 posttransplantation, all bone flaps were viable. Groups I and III survived without signs of rejection. In Group III, peak level of chimerism in peripheral blood was evaluated at day 21 (24.2%), at day 63 declined to 1.5%, and was maintained at this level thereafter. Donor-derived cells were present in the bone marrow of recipients at 28.2% at day 21 posttransplant. Histology confirmed viability of bone marrow cells in isograft during the entire follow-up and up to 35 days in treatment Group III. Bilateral VBMT induced donor-specific chimerism across the MHC barrier under the immunomodulatory protocol of αβ-TCRmAb/CsA.

Bilateral vascularized femoral bone transplant: a new model of vascularized bone marrow transplantation in rats, part I.

We present a new model of vascularized bone marrow transplantation-bilateral vascularized femoral bone (BVFB) isograft transplant based on abdominal aorta and inferior vena cava. A total of 7 BVFB isograft transplants were performed between Lewis (RT1l) rats. In the donor, both femoral bones were harvested based on the abdominal aorta and inferior vena cava. In the recipient, the harvested isograft transplants were transferred into the inguinal region (in 3 animals) and into the abdominal cavity (in 4 animals). The mean operation time was 3 hours and 35 minutes. The mean warm ischemic time was 35 minutes. The vascular pedicles of the transplants that were transferred into the inguinal region were thrombosed at day 7 posttransplantation. The vascular pedicles of transplants into the abdominal cavity were patent and the bones were viable during the follow-up period of 63 days posttransplant. We have confirmed the feasibility of BVFB transplantation based on abdominal aorta and inferior vena cava.

Calf augmentation with autologous tissue injection.

Background: Lean or asymmetric calves may cause body image problems. These deformities can be corrected by inserting a silicone calf prosthesis or silicone injection, and also through the use of an autologous fat or tissue cocktail. Methods: Thin and asymmetric parts of the leg are marked while the patient is standing. Depressed areas are observed at the anteromedial part of the tibia from the knee to the ankle. Fat tissue harvested under general anesthesia, using a syringe and a 4-mm cannula, is centrifuged to eliminate blood and lipids, antibiotic is added, and small amounts of fat grafts are injected into different layers using a cannula 15 or 26 cm in length and 3 mm in diameter. For the preparation of the tissue cocktail, tissue (dermis, fascia, fat) was cut into very small pieces measuring 0.5 mm to be passed through 16-gauge needles. The amount injected depends on the severity of deformity and the size of the legs. Rather than overcorrecting, injections are repeated if necessary, two to four times at 3-month intervals. Results: Between 1992 and 2003, 77 patients underwent calf augmentations with autologous fat and tissue cocktail injections, with follow-up from 1 to 8 years. Outcome was satisfactory in most patients, with moderate improvement in 10 patients (13 percent) and good improvement in 67 (87 percent). In 12 patients, small irregularities or asymmetries were seen after the first injection and were corrected with a second injection. No infection was reported in any case. Conclusion: Autologous augmentation and shaping offers scar-free, long-lasting results, with no late complications, and with the possibility of touchup.

Diabetic neuropathy: pathogenesis and treatment.

Neuropathy is a common and devastating complication of diabetes that contributes to mortality in most cases. Multiple factors are thought to play a major role in the pathogenesis of diabetic neuropathy, including alterations in the endoneural metabolism, defective neurotrophic factors, reduced nerve blood supply, and immune mechanisms. Studies of endoneural metabolism and nerve blood-flow alterations have focused on oxidative stress, the polyol pathway, advanced glycation, protein kinase C, and impaired essential fatty acid metabolism. Although many experimental and clinical studies have been performed to determine the most optimal strategy for preventing and treating diabetic neuropathy, tight glycemic control is the mainstay of therapy. In this article, the proposed pathophysiologic mechanisms and therapeutic approaches in diabetic neuropathy are reviewed and discussed with the relevant literature.

Crossover replantation and fillet flap coverage of the stump after ectopic implantation: a case of bilateral leg amputation.

A successful case of crossover replantation of the left foot to the stump of the right leg and temporary ectopic implantation of the right amputated foot on the forearm is described. The ectopically implanted right foot was used as a free fillet flap for the late reconstruction of the left leg stump. At the latest follow-up examination, 18 months after the accident, the patient was able to walk independently with a prosthesis on the stump of the left leg. Both the cross-replanted foot and the free filleted foot flap, used for the reconstruction of the left leg stump, have maintained adequate protective sensation. The importance of utilization of amputated parts for functional reconstruction is stressed. Crossover replantations and ectopic implantations should be considered in bilateral amputations for the salvage of at least one extremity.

The Abbé island flap for the reconstruction of severe secondary cleft lip deformities.

Primary repair of the cleft lip is often associated with secondary deformities, which require revision and secondary reconstruction. Patients with one or all of the following, a tight lip restricting use of orthodontic appliances, absence of a Cupids bow, or absence of vermilion tubercle, were treated with the Abbé island flap. A triangular muco-musculo-cutaneous island flap was designed in the central segment of the lower lip. A full-thickness incision of skin, muscle, and mucosa was made in the midline of the upper lip, dividing the lip into two segments, and the island Abbé flap was inserted. One week after surgery, the pedicle of the island flap was divided and the inset of the flap completed. Sixty patients with severe secondary cleft lip deformities (36 males and 24 females) were treated. Good aesthetic and functional results were achieved during 1 to 17 years of follow-up. Insertion of the Abbé flap resulted in release of the tight upper lip and a new, inconspicuous scar. Use of orthodontic appliances was facilitated, and tightness of the tissue, which restricted the expansion of the alveolar process, was eliminated. Adequate tissue was transferred to the upper lip, which improved the bulk of the lip and vermilion tubercle. The retrusion of the midface and the projection of the upper lip were also improved, and the upper and lower lips became better balanced. Donor site morbidities were insignificant. Use of the Abbé flap in selected patients resulted in successful reconstruction of secondary cleft lip deformities.