Early recognition of chronic rejection in a face allotransplant patient with alopecia.

The features of chronic rejection (CR) in full-face vascularized composite allotransplantation (VCA) are not well-known. Herein, we report a full-face transplant patient that experienced two episodes of acute rejection (AR) and three episodes of AR/CR over the course of 6-years. The patient noticed a small, round patch of hair loss in his beard 9 months after the second AR episode, which occurred 21 months post-transplantation. Biopsy of the alopecic patch showed lichen-planopilaris-like features, which were suggestive of early CR. Despite an increase in immunosuppressive dosages, the alopecia progressed. Following the second and third AR/CR episodes, the alopecia became more pronounced, with the addition of hyperpigmentation as well as sclerosis and telangiectasia. The findings of multiple biopsies showed CR. Based on these findings we think that alopecia with lichen-planopilaris-like histopathological features similar to grade III AR features, particularly in hair follicles appears to be an early finding of CR in the presented patient. The findings further indicate that follicular involvement may be a significant feature of CR in VCA patients and that it can present prior to sclerosis, vasculopathy, or loss of adnexa. The present case is uniquely important because of the distinctive presentation of CR, with hair follicles clinically and histopathologically affected, leading to progressive and irreversible alopecia with lichen-planopilaris-like histopathology.

A New Experimental Lymphedema Model: Reevaluating the Efficacy of Rat Models and Their Clinical Translation for Chronic Lymphedema Studies.

BACKGROUND: Our aim was to create a new rodent hind limb lymphedema model lacking the fibrosis effect induced by radiotherapy and subjected to the inhibition of lymphangiogenesis via sirolimus (rapamycin) to maintain a chronic lymphedema model and investigate its reliability for human treatment modalities. METHODS: Forty-two Sprague-Dawley rats were randomly assigned to 7 groups: (1) surgery control, (2) vehicle-surgery control, (3) vehicle control, (4) rapamycin control, (5) surgery with 1 mg/kg per day rapamycin, (6) surgery with 1.5 mg/kg per day rapamycin, and (7) surgery with 2 mg/kg per day rapamycin. All surgeries were performed on the right hind limbs, with the left hind limbs also considered as a control. The drug and its solvent were administered daily into the relevant groups intraperiteonally. The presence of lymphedema was investigated by weekly limb circumference measurements, microcomputed tomography, fluorescence lymphography using indocyanine green dye, and microscopic evaluation at the end of the sixth week to determine any histological changes in the hind limbs. RESULTS: In group 1, lymphedema was observed for 2 weeks (P = 0.032), whereas in groups 5, 6, and 7, lymphedema lasted for 3 weeks (P < 0.05.) Fluorescence using indocyanine green revealed that the edema was totally resolved after 6 weeks of surgery by a well-developed superficial lymphatic organization instead of the normal distinct vessel structure. Histologically, groups 1, 5, 5, and 7 demonstrated a significant increase in both the number of macrophages (P < 0.001) and newly formed lymphatic vessels in the right side surgically treated hind limb (P < 0.05). CONCLUSIONS: Despite the extreme surgical destruction and lymphangiogenesis inhibition in the rat model, the sustained lymphedema did not last >3 weeks. Because of the rapid neolymphangiogenesis in murines and a different wound healing mechanism, they should not be considered as an appropriate model for research on human lymphedema in first place.

The reversed paradigm of chimerism induction: Donor conditioning with recipient-derived bone marrow cells as a novel approach for tolerance induction in vascularized composite allotransplantation.

PURPOSE: To test a new approach of donor conditioning with recipient bone marrow cells (BMC) to induce tolerance in vascularized composite allograft (VCA) transplantation. METHODS: Lewis rats' (recipients) BMC were stained with PKH-26. The ACI rats (donors) were conditioned with 80 × 106 Lewis BMC, 24 or 72 hours before VCA (groin flap) transplantation. Forty-eight VCA were performed between ACI donors and Lewis recipients. In groups I and II, donors were preconditioned (24 and 72 hours before transplantation, respectively), and recipients received 7-day anti-αß-TCR/cyclosporine-A post-transplantation. In groups III and IV, donors were preconditioned (24 and 72 hours before transplantation, respectively), and recipients received no systemic immunosuppression. In group V, recipients received 7-day anti-αß-TCR/cyclosporine-A post-transplantation. In group VI, recipients received no systemic immunosuppression. Assessment included evaluation of transplant viability and induction of donor-specific chimerism via flow cytometry, immunofluorescence, and PCR. RESULTS: Groups III, IV, and VI rejected allografts, at an average of 14 ± 5.2, 10 ± 2.7, and 8 ± 0.7 days. In groups I, II, and V, the mean survival was 80 ± 18.2 (p = 0.0002), 64 ± 27.4 (p = 0.001), and 30 ± 4.7 (p = 0.02) days. In groups I and II, donor-specific chimerism in the blood decreased from 8.8 ± 3.4% and 8.6 ± 3.4% on day 7 to 3.7 ± 1.32% (p = 0.02) and 4.7 ± 2.7% when the flaps manifested grade 3 rejection. The presence of PKH-26+ Lewis BMC was confirmed in the donor's blood, bone marrow, lymphoid organs, and liver (preconditioned at 24 and 72 hours). CONCLUSIONS: Donor preconditioning is a novel approach modifying recipient's responsiveness to donor allograft and prolonging the allograft survival under short-term immunosuppression. © 2015 Wiley Periodicals, Inc. Microsurgery 36:676-683, 2016.

Total Scalp Replantation: Surgical Tricks and Pitfalls.

BACKGROUND: Two patients were successfully operated on for total scalp avulsions. METHODS: Ages were between 11 and 35 years, and both patients were female. Bilateral temporal artery and veins were used as the recipient pedicles. Interpositional vein graft harvested from the left forearm was used in 1 patient. No nerve repair was performed. RESULTS: The scalp was successfully replanted in both cases. Venous congestion and arterial insufficiency were observed in 1 patient. Successful revision of the vascular anastomosis was performed. Total necrosis of the upper helical rim was observed in 1 patient. A mean size of 3 × 3 cm of tissue necrosis was observed in the occipital region of all patients. One patient was treated with split-thickness skin grafting, whereas the other one was left for secondary healing. CONCLUSIONS: The "replace like tissue with like tissue" represents the philosophy in replantation surgery. Although reconstructive surgeries imply advanced surgical methods, scalp replantation remains the only ideal surgical modality to create an embellishing natural-looking hair-bearing scalp. In this article, we present some tricks and pitfalls of total avulsed scalp replantation as well as our skills and literature review.

Lessons learned from the first quadruple extremity transplantation in the world.

BACKGROUND: Limb transplantation is emerging as a promising area of surgery and is an indispensable alternative for prosthetic rehabilitation of amputees, the severity of which is increasing because of combat-related injuries. Successful unilateral and bilateral limb transplantations have already been performed before this operation. METHODS: We performed the first ever quadruple limb transplantation in February 2012. The limbs procured from a 40-year-old man heart-beating donor were transplanted to a 27-year-old male patient who was a quadruple amputee for the last 14 years because of an electrical injury. RESULTS: To shorten the ischemic period to a minimum, 3 separate microsurgery teams worked simultaneously. All extremities were reperfused within 8 hours of procurement, and the operation lasted for 12 hours. Metabolic load was managed by hemodialysis. One hour after the completion of the operation, cardiac arrest developed, resuscitation of which necessitated median sternotomy and temporary partial cardiopulmonary support. Despite the removal of the transplanted limbs and all efforts including continuous hemodialysis, plasmapheresis, and extracorporeal membrane oxygenation, the patient died on the fourth day after transplantation in a clinical condition of severe systemic inflammation. CONCLUSIONS: The problems we faced were difficulty of vascular access for invasive monitoring and fluid replacement, and the severe systemic inflammation effects of which could not be dealt with, despite aggressive supportive treatment. We hope that our experience will enlighten the surgeons who are willing to extend the limits of limb transplantation and serve the success of future operations.

Composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation model of bone marrow transplantation.

Cellular and vascularized bone marrow cells have been used to induce donor-specific chimerism in various models of composite tissue allotransplantation. Although thymus transplantation has been reported in the literature, the effect of thymus transplantation on chimerism levels in vascularized bone containing composite tissue allotransplantation has not been reported. In this study, a new method for composite vascularized sternal bone marrow transplant model is descried that can be applied to augment chimerism after transplantation. A total of seven composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin transplantations were performed in two groups. The first group (n = 5) was designed as an allotransplantation group and the second group (n = 2) was designed as an isotransplantation group. Composite osseomusculocutaneous sternum, ribs, thymus, and pectoralis muscles allografts were harvested on the common carotid artery and external jugular vein and a heterotopic transplantation was performed to the inguinal region of the recipient rat. Cyclosporine A monotherapy was administered in order to prevent acute and chronic allograft rejection. Animals sacrificed when any sign of rejection occurred. The longest survival was 156 day post-transplant. Assessment of bone marrow cells within sternum bone component and flow cytometry analysis of donor-specific chimerism in the peripheral blood of recipients were evaluated. Our results showed that this composite allograft carried 7.5 × 10(6) of viable hematopoietic cells within the sternum component. At day 7 post-transplant chimerism was developed in T-cell population and mean level was assessed at 2.65% for RT1(n) /CD4 and at 1.0% for RT1(n) /CD8. In this study, a new osseomusculocutaneous sternum, ribs, thymus, pectoralis muscle, and skin allotransplantation model is reported which can be used to augment hematopoietic activity for chimerism induction after transplantation.

Misdiagnosed widespread eosinophilic granuloma of the mandible.

Eosinophilic granuloma is the most common expression of Langerhans cell histiocytosis and corresponds with typical bone lesions. Early clinical signs can occur in the mandible and can cause extensive destruction of the periodontal tissues. Pathologic fracture is an unusual finding. A case of misdiagnosed eosinophilic granuloma in a 45-year-old man treated with free fibula flap and implant-supported overdenture prosthesis is reported. Free fibula flap with dental implants is a safe and reliable method for comprehensive functional and aesthetic mandibular defect reconstruction.

A new experimental reversed-flow flap model: tail artery based skin flap on the dorsum of the rat.

Reversed-flow flaps are widely preferred particularly in reconstruction of the defects of distal part of the extremities. To overcome the drawbacks faced during clinical practice of this flap type, experimental models in economical species are required. This study provides a new reversed-flow flap model on the dorsum of the rat which is supplied by the ipsilateral lateral caudal artery. It is designed as a triangle with a 4-cm long base and 5 cm long height and it is well protected from autocannibalization and environmental conditions because of its dorsal location. When compared with the present models, we believe that this simple, reproducible, and practical flap model can be considered as advantageous, and will be preferred by the researchers for future experimental studies in hemodynamics and physiology of reversed-flow flaps.

Soft-tissue management with immediate free flap transfer in segmental prosthetic replacement of proximal tibia sarcomas.

Knee reconstruction with endoprosthesis after tumor resection is accepted as superior when compared with the other methods. But sometimes soft tissue reconstruction would be a challenging problem in this way of treatment. Five patients who were operated for tumor resection in this location, followed by reconstruction were presented with their one-year post operative results. Four latissimus dorsi and one rectus abdominis myocutaneous free flaps were used in these patients in order to manage soft tissue problems. All patients underwent chemotherapy in postoperative period. All flaps were successful in one year post operative examination. In this report we would like to stress the importance of surgical planning and soft tissue reconstruction of a specific patient population. We think that large musculocutaneous flaps such as latissimus dorsi and rectus abdominis musculocutaneous flaps should be preferred in soft tissue reconstruction of knee region after tumor resection followed by prosthetic replacement. Additionally, this way of treatment is superior when compared to the other methods in order to prevent complications such as prosthesis exposure or infection.

New composite tissue allograft model of vascularized bone marrow transplant: the iliac osteomyocutaneous flap.

Vascularized bone marrow transplant (VBMT) induces donor-specific chimerism in experimental models across the major histocompatibility barrier. An experimental model for immunotolerance studies should sustain a high antigenicity with low morbidity. Accordingly, we introduced an iliac bone osteomusculocutaneous (IBOMC) transplant model in rat. It consists of a large skin component and an abundant bone marrow cells (BMC) population. We tested this model with isograft transplantations between Lewis rats (RT1(l)) and with allograft transplantation between Lewis-Brown Norway (LBN RT1(l + n)) donors and Lewis (RT1(l)) recipients under low dose of cyclosporine A monotherapy. Immunologic responses were tested for donor cell engraftment and chimerism induction. All isografts survived indefinitely and allografts were viable at 200 days post-transplant under low dose of cyclosporine A. Microangiography of the graft revealed preservation of skin, muscle, and bone components. Histologic examination confirmed viability of all allograft components without signs of rejection. Long-term engraftment of donor-origin (RT1(n)) BMC was confirmed by donor-specific chimerism (1.2%) in peripheral blood and bone marrow (1.65%) compartments and by engraftment into lymphoid organs of recipients. The IBOMC transplant proved to be a reliable composite tissue allotransplantation (CTA) model. Moreover, because of its robust bone marrow component and large skin component, it is applicable to studies on immunologic responses in CTA.

Versatility of free SCIA/SIEA flaps in head and neck defects.

Reconstruction of head and neck defects may require replacement of the bony structures, external soft tissue, and intraoral mucosa. Most cases, including maxillary defects, often require repair using only soft tissue flaps. Recently, the authors used free superficial circumflex iliac artery/superficial inferior epigastric (SCIA/SIEA) flaps for head and neck reconstruction. This was their first choice over other free flaps due to its versatile advantages. Fifteen patients underwent head and neck reconstruction with free SCIA/SIEA flaps (n = 16). No flap loss was observed; however, emergency vascular reanastomosis was performed in 3 cases to restore the blood supply in compromised flaps. Flap thinning and secondary debulking procedures were performed in 4 cases. The functional and aesthetic results were deemed as acceptable in all patients. Based on our results, we believe that the free SCIA/SIEA flap is useful for soft tissue defect reconstruction in the head and neck. It has the following advantages: (1) Large flap elevation is possible for reaching distant recipient vessels, (2) Two surgical teams may work at the same time preparing the donor and recipient regions, and (3) The flap design uses an abdominoplasty incision, which has minimal donor site morbidity.

Flow-through free latissimus dorsi flap for reconstruction of injured limbs: Evaluation of hemodynamic effects on extremity circulation.

Management of vascularized injured extremity requires careful reconstruction for continuity of leg circulation. Protection of the remaining intact vessels during free flap transfer provides condition for blood flow maintenance in the distal extremity. Latissimus dorsi muscle has the correct vessel anatomy for applying flow-through flap because it protects recipient vessel integrity during soft tissue reconstruction. Flow-through flap circulation may cause decreasing blood flow in the recipient artery and steal phenomenon in distal circulation although the main vessel remains intact. The purpose of this study was to describe blood flow changes in the recipient artery, flap pedicle, and distal leg circulation at early and long-term follow- up periods. For this purpose, evaluations of blood flows by using Doppler ultrasonography were performed in 2 vascularized injured extremities which were reconstructed with flow-through free latissimus dorsi musculocutaneous flaps. The results demonstrate that flow-through flaps in our vascularized injured extremity did not disturb distal leg circulation in spite of increased blood flow in the recipient and pedicle arteries.

Upper extremity reconstruction using free SCIA/SIEA flap.

The most suitable free flap alternative in upper extremity reconstruction has adequate and quality of tissue with consistent vascular pedicle. Free flap must provide convenient tissue texture to reconstruct aesthetic and functional units of upper extremity. Furthermore, minimal donor site morbidity is preferred features in free flap election. In our efforts to obtain the best possible outcome for patients, we chose, as a first priority, the free superficial circumflex inferior artery (SCIA)/superficial inferior epigastric artery (SIEA) flap over other free flap options for the soft-tissue reconstruction of upper extremities. The authors retrospectively report the results of 20 free SCIA/SIEA flaps for upper extremity reconstruction during the past 3 years. Nineteen of 20 flaps were successful (95%): three required emergent postoperative reexploration of the anastomosis and one failed. Flap thinning (n = 4) was performed during the flap harvest, whereas some flaps were thinned with secondary debulking (n = 4). The functional and aesthetic results were evaluated as acceptable by all patients. Based on our results, a free SCIA/SIEA flap has the following advantages in soft-tissue reconstruction of the upper extremity: (1) if necessary, flap thinning may be performed safely at the time of flap elevation and (2) flaps are harvested using a lower abdominal incision so that it causes minimal donor site scar.

Controversies in skull reconstruction.

In the early 1980s, it was shown that bone from the skull (membranous bone) maintained its volume to a significantly greater extent than bone from the rib and iliac crest regions (endochondral bone). However, the reason for this enhanced volume maintenance was not clarified for many years. On the basis of this enhanced volume maintenance, cranial bone became the ideal autogenous graft of choice for hard tissue repair. In the ensuing years, the current authors performed a large number of autogenous split skull cranial bone cranioplasties with significant success. However, the lure of an off-the-shelf material that obviates bone harvest remained. From 1995 to 2005, the senior author performed 20 full-thickness skull defect cranioplasty corrections using calcium phosphate cement (Norian Craniofacial Repair System; Synthes, Inc, West Chester, PA; Stryker-Leibinger, Kalamazoo, MI). Of these full-thickness defects, 16 were large (arbitrarily defined as greater than 25 cm2). In this paper, we report our long-term major and minor complication rates using this material. Because of our high, long-term complication rate (38%), we believe this material is contraindicated for large, full-thickness, skull defects (>25 cm2) and we have returned to autogenous cranial bone as the criterion standard for reconstruction in such patients.

Surgical rehabilitation of nasoalveolar complex in patients with alveolar clefts.

OBJECTIVE: The objective of this study was to review the outcome of surgical rehabilitation of nasoalveolar complex in patients with alveolar clefts. STUDY DESIGN: Twenty-seven patients (13 female, 14 male) with 4 bilateral and 23 unilateral alveolar clefts who were treated in our clinic during the period between 2002 and 2009 were included in the study. RESULTS: All the patients had oronasal fistulas, and all of them were closed successfully except one. Recurrence of the oronasal fistula was seen in 1 patient. Alar base was supported by onlay cortical bone in most of the patients. Eleven of the canines at the cleft site erupted after the operation in to the grafted area. Seventy-six percent (n = 16) of the 21 patients could be assigned to the successful groups 1 and 2, whereas 24% (n = 5) were assigned to the unfavorable group. There was not any insufficient result. CONCLUSIONS: Bone graft placed along the piriform margin and alar wings during alveolar bone grafting improves the results of nasal correction. Late grafting should be performed at least to support the alar base for nasal symmetry.

Free groin flap applications in the pediatric population.

The popularity of the groin flap has gradually decreased because of the disadvantages related to its short pedicle and technically demanding harvesting. We have summarized our experience with free groin flap applications in the pediatric population, which were performed by the same surgeon between 2004 and 2007. A total of 10 free groin flap transfers were performed in patients aged 3 to 13 years. Nine of the patients were operated on because of contractures of the extremities (six lower, three upper), and one patient was operated on for facial contour augmentation. The total duration of the operation was estimated to be between 2.6 and 6.1 hours (mean: 4.1 hours). A revision of the anastomosis was performed in two patients (20%), and in one of these patients (50%) partial flap failure was seen. Flap defatting via liposuction was performed in four patients (40%) in the late postoperative period. In our opinion, donor site morbidity comes into prominence particularly in the pediatric population, and we think that free groin flap should be the first choice of free flap for suitable cases in this group of patients.

Penis allotransplantation model in the rat.

In this study we present the first experimental vascularized penile allogenic transplantation model in the rat. In group 1 (n = 6), the vascular anatomy of the male rat perineal region was determined. In 12 Lewis rats of group 2 (n = 24), the penile composite graft was transplanted as isotransplant by microvascular anastomosis of the pedicle of the penis to the saphenous vessels and in another 12 Lewis rats of group 2, penile composite graft was transplanted without vascular anastomosis. In group 3 (n = 12), penis composite graft was transplanted from 6 Lewis-Brown-Norway donors to 6 Lewis recipients under CsA immunosuppression. Direct observation, somatosensory evoked potential test, histologic examination and microangiography were used to assess the viability of the transplants. All vascularized isotransplants and allotransplants survived over 200 days (still under observation) whereas all the nonvascularized grafts were necrosed at 7 days posttransplant. In this study the new penile allograft transplantation model in the rat was developed and a new method of blood supply to a vascularized composite tissue with directly artery-to-corpus spongiosum anastomosis was introduced.

Correlation of chimerism with graft size and revascularization in vascularized and nonvascularized skin allografts.

The high antigenicity of skin components of composite tissue allografts is the most challenging factor in achieving long-term viability after composite tissue allografts transplantation. The vascularization pattern of vascularized skin allografts (VSA) and nonvascularized skin allografts (NVSA) differs significantly and these differences may alter host immune responses. We hypothesized that vascularized grafts contribute to better engraftment and long-term survival. We have tested our hypothesis by transplantation of different sizes (2 x 2 cm, 4 x 4 cm, 6 x 6 cm) of VSA and NVSA across major histocompatibility complex barrier between LBN (RT1(1+n)) and Lewis (RT1(1)) rats. Correlation of revascularization process with development of donor-specific chimerism was tested. We found that the highest chimerism levels (8%-12.2% in VSA groups; 2.53%-3.92% in NVSA groups) were reached as early as 7 days in both VSA and NVSA. Chimerism decreased in both groups during 100-day follow-up and higher chimerism was found only in VSA in late posttransplant period. Revascularization, assessed by the presence of CD31 positive vessels, was significantly higher in VSA compared with NVSA and to controls (P < 0.05). A direct correlation was seen between increased skin diameter and donor chimerism in VSA, whereas inverse correlation was tested in NVSA. We have confirmed that allograft size and vascularization pattern contribute to donor chimerism development and maintenance.

Reconstruction of soft tissue defect of lower extremity with free SCIA/SIEA flap.

Free tissue transfer is the most important means of soft tissue reconstruction for the lower extremity. However, cosmetic results and donor site morbidity are only of secondary concern of lower extremity reconstruction. In our efforts to obtain the best possible outcome for patients, as our first priority we chose free superficial circumflex inferior artery (SCIA)/superficial inferior epigastric artery (SIEA) flap over other free flap options in the soft tissue reconstruction of lower extremity because of some advantages. Over the past 3 year, 25 patients underwent lower extremity reconstruction with free SCIA/SIEA flap (n = 27). Twenty-six of 27 flaps were successful (96%), 6 required emergent postoperative re-exploration of the anastomosis, and 1 failed. Although secondary debulking procedure was performed for some flaps (n = 3), most flaps had acceptable thickness for functional and esthetic outcomes especially in the pretibial, ankle, and foot defect reconstruction with an average of 1-year follow-up. Based on our results, free SCIA/SIEA flap has the following advantages in soft tissue reconstruction of lower extremity: (1) large flaps may be harvested for extensive defect and/or to reach recipient artery for passing zone of injury; (2) if necessary, final flap debulking may be performed by surgical procedure using local anesthesia; (3) the donor site is closed in a similar manner to abdominoplasty incision so that excellent cosmetic result may be achieved.