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.

Immunomodulatory Effects of Different Cellular Therapies of Bone Marrow Origin on Chimerism Induction and Maintenance Across MHC Barriers in a Face Allotransplantation Model.

Many more patients would benefit from vascularized composite allotransplantation if less toxic and safer immunosuppressive protocols will become available. Tolerance induction protocols with donor cells co-transplantation are one of the promising pathways to reduce maintenance immunosupressive regimens. We investigated the role of donor bone marrow cells (BMC), mesenchymal stromal cells (MSC) and in vivo created chimeric cells (CC) used as supportive therapies in a fully MHC-mismatched rat face transplantation model. Twenty-four fully MHC-mismatched hemiface transplantations were performed between ACI (RT1(a)) donors and Lewis (RT1(l)) recipients under combined seven-day immunosuppressive regimen of anti-αß-T-cell receptor (TCR) monoclonal antibody and cyclosporin A. We studied four experimental groups-group 1: no cellular therapy; group 2: supportive therapy with BMC; group 3: supportive therapy with MSC; group 4: supportive therapy with CC generated in a primary chimera. We evaluated clinical and histological rejection grades, transplanted cells migration, donor-specific chimerism in the peripheral blood and bone marrow compartments, and CD4(+)/CD25(+) T-cell levels. Face allograft rejection was observed at 26.8 ± 0.6 days post-transplant (PT) in the absence of cellular therapy, at 34.5 ± 1.1 days for group 2, 29.3 ± 0.8 days for group 3, and 30.3 ± 1.38 PT for group 4. The longest survival was observed in allografts supported by co-transplantation of BMC. All support in cellular therapies delayed face allograft rejection by chimerism induction and/or immunomodulatory properties of co-transplanted cells. Survival time was comparable between groups, however, further studies, with different cell dosages, delivery routes and delivery times are required.

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.

Difficult Airway Management in Field Conditions: Somalia Experience.

Difficult airway is defined as having the patient's mask ventilation or difficult tracheal intubation of an experienced anaesthesiologist. A number of reasons, such as congenital or acquired anatomical anomalies, can cause difficult intubation and difficult ventilation. Keeping all equipment ready for airway management of patients will reduce mortality and complications. In this case, it is intended that the submission of difficult airway management who encountered in mandibular reconstruction for mandible bone defect repairing with reconstruction plates before at the field conditions in Somalia.

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.

Comparison of different autogenous graft materials for reconstruction of large segment vas deferens defect: experimental study in rat.

PURPOSE: Vasectomy is one of the most common urological operations performed, and provides permanent contraception. Many vasectomized men ultimately seek vasectomy reversal because of unforeseen changes in lifestyle. Vasovasostomy has varying rates of success. In this study, we utilize vas deferens (VD), artery, and vein grafts to reconstruct 30% and 50%defects of the total vas deferens length. MATERIALS AND METHODS: Forty two male Wistar rats were divided into three groups as VD graft, carotid artery and external jugular vein transplantations. Each group was equally divided into 2 different subgroups according to the length of transplant material as 1.0 cm (n = 7) and 1.5 cm (n = 7). To evaluate whether these materials may be used for long segment vas deferens reconstruction, the patency rate, partial or total graft occlusion, and histologic examination of all specimens were examined. RESULTS: No patency was found in any of the grafts and many of them suffered destructive changes in anatomic structure. Sperm granulomas were determined around the testicular side anastomosis due to accumulated semen fluid which was in our belief, a result of aperistaltic zone caused by the grafts. CONCLUSION: When the poor results obtained in our study are put into perspective, vasoepididymostomy is the only treatment method to date for reconstruction of large segment vas deferens defects.

Myxoma of the dorsal hand.

Myxomas of the hand are rare tumours and the diameters are usually smaller than 2 cm. In this report we describe the biggest reported myxoma that localised on the dorsal hand and the comprehensively review of hand myxomas. This case is to our knowledge the first hormone-receptor-positive myxoma of the hand.

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.

Biomechanical comparison of calcium phosphate cements for split cranial bone graft donor sites.

BACKGROUND: Although harvesting of in situ split cranial bone is a well-established technique, few data have been generated regarding the biomechanical effect of bone harvest on the cranial bone donor site, and even fewer data have been generated regarding the biomechanical effect of calcium phosphate bone cement inlay on the donor site. The authors documented the weakening of the skull at the in situ cranial harvest site and determined the benefit, if any, when the site is inlayed with calcium phosphate cements. METHODS: Cadaver skulls were divided into three groups: group 1, an in situ cranial bone defect was created in the frontal bone area on one side and the mirror-image, full-thickness area was untreated; group 2, a similar defect was created in the parietal area and repaired with calcium phosphate bone cement inlay, and on the opposite side, a similar defect was created but not repaired; and group 3, donor sites were created in the parietal area bilaterally and reconstructed with different cements. Mirror-image areas were harvested and testing was performed. The Wilcoxon rank sum test was used to evaluate all mirror-image specimens. RESULTS: There was a statistically significant difference in strength to fracture when the in situ defect was compared with the in situ calcium phosphate construct (p = 0.008). No difference was demonstrated when the defect was compared with full-thickness bone or when calcium phosphate cements were compared. CONCLUSION: Repair of the defect with calcium phosphate cement significantly increased strength at the donor site and may provide added safety from injury.

Surgical treatment of posttraumatic ankylosis of the TMJ with different pathogenic mechanisms.

OBJECTIVE: Posttraumatic ankylosis of the TMJ can be caused by many different pathogenic mechanisms. Prosthetic alloplastic grafts and autogenous grafts are the options for surgical treatment. METHODS: Seven patients were examined clinically and radiologically. Autogenous interpositioners were used for treatment of TMJ ankylosis. RESULTS: No major complications were seen after surgery. Interincisal distances have significantly widened following mouth opening exercises for one year. CONCLUSIONS: Human skulls have many structure and shape differences, so it is difficult to replace a jaw joint successfully with an artificial one. Using autogenous tissues seems an appropriate choice for treatment.

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.

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.

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.

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.