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Knoedler L, Knoedler S, Allam O, Remy K, Miragall M, Safi AF, Alfertshofer M, Pomahac B, Kauke-Navarro M. Application possibilities of artificial intelligence in facial vascularized composite allotransplantation-a narrative review. Front Surg 2023; 10:1266399. [PMID: 38026484 PMCID: PMC10646214 DOI: 10.3389/fsurg.2023.1266399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 09/26/2023] [Indexed: 12/01/2023] Open
Abstract
Facial vascularized composite allotransplantation (FVCA) is an emerging field of reconstructive surgery that represents a dogmatic shift in the surgical treatment of patients with severe facial disfigurements. While conventional reconstructive strategies were previously considered the goldstandard for patients with devastating facial trauma, FVCA has demonstrated promising short- and long-term outcomes. Yet, there remain several obstacles that complicate the integration of FVCA procedures into the standard workflow for facial trauma patients. Artificial intelligence (AI) has been shown to provide targeted and resource-effective solutions for persisting clinical challenges in various specialties. However, there is a paucity of studies elucidating the combination of FVCA and AI to overcome such hurdles. Here, we delineate the application possibilities of AI in the field of FVCA and discuss the use of AI technology for FVCA outcome simulation, diagnosis and prediction of rejection episodes, and malignancy screening. This line of research may serve as a fundament for future studies linking these two revolutionary biotechnologies.
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Affiliation(s)
- Leonard Knoedler
- Department of Plastic, Hand- and Reconstructive Surgery, University Hospital Regensburg, Regensburg, Germany
- Division of Plastic Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, United States
| | - Samuel Knoedler
- Division of Plastic Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, United States
| | - Omar Allam
- Division of Plastic Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, United States
| | - Katya Remy
- Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Maximilian Miragall
- Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Ali-Farid Safi
- Craniologicum, Center for Cranio-Maxillo-Facial Surgery, Bern, Switzerland
- Faculty of Medicine, University of Bern, Bern, Switzerland
| | - Michael Alfertshofer
- Division of Hand, Plastic and Aesthetic Surgery, Ludwig-Maximilians University Munich, Munich, Germany
| | - Bohdan Pomahac
- Division of Plastic Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, United States
| | - Martin Kauke-Navarro
- Division of Plastic Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, United States
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La Padula S, Pensato R, Pizza C, Coiante E, Roccaro G, Longo B, D’Andrea F, Wirz FS, Hersant B, Meningaud JP. Face Transplant: Indications, Outcomes, and Ethical Issues-Where Do We Stand? J Clin Med 2022; 11:jcm11195750. [PMID: 36233619 PMCID: PMC9571096 DOI: 10.3390/jcm11195750] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 09/13/2022] [Accepted: 09/26/2022] [Indexed: 11/21/2022] Open
Abstract
Background: The addition of face allotransplantation (FT) to the head and neck reconstructive surgery arsenal has started a true revolution. This study is aimed at providing an extensive analysis of the current practice of composite tissue allotransplantation. Moreover, a thorough description of pre-procedural, intra-operative, and post-procedural settings, indications, contraindications, outcomes, ethical considerations, and future perspectives is provided. Methods: The authors’ experience was supplemented with a literature review performed by using the PubMed, MEDLINE, and Embase databases on 21 February 2022. The search terms used were “face transplantation indications”, “face transplantation complications”, and “face transplantation ethical issues”. Results: The most recent achievements and long-term clinical sequelae of FT are classified and summarized. A large number of records (4435) were identified. Seventy-five articles were assessed for eligibility. Publications without new data and reports with a patient follow-up < 5 years were excluded. Nineteen articles met the criteria for inclusion. Conclusions: The most recent achievements in the field of FT may be combined with cutting-edge regenerative medicine procedures and innovative immunological processing. It is paramount to build strong international networks between the world FT experts in order to achieve higher-level outcomes and reduce the complication rate. Nevertheless, the utmost caution is required in patient selection, clinical assessment, strict follow-up, and rejection management.
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Affiliation(s)
- Simone La Padula
- Department of Plastic and Reconstructive Surgery, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
- Correspondence:
| | - Rosita Pensato
- Department of Plastic and Reconstructive Surgery, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy
| | - Chiara Pizza
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Edoardo Coiante
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Giovanni Roccaro
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Benedetto Longo
- Department of Plastic and Reconstructive Surgery, Università di Roma Tor Vergata, Viale Oxford 81, 00133 Roma, Italy
| | - Francesco D’Andrea
- Department of Plastic and Reconstructive Surgery, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy
| | | | - Barbara Hersant
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Jean Paul Meningaud
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
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Girard AO, Lake IV, Lopez CD, Kalsi R, Brandacher G, Cooney DS, Redett RJ. Vascularized composite allotransplantation of the penis: current status and future perspectives. Int J Impot Res 2021; 34:383-391. [PMID: 34711953 DOI: 10.1038/s41443-021-00481-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/30/2021] [Accepted: 10/11/2021] [Indexed: 12/13/2022]
Abstract
Given the multifunctional role of the penis in daily life, penile loss can be a physically and emotionally devastating injury. Options to restore penile loss have traditionally relied on autogenous free flap, local flaps, and skin grafts. These techniques provide satisfactory outcomes but carry high rates of urologic and prosthesis-related complications. Vascularized composite allotransplantation may offer a novel solution for these patients through reconstruction with true penile tissue. Still, penile transplants pose ethical, logistical, and psychosocial challenges. These obstacles are made more complex by the limited cases detailed in published literature. A review of the literature was conducted to assay current practices for penile reconstruction. Most modern complex penile reconstructions utilize autogenous pedicled or free tissue flaps, which may be harvested from a variety of donor sites. A total of five penile transplants have been described in the literature. Of these, four report satisfactory outcomes. The advent of genital allotransplantation has recently broadened the landscape of treatment for penile loss. Reconstruction using true penile tissue through vascularized penile allotransplantation has the possibility to engender increased penile function, sensation, and overall quality of life.
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Affiliation(s)
- Alisa O Girard
- Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Division of Plastic Surgery, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ, USA
| | - Isabel V Lake
- Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Christopher D Lopez
- Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Richa Kalsi
- Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Gerald Brandacher
- Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Damon S Cooney
- Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Richard J Redett
- Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Colazo JM, Evans BC, Farinas AF, Al-Kassis S, Duvall CL, Thayer WP. Applied Bioengineering in Tissue Reconstruction, Replacement, and Regeneration. TISSUE ENGINEERING PART B-REVIEWS 2020; 25:259-290. [PMID: 30896342 DOI: 10.1089/ten.teb.2018.0325] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
IMPACT STATEMENT The use of autologous tissue in the reconstruction of tissue defects has been the gold standard. However, current standards still face many limitations and complications. Improving patient outcomes and quality of life by addressing these barriers remain imperative. This article provides historical perspective, covers the major limitations of current standards of care, and reviews recent advances and future prospects in applied bioengineering in the context of tissue reconstruction, replacement, and regeneration.
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Affiliation(s)
- Juan M Colazo
- 1Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.,2Medical Scientist Training Program, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Brian C Evans
- 3Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee
| | - Angel F Farinas
- 4Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Salam Al-Kassis
- 4Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Craig L Duvall
- 3Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee
| | - Wesley P Thayer
- 3Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee.,4Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
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Cammarata MJ, Jethanamest D, Rodriguez ED. Otologic considerations in a full face transplant recipient. Laryngoscope 2018; 129:2008-2011. [PMID: 30582171 DOI: 10.1002/lary.27624] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 09/28/2018] [Indexed: 11/06/2022]
Abstract
Facial transplantation provides a functional and aesthetic solution to severe facial disfigurement previously unresolved by conventional reconstruction. Few facial allografts have been ear containing; hence, there is limited knowledge of the postoperative otologic considerations. We describe the case of a 44-year-old man who underwent transplantation of the total face, eyelids, ears, scalp, and skeletal subunits in 2015 after an extensive thermal injury. We detail the patient's transition from osseointegrated prosthetic ears to an ear-containing facial allograft, and describe the unique surgical approach and challenges encountered. Subsequent bilateral revision meatoplasties were performed, which provided relief from stenosis of the external auditory meatus. Laryngoscope, 129:2008-2011, 2019.
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Considerations for Temporomandibular Joint Procurement in Vascularized Composite Allotransplantation. J Craniofac Surg 2018; 29:1742-1746. [PMID: 30074957 DOI: 10.1097/scs.0000000000004710] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Methods for harvest of the temporomandibular joint (TMJ) for transplantation may involve several anatomic levels. The authors aim to assess the feasibility and identify challenges with 2 such methods, resuspending the donor condyles from the recipient glenoid fossae and en bloc harvest of the joint and surrounding temporal bone with plate-fixation to the recipient skull base. Two mock face transplantations were carried out using 4 fresh cadavers. Computed tomography imaging was obtained before and after the procedures to assess the technical success of each method. Both techniques were technically successful, allowing for full passive jaw range of motion following graft transfer and appropriate condyle positioning as assessed by computed tomography. En bloc TMJ harvest allowed for transfer of the entire joint without violating its capsule or altering its biomechanics. The authors found this technique better able to avoid issues with size mismatch between the donor mandible and recipient skull base width. When no such mismatch exists, graft harvest at the level of the mandibular condyle is technically easier and less time consuming. Although both methods of TMJ harvest are technically feasible with acceptable immediate postoperative jaw position and range of motion, the en bloc technique allows for more natural jaw function with less risk of postoperative joint immobility by preserving the joint capsule and its ligamentous support.
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Anatomic Considerations for Temporomandibular Joint Vascularized Composite Allotransplantation. J Craniofac Surg 2018; 29:871-877. [PMID: 29498981 DOI: 10.1097/scs.0000000000004397] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Concomitant temporomandibular joint (TMJ) transplantation is an obvious advancement in the reconstructive armamentarium for face transplantation in scenarios involving TMJ ankylosis. This study investigates the fidelity of mandibular morphology and explores the feasibility of bilateral mandibular condyle transfer in facial vascularized composite allotransplantation. Geometric analysis was performed on 100 skeletally mature maxillofacial computed tomography scans. Exclusion criteria included mandibular trauma and dentoalveolar disease. Parameters measured were posterior height, ramus tilt, anterior height, intercondylar widths, condyle height, coronoid height, interglenoid distances, symphyseal and gonial angles, condyle and glenoid volumes, and condyle shapes. Parameters were compared by gender and ethnicity using χ, independent sample t tests, and one-way ANOVA. Correlation with age was assessed using Pearson correlation coefficients. Bilateral measurements were compared using paired-sample t tests. Mean intercondylar width was 102.5 mm (SD 7.0 mm), anterior height 21.5 mm (5.5), and posterior height 65.3 mm (7.7), Males demonstrate larger geometric parameters, for example, intercondylar width (4 mm mean difference, P = 0.005), anterior height (2.3 mm, P = 0.032), posterior height (5 mm, P = 0.001). Asians demonstrated statistically larger intercondylar width (8 mm difference to Caucasians, P < 0.001). Increased age was associated with greater anterior height, gonial angle, and symphyseal angle; decreased glenoid height; and change in condyle shape. Despite significant disparity of laterality measurements within individuals, posterior height, glenoid, and condyle volumes are equivalent. Mandibular morphology is highly variable. However, transplantation of a facial allograft including the mandible and bilateral condyles is technically and anatomically feasible in patients with concomitant TMJ pathology.
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8
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Nkenke E, Lehner B, Kramer M, Haeusler G, Benz S, Schuster M, Neukam FW, Vairaktaris EG, Wurm J. Determination of Facial Symmetry in Unilateral Cleft Lip and Palate Patients from Three-Dimensional Data: Technical Report and Assessment of Measurement Errors. Cleft Palate Craniofac J 2017; 43:129-37. [PMID: 16526915 DOI: 10.1597/04-138.1] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Objective To assess measurement errors of a novel technique for the three-dimensional determination of the degree of facial symmetry in patients suffering from unilateral cleft lip and palate malformations. Design Technical report, reliability study. Setting Cleft Lip and Palate Center of the University of Erlangen-Nuremberg, Erlangen, Germany. Patients The three-dimensional facial surface data of five 10-year-old unilateral cleft lip and palate patients were subjected to the analysis. Distances, angles, surface areas, and volumes were assessed twice. Main Outcome Measures Calculations were made for method error, intraclass correlation coefficient, and repeatability of the measurements of distances, angles, surface areas, and volumes. Results The method errors were less than 1 mm for distances and less than 1.5° for angles. The intraclass correlation coefficients showed values greater than .90 for all parameters. The repeatability values were comparable for cleft and noncleft sides. Conclusion The small method errors, high intraclass correlation coefficients, and comparable repeatability values for cleft and noncleft sides reveal that the new technique is appropriate for clinical use.
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Affiliation(s)
- Emeka Nkenke
- Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Glueckstrasse 11, 91054 Erlangen, Germany.
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Abstract
BACKGROUND Ten years after the first face transplantation, the available data in peer-reviewed literature, various media outlets, and recent specialty meetings and courses are conflicting and inconsistently reported. The purpose of this study was to consolidate the available data by means of multiple sources to reflect an accurate and current state of facial vascularized composite allotransplantation as of December of 2015. METHODS Using applied search terms pertaining to face transplantation, a systematic PubMed search, Google search, and review of Plastic Surgery Education Network News Connection e-mailed newsletters were performed, and data presented at three meetings (i.e., the most recent American Society of Reconstructive Transplantation biennial meeting, the American Society of Reconstructive Microsurgery annual meeting, and the biennial AO North America State of the Art: Face Reconstruction and Transplantation course) were consolidated to capture the most contemporary and accurate data in face transplantation. RESULTS A total of 37 face transplants have been performed (20 partial and 17 full face) from 2005 to December of 2015. A discrepancy between actual transplantations performed and peer-reviewed reports exists at multiple time points, with a propensity for underreporting. Ten cases were described through media outlets but were not reported by the surgical teams in peer-reviewed literature. Two clinical cases were not described in peer-reviewed literature or media. There have been a total of five deaths, and posttransplant malignancy and revision surgery have been underreported. CONCLUSIONS This serves as the most contemporary and all-inclusive face transplantation review. There is a critical need for timely reporting and outcome transparency in the reconstructive transplant community. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, V.
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10
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Uluer MC, Brazio PS, Woodall JD, Nam AJ, Bartlett ST, Barth RN. Vascularized Composite Allotransplantation: Medical Complications. CURRENT TRANSPLANTATION REPORTS 2016; 3:395-403. [PMID: 32288984 PMCID: PMC7101879 DOI: 10.1007/s40472-016-0113-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The objective of this review is to summarize the collective knowledge regarding the risks and complications in vascularized composite tissue allotransplantation (VCA), focusing on upper extremity and facial transplantation. The field of VCA has entered its second decade with an increasing experience in both the impressive good outcomes, as well as defining challenges, risks, and experienced poor results. The limited and selective publishing of negative outcomes in this relatively new field makes it difficult to conclusively evaluate outcomes of graft and patient survival and morbidities. Therefore, published data, conference proceedings, and communications were summarized in an attempt to provide a current outline of complications. These data on the medical complications of VCA should allow for precautions to avoid poor outcomes, data to better provide informed consent to potential recipients, and result in improvements in graft and patient outcomes as VCA finds a place as a therapeutic option for selected patients.
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Affiliation(s)
- Mehmet C. Uluer
- Department of Surgery, Division of Transplantation, University of Maryland School of Medicine, 29 S Greene Street STE 200, Baltimore, MD 21201 USA
| | - Philip S. Brazio
- Department of Surgery, Division of Transplantation, University of Maryland School of Medicine, 29 S Greene Street STE 200, Baltimore, MD 21201 USA
| | - Jhade D. Woodall
- Department of Surgery, Division of Transplantation, University of Maryland School of Medicine, 29 S Greene Street STE 200, Baltimore, MD 21201 USA
| | - Arthur J. Nam
- Department of Surgery, Division of Transplantation, University of Maryland School of Medicine, 29 S Greene Street STE 200, Baltimore, MD 21201 USA
| | - Stephen T. Bartlett
- Department of Surgery, Division of Transplantation, University of Maryland School of Medicine, 29 S Greene Street STE 200, Baltimore, MD 21201 USA
| | - Rolf N. Barth
- Department of Surgery, Division of Transplantation, University of Maryland School of Medicine, 29 S Greene Street STE 200, Baltimore, MD 21201 USA
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Choi JH, Kim KS, Shin JH, Hwang JH, Lee SY. Risk Acceptance and Expectations of Scalp Allotransplantation. Arch Craniofac Surg 2016; 17:68-76. [PMID: 28913258 PMCID: PMC5556874 DOI: 10.7181/acfs.2016.17.2.68] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 05/24/2016] [Accepted: 05/25/2016] [Indexed: 11/20/2022] Open
Abstract
Background In scalp allotransplantation, the scalp from a brain-dead donor, including hair, is transferred to a recipient with scalp defects. Opinions differ on the appropriateness of scalp allotransplantation. In order to maintain graft function and cosmetic outcomes, scalp transplantation recipients would need to receive lifelong immunosuppression treatments. The risks of this immunosuppression have to be balanced against the fact that receiving a scalp allotransplant does not extend lifespan or restore a physical function. Therefore, the present study aimed to investigate risk acceptance and expectations regarding scalp allotransplantation in different populations. Methods A questionnaire survey study was conducted. A total of 300 subjects participated; survey was conducted amongst the general public (n=100), kidney transplantation recipients (n=50), a group of patient who required scalp reconstruction due to tumor or trauma (n=50), and physicians (n=100). The survey was modified by using the Korean version of the Louisville instrument for transplantation questionnaire. Results Risk acceptance and expectations for scalp transplantation varied widely across the groups. Kidney transplantation recipients revealed the highest risk acceptance and expectations, whereas the physicians were most resistant to the risks of scalp transplantation. Conclusion Our study demonstrates that, in specific groups, scalp allotransplantation and the need for immunosuppression carries an acceptable risk despite the lack of lifeextending benefits. Our results suggest that scalp allotransplantation can be an acceptable alternative to existing scalp reconstruction surgeries in patients with pre-existing need for immunosuppression.
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Affiliation(s)
- Jun Ho Choi
- Department of Plastic and Reconstructive Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Kwang Seog Kim
- Department of Plastic and Reconstructive Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Jun Ho Shin
- Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Jae Ha Hwang
- Department of Plastic and Reconstructive Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Sam Yong Lee
- Department of Plastic and Reconstructive Surgery, Chonnam National University Medical School, Gwangju, Korea
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Diaz-Siso JR, Sosin M, Plana NM, Rodriguez ED. Face transplantation: Complications, implications, and an update for the oncologic surgeon. J Surg Oncol 2016; 113:971-5. [DOI: 10.1002/jso.24211] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 02/15/2016] [Indexed: 01/13/2023]
Affiliation(s)
- J. Rodrigo Diaz-Siso
- Hansjörg Wyss Department of Plastic Surgery; NYU Langone Medical Center; New York New York
| | - Michael Sosin
- Hansjörg Wyss Department of Plastic Surgery; NYU Langone Medical Center; New York New York
| | - Natalie M. Plana
- Hansjörg Wyss Department of Plastic Surgery; NYU Langone Medical Center; New York New York
| | - Eduardo D. Rodriguez
- Hansjörg Wyss Department of Plastic Surgery; NYU Langone Medical Center; New York New York
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Kumnig M, Jowsey-Gregoire SG. Key psychosocial challenges in vascularized composite allotransplantation. World J Transplant 2016; 6:91-102. [PMID: 27011907 PMCID: PMC4801807 DOI: 10.5500/wjt.v6.i1.91] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 12/16/2015] [Accepted: 01/08/2016] [Indexed: 02/05/2023] Open
Abstract
Psychosocial factors are important elements in the assessment and follow-up care for vascularized composite allotransplantation (VCA) and require multidisciplinary evaluation protocols. This review will highlight differences between VCA with solid organ transplantation (SOT), provide information on the psychosocial selection of VCA candidates, ethical issues, psychological outcomes, and on the need for multicenter research. VCA is primarily a life-enhancing procedure to improve recipients' quality of life and psychological well-being and it represents a potential option to provide reproduction in case of penile or uterine transplantation. The risk benefit ratio is distinctly different than SOT with candidates desiring life enhancing outcomes including improved body image, return to occupations, restored touch, and for uterine transplant, pregnancy. The Chauvet Workgroup has been convened with membership from a number of transplant centers to address these issues and to call for multicenter research. A multicenter research network would share similar evaluation approaches so that meaningful research on psychosocial variables could inform the transplant community and patients about factors that increase risk of non-adherence and other adverse psychosocial and medical outcomes.
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Edtinger K, Yang X, Uehara H, Tullius SG. Current status of vascularized composite tissue allotransplantation. BURNS & TRAUMA 2014; 2:53-60. [PMID: 27602363 PMCID: PMC5012023 DOI: 10.4103/2321-3868.130184] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Revised: 03/09/2014] [Indexed: 01/01/2023]
Abstract
Vascularized composite tissue allotransplantation (VCA) offers treatment options of complex functional deficiencies that cannot be repaired with conventional reconstructive methods. VCAs consist of blocks of functional units comprising different tissue types such as skin, bone, muscle, nerves, blood vessels, tendons, ligaments and others, and are thus substantially different from the composition of organ transplants. The field of VCA has made fascinating progresses in the recent past. Among other VCAs, numerous successful hand, face and limb transplants have been performed in the world. At the same time, specific questions in regard to innate and adaptive immunity, consequences of ischemia/reperfusion injury, immunosuppression, preservation, and regenerative capacity remain. In spite of this, the field is poised to make significant advances in the near future.
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Affiliation(s)
- Karoline Edtinger
- Division of Transplant Surgery and Laboratory of Transplant Surgery Research, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, Massachusetts 02115 USA ; Department of Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany
| | - Xiaoyong Yang
- Division of Transplant Surgery and Laboratory of Transplant Surgery Research, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, Massachusetts 02115 USA ; Division of Urology, Bejing Chao-Yang Hospital, Capital Medical University, Bejing, China
| | - Hanae Uehara
- Division of Transplant Surgery and Laboratory of Transplant Surgery Research, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, Massachusetts 02115 USA ; Department of Plastic and Reconstructive Surgery, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Stefan G Tullius
- Division of Transplant Surgery and Laboratory of Transplant Surgery Research, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, Massachusetts 02115 USA
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Zhu H, Wei X, Lineaweaver W, Li Q. Perioperative risk factors for vascularized composite allotransplantation: A systematic review and proposal of identity-defining VCA. Microsurgery 2013; 34:240-4. [PMID: 23836513 DOI: 10.1002/micr.22125] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Revised: 03/21/2013] [Accepted: 03/25/2013] [Indexed: 11/09/2022]
Affiliation(s)
- Hainan Zhu
- Department of Plastic and Reconstructive Surgery; Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai China
| | - Xian Wei
- Department of Plastic and Reconstructive Surgery; Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai China
| | - William Lineaweaver
- JMS Burn and Reconstruction Center; Crossgates River Oaks Hospital; Brandon MS
| | - Qingfeng Li
- Department of Plastic and Reconstructive Surgery; Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai China
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Ren X, Laugel MC. The next frontier in composite tissue allotransplantation. CNS Neurosci Ther 2012; 19:1-4. [PMID: 23157698 DOI: 10.1111/cns.12029] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 10/02/2012] [Accepted: 10/02/2012] [Indexed: 01/11/2023] Open
Abstract
Solid organ transplantations became a clinical option in the 1950s. The hand allograft was the pioneer of composite tissue allotransplantation (CTA), successfully started near the end of the last century despite arguments over the practicality and methods. Since then, CTA such as hand and face has continued to progress from the theoretical to clinical reality. The treatment principles, drug combinations, and mechanisms of the immunosuppression medications on which contemporary transplant surgeries have been based continue to develop as researchers and physicians gain more experience in the CTA field. It could be argued that the ethical issues associated with CTA have prevented evolution of the field rather than surgical or technical skill. This is particularly true for allo-head and body reconstruction (AHBR). How can leaders in the field of CTA develop a model that would satisfy ethical concerns? Bolstered by recent successes in the field, is it time to traverse the next frontier? Can AHBR ever be a feasible option in the clinical setting? The reader will be provided with a brief history of CTA from theory to research to clinical practice. A concise description of AHBR as it pertains to the critical procedure (i.e., surgery design) will also be discussed.
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Affiliation(s)
- Xiaoping Ren
- Clinical Translational Medicine Center, Harbin Medical University, China.
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Lin JY, Tsai FC, Wallace CG, Huang WC, Wei FC, Liao SK. Optimizing chimerism level through bone marrow transplantation and irradiation to induce long-term tolerance to composite tissue allotransplantation. J Surg Res 2012; 178:487-93. [PMID: 22484382 DOI: 10.1016/j.jss.2012.02.064] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Revised: 02/28/2012] [Accepted: 02/29/2012] [Indexed: 10/28/2022]
Abstract
BACKGROUND Mixed chimerism with long-term composite tissue allotransplant (CTA) acceptance can be achieved through allogeneic bone marrow transplantation (BMT). The present study investigated the optimal chimerism level by giving different irradiation dosages to recipients to induce tolerance to CTA. METHODS Chimera were prepared using Brown-Norway and Lewis rats with strong major histocompatibility complex incompatibility. The Lewis rats received 5 mg antilymphocyte globulin (day -1 and 10) and 16 mg/kg cyclosporine (day 0-10) and were separated into groups 1, 2, 3, 4, and 5 according to the day -1 irradiation dosage: 0, 200, 400, 600, and 950 cGy, respectively. The Lewis rats were then reconstituted with 100 × 10(6) T-cell-depleted Brown-Norway bone marrow cells (day 0) and received vascularized Brown-Norway-CTA on day 28. Chimerism was assessed monthly by flow cytometry starting on day 28 after BMT. Graft-versus-host disease (GVHD) was assessed clinically and histologically. RESULTS Chimerism, 4 weeks after BMT, averaged 0.2%, 9.2%, 30.7%, 58%, and 99.3% in groups 1 to 5, respectively. GVHD occurred as follows: groups 1 and 2, none; group 3, 1 case of GVHD; group 4, 7 cases of GVHD (of which 3 died); and group 5, 10 cases of GVHD (of which 6 died). The percentage of long-term CTA acceptance was 0%, 0%, 90%, 70%, and 40% in groups 1 to 5, respectively. The percentage of regulatory T cells was significantly lower in high-chimerism (≥ 20%, n = 15) than in low-chimerism (<20%, n = 5) rats that accepted CTA long-term . CONCLUSIONS The chimerism level correlated positively with GVHD occurrence and long-term CTA acceptance but correlated negatively with regulatory T-cell levels. Optimal chimerism for CTA acceptance through pre-CTA BMT and irradiation occurs at 20-50% at day 28 after BMT in the rat model.
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Affiliation(s)
- Jeng-Yee Lin
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Abstract
The face has functional and aesthetic importance. It represents the most identifiable aspect of an individual's physical being. Its role in a person's identity and ability to communicate can therefore not be overstated. The face also plays an important role in certain functional needs such as speech, communicative competence, eye protection, and emotional expressiveness. The latter function bears significant social and psychological import, because two thirds of our communication takes place through nonverbal facial expressions. Accordingly, the significance of reconstruction of the face is indisputable. Yet despite application of meticulous techniques and the development of innovative approaches, full functional and aesthetic reconstruction of the face remains challenging. This is because optimal reconstruction of specialized units of the face have to address both the functional and aesthetic roles of the face.
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Affiliation(s)
- Maria Siemionow
- Department of Plastic Surgery, The Cleveland Clinic, Cleveland, Ohio
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Greater efficacy of tolerance induction with cyclosporine versus tacrolimus in composite tissue allotransplants with less myeloablative conditioning. Plast Reconstr Surg 2011; 127:1141-1148. [PMID: 21364417 DOI: 10.1097/prs.0b013e3182043695] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Previous studies demonstrated that both cyclosporine and tacrolimus in combination with antilymphocyte globulin could facilitate mixed chimerism and induce tolerance to composite tissue allotransplants under partial myeloablative conditioning. The purpose of this study was to compare the efficacy of cyclosporine and tacrolimus. METHODS Brown-Norway and Lewis rats were used as composite tissue allotransplant donors and recipients, respectively. Cyclosporine groups I (n = 6), II (n = 9), and III (n = 5) received subcutaneous injection of 16 mg/kg cyclosporine (days 0 to 10); intraperitoneal injection of 5 mg of antilymphocyte globulin (days -1 and 10); and 0-, 200-, and 400-cGy total body irradiation (day -1), respectively. Tacrolimus groups IV (n = 6), V (n = 7), and VI (n = 8) received intraperitoneal injection of 1 mg/kg tacrolimus (days 0 to 10) and 5 mg of antilymphocyte globulin (days -1 and 10); and 0-, 200-, and 400-cGy total body irradiation (day -1), respectively. Recipients underwent hind-limb osteomyocutaneous flap composite tissue allotransplantation on day 0. Chimerism levels were determined 2 weeks after composite tissue allotransplantation, and acceptance was defined as complete survival of the composite tissue allotransplant to the endpoint of the experiment at 150 days. RESULTS Chimerism levels 2 weeks after composite tissue allotransplant averaged 3.4, 4.9, 29, 2.4, 4.9, and 16 percent composite tissue allotransplant, and acceptance rates were 0, 33.3, 80, 0, 0, and 13 percent in group I, II, III, IV, V, and VI, respectively. CONCLUSION Despite relatively late development for clinical use in transplantation, tacrolimus has not proved advantageous for composite tissue allotransplant acceptance and tolerance when compared with cyclosporine.
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Horner BM, Ferguson KK, Randolph MA, Spencer JA, Carlson AL, Hirsh EL, Lin CP, Butler PE. In vivo observations of cell trafficking in allotransplanted vascularized skin flaps and conventional skin grafts. J Plast Reconstr Aesthet Surg 2010; 63:711-9. [PMID: 19324598 PMCID: PMC2835845 DOI: 10.1016/j.bjps.2009.01.036] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2008] [Revised: 01/08/2009] [Accepted: 01/12/2009] [Indexed: 11/28/2022]
Abstract
The problem of allogeneic skin rejection is a major limitation to more widespread application of clinical composite tissue allotransplantation (CTA). Previous research examining skin rejection has mainly studied rejection of conventional skin grafts (CSG) using standard histological techniques. The aim of this study was to objectively assess if there were differences in the immune response to CSG and primarily vascularized skin in composite tissue allotransplants (SCTT) using in vivo techniques in order to gain new insights in to the immune response to skin allotransplants. CSG and SCTT were transplanted from standard Lewis (LEW) ad Wistar Furth (WF) to recipient transgenic green fluorescent Lewis rats (LEW-GFP). In vivo confocal microscopy was used to observe cell trafficking within skin of the transplants. In addition, immunohistochemical staining was performed on skin biopsies to reveal possible expression of class II major histocompatibility antigens. A difference was observed in the immune response to SCTT compared to CSG. SCTT had a greater density cellular infiltrate than CSG (p<0.03) that was focused more at the center of the transplant (p<0.05) than at the edges, likely due to the immediate vascularization of the skin. Recipient dendritic cells were only observed in rejecting SCTT, not CSG. Furthermore, dermal endothelial class II MHC expression was only observed in allogeneic SCTT. The immune response in both SCTT and CSG was focused on targets in the dermis, with infiltrating cells clustering around hair follicles (CSG and SCTT; p<0.01) and blood vessels (SCTT; p<0.01) in allogeneic transplants. This study suggests that there are significant differences between rejection of SCTT and CSG that may limit the relevance of much of the historical data on skin graft rejection when applied to composite tissue allotransplantation. Furthermore, the use of novel in vivo techniques identified characteristics of the immune response to allograft skin not previously described, which may be useful in directing future approaches to overcoming allograft skin rejection.
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Affiliation(s)
- Benjamin M. Horner
- Plastic Surgery Research Laboratory, Department of Surgery, WAC 435, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Plastic Surgery, Royal Free Hospital, University College London, Pond Street, Hampstead, London NW3 2QG, UK
| | - Kelly K. Ferguson
- Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Building 149-9019, 13th Street, CNY, Boston, MA 02129, USA
| | - Mark A. Randolph
- Plastic Surgery Research Laboratory, Department of Surgery, WAC 435, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Joel A. Spencer
- Center for Systems Biology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Alicia L. Carlson
- Center for Systems Biology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Erica L. Hirsh
- Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Building 149-9019, 13th Street, CNY, Boston, MA 02129, USA
| | - Charles P. Lin
- Center for Systems Biology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Peter E.M. Butler
- Department of Plastic Surgery, Royal Free Hospital, University College London, Pond Street, Hampstead, London NW3 2QG, UK
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Kulahci Y, Siemionow M. A New Composite Hemiface/Mandible/Tongue Transplantation Model in Rats. Ann Plast Surg 2010; 64:114-21. [DOI: 10.1097/sap.0b013e3181a20cca] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Siemionow M, Klimczak A. Advances in the development of experimental composite tissue transplantation models. Transpl Int 2010; 23:2-13. [DOI: 10.1111/j.1432-2277.2009.00948.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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BÅogowski W. Facial transplantation as an option in reconstructive surgery: no mountains too high? ANZ J Surg 2009; 79:892-7. [DOI: 10.1111/j.1445-2197.2009.05140.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Knobloch K, Rennekampff HO, Meyer-Marcotty M, Gohritz A, Vogt PM. [Organ transplantation, composite tissue allotransplantation, and plastic surgery]. Chirurg 2009; 80:519-26. [PMID: 19214462 DOI: 10.1007/s00104-008-1668-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Transplantations play an increasing role for plastic reconstructive surgeons. The increasing number of solid organ transplantations and the improved long-term survival rates lead to increased numbers of these patients also undergoing plastic and reconstructive procedures. Free flap transfer in solid organ transplant patients is feasible with no higher risk to both transplant function and postoperative complications than for nontransplant patients, even during immune suppression. Composite tissue allotransplantation (CTA) is an evolving field in plastic reconstructive surgery with hands, arms, partial faces, abdominal walls, and knee joints being transferred in clinical settings. However only an interdisciplinary approach using all available resources in highly selected patients after exhausting all other plastic reconstructive procedures is able to achieve reasonable results. The potential complications of long-term immune suppression and patient compliance have to be balanced with the expected and achieved functional result of CTA, whose procedures must be discussed as a potential tissue or organ transplantation, given the legal and logistic implications. The interdisciplinary cooperation of transplant surgeons, microsurgeons, psychologists, and ergo- and physiotherapists is mandatory to achieve successful CTA results.
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Affiliation(s)
- K Knobloch
- Plastische, Hand- und Wiederherstellungschirurgie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Deutschland.
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Abstract
Restoration of amputations and disfigurement are represented in ancient mythology, but the modern history of composite tissue allotransplantation begins with World War II injuries that generated seminal immunologic experiments by Medawar and co-workers. These studies led to the first successful human allografts in the 1950s by Peacock with composite tissue and Murray and co-workers with solid organs. Pharmacologic immunosuppression brought rapid growth of solid organ transplantation over the next 50 years, but composite tissue transplantation virtually disappeared. This evolution was judged to be a consequence of the greater antigenicity of skin, which that was insurmountable by the available immunosuppression. In the mid-1990s, progress in immunosupression allowed skin-bearing grafts, led by successful hand transplants, which produced a renaissance in composite tissue allotransplantation. Since then, graft types have expanded to over 10, and graft numbers to over 150, with success rates that equal or exceed solid organs. The field has emerged as one of the most exciting in contemporary medicine, although accompanied by substantial challenges and controversy. This paper reviews the origins and progress of this field, assessing its potential for future evolution.
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[Composite allotransplantation in the upper extremity: from research to clinical reality]. ACTA ACUST UNITED AC 2009; 28:67-73. [PMID: 19297231 DOI: 10.1016/j.main.2009.01.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Recent advancements in immunosuppression have made composite allotransplantation possible. To date, 38 hand allotransplantations have been performed in the world. Apart from the first case - amputated after voluntarily stopping the treatment- survival at 2-year follow-up has been 100%. After 2 years, 12 of the Chinese cases had to stop their treatment which led to complete loss of the transplanted parts. In 25 cases, results are known with a follow-up greater than 2 years. The transplanted patients all experienced one or more acute rejection episodes during the first postoperative year contrasting with only a 10% acute rejection rate following kidney transplantation. All these rejections were reversible with appropriate treatment. Extrinsic motor power was always restored, but intrinsic musculature only recovered in certain cases. Some sort of sensory discrimination was restored in 72% of the hands. All the patients had side effects related to immunosuppressive treatments, but none of these effects were life-threatening or impaired their quality of life. We think that composite allotransplantations should no longer be considered as clinical research and should be developed in accredited centres.
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Gordon C, Siemionow M, Zins J. Composite Tissue Allotransplantation: A Proposed Classification System Based on Relative Complexity. Transplant Proc 2009; 41:481-4. [DOI: 10.1016/j.transproceed.2009.01.025] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Muramatsu K, Kuriyama R, You-Xin S, Hashimoto T, Matsunaga T, Taguchi T. Chimerism studies as an approach for the induction of tolerance to extremity allografts. J Plast Reconstr Aesthet Surg 2008; 61:1009-15. [DOI: 10.1016/j.bjps.2007.12.082] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2007] [Accepted: 12/14/2007] [Indexed: 11/29/2022]
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Landin L, Cavadas PC, Gonzalez E, Rodriguez JC, Caballero A. Functional outcome after facial allograft transplantation in rats. J Plast Reconstr Aesthet Surg 2008; 61:1034-43. [DOI: 10.1016/j.bjps.2007.12.084] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2007] [Revised: 10/07/2007] [Accepted: 12/30/2007] [Indexed: 11/29/2022]
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Whitaker IS, Duggan EM, Alloway RR, Brown C, McGuire S, Woodle ES, Hsiao EC, Maldonado C, Banis JC, Barker JH. Composite tissue allotransplantation: a review of relevant immunological issues for plastic surgeons. J Plast Reconstr Aesthet Surg 2008; 61:481-92. [PMID: 18248779 DOI: 10.1016/j.bjps.2007.11.019] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2007] [Accepted: 11/16/2007] [Indexed: 12/22/2022]
Abstract
BACKGROUND Composite tissue allotransplantation of hand, facial and other tissues is now a clinical reality. The terminology, treatment principles, drug combinations, dosage schedules and mechanisms of the immunosuppression medications on which contemporary transplant surgery is based are unfamiliar to plastic surgeons and most healthcare providers outside the field of transplantation medicine. With this in mind, the purpose of this manuscript is to provide plastic surgeons with a comprehensive and understandable review of key immunological principles relevant to composite tissue allotransplantation. METHODS We present an overview of the immunological basis of composite tissue allotransplantation aimed at the plastic surgery readership, based on our own experience plus manuscripts sourced from MEDLINE, EMBASE, text books, ancient manuscripts and illustrations. RESULTS In this manuscript we provide the reader with a brief history of composite tissue allotransplantation (CTA), a concise description of the immunological terminology, treatment approaches, risks associated with immunosuppressive therapy, risk acceptance, and current research avenues relating to contemporary CTA. CONCLUSION Today, as transplant and reconstructive surgeons join forces to move hand and facial tissue allotransplantation into the clinical arena, it is important that plastic surgeons have an understanding of the major immunological principles upon which this new treatment is based.
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Affiliation(s)
- Iain S Whitaker
- Department of Surgery, University of Louisville, 511 South Floyd Street, 320 MDR Building, Louisville, KY 40202, USA
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Tuna EB, Topçuoglu N, Ilhan B, Gençay K, Kulekçi G. Staphylococcus aureus transmission through oronasal fistula in children with cleft lip and palate. Cleft Palate Craniofac J 2008; 45:477-80. [PMID: 18788867 DOI: 10.1597/06-247.1] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE To determine the presence of Staphylococcus aureus in a nasal flora and oral environment, the correlation between frequency of transmission of S. aureus and oronasal fistula size, and the pattern of methicillin resistance on S. aureus strains in children with cleft lip and palate (CLP). DESIGN Thirty-two CLP children with and without oronasal fistulas, ranging in age from 5 to 13 years were examined for oronasal fistula presence and size. Stimulated saliva samples and nasal swab samples were taken and investigated for S. aureus presence. S. aureus presence and counts were correlated with fistula presence and size. RESULTS Saliva samples showed statistical differences between the groups with and without oronasal fistulas with an area ranging from 0.80 to 28.26 mm2. The S. aureus counts were significantly higher (r = .535, p = .002) in saliva samples from children with larger oronasal fistula. The S. aureus count was not significantly different (r = -.013, p = .942) in nasal samples compared with oronasal fistula size. Methicillin resistance with disk-diffusion method was recorded as sensitive (> or =13 mm) in all S. aureus strains. CONCLUSIONS The results of this study indicate a positive correlation between fistula size and S. aureus transmission to one oral environment through oronasal fistulae, and a positive correlation between frequency of S. aureus transmission and fistula size. All S. aureus strains were sensitive to methicillin. These results may have implications for preventive treatment of CLP children.
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Affiliation(s)
- E Bahar Tuna
- Department of Pediatric Dentistry, Faculty of Dentistry, Istanbul University, Istanbul, Turkey.
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Abstract
Composite tissue allotransplantation holds a great potential for providing increased knowledge of anatomy and microsurgical experience for life-enhancing reconstructions. Many transplant cases around the world have made this a clinical reality at the present time. Composite tissue allotransplants contain multiple tissue types, including bone, muscle, vessels, nerves, skin, and immune cells and bear a huge antigenic load. Although immunosuppressive drugs are applied successfully to prevent allograft rejection, their side effects pose a barrier to worldwide use. Bone marrow therapy in many tolerance induction protocols, therefore, provides a guide to reaching the target of permanent immunotolerance. Multiple studies suggest that bone marrow is immunomodulatory and may facilitate allograft acceptance. In this review, bone marrow based therapy protocols of clinical and experimental models are presented in two major categories: solid organ and composite tissue transplantation.
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Affiliation(s)
- Maria Siemionow
- Department of Plastic and Reconstructive Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
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Abstract
Nerve allograft transplantation should be used for the repair of devastating peripheral nerve injuries that cannot be reconstructed through traditional means such as autologous nerve grafting or nerve transfer procedures. The risks of required systemic immunosuppression, although only temporary for nerve allograft recipients, preclude widespread use of this treatment modality. Translational research has led to several advancements in this field including the use of preoperative allograft cold preservation in University of Wisconsin organ preservation solution and inclusion of tacrolimus as part of the immunosuppressive regimen. Investigation of how to further diminish nerve allograft immunogenicity, speed neuroregeneration by use of agents such as tacrolimus, and promote preferential motor regeneration will further advance this field with the goal of restoring optimal function while minimizing patient morbidity.
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Affiliation(s)
- Ida K Fox
- Division of Plastic Surgery, Washington University School of Medicine, Saint Louis, Missouri
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36
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Anatomical and Technical Aspects of Harvesting the Auricle as a Neurovascular Facial Subunit Transplant in Humans. Plast Reconstr Surg 2007; 120:1540-1545. [DOI: 10.1097/01.prs.0000287992.28125.ce] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Brown CS, Gander B, Cunningham M, Furr A, Vasilic D, Wiggins O, Banis JC, Vossen M, Maldonado C, Perez-Abadia G, Barker JH. Ethical considerations in face transplantation. Int J Surg 2007; 5:353-64. [DOI: 10.1016/j.ijsu.2006.06.019] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2006] [Accepted: 06/21/2006] [Indexed: 11/28/2022]
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Abstract
In 1943, Gibson and Medawar opened the modern era of transplantation research with a paper on the problem of skin allograft rejection. Ten years later Billingham, Brent and Medawar demonstrated that it was possible to induce selective immune acceptance of skin grafts in mice, a state of tolerance. After over six decades, however, the precise mechanism of skin allograft rejection remains still ill-defined. Furthermore, it has not been possible to achieve reliably clinical tolerance allowing the widespread application of skin allotransplantation techniques. The first successful applications of skin allotransplantation have included the hand and face. However, complications from the chronic immunosuppression regimens limit the application of these techniques. Induction of tolerance to skin (and the other tissues in the allograft) would be the most effective way to overcome all these difficulties, but this is yet to be achieved reliably, stimulating some to look for other ways to surmount the current limitations. This paper summarizes alternatives to enlarge the scope of skin allotransplantation techniques, current understanding of mechanisms of skin rejection, and the utility and limitations of animal models used to study skin rejection and tolerance induction. Finally, manipulation strategies to achieve skin tolerance are outlined.
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Affiliation(s)
- Benjamin M Horner
- Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
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Shengwu Z, Qingfeng L, Hao J, Banich J, Kaiding F, Benson C, Huiyong W, Danning Z, Bing G, Qinxiu L, Lujia T, Tao Z, Yuping L, Tisheng Z. Developing a Canine Model of Composite Facial/Scalp Allograft Transplantation. Ann Plast Surg 2007; 59:185-94. [PMID: 17667414 DOI: 10.1097/sap.0b013e31802c79a5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The study developed a model of composite facial and scalp allograft transplantation in canines. Dog cadavers were used for anatomy study. Three types of autotransplantations and 2 types of allotransplantations were performed. Cyclosporin A and methylprednisolone or prednisone were given for immunosuppression. Two long-term-surviving dogs with autologous facial transplantation developed leakage of salivary secretions. In the allotransplantation group (n = 5), 1 dog presented rejection at 28 postoperative days but was successfully treated and survived long term (>402 days); 1 dog died of pulmonary infection at 29 postoperative days; 3 dogs survived (>252, >222, and >201 days). Serial electromyelogram studies revealed progressive improvement of the function of the orbicularis oculi muscle. The study indicated that the unilateral superior half of the composite facial and scalp, including one third of the inferior tarsal plate and palpebral conjunctiva (type IV flap) allograft transplantation model, was an ideal model for the study of facial allotransplantation.
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Affiliation(s)
- Zheng Shengwu
- Department of Plastic and Reconstructive Surgery, 9th Hospital, Shanghai Jiaotong University, Shanghai, China
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Tobin GR, Breidenbach WC, Pidwell DJ, Ildstad ST, Ravindra KV. Transplantation of the hand, face, and composite structures: evolution and current status. Clin Plast Surg 2007; 34:271-8, ix-x. [PMID: 17418676 DOI: 10.1016/j.cps.2007.01.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
This article reviews the world experience in the newly emerging field of composite tissue allotransplantation. These allografts contain multiple tissues that are usually musculoskeletal structures with a skin or epithelial surface, such as hand, facial structures, larynx, tongue, ear, knee/femur, abdominal wall, and penis. They represent a new transplantation field, with only a 10-year experience and just over 50 clinical cases. This review of the 10-year world experience found uniform technical success, immunologic biology, and immunosuppression regimens very similar to solid organ transplants, and success strongly correlated with adherence to guidelines for psychiatric screening, thorough preparation of patient and families, intense postoperative monitoring, and assurance of medication access. All failures reported have been caused by lapses in these parameters. This early experience shows a great potential for application of these new procedures to the most challenging reconstructive needs.
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Affiliation(s)
- Gordon R Tobin
- Division of Plastic Surgery, Department of Surgery, University of Louisville, Louisville, KY 40292, USA.
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Duhamel P, Bey E, Petit F, Cariou JL. [Experimental and clinical experience of composite tissues allotransplantation in reconstructive surgery]. ANN CHIR PLAST ESTH 2007; 52:399-413. [PMID: 17597279 DOI: 10.1016/j.anplas.2007.05.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2007] [Accepted: 05/17/2007] [Indexed: 12/22/2022]
Abstract
Composite tissue allotransplantation (CTA) is a new concept in reconstructive surgery to improve major physical defects with no current solution. Although not a life-saving procedure, tissue replacement by CTA offers great potential for improving quality of life but relies on lifelong immunotherapy. This new practice has become achievable with the refinement of microsurgical techniques, with experience gained from limb and scalp replantations, with the development of organ transplantation and the release of new immunosuppressive drugs. Experimental and clinical research made it possible. The first human cases of CTA proved the reality and the feasibility of the concept. While the early functional results of these allografts are encouraging, they will need to be assessed in the long-term, and development of less toxic - more efficient immonu-suppressive drugs will be a permanent requisite to the broadening of CTA. Although long-term outcome and potential adverse effects of chronic immunosuppression remain uncertain, as for organ transplantation, CTA is already a potential solution for some highly selected patients carrying physical disabilities such as large facial defects and bilateral hand amputation.
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Affiliation(s)
- P Duhamel
- Service de chirurgie plastique et maxillofaciale, hôpital d'instruction des Armées Percy, 101, avenue Henri-Barbusse, 92141 Clamart cedex, France.
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Abstract
The functional and aesthetic outcome following application of conventional reconstructive procedures or prosthetic materials is not satisfactory, especially in patients who have severe deformities and disabilities. Since the first successful hand transplantation in France in 1998, composite tissue allograft transplantation has gained a great deal of interest in the field of plastic surgery. It is obvious that composite tissue allograft transplantation will improve patients' life quality, but this might be at the expense of decreasing life expectancy. Currently, the main obstacle for composite tissue allograft transplantation is the use of life-long immunosuppression therapy because of their well-known side effects. In addition, the ethical, social, and psychologic issues are raised when discussing face transplantation. The long-term results of the recently performed partial face transplantations will be critical to judge the future applications of partial or total face transplantation.
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Affiliation(s)
- Maria Siemionow
- Department of Plastic Surgery A/60, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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Barker JH, Stamos N, Furr A, McGuire S, Cunningham M, Wiggins O, Brown CS, Gander B, Maldonado C, Banis JC. Research and Events Leading to Facial Transplantation. Clin Plast Surg 2007; 34:233-50, ix. [PMID: 17418674 DOI: 10.1016/j.cps.2006.10.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Facial transplantation has long captured the interest and imagination of scientists, the media, and the lay public. Facial transplantation could provide an excellent alternative to current treatments for facial disfigurement caused by burns, trauma, cancer extirpation, or congenital birth defects. This article discusses the major technical, immunologic, psychosocial and ethical hurdles that have been overcome to bring facial transplantation from an idea to a clinical reality by providing the reader with a chronologic overview of the research and events that have led this exciting new treatment into the clinical arena.
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Affiliation(s)
- John H Barker
- Department of Surgery, 511 South Floyd Street, 320 MDR Building, University of Louisville, Louisville, KY 40202, USA.
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Landin L, Cavadas PC, Carrera A, Fontdevila J, Navarro C. Human face/scalp alloflap harvesting technique. Plast Reconstr Surg 2007; 119:1114-5. [PMID: 17312531 DOI: 10.1097/01.prs.0000253537.05026.3f] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Gander B, Brown CS, Vasilic D, Furr A, Banis JC, Cunningham M, Wiggins O, Maldonado C, Whitaker I, Perez-Abadia G, Frank JM, Barker JH. Composite tissue allotransplantation of the hand and face: a new frontier in transplant and reconstructive surgery. Transpl Int 2007; 19:868-80. [PMID: 17018121 DOI: 10.1111/j.1432-2277.2006.00371.x] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Each year an estimated 7-million people in the USA need composite tissue reconstruction because of surgical excision of tumors, accidents and congenital malformations. Limb amputees alone comprise over 1.2 million of these. This figure is more than double the number of solid organs needed for transplantation. Composite tissue allotransplantation in the form of hand and facial tissue transplantation are now a clinical reality. The discovery, in the late 1990s, that the same immunotherapy used routinely in kidney transplantation was also effective in preventing skin rejection made this possible. While these new treatments seem like major advancements most of the surgical, immunological and ethical methods used are not new at all and have been around and routinely used in clinical practice for some time. In this review of composite tissue allotransplantation, we: (i) outline the limitations of conventional reconstructive methods for treating severe facial disfigurement, (ii) review the history of composite tissue allotransplantation, (iii) discuss the chronological scientific advances that have made it possible, (iv) focus on the two unique clinical scenarios of hand and face transplantation, and (v) reflect on the critical issues that must be addressed as we move this new frontier toward becoming a treatment in mainstream medicine.
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Affiliation(s)
- Brian Gander
- Department of Surgery, University of Louisville, KY 40202, USA
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Predictive value and limitations of animal models for human transplantation: do we need more models for facial transplantation? Transplant Rev (Orlando) 2006. [DOI: 10.1016/j.trre.2006.05.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Discussion. Plast Reconstr Surg 2006. [DOI: 10.1097/01.prs.0000204894.96853.d8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
Recent advances in the field of reconstructive surgery and immunology resulted in increased interest in composite tissue allograft (CTA) transplantation. Up to date, more than 50 CTA transplants have been reported in humans. A significant number of experimental studies on CTA transplants under different protocols of tolerance-inducting strategies have been reported in small-animal models. There is however, a limited number of CTA transplants performed in nonhuman primates. To reach the ultimate clinical success in CTA transplantation, more experimental studies on tolerance induction in nonhuman primates are needed to apply these immunomodulatory protocols to CTA transplants in humans. In this review, strategies for tolerance induction in the nonhuman primate model in solid organ and CTA transplants are presented in 3 major categories: chimerism induction, T-cell depletion, and costimulatory receptor blockade.
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Affiliation(s)
- Maria Siemionow
- Department of Plastic Surgery, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
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