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Clinical Considerations in Facial Transplantation

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Clinical Considerations in Facial Transplantation CLINICAL CONSIDERATIONS IN FACIAL TRANSPLANTATION by Anthony Renshaw A thesis submitted in fulfilment of the requirements of University College London for the degree of Doctor of Medicine January 2011 Department of Plastic and Reconstructive Surgery, Academic Division of Surgical & Interventional Sciences, University College London 1 Declaration I, Anthony Renshaw, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author. …………………………………………………………. 2 Abstract Facial transplantation has emerged as the next step on the reconstructive ladder for severe facial disfigurement. Clinical issues surrounding facial tissue donation are examined, comprising pre-transplant facial vessel delineation; pre-operative aesthetic matching; and attitudes towards donation. An anatomical study of 200 consecutive facial and transverse facial vessels was performed using colour Doppler ultrasound. Facial vessels were measured at three landmarks and their branching pattern documented. The facial artery main branch was detected at the lower mandibular border in 99.5% of cases, the accompanying facial vein in 97.5%. The transverse facial artery was present in 75.5% of cases, the vein found in 58%. When the facial artery was undetectable, there was transverse facial artery dominance. When the facial vein was absent it was replaced with a transverse facial vein. This provides valuable pre-operative information regarding vessel status. A quantitative eleven- point skin tonal matching scheme is described using digital analysis of facial imagery. Attitudes towards tonal mismatch in facial and hand transplantation are examined in two representative skin types. There was more scope for skin tonal mismatching in skin tone 2 (slightly tanned white) than in skin tone 6 (light golden brown) participants. Tonal mismatches were more tolerated in facial than in hand transplant simulations in both groups. More acceptable donor tonal groups exist for males than females. Targeted matching of skin tone is thus required. Attitudes and beliefs of 170 transplant professionals were examined. Areas of concern included the organ retrieval process; impact on the retrieval team and donor family. In-depth analysis of a transplant donor focus group was performed; provision of information, post- transplant contact, and post-retrieval donor facial appearance was deemed important. A method of fabricating a donor-specific artificial prosthesis within the time frame of 3 facial graft retrieval is described. Finally, a method of framing the informed consent process is described. 4 To my wife Rashi for all her support, patience and understanding 5 Statement I researched and wrote Chapter 1, collaborating with Dr Henry Stephens on aspects of tissue typing. I designed and performed the ultrasound studies, analysed the data and wrote Chapter 2, under the guidance of Mr Peter Butler. Dr Leslie Berger provided me with ultrasound training for this aspect of the study. Dr Kerrie Whitwell assisted in recruiting volunteers for the study. I designed and carried out all the studies in Chapter 3 and 4, including the creation of transplant simulations, questionnaire design, data collection and analysis. Statistical advice was obtained from Professor Paul White. Mr David Bishop assisted me in the photographic image procurement. In Chapter 5, I assembled and described the raw data from the meetings with the transplant co-ordinators obtained by Mr Peter Butler, Miss Fidelma Murphy and Dr Alex Clarke. Miss Fidelma Murphy participated in analysis of the data. The donor focus group data was obtained by Dr Alex Clarke; I analysed and described this data. I designed and carried out Chapter 6, with technical assistance from Mr Teerathraj Chooneea. All projects fulfilled the requirements of the Helsinki Agreement and received prior ethical approval either from the University College London Hospitals (UCLH) Ethics Committee or the Ethics Committee of the Royal Free Hospital, London. All human subjects gave prior written consent to publication of data within this thesis, which specifically included the publication of identifiable images. 6 List of Publications and Thesis Work Outcomes Renshaw A , Whitwell KA, Berger L, Butler PE. The use of colour Doppler ultrasound in the assessment of vessels for facial transplantation. Annals of Plastic Surgery 2007; 59 (1):82-86 Renshaw A , Clarke A, Diver AJ, Butler PE. Facial transplantation: a real option in facial reconstruction? International Journal of Surgery 2006; 4(2):94-96 Renshaw A , Chooneea T, Clarke A, Butler PE. An artificial prosthesis to reconstruct donor defects following facial transplantation. Clinical Transplantation 2007; 21 (4):574-576 Renshaw A , Clarke A, Diver AJ, Ashcroft RE, Butler PE. Informed consent for facial transplantation. Transplant International 2006; 19 : 861-867 Clarke A, Murphy F, Brough V, Renshaw A , Butler PE. Transplant co-ordinators’ attitudes to facial transplantation. Progress in Transplantation 2007; 17 (3):1-3 Renshaw A , Clarke A, Brough V, White P, Guzdar E, Bishop D, Butler PE. Skin tonal matching in facial and hand allotransplantation. 7th International Symposium on Composite Tissue Allotransplantation, Seefeld, Austria, 2007 Renshaw A , Whitwell KA, Berger L, Butler PE. The use of colour Doppler sonography in the assessment of vessels for facial transplantation. British Association of Plastic Reconstructive and Aesthetic Surgeons Winter Meeting, Royal College of Surgeons of England, London, UK, 2006 Diver AJ, Renshaw A , Clarke A, Butler PE. The pre-operative protocol for facial transplantation. Appearance Matters 2 ‘Developing Theory & Practice,’ The Assembly Rooms, Bath, UK, 2006 7 List of Abbreviations ANOVA Analysis of Variance CDC Complement-Dependent Lymphocytotoxic Cm Centimetres CMV Cytomegalovirus CTA Composite Tissue Allotransplantation EBV Epstein-Barr Virus FA Facial Artery FAMM Facial Artery Musculomucosal FV Facial Vein HBV Hepatitis B Virus HCV Hepatitis C Virus HHV Human Herpes Virus HIV Human Immunodeficiency Virus HLA Human Leukocyte Antigen HTLV Human T-cell Lymphotropic Virus Hz Hertz ICU Intensive Care Unit IgG Immunoglobulin G JPEG Joint Photographic Experts Group LC Lateral Canthus MHC Major Histocompatibility Complex MHz Megahertz MIC MHC Class I Chain-Related 8 Mm Millimetres MSE Mean Standard Error PLS Psychosocial Levels System PTLD Post-Transplantation Lymphoproliferative Disorder RGB Red, Green, Blue RNA Ribonucleic Acid SD Standard Deviation ST Skin Tone TERS Transplantation Evaluation Rating Scale TIFF Tagged Image File Format TFA Transverse Facial Artery TFV Transverse Facial Vein UCLH University College London Hospitals UVA Ultraviolet A 9 Table of Contents Declaration.................................................................................................................... 2 Abstract ......................................................................................................................... 3 Statement ...................................................................................................................... 6 List of Publications and Thesis Work Outcomes ...................................................... 7 List of Abbreviations ................................................................................................... 8 Table of Contents ....................................................................................................... 10 List of Figures ............................................................................................................. 14 List of Tables .............................................................................................................. 21 Acknowledgements .................................................................................................... 23 Chapter 1 .................................................................................................................... 24 1. The Evolution of Facial Transplantation ..................................................... 24 1.1. Facial Disfigurement and its Sequelae ...................................................... 24 1.2. Facial Reconstruction ................................................................................ 26 1.3. The History of Composite Tissue Allotransplantation .............................. 27 1.4. The Recent History of Human Facial Transplantation .............................. 28 1.5. Minimizing Rejection in Facial Transplantation ....................................... 31 1.5.1. Human Leucocyte Antigen Matching in Organ Transplantation ....... 31 1.5.2. HLA Matching in CTA ...................................................................... 33 1.5.3. HLA Matching in CTA Animal Models ............................................ 33 1.5.4. HLA Matching in Human CTA Trials ............................................... 35 1.5.5. Crossmatching .................................................................................... 38 1.5.6. Blood Group Matching....................................................................... 43 1.6. The Matching of Infectious Disease Status ............................................... 44 1.6.1. Hepatitis and HIV..............................................................................
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