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Penile Allotransplantation for Total Phallic Loss Due to Ritual Circumcision: Proof of Concept

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Penile Allotransplantation for Total Phallic Loss Due to Ritual Circumcision: Proof of Concept Penile allotransplantation for total phallic loss due to ritual circumcision: Proof of concept A van der Merwe MR Moosa Penile allotransplantation for total phallic loss due to ritual circumcision: Proof of concept André van der Merwe Presented in fulfillment of the requirements for the degree of Doctor of Philosophy Division of Urology Faculty of Medicine and Health Sciences Stellenbosch University South Africa Primary supervisor Professor MR Moosa Department of Medicine Faculty of Medicine and Health Sciences Stellenbosch University South Africa December 2020 Stellenbosch University https://scholar.sun.ac.za TABLE OF CONTENTS PAGE 1. Declaration, Acknowledgments and Summary. ............................................................. 2 2. Doctoral Office approval .......................................................................................... 7 3. Human Research Ethics approval ........................................................................... 8 4. General Introduction ............................................................................................... 10 5. Chapter 1. Penile allotransplantation for penis amputation following ritual circumcision: a case report with 24 months of follow-up…………………………….17 6. Update on the status of the first penile transplant recipient at six years and six months ............................................................................................ 28 7. Chapter 2. Lessons learned from the world's first successful penis allotransplantation ........................................................................................ 32 8. Chapter 3. Penis allotransplantation for penis amputation following ritual circumcision: Report of a second case with 40 months follow-up ................. 39 9. Chapter 4. Ethical and societal challenges in penis transplantation ....................................................................................................... 55 10. Chapter 5. Living with someone else’s penis: The lived experiences of two South African penile allograft recipients ............................................................... 75 11. Chapter 6. Penis transplantation: A review ........................................................... 98 12. Conclusion ............................................................................................................ 132 13. Addendum A. Book chapter: Penile transplantation: The last frontier in penile reconstruction ....................................................................................................... 136 14. Addendum B. Book chapter: The role of penile transplantation after penis cancer surgery ................................................................................................................. 144 15. Addendum C. Rebuttal. In response to an argument against penile transplantation ...................................................................................................... 155 16. Addendum D. Plenary and sub-plenary conference proceedings reated to the dissertation....................................................................................................158 1 Stellenbosch University https://scholar.sun.ac.za DECLARATION By submitting this dissertation electronically, I declare that the entirety of the work contained therein is my own, original work, that I am the sole author thereof (save to the extent explicitly otherwise stated), that reproduction and publication thereof by Stellenbosch University will not infringe any third party rights and that I have not previously in its entirety or in part submitted it for obtaining any qualification. This dissertation includes five original papers published in peer-reviewed journals or books and four unpublished publications. I am the first author of all nine publications and contributed 60 -100% of all the papers. The development and writing of the papers (published and unpublished) were the principal responsibility of myself. Signed by André van der Merwe Date: 9 August 2020 Copyright ©2020 Stellenbosch University All rights reserved. 2 Stellenbosch University https://scholar.sun.ac.za ACKNOWLEDGEMENTS I thank my supervisor, Professor Rafique Moosa, for his time and effort to majorly contribute to the success of this project, all the publications we produced, and this doctoral dissertation. I am also very deeply indebted to the Western Cape Government and Tygerberg Hospital, in particular Dr André Muller, Dr Kurt Maart, Dr Dimitri Erasmus, and Dr Beth Engelbrecht for allowing these cases to be managed as ‘clinical incidents’ at Tygerberg Academic Hospital. I am grateful to Professor Jimmy Volmink, Dean at the Faculty of Medicine and Health Sciences (FMHS), for his wonderful support. I had the immense privilege of working with a wonderful research team that consisted of junior and senior Urologists/Transplant Surgeons (Dr Amir Zarrabi, Dr Zamira Keyser, Dr Pieter Spies, Dr Farzana Cassim, Dr Hilgard Ackerman, Dr Danelo Du Plessis, Dr Louw-Waldi Vlok, Dr Rupert Pretorius, Dr Dedan Opondo, Dr Talal Al- Qaoud, Dr Guglielmo Mantica, Dr Stephan Kruger, Dr Triegaardt Viljoen, Dr Siseko Silolo, Dr Gerard Grobler and Dr Alex Szpytko); Nephrologists (Dr Johan Nel, Dr Karla Bezuidenhout and their registrars); Plastic Surgeons (Prof Frank Graewe, Dr Alex Zuhlke and their registrars), Psychologist (Mr. Colin Mitchell), Ethicist (Dr Nicola Barsdorf) and transplant coordinators (Sr Bertha Bailey and Sr Coetzee). Sr Bailey cared incredibly much for the patients and became known as their ‘mother’. Finally, none of our teamwork would have been successful without the dedication and support of the nursing staff in Ward A7. I thank the Media Office at Stellenbosch University (Me Ronel Bester and Me Wilna Stassen) for the professional manner in which they handled the press releases and media storm that followed the announcement of the first penis transplant; the qualitative team, Dr Chantelle Scott and Dr Yoesrie Toefy for helping with the interviews, transcribing and making sense of the data, Dr Heidi van Deventer for her support in copy editing, writing up and submitting all our publications, and Dr Karis Moxley for her incredible science writing perspicacity. I thank Dr Zamira Keyser for her incredible support during this project. I thank my international friends and colleagues who supported me more than many realise during this project: 3 Stellenbosch University https://scholar.sun.ac.za Professor Andreas Gross (Hamburg, Germany) for support from the start of the project; we were dining out the evening just before entering the operating theatre for transplanting the first case in this dissertation. Professor Alex Bachmann (Basel, Switzerland) for teaching me innovation and stating, “if you’re not the first in medicine to do something, find something else.” Professor Richard Santucci (Austin, Texas) for teaching me the principles of reconstructive surgery and stating, “you’re going to do the work anyway, you can just as well make a big splash!.” Professor Francisco Martins (Lisbon, Portugal) for teaching me reconstructive surgery principles and also inviting me to write two chapters in authoritative textbooks of which he is he is the editor. Professor Gernot Bonkat (Basel, Switzerland) for starting this journey at the beginning with me and supporting me all the way to the end. Then, a special word of thanks to our patients, the poorest of the poor and most discriminated against group of humans I am aware of, for bravely participating and seeing me through the difficult times when the project appeared to stall, by saying the words that I shall never forget ‘you’ve got to help us, doc.’ Lastly and mostly, I thank my three lovely boys, Henry (17), Theuns (14), and André Jnr. (12), whose loveliness transcends all, for accompanying me on this challenging journey. I dedicate this dissertation to them. 4 Stellenbosch University https://scholar.sun.ac.za SUMMARY Ritual circumcision is an important tradition practiced by many African cultures in South Africa. These circumcisions occasionally result in severe penile mutilations, and many men are rendered aphallic as a result. Phalloplasty represents conventional treatment for these cases. However, this type of surgery has many challenges, which make it an undesirable treatment option, particularly in low- to middle-income settings, such as South Africa. Therefore, we considered alternatives to phalloplasty that were technically feasible and cost-effective. Penile allotransplantation was largely unexplored as a therapeutic option at the inception of the study in 2011, and it was uncertain if a penis transplant would restore all the functions of a normal penis. We undertook a proof of concept investigation and explored the feasibility of penile transplantation in our resource- constrained hospital setting. This is a prospective mixed-methods observational study. Following Human Research Ethics Committee approval, ritual circumcision related aphallic patients attending the Urology Clinic at Tygerberg Academic Hospital were invited to participate. Informed consent was obtained following the intense briefing of candidates over several visits. Various blood tests were conducted, after which selected patients were waitlisted. The first donor became available in December 2014, and the most suitable recipient was selected based on blood group matching and a negative T-cell cross match. The donor penis was retrieved and transplanted by using the same basic principles of vascularised free
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