Composite tissue allograft

from Wikipedia, the free encyclopedia

Under the composite tissue allografts (engl. For Various tissue transplantation or composite tissue transplant ) or shortened CTA refers to a transplant of composite fabrics from a dead person (donor) to another (recipient) as part of a transplant . It is therefore a special form of allotransplantation . The individual tissue types are different, but connected to one another and form a single part of the body. This is e.g. B. the case with one hand. In the case of a CTA, the tissue transplanted in this way is also called composite tissue allograft .

Since some parts of the body, such as the face, arm, leg, etc., can only be reconstructed poorly or not at all after loss and no adequate replacement can be found in prostheses , the CTA represents a real option for some patients in restoring their full functionality. Transplant surgery has thus advanced into a field in which it is no longer just a question of saving lives, but also of improving the quality of life.

The CTA can deliver good and appealing results, especially when compared to conventional methods, when e.g. B. is about giving the patient a new face. However, it is also controversial - the main point of criticism is the lifelong use of drugs that suppress the immune system ( immunosuppressants ), although the CTA is not a vital measure - and is therefore only carried out in strictly selected patients.

Historical

The history of composite tissue allografts is actually older than that of organ donation itself.

According to legend, the brothers Cosmas and Damian succeeded in replacing a rotten leg with that of a dead man in the early Middle Ages. In the 15th and 16th centuries, this story inspired numerous painters to take pictures that represented the first ever transplant. Over a thousand years later, the Italian doctor Gaspare Tagliacozzi describes the transplant of a slave's nose to his master. Finally, Alexis Carrel experimented with the transplantation of dog legs as early as 1906, but encountered massive problems with rejection , so that all dogs died.

The first attempt at a human hand transplant was made in 1964 in Ecuador using azathioprine and steroids for immunosuppression, but the hand had to be removed after two weeks due to progressive rejection. It was only with the development of more modern immunosuppressants in the 1980s and 1990s that it was possible to better control the body's rejection reactions. With the then cyclosporin  A, however, it was still impossible to transplant allografts (the transplanted organ), which consisted of composite tissue with skin. In 1997, a successfully prevented rejection reaction in a CTA was finally reported by using a therapy consisting of tacrolimus , mycophenolate mofetil (MMF) and prednisone for immunosuppression. This was followed by the world's first successful hand transplant in France on September 23, 1998, and two further transplants within a further year, namely on January 23, 1999 in Louisville (Kentucky) and on September 21, 1999 in Guangzhou (China). On February 2, 2001, however, the first hand transplanted (France) had to be removed again due to difficulties with immunosuppression.

The first bilateral (bilateral) hand transplantation continued in 2000, the first allogeneic face transplantation in 2005 and the first bilateral arm transplantation in 2008 in Munich. Since then, over 65 hand and 15 partial face transplants have been performed worldwide (as of 2011).

In animal experiments , even head transplants were successful ; Vladimir Petrovich Demichow is considered a pioneer in this regard.

Method and procedure

for a special procedure for the individual types of transplantation see:

Preoperative procedure - conditions for a CTA

With a composite tissue allograft, as with any operation, you always have to weigh the prospects against the existing risk. CTAs that have been carried out to date have therefore only been carried out in strictly selected patients for whom the exhaustion of all conservative and conventional surgical treatment options did not lead to an appealing result. The suitability (also the psychological) of the patient is essential for a good result with the CTA, especially with a view to keeping the probability of rejection due to psychopathological reactions as low as possible.

A transplant always poses a certain psychological challenge to the patient; he has to accept the transplant as a new part of himself, even though it comes from another person. This is particularly difficult with CTA, as in most cases the graft is visible and likely has a major impact on the patient's self-image. This is especially true of a face transplant , of course. Applicants for a CTA therefore often have to undergo intensive psychological screening and are psychologically prepared for the upcoming transplant in numerous discussions.

Furthermore, a potential candidate for a CTA must be in good physical condition. This is necessary on the one hand to survive the procedure without major complications, but on the other hand to be able to live well despite lifelong immunosuppression.

K. Knobloch and others therefore defined the following inclusion and exclusion criteria for (partial) face transplantation in adults:

Inclusion criteria Exclusion criteria
total bilateral destruction of the orbicularis oculi muscle (eye ring muscle) or the orbicularis oris muscle (sphincter muscle of the mouth) Unstable psychological situation of the patient
Evaluation (assessment) by a committee of experts Immediate reconstruction after the injury
Psychiatric evaluation Addictions (e.g. alcohol)
Existing health insurance cancer

Furthermore, these points were described as possible indications for a CTA:

  • Unilateral or bilateral amputation of the upper extremity at the level of the wrist, forearm or upper arm
  • possibly elongated brachial plexus defects
  • defects in the facial area that cannot be reconstructed in any other way
  • missing or otherwise reconstructable abdominal wall defects
  • Penis transplant
  • vascularized knee transplant
  • Larynx transplant
  • Amputation of the feet or lower legs on both sides

Operational approach

Composite tissue allografts are not simple procedures, usually take several hours and require several teams to operate at the same time. The surgical procedure for the various forms of CTA can differ from one another, for example in the case of a hand transplant it is necessary to connect the bones of the donor and recipient. In any case, knowledge of microsurgery is required for a CTA , which makes this type of transplantation possible in the first place, since nerves , blood vessels and tendons have to be connected to one another. The preparation of the body part on the recipient and on the donor can easily pose challenges for the surgeon: The corresponding areas are often anatomically complex and require a high degree of precision. The procedure also carries the risk of high blood loss in the recipient.

Postoperative procedure / result

The patient initially remains in the intensive care unit for a few days before he can be transferred to a normal ward. This is followed by a one or two week hospital stay, but this number can fluctuate widely and depends on many different factors. During this time there is also psychological and physiotherapeutic care. After their discharge, the transplant recipients have to come to the hospital for routine examinations, among other things to rule out a rejection reaction. These routine visits will become less and less frequent over time - if no complications arise.

An immediate function of the new body part is not possible with a CTA. The axons of all nerve cells in the transplant die after the operation at the latest, only the myelin sheaths remain , so that the nerve cells of the body first have to grow into the new part of the body. This happens at a rate of about one millimeter per day, so that it takes about three to four months for a face transplant and two years for an arm transplant before a feeling is restored in the entire body part. Physiotherapy, electrotherapy, and neurocognitive treatment are used, depending on the procedure, to help the patient get used to their new body part.

Together with the nerve cells, new blood vessels are also formed in the transplanted tissue ( collateralization ), so that the blood supply improves over time, as recent studies on three patients have shown. Surgeons hope that this knowledge will help plan future transplants.

It was also shown that the motor cortex in the brain re a new hand integrate can. In this way, up to 75% of the functionality of a normal face or a normal hand can be achieved. This very good functional result in connection with an appealing aesthetic enables the patient to (almost) completely return to social life and avoid most psychological problems.

Immunosuppression

In principle, the same immune suppressing drugs are used for CTAs as for other transplants. That would be a calcineurin inhibitor, MMF or rapamycin and steroids. In fact, it has not yet been confirmed that the dose of the medication should be significantly increased.

In the case of CTA, however, you have to pay closer attention to a possible rejection reaction, since the skin, as a barrier to the outside world, is equipped with a particularly aggressive immune system. For example, the body fights a new hand two out of three times. However, such a rejection reaction can usually be controlled with cortisone. A 2005 study also suggests that skin is at greater risk of rejection. Markers for the extent of rejection are the expression of the genes CD68, Foxp3 and INDO ( indolamine-2,3-dioxygenase ) and the amount of CD4 / 8, which increases with the severity of the rejection. The intercellular adhesion molecule-1 and E-selectin also correlate with the rejection. In contrast, the rejection reaction can evidently be prevented experimentally in animal experiments with a combination of efomycin M, antithymocyte globulin and tacrolimus .

There is no systematic recording or compilation of the most important points and treatment options in this context, so that individual reactions must be made on a case-by-case basis.

How exactly a composite tissue allograft behaves in the long term is still unknown. As the axons grow, a feeling in the new body part will slowly re-establish itself and the functionality will presumably continue to improve, but these successes may be reversed by an immune reaction of the body and rejection occurs. In organ transplants, it has been found that 10 to 15 years after the operation, the function of the organ is slowly lost in some patients. The exact causes of this phenomenon, known as chronic rejection , are still unknown - attempts to explain it range from immunological problems to the toxicity of the immunosuppressive drugs themselves. It is not clear whether this form of rejection can also occur with CTAs. On the other hand, it is also possible that a kind of acceptance of the new body part can occur and the dose of the immunosuppressive drugs can be reduced.

For the CTA it is therefore crucial to introduce new immunosuppressants with fewer side effects or, if possible, to induce tolerance to the allograft and thus to be able to do without these drugs entirely . One approach of recent research is the treatment of dendritic cells in vitro with the chemotherapeutic agent mitomycin C , which leads to a lack of activation of the T cells and thus to tolerance induction. Treatment with mitomycin C therefore has an immunosuppressive effect, albeit a minor one, which needs further research to be improved.

Advantages and opportunities

The main advantages of CTA are that it can regain lost functionality while avoiding the usual disadvantages of conventional methods. Classic reconstructive surgery has the decisive disadvantage that, for the best results in terms of function and aesthetics, original tissue must actually be used to reconstruct the relevant area. However, this is often not possible, either because the tissue was completely destroyed or because it was simply never present (e.g. in the case of malformations ). In these cases it is therefore necessary either to replicate tissue that has been destroyed with the help of the body's own tissue or to provide the necessary replacement with prostheses. However, some parts of the body cannot be adequately replaced with prostheses and, in turn, with some autografts the result is not aesthetically pleasing. In particular, when reconstructing the face, only very poor results can be achieved when working with the body's own tissue that comes from other body regions, and the patients get a “ mask-like ” appearance. Patients with such disfigured faces often suffer from their appearance for the rest of their lives and have massive psychological problems. In contrast, the CTA in the form of a (partial) face transplant manages to achieve good to very good results. This can also be seen in the example of Isabelle Dinoire , a French woman who was operated on in 2005 and who was able to smile again just a year after the operation.

Cons and criticism

The main point of criticism of the CTA is the fact that it does not mean a life-saving measure for the patient, but that immunosuppressive medication must be taken for life if a rejection reaction is not to occur. However, depending on the preparation, these drugs have numerous different undesirable side effects , e.g. B. diabetes , high blood pressure, deterioration in kidney function and the like. a., and continue to increase the risk of developing cancer or infections.

Another problem is what happens to the patient in the event of rejection. With Isabelle Dinoire, for example, the facial scar was enlarged in the course of the transplant in order to be able to use the donor tissue better. It would then be even more distorted. The deceased donor is also disfigured - especially in the case of a face transplant. This can be a great psychological burden for the affected family and relatives and requires a very sensitive approach on the part of the transplant team. But there are also concerns about the psyche of the recipient: It is argued that living with the face of a dead stranger can be too great a psychological burden.

Web links

Individual evidence

  1. ↑ Karsten Knoblock, Hans-Günther Machens, Peter M. Vogt: Composite Tissue Allotransplantation (CTA) - is it really a pure tissue donation? at the 128th Congress of the German Society for Surgery , 3. – 6. May 2011, Munich. doi: 10.3205 / 11dgch422
  2. ↑ Nina Ofer (coordination), Nicole Schorr: Research group "Composite Tissue Allotransplantation 1" ( Memento of the original from May 18, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.bgu-ludwigshafen.de
  3. ^ K. Knoblock, PM Vogt: The reconstructive sequence of the 21st century . In: The surgeon. May 2010, Springer Verlag. doi: 10.1007 / s00104-010-1917-3
  4. ^ Miracle of the Black Leg: Honorable Act or Exploitation . ( Memento of the original from May 22, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 4th March 2014.  @1@ 2Template: Webachiv / IABot / www.theroot.com
  5. ↑ Olaf Wieser and others: Anatomy - the miracle of human beings · Bones · Muscles · Organs · Nervous system . Neuer Kaiser Verlag, Klagenfurt, new edition 2006, p. 10
    Title of the Italian-language original edition: Atlante de Anatomia. Giunti Gruppo Editoriale, Firenze, 2000.
  6. ↑ MT Gnudi et al: The sympathetic slave. In: The Life and Times of Gaspare Tagliacozzi. Zeitlin and Ver Brugge, Los Angeles CA 1976.
  7. ↑ U. Schulte: Nobel Prize in Medicine 2012: Alexis Carrel. Universal Lexicon, 2012.
  8. ↑ Stefan Schneeberger, Luis Landin, Jerzy Jableki, Peter Butler, Christoph Hoehnke, Gerald Brandacher, Emmanuel Morelon: Achievement and challenges in composite tissue allotransplantation. In: Transplant International. May 9, 2011, doi: 10.1111 / j.1432-2277.2011.01261.x
  9. ↑ John H. Barker, Cedric G. Francois, Johannes M. Frank, Claudio Maldonado: Composite Tissue Allotransplantation . In: Transplant Forum. March 15, 2002.
  10. ^ CG Francois, WC Breidenbach, C. Maldonado, TP Kakoulidis, A. Hodges, JM Dubernard, E. Owen, G. Pei, X. Ren, JH Barker: Hand transplantation: comparisons and observations of the first four clinical cases . In: Microsurgery . tape 20 , no. 8 , 2000, ISSN  0738-1085 , p. 360-371 , PMID 11150985 .
  11. ↑ Nicola Siegmund-Schultze: Transplantation Medicine: For the first time complete arms transplanted . In: Deutsches Ärzteblatt. 2008.
  12. ↑ a b M. Kumnig et al .: Composite Tissue Allotransplantation . ( Memento of the original of July 13, 2015 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. In: Wiener Klinisches Magazin. 03/2011, Springer Verlag. @1@ 2Template: Webachiv / IABot / www.springermedizin.at
  13. ^ Wolfgang Neundorf: Science and Criticism - Criticism of Science , as of April 12, 2009.
  14. ↑ Mary Amanda Dew, Robert L Kormos, Loren H Roth, Srinivas Murali, Andrea DiMartini, Bartley P Griffith: Early post-transplant medical compliance and mental health predict physical morbidity and mortality one to three years after heart transplantation . April 1998. In: The Journal of Heart and Lung Transplantation. June, 1999. doi : 10.1016 / S1053-2498 (98) 00044-8
  15. ↑ Hand Transplantation and Psychiatric Issues , handtransplant.com, Kentucky One Health Jewish Hospital · Chrisine M. Kleinert Institute for Hand and Microsurgery · Kleinert Kutz Hand Care Center · University of Louisville.
  16. ↑ Christina Berndt: The face of the other . In: Süddeutsche Zeitung . December 19, 2008.
  17. Jump up ↑ MM Klapheke, C. Marcell, G. Taliaferro, B. Creamer: Psychiatric assessment of candidates for hand transplantation. In: Microsurgery. 2000. doi : 10.1002 / 1098-2752 (2000) 20: 8 <453 :: AID-MICR18> 3.0.CO; 2-Y
  18. ↑ Information for potential Hand Transplant Patients , handtransplant.com, Kentucky One Health Jewish HospitalChrisine M. Kleinert Institute for Hand and MicrosurgeryKleinert Kutz Hand Care CenterUniversity of Louisville.
  19. ↑ For Patients: Composite Tissue Allotransplantation , The American Society for Reconstructive Transplantation.
  20. ↑ a b K. Knobloch, HO Rennekampff, M. Meyer-Marcotty, A. Gohritz, PM Vogt: Organ transplantation, tissue transplantation and plastic surgery. In: The surgeon. Springer Medizin Verlag, June 2009, doi: 10.1007 / s00104-008-1668-6
  21. ↑ Bohdan Pomahac, Julian Pribaz, Donald Annino, Dennis P. Orgill, Christian Sampson, Elof Eriksson, Stephanie Caterson, Yoon Chun: Face Allotransplantation for treatment of a high voltage midfacial injury . Brigham and Women's Hospital, Boston MA, American Association of Plastic Surgery, 89th Annual Meeting.
  22. ↑ 3D Images of Hand Transplant. handtransplant.com, Kentucky One Health Jewish Hospital Christine M. Kleinert Institute for Hand and Microsurgery Kleinert Kutz Hand Care Center University of Louisville
  23. ↑ Hand Transplant Surgical Procedure Animation. handtransplant.com, Kentucky One Health Jewish Hospital Christine M. Kleinert Institute for Hand and Microsurgery Kleinert Kutz Hand Care Center University of Louisville
  24. ↑ Jesse Selber, Richard Andressy, John Holcomb: Composite Tissue Allotransplantation (CTA) . MD Anderson Cancer Center, University of Texas.
  25. ^ Before, During and After a Facial Transplant . ( Memento of the original from May 25, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Brigham and Womens Hospital, March 17, 2014. @1@ 2Template: Webachiv / IABot / www.brighamandwomens.org
  26. ↑ Our Hand and Arm Transplant Services . ( Memento of the original from May 25, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Brigham and Womens Hospital, Feb. 14, 2013. @1@ 2Template: Webachiv / IABot / brighamandwomens.org
  27. ↑ Our Services . ( Memento of the original from May 25, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Brigham and Womens Hospital, March 17, 2014. @1@ 2Template: Webachiv / IABot / brighamandwomens.org
  28. ↑ Simone W. Glaus, Philip J. Johnson, Susan E. Mackinnon: Clinical Strategies to Enhance Nerve Regeneration in Composite Tissue Allotransplantation. In: Hand Clinics. November 2011, PMC 3212838 (free full text) doi: 10.1016 / j.hcl.2011.07.002
  29. ↑ Susanne Donner: That's life with the face of the dead . Die Welt , December 9, 2013.
  30. ↑ Christina Berndt: Now I'm ready . Süddeutsche Zeitung , May 17, 2010.
  31. ↑ Anna Fischhaber: I will not give it away anymore . Süddeutsche Zeitung , May 17, 2010.
  32. ↑ Blood vessels re-branch after a face transplant . In: Luxemburger Wort. 5th December 2013.
  33. ↑ Martin Kumnig, Gerhard Rumpold, Annemarie Weissenbacher, Johann Pratschke, Gerald Brandacher, Stefan Schneeberger, Theresa Hautz: Composite Tissue Allotransplantation . In: Wiener Klinisches Magazin. June 2011, print- ISSN  1869-1757 , online- ISSN  1613-7817 , doi: 10.1007 / s00740-011-0361-4
  34. ↑ Laurent Lantieri, Jean-Paul Meningaud, Philippe Grimbert, Frank Bellivier, Jean-Pascal Lefaucheur, Nicolas Ortonne, Marc-David Benjoar, Philippe Lang, Pierre Wolkenstein: Repair of the lower and middle parts of the face by composite tissue allotransplantation in a patient with massive plexiform neurofibroma: a 1-year follow-up study . In: The Lancent. Elsevier, August 2008.
  35. ↑ Bruce Swearingen, Kadiyala Ravindra, Hong Xu, Shengli Wu, Warren C. Breidenbach, Suzanne T. Ildstad: The Science of Composite Tissue Allotransplantation. In: transplant. September 15, 2008. PMC 2629383 (free full text) doi: 10.1097 / TP.0b013e318184ca6a
  36. ↑ H. Madani, S. Hettiaratchy, A. Clarke, PEM Butler: Immunosuppression in an emerging field of plastic reconstructive surgery: composite tissue allotransplantation . In: Journal of Plastic, Reconstructive and Aesthetic Surgery. March 2008.
  37. ↑ Christina Berndt: They look like they used to . Sueddeutsche.de, May 17, 2010.
  38. ↑ Jean Kanitakis, Palmina Petruzzo, Denis Jullien, Lionel Badet, Maria Clara Dezza, Alain Claudy, Marco Lanzetta, Nadey Hakim, Earl Owen, Jean-Michel Dubernard: Pathological score for the evaluation of allograft rejection in human hand (composite tissue) allotransplantation , European Journal of Dermatology.
  39. ↑ T. Hautz, B. Zelger, J. Grahammer, C. Krapf, A. Amberger, G. Brandacher, L. Landin, H. Müller, MP Schön, P. Cavadas, AWP Lee, J. Pratschke, R. Margreiter , S. Schneeberger: Molecular Markers and Targeted Therapy of Skin Rejection in Composite Tissue Allotransplantation. In: American Journal of Transplantation. March 26, 2010. doi: 10.1111 / j.1600-6143.2010.03075.x
  40. ↑ Linda C. Cendales, Allan D. Kirk, J. Margaret Moresi, Phillip Ruiz, David E. Kleiner: Composite Tissue Allotransplantation: Classification of Clinical Acute Skin Rejection . February 15, 2006, In: Transplantation Journal. doi: 10.1097 / 01.tp.0000185304.49987.d8
  41. ^ François Petit, Alicia B. Minns, Jean-Michel Dubernard, Shehan Hettiaratchy, WP Andrew Lee: Composite Tissue Allotransplantation and Reconstructive Surgery. In: Annals of Surgery. January 2003, PMC 1513974 (free full text).
  42. ↑ Patrick Illinger: Interview with Uwe Koch-Gromus: Other arms are better than none . In: Süddeutsche Zeitung . May 17, 2010.
  43. ↑ Jurij Kiefer: Influence of mitomycin C treated mononuclear cells of the peripheral blood on the immune reaction after composite tissue allograftation . (PDF) Doctoral thesis in surgery, doctoral supervisor: G. Germann
  44. ^ Brian Gander, Charles S. Brown, Dalibor Vasilic, Allen Furr, Joseph C. Banis Jr, Michael Cunningham, Osborne Wiggins, Claudio Maldonado, Iain Whitaker, Gustavo Perez-Abadia, Johannes M. Frank and John H. Barker: Composite tissue allotransplantation of the hand and face: a new frontier in transplant and reconstructive surgery . (PDF) In: Transplant International. ISSN  0934-0874 , doi: 10.1111 / j.1432-2277.2006.00371.x
  45. ↑ Face transplants 'on the horizon' . BBC News, Nov. 27, 2002.
  46. ^ Elie Levine, Linda Degutis, Thomas Pruzinsky, Joseph Shin, John A. Persing: Quality of Life and Facial Trauma: Psychological and Body Image Effects . In: Annals of Plastic Surgery. May 2005.
  47. ^ Organ donation Sueddeutsche.de, May 25, 2012.
  48. ↑ Esther Vögelin: Hand Transplantation - Fiction or Reality? In: Therapeutic review. 2011, Verlag Hans Huber, doi: 10.1024 / 0040-5930 / a000237
  49. ↑ Face transplant : The patient is fine . Focus Online, December 17, 2008.
  50. ↑ Which side effects can occur with immunosuppression? ( Memento of the original from May 18, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Transplant Center Campus Benjamin Franklin, Charité 2015.  @1@ 2Template: Webachiv / IABot / transplantation-cbf.charite.de
  51. ↑ Jörg Isert: The man behind the new smile  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. , Stern, April 4, 2007.@1@ 2Template: Toter Link / www.stern.de  
  52. ↑ Christian J. Vercler: Ethical Issues in Face Transplantation , In: AMA - Journal of Ethics. May 2010.
  53. ^ Charles S. Brown, Brian Gander, Michael Cunningham, Allen Furr, Dalibor Vasilic, Osborne Wiggins, Joseph C. Banis Jr., Marieke Vossen, Claudio Maldonado, Gustavo Perez-Abadia and John H. Barker: Ethical Considerations in Face Transplantation , In: International Journal of Surgery. October 2007. doi: 10.1016 / j.ijsu.2006.06.019