- Email: [email protected]
Is Mexico Ready for Face Transplantation?
Is Mexico Ready for Face Transplantation? M. Iglesiasa,*, P. Butróna, A.I. Osuna-Leala, L. Abarca-Pereza, M.J. Sosa-Ascencioa, M.A. Moran-Romeroa, A.U. Cruz-Reyesa, F.J. Pineda-Gutierreza, D.A. Leon-Lopeza, M.N. García-Alvareza, J. Alberub, M. Vilatobab, R.P. Leal-Villalpandoc, J. Zamudio-Bautistac, V.M. Acosta-Navac, and J. Gonzalezd a
Department of Plastic Surgery, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; Department of Transplantation, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; c Department of Anesthesiology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; and d Department of Psychiatry, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico b
ABSTRACT With the limitations of surgical reconstructive procedures, the growing number of gunshot wounds, burns, and work accidents in Mexico that result in complex facial deformities leaves only 1 optiondface transplantation. The National Institute of Medical Sciences and Nutrition “Salvador Zubiran” (INCMNSZ) has performed transplants since 1971. We at INCMNSZ undertook the 1st bilateral upper-limb transplantation in Latin America in 2012. We are willing to continue in this manner toward conducting face transplantation at our institute. To this end, we identified and solved various challenges. The 1st challenge was acceptance and inclusion of vascularized composite allotransplantation (VCA) within general Mexican health law and approval of the face transplantation procedure. Subsequently, the health ministry provided a license to INCMNSZ to perform the procedure. The 2nd challenge concerned who would pay for the procedure. The costs will be paid by the patient (1st-party payer), social security institutions (2nd-party payers), and the health ministry (3rd-party payer). The 3rd challenge was to maintain ongoing surgical training of the team using cadavers. The fourth challenge was to locate donors; toward this end, we developed a campaign for promoting face donation in social media, making a comic book, and training organ and tissue coordinators to further VCA. Thus, INCMNSZ has the legal, administrative, medical, and surgical wherewithal to accomplish face transplantation.
S
INCE the 1st renal transplantation in 1954, performed by Joseph Murray [1], to the 1st full-face transplantation in 2004 in France, a new era of vascularized composite allotransplantation (VCA) has emerged. VCA includes skin, muscles, vessels, bones, tendons, fat tissue, and nerves [2], and it presents new challenges for immunologic therapy. The growing demand for organ transplants in Mexico requires the development of new systems of donation and transplantation as well as specific policies focused on ethical and legal support for universal access for patients [3]. However it is important to establish that because VCA does not involve vital organs, it represents a medical challenge for the recipients as well as regarding donor selection and acceptance by the donors’ families [4]. In 2012, the 1st upper-limb transplantation in Latin America [5] was performed at the National Institute of
Medical Sciences and Nutrition “Salvador Zubiran” (INCMNSZ). We performed the case of a 52-year-old man who suffered a high-voltage electrical burn requiring amputation of his upper limbs. He underwent bilateral proximal forearm transplantation in Mexico. At 3-year follow-up, immunosuppressive treatment has not led to metabolic, oncologic, or infectious complications. The extrinsic muscles of the wrist and digits have good function. Although the intrinsic muscles demonstrated electrical activity 15 months after surgery, clinically they are nonuseful. After 3 years, hand function is sufficient to allow the patient to grasp lightweight and medium-sized objects. The patient’s Disabilities of the Arm, Shoulder, and Hand score *Address correspondence to Martin Iglesias, MD, Monte de Antisana 47, Jardines en la Montaña, Mexico DF, CP 14210. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.05.020
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1998
Transplantation Proceedings, 47, 1998e2002 (2015)
FACE TRANSPLANTATION IN MEXICO
1999
Table 1. Reasons for the 29 Face Transplantations Reported to Date Injury
No of Patients
Gunshot wound Burns Electric burn Animal attack Neurofibromatosis Chemical burn Cancer Vascular tumor Closed trauma Industrial accident Not reported
10 4 3 3 3 1 1 1 1 1 1
improved from 50.00 points to 30.83 points, and his Hand Transplantation Score System rating is good, at 69/73 (right/ left) out of 100. The patient and his family are very satisfied with the functional and esthetic outcomes. To perform that transplantation, administrative, legal, medical, and surgical procedures were implemented. The INCMNSZ is making efforts to continue this line of work and aims to carry out face transplantation. Face transplantation has the goal of full restoration of facial functions (ventilation, phonation, and mastication). It represents an opportunity for patients who have suffered complex facial injuries that can not be restored by traditional reconstructive techniques to reestablish their social and professional lives [2,4,6,7]. We strongly believe that with the proper indications, face transplantation is the best option for facial restitution [8]. Nevertheless, it is important to evaluate the risk-benefit ratio because immunosuppressive therapy involves an increasing risk for malignancy, infections, and systemic toxicity [2,9]. To date, 29 facial transplantation procedures have been reported around the world [10]. The reasons for performing the face transplantation are presented in the Table 1. Each time, they have been conducted using more complex VCA and achieved better results [9,10].
In the United States, 478,400 cases of gunshot wounds (GSWs) were reported in 2011, of which 97.4% were nonfatal [11]. This type of injury accounts for 35% of the cases for facial transplantation. In 2013, Moye-Elizalde et al reported 1,281 patients with GSWs in Ciudad Juarez, Chihuahua, Mexico; of those, 9.09% had complex facial injuries [12]. The Mexican Institute of Social Security (IMSS) reported 46,666 accidents at the workplace in 2013 that affected the face and neck regions; among those, there were 927 cases of wounds, 982 trauma, 1,341 burns, and 8 amputations [13]. The IMSS defines amputation as extensive mutilation of the maxilla, mandible, nose, and soft tissue representing 90%e100% of the face [14]. The incidence of GSWs is increasing in Mexico. GSWs involve burns and injuries, which can lead to severe psychiatric impact and several facial deformities that may compromises the patients’ vision, ventilation, and swallowing and lead to considerable economic losses. We therefore support facial transplantation as a promising therapy for selected patients in Mexico. ADVANTAGES OF INCMNSZ FOR FACIAL TRANSPLANTATION
The INCMNSZ has been evolved in organ transplantation program since 1967 [3]. The 2nd kidney transplantation and the 1st liver transplantation in Mexico were performed in the INCMNZ [15,16]. Since then, the solid organ transplantation program has been continuous and permanent. This experience has allowed establishing the Vascularized Composite Allotransplants program. Consequently, the 1st bilateral forearm transplantation was performed in 2012 [5]. Today, the INCMNSZ has the experience to conduct a face transplant program [Fig 1]. CHALLENGES IN ESTABLISHING A FACIAL TRANSPLANTATION PROTOCOL
During the past 10 years of research, we at INCMNSZ have had the following difficulties regarding the implementation of a face transplant program.
Fig 1. History of transplantation in Mexico since 1st renal transplantation. Abbreviations: IMSS, Mexican Institute of Social Security; INCMNSZ, National Institute of Medical Sciences and Nutrition “Salvador Zubiran.”
2000
IGLESIAS, BUTRÓN, OSUNA-LEAL ET AL
Table 2. Cost Analysis of Face Transplantation in Different Countries Aspects
USA
France
Mexico*
Pre-transplantation evaluation Surgery Peri-transplantation supplies Post-transplantation follow-up and treatment for 1 year Total
$206,646 $79,625 $153,268 $74,236
$18,029 $84,861 $18,674 $39,383
$6,309 $1,741 $40,000 $37,737
$513,775
$160,949
$84,787
Note. The costs are all in United States dollars (USD). *Probable costs.
Journal published a new regulationdthe General Law on Transplantationdthat defines VCA as “a complex tissue used in transplantation, including musculoskeletal tissue, by means of vascular anastomosis and applied to the extremities and face” [18]. Thereafter the Protocol of Vascularized Composite AllotransplantationdFace was approved on June 26, 2014, by the Health Secretary, CENATRA, and INCMNSZ. With these new regulations, the upper extremities and face are managed under the same conditions as solid organs. Second Challenge: Various Aspects and Economic Difficulties With Face Transplants
First Challenge: Legal and Ethical Policies in Mexico
The Aguascalientes Document outlines the controversies surrounding the establishment of transplant programs in Latin America and the Caribbean [17]. Nevertheless, the marked increase in the number of patients awaiting donors has led to the unification of criteria and proceedings toward ensuring the accessibility, transparency, and quality of these procedures in this region. It is necessary that the basic bioethical issues be fulfilled: dignity, beneficence, integrity, nonmaleficence, caution and vulnerability, autonomy, responsibility, and local justice. Moreover, the growing demand for organ transplants has obliged Mexico to develop systems that promote and enable donation and transplantation. Toward providing universal access, Mexico has also promoted specific policies framed in an ethical and legal context that consider the common good [17]. However, Mexico lacks policies about VCA, so we assumed the task of initiating a process for creating policies regarding the legalization of such transplants. At the beginning of our upper-limb transplantation program, we found that Mexico possessed no legal regulations regarding VCA. As a result, INCMNSZ, through the Subcommittee of Composite Tissue Transplantation (SCOTTCO) and the National Transplantation Center (CENATRA), had to undertake administrative and juridical actions to define such a procedure. On March 26, 2014, the Federation Official
A face transplant program requires financial support [19]. Transplant programs in the United States are funded primarily by the Department of Defense [6]. In Mexico, the face transplant program will be financed on a tripartite basis: 1) the health ministry; 2) such institutions of social medical security as the IMSS and Institute for Social Security and Services for State Employees; and 3) the patient. At INCMNSZ, patients are classified into 7 levels according to their incomes. Level I involves the lowest charges for the patient and receives the highest subsidy. With increasing level, the charges for the patient become higher and the subsidy lower. With this system, facial transplantation can be performed because patients receive a subsidy from the health ministry (3rd-party payer), which ranges from 0 to 96% of the costs. The costs involve the following: 1) pre-transplantation evaluationdlaboratory costs, imaging studies, and specialist consultation; 2) inpatient costsdsurgical procedure, intensive care unit charges for 1 week and 1 month of hospital stay. Institutions of social medical security (2nd-party payer) cover the costs of immunosuppressive therapy for induction, long-term maintenance, and drugs necessary in case of acute rejection, complications such as infections, or metabolic alterations. Finally, the patient (1st-party payer) covers some costs, such as medication, transportation, and splints. It is also important to note that the Carlos Slim Foundation and the Life
Table 3. Recipient Selection Criteria 1. Any sex, race, skin tone, and ethnicity. 2. Ages 18e60 years. Patients with different ages will be evaluated by SCOTTCO. 3. No medical problems and/or coexisting serious psychologic issues that contraindicate the procedure. 4. Damage/trauma/deficit or facial deformities that represent >25% of the facial surface and compromise the functionality of the deep structures or include medial structures (eyelids, nose, lips), whose repair is impossible, not favorable, or unsatisfactory by means of the usual techniques of reconstruction. 5. Desire to improve their quality of life. 6. No oncologic diseases, or remission >10 years. Patients with previous solid organ transplantation will be evaluated by SCOTTCO. 7. Negative serology for HIV, HBV, and HCV. 8. No reliance on addictive substances (1 year of abstinence). 9. Capability to afford the immunosuppressive treatment and/or Institute of Social Security support 10. Negative cross-match with the donor and panel reactive antibodies <30%. Patients with other immunologic characteristics will be valued by SCOTTCO. 11. Basic anatomic elements to ensure nerve and vascular anastomosis (artery/vein facial and/or transverse facial transplants for partial, and external carotid for total face transplants; facial nerve, trigeminal, supraorbital, infraorbital, and branches of the mental nerve). 12. Complete knowledge of the benefits and risks of the procedure, which will be ratified with the signing of informed consent. Abbreviations: SCOTTCO, Subcommittee of Composite Tissue Transplantation; HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus.
FACE TRANSPLANTATION IN MEXICO
2001
Table 4. Recepient Exclusion Criteria 1. Active infections. 2. Conditions with high cardiovascular risk or autoimmune diseases. 3. Renal insufficiency (rate of creatinine clearance <60 mL/min, serum creatinine >1.5 mg/100 mL). 4. Psychologic disorders (body dysmorphic disorder), not controlled psychiatric disorders. 5. Presence of malignant tumors. Patients with facial deficits secondary to radical resection of tumors of the head and neck will be evaluated by SCOTTCO. 6. Financial insufficiency or lack of Social Security support 7. Lack of family support. 8. Unrealistic expectations on the treatment. 9. Use of addictive or illegal substances. 10. Pregnancy or desire of pregnancy in the 1st year after transplantation. Abbreviation: SCOTTCO, Subcommittee of Composite Tissue Transplantation.
and Transplant Association provide financial support for original cutting-edge research projects, and they have made an agreement with INCMNSZ to provide donations for the face transplant program. Secondary surgeries also will be financed on a tripartite basis as just described. All of these costs are clarified with the patient and the authorities and signed in the informed consent before the patient is signed on to the waiting list. Based on our upper-limb transplantation experience, we calculated the face transplantation costs as follows: 1) pretransplantation stage: $6,309 (values are in United States dollars throughout), including specialist evaluation, laboratory costs, and imaging; 2) peri-transplantation stage: $40,000, including medical supplies, transfusion procedures, intensive care unit stay for 1 week, and hospital stay for 1 month; 3) surgical procedure: $1,741; and 4) posttransplantation stage: $37,737, including specialist followup, laboratory costs, imaging, and immunosuppressive treatment, which covers induction treatment ($10,355) and maintenance for 1 year ($15,658). The total amount is USD $85,787. Without subsidy, this amount is contrasted with
that for Siemionow et al’s [19] and Lantieri et al’s [20] programs (Table 2). A Level III patient, receiving a 64% subsidy and full coverage for immunosuppressive medication, would have to pay $20,895 for the 1st year. Third Challenge: Capacity of Multidisciplinary Team
Face transplantation is not a routine procedure in any hospital. It therefore demands the assembly, training, and education of a multidisciplinary team so that the transplant can be conducted in optimal fashion. We requested the assistance of the National Autonomous University of Mexico to allow us to practice our surgical approach on cadavers to perfect our techniques and be prepared for any difficulties that might occur. Our multidisciplinary team includes plastic surgeons, transplant surgeons, infectologists, psychiatrists, social workers, anesthesiologists, and others. In this way, it is intended that INCMNSZ will be able to achieve the best possible results and confer the greatest benefits for the recipient. Fourth Challenge: Finding Donors
Following the drawing up of the health ministry’s new guidelines relating to transplantation, SCOTTCO assumed the task of establishing the criteria for inclusion and exclusion for both recipients and donors. Those criteria are described elsewhere [6,20,21] and listed in Tables 3e5. One disadvantage with INCMNSZ is the absence of a trauma unit. That limits the search and identification of patients with complex wounds or burns that require face transplants. Therefore, SCOTTCO focuses on broadcast media and social networks to inform the general public about face transplants. The efforts include providing information about patients worldwide who have undergone face transplants, the benefits and limitations of this procedure, the requirements for recipient selection, and recipient benefits in terms of functional and psychologic factors toward achieving social and professional reintegration and improving the recipient’s quality of life. SCOTTCO has developed a comic to raise public awareness about the
Table 5. Donor Selection Criteria 1. Brain death, proven in the same way as with any donor, with hemodynamic stability. 2. Multiorgan donor. 3. No systemic diseases and/or that affect the local anatomy and/or function of the face (sepsis unresolved, active TB disease, viral encephalitis, any malignancy, craniofacial deformities, neuropathy, etc). 4. Written consent of the responsible direct family, obtained through the persons accredited by CENATRA, clearly stating that facial tissue will be removed, partially or fully, including components of skin, muscle, and bone depending on the case. 5. The donor must have anatomic similarity in appearance to the receiver (sex, color, texture, distribution of body hair, dimensions, etc). 6. The age of the donor must be compatible in viability and function with the receiver, 10 years younger (to 18 years) to 10 years older. 7. The dimensions of the face donated should be approximately equal to those of the receiver on the basis of the head circumference, with a variation of 4%. 8. Seronegativity for HBV, HCV, syphilis, brucellosis, and HIV. 9. Blood type equal or compatible to the receiver. 10. Face donated with anatomic integrity without traumatic and/or surgical history. 11. History of no use of IV drugs, tattoos, and piercings in the past 6 months. Abbreviations: TB, tuberculosis; CENATRA, National Center of Transplants; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IV, intravenous.
2002
benefits of the face transplant program toward promoting face donation. This campaign has come about through governmental institutions and Mexican associations of general medicine, orthopedics, and plastic surgery nationwide toward promoting face transplantation as a feasible, effective, and reliable therapeutic alternative in the country. To promote a growing number of donors, CENATRA and the National Autonomous University of Mexico have included VCA (upper-extremity and face transplantation) in their Graduate Program for Coordinators of Organs and Tissues for Transplantation Purposes. In addition, CENATRA has instructed our team’s junior staff as national transplantation coordinators; they are certified to deal with problems related to preparing donors’ families in the donation process. There are currently 6 national transplantation coordinators, and they are able to deal with the challenge of face transplantation. INCMNSZ has made agreements with the Chihuahua State’s Central Hospital to expand the network to locate face donors. CONCLUSION
There is currently little knowledge about VCA in Mexico. In the development of our face transplant program, we have accomplished the following goals: encouraged the Mexican health ministry to establish official guidelines for VCA, created a multidisciplinary interagency team trained in this type of transplantation, set up campaigns to promote face donation, and trained specialists for organ and tissue donation purposesdspecifically for the face and upper extremities. INCMNSZ is prepared to attain the goals of evaluating likely receptors with complex facial injuries and performing face transplantation in Mexico in less than 5 years’ time. REFERENCES [1] Merrill JP, Murray JE, Harrison JH, et al. Successful homotrasplantation of the human kidney between identical twins. JAMA 1956;160:27e82. [2] Smeets R, Rendenbach C, Birkelbach M, et al. Face transplantation: on the verge of becoming clinical routine? Biomed Research Int 2014;2014:907272.
IGLESIAS, BUTRÓN, OSUNA-LEAL ET AL [3] Secretaria de Salud. [Action program: transplants]. Mexico. 1st ed. 2001. Spanish. [4] Losee JE, Fletcher DR, Gorantla VS. Human facial allotransplantation: patient selection and pertinent considerations. J Craniofac Surg 2012;23:260e4. [5] Iglesias M, Butrón P, Alberú-Gómez J, et al. [The importance of not remaining with folded arms: upper extremity transplantation]. Cir Gen 2013;35(Suppl 2):S133e8. Spanish. [6] Bueno EM, Diaz-Siso JR, Pomahac B. A multidisciplinary protocol for face transplantation at Brigham and Women’s Hospital. J Plast Reconstr Aesthet Sure 2011;64:1572e9. [7] Infante-Cossio P, Barrera-Pulido F, Gomez-Cia T, et al. Facial transplantation: a concise update. Med Oral Patol Oral Cir Bucal 2013;18:e263e71. [8] González-García I, Lyra-Gonzalez I, Medina-Preciado D, et al. Face transplant: is it feasible in developing countries? J Craniofac Surg 2013;24:309e12. [9] Khalifian S, Brazio PS, Mohan R, et al. Facial transplantation: the first 9 years. Lancet 2014;384:2153e63. [10] Fischer S, Kuekelhaus M, Pauzenberger R, et al. Functional outcomes of face transplantation. Am J Transplant 2015;15:220e33. [11] Planty M, Truman JL. Firearm violence, 1993-2011. Washington, DC: Bureau of Justice Statistics, US Department of Justice; 2013. [12] Moye-Elizalde GA, Ruiz-Martinez F, Suarez-Santamaria JJ, et al. [Epidemiology of gunshot wounds at Ciudad Juarez, Chihuahua General Hospital]. Acta Ortop Mex 2013;27:221e35. Spanish. [13] Instituto Mexicano del Seguro Social. Salud en el trabajo. [Statistical review 2013]. México: IMSS; 2013. Chapter VI. Spanish. [14] Ley Federal del Trabajo. Diario oficial de la federación 1970. México. Last update November 30, 2012. [15] Peña JC. [Renal transplant history in the INCMNSZ (1966)]. Rev Invest Clin 2005;57:120e3. Spanish. [16] Diliz H, Orozco H, Kershenobich D, et al. [Liver transplantation in Mexico. Report of the first successful case]. Rev Gastroenterol Mex 1991;56:33e8. Spanish. [17] Baquero A, Alberu J. [Ethical challenges in transplant practice in Latin America: the Aguascalientes Document]. Nefrologia 2011;31:275. Spanish. [18] Secretaría de Salud. [General Health Law Regulation: Transplantation]. México DF: Diario Oficial de la Federación; March 26, 2014. Spanish. [19] Siemionow M, Gatherwright J, Djohan R, et al. Cost analysis of conventional facial reconstruction procedures followed by face transplantation. Am J Transplant 2011;11:379e85. [20] Lantieri L, Hivelin M, Audard V, et al. Feasibility, reproducibility, risks and benefits of face transplantation: a prospective study of outcomes. Am J Transplant 2011;11:367e78. [21] Siemionow M, Gordon CR. Overview of guidelines for establishing a face transplant program: a work in progress. Am J Transplant 2010;10:1290e6.
Department of Plastic Surgery, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; Department of Transplantation, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; c Department of Anesthesiology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; and d Department of Psychiatry, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico b
ABSTRACT With the limitations of surgical reconstructive procedures, the growing number of gunshot wounds, burns, and work accidents in Mexico that result in complex facial deformities leaves only 1 optiondface transplantation. The National Institute of Medical Sciences and Nutrition “Salvador Zubiran” (INCMNSZ) has performed transplants since 1971. We at INCMNSZ undertook the 1st bilateral upper-limb transplantation in Latin America in 2012. We are willing to continue in this manner toward conducting face transplantation at our institute. To this end, we identified and solved various challenges. The 1st challenge was acceptance and inclusion of vascularized composite allotransplantation (VCA) within general Mexican health law and approval of the face transplantation procedure. Subsequently, the health ministry provided a license to INCMNSZ to perform the procedure. The 2nd challenge concerned who would pay for the procedure. The costs will be paid by the patient (1st-party payer), social security institutions (2nd-party payers), and the health ministry (3rd-party payer). The 3rd challenge was to maintain ongoing surgical training of the team using cadavers. The fourth challenge was to locate donors; toward this end, we developed a campaign for promoting face donation in social media, making a comic book, and training organ and tissue coordinators to further VCA. Thus, INCMNSZ has the legal, administrative, medical, and surgical wherewithal to accomplish face transplantation.
S
INCE the 1st renal transplantation in 1954, performed by Joseph Murray [1], to the 1st full-face transplantation in 2004 in France, a new era of vascularized composite allotransplantation (VCA) has emerged. VCA includes skin, muscles, vessels, bones, tendons, fat tissue, and nerves [2], and it presents new challenges for immunologic therapy. The growing demand for organ transplants in Mexico requires the development of new systems of donation and transplantation as well as specific policies focused on ethical and legal support for universal access for patients [3]. However it is important to establish that because VCA does not involve vital organs, it represents a medical challenge for the recipients as well as regarding donor selection and acceptance by the donors’ families [4]. In 2012, the 1st upper-limb transplantation in Latin America [5] was performed at the National Institute of
Medical Sciences and Nutrition “Salvador Zubiran” (INCMNSZ). We performed the case of a 52-year-old man who suffered a high-voltage electrical burn requiring amputation of his upper limbs. He underwent bilateral proximal forearm transplantation in Mexico. At 3-year follow-up, immunosuppressive treatment has not led to metabolic, oncologic, or infectious complications. The extrinsic muscles of the wrist and digits have good function. Although the intrinsic muscles demonstrated electrical activity 15 months after surgery, clinically they are nonuseful. After 3 years, hand function is sufficient to allow the patient to grasp lightweight and medium-sized objects. The patient’s Disabilities of the Arm, Shoulder, and Hand score *Address correspondence to Martin Iglesias, MD, Monte de Antisana 47, Jardines en la Montaña, Mexico DF, CP 14210. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.05.020
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1998
Transplantation Proceedings, 47, 1998e2002 (2015)
FACE TRANSPLANTATION IN MEXICO
1999
Table 1. Reasons for the 29 Face Transplantations Reported to Date Injury
No of Patients
Gunshot wound Burns Electric burn Animal attack Neurofibromatosis Chemical burn Cancer Vascular tumor Closed trauma Industrial accident Not reported
10 4 3 3 3 1 1 1 1 1 1
improved from 50.00 points to 30.83 points, and his Hand Transplantation Score System rating is good, at 69/73 (right/ left) out of 100. The patient and his family are very satisfied with the functional and esthetic outcomes. To perform that transplantation, administrative, legal, medical, and surgical procedures were implemented. The INCMNSZ is making efforts to continue this line of work and aims to carry out face transplantation. Face transplantation has the goal of full restoration of facial functions (ventilation, phonation, and mastication). It represents an opportunity for patients who have suffered complex facial injuries that can not be restored by traditional reconstructive techniques to reestablish their social and professional lives [2,4,6,7]. We strongly believe that with the proper indications, face transplantation is the best option for facial restitution [8]. Nevertheless, it is important to evaluate the risk-benefit ratio because immunosuppressive therapy involves an increasing risk for malignancy, infections, and systemic toxicity [2,9]. To date, 29 facial transplantation procedures have been reported around the world [10]. The reasons for performing the face transplantation are presented in the Table 1. Each time, they have been conducted using more complex VCA and achieved better results [9,10].
In the United States, 478,400 cases of gunshot wounds (GSWs) were reported in 2011, of which 97.4% were nonfatal [11]. This type of injury accounts for 35% of the cases for facial transplantation. In 2013, Moye-Elizalde et al reported 1,281 patients with GSWs in Ciudad Juarez, Chihuahua, Mexico; of those, 9.09% had complex facial injuries [12]. The Mexican Institute of Social Security (IMSS) reported 46,666 accidents at the workplace in 2013 that affected the face and neck regions; among those, there were 927 cases of wounds, 982 trauma, 1,341 burns, and 8 amputations [13]. The IMSS defines amputation as extensive mutilation of the maxilla, mandible, nose, and soft tissue representing 90%e100% of the face [14]. The incidence of GSWs is increasing in Mexico. GSWs involve burns and injuries, which can lead to severe psychiatric impact and several facial deformities that may compromises the patients’ vision, ventilation, and swallowing and lead to considerable economic losses. We therefore support facial transplantation as a promising therapy for selected patients in Mexico. ADVANTAGES OF INCMNSZ FOR FACIAL TRANSPLANTATION
The INCMNSZ has been evolved in organ transplantation program since 1967 [3]. The 2nd kidney transplantation and the 1st liver transplantation in Mexico were performed in the INCMNZ [15,16]. Since then, the solid organ transplantation program has been continuous and permanent. This experience has allowed establishing the Vascularized Composite Allotransplants program. Consequently, the 1st bilateral forearm transplantation was performed in 2012 [5]. Today, the INCMNSZ has the experience to conduct a face transplant program [Fig 1]. CHALLENGES IN ESTABLISHING A FACIAL TRANSPLANTATION PROTOCOL
During the past 10 years of research, we at INCMNSZ have had the following difficulties regarding the implementation of a face transplant program.
Fig 1. History of transplantation in Mexico since 1st renal transplantation. Abbreviations: IMSS, Mexican Institute of Social Security; INCMNSZ, National Institute of Medical Sciences and Nutrition “Salvador Zubiran.”
2000
IGLESIAS, BUTRÓN, OSUNA-LEAL ET AL
Table 2. Cost Analysis of Face Transplantation in Different Countries Aspects
USA
France
Mexico*
Pre-transplantation evaluation Surgery Peri-transplantation supplies Post-transplantation follow-up and treatment for 1 year Total
$206,646 $79,625 $153,268 $74,236
$18,029 $84,861 $18,674 $39,383
$6,309 $1,741 $40,000 $37,737
$513,775
$160,949
$84,787
Note. The costs are all in United States dollars (USD). *Probable costs.
Journal published a new regulationdthe General Law on Transplantationdthat defines VCA as “a complex tissue used in transplantation, including musculoskeletal tissue, by means of vascular anastomosis and applied to the extremities and face” [18]. Thereafter the Protocol of Vascularized Composite AllotransplantationdFace was approved on June 26, 2014, by the Health Secretary, CENATRA, and INCMNSZ. With these new regulations, the upper extremities and face are managed under the same conditions as solid organs. Second Challenge: Various Aspects and Economic Difficulties With Face Transplants
First Challenge: Legal and Ethical Policies in Mexico
The Aguascalientes Document outlines the controversies surrounding the establishment of transplant programs in Latin America and the Caribbean [17]. Nevertheless, the marked increase in the number of patients awaiting donors has led to the unification of criteria and proceedings toward ensuring the accessibility, transparency, and quality of these procedures in this region. It is necessary that the basic bioethical issues be fulfilled: dignity, beneficence, integrity, nonmaleficence, caution and vulnerability, autonomy, responsibility, and local justice. Moreover, the growing demand for organ transplants has obliged Mexico to develop systems that promote and enable donation and transplantation. Toward providing universal access, Mexico has also promoted specific policies framed in an ethical and legal context that consider the common good [17]. However, Mexico lacks policies about VCA, so we assumed the task of initiating a process for creating policies regarding the legalization of such transplants. At the beginning of our upper-limb transplantation program, we found that Mexico possessed no legal regulations regarding VCA. As a result, INCMNSZ, through the Subcommittee of Composite Tissue Transplantation (SCOTTCO) and the National Transplantation Center (CENATRA), had to undertake administrative and juridical actions to define such a procedure. On March 26, 2014, the Federation Official
A face transplant program requires financial support [19]. Transplant programs in the United States are funded primarily by the Department of Defense [6]. In Mexico, the face transplant program will be financed on a tripartite basis: 1) the health ministry; 2) such institutions of social medical security as the IMSS and Institute for Social Security and Services for State Employees; and 3) the patient. At INCMNSZ, patients are classified into 7 levels according to their incomes. Level I involves the lowest charges for the patient and receives the highest subsidy. With increasing level, the charges for the patient become higher and the subsidy lower. With this system, facial transplantation can be performed because patients receive a subsidy from the health ministry (3rd-party payer), which ranges from 0 to 96% of the costs. The costs involve the following: 1) pre-transplantation evaluationdlaboratory costs, imaging studies, and specialist consultation; 2) inpatient costsdsurgical procedure, intensive care unit charges for 1 week and 1 month of hospital stay. Institutions of social medical security (2nd-party payer) cover the costs of immunosuppressive therapy for induction, long-term maintenance, and drugs necessary in case of acute rejection, complications such as infections, or metabolic alterations. Finally, the patient (1st-party payer) covers some costs, such as medication, transportation, and splints. It is also important to note that the Carlos Slim Foundation and the Life
Table 3. Recipient Selection Criteria 1. Any sex, race, skin tone, and ethnicity. 2. Ages 18e60 years. Patients with different ages will be evaluated by SCOTTCO. 3. No medical problems and/or coexisting serious psychologic issues that contraindicate the procedure. 4. Damage/trauma/deficit or facial deformities that represent >25% of the facial surface and compromise the functionality of the deep structures or include medial structures (eyelids, nose, lips), whose repair is impossible, not favorable, or unsatisfactory by means of the usual techniques of reconstruction. 5. Desire to improve their quality of life. 6. No oncologic diseases, or remission >10 years. Patients with previous solid organ transplantation will be evaluated by SCOTTCO. 7. Negative serology for HIV, HBV, and HCV. 8. No reliance on addictive substances (1 year of abstinence). 9. Capability to afford the immunosuppressive treatment and/or Institute of Social Security support 10. Negative cross-match with the donor and panel reactive antibodies <30%. Patients with other immunologic characteristics will be valued by SCOTTCO. 11. Basic anatomic elements to ensure nerve and vascular anastomosis (artery/vein facial and/or transverse facial transplants for partial, and external carotid for total face transplants; facial nerve, trigeminal, supraorbital, infraorbital, and branches of the mental nerve). 12. Complete knowledge of the benefits and risks of the procedure, which will be ratified with the signing of informed consent. Abbreviations: SCOTTCO, Subcommittee of Composite Tissue Transplantation; HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus.
FACE TRANSPLANTATION IN MEXICO
2001
Table 4. Recepient Exclusion Criteria 1. Active infections. 2. Conditions with high cardiovascular risk or autoimmune diseases. 3. Renal insufficiency (rate of creatinine clearance <60 mL/min, serum creatinine >1.5 mg/100 mL). 4. Psychologic disorders (body dysmorphic disorder), not controlled psychiatric disorders. 5. Presence of malignant tumors. Patients with facial deficits secondary to radical resection of tumors of the head and neck will be evaluated by SCOTTCO. 6. Financial insufficiency or lack of Social Security support 7. Lack of family support. 8. Unrealistic expectations on the treatment. 9. Use of addictive or illegal substances. 10. Pregnancy or desire of pregnancy in the 1st year after transplantation. Abbreviation: SCOTTCO, Subcommittee of Composite Tissue Transplantation.
and Transplant Association provide financial support for original cutting-edge research projects, and they have made an agreement with INCMNSZ to provide donations for the face transplant program. Secondary surgeries also will be financed on a tripartite basis as just described. All of these costs are clarified with the patient and the authorities and signed in the informed consent before the patient is signed on to the waiting list. Based on our upper-limb transplantation experience, we calculated the face transplantation costs as follows: 1) pretransplantation stage: $6,309 (values are in United States dollars throughout), including specialist evaluation, laboratory costs, and imaging; 2) peri-transplantation stage: $40,000, including medical supplies, transfusion procedures, intensive care unit stay for 1 week, and hospital stay for 1 month; 3) surgical procedure: $1,741; and 4) posttransplantation stage: $37,737, including specialist followup, laboratory costs, imaging, and immunosuppressive treatment, which covers induction treatment ($10,355) and maintenance for 1 year ($15,658). The total amount is USD $85,787. Without subsidy, this amount is contrasted with
that for Siemionow et al’s [19] and Lantieri et al’s [20] programs (Table 2). A Level III patient, receiving a 64% subsidy and full coverage for immunosuppressive medication, would have to pay $20,895 for the 1st year. Third Challenge: Capacity of Multidisciplinary Team
Face transplantation is not a routine procedure in any hospital. It therefore demands the assembly, training, and education of a multidisciplinary team so that the transplant can be conducted in optimal fashion. We requested the assistance of the National Autonomous University of Mexico to allow us to practice our surgical approach on cadavers to perfect our techniques and be prepared for any difficulties that might occur. Our multidisciplinary team includes plastic surgeons, transplant surgeons, infectologists, psychiatrists, social workers, anesthesiologists, and others. In this way, it is intended that INCMNSZ will be able to achieve the best possible results and confer the greatest benefits for the recipient. Fourth Challenge: Finding Donors
Following the drawing up of the health ministry’s new guidelines relating to transplantation, SCOTTCO assumed the task of establishing the criteria for inclusion and exclusion for both recipients and donors. Those criteria are described elsewhere [6,20,21] and listed in Tables 3e5. One disadvantage with INCMNSZ is the absence of a trauma unit. That limits the search and identification of patients with complex wounds or burns that require face transplants. Therefore, SCOTTCO focuses on broadcast media and social networks to inform the general public about face transplants. The efforts include providing information about patients worldwide who have undergone face transplants, the benefits and limitations of this procedure, the requirements for recipient selection, and recipient benefits in terms of functional and psychologic factors toward achieving social and professional reintegration and improving the recipient’s quality of life. SCOTTCO has developed a comic to raise public awareness about the
Table 5. Donor Selection Criteria 1. Brain death, proven in the same way as with any donor, with hemodynamic stability. 2. Multiorgan donor. 3. No systemic diseases and/or that affect the local anatomy and/or function of the face (sepsis unresolved, active TB disease, viral encephalitis, any malignancy, craniofacial deformities, neuropathy, etc). 4. Written consent of the responsible direct family, obtained through the persons accredited by CENATRA, clearly stating that facial tissue will be removed, partially or fully, including components of skin, muscle, and bone depending on the case. 5. The donor must have anatomic similarity in appearance to the receiver (sex, color, texture, distribution of body hair, dimensions, etc). 6. The age of the donor must be compatible in viability and function with the receiver, 10 years younger (to 18 years) to 10 years older. 7. The dimensions of the face donated should be approximately equal to those of the receiver on the basis of the head circumference, with a variation of 4%. 8. Seronegativity for HBV, HCV, syphilis, brucellosis, and HIV. 9. Blood type equal or compatible to the receiver. 10. Face donated with anatomic integrity without traumatic and/or surgical history. 11. History of no use of IV drugs, tattoos, and piercings in the past 6 months. Abbreviations: TB, tuberculosis; CENATRA, National Center of Transplants; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IV, intravenous.
2002
benefits of the face transplant program toward promoting face donation. This campaign has come about through governmental institutions and Mexican associations of general medicine, orthopedics, and plastic surgery nationwide toward promoting face transplantation as a feasible, effective, and reliable therapeutic alternative in the country. To promote a growing number of donors, CENATRA and the National Autonomous University of Mexico have included VCA (upper-extremity and face transplantation) in their Graduate Program for Coordinators of Organs and Tissues for Transplantation Purposes. In addition, CENATRA has instructed our team’s junior staff as national transplantation coordinators; they are certified to deal with problems related to preparing donors’ families in the donation process. There are currently 6 national transplantation coordinators, and they are able to deal with the challenge of face transplantation. INCMNSZ has made agreements with the Chihuahua State’s Central Hospital to expand the network to locate face donors. CONCLUSION
There is currently little knowledge about VCA in Mexico. In the development of our face transplant program, we have accomplished the following goals: encouraged the Mexican health ministry to establish official guidelines for VCA, created a multidisciplinary interagency team trained in this type of transplantation, set up campaigns to promote face donation, and trained specialists for organ and tissue donation purposesdspecifically for the face and upper extremities. INCMNSZ is prepared to attain the goals of evaluating likely receptors with complex facial injuries and performing face transplantation in Mexico in less than 5 years’ time. REFERENCES [1] Merrill JP, Murray JE, Harrison JH, et al. Successful homotrasplantation of the human kidney between identical twins. JAMA 1956;160:27e82. [2] Smeets R, Rendenbach C, Birkelbach M, et al. Face transplantation: on the verge of becoming clinical routine? Biomed Research Int 2014;2014:907272.
IGLESIAS, BUTRÓN, OSUNA-LEAL ET AL [3] Secretaria de Salud. [Action program: transplants]. Mexico. 1st ed. 2001. Spanish. [4] Losee JE, Fletcher DR, Gorantla VS. Human facial allotransplantation: patient selection and pertinent considerations. J Craniofac Surg 2012;23:260e4. [5] Iglesias M, Butrón P, Alberú-Gómez J, et al. [The importance of not remaining with folded arms: upper extremity transplantation]. Cir Gen 2013;35(Suppl 2):S133e8. Spanish. [6] Bueno EM, Diaz-Siso JR, Pomahac B. A multidisciplinary protocol for face transplantation at Brigham and Women’s Hospital. J Plast Reconstr Aesthet Sure 2011;64:1572e9. [7] Infante-Cossio P, Barrera-Pulido F, Gomez-Cia T, et al. Facial transplantation: a concise update. Med Oral Patol Oral Cir Bucal 2013;18:e263e71. [8] González-García I, Lyra-Gonzalez I, Medina-Preciado D, et al. Face transplant: is it feasible in developing countries? J Craniofac Surg 2013;24:309e12. [9] Khalifian S, Brazio PS, Mohan R, et al. Facial transplantation: the first 9 years. Lancet 2014;384:2153e63. [10] Fischer S, Kuekelhaus M, Pauzenberger R, et al. Functional outcomes of face transplantation. Am J Transplant 2015;15:220e33. [11] Planty M, Truman JL. Firearm violence, 1993-2011. Washington, DC: Bureau of Justice Statistics, US Department of Justice; 2013. [12] Moye-Elizalde GA, Ruiz-Martinez F, Suarez-Santamaria JJ, et al. [Epidemiology of gunshot wounds at Ciudad Juarez, Chihuahua General Hospital]. Acta Ortop Mex 2013;27:221e35. Spanish. [13] Instituto Mexicano del Seguro Social. Salud en el trabajo. [Statistical review 2013]. México: IMSS; 2013. Chapter VI. Spanish. [14] Ley Federal del Trabajo. Diario oficial de la federación 1970. México. Last update November 30, 2012. [15] Peña JC. [Renal transplant history in the INCMNSZ (1966)]. Rev Invest Clin 2005;57:120e3. Spanish. [16] Diliz H, Orozco H, Kershenobich D, et al. [Liver transplantation in Mexico. Report of the first successful case]. Rev Gastroenterol Mex 1991;56:33e8. Spanish. [17] Baquero A, Alberu J. [Ethical challenges in transplant practice in Latin America: the Aguascalientes Document]. Nefrologia 2011;31:275. Spanish. [18] Secretaría de Salud. [General Health Law Regulation: Transplantation]. México DF: Diario Oficial de la Federación; March 26, 2014. Spanish. [19] Siemionow M, Gatherwright J, Djohan R, et al. Cost analysis of conventional facial reconstruction procedures followed by face transplantation. Am J Transplant 2011;11:379e85. [20] Lantieri L, Hivelin M, Audard V, et al. Feasibility, reproducibility, risks and benefits of face transplantation: a prospective study of outcomes. Am J Transplant 2011;11:367e78. [21] Siemionow M, Gordon CR. Overview of guidelines for establishing a face transplant program: a work in progress. Am J Transplant 2010;10:1290e6.