face transplants

Researchers weigh the long-term risks and benefits of face transplants in seven individuals.

 

Face transplants. The mere mentioning of these two words is enough to trigger medical and ethical debates around the world. And although these debates may have been deliberated for many years before the world’s first transplant procedures, they have evolved into something much more complicated. The central debate, however, questions whether the benefits of face transplants outweigh the risks. It is this question that researchers recently sought to answer.

In 1999, surgeons performed the first successful human hand transplant. This surgery showed that vascularized composite allotransplants were possible, and it was a surgery that foreshadowed the birth of face transplants at the turn of the millennium. In 2005, surgeons performed the first face transplant on Isabelle Dinoire, who had been mauled by her dog while she slept after she attempted suicide. Since then, more than 37 individuals have undergone face transplants so far. With this number rising with increasingly complex procedures, it is a crucial time for researchers to answer the highly debated question: should we do face transplants?

However, full reports on face transplants have been limited. Only two-thirds of face transplants have been reported in case series, and these reports have only focused on the technical aspects and short-term outcomes limited to one year of follow-up after the surgery. And although there are many reviews, editorials, and animal studies showing successful full face transplants, researchers have not found a prospective study with predefined primary and safety endpoints that had been systematically collected and analysed over a long-term follow-up period.

To address this, a recently published study in The Lancet aimed to answer the debated question of whether or not we should do face transplants, by first asking: what are the long-term risks and benefits of face transplants?

To do so, researchers performed a single-centre, prospective, open study between January 2000 and December 2009. Researchers first assessed 20 patients with facial defects relating to tumors, burns, and ballistic trauma. After excluding patients with recent history of cancer and unstable psychiatric conditions, they were left with 10 patients with non-reconstructable facial defects. However, three more of these patients were excluded after two of them presented with intense HLA sensitization (in which a transplant could cause acute rejection) and after the other developed melanoma with a poor prognosis.

Surgeons performed facial transplants on a total of seven individuals: four with self-inflicted facial ballistic trauma (gunshot injuries), two with neurofibromatosis 1 (growth of tumors along nerves of the skin, brain, and other parts of the body), and one burn patient. The inclusion of these seven individuals required unanimous approval by professionals across many disciplines. The face transplants, donated by heart-beating brain-dead donors, occurred between January 21, 2007 and April 16, 2011.

After the 6-month follow-up, individuals underwent clinical assessment every three months, and supplemental examinations at 3 months, 6 months, and 12 months and then every year, and also when health professionals noticed any clinical signs of rejection. The patients underwent rehabilitation that included speech therapy, range-of-motion exercises, and sensory re-education. They also underwent functional assessments by physical and speech therapists and psychological evaluations. They answered quantitative, subjective health-related quality of life assessments using the validated Short Form 36 health (SF-36) questionnaire.

The researchers measured the risks through serious adverse events, and the benefits through quality of life, determined by questionnaires and functional assessments.

Over the course of this study, two of the transplanted patients died. One died 65 days after the operation, because of a pseudomonas infection on the altered transplants. The other died by suicide, after struggling with interpersonal and financial problems, despite having good aesthetic and functional outcomes.

All the patients experienced infectious complications in the first months after the surgeries. Any late complications were mostly due to side-effects of immunosuppressive therapy, a therapy that is required so that the immune system does not reject the transplant.

Overall, all the patients who survived the early post-operative period presented with functional transplants at an average follow-up of six years. Both recipients and their families reported being satisfied with their transplants, confirming that they led “normal lives.” Quality of life showed improvement in all patients, and all the patients also considered their transplants to be their own face, reflecting their personality and emotions. None of the patients reported that they regretted having undergone the transplantation. Four of the patients have also found part or full-time employment.

However, improvements in the patients’ social integration depended on their psychiatric and social background. The researchers note that despite good functional results and improvement in quality of life, pre-existing mental disorders signify long-term risks. This means that patient selection is of crucial importance to the success of these surgeries.

For example, patients with gunshot injuries with pre-existing mental disorders had difficult follow-ups, highly variable compliance, repeated rejection episodes, poor or absent social reintegration, and lower quality of life than the other patients at long-term follow-up. The researchers note that these differences highlight the need for a multidisciplinary screening.

It is also important to note that burn patients are often HLA-sensitized. HLA sensitization occurs after repeated blood transfusions (in ballistic trauma and burn patients) or skin allografts. Antibodies to HLA, an acronym for human leukocyte antigen, are a significant barrier to transplantation. HLA-sensitized patients have increased risk of rejection, and require substantial immunosuppressive therapy which can lead to more side effects of immunosuppression as well as poorer graft outcomes.

Because of these findings, the researchers insist that the risk-benefit ratio analysis must consider HLA sensitization and any previous psychiatric instability as high risks of failure for the transplant and social benefit. They write that “face transplant programmes might benefit from optimized assessment and management of psychosocial issues and of immunosuppressive regimen, particularly in sensitized patients.” They also note that patients must be informed about early, life-threatening, infectious complications of immunosuppression.

The researchers conclude their study with this statement:

“Ultimately, if one answers, ‘yes’ to the question, ‘Should we continue performing face transplants?’ moderation and prudence are indicated for patient selection, long-term monitoring in clinical research programs and strict controls by institutional review board are mandatory. These seem to be the ethical requirements of the next face transplants.”

 

 

 

Written By: Jessica Gelar, HBSc

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