Organ Replacement, Facial Deformity, and Plastic Surgery

Annual Oration 1972

By Joseph E. Murray, M.D.

Plastic surgery, second only to obstetrics as the oldest surgical specialty, is tested most rigorously in the treatment of facial deformities. Through the centuries the mutilated nose cut off as punishment for murder, theft, or infidelity, the congenital cleft lip, and the face eaten by cancer or torn by trauma have forced the reconstructive surgeon to seek imaginative ways to restore both function and an aesthetically acceptable appearance.

Whenever possible, surgical repair is performed by joining together adjacent areas; often, however, additional tissues such as grafts of skin, cartilage, fascia, or bone are needed to replace the missing or injured parts (Fig. 1). These grafts supply only the framework or bulk rather than replace missing cellular functions. The ultimate in reconstruction is total replacement of an old defective part by a new one. Although not yet possible for facial defects, organ replacement is an effective, accepted, and still developing treatment for renal failure.

In this discourse I will trace my involvement in organ transplantation to the current interest in craniofacial defects and then conclude with observations on the role of plastic surgeons in the delivery of health care for today's society.

Organ Replacement

People often ask how I, a plastic surgeon, became so involved in kidney transplantation. It started during World War II on our Plastic Surgical Service at Valley Forge General Hospital in Pennsylvania headed by Dr. J. B. Brown and Dr. Bradford Cannon. There many burned patients were dying for lack of sufficient unburned skin to be used as grafts. The obvious answer was to use skin from other human beings, but the immunological barrier standing between all humans, except for monozygotic twins, prevents permanent survival of skin allograft and therefore limits their usefulness.

1972_Figure1

Figure 1: Variety of Autogenous Grafts Available to Restore Function and Appearance.

After World War II and completion of training, on my return to the Peter Bent Brigham Hospital I wanted to study the mechanism of rejection of skin allografts. At that time, in 1951, the Medical Service under Dr. G W. Thorn had developed a strong interest in hypertension and renal disease. Dr. J. P. Merrill and Dr. C. W. Walter had devised a functioning artificial kidney, Dr. J. H. Harrison was Chief of Urology, Dr. D. M. Hume had begun a series of unmodified kidney transplants in man, and under Dr. F. D. Moore's guidance, I decided to use the kidney rather than skin as a laboratory test allograft.

In the early 1900's Carrel, having perfected the surgical technics for vascular anastomoses, had shown that kidney autografts in dogs survived for a long time, whereas allografts transplanted by the same technic functioned for only a few days and then were rejected with an intense, local, non-suppurative reaction.

It was strange that even as late as 1951, there was a consensus that renal autografts would not function permanently even though no immunologic barrier existed between donor and host. Deterioration in renal autograft function was assumed to be due to absence of nerve supply, to abnormal lymphatic drainage, to ascending infection from the cutaneous ureterostomy, or to other, unknown circumstances. By 1954, I had studied in the Surgical Research Laboratory at Harvard Medical School a number of dogs with life-sustaining autografts and demonstrated that a solitary autograft could function indefinitely with normal renal function if the autografted kidney were placed in a proper thermal environment intra-abdominally, with good ureteral drainage into the bladder, and with vascular anastomoses performed as described by Carrel.

Therefore when the first identical twin dying of uremia was referred to the Peter Bent Brigham Hospital in the autumn of 1954, we had available a proved laboratory model for the human operation. The immediate and complete success of this first human twin transplant served as a major stimulus for our endeavors to break the immunologic barrier and to bring the benefits of organ replacement to uremic patients, most of whom were young and otherwise healthy. One of our twin recipients receiving a transplant in May, 1956, completed a normal pregnancy 16 months later; today, she has normal renal function, has had two children, leads a normal life, and is the world's longest survivor of a renal transplant.

Dr. F. D. Moore, in his book, Transplant, the Give and Take of Tissue Transplantation, gives a lively account of the development of organ transplantation. He mentions the use of total-body x-irradiation tested in the late 1950's as an immunosuppressive agent in mice, rabbits, and dogs. This total-body x-ray protocol followed by bone-marrow infusion and then by the renal allograft proved difficult to adapt to man. From many attempts at the Peter Bent Brigham Hospital only one successful transplant resulted, a young man given a transplant in January, 1959, from his di-zygotic twin brother. Today, he has obtained his Ph.D. in Philosophy, has married, has good renal function and leads a normal life — the longest surviving renal-allograft recipient in the world. During these years Hamburger and Küss, in Paris, working separately, also achieved isolated unpredictable successes with the use of related living donors.

The real impetus to worldwide kidney transplantation came from the use of immunosuppressive drugs, which were more efficient and less dangerous than total body irradiation, with an additional advantage that the dosage could be continuously adjusted. After Schwartz and Dameshek, in 1959, produced in rabbits a specific drug-induced immunologic tolerance to human serum albumin after the use of 6-mercaptopurine (6-MP), Calne and Zukoski independently achieved considerable prolongation of renal allografts in dogs with the use of the same agent.

Azathioprine, the imidazole derivative of 6-MP, was soon found by Calne and me to be more effective and less toxic than 6-MP. In the previous nine years in our laboratory we had never achieved a single survival of a canine renal allograft beyond 15 days. During the year 1960, using azathioprine in varying doses and combinations, we could produce healthy, bilateral nephrectomized, renal allografted dogs of continually longer duration — 42 days, 78 days, and then over 100 days. Those were exciting times. We used azathioprine first for a human recipient of a renal allograft in 1961. A patient given a transplant in April, 1962, became the first human being to survive beyond one year after receiving a kidney from a cadaver.

Many other centers in Paris, Edinburgh, London, Richmond, Los Angeles, and Denver were extremely active at this time, and increasing numbers of long surviving recipients from parental, sibling, and cadaveric donors were being obtained. Groth, in his recently published Landmarks in Clinical Renal Transplantation, mentions Goodwin, who added the use of steroids, Starzl and Hume, who produced for the first time good results in a majority of patients, Dausset and Terasaki, who first applied histocompatibility tests to select the most suitable donor-recipient combinations, Franksson, who used thoracic-duct drainage of lymphocytes as an immunosuppressive aid, and Woodruff, whose work led to the use of antilymphocyte globulin in clinical transplantation.

Today, about 75 per cent of living related donor transplants function at two years, with only slight loss thereafter; for cadaveric donor transplants about 50 per cent function for two years but with a greater loss over the following years. Transplant failure does not mean death of the patient because most patients return to hemodialysis awaiting a second, third, or even a fourth transplant.

Better tissue typing and donor-recipient matching are required to achieve further improvement. Also needed are more specific and less toxic methods of immune suppression. Available drugs are far from ideal agents, although when effective they allow patients to live full lives, to have normal children, and to perform unlimited physical activity except as related to physical injury to the transplant. The marked improvement in organ preservation, especially by Beizer, allows up to 48 to 72 hours of kidney storage — ample time for tissue typing, for shipping the organ anywhere in the world to the best matched recipient, and for optimal preparation for an elective operation.

Although the kidney remains by far the most frequently transplanted organ, over 10,000 having been recorded, liver and heart transplants have been successful. Starzl, using Moore's technic, has several liver-transplant survivors beyond two years, and Calne one beyond three years. Shumway's group has several recipients of cardiac transplants surviving for over three years with excellent quality of life. Their overall survival figures are actually better than those seven years ago for cadaveric renal grafts.

To conclude this phase of the discourse on organ replacement, it is ironic that skin, the first tissue to be studied extensively, has proved to be the most difficult to allograft successfully. Skin, together with lung, are the barriers between our internal milieu and the external environment, and hence, ideologically, the most highly developed to detect and react against foreign substances — witness hives and asthma as the most common hypersensitivity states. Although the treatment of burns has been improved by use of preserved skin allografts, they serve only as temporary, not permanent, biologic dressings.

Facial Deformity

How does all this relate to facial deformity? Currently, transplantation of an intact orbit, jaw, nose, palate, or esophagus does not apply; yet the seed has been planted, and investigations are under way in the field of craniofacial defects in a manner reminiscent of the early days of transplantation.

In 1957 a nine-year-old boy with rhabdomyosarcoma of the orbit, recurrent after x-ray therapy and two surgical resections, was referred to the late Dr. Donald Matson, of Harvard Medical School, Children's Hospital Medical Center and Peter Bent Brigham Hospital. Dr. Matson's prior experience with similar situations had been dismal, with patients dying piteously of local disease but with no distant metastases. Together, we developed and performed radical surgical resection of all bone, muscle, and sinus tissues between the frontal and temporal lobes of the brain, as far posteriorly as the anterior clinoid process, and inferiorly to the hard and soft palate. The immediate repair was by a split-thickness skin graft. Three years later a pedicle flap was substituted to give better protection. Today, this grown man has completed his education, leads a normal life and as a hobby water-skis and does underwater diving. This experience with combined cranio-orbito-facial resection and reconstruction has been adapted with success for other patients and other types of tumors; in addition it has increased our interest in other varieties of craniofacial problems.

Around 1960 Dr. L. Swanson, currently chief of dental services at Children's Hospital Medical Center, and I started our collaborative treatment of children and young adults with mandibular prognathism (Fig. 2), secondary cleft lip and palate defects, first and second branchial-arch syndromes, and varieties of maxillary and mandibular hypogenesis. At first our therapy was more or less routine, but it soon became apparent that many observed deformities did not fit into standard patterns or syndromes. For example, in some patients, after early trauma, defects mimicking congenital syndromes developed; in others, after cranial-nerve resection for brain tumors, hypertrophie growth patterns developed in the distantly denervated orbital and malar bones. In still other patients with longitudinal growth studies, secondary and tertiary defects became apparent that could have been prevented by correction of the primary defect at an earlier age.

In the mid-1960's, the first generation of patients with craniosynostoses successfully treated by Drs. Ingraham and Matson were growing up with excellent brain function but with faciostenosis, failure of the mid-face to grow. Some patients showed exophthalmos secondary to hypoplasia of the bony orbit, recession of the cheeks and malar areas, marked maxillary underdevelopment, and malocclusion.

1972_Figure2

Figure 2: Preoperative (Left) and Postoperative (Right) Views of a 16-Year-Old Girl after Osteotomy and Setback of the Mandible for Prognathism (A).

Here was a new problem demanding a fresh look. The existing routine treatment consisted of secondary procedures unsatisfactory to both patient and surgeon. If our analyses were correct and the primary deficit was failure of growth centers at the base of the skull, the obvious correction would be to detach all facial structures from the skull and advance them as a single unit, thus enlarging the bony orbit to allow space for the eye, advancing the maxillary alveolus and teeth to obtain good occlusion and restoring symmetry of the cheeks and nose as well (Fig. 3).

We planned for the procedure for over a year, studying fresh anatomic specimens to determine sites for the osteotomies and to note the directional pull of the muscles and ligaments. In 1966 we performed the first such operation in the United States. It proved successful and has been performed with increasing frequency since. One patient received an unexpected postoperative bonus with improvement in hearing so striking that she discarded her hearing aid.

One year later we learned that Dr. Tessier, plastic surgeon in Paris, had previously performed not only similar procedures but also more complex osteotomies to correct hypertelorism and nasal encephaloceles. In 1959 Tessier had begun his surgical analysis of faciostenosis, hypertelorism, facial encephaloceles, and other major defects. After trial operations he discontinued his attempts until 1964, when he performed a second but still unsuccessful series of test procedures. After more study finally in the mid-1960's he achieved success. His work, first published in 1967 and reprinted in English, serves as a model for skill and scholarship throughout the world.

1972 Figure 3

Figure 3: Teen-Age Girl with Residual Midfacial Stenosis (Preoperative Views on the Left) after Successful Craniectomies in Infancy for Craniosynostosis.

During the past four years Dr. Swanson and I have continued our analysis and treatment of these craniofacial problems, including hypertelorism. In addition we have developed a compound silicone-osseous prosthesis for mandibular reconstruction that combines the benefits of excellent contour and nonreactivity of the silicone with the permanent healing attributes of autogenous bone grafts.

The first international conference on craniofacial defects in October, 1971, organized by Converse and Pruzansky, brought together geneticists, embryologists, cell biologists, dental disciplines, speech pathologists, neurosurgeons, ophthalmologists, and otologists, as well as plastic surgeons. Only a few groups in the world are currently involved in treating these types of patients. Over the next decade the field will grow, perhaps as rapidly as transplantation did during the 1960's. To obtain maximum benefit for the patient and to achieve optimal scientific output, clinical groups must maintain close associations with the related basic sciences.

Role of Plastic Surgery in Delivery of Health Care

The plastic surgeon has a twofold responsibility — to the individual patient under his care and for the delivery of services on a nationwide basis. Whether the defect is congenital, traumatic, neoplastic or esthetic, reconstructive surgery must be defined in its broadest sense, not just correction of a defect but rehabilitation of the patient for life's responsibilities. In some medical circles (probably more so in a university setting) there is a tendency to downgrade esthetic or cosmetic surgery. In my opinion, this is a serious error. We cannot deny the social or personal importance of disfigurement, real or subjective. There will always be public demand for esthetic surgery. It is imperative that it be performed by qualified surgeons who will not act with crass commercialism and dispense technics on demand. Rather, the plastic surgeon must act with experience and judgment to weed out the patients for whom surgery will bring only further mental turmoil. When Blair, in 1938, was establishing the American Board of Plastic Surgery, he wanted to maintain a close relation with general surgery so that surgeons primarily interested in reconstruction would remain in the mainstream and not be relegated to a "fringe practice around the corner."

What sort of patient seeks esthetic surgery, say, for a face lift? It may be a recently widowed or divorced woman seeking employment, an airline stewardess approaching the late 30's, a happily married man or woman 60 or 70 years old who just doesn't like sagging cheeks and neck and baggy eyelids. Once the patient has learned the facts about time involved, discomfort, expense, and possible complications and decides to go ahead with the operation, he or she deserves the same consideration and respect as any other hospitalized patient.

Much to my pleasure, my colleagues frequently call me to suture facial lacerations on themselves or their families; do not members of the general public likewise deserve the skills of plastic surgery when they go to the Emergency Ward of their community hospital? The effective delivery of complete reconstructive surgery must be available to all society, not to just a segment. One estimate by a prepaid group plan sets the need of one plastic surgeon for every 1/2-million population. This is certainly unrealistic. Such a ratio indicates either that many categories of plastic surgical care that the patient considers his right would be delayed or omitted or that the work would be performed by others in the absence of a trained reconstructive surgeon. More realistic figures presented by Dr. Jurkiewicz at the 1970 meeting of the American Society of Plastic and Reconstructive Surgery indicate that at least 1000 more trained plastic surgeons are needed in this country immediately, and that number might conceivably be quadrupled within the next few years.

The present annual output of roughly 100 certified plastic surgeons is inadequate to cope with demand and will remain so while only 1/3 of this country's medical schools support training programs in the specialty. Currently, there are 101 residency programs in plastic surgery with 250 residents in training, with the lowest percentage of foreign medical graduates of any specialty, including the specialty of general surgery. The current ratio per million population is eight for plastic surgery, 24 for otolaryngology, 42 for orthopedics, and 133 for general surgery. It is obvious that more well trained plastic surgeons are needed. The massive study on surgical manpower, directed by Dr. F. D. Moore under the Study of Surgical Services of the United States (SOSSUS), sponsored jointly by the American College of Surgeons and the American Surgical Association, will shed more light on needs and probably bear out the estimates made in 1970, especially since tightening of surgical standards will lead to a further demand for qualified surgeons.

In my opinion, every hospital should have at least one and preferably two certified plastic surgeons on its active staff. Such a recommendation does not imply that these plastic surgeons should take exclusive care of all patients for each of the disease categories mentioned earlier. It does mean, however, that all patients in these hospitals will have the benefit of the reconstructive surgical skills needed for their specific conditions.

While the production of more trained plastic surgeons is awaited, proper utilization of currently available manpower demands attention. Within inner cities maldistribution is potentially correctable with proper and effective planning. The rural areas offer a different challenge. The American Board of Plastic Surgery lists no certified plastic surgeon in Idaho or Montana, and no more than two in each of the nine states of Arkansas, Delaware, Iowa, Maine, Nebraska, North Dakota, Vermont, West Virginia, and Wyoming. Thus, a sizable segment of the population lacks available plastic surgeons. The problem relates not only to this specialty, for in 1/3 of the nation's counties, the physician census is about 30 per cent of the general average.

Conclusions

Specialization and even subspecialization such as surgery of deafness, retinal detachment, and hip replacement have developed in response to public demand. We doctors must remain in the mainstream of medicine and surgery in the broadest sense while pursuing areas of special interests. Progress in other disciplines often dictates which fields of research and study are ready for clinical exploitation. The work on craniofacial defects may follow the pattern of transplantation biology; transplantation gave a clinical stimulus and orientation to immunology, and perhaps craniofacial studies will in a similar way influence genetics and embryology.

The plastic surgeon with adequate background in basic surgery is in a good position to select and participate in new areas of clinical research. He not only derives immediate personal gratification in performing surgery to benefit a fellow human but also receives intellectual stimuli from fellow scientists in efforts to teach and expand knowledge. If he is really fortunate, he may even be invited to give the Annual Discourse before the Massachusetts Medical Society — an honor and privilege that I have appreciated and cherish.

_______________

Murray, Joseph E. "Organ Replacement, Facial Deformity, and Plastic Surgery." New England Journal of Medicine 287, no. 21 (1972): 1069-74.


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