Kapila H

Human hand allograft: report on first 6 months

BACKGROUND Long-term survival of animal limb allografts with new immunosuppressant combinations and encouraging results of autologous limb replantations led us to believe that clinical application of hand transplantation in human beings was viable. METHODS On Sept 23, 1998, we transplanted the right distal forearm and hand of a brain-dead man aged 41 years on to a man aged 48 years who had had traumatic amputation of the distal third of his right forearm. The donors arm was irrigated with UW organ preservation solution at 4 degrees C, amputated 5 cm above the elbow, and transported in a cool container. We dissected the donor limb and the recipients arm simultaneously to identify anatomical structures. Appropriate lengths of viable structures were matched. Transplantation involved bone fixation, arterial and venous anastomoses (ischaemic time 12.5 h), nerve sutures, joining of muscles and tendons, and skin closure. Immunosuppression included antithymocyte globulins, tacrolimus, mycophenolic acid, and prednisone. Maintenance therapy included tacrolimus, mycophenolic acid, and prednisone. Follow-up included routine post-transplant laboratory tests, skin biopsies, intensive physiotherapy, and psychological support. FINDINGS The initial postoperative course was uneventful. No surgical complications were seen. Immunosuppression was well tolerated. Mild clinical and histological signs of cutaneous rejection were seen at weeks 8-9 after surgery. These signs disappeared after prednisone dose was increased (from 20 mg/day to 40 mg/day) and topical application of immunosuppressive creams (tacrolimus, clobetasol). Intensive physiotherapy led to satisfactory progress of motor function. Sensory progress (Tinels sign) was excellent and reached the wrist crease (20 cm) on day 100 for the median and ulnar nerves, and at least 24 cm to the palm by 6 months when deep pressure, but not light touch sensation, could be felt at the mid palm. INTERPRETATION Hand allotransplantation is technically feasible. Currently available immunosuppression seems to prevent acute rejection. If no further episode of rejection occurs, the functional prognosis of this graft should be similar to if not better than that reported in large series of autoreconstruction.

HAND TRANSPLANTATION: ETHICS, IMMUNOSUPPRESSION AND INDICATIONS

Experimentation (. . .) is justified primarily by the individual’s and not by the community’s interest. However, this does not exclude that, provided that one’s own substantial integrity is preserved, the patient could legitimately bear a part of the risks to contribute with his/her initiative to the progress of medicine, and in this way, to the welfare of the community. Within the community, the purpose of medicine is to free the human being from the infirmities that block him, and from the psycho-somatic fragilities that humiliate him John Paul II From the address to the participants to two surgical meetings in Rome, Italy October 27, 1980

Peripheral nerve regeneration in human hand transplantation

WHEN a major peripheral nerve is rejoined microsurgically after complete severance it may regenerate distally at a rate of up to 1 mm/d in adults. Regeneration can proceed steadily even through two completely severed and then meticulously individually repaired anastomoses along the same nerve. A long nerve homograft can also be expected to regenerate, but at a slighter slower rate. On September 23, 1998, a cadaver right distal forearm and hand were transplanted onto a 47-year-old amputee in Lyon, France. The different tissues were joined at different levels due to their anatomic location and condition. With a reference point at the wrist crease, the ulnar and median nerves were joined 20 and 21 cm, respectively, proximal to it. Sensory and motor nerve regeneration was assessed independently by a group of hand therapists—first by assessment of Tinel signs, followed by Semmes‐Weinstein microfilaments, NCS, pinprick, hot and cold, and light and deep pressure. Rapid regeneration was observed immediately postoperatively, with the Tinel sign advancing to the wrist crease by 100 days (200 and 210 mm, respectively, for the ulnar and median nerve). At 300 days, regeneration was at 330 mm and reached all fingertips (360 mm) at 365 days. Intrinsic muscle activity appeared into the abductor digiti minimi muscle at 12 months and was detected as very weak in the other intrinsic muscles at 16 months. Currently, muscle activity is also present in the first dorsal interosseous muscle. The remarkable speed of nerve regeneration may be due in part to the effect of FK 506, which serves not only as a very effective immunosuppressant drug but has a well-defined action in removing some of the inhibiting factors presently slowing normal nerve regeneration. FK 506 protects neural cells from ischemia and blocks neuronal apoptosis. Subsequent to protective sensation reaching to his fingertips at 1 year postoperatively, the patient has reported gradually more specific feeling, and at almost 2 years postoperation could discriminate pain, hot and cold, and “sharp” and “blunt” sensation in his palms and all digits. There have been several episodes during which the patient left the intensive care of our team (for periods of 3 months, several weeks, and lately for .3 months). Because routine blood drug levels and biopsies (with subsequent adjustments of dosages) were not possible, and as routine physiotherapy was also neglected for months at a time, recovery