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Ornithine transcarbamylase (OTC) deficiency is an X chromosome-linked disorder causing hyperammonemic encephalopathy with a very poor prognosis. We describe here two patients with OTC deficiency, one a late-onset female patient (case 1) and the other a neonatal-onset male patient (case 2), who were successfully treated with orthotopic liver transplantation (OLTx). The OTC activity in the excised liver was 10% and 0% of control respectively. Hyperammonemic encephalopathy was controlled with medical therapy in case 1 until the age 5 years, but the complicated course in case 2 in which hyperammonemia required peritoneal dialysis and hemodialysis in the neonatal period necessitated OLTx with a reduced-size liver at the age of 80 days. Both patients had restoration of serum ammonia level to normal in 2 and 3 days after liver replacement, and both patients have normal neurological and developmental status after 2 and 0.5 years of postoperative follow-up. These cases illustrate not only the metabolic cure of this disorder, but also the need to preserve neurological integrity by aggressive medical management of the hyperammonemia preoperatively and early surgical intervention when indicated, even if this is required very early in life. © 1995.

Background. Two children with life-threatening disorders underwent intestinal transplantation; one multivisceral transplantation excluding the liver, and the second transplantation of the liver, small bowel, and colon. Methods. Involvement of the native rectum necessitated resection and replacement with the transplanted allograft. To prevent a permanent colostomy, a pull-through of the allograft colon was performed. Results. Both patients had a stormy early postoperative course, mainly because of the complexities of intestinal transplantation, but with eventual recovery, including improvement of rectal function. Conclusions. These are the first two known cases in which a transplanted large intestine was used for a pull-through procedure. © 1995 Mosby-Year Book, Inc.

Although liver biopsy is a very useful procedure used frequently in the diagnosis and management of liver dysfunction occurring after orthotopic liver transplantation, complications can occur with its use. An unusual complication of arterioportal fistula is reported here. Based upon this small series of an unusual event and the knowledge that the posttransplant liver may be more hypervascular than prior to OLTx and that it is uniquely susceptible to hepatic infarction and abscess formation, any attempt at fistula closure should be considered carefully prior to initiating the therapy (15). Unless a serious complication occurs [such as a transient biliary obstruction due to hemobilia as occurred in case 2, portal hypertension as also occurred in case 2, or systemic sepsis or other symptoms develop related directly to the fistula], simple observation may be the best choice of action. Should therapy be required, hepatic arterial embolization should be reserved for adults with intrahepatic fistulas. Primary surgical closure of intrahepatic fistula should be reserved for cases of extrahepatic fistula. © 1995 Plenum Publishing Corporation.

We correlated donor and recipient factors with graft outcome in 436 adult patients who underwent 462 liver transplants. Donor variables analyzed were age, gender, ABO blood group, cause of death, length of stay in the intensive care unit, use of pressors or pitressin, need for cardiopulmonary resuscitation, terminal serum transaminases, and ischemia time. Recipient variables analyzed were age, gender, primary diagnosis, history of previous liver transplant, ABO blood group, cytotoxic antibody crossmatch, United Network for Organ Sharing (UNOS) status, and waiting time (except for the cross-match results, they were all known at the time of the operation). The endpoint of the analysis was graft failure, defined as patient death or retransplantation. Using multivariate analysis, graft failure was significantly associated with donor age, donor gender, previous liver transplantation, and UNOS 4 status of the recipient. The effect of donor age became evident only when they were older than 45 years. Livers from female donors yielded significantly poorer results, with 2-year graft survival of female to male 55% (95% CI, 45% to 67%); female to female, 64% (95% CI, 54% to 77%); male to male, 72% (95% CI, 66% to 78%); and male to female, 78% (95% CI, 70% to 88%). The only donors identified as questionable for liver procurement were old (-60 years) women in whom the adverse age and gender factors were at least additive. However, rather than discard even these livers, in the face of an organ shortage crisis, their individualized use is suggested with case reporting in a special category. © 1995.

The authors report on six pediatric liver transplant recipients for whom allograft tolerance occurred shortly after transplantation (ie, less than 1.5 years). All the patients had associated life-threatening viral complications. They are currently immmunocompetent. The tolerant state may be related to the development of a TH2 cytokine pattern. © 1994.

Graft-versus-host disease (GVHD) remains a major complication of bone marrow transplantation. This report describes reversal of GVHD by infusion of stored recipient bone marrow following combined liver-bone marrow allotransplantation. Graft-versus-host disease developed at the end of the first postoperative week. The skin involvement progressively spread to approximately 80% of the body surface and was not affected by modification of the immunosuppressive treatment. On the 42nd and 43rd postoperative day 1.23 × 108 and 1.6 × 108 autologous bone marrow cells per kg of recipient body weight were infused. The skin rush began to dramatically improve and resolved within 2 wk from the autologous marrow infusion. Autologous bone marrow storage previous to allogeneic bone marrow transplantation for tolerance induction could constitute a safety net in case of occurrence of GVHD. © 1994.

Intestinal transplantation is often the only alternative form of treatment for patients dependent on total parenteral nutrition for survival. Although a limited number of intestinal transplantations have been performed, results with FK 506 immunosuppression are comparable to those for other organ transplants. The impact of successful intestinal transplantation on gastroenterology will likely be similar to the impact of kidney and liver transplantation on nephrology and hepatology.

Intestinal transplantation, solitary (n = 3) or in combination with the liver (n = 7), was performed in 10 pediatric patients with intestinal failure. The liver was only replaced if there was liver failure and portal hypertension. Immunosuppression was based on FK 506. Two patients died, one of graft-versus-host disease and one of lymphoproliferative disease. One patient was still in the intensive care unit 1 month posttransplantation due to perioperative complications. The function of the intestinal grafts in the remaining patients is normal. All nutrition and medications including immunosuppression are being administered enterally. This series indicates that small bowel transplantation, alone or in combination with the liver, is feasible in pediatric patients. © 1993.

An increased frequency of kidney rejection has been reported in diabetic patients who have simultaneous pancreas and kidney transplantation compared with patients who have a kidney transplant alone. Kidney graft outcome is similar in the two groups. The mechanism for increased kidney graft rejection with a simultaneous pancreas graft is not clear. It is ascribed to the immunogenicity of the exocrine pancreas that initiates migration of activated cells from the peripheral blood that are entrapped in the kidney. Since the volume of the transplanted tissue is less in islet transplantation (usually <2 ml) than in pancreas transplantation, one might not expect an increased frequency of kidney rejection in islet cell recipients. We looked at biopsy- proven kidney rejection episodes in patients who had combined kidney and islet transplants and compared this with the frequency of rejection in diabetic and nondiabetic patients who underwent a kidney transplant alone under the same immunosuppression. Diabetic patients who had kidney islet transplants (n=9) had a higher frequency of rejection (100%) compared with diabetic patients (n=107, 55.1%) and nondiabetic patients (n=327, 65%) who had a kidney transplant alone. The 1-year graft and patient survival rates were not different among the groups. Although the number of patients is small, it would appear that transplantation of a low volume of islet cells with high purity can lead to an increased frequency of kidney rejection. This is unlikely to be explained solely on the basis of fewer antigen matches in these recipients but may reflect the inherent immunogenicity of the purified islet preparations. Alternatively, there may be an effect of their direct infusion into the portal vein.

Twenty-three children with Alagille's syndrome and end-stage liver disease underwent liver transplantation with cyclosporine and low-dose steroid immunosuppression. Two to 9 years (mean, 4.4 years) after surgery, 13 (57%) of the children were still alive, with normal liver function. Three of the fatalities were due to cardiovascular failure secondary to associated cardiopulmonary disease. Mortality was higher among patients who had more severe cardiac disease and patients who had previously undergone a Kasai procedure. Although it has a higher than average risk, liver transplantation can be efficacious in patients with Alagille's syndrome and end-stage liver disease. (Arch Surg. 1993;128:337-339). © 1993, American Medical Association. All rights reserved.

A clinical trial of intestinal transplantation was initiated at the University of Pittsburgh in May 1990. Eleven children received either a combined liver/small bowel graft (n = 8) or an isolated small bowel graft (n = 3). Induction as well as maintenance immunosuppression was with FK-506 and steroids. Four patients were male, and seven were female; the age range was 6 months to 10.2 years. There were 3 deaths (all in recipients of the combined liver/small bowel graft), which were attributed to graft-versus-host disease (n = 1), posttransplant lymphoproliferative disease (n = 1), and biliary leak (n = 1). Transplantation of the intestine has evolved into a feasible operation, with an overall patient and graft survival rate of 73%. These survivors are free of total parenteral nutrition, and the majority are home. These encouraging results justify further clinical trials.

During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure.

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft- versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection.

Thirteen out of 268 children (<18 years old) underwent hepatic transplantation (OLT) for end-stage liver disease (ESLD) associated with arteriohepatic dysplasia (AHD). Seven children are alive and well with normal liver function. Six children died, four within 11 days of the operation and the other two at 4 and 10 months after the OLT. Vascular complications with associated septicemia were responsible for the deaths of three children. Two died of heart failure and circulatory collapse, secondary to pulmonary hypertension and congenital heart disease. The remaining patient died of overwhelming sepsis not associated with technical complications. Seven patients had a portoenterostomy or portocholecystostomy early in life; five of these died after the OLT. Severe cardiovascular abnormalities in some of our patients suggest that complete hemodynamic monitoring with invasive studies should be performed in all patients with AHD, especially in cases of documented hypertrophy of the right ventricle. The improved quality of life in our surviving patients confirms the validity of OLT as a treatment of choice in cases of ESLD due to AHD. © 1992 Springer-Verlag.

Sixteen recipients of neonatal liver grafts were compared with 114 contemporaneous pediatric recipients of grafts from older donors. Graft and patient survival were worse in the neonatal group although the differences were not statistically significant. Patients with neonatal livers who had no technical complications required a longer time postoperatively to correct jaundice and a prolonged prothrombin time. These functional differences were limited to the 1st postoperative month and the end result was the same as with liver transplantation from older donors. © 1992 Springer-Verlag.