The many faces of multivisceral transplantation

The transplantation of multiple abdominal viscera, including liver-duodenum-pancreas, liver-stomach-duodenum-pancreas and liver-intestine, is being performed with increasing frequency and success. These procedures and other variations are derived from a seldom used multivisceral operation in which all of the foregoing organs are transplanted en bloc. It is described herein how the full multivisceral transplantation and its less extensive derivatives are based on the same principles of procurement, preservation and postoperative management. With all of these multiple organ permutations and with intestinal transplantation alone, management is complicated by inclusion in the grafts of a large lymphoreticular component that is capable of causing graft versus host disease (GVHD). Because of a systematic error in therapeutic philosophy, past efforts have been directed at altering or damaging the lymphoreticular cells by pretreatment of the donor or of the organs with drugs, irradiation or other means. From recent observations, the alternative approach is suggested of keeping these lymphoid depots intact, which then become the site of two way cell traffic after transplantation. With the use of powerful immunosuppression, such as that provided with FK 506, the donor lymphoreticular cells can circulate in the recipient without causing clinical GVHD, and the lymphoreticular cells in the graft become those of the recipient (local chimerism) without causing rejection. Even with avoidance of rejection and GVHD, metabolic interrelations between the grafted organs, and also between the graft organs and retained recipient viscera can affect the fate of the individual transplanted organs or retained recipient organs. The best delineated of these metabolic influences are mediated by the endogenous splanchnic hepatotrophic factors, of which insulin has been the most completely studied. An understanding of these various immunologic and nonimmunologic factors combined with more potent immunosuppression that is now available is sure to stimulate efforts at transplantation of abdominal organs and particularly of the hollow viscera that have resisted such clinical efforts

What have we learned about primary liver transplantation under tacrolimus immunosuppression? - Long-term follow-up of the first 1000 patients

Objective: To summarize the long-term efficacy and safety of tacrolimus in orthotopic liver transplant (OLT) recipients, as well as to examine the factors that influence long-term morbidity and mortality rates. Background: Tacrolimus (FK506, Prograf) was introduced as primary immunosuppression for primary liver transplantation in 1989; many subsquent trials have verified the association of tacrolimus with decreased rates of acute rejection and steroid-resistant rejection after OLT. Cumulative experience with tacrolimus has also defined its short- and intermediate-term toxicity. Methods: One thousand consecutive patients undergoing primary OLT at a single center from August 1989 to December 1992, under tacrolimus immunosuppression, were followed until January 1999. Patients were categorized by age. Mean follow-up was 93.4 ± 11 months after OLT. Patient survival, graft survival (with corresponding causes of death and retransplantation), and rejection rates (and corresponding doses of immunosuppression) were examined as efficacy parameters. Hypertension, renal function, incidence of malignancies, incidence of diabetes, and other toxicities were examined as safety parameters. Results: Actual 6-year overall patient survival rate was 68.1% and graft survival rate was 62.5%, with significant differences in the patterns of survival among the different age groups. After the first post-OLT year, infection, recurrence of disease, de novo malignancies, and cardiovascular events were the main causes of graft loss and death during the long-term follow-up. Graft loss related to either acute or chronic rejection was rare. The rate of acute rejection beyond 2 years was approximately 3% per year, and most were steroid-responsive. Approximately 70% of the patients were receiving tacrolimus monotherapy beyond year 1; at the latest follow-up, 74.2% were maintained on tacrolimus alone. In 6.1% of the survivors, end- stage renal disease developed during the follow-up period, requiring either dialysis or kidney transplantation. Hyperkalemia and hypertension was observed in approximately one third of the patients. Insulin-dependent diabetes mellitus (including patients who had diabetes before the transplant) was observed in 14% in year 1, dropping to 11% in year 7. In 82 patients, de novo malignancies developed; in 41 patients, lymphoproliferative disorders developed during the entire follow-up period. Conclusions: Long-term patient and graft survival rates are excellent under tacrolimus immunosuppression. Pediatric patients have a better long-term outcome than adults, in part because of the limited recurrence of the original disease, which was the most common cause of late graft loss (other than patient death, most commonly the result of late de novo malignancies and cardiovascular events). Graft loss from late rejection was rare

Logistics and technique for combined hepatic-intestinal retrieval

During a 13-month period, en bloc liver-small bowel cadaveric grafts were procured for seven children and one adult. All liver grafts functioned immediately, and all but one of the recipient patients recovered. Return of absorptive small bowel function was slow, but the integrity of the bacterial intestinal barrier was not disrupted. The described technique allows the procurement of other abdominothoracic organs, with the exception of the whole pancreas

Outcome analysis of 71 clinical intestinal transplantations

Objective: The aim of the study was to determine risk factors associated with graft failure and mortality after transplantation of the intestine alone or as pad of an organ complex. Summary Background Data: Even with modern immunosuppressive therapies, clinical intestinal transplantation remains a difficult and unreliable procedure. Causes for this and solutions are needed. Methods: Between May 1990 and February 1995, 71 intestinal transplantations were performed in 66 patients using tacrolimus and low-dose steroids. The first 63 patients, all but one treated 1 to 5 years ago, received either isolated grafts (n = 22), liver and intestinal grafts (n = 30), or multivisceral grafts (n = 11). Three mere recipients of allografts who recently underwent surgery and one undergoing retransplantation were given unaltered donor bone marrow cells perioperatively as a biologic adjuvant. Results: Of the first 63 recipients, 32 are alive: 28 have functioning primary grafts and 4 have resumed total parenteral nutrition after graft enterectomy. Thirty-five primary grafts were lost to technical and management errors (n = 10), rejection (n = 6), and infection (n = 19). Regression analysis revealed that duration of surgery, positive donor cytomegalovirus (CMV) serology, inclusion of graft colon, OKT3 use, steroid recycle, and high tacrolimus blood levels contributed to graft loss. All four intestine and bone marrow recipients are alive for 2-3 months without evidence of graft- versus-host disease. Conclusion: To improve outcome after intestinal transplantation with previous management protocols, it will be necessary to avoid predictably difficult patients, CMV seropositive donors, and inclusion of the graft colon. Bone marrow transplantation may further improve outcome by ameliorating the biologic barriers of rejection and infection and allowing less restrictive selection criteria

Incidence and treatment of rejection episodes in primary orthotopic liver transplantation under FK 506.

FK 506 therapy with low doses of steroids was adequate to control rejection in most liver recipients. Rejection episodes were readily reversed with single IV doses of methylprednisone or hydrocortisone. Short courses of OKT3 (3 to 5 days 5-10 mL) controlled severe rejections. The rate of retransplantation directly due to rejection was low (1.6%). There was a limited need for steroids either early or out to 6 to 12 months