Robert T. Schweizer

Noncompliance in organ transplant recipients.

The frequency of noncompliance with postoperative medical therapy ranges from 2% to 43% in organ transplant recipients and causes more graft loss than uncontrolled rejection in compliant patients. Retrospective and prospective studies undertaken at our center showed no difference in the rate of noncompliance between males and females or between recipients of cadaveric kidneys and those from living, related donors. Patients less than 20 years of age were statistically the most noncompliant (p = 0.0001) compared with those over 40 years. A significant difference in compliance was seen among blacks, Hispanics, and non-Hispanic whites, with the greatest frequency in blacks. This was not due to race, but to socioeconomic status, with those in the low socioeconomic group the most noncompliant. Problems of noncompliance may be reduced if they are identified early in the treatment course.

PREGNANCY IN RENAL TRANSPLANT PATIENTS A REVIEW

SUMMARY A questionnaire survey and review of the literature show that pregnancy can be well tolerated in most women with renal transplants. Fifty-two per cent of the renal transplant recipients who became pregnant had full-term infants with no serious complications. With therapeutic abortions excluded, 71% of the 308 pregnancies permitted to continue resulted in full-term infants. Rejection episodes were occasionally a serious problem, occurring in 9% of the pregnancies. Mechanical interference with renal excretion or preventing vaginal delivery occurred in 5.6% of the cases. Hypertension and proteinuria, often existing prior to pregnancy, became frequently increased during pregnancy. Infections not associated with rejection were common but easily controlled in most cases. Prematurity was frequent but related to renal function and the time interval from transplant to conception. The most serious infant complications were related to prematurity. Unknown is the future of these infants and their progeny because of their intrauterine exposure to immunosuppressive drugs.

Liver transplant for metastatic neuroendocrine tumor.

Generally, the results of liver transplantation for metastic liver disease have not been favorable. One exception has been the unique group of neuroendocrine tumors, the slow growth of which allows liver transplantation to effectively palliate and control symptoms. We report two cases: (a) A 51-year-old man who underwent orthotopic liver transplantation and resection of the pancreatic primary tumor for a nonfunctioning malignant neuroendocrine tumor with features of both carcinoid and islet-cell glucagonoma remains symptom-free and without evidence of tumor recurrence at 13 months follow-up. (b) A 47-year-old man who underwent orthotopic liver transplantation and Whipple resection fo a metastatic isletcell tumor in the head of the pancreas is fully recovered at 5 months follow-up.

Noncompliance in Organ Transplant Recipients

The frequency of noncompliance with postoperative medical therapy ranges from 2% to 43% in organ transplant recipients and causes more graft loss than uncontrolled rejection in compliant patients. Retrospective and prospective studies undertaken at our center showed no difference in the rate of noncompliance between males and females or between recipients of cadaveric kidneys and those from living, related donors. Patients less than 20 years of age were statistically the most noncompliant (p=0.0001) compared with those over 40 years. A significant difference in compliance was seen among blacks, Hispanics, and non‐Hispanic whites, with the greatest frequency in blacks. This was not due to race, but to socioeconomic status, with those in the low socioeconomic group the most noncompliant. Problems of noncompliance may be reduced if they are identified early in the treatment course.

Preservation and transplantation of human cadaver kidneys.

In the last 4 years, 210 human cadaver kidneys have been stored by pulsatile perfusion for periods ranging from 4 1/2 to 50 hr. Of these 210 kidneys, 180 were subsequently transplanted. The following results are reported: incidence of postoperative dialysis for tubular necrosis, final renal function, complications, and patient and graft survival. Perfusion characteristics combined with warm ischemia time and donor serum creatinine at time of death have proved to be excellent criteria for graft viability. The clinical results show that this method of storage is efficient, reliable, and produces kidneys of excellent quality.

CYCLOSPORINE AND ANTI-INTERLEUKIN-2 RECEPTOR MONOCLONAL-ANTIBODY THERAPY SUPPRESS ACCELERATED REJECTION OF RAT CARDIAC ALLOGRAFTS THROUGH DIFFERENT EFFECTOR MECHANISMS

Increasing numbers of sensitized patients are either precluded from receiving an allograft or experience accelerated rejection which may be refractory to conventional therapy. Using a rat model, we have shown that accelerated (24 hr) rejection of LBN cardiac Tx in LEW rats sensitized with BN skin grafts 7 days earlier, could be prevented by treatment with cyclosporine (15 mg/kg/day x7 days, Tx survival about 42 days) or ART-18, an anti-IL-2R mAb (300 micrograms/kg/day x10 days i.v., Tx survival about 16 days). In this study, we evaluated intragraft mechanisms responsible for these effects by immunoperoxidase localization of relevant humoral mediators (IgG, IgM, C3, cross-linked fibrin), graft infiltrating cells (GIC), and associated cytokines (IL-2, IFN-g, tumor necrosis factor [TNF], or cytokine receptors (IL-2R). Tx rejected in fulminating fashion by 24 hr in sensitized hosts showed extensive and progressive endothelial deposition of IgG, C3, and fibrin from 2 hr, followed by an influx of neutrophils at 3 hr, and peak numbers of GIC by 18 hr (88.8 +/- 20.3 leukocytes/field). At 18 hr, GIC consisted of neutrophils (26%), T cells (20%, greater than 90% of which were OX-8+), and monocytes/macrophages (53%), whereas B cells were absent. By 18 hr, up to 20% of GIC were IFN-g+, 10% were IL-2R+, and 10% were IL-2+, consistent with labeling of 20% of cells with OX-22. Widespread endothelial and mononuclear cell labeling for TNF and the procoagulant molecular tissue factor (TF) were also noted. In contrast to untreated grafts, CsA treatment essentially abolished intragraft Ig, C3, and fibrin deposition. Moreover, despite dense cell infiltration at 24 hr (total GIC 55.3 +/- 13.4/field), analysis of CsA-treated Tx showed markedly decreased neutrophils (0.5%), with increased T cells (35%) and similar proportions of macrophages (66%). In addition to the reduction in neutrophils, Ig and C3, fewer IL-2R+ (6%) and OX-22+ (3%) cells, considerably less TNF and TF, and almost no IL-2+ or IFN-g+ GIC (less than 1%) were detected. Surprisingly, ART-18 treatment also greatly decreased but did not abolish endothelial deposition of C3, IgG, or IgM, whereas widespread endothelial and mononuclear labeling for fibrin, TNF, and TF remained. In addition, GIC (about 54.8 +/- 16.1/field) contained only moderately reduced numbers of neutrophils (31%) and the proportions of T cells (27%) and macrophages (49%) were generally comparable to those of rejecting Tx in untreated rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Prevention of wound infections by topical antibiotics in high risk patients

A study was made of the efficacy of local antibiotics in the prevention of postoperative wound infections in 354 recipients of renal transplants. There was a statistically significant difference in the rates of wound infection between patients treated with and patients treated without antibiotics, in both primary and secondary wounds. No deleterious local or systemic side effects occurred. From this study we conclude that local antibiotics, such as bacitracin and neomycin, should be used for all wounds in transplant recipients, and their use in other types of surgery is recommended.

A regional experience with emergency liver transplantation.

Liver transplantation for patients requiring life-support results in the lowest survival and highest costs. A ten year (1983-1993) regional experience with liver transplantation for critically ill patients was undertaken to ascertain the fate of several subgroups of patients. Of the 828 liver transplants performed at six transplant centers within the region over this period, 168 (20%) were done in patients who met todays criteria for a United Network of Organ Sharing (UNOS) status 1 (emergency) liver transplant candidate. Recipients were classified according to chronicity of disease and transplant number (primary-acute, primary-chronic, reTx-acute, reTx-chronic). Overall one-year survival was 50% for all status 1 recipients. The primary-acute subgroup (n = 63) experienced a 57% one-year survival compared with 50% for the primary-chronic (n = 51) subgroup (P = 0.07). Of the reTx-acute recipients (n = 43), 44% were alive at one year in comparison with 20% for the reTx-chronic (n = 11) group (P = 0.18). There was no significant difference in survival for the following: transplant center, blood group compatibility with donors, age, preservation solution, or graft size. For patients retransplanted for acute reasons (primary graft nonfunction (PGNF) or hepatic artery thrombosis [HAT]), survival was significantly better if a second donor was found within 3 days of relisting (52% vs. 20%; P = 0.012). Over the study period progressively fewer donor organs came from outside the region. No strong survival-based argument can be made for separating, in allocation priority, acute and chronic disease patients facing the first transplant as a status 1 recipient. Clearly patients suffering from PGNF or HAT do far better if retransplanted within 3 days. Establishing an even higher status for recipients with PGNF, perhaps drawing from a supraregional donor pool, would allow surgeons to accept more marginal donors, thus potentially expanding the pool, without significantly compromising patient survival. Retransplantation of the recipient with a chronically failing graft who deteriorates to the point of needing life-support is nearly futile, and in todays health care climate, not an optimal use of scarce donor livers.

Management of antacid impactions in hemodialysis and renal transplant patients

Ten cases of intestinal obstruction caused by antacid impactions in renal transplant and hemodialysis patients were added to 16 reports in the literature. In six instances, operative intervention was necessary because of failure of vigorous medical therapy. Three patients who died had perforation of the colon at sites of stercoral ulceration due to firm antacid impactions. Aggressive medical and surgical management of constipation and fecal impaction is recommended. The outlook is grim once colonic perforation has occurred.

In situ cadaver kidney perfusion: experimental and clinical studies.

Lactated Ringers and Collins C2 solutions were compared in different volumes for rapid intra-aortic in situ cooling of pig cadaver kidneys. Both solutions in large volumes caused renal damage when compared with ex vivo flushed controls, although C2 was less injurious. When used for in situ cooling of human cadaver kidneys in volumes less than 1,500 ml/kidney, the two solutions were comparable and did not cause injury when compared with controls. In situ cooling permitted longer excision time (cold ischemia) and is recommended for lessening warm ischemia time in selected cases.