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Introduction: Pancreatic transplantation (PTx) with portal venous delivery of insulin and enteric drainage of the exocrine secretion is more physiologic than bladder-systemic (BS) drainage. With portalenteric (PE) PTx, the diagnosis of acute rejection (AR) requires a percutaneous biopsy. The roux-en-y (RNY) venting jejunostomy in patients with PEPTx offers a novel approach to monitor rejection and prevent anastomatic leaks. Methods. From January 1996 to December 1998, we performed 17 simultaneous kidney/pancreas transplants (SKPTx). The initial 4 patients underwent BS drainage and the subsequent 13 patients underwent RNY venting jejunostomy with PE drainage. All patients were treated with quadruple therapy. There were 9 males, 14 patients were Caucasian with a mean age of 32 yr (range 30-54 yr), and a mean pre-transplantation duration of diabetes of 25 yr. Six patients underwent endoscopic donor duodenal biopsy through the jejunostomy to rule out clinically suspected AR. Gastrograffin was inserted into the jejunostomy to examine the integrity of anastamosis when indicated. In 9 out of 13 patients, the venting jejunostomy was taken down 9-12 months post-transplantation after allograft function was stable. Results. Actual patient, kidney, and pancreas graft survival rates were 100, 100 and 94%, respectively, after a mean follow-up of 16 months. Renal allografts functioned immediately in 89% of patients. The mean length of hospital stay was 19 d. Four (23%) patients (2 with BS drainage and 2 with PE drainage) suffered an AR episode in the first month, and 4 (23%) patients had five AR from 3-36 months post-transplantation. Other complications were post-operative bleeding in 3 patients, wound infection in 2 patients and a proximal duodenal stump leak in 1 patient. In patients with clinical rejection, endoscopy through the venting jejunostomy showed inflamed, friable doudenal mucosa and doudenal biopsy findings were compatible with AR. Conclusion. These preliminary results suggest that RNY venting jejunostomy with PE drainage can be used safely to diagnose and monitor pancreas AR and to diagnose and prevent anastamotic leaks. This technique will be even more useful to visualize transplanted duodenal mucosa, collect pancreatic secretions (amylase) for analysis and perform endoscopic retrograde cholangiopancreatography if needed to obtain pancreatic biopsies.

Introduction. Organ transplantation has become an accepted means of treating end-stage organ disease in recent years with acceptable patient and graft survival. Transplant recipients have an increased risk of infectious complications due to multiple factors including decreased host resistance from chronic end-stage organ failure as well as from the immunosuppression required to prevent graft rejection. Hypothesis. Therefore, the use of contaminated allografts could result in life-threatening infections in organ recipients. Method. In this study, transplant patients receiving organs from donors with positive blood or urine cultures, from 1993 to 1997, were retrospectively reviewed. Results. There was a total of 599 organ donors in our state. Forty-six (7.5%) had positive blood cultures and 25 (4.5%) had positive urine cultures. A total of 179 patients received organs from these contaminated donors, 36 of which were transplanted at our center. In this group, there were 16 kidney, 9 liver, and 11 heart transplants. Both donors and recipients received prophylactic broad-spectrum antibiotics, which were adjusted based on culture and sensitivity results. The most common organisms isolated from the blood were staphylococci followed by streptococci and Gram-negative organisms. Three of the 9 liver transplant patients in the series died with a mortality of 33%. Two of the 3 patients who died had sepsis but the responsible organisms were different from those recovered from the donor. The rest (66%) did well and have acceptable liver function. None of the 16 renal transplant recipients developed an infection and all survived. One patient developed acute irreversible rejection requiring transplant nephrectomy. There was one death in the heart transplant group resulting in a mortality of 9%. This death was not attributed to infectious processes. Three of 11 heart transplant patients grew organisms in the post-operative period that were similar to those found in the corresponding donors. However, no patient suffered significant morbidity or mortality from these infections and all recovered. The recipients of contaminated organs had levels of organ function similar to those of randomly chosen recipients of non-contaminated organs, and both groups had similar lengths of hospital stay. Conclusion. Only 3 of 36 organ recipients had infections caused by organisms found in the contaminated donor organs for a rate of 8%. Contaminated donor organs seem to fare as well as non-contaminated donor organs and there was no increase in morbidity or mortality. Contamination of organs should not be an absolute contraindication to the use of these organs in transplantation.

Background. Researchers have shown that reperfusion of ischemic tissues initiates a complex series of reactions that paradoxically injure tissues. Although several mechanisms have been proposed to explain the pathobiology of ischemic/reperfusion (I/R) injury, much attention has focused on adhesion molecules. Our research is intended to show the kinetics of P-selectin in the liver in response to I/R injury.Methods. Left-lobar hepatic ischemia was induced for 30 min in 35 C57BL-6 mice and 20 P-selectin-deficient (K-O) mice. P-selectin expression was measured in these mice at 20 min, 2, 5, 12 and 24 h reperfusion times, as well as in control and sham animals. The animals were injected with radio-labeled P-selectin monoclonal antibody and the organs were harvested for counts/g tissue, expressed as the percentage injected dose. Serum liver enzymes were measured and pathological sections of ischemic and control livers were performed. The unpaired t-test was used for statistical analysis.Results. P-selectin expression showed two peaks in this animal model. The first peak was at 20 min and the second peak at 5 h of reperfusion (p

Organ transplantation has become an accepted means of treating end-stage organ disease in recent years with acceptable patient and graft survival. Transplant recipients have an increased risk of infectious complications due to multiple factors including decreased host resistance from chronic end-stage organ failure as well as from the immunosuppression required to prevent graft rejection.Therefore, the use of contaminated allografts could result in life-threatening infections in organ recipients.In this study, transplant patients receiving organs from donors with positive blood or urine cultures, from 1993 to 1997, were retrospectively reviewed.There was a total of 599 organ donors in our state. Forty-six (7.5%) had positive blood cultures and 25 (4.5%) had positive urine cultures. A total of 179 patients received organs from these contaminated donors, 36 of which were transplanted at our center. In this group, there were 16 kidney, 9 liver, and 11 heart transplants. Both donors and recipients received prophylactic broad-spectrum antibiotics, which were adjusted based on culture and sensitivity results. The most common organisms isolated from the blood were staphylococci followed by streptococci and Gram-negative organisms. Three of the 9 liver transplant patients in the series died with a mortality of 33%. Two of the 3 patients who died had sepsis but the responsible organisms were different from those recovered from the donor. The rest (66%) did well and have acceptable liver function. None of the 16 renal transplant recipients developed an infection and all survived. One patient developed acute irreversible rejection requiring transplant nephrectomy. There was one death in the heart transplant group resulting in a mortality of 9%. This death was not attributed to infectious processes. Three of 11 heart transplant patients grew organisms in the post-operative period that were similar to those found in the corresponding donors. However, no patient suffered significant morbidity or mortality from these infections and all recovered. The recipients of contaminated organs had levels of organ function similar to those of randomly chosen recipients of non-contaminated organs, and both groups had similar lengths of hospital stay.Only 3 of 36 organ recipients had infections caused by organisms found in the contaminated donor organs for a rate of 8%. Contaminated donor organs seem to fare as well as non-contaminated donor organs and there was no increase in morbidity or mortality. Contamination of organs should not be an absolute contraindication to the use of these organs in transplantation.

Pancreatic transplantation (PTx) with portal venous delivery of insulin and enteric drainage of the exocrine secretion is more physiologic than bladder-systemic (BS) drainage. With portal-enteric (PE) PTx, the diagnosis of acute rejection (AR) requires a percutaneous biopsy. The roux-en-y (RNY) venting jejunostomy in patients with PEPTx offers a novel approach to monitor rejection and prevent anastomatic leaks.From January 1996 to December 1998, we performed 17 simultaneous kidney/pancreas transplants (SKPTx). The initial 4 patients underwent BS drainage and the subsequent 13 patients underwent RNY venting jejunostomy with PE drainage. All patients were treated with quadruple therapy. There were 9 males, 14 patients were Caucasian with a mean age of 32 yr (range 30-54 yr), and a mean pre-transplantation duration of diabetes of 25 yr. Six patients underwent endoscopic donor duodenal biopsy through the jejunostomy to rule out clinically suspected AR. Gastrograffin was inserted into the jejunostomy to examine the integrity of anastamosis when indicated. In 9 out of 13 patients, the venting jejunostomy was taken down 9-12 months post-transplantation after allograft function was stable.Actual patient, kidney, and pancreas graft survival rates were 100, 100 and 94%, respectively, after a mean follow-up of 16 months. Renal allografts functioned immediately in 89% of patients. The mean length of hospital stay was 19 d. Four (23%) patients (2 with BS drainage and 2 with PE drainage) suffered an AR episode in the first month, and 4 (23%) patients had five AR from 3-36 months post-transplantation. Other complications were post-operative bleeding in 3 patients, wound infection in 2 patients and a proximal duodenal stump leak in 1 patient. In patients with clinical rejection, endoscopy through the venting jejunostomy showed inflamed, friable doudenal mucosa and doudenal biopsy findings were compatible with AR.These preliminary results suggest that RNY venting jejunostomy with PE drainage can be used safely to diagnose and monitor pancreas AR and to diagnose and prevent anastamotic leaks. This technique will be even more useful to visualize transplanted duodenal mucosa, collect pancreatic secretions (amylase) for analysis and perform endoscopic retrograde cholangiopancreatography if needed to obtain pancreatic biopsies.

Mechanisms of injury in hepatic ischemia/reperfusion injury are poorly defined. Leukocytes are thought to be important in the final mechanism of hepatic damage. We intend to show the time course of abnormal leukocyte activity in the liver after ischemia/reperfusion (I/R) injury. Left lobar hepatic ischemia was induced for 20 min in anesthetized C57B1-6 mice. Measurements were taken at control, reperfusion, and matching sham times (no ischemia) of 2, 5, 12, and 24 h. Measurements were taken using rhodamine and fluorescein enhanced intravital microscopy. Post sinusoidal venules were evaluated for numbers of rolling leukocytes, leukocyte saltation, and leukocyte velocity. Data are expressed as number of rolling leukocytes per 100 microns venule length (2 min). Statistical analysis was by ANOVA. The number of rolling leukocytes at 5, 12, and 24 h of reperfusion (p0.001) was significantly higher than control and sham-operated animals. Leukocyte velocities were significantly slower in the 12 h I/R group when compared to sham animals (p0.001). These data show that there are definable and quantifiable changes in leukocyte kinetics in the liver after ischemia/reperfusion. These changes, which lasted for 24 h, are likely due to upregulation of various endothelial cell adhesion molecules. Delineation of these mechanisms may be important in disease states such as shock, sepsis, and hepatic transplantation.

In previous studies we reported a solid-phase, enzyme-linked immunoassay (ELISA) that can be used to quantitate the soluble fraction of human histocompatibility leukocyte class I antigens (S-HLA-I) and study their relevance in transplantation. In this study we determined the concentration and distribution of S-HLA-I in patients with end-stage liver disease (ESLD), as well as in liver transplant recipients. Sera were obtained from 51 patients with ESLD and 40 donor-recipient pairs. We analyzed the S-HLA-I in sera obtained from liver donors, as well as from liver transplant recipients (patients with ESLD), with sera from the latter obtained before and at various intervals up to 3 yr after transplantation. The results of the analyses justify the following conclusions: 1) Patients with ESLD had mean values of S-HLA-I (909 +/- 596 ng/ml) greater than those for the normal population (643 ng/ml) (P0.05); the S-HLA-I secretion decreased with increasing severity of liver disease. 2) Patients with tumors had mean S-HLA-I levels (399 ng/ml) significantly lower than those in patients with ESLD related to other causes. 3) In liver transplant recipients the S-HLA-I levels stabilized at approximately 1 month after transplant and remained relatively stable thereafter (mean level 950 +/- 536 ng/ml). The observed levels were also greater than those for the normal population (P0.05). 4) Preoperative and postoperative S-HLA-I values in liver transplant recipients demonstrated a biphasic distribution, dividing patients into high- and low-secretor groups. 5) During the post-transplant observation period, of these selected liver transplant recipients there was no difference between high- and low-secretor groups in the incidence of rejection (high, 70%; low, 67%), graft survival (high, 95%; low, 94%), or patient survival (high, 95%; low, 94%). 6) Measurement of the total amount of S-HLA-I, containing yet undefined ratios of both donor and recipient S-HLA-I, cannot be used to predict a state of tolerance in liver transplant recipients.

Anti-lymphocytes induction therapy in renal transplants remains controversial relative to efficacy and cost benefit. It has been suggested that shortening the duration of induction therapy from 14 to 7 d would provide adequate efficacy at less cost. Our objective was to compare the efficacy and complications of short (7 d or less, group A) versus standard (14 d or more, group B) duration of OKT3 induction therapy in renal allograft recipients. We performed a retrospective review of all renal allografts performed between July 1989 and September 1994. Two groups were identified based on the duration of OKT3 induction therapy. There were no significant differences between group A or B in the distribution of age, sex, race, degree of HLA matching, and etiology or renal failure. Patients in group B experienced fewer rejections at 3 and 12 months (p = 0.0236 and p = 0.0065, respectively) as well as fewer viral infections during the first year of follow-up (p = 0.0435). No difference on the mean number of bacterial or fungal infections existed between the two groups. There were no statistically significant differences in patient or graft survival, although patients in group B had a tendency towards increased 1-yr graft survival.

This paper provides the current data which has been accrued by the UNOS National Scientific Registry as a result of the mandatory sharing of 6-antigen matched kidneys. The 6-month graft survival does not show, as yet, any benefit for first grafts (N = 72), but does show substantial benefit for repeat grafts (N = 25). No penalty from sharing could be demonstrated since graft survival for local and shared organs was the same. The rationale for two new UNOS policies are discussed: (1) mandatory sharing of phenotypically identical kidneys, (2) the "payback system" for shared kidneys. Finally, some personal comments of the author regarding the importance of the National Organ Procurement and Transplant Network are recorded.