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BACKGROUND: Transplantation of solitary pediatric renal allografts from donors 2 years of age or younger into adult recipients is controversial. METHODS: Between 1998 and 2001, 15 solitary renal allografts from pediatric donors 2 years of age or younger were transplanted into adult recipients. Thirty-three en bloc renal allografts transplanted between 1994 and 2001 were used for comparison. En bloc kidneys were considered for separation if they measured greater than or equal to 6 cm in length. Renal function (creatinine clearance [CrCl]) was estimated using the Cockroft-Gault formula. RESULTS: Two-year graft survival for the solitary and en bloc groups were 93% and 77%, respectively (P =0.405). Five grafts were lost because of arterial thrombosis (four en bloc and one solitary). Ureteral complications occurred in three grafts in the en bloc group. One-year postoperative CrCl of the surviving solitary (n=14) and en bloc (n=26) grafts were 51.4+/-26.2 mL/min and 55.1+/-27.5 mL/min (P >0.05), respectively. Donor weight and kidney length were greater in the solitary group (14.3+/-3.5 kg and 6.3+/-0.4 cm, respectively) compared with the en bloc group (10.8+/-2.6 kg and 5.9+/-0.3 cm, respectively) (P =0.001 and P

A panel of ethicists, organ procurement organization executives, physicians, and surgeons was convened by the sponsorship of the American Society of Transplant Surgeons to determine whether an ethically acceptable pilot trial could be proposed to provide a financial incentive for a family to consent to the donation of organs from a deceased relative. An ethical methodology was developed that could be applied to any proposal for monetary compensation to elucidate its ethical acceptability. An inverse relationship between financial incentives for increasing the families' consent for cadaver donation that clearly would be ethically acceptable (e.g., a contribution to a charity chosen by the family or a reimbursement for funeral expenses) and those approaches that would more likely increase the rate of donation (e.g., direct payment or tax incentive) was evident. The panel was unanimously opposed to the exchange of money for cadaver donor organs because either a direct payment or tax incentive would violate the ideal standard of altruism in organ donation and unacceptably commercialize the value of human life by commodifying donated organs. However, a majority of the panel members supported reimbursement for funeral expenses or a charitable contribution as an ethically permissible approach. The panel concluded that the concept of the organ as a gift could be sustained by a funeral reimbursement or charitable contribution that conveyed the appreciation of society to the family for their donation. Depending on the amount of reimbursement provided for funeral expenses, this approach could be ethically distinguished from a direct payment, by their intrusion into the realm of altruism and voluntariness. We suggest that a pilot project be conducted to determine whether this kind of a financial incentive would be acceptable to the public and successful in increasing organ donation.

CD80 and CD86 (also known as B7-1 and B7-2, respectively) are both ligands for the T cell costimulatory receptors CD28 and CD152. Both CD80 and CD86 mediate T cell costimulation, and as such, have been studied for their role in promoting allograft rejection. In this study we demonstrate that administering monoclonal antibodies specific for these B7 ligands can delay the onset of acute renal allograft rejection in rhesus monkeys. The most durable effect results from simultaneous administration of both anti-B7 antibodies. The mechanism of action does not involve global depletion of T or B cells. Despite in vitro and in vivo evidence demonstrating the effectiveness of the anti-B7 antibodies in suppressing T cell responsiveness to alloantigen, their use does not result in durable tolerance. Prolonged therapy with murine anti-B7 antibodies is limited by the development of neutralizing antibodies, but that problem was avoided when humanized anti-B7 reagents are used. Most animals develop rejection and an alloantibody response although still on antibody therapy and before the development of a neutralizing antibody response. Anti-B7 antibody therapy may have use as an adjunctive agent for clinical allotransplantation, but using the dosing regimens we used, is not a tolerizing therapy in this non-human primate model.

Background Alloimmunization can present a virtually insurmountable barrier to kidney transplantation. Past protocols to desensitize patients using plasmapheresis and cyclophosphamide have not been broadly applied because of the fear of complications, including high rates of immunologic failure. Methods Fifteen patients with a positive donor-recipient cross-match were desensitized with plasmapheresis to permit live donor (LD) transplantation under newer maintenance immunosuppressants. Pretransplant the patients received plasmapheresis three times weekly for a planned maximum of six treatments, plus intravenous hyperimmune globulin, tacrolimus, mycophenolate mofetil, and prednisone. Patients who were successfully desensitized and received transplants were given 10 days of OKT3 postoperatively. Results Eleven of the 15 patients became anti-human globulin cross-match-negative after one to five plasmapheresis treatments and underwent LD transplantation. Relatively low initial titers of donor-specific antibody were predictive of successful attainment of a negative cross-match. Few side effects and rejection episodes were observed. All transplant patients remain dialysis-free after 3-26 months of follow-up. Conclusion A positive cross-match is not necessarily a contraindication to LD transplantation, especially for patients with low donor-specific alloantibody titers.

Simultaneous cadaver kidney pancreas transplantation (SPK) and sequential pancreas after kidney transplantation (PAK) are typically the only options for uremic or posturemic Type 1 diabetic patients who wish to undergo pancreas transplantation. Together they account for more than 99% of all pancreas transplants for uremic or posturemic diabetic patients. 1 SPK transplantation is more widely used than KTA followed by PAK, because SPK is a single operation and there is an “immunologic advantage” for the pancreas because the kidney can serve as a reliable marker for rejection of the pancreas. 2 However, some advocate PAK transplantation if there is a willing living kidney donor. 3 Use of a well-matched living-donor kidney can double the expected renal allograft survival half-life. 4 Living kidney donation also shortens the waiting time for transplantation and expands the organ donor pool. 5 The 1-year pancreas graft survival rate for SPK transplantation is now 83%. 1 During the past 3 to 4 years, the 1-year pancreas graft survival rate for PAK recipients has improved from 54% survival to 71%, shrinking the “immunologic advantage” of combining a cadaver pancreas with a kidney from the same donor. 1,3,6 The use of percutaneous pancreas biopsy coupled with tacrolimus-based immunosuppression results in equivalent success of solitary pancreas and SPK transplantation. 3 Largely because of these results, and because of the distinct advantages of living kidney donation, we have developed a new approach for uremic Type 1 diabetic patients: simultaneous cadaver-donor pancreas and living-donor kidney transplantation (SPLK). More than half of our uremic type I diabetic patients who desire pancreas transplantation now opt for SPLK. Selection of SPLK is generally limited only by the availability of a living donor. As a single procedure, SPLK has obvious advantages over the standard living-donor kidney transplant followed by PAK. Moreover, because the SPLK kidney is from a living donor, there may be both short-term and long-term benefits over SPK transplantation. Potential benefits of SPLK for Type 1 diabetic uremic patients include a shorter waiting time for transplantation and better early and long-term renal graft function. Generalized use of SPLK transplantation would expand the renal organ donor pool, thus benefiting all patients waiting for a kidney transplant. The main drawback to SPLK, coordination of a living donor nephrectomy with a cadaver pancreas transplant, is easily overcome. This paper describes the technique of SPLK and reviews the results of our first 30 consecutive cases. Comparison is made with contemporaneous consecutive series of primary SPK and PAK transplants.

Background. This study examines the current cost of live donor (LD) transplantation at our institution, and compares it with that of dialysis. Methods. The study population consisted of 184 consecutive adult recipients of laparoscopically procured LD kidney transplants. Cost-containment measures instituted during this series included elimination of routine postoperative antilymphocyte induction and an accelerated discharge clinical pathway with planned discharge of the recipient on postoperative day (POD) 2. Costs of the transplants to Medicare were estimated from hospital charges, readmission rates, and immunosuppressant usage. These were compared with published costs of dialysis to Medicare in terms of a fiscal transplant-dialysis break-even point. Results. Kaplan-Meier patient and graft survival rates at 1 year were 97 and 93%, respectively. Among patients followed for at least 90 days and treated with no induction and either cyclosporine-mycophenolate mofetil or tacrolimus-mycophenolate mofetil, acute rejection rates were low (27.6 and 13.9%, respectively). In the last 124 patients, 32.3% were discharged by POD 3 and 71.8% by POD 6, with corresponding mean transplant hospital charges (excluding organ acquisition) of $11,873 and $17,350, respectively. The 30-day readmission rate for patients discharged on the accelerated pathway by POD 3 was only 16%. The least expensive subgroup in the present study (30% of patients) was that of patients discharged by POD 6 and not readmitted during the first year; the break-even point with dialysis costs was calculated as 1.7 years after the transplant. Conclusions. The cost of LD transplants can be safely reduced by elimination of routine postoperative antilymphocyte immune induction and by an early discharge clinical pathway. Uncomplicated LD kidney transplants, meaning those with a short length of stay in the hospital after transplantation and no need for readmission within the first year, accrue savings over dialysis within 2 years.

The oral dose recommendation for FK506 (Fujisawa Pharmaceutical, Deerfield, IL) after liver transplantation has, to date, made no distinction between adult and pediatric patients. Sixteen pediatric and 33 adult liver transplant patients treated long term with oral FK506 were studied. Initial FK506 doses were 0.3 mg/kg/day p.o. or 0.15 mg/kg/day i.v. Thereafter, doses were adjusted to achieve therapeutic FK506 serum levels (0.5-3.0 ng/ml, ELISA liquid/liquid separation) and to maintain an acceptable serum creatinine. FK506 (in mg/kg/day), FK506 levels, and liver function were assessed at monthly intervals on outpatient visits. The mean age of 16 pediatric patients was 5.3 +/- 3.5 years and of 33 adult patients was 49 +/- 12 years. Mean days of FK506 therapy were 284 +/- 136 for pediatric patients and 239 +/- 112 for adult patients. For each time period, pediatric patients required a significantly higher dose of FK506 compared to adult patients (P < 0.001). The overall mean pediatric dose for the first year was 0.46 +/- 0.4 mg/kg/day compared to the mean adult dose of 0.13 +/- 0.01 mg/kg/day. The ratio of pediatric to adult oral FK506 dose requirements ranged from 2.7 to 4.4 over the 1 year of followup. FK506 levels monitored at the same time points showed no significant differences at any month between pediatric and adult patients. We conclude that the oral dose per kilogram per day of FK506 required to maintain similar FK506 levels is significantly greater in pediatric patients compared to adult recipients during the first year of follow-up. Pediatric recipients require substantially more, and adult recipients substantially less, than the recommended oral FK506 dose to achieve a therapeutic effect.

Six hundred sixty-six patients received 792 liver transplants between February 1, 1984 and September 30, 1991. Biliary reconstruction was by choledochocholedochostomy (CDCD) with T-tube (n = 509) or Roux-en-Y choledochojejunostomy (CDJ) (n = 283). Twenty-five patients (4%) developed biliary strictures. Anastomotic strictures were more common after CDJ (n = 10, 3.5%) than for CDCD (n = 3, 0.6%). Intrahepatic strictures developed in 12 patients. Six patients had occult hepatic artery thrombosis (HAT). The other six patients received grafts in which cold ischemia time exceeded 12 hours. Anastomotic strictures were successfully managed by percutaneous dilation (PD) in five patients (n = 10), operation in three (n = 6), with retransplantation required in two patients. Intrahepatic strictures were managed by PD in seven, retransplantation in one, and expectantly in four patients. Of 25 patients, 19 (76%) are alive with good graft function. In three of six deaths, the biliary stricture was a significant factor to the development of sepsis and allograft failure. The authors conclude that (1) anastomotic strictures are rare after LT; (2) the development of biliary strictures may signify occult HAT; (3) PD is effective for most strictures; and (4) extended cold graft ischemia (less than 12 hours) may be injurious to the biliary epithelium, resulting in intrahepatic stricture formation.

Delayed renal allograft function (DGF) is a factor for acute rejection and chronic allograft nephropathy. Cold ischemia time (CIT) is associated with an increased in DGF. Twenty patients receiving allografts with CIT>12 were enrolled in a double-blinded, randomized (1:1), placebo-controlled study to assess vasodilatation with fenoldopam (Abbott; dopamine-1 receptor agonist) on DGF. Fenoldopam infusion began at arterial anastomosis at 0.025 μg/kg/min and titrated to 0.1 μg/kg/min continued for 48 h postop (PO). Immunosuppression included steriods, MMF, and calcinurin inhibitors begun 36 h PO. Antibody induction (AI) using antithymocyte globulin (rabbit) (AT-G(r); Sangstat) was added halfway through the study to African-Americans and for PRA>40%. The need for dialysis, cumulative urine output (UOP), and creatinine (Cr) at PO day 7, 14, and 30 were compared. Eighteen patients completed the study drug infusion. Demographics of groups were not different. There was no difference between fenoldopam and controls for dialysis, UOP at 48 and 72 h, or Cr at 7, 14, or 30 days. There was a difference in UOP when AI (n=7) was compared to non-AI (n=11). At 48 h non-AI UOP 4796+/−3284 ml compared to AI UOP 8960+/−5130 ml (p=0.050). At 72 h, non-AI patients had UOP of 6824+/−4547 ml compared to AI patients with UOP of 12196+/−5868 ml (p=0.044). There was a trend to a lower Cr at day 7 for AI 2.7+/−2.1mg/dl compared to 4.9+/−3.0 mg/dl in non-AI (p=0.11). There was no difference in dialysis or Cr at day 14 and 30 between the AI and non-AI patients. AI with AT-G(r) significantly increases UOP in allografts with CIT>12 h, whereas vasodilatation did not. Therapy for DGF may include AT-G(r) AI.

Background Bleeding following liver resection continues to be a significant morbidity of the procedure. Fibrin sealants represent an improvement over conventional topical hemostatic agents, because they contain components that actively form clot. However, most available agents contain nonhuman protein, which represents an immunologic risk. Hypothesis An investigational surgical fibrin sealant (Crosseal; American Red Cross, Washington, DC) composed of human clottable proteins and human thrombin is more effective than standard topical hemostatic agents in reducing the time required to achieve hemostasis after liver resection. Design Prospective, randomized, controlled trial. Setting Fifteen major referral centers in the United States and the United Kingdom. Methods After liver resection using standard surgical techniques, 121 patients seen between May 1999 and May 2000 were randomized to treatment with a 2-component fibrin sealant (n=58) or to standard topical hemostatic agents, used singly or in combination (n=63). Up to 10 mL of Crosseal was administered by a spray applicator, as recommended by the manufacturer, whereas agents used in the control group were applied according to their instructions for use. Main Outcome Measures The primary outcome measured was time to hemostasis. Secondary outcomes measured included blood loss between application of the hemostatic agent and closure of the abdomen, duration of postoperative biliary drainage, and the occurrence of complications, defined a priori as reoperation for any reason, development of abdominal fluid collections, or bilious appearance of drained fluid for at least 1 day postoperatively. Results The mean time to hemostasis was 282 seconds with Crosseal, compared with 468 seconds with standard agents (2-sided; P =.06), for the 116 efficacy-evaluable patients. Hemostasis was achieved within 10 minutes in 53 patients (91.4%) treated with the study fibrin sealant and in 44 control patients (69.8%)(2-sided; P =.003). Intraoperative blood loss was similar in the 2 groups. In the Crosseal group, the percentage of patients developing postoperative complications was 17.2%, compared with 36.5% in the control group (2-sided; P =.02). Conclusions Compared with the use of standard topical hemostatic agents, Crosseal fibrin sealant significantly reduced the time to achieve hemostasis following liver resection. Patients treated with the new fibrin sealant also experienced significantly fewer postoperative complications.

The increased use of central venous access primarily for hemodialysis has led to a significant increase in clinically relevant central venous occlusive disease (CVOD). The magnitude of and the optimal therapy for CVOD are not clearly established. The purpose of this study is to define the problem of CVOD and determine the success of percutaneous therapy for relieving symptoms and maintaining central venous patency.Patients presenting with disabling upper-extremity edema suggestive of central venous stenosis or occlusion during a 3-year period were evaluated by venography of the upper extremity and central veins. Percutaneous venous angioplasty (PTA) and/or stent placement was performed as clinically indicated. The success of therapy was assessed, and the patients were observed to determine the incidence of recurrence and additional procedures. Recurrent lesions underwent similar evaluation and treatment.A total of 32 sides were treated in 29 patients with a mean of 1.9 interventions per side treated. Hemodialysis-related lesions were the underlying cause in 87% with the remaining 13% related to previous central venous catheterization. The lesions involved the axillary, subclavian, and innominate veins with complete venous occlusion in six (19%) cases. Percutaneous angioplasty was followed by stent placement in six (19%) cases. The procedure was a technical success and was performed without complications in all cases (100%). Mean follow-up was 16.5 months (range, 4-36 months). On average, patient symptoms were controlled for 6.5 months after the initial intervention. Recurrent edema led to additional PTA in 20 (63%) cases. Fifty percent (n = 14) of patients with an arteriovenous fistula (AVF) experienced recurrent symptoms after initial and/or repeat PTA and required AVF ligation. Complete resolution after the initial PTA was predictive of long-term success.Central venous occlusive disease has emerged as a significant clinical problem. Percutaneous venous angioplasty can provide temporary symptomatic relief; however, multiple procedures are often required and long-term relief is rarely achieved.

Many ethical considerations surround living kidney donation, some of which are not anticipated. We present a case in which misattributed paternity was inadvertently discovered during the workup of a father and son and present arguments for and against disclosure of this information. We recommend that transplant programs advise patients participating in living organ donor programs that misattributed paternity might be discovered during routine preoperative testing and that protocols for dealing with complex ethical issues be in place.

OBJECTIVE To evaluate the strategies instituted by the authors' center to decrease the time to transplantation and increase the rate of transplantation for African-Americans, consisting of a formal education program concerning the benefits of living organ donation that is oriented to minorities; a laparoscopic living donation program; use of hepatitis C-positive donors in documented positive recipients; and encouraging vaccination for hepatitis B, allowing the use of hepatitis B core Ab-positive donors. SUMMARY BACKGROUND DATA The national shortage of suitable kidney donor organs has disproportional and adverse effects on African-Americans for several reasons. Type II diabetes mellitus and hypertension, major etiologic factors for end-stage renal disease, are more prevalent in African-Americans than in the general population. Once kidney failure has developed, African-Americans are disadvantaged for the following reasons: this patient cohort has longer median waiting times on the renal transplant list; African-Americans have higher rates of acute rejection, which affects long-term allograft survival; and once they are transplanted, the long-term graft survival rates are lower in this population than in other groups. METHODS From March 1990 to November 2001 the authors' center performed 2,167 renal transplants; 944 were in African-Americans (663 primary cadaver renal transplants and 253 primary Living donor renal transplants). The retransplants consisted of 83 cadaver transplants and 17 living donor transplants. Outcome measures of this retrospective analysis included median waiting time, graft and patient survival rates, and the rate of living donation in African-Americans and comparable non-African-Americans. Where applicable, data are compared to United Network for Organ Sharing national statistics. Statistical analysis employed appropriate SPSS applications. RESULTS One- and 5-year patient survival rates for living donor kidneys were 97.1% and 91.3% for non-African-Americans and 96.8% and 90.4% for African-Americans. One- and 5-year graft survival rates were 95.1% and 89.1% for non-African-Americans and 93.1% and 82.9% for African-Americans. One- and 4-year patient survival rates for cadaver donor kidneys were 91.4% and 78.7% for non-African-Americans and 92.4% and 80.2% for African-Americans. One- and 5-year graft survival rates for cadaver kidneys were 84.6% and 73.7% for non-African-Americans and 84.6% and 68.9% for African-Americans. One- and 5-year graft and patient survival rates were identical for recipients of hepatitis C virus-positive and anti-HBc positive donors, with the exception of a trend to late graft loss in the African-American hepatitis C virus group due to higher rates of noncompliance, an effect that disappears with censoring of graft loss from that cause. The cadaveric renal transplant median waiting time for non-African-Americans was 391 days compared to 734 days nationally; the waiting time for African-Americans was 647 days compared to 1,335 days nationally. When looking at all patients, living and cadaver donor, the median waiting times are 220 days for non-African-Americans and 462 days for African-Americans. CONCLUSIONS Programs specifically oriented to improve volunteerism in African-Americans have led to a marked improvement in overall waiting time and in rates of living donation in this patient group. The median waiting times to cadaveric renal transplantation were also significantly shorter in the authors' center, especially for African-American patients, by taking advantage of the higher rates of hepatitis C infection and encouraging hepatitis B vaccination. These policies can markedly improve end-stage renal disease care for African-Americans by halving the overall waiting time while still achieving comparable graft and patient survival rates.

During the past few years, we have witnessed a significant improvement in pancreas graft survival rates, resulting in a dramatic increase in the number of pancreas transplants performed. In 1998, more than 1,200 pancreas transplants were performed in the United States, a 15% increase from the previous year. 1 The technique of draining the pancreatic duct into the donor jejunum that was originally described 2 has historically been associated with a high incidence of intraabdominal infections. As a result, the modified technique of bladder drainage 3 gained wide acceptance as the method of choice for pancreatic duct drainage. Recently, enteric duct drainage has been readopted by many pancreas transplant centers primarily to avoid the well-known metabolic and urologic complications of bladder drainage. According to the International Pancreas Transplant Registry, 1 the proportion of enteric-drained procedures has continuously increased, concomitant with the number of centers using this technique. In 1995, 29% of all transplant centers performed at least one enteric-drained pancreas transplant, but by 1998, 98% of the transplant centers in the United States had at some point used enteric drainage. The graft survival and technical failure rates are comparable to those of bladder-drained pancreatic grafts. With recognition that more than 20% of bladder-drained grafts have to be converted to enteric drainage by 2 years, enteric drainage with systemic venous drainage has emerged as the procedure of choice. Systemic venous drainage of pancreas transplants has been associated with hyperinsulinemia, 4–6 which itself has been associated with dyslipidemia. 7 This raised the concern that pancreas transplantation with systemic venous drainage might promote accelerated atherosclerosis independent from the dyslipidemic effects of immunosuppressive medication. 4,8 To circumvent this problem, in 1992 Rosenlof et al 9 described a more physiologic technique of draining the transplanted pancreas into the recipient’s portal circulation via the splenic vein. The technique was later modified by Gaber et al. to drain directly into the superior mesenteric vein. 10 This technique has resulted in significantly reduced plasma insulin and C-peptide levels 11 as well as improvements in lipoprotein composition. 12 However, the immunologic benefits, although alluded to in a small number of patients, 13 were not confirmed by appropriate comparisons of systemic- and portal-drained procedures in a larger series. Numerous experimental models have shown an immunomodulatory role of the liver after exposure of donor antigen into the portal vein. It is possible, therefore, that drainage of the transplanted pancreas into the portal vein mimics these experimental models and elicits a degree of immunomodulation. The purpose of this study was to assess whether an immunologic or survival advantage exists in portal venous versus systemic venous drainage in both solitary pancreas transplants and in combined kidney and pancreas transplants.

We report a case of a 62-yr-old man with chronic hepatitis B virus (HBV)-related cirrhosis who developed hepatic decompensation after being started on lamivudine requiring liver transplantation. Decompensated liver disease while on lamivudine has been previously reported on two occasions, both HIV coinfected patients on a combination of nucleoside analogues. Our patient is alive and well nearly 2 yr after successful liver transplantation.

Objective To examine the impact of laparoscopic nephrectomy and recipient education on the proportion of kidney recipients who could identify a potential live donor, and on the live donor (LD) transplantation rate. Summary Background Data Laparoscopic donor nephrectomy (LDN) results in less postoperative surgical pain, a shorter hospital stay, and quicker recovery than the standard open donor nephrectomy (ODN). The authors hypothesized that the availability of this less invasive surgical technique would enhance the willingness of family and friends to donate. Methods The study population consisted of 3,298 end-stage renal disease patients referred for kidney transplant evaluation between November 1991 and February 2000, divided into three groups. The first group received no formal LD education and had only ODN available. The second group received formal education about the LD process and had only ODN available. The third group had both formal LD education and LDN available. Records were examined to determine what proportion of each group had any potential donors tissue-typed, and the rate at which they received an LD transplant. Results Before LDN availability and formal LD education, only 35.1% of referrals found a potential donor, and only 12.2% received an LD transplant within 3 years. Institution of a formal education program increased the volunteer rate to 39.0%, and 16.5% received an LD transplant. When LDN became available, 50% of patients were able to find at least one potential donor, and within 3 years 24.7% received an LD transplant. Regression analysis indicated that availability of LDN was independently associated with a 1.9 relative risk of receiving an LD transplant. Kaplan-Meier death-censored 1- and 3-year graft survival rates for ODN transplants were 95.8% and 90.6%, versus 97.5% and 94.8% for LDN. Conclusions The availability of LDN and an LD family education program has doubled the live donor transplantation rate, and outcomes remain excellent.

In this randomized controlled trial comparing FK-506 to CsA, we report parameters of nephrotoxicity in adult patients surviving > 90 days after orthotopic liver transplant (OLT). Patients randomized to FK-506 first received 0.15 mg/kg IV/day followed by 0.3 mg/kg PO/day. Doses were modified to avoid toxicity and to achieve FK-506 levels of 0.5 to 1.5 ng/ml. CsA was administered in the usual manner with dose adjustments to whole blood HPLC levels. A pre-OLT glomerular filtration rate (GFR) of > or = 30 ml/min/1.73/m2 and/or serum creatinine < or = 2.0 mg/dl were required for inclusion in the study. GFRs were obtained at post OLT days 28, 180, and 360. Other parameters of renal function evaluated were creatinine, magnesium, serum electrolytes, blood pressure, use of antihypertensives, and magnesium supplements. There were 38 patients in the FK-506 group and 34 in the CsA group. The mean days of follow up for each group was similar: 456 +/- 135 days for the FK-506 group and 451 +/- 112 days for the CsA group. The mean oral dose for the FK-506 group ranged from 0.13-0.16 mg/kg/day with mean FK-506 levels of 0.6-0.8 ng/ml. In the FK-506 group, there was a significant fall in the pre-transplant GFR from 89 +/- 31 ml/min/173 m2 to 43 +/- 15 ml/min/173 m2 at day 360. Similarly, for the CsA group, the pre-transplant GFR of 75 +/- 31 ml/min/1.73 m2 fell to 49 +/- 17 ml/min/1.73 m2 at day 360. At each time point studied, there was no significant difference in mean GFR between the two groups. There were no significant differences in the monthly mean values for creatinine, electrolytes, magnesium, or blood pressure between the two groups. Magnesium levels were in the low normal range (1.4-1.6 mEq/L), and the mean potassium levels in the high normal range (4.4-4.7 mEq/L). In both groups, a similar number of patients required magnesium supplementation or hypertensive medications. The nephrotoxicity of FK-506 given at low oral doses and with concomitant low levels was comparable to that of CsA. The two drugs were remarkably similar in their spectrum of electrolyte disturbances and incidence of hypertension.

Arterial ketone body ratio (AKBR) was measured serially in 49 pediatric orthotopic liver transplantations. The AKBR pattern correlated with hepatic synthetic function, as well as with short-term graft and patient survival. A rapid recovery pattern of AKBR to above 1.0 within 40 hr after reperfusion was associated with 94% graft and patient survival. Pediatric liver grafts were found to have better tolerance to low energy levels when compared with previously published data for adult OLT. The salvage rate of pediatric grafts exhibiting a slow recovery pattern (AKBR 0.7-1.0) was 71%. No recovery pattern (AKBR0.7) was seen in all 6 cases of primary nonfunction, and in 3 of 4 cases of early hepatic artery thrombosis (HAT). All these grafts were lost; however, 56% of the children in this group survived retransplantation. Unlike the PNF grafts, the no recovery pattern after HAT was characterized by gradual improvement of the synthetic function, despite the low energy state.

The Budd-Chiari syndrome is an unusual form of portal hypertension caused by hepatic vein occlusion, which results in centrilobular congestion and necrosis. Its overall mortality rate exceeds 50% at 2 years, and optimal treatment remains controversial. To determine optimal therapy on the basis of clinical and angiographic data, we retrospectively analyzed 30 patients with this disease treated at the University of California, Los Angeles or the University of Southern California School of Medicine between 1955 and 1985. Twelve patients were treated conservatively with diuretics, anticoagulants, paracentesis, and/or peritoneal-venous shunt. Eighteen patients were treated by definitive surgery: side-to-side portocaval shunt (four), mesocaval shunt (four), side-to-side splenorenal shunt (one), liver transplantation (two), transatrial membranotomy (TM) (two), TM followed by inferior vena cava reconstruction (IVCR) (one), TM followed by mesocaval shunt (one) simultaneous IVCR and side-to-side portocaval shunt (one), IVCR (one), and azygousatrial shunt followed 4 years later by a splenopulmonary shunt (one). Overall the surgical group had survival rates superior to the medical group, with a 2-year survival rate of 54% for the surgical group vs. 9% for the medical group (p

Fifteen patients who had a prior portasystemic shunt underwent orthotopic liver transplantation. Shunt types were portacaval in six patients, H-graft mesocaval in six, distal splenorenal in two, and proximal splenorenal in one. Mean blood loss and hospital stay were highest in the portacaval group. Retransplants (two patients) and deaths (two patients) also were limited to this group. In this report, technical considerations, advantages, and disadvantages of the various shunt types are described. Management of patients with late stages of portal hypertension must include estimation of the effects of a portasystemic shunt on subsequent liver transplantation. It is concluded that portacaval shunts should be avoided in patients who may be considered for transplantation. Distal splenorenal shunts are best performed in younger patients with intractable variceal bleeding who are not expected to require transplantation in the near future. A mesocaval H-graft is the shunt of choice in patients who are current liver transplant candidates.

One hundred six liver biopsy specimens from 34 orthotopic liver transplant (OLT) patients were examined and the histologic findings correlated with the clinical course of the patients to determine if specific morphologic patterns were associated with specific causes of acute allograft dysfunction. The principle causes of allograft injury in these patients appeared to be acute rejection and ischemic injury, with rarer cases of viral infection and biliary obstruction. Graft rejection causing transient liver dysfunction was associated with a mixed inflammatory infiltrate in the portal tracts and involving the interlobular bile ducts. Rejection resulting in severe, persistent dysfunction was associated with destruction and loss of the interlobular bile ducts or portal inflammation, followed by acute centrilobular hepatocyte necrosis. Ischemic liver injury was characterized by hepatocyte ballooning and/or hepatocyte necrosis. Ischemic injury causing transient graft dysfunction demonstrated focal, limited areas of hepatocyte necrosis or transient centrilobular hepatocyte ballooning. Severe ischemic injury resulting in persistent dysfunction caused diffuse hepatocyte necrosis or centrilobular ballooning followed by centrilobular hepatocyte loss and severe cholestasis with evidence of bile duct epithelial injury. The histologic patterns observed were not pathognomonic; radiologic studies, bile cultures, and other laboratory tests were necessary to rule out biliary or vascular obstruction and bacterial cholangitis. However, liver biopsies, especially serial biopsies, were helpful in suggesting the probable cause of liver dysfunction and in predicting subsequent allograft recovery or failure.

Objectives The increased use of central venous access primarily for hemodialysis has led to a significant increase in clinically relevant central venous occlusive disease (CVOD). The magnitude of and the optimal therapy for CVOD are not clearly established. The purpose of this study is to define the problem of CVOD and determine the success of percutaneous therapy for relieving symptoms and maintaining central venous patency. Methods Patients presenting with disabling upper-extremity edema suggestive of central venous stenosis or occlusion during a 3-year period were evaluated by venography of the upper extremity and central veins. Percutaneous venous angioplasty (PTA) and/or stent placement was performed as clinically indicated. The success of therapy was assessed, and the patients were observed to determine the incidence of recurrence and additional procedures. Recurrent lesions underwent similar evaluation and treatment. Results A total of 32 sides were treated in 29 patients with a mean of 1.9 interventions per side treated. Hemodialysis-related lesions were the underlying cause in 87% with the remaining 13% related to previous central venous catheterization. The lesions involved the axillary, subclavian, and innominate veins with complete venous occlusion in six (19%) cases. Percutaneous angioplasty was followed by stent placement in six (19%) cases. The procedure was a technical success and was performed without complications in all cases (100%). Mean follow-up was 16.5 months (range, 4-36 months). On average, patient symptoms were controlled for 6.5 months after the initial intervention. Recurrent edema led to additional PTA in 20 (63%) cases. Fifty percent (n = 14) of patients with an arteriovenous fistula (AVF) experienced recurrent symptoms after initial and/or repeat PTA and required AVF ligation. Complete resolution after the initial PTA was predictive of long-term success. Conclusions Central venous occlusive disease has emerged as a significant clinical problem. Percutaneous venous angioplasty can provide temporary symptomatic relief; however, multiple procedures are often required and long-term relief is rarely achieved.

2 observations rares: rupture d'anevrysme de l'artere splenique peu apres transplantation hepatique. Une malade meurt de choc hemorragique malgre la tentative de traitement chirurgical, l'autre est traitee efficacement par splenectomie

• Conventional treatment of acute liver allograft rejection has included high doses of corticosteroids and antithymocyte globulin. Urgent retransplantation was the only option for patients who failed to respond. We report our initial experience with the use of monoclonal anti—T3-cell antibody (OKT3) in 25 patients with acute hepatic allograft rejection that was resistant to steroid and/or antithymocyte globulin therapy. Twenty-four of 25 patients had a response to OKT3, which was complete in 14 and partial in ten. With a mean follow-up of 8.2 months, allograft salvage has been 80% and patient survival 88%; two patients underwent successful retransplantation. Side effects have been mild and well tolerated. Repeated rejection has occurred in 40% of patients, but these episodes have responded to steroid therapy. We conclude that OKT3 is well tolerated and highly effective in reversing severe episodes of acute hepatic allograft rejection that is resistant to highdose steroid therapy. ( Arch Surg 1987;122:1120-1123)

A clinical program in liver transplantation was begun at UCLA in 1984 after a period of laboratory investigation. The first 100 orthotopic liver transplants (OLT) were performed in 83 patients (43 adults and 40 children) between February 1, 1984 and November 1, 1986. Donors and recipients were matched only for size and ABO blood group compatibility, with OLT performed across blood groups in 28 patients. Standard operative techniques were used, including venous-venous bypass in adults. Arterial reconstruction was performed using an aortic Carrel patch or "branch patch" in 65% of cases and by end-to-end or aortic conduit techniques in the remainder. The hepatic artery thrombosis rate was 5%. Biliary reconstruction was choledochocholedochostomy in 67 OLT and Roux-en-Y choledochojejunostomy in 33 (complication rate of 24% and 24%, respectively). Average lengths and ranges of donor liver ischemia, operating time, and blood replacement were 4 hours (range: 1-10 hours), 7.6 hours (range: 4-15 hours), and 17 units packed cells (range: 2-220 units). Immunosuppressive regimen was cyclosporine-steroid combination, with monoclonal anti-T-cell antibody (OKT3) used for refractory rejection. All patients had one or more complications: pulmonary (78%), infectious (51%), renal dialysis (25%), neurologic (22%). All patients had at least one episode of acute rejection, and 3.6% had chronic rejection. Retransplantation was needed in nine patients once and in four patients twice. The overall retransplant survival rate was 54%, and two of four patients who received a second retransplant are alive. Sixty-three of the 83 patients (76%) are alive (adults 72%, children 80%). The 1- and 2-year actuarial survival rate is 73% (adults 68%, children 78%). Thirty-eight of 43 patients (88%) who had transplantation in the past year are alive. Of 14 perioperative variables assessed as predictors of early mortality, only postoperative dialysis (p less than 0.0005) and presence of severe rejection (p less than 0.01) had statistical significance. Seventy per cent of adults returned to work, and 84% of children had normal or accelerated growth. A new program in liver transplantation provides a dramatic option in patient care and an academic stimulus to the entire medical center.

A group of 52 liver transplant patients was prospectively randomized to receive prophylactic immunosuppressive therapy consisting of either Orthoclone OKT3 for 14 days, azathioprine, and steroids (25 patients); or cyclosporine, azathioprine, and steroids (27 patients). The groups were similarly matched for age, diagnosis, and Child's classification. The patients were studied to determine the effect of these two regimens on the incidence of rejection, infection, renal dysfunction, and mortality. Seven rejection episodes, as determined by clinical and histological criteria, occurred in seven of 25 patients (28%) receiving OKT3 compared with 18 episodes in 27 patients (67%) receiving cyclosporine during the first 14 days after transplantation (P less than 0.02). In 20% of the OKT3 patients, CD3+ levels of greater than 10% developed during therapy, and 16% of the patients developed anti-OKT3 antibodies during OKT3 treatment. Five patients were retreated with OKT3 for steroid-resistant acute rejection episodes; all had resolution of the rejection episode. Infectious complications were similar in each group. Renal function, as measured by serum creatinine, was significantly better with OKT3 than with cyclosporine (P less than 0.003) at 14 days. We conclude that prophylactic OKT3 is effective in reducing the number of early rejection episodes after liver transplantation; after 14 days the incidence of rejection is similar; reuse of OKT3 has been successful in liver transplant patients; infectious complications are similar between OKT3 and cyclosporine; and OKT3 preserves renal function better than cyclosporine and is thus indicated in patients with compromised preoperative renal function.

• Seventy-two patients who underwent orthotopic liver transplantation (OLT) were studied to identify perioperative variables that would predict survival and intraoperative blood loss. Survival and intraoperative blood loss were not affected by encephalopathy, length of donor liver ischemia, or any of the preoperative laboratory values studied. Survival was significantly decreased in patients requiring postoperative dialysis (41%) and in patients who had severe rejection requiring retransplantation (33%). Intraoperative blood loss was significantly greater in patients over 50 years of age (11.6 blood volumes) and patients with biliary atresia (8.7 blood volumes). These results may aid in choosing future recipients for orthotopic liver transplantation and in anticipating the postoperative support needed. ( Arch Surg 1987;122:1109-1111)

• Thirty-five patients received 42 liver homografts between February 1984 and August 1985. One or more infections developed in 23 patients (66%) some time after transplantation. An average of 2.5 infections per infected patient occurred. Of 37 bacterial infections, two thirds were either bacteremias or localized intra-abdominal infections. The median onset was 29 days after operation. Thirteen viral infections were identified, with a median onset of 18 days after operation. Nine fungal infections, six disseminated and three localized, were identified, with a median onset of nine days after operation. Infection was the primary cause of death in five (14%) of 35 patients. Fatal infections were evenly distributed among bacterial (two), fungal (three), and viral (two) pathogens. Despite advances in surgical techniques and the use of cyclosporine, infection after orthotopic liver transplantation is a serious problem. Certain patients can be identified as high risks for infection and require an aggressive diagnostic workup followed by early institution of antimicrobial therapy. ( Arch Surg 1988;123:360-364)