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Background: Anti-HIV-1 IgM antibody is an important immunoassay target for early HIV antibody detection., Objectives: The objective of this study is to determine if the early HIV antibody sensitivity of the 60s INSTI test is due to detection of anti-HIV-1 IgM in addition to IgG., Study Design: To demonstrate HIV gp41 IgM antibody capture by the INSTI HIV-1 gp41 recombinant antigen, an HIV-IgM ELISA was conducted with commercial HIV-1 seroconversion samples. To demonstrate that the INSTI dye-labelled Protein A-based colour developer (CD) has affinity to human IgM, commercial preparations of purified human immunoglobulins (IgM, IgD, IgA, IgE, and IgG) were blotted onto nitrocellulose (NC) and probed with the CD to observe spot development. To determine that INSTI is able to detect anti-HIV-1 IgM antibody, early seroconversion samples, were tested for reduced INSTI test spot intensity following IgM removal., Results: The gp41-based HIV-IgM ELISA results for 6 early seroconversion samples that were INSTI positive determined that the assay signal was due to anti-HIV-1 IgM antibody capture by the immobilised gp41 antigen. The dye-labelled Protein-A used in the INSTI CD produced distinct spots for purified IgM, IgA, and IgG blotted on the NC membrane. Following IgM removal from 21HIV-1 positive seroconversion samples with known or undetermined anti-HIV-1 IgM levels that were western blot negative or indeterminate, all samples had significantly reduced INSTI test spot intensity., Conclusions: The INSTI HIV-1/HIV-2 Antibody Test is shown to detect anti-HIV-1 IgM antibodies in early HIV infection which enhances its utility in early HIV diagnosis., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: For broader utilization of rapid HIV antibody assays in point-of-care (POC) settings, methods should be simple enough to be performed with accuracy by untrained test providers, using only the test manufacturer's written instructions., Objective: To demonstrate that the INSTI HIV-1 Antibody Test is simple and accurate enough to be successfully run by untrained operators in a POC setting., Study Design: A prospective study was conducted to compare the results of the FDA-cleared, INSTI HIV-1 Antibody Test (INSTI, bioLytical Laboratories Inc., Richmond, BC, Canada) used by untrained operators on finger-stick whole blood to results obtained by trained laboratory professionals using FDA-cleared comparator methods (CM) on matching venous blood. A total of 1388 subjects were recruited into the study in three diverse US POC sites. One central laboratory was used for CM testing. Untrained operators and experienced laboratory professionals also conducted a study on prepared plasma specimens to compare limit of detection (LoD) abilities., Results: Of the 517 HIV positive subjects (34 new positives and 483 known positives) the concordance between INSTI performed by untrained operators and CM performed by trained laboratory professionals was 100% (95% CI=99.3-100%). Concordance for HIV negative results (n=871) was 99.8% (95% CI=99.2-99.9%). There were no significant differences in INSTI limit of detection between untrained operators and laboratory professionals., Conclusions: Untrained operators with no laboratory background were able to perform and interpret the results of INSTI on finger-stick blood and LoD specimens with a high degree of accuracy by following only the manufacturer's written instructions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Hypothesis: The true extent of morbidity among live liver donors remains poorly understood. In this unique and often high-profile area of surgery, the development of standards for defining and reporting complications would foster a better understanding of the incidence and magnitude of such adverse events (AEs)., Design: Retrospective review of AEs among live liver donors., Setting: University-affiliated teaching hospital., Patients and Methods: Of 202 individuals undergoing evaluation for live liver donation, 42 (20.8%) proceeded to surgery. Thirty-four underwent a right lobectomy without the middle hepatic vein; 3, a left lateral segmentectomy. Any event causing a deviation from a patient's ideal course was considered an AE and subsequently classified according to a derived framework. Morbidity was defined as 1 or more AEs., Main Outcome Measures: Incidence, timing, type, severity, and impact of AEs., Results: No deaths or significant hepatic dysfunction occurred. In 5 (12%) of the 42 donors, the hepatectomy was aborted for anatomic reasons before parenchymal transection. Eight (22%) of the remaining 37 experienced 11 AEs, of which 10 completely resolved, whereas 1 AE (3%) resulted in a permanent disability (brachial plexopathy). The overall incidence of AEs was 0.30 per case. Ten (91%) of the 11 AEs presented within the first postoperative month., Conclusions: Most live liver donations are uncomplicated or do not lead to permanent consequence. The adoption of a standards-based classification framework for AEs in live liver donors would allow for an inclusive, consistent, and universally applicable method to collect, analyze, and report donor morbidity.

Objective: To analyze a single center's 13-year experience with 569 pediatric orthotopic liver transplants for end-stage liver disease., Summary Background Data: Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. Innovative surgical techniques and improved immunosuppression have broadened the application of liver replacement for affected children. However, liver transplantation in the child remains challenging because of the scarcity of donor organs, complex surgical technical demands, and the necessity to prevent long-term complications., Methods: The medical records of 440 consecutive patients younger than 18 years of age undergoing orthotopic liver transplantation for end-stage liver disease from March 20, 1984, to November 15, 1997, were reviewed. Results were analyzed using Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival rates were determined at 1, 3, 5, and 10 years. The type and incidence of posttransplant complications were determined, as was the quality of long-term allograft function. The median follow-up period was 4.1 years., Results: Biliary atresia was the most common cause (50.4%) of endstage liver disease in this patient population. The median recipient age was 2.4 years; 239 patients (54%) were younger than 3 years of age and 1 11 patients (25%) were younger than 1 year of age. There were 471 whole organs, 29 were ex vivo reduced size, 33 were living-related donor, and 36 were in situ split-liver allografts. Three hundred forty-three (78%) patients underwent a single allograft, whereas 97 patients required retransplantation; hepatic artery thrombosis was the most common indication for retransplantation (55 patients). The 1-, 3-, 5-, and 10-year actuarial patient survival rates were 82%, 80%, 78%, and 76%, respectively; allograft survival rates were 68%, 63%, 60%, and 54%. Long-term liver function remains excellent: current median follow-up values for total bilirubin and aspartate aminotransferase were 0.5 mg/dl and 54 IU/L, respectively. Cox multivariate regression analysis demonstrated that pretransplant patient age, the era of transplantation, and the number of allografts performed significantly and independently predicted patient survival rates, whereas allograft type and pretransplant diagnosis did not., Conclusions: Liver transplantation in the pediatric patient is a durable procedure that provides excellent long-term survival. Although there have been overall improvements in patient outcome with increased experience, the effect is most pronounced for patients younger than 1 year of age. Retransplantation, although effective in a meaningful number of patients, continues to carry a progressive decrement in survival with the number of allografts performed. Use of living-related and in situ split-liver allografts has dramatically reduced waiting times for small children and has improved patient survival.

Objective: To review the clinical characteristics, outcomes, and risk factors for survival among 57 pediatric patients undergoing orthotopic liver transplantation for fulminant hepatic failure at the University of California, Los Angeles, Center for the Health Sciences., Design: The medical records of 57 consecutive pediatric patients undergoing orthotopic liver transplantation for fulminant hepatic failure from July 1, 1984, to June 25, 1997, were reviewed and survival data were analyzed via univariate and multivariate statistical methods. The type and incidence of posttransplant complications were determined as was the quality of long-term graft function. Median follow-up period was 3.38 years (range, 0-10.02 years)., Results: The 1-, 3-, and 5-year actuarial patient survival rates were 77%, 77%, and 77%, respectively, while graft survivals were 73%, 65%, and 65%. Stepwise Cox regression analysis revealed that recipient age and ventilator dependency at the time of transplantation were independently and significantly correlated with patient survival, whereas no association was found between survival and grade of encephalopathy, prior abdominal surgery, recipient weight, pretransplantation values for total bilirubin or prothrombin time, ABO match, allograft type, peak posttransplantation aspartate aminotransferase levels, or the presence of posttransplantation hepatic artery thrombosis. Non-ventilator-dependent patients demonstrated a 96% 1-, 3-, and 5-year survival as compared with only 56% at these same time points for those children requiring ventilator support at the time of transplantation (P < .001). At the time of most recent follow-up, median values for total bilirubin and aspartate aminotransferase concentrations were 10.3 micromol/L (0.6 mg/dL) and 56 U/L, respectively, in the 40 surviving patients., Conclusions: In children undergoing liver transplantation for fulminant hepatic failure: (1) overall results are comparable to those achieved for less emergent non-neoplastic indications in this same age group; (2) ventilator dependency prior to transplantation is the strongest predictor of ultimate survival, followed by recipient age; (3) 5-year survival exceeds 90% in recipients who are ventilator independent immediately prior to liver transplantation but is significantly compromised once the need for mechanical ventilation supervenes, particularly in those younger than 4 years; and (4) prompt referral and timely liver replacement are the cornerstones of optimal outcome.

Background: We retrospectively reviewed 213 consecutive patients who received their first liver allograft between January 1 and December 31, 1993, in order to study the impact of ischemia/preservation/reperfusion injury (IPRI) on patient and graft outcome., Methods: The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr after transplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax<600 U/L (n=46); group 2, ASTmax=600-2000 U/L (n=97); group 3, ASTmax>2000-5000 U/L (n=50), and group 4, ASTmax>5000 U/L (n=17). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and United Network for Organ Sharing (UNOS) status as covariates., Results: Groups were comparable with respect to age, UNOS status at the time of transplantation, and diagnostic case mix. Median follow-up was 644 days. The overall incidence of primary graft nonfunction (PNF) was 7.6%. PNF incidence was significantly correlated with the severity of IPRI (0%, 4%, 10%, and 41% for groups 1 to 4, respectively, P < 0.0001), but this impact was confined to the respective rates of retransplantation as early patient survival was unaffected. The 1-year survival of patients whose initial grafts manifested extreme IPRI (group 4) was significantly inferior to recipients in the three other groups (77%, 71%, 73%, and 52% for groups 1 to 4, respectively, P=0.03). This increased mortality was confined to patients who never achieved discharge from their initial hospitalization, with no significant differences between groups being detected in the survival of those patients who were discharged (84%, 80%, 85%, and 81% for groups 1 to 4, respectively, P=NS). Although overall 1-year graft survival was strongly correlated with the extent of IPRI (77%, 67%, 62%, and 41% for groups 1 to 4, respectively, P=0.001), this correlation was abolished when survival of grafts not lost to PNF was examined at 1 and 2 years. Stepwise Cox regression analysis confirmed the independent association between ASTmax and patient and graft survival. The long-term quality of allograft function as well as the incidence of chronic rejection and biliary complications were unrelated to the extent of IPRI., Conclusions: We conclude that: (1) patient survival is influenced by IPRI only when it is extreme (ASTmax>5000 U/L), provided parameters of graft function are used in conjunction with aminotransferase values to assess the need for prompt retransplantation; (2) short-term graft survival is proportional to the extent of IPRI, but grafts that are not lost to PNF have equivalent 1- and 2-year survival irrespective of the magnitude of IPRI; (3) 40% of grafts with extreme IPRI are lost to PNF, but the same proportion also provide long-term function; and (4) for surviving grafts, long-term biochemical function as well as the incidence of biliary complications and of chronic rejection are unrelated to the extent of IPRI.

The clinical characteristics and outcome of posttransplantation aplastic anemia (AA) were determined in 12 of 1,736 patients (0.007%) undergoing orthotopic liver transplantation (OLT) that were afflicted with AA. None of the affected patients had a history of hematologic disease. Median patient age was 53 years (range, 2-61 years); 10 of the affected patients were men, and 2 were women. The etiologies of AA included non-A, non-B, non-C fulminant hepatic failure (FHF) (3 patients), graft-versus-host disease (4 patients), Parvovirus-induced (1 patient), and idiopathic (4 patients). The median duration between OLT and the onset of AA was 12 days (range, 11-14 days) in the 3 patients undergoing OLT for FHF; in contrast, AA developed in the other 9 patients at 37 days (range, 27-51 days) after OLT. Eleven patients were treated with reduction of their cyclosporine or tacrolimus dosage, granulocyte colony-stimulating factor, anti-thymocyte globulin, and Solumedrol. Two of the 3 patients developing AA following OLT for FHF achieved hematologic recovery 21 and 92 days after diagnosis. In contrast, all 9 non-FHF patients developing AA after OLT died, 5 due to infectious complications and 4 following intracranial bleeding. AA is an unusual complication of OLT. In the setting of FHF, it affects young males in the early posttransplantation period, and, when infectious complications can be avoided, remission and stable allograft function can be anticipated. However, in the non-FHF patient, AA occurs in older individuals later in the posttransplantation period and has a uniformly poor outcome.

Background: The shortage of cadaveric donor livers is the rate-limiting step in clinical liver transplantation. Split liver transplantation provides a means to expand the cadaveric donor pool. However, this concept has not reached its full potential because of inferior patient and graft survival and high complication rates when traditional ex vivo split techniques are used. Therefore we sought to evaluate the safety, applicability, and effectiveness of a new technique for split liver transplantation., Methods: This study consists of 15 in situ split liver procurements, which resulted in 28 liver transplants. In situ splitting of selected livers from hemodynamically stable cadaveric donors was performed at the donor hospital without any additional work-up or equipment being needed. In situ liver splitting is accomplished in a manner identical to the living-donor procurement. This technique for liver splitting results in a left lateral segment graft (segments 2 and 3) and a right trisegmental graft (segments 1 and 4-8). This procedure required the use of the donor hospital operating room for an additional 1.5-2.5 hr and did not interfere with the procurement of 30 kidneys, 12 hearts, 7 lungs, and 9 pancreata from these same donors., Results: The 6-month and 1-year actuarial patient survival rates were 92% and 92%, respectively, while the 6-month and 1-year actuarial graft survival rates were 86% and 86%, respectively. The 6-month and 1-year actuarial patient survival rate of patients who received a left lateral segment graft was 100% and 100%, respectively, while those who received a right trisegmental graft had 6-month and 1-year rates of 86% and 86%, respectively. The actuarial death-censored graft survival rates at 6 months and 1 year were 80% and 80%, respectively, for the left lateral segment grafts, and 93% and 93%, respectively, for the right trisegmental grafts. Alograft and patient survival was independent of United Network for Organ Sharing status at the time of liver transplantation. No patient developed a biliary stricture, required re-exploration for intra-abdominal hemorrhage, or suffered from portal vein, hepatic vein, or hepatic artery thrombosis, Conclusions: In situ split liver transplantation can be accomplished without complications and provides results that are superior to those obtained previously with ex vivo methods. It abolishes ex vivo benching and prolonged ischemia times and provides two optimal grafts with hemostasis accomplished. This technique decreases pediatric waiting time and allows adult recipients to receive right-sided grafts safely. In situ splitting is the method of choice for expanding the cadaveric liver donor pool.

Objective: To determine whether increased immunosuppression is a contributor to poor outcome in hepatitis C-infected orthotopic liver transplant (OLT) recipients, we retrospectively analyzed the consequences of using OKT3 in our program for steroid-resistant rejection (SRR)., Methods: We compared the histological recurrence of HCV in two contemporary cohorts of OLT recipients. Group 1 consisted of HCV-positive patients who received OKT3 for SRR (n = 19). Group 2 (n = 33) consisted of age-, gender-, and initial immunosuppression-matched HCV-positive controls who were treated with at least one steroid pulse for acute cellular rejection but who did not require treatment with OKT3. Liver biopsies were obtained per protocol within the first month and as necessary to evaluate abnormalities in serum liver chemistries., Results: Mean and median follow-up were comparable for the two groups. Recurrence of HCV was diagnosed by histological verification and was documented in 16 of 19 (84.2%) group 1 patients versus 17 of 33 (51.5%) group 2 patients (p = 0.03). The interval to recurrence was significantly shorter in patients who received OKT3 (p = 0.028). Logistic regression identified OKT3 as a significant risk factor for the recurrence of HCV within the first year post-OLT (p = 0.0004). The histological severity score, based on the most recent liver biopsy at long-term follow-up or the explant biopsy if the patient required retransplantation, was significantly higher in group 1. Moreover, cirrhosis was demonstrable in a greater proportion of allografts in patients who had received OKT3 at some point (26.3% vs. 6%, p = 0.028). Long-term follow-up revealed a trend toward higher alanine aminotransferase levels (p = 0.05) and total bilirubin (p = 0.08) in group 1 patients., Conclusions: Our data suggest that allograft hepatitis in patients with preexisting HCV occurs earlier and with greater severity in patients treated with OKT3 for SRR, compared with age-, gender-, and initial immunosuppression-matched contemporary controls. Treatment of SRR with OKT3 may jeopardize long-term allograft function and survival in HCV-infected recipients by enhancing viral hepatitis recurrence. Clearly, the recognition of recurrent HCV and differentiation from acute cellular rejection remains a crucial issue in managing the OLT recipient with HCV.

Objective: The purpose of this study was to develop a bioartificial liver (BAL) to treat patients with severe liver failure until they can be either transplanted or recover spontaneously., Summary Background Data: Severe acute liver failure is associated with high mortality. Liver transplantation has emerged as an effective therapy for patients who did not respond to standard management. However, because of the donor organ shortage and urgent need for transplantation, many patients die before they can be transplanted and others do not survive after transplantation, primarily because of intracranial hypertension., Methods: Three groups of patients with severe acute liver failure were treated with the BAL. In group 1 (n = 18) were patients with fulminant hepatic failure (FHF), in group 2 (n = 3) were patients with primary nonfunction (PNF) of a transplanted liver, and in group 3 (n = 10) were patients with acute exacerbation of chronic liver disease. Patients in groups 1 and 2 were candidates for transplantation at the time they entered the study, whereas patients in group 3 were not., Results: In group 1, 16 patients were "bridged" successfully to transplantation, 1 patient was bridged to recovery without a transplant, and 1 patient died because of concomitant severe pancreatitis. In group 2, all patients were bridged successfully to retransplantation. In group 3, two patients were supported to recovery and successful transplants at later dates; the other eight patients, although supported temporarily with the BAL, later died because they were not candidates for transplantation., Conclusions: The authors' clinical experience with the BAL has yielded encouraging results. A randomized, controlled, prospective trial (phase II-III) is being initiated to determine the efficacy of the system.

Objective: The purpose of this study was to analyze a single center's 12-year experience with 127 orthotopic liver transplantations (OLT) for primary sclerosing cholangitis (PSC)., Summary Background Data: Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown origin that occurs most commonly in young men and is associated frequently (70-80%) with inflammatory bowel disease (IBD). Patients with PSC also are at risk for the development of cholangiocarcinoma (CCA) and those with IBD for colon carcinoma. Although the course of PSC is variable, it frequently is progressive, leading to cirrhosis and requirement for OLT., Methods: The medical records of 127 consecutive patients undergoing OLT for PSC from July 1, 1984, to May 30, 1996, were reviewed. Actuarial patient and graft survival was determined at 1,2, and 5 years. The incidence and outcome of patients with CCA, recurrent sclerosing cholangitis, and post-transplant colon carcinoma was determined. Results were analyzed by way of stepwise Cox regression to determine the statistical strength of independent associations between pretransplant covariates and patient survival. The median follow-up period was 3.01 years. Incidental cholangiocarcinoma (ICCA) was defined as a tumor < 1 cm in size that was discovered at the time of pathologic sectioning of the explanted liver., Results: Ninety-two patients (72%) had associated IBD. Seventy-nine (62%) had undergone previous biliary tract surgery. One hundred seven patients (84%) received a single graft, whereas 20 patients (16%) required 22 retransplants. Patients received either cyclosporine- (n = 76) or tacrolimus- (n = 51) based immunosuppression. The 1-, 2-, and 5-year actuarial patient survivals were 90%, 86%, and 85%, respectively, whereas graft survival was 82%, 77%, and 72%, respectively. The presence of previous biliary surgery had no effect on patient survival. Ten patients (8%) had ICCA and their survival was not significantly different from patients without ICCA (100%, 83%, and 83% at 1, 2, and 5 years, respectively). Four patients were known to have CCA at the time of OLT, all recurred within 6 months, and had a significantly worse outcome (p < 0.0001). Recurrent sclerosing cholangitis developed in 11 patients (8.6%). The patient and graft survival in this group was not different from those in whom recurrence did not develop (patient; 100%, 90%, and 90%; graft: 80%, 70%, and 52%). Thirty patients (23%) underwent colectomy after liver transplantation for dysplasia-carcinoma or symptomatic colitis. Of the nine covariates entered into the Cox multivariate regression analysis, only common bile duct frozen section biopsy specimen showing CCA was predictive of a survival disadvantage., Conclusions: Liver transplantation provides excellent patient and graft survival rates for patients affected with PSC independent of pretransplant biliary tract surgery. Incidental cholangiocarcinoma does not affect patient survival significantly. However, known CCA or common duct frozen section biopsy specimen or both showing CCA are associated with poor recipient survival, and OLT should be proscribed in these cases. Recurrent PSC occurs in approximately 9% of cases but does not affect patient survival. Post-transplant colectomy does not affect patient survival adversely.

Background: Hepatic artery thrombosis (HAT) after liver transplantation for biliary atresia (BA) is a serious complication that most often leads to retransplantation (re-OLT). The purpose of the present study was: (1) to identify risk factors associated with HAT and (2) to analyze the impact of recently introduced microsurgical hepatic arterial reconstruction (MHR) on the incidence of HAT, subsequent need for re-OLT, and patient survival., Methods: A retrospective review of 194 patients transplanted for BA was performed. One hundred and sixty-six patients (group 1) underwent conventional arterial reconstruction and 28 (group 2) had MHR., Results: Actuarial survival for patients with HAT was significantly worse than for patients without HAT at 1, 2, and 5 years (71%, 61%, and 57% versus 85%, 85%, and 85%, P = 0.0007). Stepwise logistic regression analysis revealed that the risk of HAT correlated best with the type of arterial reconstruction (P = 0.007) followed by pretransplant bilirubin concentration (P = 0.04) and the number of acute rejection episodes (P = 0.03). In group 1, 32 patients developed HAT (19%), and of these, 18 underwent re-OLT for HAT. No patient in group 2 developed HAT (P = 0.006 versus group 1). One-year actuarial patient survival was 81% in group 1 and 100% in group 2 (P = 0.02)., Conclusions: In OLT for BA, (1) the predominant risk factor for HAT is the technique of arterial reconstruction, and (2) MHR markedly reduces the incidence of HAT and the need for re-OLT while improving patient survival.

To determine the impact of different flush and reperfusion techniques on postreperfusion syndrome (PRS) and postoperative graft function, 100 transplants were randomly assigned into four groups as follows: group 1 (n=31), portal vein flush, no vena caval venting; group 2 (n=21), hepatic arterial flush, no vena caval venting; group 3 (n=29), portal vein flush with vena caval venting; and group 4 (n=19), hepatic artery flush with vena caval venting. Donor and recipient characteristics were similar. Extensive intraoperative and postoperative monitoring was performed and measurements were documented immediately before reperfusion and at 1, 5, 15, and 30 min after reperfusion. PRS was defined by three criteria: mean arterial pressure (MAP) <60 mmHg at 1 min after reperfusion, MAP <60 mmHg at 5 min after reperfusion, and a decrease of 30% or more for the MAP percent area under the curve during the initial 5 min after reperfusion (%AUC). Using these definitions, the overall incidence of PRS was 21%, 8%, and 43%, respectively. Group 1 was the most hemodynamically stable; the incidence of PRS in group 1 was 2/31 (7%) at 1 min and 8/31 (25%) using %AUC criteria compared with 7/21 (33%) at 1 min and 12/21 (57%) using %AUC criteria for group 2 (P<0.05). The patients in groups 3 and 4 (vena caval venting) demonstrated smaller percentage increases in serum potassium levels (as determined by %AUC; 4.3+/-6.8 and 0.3+/-5.4, vs. 15.1+/-8.1 for group 1 and 22.9+/-8.2 for group 2). The difference between group 4 and group 2 was statistically significant (P<0.05). The increases in serum potassium did not translate into increased cardiac or hemodynamic instability. Combining all data obtained over the first 30 min after reperfusion, there was no statistically significant difference in hemodynamic or biochemical changes noted among the four groups. Postoperative liver function was similar among the four groups. We conclude that portal vein flush without vena caval venting provided a lower incidence of PRS than any other technique. Vena caval venting decreased the release of potassium into the circulation. Postoperative graft function was not significantly affected by flush and reperfusion techniques.

Eight (0.59%) of 1,347 patients who underwent liver transplantation at the UCLA Medical Center (Los Angeles) developed coccidioidomycosis. Whereas only one case occurred during the first 8 years and 10 months of the UCLA Liver Transplant Program (February 1984 to December 1992), seven cases occurred within the following 23-month period (December 1992 to November 1994). The median time of onset for infection after transplantation was 8 weeks (range, 4-312 weeks). Clinical presentations of patients with coccidioidomycosis included pneumonia (six cases), pneumonia with meningitis (one case), hepatitis (one case), and monoarticular arthritis (one case). Despite therapy with amphotericin B alone (six cases) or amphotericin B plus fluconazole (two cases), infection was fatal in four of eight cases. As of this writing, the four surviving patients are receiving chronic maintenance therapy with either fluconazole (three patients) or itraconazole (one patient). These experiences show that coccidioidomycosis can be a serious and frequently fatal infection after liver transplantation and that the incidence of this disease appears to be increasing.

Use of the supraceliac aorta for hepatic arterial reconstruction of the transplanted liver in the setting of inadequate recipient celiac and hepatic arterial inflow has been advocated and has resulted in a decreased hepatic artery thrombosis rate in both the adult and pediatric populations. Over the past 6 years, we have utilized the supraceliac aorta in more than 200 patients without complication. However, in this communication, we report a major neurologic complication that resulted in anterior spinal artery syndrome.

Liver disease due to hepatitis C (HCV) is an increasingly frequent indication for orthotopic liver transplantation (OLT). The aim of the current study was to analyze the causes of graft loss following OLT for chronic hepatitis C and the longterm outcome following retransplantation in a large university program. Between January 1990 and December 1995, 1183 patients underwent primary OLT at our center. In 304 patients, HCV was diagnosed by seropositivity and/or polymerase chain reaction. Fifty-six (18.4%) of these patients underwent retransplantation. The 36 patients retransplanted for primary non-function were excluded from further analysis. The other indications for regrafting (>30 days following primary transplant) included hepatic artery thrombosis (5), chronic rejection (4), severe HCV recurrence (5), and other etiologies (6). The cumulative survival rates for the 248 patients who received 1 OLT (group 1) were 84% after one year and 75% after three years. The corresponding rates for the 20 non-PNF patients who were retransplanted (group 2) were 60% and 43%, respectively (P<.0001). Moreover, logistic regression analysis confirmed that patients in group 2 were more than 4 times likely to die than patients in group 1 (P<.0034; risk ratio, 4.2; 95% confidence interval 1.61 to 11.37). Patients undergoing retransplantation had a high incidence of serious infectious complications leading to mortality. Two additional patients with severe recurrent HCV died awaiting liver retransplantation. Eight of the 304 total patients (2.6%) transplanted for chronic HCV developed graft failure secondary to HCV recurrence and 6 of the 8 were retransplanted; 3 of the 6 patients retransplanted are alive without evidence of histologic recurrence (mean follow-up less than 1 year). In summary, despite the high frequency of recurrent histologic evidence of HCV following primary OLT (70% at 3 years), graft loss attributable solely to HCV is an infrequent finding. Retransplantation per se is a risk factor for a fatal outcome, and the indication for reOLT does not appear to impact ultimate outcome. Serious infectious complications were the leading cause of mortality in patients retransplanted. Furthermore, given the indolent natural history of HCV, longer follow-up is necessary to determine the ultimate rate of graft loss due to HCV recurrence.

This study was designed to determine the frequency of hyperlipidemia after orthotopic liver transplantation and whether treatment with a hydroxy-methylglutaryl coenzyme A reductase inhibitor was safe and efficacious. Cholesterol levels were assessed in 45 consecutive adult liver transplants (mean +/- SE). Four of 22 patients on cyclosporine (CsA) (18%) and three of 23 patients on FK506 (13%) had levels >225 mg/dl at 12 months (cholesterol levels for patients on CsA [total n=22]: pre-Tx = 140+/-11, 1 month = 183+/-36,3 months = 221+/-12, 6 months = 211+/-11, 12 months = 202+/-14 [P<0.01 vs. pre-Tx]; FK506 [total n=23]: Pre-Tx = 151+/-13, 1 month = 187+/-22, 3 months = 188+/-10, 6 months = 184+/-13, 12 months = 164+/-9 [P=0.02 vs. CsA]). A separate cohort of patients with stable graft function, cholesterol >225 mg/dl, and two additional risk factors for coronary artery disease were started on pravastatin. Ninety-eight patients were enrolled. Sixteen patients (16%) discontinued the drug because of subjective complaints. No episodes of rhabdomyolysis or hepatotoxicity occurred (cholesterol levels for patients on CsA [total n=65]: pretreatment = 251+/-7, 6 months = 220+/-7 [P=0.01 vs. pretreatment], 12 months = 224+/-8 [P=0.01 vs. pretreatment]; FK506 [total n=17]: pretreatment = 251+/-17, 6 months = 219+/-17, 12 months = 208+/-17 [P=0.08 vs. pretreatment]). Natural killer cells isolated from normal volunteers (n=14) exhibited 27+/-9% specific lysis. Patients on FK506 or cyclosporine-based immunosuppression alone (n=11) exhibited 20+/-4% specific lysis. Standard immunosuppression plus pravastatin (n=10) decreased lysis to 0.2+/-10% (P<0.02 vs. controls and standard immunosuppression). We conclude: (1) posttransplant hyperlipidemia occurs less frequently in liver transplant patients than in renal or cardiac transplants; (2) pravastatin is safe and efficacious for cholesterol reduction in liver transplant patients; and (3) pravastatin coadministered with standard immunosuppression reduces natural killer cell-specific lysis in these recipients.

From 1988 to 1993, UCLA completed 938 first and 1,146 total orthotopic liver transplants (OLT). Race analysis demonstrated a 1-year patient survival of 89% in Blacks (n = 45) versus 80% in Whites (n = 492, p < 0.02), with no significant difference shown between Hispanics (n = 278) and Whites. The 1-year patient survival in Asians was 50% (n = 58, p < 0.02 vs. Whites) even when hepatitis B was excluded (59%, n = 43). The 1-year patient survival of hepatitis B surface antigen positive Asians (n = 15) was only 21% (p < 0.02 vs. all others). OLT patients whose panel reactive antibody (PRA) was < 10% (n = 339) demonstrated no graft or patient survival advantage versus recipients whose PRA was > 10% (n = 71). A positive antidonor flow cytometry crossmatch (> 30 mean channel shifts, n = 76) was associated with a decreased 1-year graft survival (56% vs. 73%, p < 0.05) when compared to flow negative recipients (n = 185). Graft survival for 0 DR mismatches was 74% at 1 year compared with 57% for 1 DR mismatches (p < 0.02) and 59% for 2 DR mismatches (p < 0.02).

To study the effect of immunosuppressive reduction on the incidence and consequence of late acute rejection (LAR) in liver allograft recipients, mean daily prednisone dose, mean cyclosporine A (CsA) trough and nadir levels were retrospectively reviewed for the nearest 12-week period preceding six episodes of LAR in five liver allograft recipients (group 1). Results were compared with those from a cohort of 12 liver allograft recipients who did not develop LAR (group 2). LAR was defined as acute rejection occurring more than 365 days post-transplantation. Median follow-up for both groups was similar (504 days, range 367 to 1050, versus 511 days, range 365 to 666, not significant). Mean trough CsA levels were lower in patients with LAR compared with those without (224 +/- 66 ng/mL versus 233 +/- 49 ng/mL) but the difference was not statistically significant. In contrast, mean daily prednisone dose (2.5 +/- 1.6 mg/day versus 6.5 +/- 2.9 mg/day, P = 0.007) and CsA nadir values (129 +/- 60 ng/mL versus 186 +/- 40 ng/mL, P = 0.03) were significantly lower in patients who developed LAR compared with those who did not. Five of six episodes (83%) of LAR occurred in patients receiving less than 5 mg/day of prednisone, versus a single LAR episode in only one of 12 patients (8%) receiving prednisone 5 mg/day or more (P = 0.004). In all but one instance, LAR responded to pulse methylprednisolone without discernible affect on long term graft function. The authors conclude that liver allograft recipients remain vulnerable to acute rejection beyond the first post-transplant year; and reduction of immunosuppressive therapy, particularly prednisone, below a critical, albeit low dose, threshold increases the risk of LAR.

Jehovah's Witness patients who refuse transfusions have generally not been felt to be candidates for liver transplantation owing to the frequent requirement for blood transfusions during liver transplantation. This is the first report to our knowledge of successful emergent liver transplantation without the use of blood or blood products in a Jehovah's Witness. The surgical and anesthetic strategies employed in achieving a successful outcome are discussed.

Objective: The authors analyze a single center's 11-year experience with 190 orthotopic liver transplants for congenital biliary atresia., Summary Background Data: Hepatic portoenterostomy generally is the initial treatment for children with congenital biliary atresia. Despite multiple modifications of the hepatic portoenterostomy, two thirds of treated patients still develop recurrent cholestasis, portal hypertension, cholangitis, and cirrhosis. Therefore, the only hope of long-term survival in the majority of children with congenital biliary atresia is definitive correction with orthotopic liver transplantation., Methods: The medical records of 190 consecutive patients undergoing orthotopic liver transplantation for congenital biliary atresia from July 1, 1984 to February 29, 1996 were reviewed. Results were analyzed via Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival was determined at 1, 2, and 5 years. The type and incidence of post-transplant complications were determined, as was the quality of long-term graft function. The median follow-up period was 3.21 years., Results: The liver grafts were comprised on 155 whole-organ, 24 reduced-size, and 11 living donor organs. Median pretransplant values for recipient age, weight, and total bilirubin were 1.4 years, 12.3 kg, and 13.8 mg/dL, respectively. One hundred sixty-four patients (86%) had undergone prior hepatic portoenterostomy. Eighty-seven patients (46%) were United Network for Organ Sharing (UNOS) status 1 or 2 at the time of liver transplantation. The majority (15/24, 62%) of reduced-size graft recipients were UNOS status I at the time of transplantation. One hundred fifty-nine patients (84%) received a single graft, whereas 31 patients required 37 retransplants. The 1, 2, and 5 year actuarial patient survival rates were 83%, 80% and 78% respectively, whereas graft survival rates were 81%, 77%, and 76%, respectively. Cox multivariate regression analysis demonstrated that pretransplant total bilirubin, UNOS status, and graft type significantly predicted patient survival, whereas recipient age, weight, and previous hepatic portoenterostomy did not. Current median follow-up values for total bilirubin and aspartate aminotransferase levels in the 154 surviving patients were 0.5 mg/dL and 34 international units/L, respectively., Conclusion: Long-term patient survival after orthotopic liver transplantation for congenital biliary atresia is excellent and is independent of recipient age, weight, or previous hepatic portoenterostomy. Optimal results are obtained in this patient population when liver transplantation is performed before marked hyperbilirubinemia, and when possible, using a living-donor graft.

The tremendous success of OLT as a highly effective treatment for patients with end-stage liver disease has resulted in a rapid increase in the number of candidates for the procedure. Refinements in organ preservation, improvements in surgical technique and immunosuppression, and better postoperative management have contributed to improved survival rates. The discrepancy between the paucity of organs and the increasing numbers of potential recipients will continue to worsen until there are extraordinary breakthroughs in providing alternatives to human whole-organ livers, such as xenografts or cultured hepatocyte infusions. For now, the vast majority of patients with life-threatening liver disease are not likely to receive a liver graft. Thus, the issues of patient selection and timing of OLT have become even more relevant. Prompt referral to a transplant center is not only in the patient's best interest, but also it has been shown to be cost-effective. Over the last 30 years, it has become clear that hepatic malignancy, initially a common reason for OLT, should be an indication for transplantation only in highly selected individuals. The role of adjuvant chemotherapy needs to be defined, and proven treatment alternatives need to be developed. New antiviral agents may enable a large group of patients with chronic hepatitis B to be successfully transplanted, placing even greater demands on the already limited supply of donor livers. Hepatitis B appears to be species specific, and it is conceivable that xenotransplantation from a nonsusceptible donor species may confer protection to HBV reinfection, eliminating the problems of an inadequate donor supply. Until novel approaches, including xenotransplantation, gene therapy, or replacement of hepatic function by cultured hepatocyte infusions, become a widespread reality, future allocation policies may highlight outcome as well as urgency as a fundamental variable to determine if transplantation is reasonable. Survival rates have been shown to fall with advancing levels of urgency, resulting in a conflict between equity and efficacy in organ allocation. As waiting lists for liver transplantation continue to grow, it is becoming increasingly apparent that patients must be referred to a transplant center earlier in the course of liver disease.

Objective: To analyze the impact of preexisting portal vein thrombosis (PVT) on the operative management and outcome of liver transplantation., Design: Retrospective review of 1423 patients who received transplants over 11 years., Setting: Tertiary referral center., Patients or Other Participants: Seventy patients who underwent liver transplantation who had preexisting PVT., Interventions: Portal vein thromboendovenectomy, vein grafting, or use of portal collateral veins for inflow during liver transplantation., Main Outcome Measures: Postoperative PVT, intraoperative transfusion, retransplantation rate, 30-day and 1-year actuarial survival rates., Results: Operative management consisted of thromboendovenectomy in 61 cases, vein graft to the superior mesenteric vein in 6 cases, and vein graft to other mesenteric veins in 3 cases. The incidence of posttransplant PVT was 3% (n = 2). The mean +/- SD transfusion requirement was 23 +/- 18 U. The 1-year actuarial survival rate was 74% but improved from 66% in the first 35 cases to 82% in the latter 35 cases., Conclusions: Thromboendovenectomy is the procedure of choice for PVT. Results of liver transplantation in patients with PVT improve significantly with experience gained and are equivalent to results in patients without PVT.

With the growing shortage of available liver donors, many donors with risk factors that would have traditionally precluded liver procurement are now being considered. In this prospective study, we evaluated 50 "marginal" liver donors with pre-procurement abdominal ultrasounds and correlated results with findings at procurement and with subsequent allograft function. The results show that the ultrasounds have a specificity of 96% and a sensitivity of 68% in predicting abnormalities in donor livers that precluded transplantation. In addition, using ultrasound to screen marginal donors would result in significant savings in manpower and hospital resource utilization without "missing" any normal liver organs. Our results also show that, when properly selected, livers from donors with one or more high-risk factors function well with acceptable primary nonfunction rates.

It is our experience that warm dissection in the porta hepatis as well as extensive organ mobilization during combined pancreas-liver procurements may cause posttransplant dysfunction of the liver. To avoid this, we recently utilized a rapid en bloc procurement technique with minimal warm dissection and division of the liver and pancreas ex vivo. Fifteen procurements were performed using this rapid en bloc technique; seventeen procurements involved extensive dissection followed by sequential in situ procurement of the liver and pancreas grafts. The control group consisted of 15 age-matched patients who received livers when no pancreas was harvested. Dissection time was 157 +/- 13 min (mean +/- SEM) in the in situ group, 78 +/- 3 min in the en bloc group (P<0.02), and 51 +/- 6 min in the liver only group (P<0.02). There was no difference in donor age, cold ischemia time, or recipient United Network for Organ Sharing status. Pancreata obtained using the en bloc technique all had immediate function and there were no episodes of acute pancreatitis. Early liver graft function, as assessed by lactate dehydrogenase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and total bilirubin levels, was significantly lower in the en bloc and liver only group when compared with the in situ group. The total hospital stay was also significantly lower in these groups. We conclude that the rapid en bloc technique decreases operative time during the donor operation. Procurement-related injury to the liver graft is minimized without compromising pancreas graft function.

Bone marrow transplantation (BMT) is a highly successful and curative therapy for many primary hematologic malignancies. However, hepatic dysfunction and failure are important causes of morbidity and mortality in this patient group after BMT. Hepatic failure can occur as a result of involvement by graft-versus-host disease (GVHD) or as a result of veno-occlusive disease (VOD). Therapies for these complications are often ineffective, especially for VOD, as approximately one fourth of patients develop irreversible liver disease and die of multiorgan failure. Accordingly, we have reviewed our center's experience with orthotopic liver transplantation (OLT) to manage the hepatic complications of BMT. We describe two patients who were treated with OLT after developing hepatic failure post-BMT. One patient had VOD with mild cutaneous and gastrointestinal GVHD; in the other patient, the pathophysiologic process affecting the liver was severe GVHD. Based on our center's experience and review of the literature, we believe OLT should be considered in patients with severe hepatic dysfunction post-BMT.

Unlabelled: BACKGROUND AND DEMOGRAPHICS: Clinical course was reviewed for 19 whole organ pancreas transplant recipients at UCLA between 11/14/93 and 5/31/95, 18 of which were simultaneous pancreas kidney transplants and 1 of which was an isolated pancreas after kidney transplant. The initial 4 pancreatic grafts were procured by classical warm dissection techniques while the remaining 15 were procured by rapid en bloc technique. Mean recipient age, duration of diabetes, and daily insulin requirements were 38 years, 25 years, and 45 units, respectively. Bladder drainage of exocrine secretions was used primarily in 18 cases and primary enteric drainage in one., Results: All recipients manifested immediate dialysis and insulin independence. Actuarial patient and graft survival were 100% and 89%, respectively, at a mean follow-up of 396 days (range, 150-660 days). Mean maximal serum amylase on the first postoperative day was 366 U/dL. There were no instances of pancreatic graft vascular thrombosis. Three patients experienced pancreatic leaks (16%), 1 of which resulted in graft loss. Six month posttransplant Hgb A1c was within normal range and significantly lower than pretransplantation values (5.1 vs 10.7, P = 0.002). Mean length of initial hospitalization was 15 days, with 100% of patients requiring at least one read mission. Fifty-eight percent of patients experienced rejection episodes. Ninety-one percent of patients responding to a quality of life survey reported improvement in general sense of well-being after transplantation., Conclusions: It is concluded that high rates of success may be possible with whole organ pancreas transplantation, even in new programs. Rapid en bloc dissection is a safe, expeditious method of pancreas procurement. Successful pancreatic transplantation is associated with freedom from exogenous insulin administration, normalization of glycated hemoglobin, and subjective improvement in quality of life. However, this modality is associated with higher rates of rejection and readmission, and longer duration of hospitalization when compared with isolated kidney transplantation.

In order to study further whether a relationship exists between the extent of ischemia-preservation-reperfusion injury (IPRI) and acute rejection (AR) events in liver allografts, we retrospectively reviewed 213 consecutive cyclosporine-treated patients who received their first liver allograft between 1/1/93 and 12/31/93. Of these, 178 fulfilled the study inclusion criteria. The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr posttransplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax < 600 IU/L (n = 43); group 2, ASTmax 600-2000 IU/L (n = 86); and group 3, ASTmax > 2000 IU/L (n = 49). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and UNOS status as covariates. At a median follow-up of 271 days there were no statistically significant differences between groups with respect to the incidence of a first episode of AR (47%, 55%, 51%, respectively, P = NS), the timing of AR (respective medians, 9, 10, and 10 days, P = NS), or the proportion of patients treated with OKT3 (9%, 20%, 12%, respectively, P = NS) or converted to FK506 (16%, 12%, 10%, P = NS). Cox regression confirmed the lack of an independent association between the extent of IPRI and any of these outcomes. We conclude that in UW-preserved, cyclosporine-treated primary liver allografts, no correlation exists between the extent of IPRI and the incidence, timing, severity, or refractoriness of clinically defined AR events.

Objective: The aim of this study was to evaluate the effect of postoperative adjuvant chemotherapy on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC)., Summary Background Data: Historically, liver transplantation for HCC has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics., Methods: Twenty-five patients were placed on 6 months of intravenous fluorouracil, doxorubicin, and cisplatin after OLT. Risk factors, recurrence rates, and survival rates were analyzed and compared with historic controls., Results: Overall long-term survival in the protocol patients was 46% at 3 years, improved over our historic controls of 5.8% at 3 years (p = 0.0001). Overall recurrence rate was 20% (n = 4). Possible risk factors, such as tumor size, vascular invasion, multifocality, capsular invasion, and tumor differentiation, were not found to be significantly predictive of survival. Three patients with long-term, disease-free survival had tumors > 5 cm. Side effects from chemotherapy were common, but rarely severe., Conclusions: This study suggests that adjuvant chemotherapy after transplantation for HCC can provide long-term cure and may improve survival, even in patients with stage III and IV disease.

Background: Living-donor (LD) liver transplantation has been developed as an alternative to overcome the shortage of cadaver donor organs for pediatric recipients., Patients and Methods: We reviewed our experience with 9 LD transplants performed between August 25, 1993 and August 3, 1994. The median recipient age and weight were 13 months and 10 kilograms. Left lateral segments from parental donors, with aortic inflow via saphenous vein grafts, were used in all cases., Results: At a median follow-up of 160 days, all donors were alive and well. Recipient and graft survival were both 89%. Rates of hepatic artery thrombosis, portal vein thrombosis, biliary complications, and acute rejection were 22%, 11%, 11%, and 67%, respectively., Conclusions: Excellent outcome can be achieved with LD liver transplantation in small children with minimal donor risk. This procedure has the potential to emerge as the preferred treatment for pediatric liver transplant candidates for whom it is an option.

Background: Bleeding complications and blood product consumption have been a major concern during liver transplantation. Prevention of plasminogen activation and fibrinolysis by aprotinin administration has been shown to reduce perioperative bleeding during operations associated with high blood-product consumption., Patients and Methods: Use of blood-products (packed red cells, frozen plasma, platelets, and cryoprecipitate) was analyzed both during the three stages of orthotopic liver transplantation and during total hospitalization of the 26 patients transplanted without aprotinin and the subsequent 40 patients with aprotinin. A similar analysis was performed for 15 patients immediately before and after the introduction of aprotinin to eliminate the "learning curve" effect for liver transplantation. The effect of epsilon-amino-caproic acid was analyzed as 13 patients received neither epsilon-aminocaproic acid nor aprotinin and 13 patients received epsilon-aminocaproic acid but not aprotinin., Results: There was a significant reduction in total hospital use of cryoprecipitate, frozen plasma, platelets, and red cells in the aprotinin-treated patients. This reduction was seen during the anhepatic and reperfusion stages of liver transplantation. There was no difference in blood product consumption between the groups who were or were not treated with epsilon-aminocaproic acid., Conclusion: Aprotinin significantly reduces the need for red cell, frozen plasma, platelet, and cryoprecipitate transfusion use during orthotopic liver transplantation, and appears to be more efficacious than epsilon-aminocaproic acid.

In order to investigate the capacity of the 21-amino-steroid, U74006F, to mitigate ischemic/reperfusion injury (IRI), we studied lipid peroxidation and glomerulotubular function in a rat model of IRI. U74006F, superoxide dismutase (SOD), and their respective vehicles were administered preischemia and prereperfusion to Brown Norway rats subjected to 45 or 60 min of bilateral normothermic ischemia. Lipid peroxidation was assessed by assay of thiobarbituric acid reactive products (TBA-RP) in a forced peroxidation reaction with t-butylhydroperoxide while renal function was assessed by timed determinations of serum creatinine, creatinine clearance, urine volume, and fractional excretion of sodium (FeNa+). Twenty-four hours following a 60-min ischemic insult and uninephrectomy, the glomerular filtration rate (GFR) was markedly reduced in the IRI + vehicle group compared to controls as reflected by a significant elevation in mean serum creatinine (0.138 +/- 0.018 vs 0.045 +/- 0.002 mumole/liter, P < 0.05) and a significant reduction in mean creatinine clearance (0.200 +/- 0.076 vs 1.130 +/- 0.153 ml/min, P < 0.05). Neither U74006F nor SOD afforded protection against this marked fall in GFR. In contrast, U74006F significantly attenuated both the diuresis (UVol) and the increase in fractional excretion of filtered sodium (FeNa+) seen post-IRI. At 24 hr post-IRI, mean UVol was 22.50 +/- 4.57 ml/day and FeNa+ 1.35 +/- 0.16% in the IRI+vehicle group compared to 11.48 +/- 2.00 ml/day and 0.82 +/- 0.22%, respectively, in the IRI+U74006F group (P < 0.05). While SOD also proved partially protective of tubular function, the effect was not as pronounced as that observed with U74006F.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To evaluate the first 1000 liver transplants performed at UCLA Medical Center to determine factors responsible for improved results., Summary Background Data: Liver transplant has evolved impressively since the first case was performed in 1963. The 1980s have highlighted this progress with the development of better organ preservation, standardization of operative procedure, improved immunosuppressive agents, and better understanding of patient selection., Methods: The first 100 consecutive liver transplants (group 1) performed from February 1984 through October 1986 were compared with the last 200 (group 2) performed between September 1991 and June 1992. An analysis was made of donor use; changes in patient candidacy; patient care variables; morbidity and mortality; survival data; and hospital resource use., Results: In group 1, 31% of donors were refused because of medical unsuitability compared with 4% in group 2 (p < 0.0001). In group 1, alcoholic patients comprised 1% of liver transplant candidates compared with 20% group 2 (p < 0.0001). High-risk patients (United Network for Organ Sharing criteria 4) only comprised 11% of patients in group 1 compared with 37% in group 2 (p < 0.0001). Operative time (7.6 hours compared with 5.4 hours), packed cell replacement (17 units compared with 9.5 units), intensive care unit stay (10 days compared with 5 days), and hospital stay (50 days compared with 31 days) were all significantly improved (p < 0.05). In group 1, the 1-year survival rate was 73% and improved to 88% in group 2 (p < 0.0001)., Conclusions: Despite unfavorable donor characteristics (obesity, cause of death, age, hypotension), most organs function well and should not be refused based on history alone. The older and high-risk patient (renal failure, ventilator dependence, portal vein pathology, and so on) is routinely transplanted with good success. Despite liberalization of both donor and recipient criteria, patient survival after liver transplant is improved, use of hospital resources is maximized, and cost reduction is achieved.

The goals of pancreatic transplantation are to improve the quality of life for the diabetic patient, reverse the metabolic abnormalities of diabetes, and prevent the dreaded secondary complications. Although transplantation of the whole pancreas is the only therapy that reliably achieves euglycemia, the complications associated with this procedure and the need for immunosuppression make it undesirable except to a select subpopulation of type I diabetic patients. Islet cell transplantation is the exciting alternative; however, insulin independence has been achieved in only 10% to 20% of patients. Although advances in technology could make islet transplantation the treatment of choice for type I diabetic patients, islet transplantation currently remains an experimental procedure. Diabetes is not commonly considered a surgical disease, but surgeons have made major contributions to its treatment and must remain active in the development of new treatment modalities for this debilitating disease.

Twenty-two cirrhotic patients who underwent hepatic resection from July 1989 to March 1991 at Vancouver General Hospital were analyzed prospectively in order to determine whether there was any preoperative evaluation of liver function that would help identify those patients who would not survive hepatic resection. Patients were analyzed on the basis of age, type of resection, and a variety of so-called standard liver function tests. In addition, all patients were evaluated preoperatively with an indocyanine green (ICG) clearance test, a relatively new test that we attempted to evaluate in terms of its role in hepatic resection in cirrhotic patients. Parametric statistical evaluation used included Student's t-test and multivariate regression, as well as discriminate analysis. The nonparametric evaluation used was the Wilcoxon rank sum test. Overall, the 30-day mortality rate was 18%, with those patients who did not survive resection having a significantly lower ICG clearance than those who underwent successful resection (p less than 0.0001). No other liver function test was useful in determining the outcome of resection. Similarly, neither age nor type of resection appeared to influence outcome. Use of discriminate analysis (p = 0.0029) allowed the identification of a cutoff point for ICG clearance below which hepatic resection should not be attempted.

Driven by the technological and immunological innovations of the past decade, paediatric transplantation has evolved quickly to occupy an important clinical role in the management of vital organ failure. With this success, the focus of clinical attention has moved progressively from an institutional to a more comprehensive community perspective, and the long-term success of transplantation has assumed greater importance in the evaluation of risk and benefit. Five-year patient survival now exceeds 90% after living donor or cadaveric renal transplantation, 70% following heart or liver transplantation, and approaches 60% at 2 years for the more developmental procedures of heart/lung and lung transplantation. Successful transplantation is accompanied by compelling evidence of improved quality of life. The earliest and most prominent gain is in physical capability, with a progressive re-establishment of social and psychological functioning compared to age-appropriate developmental norms. More than 75% of long-term recipients are in school or employed with a high rating of life satisfaction. Rehabilitation is threatened, however, by the complications of long-standing organ failure and long-term immunosuppression. These principally encompass skeletal and developmental disorders, metabolic abnormalities, cardio-vascular disease, renal dysfunction, and chronic infection or malignancy arising as a result of impaired immune surveillance. Prevention or effective management of these debilitating sequelae is a principal goal in the changing paradigm of organ transplantation for the current decade.

The frequency of pancreatic carcinoma appears to be increasing. Effective treatment is essential for most patients whose tumours are unresectable. Definitive treatment by stenting techniques are currently limited to those patients who are high surgical risks, elderly, present with metastatic disease or refuse the surgical option. Surgical bypass offers the best palliation and should reliably decompress the biliary obstruction caused by the tumour with the least surgical trauma. Roux-en-Y choledochojejunostomy (CDJ), with or without a gastroenterostomy, is usually the preferred method of bypass; however, for patients with a distended gallbladder this procedure is often made easier by its removal. Even then providing a proximal, tension-free anastomosis can be challenging. In 13 consecutive patients who still had a gallbladder and required a biliary bypass for carcinoma of the pancreas, the authors interposed the gallbladder between the proximal bile ducts and a Roux-en-Y loop. This procedure could be done more quickly than CDJ and performed well.

To compare the effect of type of induction immunosuppression on the quality of initial renal allograft function, we identified 35 cadaver donor kidney pairs in which one recipient of a kidney from a given pair received induction immunosuppression with Minnesota antilymphocyte globulin (MALG group) while the recipient of the contra-lateral kidney received cyclosporine from day zero (CsA group). In the absence of an existing quantitative measure to assess and compare the status of those grafts that function primarily, we defined the half-life of creatinine elimination (t1/2SCr) as such an outcome measure based on a review of creatinine elimination kinetics. All organs were procured with in-situ perfusion and en-bloc removal. Total cold storage times, rewarm times, and perioperative management were comparable for the two groups. In the MALG group, the mean t1/2SCr) was not different from that in the CsA group (1.38 +/- 0.96 days vs 1.35 +/- 1.2 days P = NS). Multiple regression analysis performed on the differences in recipient age, number of DR-B locus matches, total cold ischemia time, rewarm time, and central venous pressure at reperfusion of a given donor pair demonstrated no significant impact of any of these differences on the difference in t1/2SCr for the same pair set in this sample. The nadir of serum creatinine achieved in the first five days posttransplant was somewhat higher in the CsA group (234 +/- 131 mumol/L) as compared with the MALG group (200 +/- 132 mumol/L) but the difference was not significant. A similar nonsignificant trend was observed in the comparison of mean serum creatinine values at 30 days posttransplant (MALG group: 158 +/- 62 mumol/L vs. CsA group: 200 +/- 141 mumol/L). Only one of seventy recipients (CsA group) was dialyzed within the first 5 days posttransplant for an overall incidence of ATN of less than 2%. Fourteen of 35 (40%) recipients in both groups received treatment for acute rejection. The mean time to first treatment for acute rejection episode was shorter in the CsA group than the MALG group (10 +/- 8 days vs 23 +/- 24 days, P = 0.055). Graft survival at one year was not different for the two groups (92% vs. 87% for the MALG and CsA groups respectively, P = NS).(ABSTRACT TRUNCATED AT 400 WORDS)

Cytomegalovirus infection is an important cause of morbidity and mortality in immunocompromised individuals. The disease is usually systemic in expression although localized infection can occur, particularly in the lung, liver, retina and gastrointestinal tract. We report a case of cytomegalovirus epididymitis with limited systemic manifestations occurring 2 months after renal transplantation in a patient immunosuppressed with azathioprine, prednisone and cyclosporine. Diagnosis was confirmed by observation of typical cytopathic changes in epididymal cells. Clinical resolution occurred with epididymo-orchiectomy and 9-(1,3-dihydroxy-2-proproxymethyl)guanine therapy. To our knowledge this presentation has not been described previously in the transplant literature and it is extremely rare in other forms of inherited or acquired immune deficiency.