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R W Busuttil

Publications and source records attributed to R W Busuttil.

At least 217 records · Page 12Linked to original sources

The long-term outcome of OKT3 compared with cyclosporine prophylaxis after liver transplantation.

We report the long-term follow-up (greater than 1 year) of 46 patients (12 pediatric) randomized to receive OKT3 for the first 14 days after OLT with low-dose steroids compared with 39 patients (8 pediatric) who received cyclosporine, steroids, and azathioprine. The mean period of follow-up for survivors was 648 +/- 261 days for the OKT3 group and 682 +/- 216 days for the cyclosporine group. Of the OKT3 patients, 46% were rejection-free in the first month compared with 31% of CsA-treated patients (P = NS). Rejection occurred after 1 month in 21% of the OKT3 group patients compared with 19% of the CsA group patients. One patient in each group developed vanishing bile duct syndrome. Eight patients in the OKT3 group and 13 in the CsA group experienced steroid-resistant rejection and required OKT3 rescue. In the 8 patients in whom OKT3 was reused, 4 had a positive ELISA after prophylaxis, and in 6, CD3-positive cells were greater than 10% during OKT3 reuse. Five patients resolved the episode. Of patients receiving OKT3 prophylaxis, 39% developed anti-OKT3 antibodies. In the OKT3 group 83% of patients and in the CsA group 75% currently have normal liver function. There was no difference in serum creatinine for either adult or pediatric recipients at 12 months in the two groups. Eight episodes (2 CMV) of severe infection occurred after 1 month in the OKT3 group compared to 11 (4 CMV) in the CsA group. Graft survival, 63% for the OKT3 group and 73% for the CsA group, and patient survival, 67% for the OKT3 group and 84% for the CsA group, were not significantly different in the two groups. We recommend reserving the use of OKT3 for resistant rejection or when cyclosporine is contraindicated, as we can show no long-term benefit from its routine prophylactic use.

Antibodies, Monoclonal↗

Diagnosis of portal vein thrombosis: value of color Doppler imaging.

This study was undertaken to determine the accuracy of color Doppler imaging in the diagnosis of portal vein thrombosis. Two hundred fifteen patients were studied with color Doppler imaging to determine patency of the main portal vein. Sonographic findings were confirmed in 75 patients, aged 19 to 66 years. Correlation with angiography was obtained in 13 patients, and surgical correlation was obtained in the remaining 62. Nine patients had portal vein thrombosis on the basis of these gold standards. Sonograms were classified as showing either patency or thrombosis, depending on the ability to show color flow within the main portal vein. Agreement between sonography and angiography or surgery was found in 69 patients (61 patent, eight thrombosed). One patient with a patent portal vein at sonography was found to have a thrombosed vessel at surgery, whereas five patients without portal venous flow at sonography had patent vessels at angiography (one patient) or surgery (four patients). Overall sensitivity and specificity for detection of portal vein thrombosis were 89% and 92%, with an accuracy of 92%, a false-negative rate of 0.11, a negative predictive value of 0.98, and a positive predictive value of 0.62. We postulate that the majority of errors in our study occurred in vessels that, although patent, had only sluggish flow, which could not be resolved because of technical limitations. We conclude that color Doppler imaging is a valuable screening procedure for the assessment of portal vein patency. If the sonogram shows a patent portal vein, no further studies are required. However, a lack of demonstrable flow does not always indicate thrombosis, and other imaging studies should be performed for confirmation.

Adult↗

The hepatorenal syndrome in liver transplant recipients.

The hepatorenal syndrome (HRS) is a well-known complication of liver failure, and medical treatment is usually not successful unless liver function can be improved. The authors review their experience with 130 adults undergoing orthotopic liver transplantation (OLT) over a 20-month period to determine the incidence of HRS and its effects on patient outcome, need for hemodialysis (HD), and the degree of recovery of renal function. The clinical diagnosis of HRS preoperatively was made by using criteria to exclude prerenal azotemia, acute tubular necrosis, and primary renal diseases. Nineteen patients were identified as having the HRS for a preoperative incidence of 15.1 per cent. Overall, 41 of the 126 patients reviewed required postoperative HD, and the mortality in this group was 54 per cent. Fifty-eight per cent of the HRS patients were dialyzed postoperatively vs 28 per cent of non-HRS patients. The mean posttransplant creatinine improved over time in the HRS patients while it worsened slightly in the non-HRS group. At 12 weeks posttransplant, there was a significant difference in the mean creatinine levels (1.8 +/- 0.3 mg/dl vs 1.2 +/- 0.04 mg/dl, P = .001). However, at 24 weeks the small difference was not statistically significant between the two groups (1.6 +/- 0.15 mg/dl vs 1.3 +/- 0.06 mg/dl, P = NS). The current survival of the hepatorenal group is comparable to the nonhepatorenal patients at a follow-up of 6 to 25 months: 68 per cent vs 78 per cent, P = NS. The authors conclude that liver transplantation reverses the HRS, and that hepatorenal patients can undergo liver transplantation with outcomes comparable to nonhepatorenal patients.

Cause of Death↗

Liver transplantation at UCLA: report of clinical activities.

Liver transplantation remains the treatment of choice for many forms of end-stage liver disease. In most large series, 5-year actuarial survival is greater than 70%. The majority of the morbidity and mortality occurs in the first 6 months posttransplant; as these figures have improved, so have overall survival rates. Infants under 1 year of age have a survival rate below that of older patients; in addition, a severe organ shortage for these patients continues. The use of reduced grafts has ameliorated the problem to a certain extent; however, further expansion of the donor pool is still necessary. Progress has also been made in the postoperative management of transplant patients. We currently follow AKBR and TNF levels in all patients to aid in the diagnosis of primary nonfunction and acute rejection, respectively. The introduction of additional immunosuppressive agents has instigated several large clinical trials. CsA, however, remains the gold standard to which these drugs must be compared.

Actuarial Analysis↗

The use of the supraceliac aorta for hepatic arterial revascularization in transplantation of the liver.

Thrombosis of the hepatic artery during the early post hepatic transplant period results in massive hepatocyte necrosis, bile duct damage and subsequent graft loss. The incidence of this complication is increased when hepatic arterial reconstruction is possible only by the placement of an interposition infrarenal iliac artery graft. We describe 45 hepatic transplants with difficult arterial reconstruction in which the supraceliac aorta was used for arterial reconstruction. Indications for using the supraceliac aorta as the primary site for arterial reconstruction were inadequate inflow through a narrow recipient common hepatic artery in 51 per cent, previously thrombosed common hepatic artery in 27 per cent, mechanical obstruction of the celiac axis in 13 per cent or intimal dissection in 9 per cent. Direct anastomosis of the donor hepatic artery to the supraceliac aorta was achieved in 22 patients, reducing the need for a graft by 49 per cent. Short segments of iliac artery graft (17 patients) or aortic conduit (six patients) to the supraceliac aortas were required because of insufficient length of the donor artery. The incidence of arterial thrombosis and graft loss were zero per cent in adults and 12.5 per cent in children, both significantly less when compared with the 23.0 to 70.0 per cent thrombosis rate when graft is placed in an infrarenal position. We conclude that routine use of the supraceliac aorta for difficult hepatic arterial reconstruction decreases the need for arterial grafts, the incidence of hepatic arterial thrombosis and loss of hepatic grafts.

Adult↗

Association of primary sclerosing cholangitis with HLA-DRw52a.

We sought to determine whether there are specific HLA haplotypes in patients with either primary sclerosing cholangitis or primary biliary cirrhosis. Surprisingly, 100 percent of the 29 patients with primary sclerosing cholangitis had the HLA-DRw52a antigen, which is normally present in 35 percent of the population (relative risk, 109.5; P less than 0.00001). Fifteen of these patients had a single common haplotype: A1,B8,Cw7,DRw17,DQw2,DRw52a. In the remaining 17 patients there was a loss of at least one of these antigens. Of the 15 patients with the common haplotype, 12 also had ulcerative colitis, thereby linking the occurrence of ulcerative colitis in patients with primary sclerosing cholangitis to the presence of this haplotype. Although there was no association in 35 patients between primary biliary cirrhosis and specific HLA haplotypes, there was a significant association of the disease with DRw8 (relative risk, 3.1; P = 0.02). We conclude that the development of primary sclerosing cholangitis involves a strong genetic predisposition. Since the association of primary sclerosing cholangitis with HLA-DRw52a appears to be total, HLA typing should be helpful in differentiating this disease from primary biliary cirrhosis.

Cholangitis, Sclerosing↗

Is liver transplantation justified for the treatment of hepatic malignancies?

Twenty-eight patients received orthotopic liver transplants for malignant disease between February 1, 1984, and December 31, 1989. Preoperative diagnoses included hepatocellular carcinoma (n = 16), cholangiocarcinoma (n = 3), other primary hepatic tumors (n = 6), and metastatic diseases to the liver (n = 3). Overall actuarial survivals at 6 months, 1 year, and 5 years were 67.3%, 51%, and 31%, respectively. Long-term survival longer than 5 years was achieved in 3 patients. The recurrence rate in patients surviving longer than 3 months is 48% (median, 7 months). Hepatocellular carcinoma and cholangiocarcinoma had the poorest survival and highest recurrence rates. Specific prognostic factors correlating with survival or recurrence could not be elucidated. These results indicate that orthotopic liver transplants can provide long-term cure and palliation for malignant disease; however, patient selection is extremely important in predicting outcome.

Adenoma, Bile Duct↗

Anti-tumor necrosis factor antibody enhances allograft survival in rats.

We have recently observed significantly elevated serum tumor necrosis factor-alpha (TNF-alpha) levels during human liver allograft rejection. Although increased TNF activity has been reported in rejecting rat cardiac and renal allografts, this represents the first report of an animal model utilizing immunotherapy directed against TNF. Intraabdominal heart transplants (Buffalo to Lewis) were performed. Cardiac rejection was defined as cessation of a palpable beat and confirmed at laparotomy. Control animals received no immunotherapy and experienced rejection on Postoperative Day 11 +/- 0.4 (mean +/- SEM). Experimental animals received immunotherapy either intraperitoneally (ip) or intravenously (iv) from Days 1 to 10. Intraperitoneally administered anti-TNF-alpha prolonged graft survival to 16 +/- 2.7 days (P less than 0.05 vs controls), iv administration prolonged survival to 15 +/- 1.4 days (P less than 0.004). Animals treated with ip anti-TNF-beta survived 17 +/- 1.7 days (P less than 0.002 vs controls). Conversely, administration of purified TNF-alpha to graft recipients decreased graft survival to 7 +/- 0.4 days (P less than 0.001 vs controls). Serum samples analyzed in an L929 bioassay showed increased cytotoxic activity in control animals, corresponding to an increase in circulating TNF. This activity was partially abrogated in animals receiving immunotherapy. These data demonstrate that circulating levels of TNF are increased during rejection. Immunotherapy with anti-TNF-alpha or anti-TNF-beta prolongs graft survival, suggesting that TNF may play a role in the pathogenesis of acute allograft rejection.

Animals↗

Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections.

We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections. We included the Acute Physiology and Chronic Health Evaluation (APACHE II) index of severity and excluded patients without established infection. Two hundred ninety patients were enrolled, of whom 162 were evaluable. Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality, we found a significant correlation for both with APACHE II score (p less than 0.0001 for both). Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients (p = 0.043). The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients (p = 0.018). This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement. Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram-negative organisms. For failures the maximum peak was 6.4 +/- 1.9 micrograms/mL, and time to maximum peak was 4.6 +/- 5.2 days. For successes the maximum peak was 6.1 +/- 1.7 micrograms/mL, occurring at 3.8 +/- 2.6 days. This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen.

Abscess↗