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Biomedical subjects

R W Busuttil

Publications and source records attributed to R W Busuttil.

At least 127 records · Page 7Linked to original sources
PubMed1996

Improved results of liver transplantation in patients with portal vein thrombosis.

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.

Actuarial Analysis↗
PubMed1996

Orthotopic liver transplantation for bone-marrow transplant-associated veno-occlusive disease and graft-versus-host disease of the liver.

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.

Adult↗
PubMed1996

Failure of ganciclovir prophylaxis to prevent allograft reinfection following orthotopic liver transplantation for chronic hepatitis B infection.

The effect of ganciclovir prophylaxis on reinfection of hepatic allografts by hepatitis B virus (HBV) was studied in 26 patients undergoing orthotopic liver transplantation (OLT) for decompensated cirrhosis due to HBV. Patients were randomized to receive either ganciclovir (6 mg/kg/day intravenously for a total of 100 days) or acyclovir (10 mg/kg every 8 hours intravenously until discharged and then 800 mg orally every 6 hours) for a total of 100 days after OLT as part of a study of prophylaxis against cytomegalovirus infection. All patients received hepatitis B immunoglobulin (HBIG), 10,000 units intravenously, during the anhepatic phase, daily for the first 7 days, after OLT, and then every 4 weeks for 6 months, Seven of 12 (58%) patients in the ganciclovir group developed recurrent HBV, compared with 6/14 (46%) of the acyclovir group (nonsignificant). No significant difference was observed in time to recurrent HBV in the ganciclovir group (mean 13.2 months) compared to the acyclovir group (mean 11 months). Our results suggest that ganciclovir administered prophylactically for 100 days after OLT does not prevent or delay graft reinfection by HBV.

Acyclovir↗
PubMed1996

The role of whole organ pancreas transplantation in the treatment of type I diabetes.

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.

Adult↗
PubMed1996

Liver transplantation in the morbidly obese.

STUDY OBJECTIVE: To test the hypothesis that morbid obesity implies increased difficulty of liver transplantation and increased risk of adverse outcome. DESIGN: Retrospective review of medical records of 40 morbidly obese patients using a control cohort of patients transplanted just before and after the obese patients. SETTING: University medical center. PATIENTS: All morbidly obese patients who underwent liver transplantation over a 52-month period were included. Forty adult patients met criterion for morbid obesity with body mass index greater than 30 kg/m2. Records for 61 time-matched controls were reviewed. MEASUREMENTS AND MAIN RESULTS: Demographic, intraoperative, and postoperative data were collected including preoperative diagnoses, laboratory and pulmonary function tests, intraoperative transfusion requirements and length of surgery postoperative complications, and survival. Data were analyzed using Student's t-tests, and Chi-square analyses as appropriate, with significance considered a p-value less than 0.05. Obese patients were more hypoxemic than controls prior to surgery (PaO2, 82.9 +/- 3.5 vs. 93.0 +/- 3.0 mmHg), were more likely to be diabetic, and had higher creatinine levels (3.0 +/- 0.6 vs. 1.7 +/- 0.2 mg/dl). Despite this evidence of multi organ dysfunction, intraoperative and postoperative pulmonary and cardiac complications did not differ between groups. Though more obese patients had prior cholecystectomy, length of surgery and intraoperative transfusion requirements were not different between groups. Obese patients did not have an increased incidence of reoperation for wound problems, and lengths of intensive care unit and hospital stays did not differ between groups. Graft and patient survival were similar in obese and nonobese liver transplant recipients. CONCLUSION: Morbid obesity alone does not predispose to increased complications or decreased survival after liver transplantation.

Adult↗
PubMed1996

Determination of the presence of interleukin-6 in bile after orthotopic liver transplantation. Its role in the diagnosis of acute rejection.

OBJECTIVE: The authors evaluated the significance of interleukin-6 (IL-6) in bile in the diagnosis of acute rejection after liver transplantation. SUMMARY BACKGROUND DATA: Interleukin-6 in blood has not been shown to be useful as a marker of acute rejection in clinical liver transplantation. In a rat liver transplantation model, the authors have found that bile IL-6 levels correlated well with the severity of rejection as determined histologically, whereas kinetics of serum IL-6 differed among rats without any definite feature related to graft rejection. METHODS: Fifty-one patients who underwent orthotopic liver transplantation between May 1990 and February 1991 at the University of California, Los Angeles, were included in the study. After liver transplantation, bile and blood were collected daily, and IL-6 levels were measured by the enzyme-linked immunosorbent assay. RESULTS: Bile IL-6 increased to 1228 +/- 317 pg/mL on the day of transplantation and decreased to 50 pg/mL or less within 48 hours. Patients who had uneventful postoperative courses had low levels of bile IL-6 throughout their hospitalization. In patients with acute rejection, bile IL-6 significantly increased (1090 +/- 990 pg/mL; p<0.05), but decreased in response to antirejection therapy. In patients who had liver dysfunction due to ischemic change or sepsis, bile IL-6 did not increase. Patients with cholangitis had significantly increased levels of bile IL-6 (146 +/- 47; p<0.05). Interleukin-6 in blood increased with many kinds of complications other than rejection and seemed to be less specific than that in bile. CONCLUSIONS: Measurement of IL-6 in bile may be a useful, noninvasive tool for diagnosing acute rejection.

Acute Disease↗
PubMed1996

Orthotopic liver transplantation for congenital biliary atresia. An 11-year, single-center experience.

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.

Actuarial Analysis↗
PubMed1996

UCLA liver transplantation: analysis of immunological factors affecting outcome.

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).

Adult↗
PubMed1996

Liver transplantation for fulminant hepatic failure in a Jehovah's Witness.

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.

Adult↗
PubMed1995

A randomized prospective trial of steroid withdrawal after liver transplantation.

The safety of steroid withdrawal in orthotopic liver transplant (OLT) recipients has been studied in a prospective trial with a comparison control group. Sixty-four recipients of ABO-compatible grafts (42 adults, 22 children) were randomized into a steroid withdrawal (SW) group and a control group. Inclusion criteria included survival > one year post-OLT and no rejection > six months after OLT. Exclusion criteria included previous graft loss secondary to rejection, > two episodes of documented rejection, patients transplanted for autoimmune hepatitis, and patients unable to receive azathioprine. Target HPLC cyclosporine levels in both groups were 100-200 ng/ml. Thirty-three patients entered the SW group and 31 the control group at a mean of 3.5 years after OLT; follow-ups were 592 and 527 days, respectively. Two patients in each group developed biopsy-proven rejection. In the SW group one patient rejected at three months, the other at nine months. Both rejection episodes resolved with only reinstitution of oral prednisone. Of the two patients who rejected in the control group (one at 7 months, one at 11 months) one required conversion to tacrolimus and the other intravenous steroids. There were no significant differences between the two groups for prednisone, azathioprine, cyclosporine doses, cyclosporine levels, liver function tests, and white blood cell counts at base line compared with 12 months. Fasting serum cholesterol in the SW group decreased from 194 +/- 44 mg/dl at baseline to 175 +/- 37 mg/dl at one year, whereas in the control group cholesterol rose from 180 +/- 48 mg/dl to 193 +/- 44 mg/dl. In pediatric patients no significant difference in age-adjusted height velocities over one year was seen between the two groups. We concluded that dual therapy with cyclosporine and azathioprine in stable long-term liver allograft recipients is not associated with an increase in rejection incidence. Prednisone withdrawal may be associated with an improvement in lipid profiles.

Adult↗
PubMed1995

Long-term ganciclovir prophylaxis eliminates serious cytomegalovirus disease in liver transplant recipients receiving OKT3 therapy for rejection.

We conducted a trial of long-term ganciclovir prophylaxis for prevention of cytomegalovirus (CMV) disease in liver transplant recipients receiving OKT3 therapy for rejection. Intravenous ganciclovir (6 mg/kg once a day, Monday through Friday) was initiated on the same day OKT3 therapy was started and continued for 4 or more weeks. Fifty-one consecutive adult patients (80% CMV seropositive, 20% CMV seronegative) were evaluated. Due to the patient's noncompliance or the primary physician's decision, 6 patients received less than 2 weeks of ganciclovir. Three of these 6 (50%) developed CMV disease (hepatitis 1, CMV syndrome 2). In contrast, of 45 patients receiving 4 or more weeks of prophylactic ganciclovir, only 1 (2.2%) developed CMV disease (hepatitis). There were no cases of CMV disease among 29 patients who received 6 or more weeks of ganciclovir. Reversible neutropenia in 2 patients (4.4%) was the only side effect associated with long-term ganciclovir. Complications from central intravenous catheters did not occur. These results suggest that CMV can be eliminated as a significant pathogen in liver transplant recipients receiving OKT3 for rejection by the long-term administration of prophylactic gnaciclovir, which is safe.

Adult↗
PubMed1995

Correlation between donor age and the pattern of liver graft recovery after transplantation.

We have observed an increased rate of delayed nonfunction (DNF) of liver grafts procured from older donors. The aim of this study was to correlate donor age and the patterns of graft failure after transplantation. Pattern of liver injury, synthetic function, and graft survival in recipients receiving liver grafts from donor older than age 50 (group I, n = 95) were compared with matched cohort of recipients transplanted with grafts from donors age 20-30 (group III, n = 50). Primary nonfunction (PNF) of the graft was defined as non-recoverable hepatocellular function necessitating emergency retransplantation within 72 hr. DNF was defined as marginal graft function necessitating retransplantation within one month. Recipient characteristics, including age and preoperative UNOS status, were similar between groups. Ischemic/reperfusion injury, reflected by SGOT and SGPT was more severe in older donors. PNF occurred at similar frequencies for all groups (7%). Normal liver function was regained in 76% of recipients in group I, and in 92% in group II. However, cholestatic pattern was observed in recipient of grafts from group I donors. Rapid rise in bilirubin, despite normalization of prothrombin time and liver transaminases, was the hallmark of DNF. DNF resulted in higher retransplantation rate in group I (24% vs. 8% in group II). Donor age did not affect patient survival. Liberalizing criteria for donor selection, and acceptance of older donors is a calculated risk. Over 75% of the recipients will regain normal liver function. However, a higher number of these grafts will exhibit slow recovery after transplantation, and a significant rate of DNF. Recognition of such pattern and early retransplantation should decrease mortality.

Adult↗
PubMed1995

Biliary tract complications after orthotopic liver transplantation. Endoscopic approach to diagnosis and therapy.

This study was undertaken to further define the role of endoscopic methods in the evaluation and treatment of biliary tract complications after liver transplantation and to determine the efficacy and safety of this approach. Fifty liver transplant patients were referred for endoscopic evaluation of a suspected biliary tract complication. Two patient groups were identified based on the indication for the endoscopic retrograde cholangiopancreatography (ERCP): Group 1 was suspected of having biliary fistula and group 2 was suspected of having bile duct obstruction. Group 1 consisted of 35 patients who developed bile peritonitis after inadvertent migration of the T-tube or intentional T-tube removal. Group 2 consisted of 15 patients who developed cholestatic hepatic chemistries in the absence of allograft rejection on liver biopsy. ERCP identified a biliary fistula at the T-tube insertion site into the bile duct in 32 (91%) group 1 patients. Twenty-six of 26 treated with a nasobiliary tube had fistula closure at a mean 5.2 days. Five of 6 treated with a stent, with or without sphincterotomy, had no leak at the time of stent removal (mean, 45 days). ERCP identified a cause for the cholestatic hepatic chemistries in 11 (73.5%) group 2 patients, including bile duct stones (n = 4), anastomotic (n = 3) or intrahepatic (n = 2) strictures, bile duct necrosis (n = 1), and hemobilia (n = 1). Five of the 5 patients undergoing endoscopic therapy were treated successfully. The endoscopic complication rate was 4% and the 30-day mortality rate was 2%. During a mean follow-up of 15 months, 94% of the patients who were treated successfully had no recurrent biliary tract disease. The results of this study suggest that ERCP is an effective modality in the evaluation of patients with suspected biliary tract complications after liver transplantation. In selected patients, endoscopic therapy obviates the need for additional surgical or percutaneous intervention.

Adult↗
PubMed1995

Randomised comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients.

Despite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients. At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday until day 100) or acyclovir (10 mg/kg intravenously every 8 h from postoperative day 1 to day of discharge, then 800 mg orally four times a day until day 100). Patients were followed for development of CMV infection, CMV disease, and drug-related toxicity by frequent cultures, serological tests, laboratory measurements, and tissue biopsies. During the first 120 days after transplant, CMV infection occurred in 48 of 126 (38%) acyclovir patients but in only 6 of 124 (5%) ganciclovir patients (p < 0.0001). Similarly, symptomatic CMV disease developed in 12 of 126 (10%) acyclovir patients but in only 1 of 124 (0.8%) ganciclovir patients (p = 0.002). Ganciclovir reduced the incidence of CMV infection in both CMV antibody positive (37 vs 4%, p = 0.001) and negative patients (42 vs 11%, p = 0.06). In a multivariate analysis of donor-recipient CMV antibody status and other risk factors, prophylactic ganciclovir was the most significant factor protecting against CMV infection (p < 0.0001) and disease (p = 0.001). Ganciclovir and acyclovir were generally well-tolerated. Incidences of leukopenia, thrombocytopenia, renal failure, and other adverse events were similar in the two groups. CMV can be eliminated almost completely as a significant pathogen in liver transplant recipients by the long-term administration of prophylactic ganciclovir. In addition, the treatment is safe.

Acyclovir↗
PubMed1995

Adenovirus-mediated gene transfer in the transplant setting. Part III. Variables affecting gene transfer in liver grafts.

We have established a system of efficient gene transfer to liver grafts using adenovirus vectors. The purpose of this study was to examine variables affecting gene transfer to rat liver grafts during cold preservation. Our results demonstrate that gene transfer efficiency was directly correlated with the ratio of vector to hepatic cells (multiplicity of infection [MOI] and the length of exposure to the vector. At MOIs of 10:1 and 50:1, the hepatic cell transduction rate was 25-30% and 100%, respectively. However, higher MOI was associated with significant mortality. Prolonging the cold preservation/exposure time resulted in an increased transduction rate (50% at MOI of 10:1). Similar gene transfer efficiencies were observed when the vector was diluted in lactated Ringer's or University of Wisconsin solution. Recombinant protein production was evident within 12 hr after reperfusion, and increased to a peak level within 48 hr. These results suggest a predictable pattern of gene transfer and expression after ex vivo transduction of liver grafts with adenovirus vectors. These data are essential in directing desirable levels of recombinant protein within the transplanted organ.

Adenoviridae↗