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C R Shackleton

Publications and source records attributed to C R Shackleton.

At least 37 records · Page 2Linked to original sources
PubMed1996

A prospective study on the reliability and cost effectiveness of preoperative ultrasound screening of the "marginal" liver donor.

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.

Costs and Cost Analysis↗
PubMed1996

Rapid en bloc technique for pancreas-liver procurement. Improved early liver function.

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.

Adult↗
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

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

Indications for and timing of liver transplantation.

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.

Contraindications↗
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

Late acute rejection occurring in liver allograft recipients.

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.

Acute Disease↗
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

Lack of correlation between the magnitude of preservation injury and the incidence of acute rejection, need for OKT3, and conversion to FK506 in cyclosporine-treated primary liver allograft recipients.

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.

Cyclosporine↗
PubMed1995

Living-donor liver transplantation at UCLA.

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.

Adolescent↗
PubMed1995

Aprotinin reduces the need for blood products during liver transplantation.

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.

Adolescent↗
PubMed1995

Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma.

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.

Actuarial Analysis↗
PubMed1994

Effect of a 21-aminosteroid, U74006F, on lipid peroxidation and glomerulotubular function following experimental renal ischemia.

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)

Animals↗
PubMed1994

One thousand liver transplants. The lessons learned.

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.

Adult↗