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K M Olthoff

Publications and source records attributed to K M Olthoff.

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

Adenovirus-mediated gene transfer in the transplant setting: early events after orthotopic transplantation of liver allografts expressing TGF-beta1.

We hypothesized that adenovirus mediated gene transfer of TGF-beta1 into liver grafts would enhanced local expression of this recombinant protein and down-regulate inflammatory and alloreactive immune response. A full length DNA encoding the murine TGF-beta1 was used to replaced the E1 region of adenovirus type 5 (AdmTGF-beta1). Expression and protein production of biologically active murine TGF-beta1 was tested in AdmTGF-beta1-transduced Hep G2 cells and TGF-beta-sensitive MV1 cells. In the transplant setting, the replication-defective vector was used to perfused cold preserved ACI liver allograft prior to transplantation into Lewis recipients. Control livers were similarly perfused with cold lactated Ringer's solution and were followed without immunosuppression. Animals were sacrificed at 1, 3, and 5 days after transplantation. Intragraft cytokine levels of TNFalpha, and IFNgamma were determined using ELISA and quantitative PCR. TGF-beta1 ELISA of culture supernatants from AdmTGF-beta1 transduced hepatocyte cell line Hep G2 excreted TGF-beta1 in quantities directly correlated with multiplicity of infection (MOI, vector:hepatic cell ratio). The biological activity of the excreted recombinant protein was confirmed by growth inhibition of MV1 TGF-beta-sensitive cells. Enhanced production of TGF-beta1 in transduced allografts was associated with decreased levels of TNFalpha and IFNgamma when compared with nonimmunosuppressed controls. Adenovirus-mediated gene transfer of murine TGF-beta1 into hepatic cells results in the expression of biologically active protein. Transduction of allografts with TGF-beta1 down-regulates TNFalpha and IFNgamma production early after orthotopic transplantation. Graft transduction with TGF-beta1 offers a novel approach to study the effects of single immune modulator on alloreactive immune response, T cell function, and cytokine cascade.

Adenoviridae↗
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

Etiology and management of symptomatic adult hepatic artery thrombosis after orthotopic liver transplantation (OLT).

Hepatic artery thrombosis (HAT) after adult orthotopic liver transplantation (OLT) is associated with fulminant sepsis and irretrievable loss of the graft. The purpose of this study was 1) to identify recipients at risk for the development of HAT; 2) to define early signs and methods for diagnosis; 3) to determine surgical treatment strategies following diagnosis of HAT. The charts of 680 adults who underwent primary OLT were reviewed. Eleven patients were symptomatic from HAT. Operative data revealed problematic arterial reconstruction in 9/11, and were related to inadequate recipient inflow, necessitating an interposition allogeneic iliac graft in seven patients, or anastomosis to aberrant right hepatic artery in two recipients. Early HAT in 4/11 occurred within 4 weeks after transplantation, whereas late thrombosis in 7/11 was identified 30 days to 1 year after OLT. The postthrombosis course was manifested by elevated liver transaminases (7/11), sepsis and recurrent cholangitis (9/11), or gas gangrene of the liver (4/11). The treatment modalities included thrombectomy and revision of the arterial anastomosis (1/11), emergency hepatectomy with temporary portocaval shunt (2/11), and urgent retransplantation (5/11). Antibiotic therapy and elective retransplantation was the treatment in 4/11. Overall 1-year patient survival and satisfactory graft function was 45 percent.

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

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

Transduction of hepatic allografts achieves local levels of viral IL-10 which suppress alloreactivity in vitro.

The application of gene therapy in transplantation might be targeted at immunoregulation within the donor graft. Viral IL-10 (vIL-10) down-regulates antigen presenting cells (APC) and effector functions in in vitro and in vivo models of alloreactivity. In the current study, we have constructed a replication-defective adenovirus bearing the cDNA encoding viral IL-10 and examined the level and chronicity of its expression in rat liver allografts up to 7 days after orthotopic transplantation. The results demonstrate that liver allografts may be efficiently transfected with adenovirus expressing viral IL-10. Detection of the recombinant viral cytokine was limited to the allograft without measurable levels in peripheral blood. In parallel, the effect of vIL-10 on mixed leukocyte reaction is also assessed using peripheral blood lymphocytes obtained from naive donor and recipient animals. Equivalent levels of viral IL-10 (5-10 ng/ml) achieved after adenovirus-mediated gene transfer suppress the in vitro alloreactivity of peripheral blood lymphocytes up to 70%. Adenovirus-mediated gene transfer of viral IL-10 offers the promise of effectively and favorably altering the alloreactive immune response.

Adenoviridae↗
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

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↗
PubMed1995

Evaluation, operative management, and outcome after liver transplantation in children with biliary atresia and situs inversus.

INTRODUCTION: Biliary atresia, a common indication for liver transplantation, can be associated with situs inversus. Our experience with liver transplantation in children (n = 6) was reviewed retrospectively. PATIENTS AND METHODS: Preoperative duplex sonography, computerized tomography, and visceral angiography were obtained. Vascular anomalies identified included preduodenal portal vein (6/6), interrupted inferior vena cava (5/6), and aberrant hepatic artery (4/6). RESULTS: The liver graft was placed in a midline position. Venous continuity was achieved by donor suprahepatic inferior vena cava to recipient hepatic cloaca and direct end-to-end portal anastomosis. The donor infrahepatic inferior vena cava was oversewn. Arterial continuity was restored using either a direct branch-patch anastomosis (3/6) or a supraceliac aortic interposition graft (3/6). In retrospect, preoperative diagnostic work-up was noncontributory and outcome was not complicated by pre-existing situs inversus. CONCLUSION: Situs inversus in liver recipients requires operative technical modifications, but does not change outcome. Furthermore, extensive preoperative work-up should be avoided.

Biliary Atresia↗
PubMed1993

Radical resection combined with liver transplantation for foregut tumors.

Between February 1984 and July 1992, six adults with advanced pancreatic adenocarcinoma (n = 1), pancreatic neuroendocrine tumor (n = 2), and cholangiocarcinoma (n = 3) underwent radical foregut resections (n = 3) or radical pancreaticoduodenectomy (n = 3) combined with liver transplantation. The major postoperative complications included diarrhea (n = 4), pancreaticojejunostomy leak (n = 3), infection (n = 7), malnutrition (n = 3), refractory ascites (n = 2), and late hepatic artery thrombosis (n = 1). Tumor recurrence occurred in one patient. The actuarial survival for the group is 82 per cent at 1 year and 55 per cent at 2 years. The results demonstrate that radical pancreaticoduodenectomy/foregut resections combined with liver transplantation offer potential surgical cure of malignancies involving these organs. However, the procedure is formidable, with frequent complications.

Adenocarcinoma↗
PubMed1992

Liver resection for primary neoplasms.

Resection is the treatment of choice for almost all hepatic neoplasms. Improvements in operative techniques and perioperative patient management have resulted in low morbidity and mortality. Patients with underlying chronic liver disease in association with hepatic malignancy now can be offered either subsegmental resection or liver transplantation in selected cases. The role of cryosurgery and alcohol injection in patients who are not candidates for resection should become clearer once longer follow-up data are available.

Adenoma, Bile Duct↗
PubMed1991

Monoclonal anti-tumor necrosis factor-alpha antibody treatment of rat cardiac allografts: synergism with low-dose cyclosporine and immunohistological studies.

Tumor necrosis factor (TNF) levels have been reported to be elevated during episodes of human renal, hepatic, and cardiac transplant rejection. In addition, we have shown polyclonal anti-TNF antibodies to have immunosuppressive effects. The present study was performed to evaluate the efficacy of a monoclonal anti-TNF-alpha antibody in rat cardiac transplantation as the sole immunosuppressant and in conjunction with low-dose cyclosporine (CsA). We also performed immunohistological studies to localize intragraft TNF and evaluate graft infiltrating cells (GICs), and we measured serum TNF levels by an ELISA. Untreated Buffalo to Lewis heterotopic rat cardiac transplants reject in 10.5 +/- 0.4 days. A 10-day induction course of CsA (2 mg/kg/day, po) prolonged survival to 16.7 +/- 2.7 days (P less than 0.05 vs control), and 10 days of anti-TNF (2000 U/day, ip) prolonged survival to 22.6 +/- 0.8 days (P less than 0.05 vs control). Combination of anti-TNF plus CsA synergistically prolonged graft survival to 40.7 +/- 1.8 days. Three-day courses of anti-TNF were moderately effective (13.7 +/- 0.5 days, P less than 0.05 vs control) and were also synergistic with CsA (27.8 +/- 2.2). Intragraft TNF localization using immunoperoxidase showed extensive perivascular and mononuclear cell staining in control hearts vs minimal staining in anti-TNF-treated groups. Likewise, serum TNF levels were significantly lowered for treated groups vs control (83.1 +/- 14.0 pg/ml for control; 39.5 +/- 13.8 for anti-TNF; and 13.4 +/- 5.4 for anti-TNF + CsA; P less than 0.05 vs control for all groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

PGE1 reduces injury in hepatic allografts following preservation.

Prostaglandins of the E series have been shown to decrease renal and hepatic ischemic injury as well as improve hepatic function in patients with primary nonfunction following transplantation. We wished to determine the effect of prostaglandin E1 (PGE1) on hepatic allograft reperfusion injury in the isolated perfused rat liver (IPRL) model. Livers were harvested from adult male Sprague-Dawley rats and the bile duct, portal vein, and suprahepatic vena cava were cannulated. Control livers were placed immediately on the IPRL apparatus and perfused for 2 hr with a blood-Kreb's solution. Group A and B allografts were stored for 8 hr in heparinized lactated Ringer's solution at 4 degrees C. Group A livers were then perfused with a PGE1 infusion at 0.1 micrograms/kg/min while B livers received a placebo infusion of NS at the same rate. Temperature, pH, and inflow pressures were kept constant. Oxygen consumption, portal flow, and resistance were calculated for each group and found not to be statistically different. LDH, SGOT, superoxide anion (SOA), and bile flow were measured at 30-min intervals. At the end of the 2-hr perfusion, the placebo Group B (N = 5) had LDH, SGOT, and SOA higher than those of either Group A (N = 5) or control (N = 4) livers. The difference between Group A and Group B was significant for SGOT and SOA (P less than 0.05). Bile flow was highest in the control group (24.2 +/- 1.8 microliters/g/30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1991

Liver transplantation in children.

Although liver transplantation is now accepted as the ideal therapy for end-stage liver disease, relatively few centers have gained a large experience in children, and good results have been elusive. Technical difficulty and a high incidence of graft failure are among the obstacles to success. At the University of California at Los Angeles, 39% of our liver transplants are in the patients who are younger than 18 years. We have analyzed our experience with 103 patients to emphasize factors important to a favorable outcome with the procedure. One hundred twenty-three transplants were performed in 103 children (mean age, 5.2 years; 48% younger than 3 years). No reduced-size grafts were used. Scrupulous attention to technical details of the vascular reconstruction, including frequent use of the supraceliac aorta of the recipient and interrupted suture techniques, ensured construction of sound hepatic artery and portal vein anastomoses at the first operation. Preoperative exchange transfusions were used if the prothrombin time was prolonged beyond 7 seconds, resulting in an average blood loss of only 3.3 volumes. Cyclosporine dosage was maintained in the high therapeutic range for the first 4 weeks, and anti-T-cell antibody (OKT3) was used for rejection (38%). Amphotericin prophylaxis was used for biliary atresia patients with multiple previous operations. Eighty-two of one hundred three patients (80%) are alive. There were no intraoperative deaths. Actuarial survival rates at 6 months, 1 year, and 5 years are 80%, 79%, and 77%, respectively. Survival of patients who underwent transplantation at age less than 1 year is 65% versus 85% at age more than 1 year (p = 0.08). Retransplantation was performed in 19 patients (18%), with a survival rate of 58%. Hepatic artery thrombosis, the most frequent technical complication, occurred in only 16 patients (13%). Survival rates of ABO identical-match versus nonidentical-match grafts were 96% and 60%, respectively (p = 0.02). Graft survival was only 47% if more than one steroid cycle was needed, compared to 75% survival with OKT3 treatment. Despite impairment of renal function (glomerular filtration rate [GFR] less than 80 cc/kg/min) in 54% of patients and hypertension requiring therapy in 27%, 90% of the children demonstrated enhancement of growth, development, and functional status. The following conclusions were made. (1) Pediatric liver transplantation is the treatment of choice for all types of end-stage liver disease and should be considered early. (2) Factors that enhance survival include technical precision, aggressive retransplantation, antifungal chemoprophylaxis and therapy, and judicious immunosuppression with use of OKT3 for rejection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗