Arterial complications have a major impact on survival after liver transplantation (LTx). The aim of this study was to examine arterial complications in adults and children after LTx. A total of 1000 consecutive primary LTx patients [mean age 40.5 years: 600 males, 400 females, 834 adults; 166 children (age <18 years)] were studied. Forty-two patients (4.2%; 31 adults, 11 children) developed hepatic artery thrombosis (HAT). Thrombosis in children occurred significantly early (mean 5.4 days) compared with adults (mean 418.7 days, P = 0.0001). Nonthrombotic complications occurred in 30 patients (29 adults, one child). Overall, 13-year patient survival after HAT was 43.2% (72.7% children, 32.9% adults). For nonthrombotic complications, 54.3% of adults died and 69.4% grafts were lost. An overall incidence of 4.2% thrombotic and 3.2% nonthrombotic complications was observed. Rate of HAT was higher in children, but survival was better compared with adults.
Background. Tacrolimus has been increasingly used for liver transplantation during the last decade. The drug has immunological advantages in short- to medium-term follow-up. However, data on longitudinal follow-up are lacking.Aim. The aim of the present report was to examine the impact of tacrolimus in primary adult and pediatric liver transplantation (LTx) patients.Material and method. One thousand consecutive primary LTx patients were performed under tacrolimus between August 1989 and December 1992 were followed up until August 2004. Mean follow-up was 13.4 +/- 0.92 (range, 11.7-15) years. There were 600 males and 400 females with a mean age of 42.6 +/- 20.2 years. There were 166 children (age 18 years or younger) and 834 adults, of whom 204 were older than 60 years (seniors).Results. Four hundred ninety-seven (49.7%) patients died in the follow-up period. The overall 15-year actuarial patient survival rate was 51.4%. The survival rate for children was significantly better (81.3%) compared with adults (47.5%) and seniors (36.4%) (P = .0001). One hundred fifty-one patients received a second LTx, 22 patients received a third LTx, and 4 patients. received a fourth LTx. Over all 15 years the actuarial graft survival rate was 46.1%. At last follow-up, 69.1% of patients were off steroids. The majority of late deaths were due to age-related complications, recurrence of disease, and De novo cancers.Conclusion. The data on longitudinal follow-up have shown actuarial survival for children to be significantly better than in adults and seniors. Graft loss from immunological causes are rare even with long-term follow-up.
Background. Occurrence of posttransplant lymphoproliferative disorder (PTLD) after transplantation is known. Drastic reduction or withdrawal of immunosuppression with anti-viral therapy for Ebstein-Barr virus (EBV) is the primary treatment for all PTLD. Many PTLD are B cell in origin have CD20 antigen on the cell surface. Rituximab is a chimeric anti CD20 antibody, which has been used to treat PTLD with variable success. This study aims to report long-term experience with rituximab for PTLD from a single center. Methods. Seventeen patients (13 male, 4 female, mean age 51.2 years) received rituximab to treat PTLD. Five patients received rituximab with drastic reduction in immunosuppression (primary). Nine patients received rituximab after failure of primary therapy (rescue) and three patients received it after resolution of PTLD (prophylactic). Mean follow-up period was 60 months. Results. Overall 1-, 3-, and 5-year patient survivals were 64.7%, 47.1% and 35.3%, respectively. In the primary group, three patients had complete and one had partial response; however, only two (40%) patients are currently alive. In the rescue group, none of the patients had a complete response, four patients had partial response, and only two (22%) patients are currently alive. In the prophylactic group, two patients died at 28 and 41 months due to recurrence and graft failure, respectively. Conclusion. Sixty percent (3 of 5) of patients who received rituximab as primary therapy had complete resolution, and 44% (4 of 9) of patients who received it as rescue therapy had partial response. Overall 5-year patient survival was a disappointing 35%.
Introduction. To eliminate mortality and morbidity risk in living related liver donors, we developed a new surgical technique to resect hepatic parenchyma using an ultrasonic surgical aspirator in association with a monopolar floating ball cautery.surgical aspirator in association with a monopolar floating ball cautery. Methods. We performed 17 right hepatectomies and 2 left hepatectornies using this technique. We performed a retrospective analysis of perioperative mortality, length of hospitalization (LOS), blood transfused during surgery (IBT), intraoperative blood lost (IBL), biliary complications (BC), and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) peak in the first postoperative week. This group of patients (Group A) was compared, using the analysis of variance (ANOVA) test (P <.05) with 2 different groups of 19 patients: Group B with liver neoplasms that had the same technique as Group A, and Group C wherein a crushing clamp technique was used.Results. All of the analyzed variables showed significative statistical differences, especially between Group A and Group C (IBL, P <.000; IBT, P <.006; LOS, P <.028; BC, P <.000; AST peak, P <.041; and ALT peak, P <.023).Discussion. The association of these 2 techniques seems to reduce the LOS, and the need for intraoperative blood transfusions. Moreover, the surgical complications (biliary leaks) and the postoperative parenchymal cytonecrosis seem to be less using this technique.
P501 Aims: The small-for-size graft syndrome (SFSS) is a signifcant source of morbidity and mortality following adult living donor liver transplantation (ALDLT) and graft size is only one factor determining its development. This study outlines our experience with the clinical and pathologic spectra of the SFSS. Methods: 39 consecutive ALDLT were performed between 11/00 and 09/03. The mean age of transplant recipients was 49±12 years (22F, 17M). MELD scores at the time of transplant ranged from 7-37 (mean 14±6). The transplanted lobes included 2 left lobes, 2 left lateral segments (LLS) and 35 right lobes. Graft to recipient weight ratios (GRWR) of the transplanted grafts ranged from 0.6-2.3 (mean 1.3±0.4). Two patients were transplanted with a GRWR≤0.8. All complications were reviewed. A diagnosis of SFSS, defined as coagulopathy, ascites and cholestasis was made in 5/39 (13%) patients. Patients diagnosed with biliary stenosis or hepatic artery (HA) stenosis were excluded. A diagnosis of HA thrombosis was considered in 3/5 patients based on angiographic findings of poor or no visualization of the HA. Technical problems were not identified at re-operation or retransplant and they are included in the group. H+E sections of liver biopsies and failed allograft specimens, obtained at varying intervals from days to weeks post transplant, were retrospectively reviewed. Results: 5 patients (1F, 4M) ranging in age from 25-63yrs (mean 48±17yrs) were diagnosed with SFSS. The pre-transplant MELD score was 11.2±4.4. Grafts consisted of 3R lobes, 1L lobe and 1LLS. Graft to recipient weight ratios (GRWR) were 1.0±0.3, range 0.6-1.4. (1/5 patients had a GRWR <0.8). Operative procedures were uncomplicated and biliary reconstruction was duct to duct in 2 patients and Roux-en-Y anastomosis in 3 patients. The peak post-operative bilirubin was 23±12mg/dl (range: 9.3-40). 3/5 patients were retransplanted at 16±3 days. 3/5 patients died, 2 post retransplantation. 2/5 patients are alive at 29 and 30 mos. Compared to patients with no graft loss this group did not differ with respect to pre-operative complications, warm and cold ischemia times, transfusion requirements, cardiac output or cardiac index. Examination of liver biopsies and failed allograft specimens obtained days to weeks post transplant revealed histopathologic findings that followed a characteristic pattern of progression in the most seriously affected grafts. Portal vein (PV) endothelial denudation and subendothelial and interstitial hemorrhage was seen within days. Partial or complete thrombosis of PV branches occured within weeks with centrilobular cholestasis, microvesicular steatosis, ductular reaction and evidence of severe HA vasospasm. Failed allografts showed evidence of functional de-arterialization because of intense HA vasospasm and/or arterial thrombosis, accompanied by perihilar bile duct necrosis and parenchymal infarcts. One patient with SFSS survived with his original graft and liver biopsy showed evidence of nodular regenerative hyperplasia. ACR was seen in 4/5 patients diagnosed with SFSS and the significance of this is unclear. Conclusions: The pathophysiologic SFSS is present in most reduced size organs and is a result of PV hyper-perfusion that causes intra-hepatic PV branch thrombi, and leads to significant HA vasospasm. At its most severe, a SFS graft becomes functionally de-arterialized. Additional insults such as rejection can exacerbate the problem.
P118 Aims: To assess clinical outcomes using livers from controlled NHBD in the era of organ shortage with report on survival and complications on the largest single center experience with up to 10 years of follow-up. Methods: 61 liver transplants performed in 60 patients from NHBD between 1994-2004. Donors ranged between 4-68 years old (mean 38±16), with arrest to cross-clamp time of 6±5 minutes. Organs were flushed with Viaspan (45) or HTK (16) solutions using aortic cannulation. During this period 32 livers were discarded for documented anatomic and histologic reasons. The age of the recipients ranged from 18-69 years (50±11). Since mid-2002, we accepted NHBD livers recovered by other programs. 18 livers were imported (three transcontinental) and 14 transplanted. Results: Cold ischemia time was 358-1056 (630±144) minutes. Primary Non-Function (PNF) occurred in 6 patients (10%). Four retransplanted and three survived, two other died of sepsis. Hepatic artery thrombosis (HAT) occurred in 6 (11%) patients; three retransplanted and one survived; two died without re-transplantation and one survived with reconstruction. Biliary strictures or leaks were seen in 11 (18%) patients which four were irreversible (two required retransplantation, one died before re-transplantation and one re-listed). Nine patients were re-transplantaed for HAT (3), PNF (4) or biliary complications (2). Livers from NHBD were used to re-transplant seven emergency patients and five survived. Overall mortality in the group was 13 patients with 1-, 5-, and 10-year patient and graft survival of 80%, 78%, 76%, and 69%, 67% and 67% respectively. Organs procured by other programs did not show any difference in function or complications. Conclusions: The rate of PNF and major biliary complications was significantly higher than organs from heartbeating donors, leading to lower early graft survival, although long-term survival was not different. Thus, controlled NHBD remain an acceptable source of organs in the era of organ shortage.
4158 Background: There are no drugs that have accepted response rates for unresectable cholangiocarcinoma and the presence of underlying cirrhosis in about 80 % of patients with HCC, makes regional chemotherapy hazardous. New chemotherapeutic agents need to be identified that are less toxic to the liver that has already been damaged by chronic hepatitis or cirrhosis. Method: Gemcitabine was evaluated for its safety and effectiveness in 44 pts with CC and 30 pts with HCC, with bilirubin grade I hematologic toxicity was seen in any pt. No pt went into irreversible liver failure. However, 8 of 30 pts with HCC had transient elevations of bilirubin. No pts with CC had any hepatic toxicity. Results: CT responses were often difficult to estimate for CC, since central lesions were often ill-defined on any non-invasive radiologic study. However, 8 CC pts are alive > 24 mo, 15 pts are alive at 12–24 mo, 14 pts died at 6–12 mo and 7 pts died at 6 mo. Currently, 6 pts have died, all > 3 mo and < 9 mo and all from tumor progression. Conclusions: these initial results show that TACE with Gemcitabine is safe, even in the liver with cirrhosis, provided that the starting bilirubin is < 1.5 mg/dL and can result in partial responses. It looks particularly interesting for pts with unresectable CC. Longer follow-up will determine the survival effects. No significant financial relationships to disclose.
O304 Aim: To examine patient and graft survival with associated complications. Material&Method: One thousand consecutive patients (M=600,F=400) mean age 42.5 ±20.2, 834 adults (age>18years) and 166 children (age<18 years) received primary LTx between Aug, 1989 and Dec. 1992, were followed until April 2004 with mean follow up of 13±0.92 years (range11 to 15) Results: Overall patient / graft survival at 14 year 52.1%/ 47.9% respectively. Safety profiles: ">Rejection: 635 patients experienced at least one episode of acute rejection and 23 grafts were lost from chronic rejection. CNS complication: 307 (307%) patients experienced neurological complications (32.3 % adult and 20.4% in children) consisting of confusion, seizure disorder, peripheral neuropathy, severe headache, Cerebropontine Myelinosis, dysarthria and others. Renal function: Thirty patients received kidney transplant and 51 patients required dialysis. Infection: Bacterial, viral and fungal infection occurred in 355 (35.1%), 270 (22%) and 76 (7.6%) of patients respectively. PTLD: 43 patients developed PTLD, adults 25 (3%), 18 (10.8%) in children. Denovo Cancer: 95 patients (9.5%) developed denovo cancer including 37 skin cancers.FigureConclusion: While multiple and often times, severe complications can occur following LTx, the overall survival of these patients is excellent. However, the impacts of various combinations of complications need further evaluation. Future studies should be directed towards reduction in rate of complications and prevention of multiple complications to improve patient and graft survival.
We have proposed that the mechanisms of alloengraftment and variable acquired tolerance can be facilitated by minimum posttransplant immunosuppression. It was further suggested that the efficacy of minimalistic treatment could be enhanced by preoperative recipient conditioning with an antilymphoid antibody preparation. A total of 76 adults (38 hepatitis C virus [HCV], 38 HCV) were infused with 30 mg alemtuzumab before primary cadaveric liver transplantation and maintained afterward on daily monotherapy unless breakthrough rejection mandated additional agents. In stable patients, the intervals between tacrolimus doses were lengthened ("spaced weaning") after approximately 4 months. Eighty-four contemporaneous nonlymphoid-depleted liver recipients (58 HCV, 26 HCV) were treated with conventional postoperative immunosuppression. The overall incidence of rejection was similar with the two strategies of immunosuppression. With follow-ups of 14 to 22 months, patient and primary graft survival in HCV cases are 97% and 90%, respectively, with alemtuzumab depletion plus minimal immunosuppression versus 71% and 70%, respectively, under conventional immunosuppression. In HCV recipients, current patient and graft survival in the alemtuzumab-pretreated group are 71% and 70% versus 65% and 54%, respectively, under conventional treatment. With both strategies of immunosuppression, the adverse effect of preexisting HCV on survival parameters and graft function already was significant at the 1-year milestone, but its extent was not evident until the second year. With or without HCV, 62% of the 64 surviving lymphoid-depleted patients are on spaced immunosuppression, and four patients receive no immunosuppression. Lymphoid depletion with alemtuzumab and minimalistic maintenance immunosuppression is a practical strategy of liver transplantation in HCV recipients but not HCV recipients.