Split-liver transplantation: One plus one doesn't always equal two

Surgical reduction of donor livers to treat small children has been performed successfully in several centers. While this procedure improves the allocation of livers, it does not increase the organ supply. We have extended reduced-size orthotopic liver transplantation (OLT) to treat 18 patients with 9 livers, accounting for 26% of our transplants during a 10-month period and have evaluated the results. In 18 split liver OLTs, patient survival was 67% and graft survival was 50%. In comparison, for 34 patients treated with full-size OLT during the same period, patient survival was 84% (p = 0.298) and graft survival was 76% (p = 0.126). Biliary complications were significantly more frequent in split grafts, occurring in 27%, as compared to 4% in full-sized grafts (p = 0.017). Primary nonfunction (4% versus 5.5%) and arterial thrombosis (6% versus 9%) occurred with similar frequency in split and full-size OLT (p = not significant). These results demonstrated that split-liver OLT is feasible and could have a substantial impact in transplant practice. We believe that biliary complications can be prevented by technical improvements and that split-liver OLT will improve transplant therapy by making more livers available. The University of Chicago program in pediatric liver transplantation continues actively to seek innovative surgical solutions to problems related to the management of children with end-stage liver disease. Among the most important problems facing these children is a shortage of donor organs, which results from three factors in addition to the actual supply of pediatric donors: the concentration of pediatric liver disease in the population younger than 2 years; the necessity for a graft that is small enough; and the epidemiology of accidents and other events that lead to organ donation. Transplantation using a liver love as a graft overcomes size disparity and shifts the available supply of organs fromolder donors to tounger recipients. This work describes the technical aspects of recent innovations in the use of liver lobes in pediatric transplantation, simple reduced-size liver transplantation (RLT), split-liver transplantation (SLT), orthotopic auxiliary liver grafting (ALT), and transplantation using a living related donor (LRLT), and compares their results. Since November 1986 a total of 61 procedures have been performed in which a liver lobe was used as a graft: 26 RLT;30 SLT,25 in children and 5 in adults; 5 LRLT; and 1 ALT. Overall 62% of transplants performed in children have involved using a liver lobe as a graft. The rates of ccomplications are somewhat higher than with whole-liver transplantation, but this may not be entirely the result of the complex procedures. Split liver transplantation is associated with complications in donors and recipients, but to date survival is 100%. Orthotopic auxillary liver transplatation effectively corrected the metabolic defect n one patient with ornithine transcarbamylase deficiency. Overall the various modalities of using graft reduction have reduction have resulted in postoperative results similar to those aachieved with full-size grafts, while pretransplantation mortality has been limited to less than 2%. Thous the use of grafts as liver lobes accomplisshes the goal of reducing global mortality among children with end-stage liver disease, but at the cost of increased surgical complexity and more postoperative complications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38365/1/1840140327_ftp.pd

Orthotopic liver transplantation for urea cycle enzyme deficiency

Hyperammonemia, abnormalities in plasma amino acids and abnormalities of standard liver functions were corrected by orthotopic liver transplantation in a 14‐day‐old boy with carbamyl phosphate synthetase‐I deficiency and in a 35‐yr‐old man with argininosuccinic acid synthetase deficiency. The first patient had high plasma glutamine levels and no measureable citrulline, whereas citrulline values were markedly increased in Patient 2. Enzyme analysis of the original livers showed undetectable activity of carbamyl phosphate synthetase‐I in Patient 1 and arginosuccinic acid synthetase in Patient 2. Both patients were comatose before surgery. Intellectual recovery of patient 1 has been slightly retarded because of a brain abscess caused by Aspergillus infection after surgery. Both patients are well at 34 and 40 mo, respectively, after surgery. Our experience has shown that orthotopic liver transplantation corrects the life‐threatening metabolic abnormalities caused by deficiencies in the urea cycle enzymes carbamyl phosphate synthetase‐I and arginosuccinic acid synthetase. Seven other patients–six with ornithine transcarbamylase deficiency and another with carbamyl phosphate synthetase‐I deficiency–are known to have been treated elsewhere with liver transplantation 1 1/2 yr or longer ago. Four of these seven recipients also are well, with follow‐ups of 1 1/2 to 5 yr. Thus liver transplantation corrects the metabolic abnormalities of three of the six urea cycle enzyme deficiencies, and presumably would correct all. (Hepatology 1992;15:419–422). Copyright © 1992 Wiley Subscription Services, Inc

Comparison of the collagen haemostat Sangustop(R) versus a carrier-bound fibrin sealant during liver resection; ESSCALIVER-study

Background: Haemostasis in liver surgery remains a challenge despite improved resection techniques. Oozing from blood vessels too small to be ligated necessitate a treatment with haemostats in order to prevent complications attributed to bleeding. There is good evidence from randomised trials for the efficacy of fibrin sealants, on their own or in combination with a carrier material. A new haemostatic device is Sangustop(R). It is a collagen based material without any coagulation factors. Pre-clinical data for Sangustop(R) showed superior haemostatic effect. This present study aims to show that in the clinical situation Sangustop(R) is not inferior to a carrier-bound fibrin sealant (Tachosil(R)) as a haemostatic treatment in hepatic resection. Methods: This is a multi-centre, patient-blinded, intra-operatively randomised controlled trial. A total of 126 patients planned for an elective liver resection will be enrolled in eight surgical centres. The primary objective of this study is to show the non-inferiority of Sangustop(R) versus a carrier-bound fibrin sealant (Tachosil(R)) in achieving haemostasis after hepatic resection. The surgical intervention is standardised with regard to devices and techniques used for resection and primary haemostasis. Patients will be followed-up for three months for complications and adverse events. Discussion: This randomised controlled trial (ESSCALIVER) aims to compare the new collagen haemostat Sangustop(R) with a carrier-bound fibrin sealant which can be seen as a "gold standard" in hepatic and other visceral organ surgery. If non-inferiority is shown other criteria than the haemostatic efficacy (e.g. costs, adverse events rate) may be considered for the choice of the most appropriate treatment. Trial Registration: NCT0091861

Experience With Radical Resection in The Management of Proximal Bile Duct Cancer

Multiple surgical and nonsurgical approaches have been advocated for the treatment of proximal bile duct cancer. However, survival appears longest when a resection can be performed. Fifteen patients treated at a university center were managed with an aggressive surgical approach. Resection of the tumor was performed in 13 of 15 patients (87%). Of the patients undergoing resection, major hepatic resection was performed in 8 (62%), while excision of vessels with reconstruction was performed in 5 (38%). Eleven of the 13 resected patients (85%) were discharged from the hospital. Clinical symptoms of recurrent disease occurred between 3 and 36 months after surgery in 7 patients, 6 of whom have died. Three other patients are alive at 5, 21, and 36 months without clinical evidence of recurrence. There was no correlation between the completeness of resection and the duration of disease-free survival

Segmental Liver Transplantation From Living Donors Report of the Technique and Preliminary Results in Dogs

A technique of orthotopic liver transplantation using a segmental graft from living donors was developed in the dog. Male mongrel dogs weighing 25–30 kg were used as donors and 10–15 kg as recipients. The donor operation consists of harvesting the left lobe of the liver (left medial and left lateral segments) with the left branches of the portal vein, hepatic artery and bile duct, and the left hepatic vein. The grafts are perfused in situ through the left portal branch to prevent warm ischemia. The recipient operation consists of two phases: 1total hepatectomy with preservation of the inferior vena cava using total vascular exclusion of the liver and veno-venous bypass, 2implantation of the graft in the orthotopic position with anastomosis of the left hepatic vein to the inferior vena cava and portal, arterial and biliary reconstruction. Preliminary experiments consisted of four autologous left lobe transplants and nine non survival allogenic left lobe transplants. Ten survival experiments were conducted. There were no intraoperative deaths in the donors and none required transfusions. One donor died of sepsis, but all the other donor dogs survived without complication. Among the 10 grafts harvested, one was not used because of insufficient bile duct and artery. Two recipients died intraoperatively of air embolus and cardiac arrest at the time of reperfusion. Three dogs survived, two for 24 hours and one for 48 hours. They were awake and alert a few hours after surgery, but eventually died of pulmonary edema in 2 cases and of an unknown reason in the other. Four dogs died 2–12 hours postoperatively as a result of hemorrhage for the graft's transected surface. An outflow block after reperfusion was deemed to be the cause of hemorrhage in these cases. On histologic examination of the grafts, there were no signs of ischemic necrosis or preservation damage

Complications of right lobe living donor liver transplantation

Background/Aims: Right lobar living donor liver transplantation (LDLT) has been controversial because of donor deaths and widely variable reports of recipient and donor morbidity. Our aims were to ensure full disclosure to donors and recipients of the risks and benefits of this procedure in a large University center and to help explain reporting inconsistencies. Methods: The Clavien 5-tier grading system was applied retrospectively in 121 consecutive adult right lobe recipients and their donors. The incidence was determined of potentially (Grade III), actually (Grade IV), or ultimately fatal (Grade V) complications during the first post-transplant year. When patients had more than one complication, only the seminal one was counted, or the most serious one if complications occurred contemporaneously. Results: One year recipient/graft survival was 91%/84%. Within the year, 80 (66%) of the 121 recipients had Grade III (n = 54) Grade IV (n = 16), or Grade V (n = 10) complications. The complications involved the graft's biliary tract (42% incidence), graft vasculature (15%), or non-graft locations (9%). Complications during the first year did not decline with increased team experience, and adversely affected survival out to 5 years. All 121 donors survive. However, 13 donors (10.7%) had Grade III (n = 9) or IV (n = 4) complications of which five were graft-related. Conclusions: Despite the satisfactory recipient and graft survival at our and selected other institutions, and although we have not had a donor mortality to date, the role of right lobar LDLT is not clear because of the recipient morbidity and risk to the donors. © 2009 European Association for the Study of the Liver

Themes of liver transplantation

Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as healthcare standards, the ethical, legal, equity, and the other humanism issues of Theme V have been resolved less conclusively than the medical-scientific problems of Themes I-IV. Copyright © 2010 by the American Association for the Study of Liver Diseases

Imaging evaluation of the liver using multi-detector row computed tomography in micropigs as potential living liver donors

The shortage of organ donors has stimulated interest in the possibility of using animal organs for transplantation into humans. In addition, pigs are now considered to be the most likely source animals for human xenotransplantation because of their advantages over non-human primates. However, the appropriate standard values for estimations of the liver of micropigs have not been established. The determination of standard values for the micropig liver using multi-detector row computed tomography (MDCT) would help to select a suitable donor for an individual patient, determine the condition of the liver of the micropigs and help predict patient prognosis. Therefore, we determined the standard values for the livers of micropigs using MDCT. The liver parenchyma showed homogenous enhancement and had no space-occupying lesions. The total and right lobe volumes of the liver were 698.57 ± 47.81 ml and 420.14 ± 26.70 ml, which are 51.74% and 49.35% of the human liver volume, respectively. In micropigs, the percentage of liver volume to body weight was approximately 2.05%. The diameters of the common hepatic artery and proper hepatic artery were 6.24 ± 0.20 mm and 4.68 ± 0.13 mm, respectively. The hepatic vascular system of the micropigs was similar to that of humans, except for the variation in the length of the proper hepatic artery. In addition, the diameter of the portal vein was 11.27 ± 0.38 mm. In conclusion, imaging evaluation using the MDCT was a reliable method for liver evaluation and its vascular anatomy for xenotransplantation using micropigs

Living donor liver transplantation for neonatal hemochromatosis using non-anatomically resected segments II and III: a case report

<p>Abstract</p> <p>Introduction</p> <p>Neonatal hemochromatosis is the most common cause of liver failure and liver transplantation in the newborn. The size of the infant determines the liver volume that can be transplanted safely without incurring complications arising from a large graft. Transplantation of monosegments II or III is a standard method for the newborns with liver failure.</p> <p>Case presentation</p> <p>A three-week old African-American male neonate was diagnosed with acute liver failure secondary to neonatal hemochromatosis. Living-related liver transplantation was considered after the failure of intensive medical therapy. Intra-operatively a non-anatomical resection and transplantation of segments II and III was performed successfully. The boy is growing normally two years after the transplantation.</p> <p>Conclusion</p> <p>Non-anatomical resection and transplantation of liver segments II and III is preferred to the transplantation of anatomically resected monosegements, especially when the left lobe is thin and flat. It allows the use of a reduced-size donor liver with intact hilar structures and outflow veins. In an emergency, living-related liver transplantation should be offered to infants with liver failure secondary to neonatal hemochromatosis who fail to respond to medical treatment.</p