Benefit of an implanted solid barrier for the feasibility of a sequence of three different hepato-biliary operations in a small animal model.

BACKGROUND: Current liver surgery includes complex multi-stage procedures such as portal vein ligation (PVL) followed by extended liver resection, especially in patients with Klatskin tumours. The risk for severe adhesions increases with every procedure. Finally, this complex sequence could fail because of malignant adhesions. Therefore, we proved the hypothesis of reducing malignant adhesions and increasing feasibility of a sequence with three hepato-biliary operations by implantation of a solid barrier. MATERIALS AND METHODS: We operated in male rats (n=40). Our sequence included as 1st operation bile duct ligation mimicking Klatskin III° or IV°, the 2nd operation was a selective portal vein ligation (sPVL) and 3rd procedure was a 70% liver resection. The mechanical barrier (part of a sterile glove) was implanted at the end of the first operation between the upper (median lobe+left lateral lobe [ML+LLL]) and lower (right lobe+caudate lobe [RL+CL]) rat liver lobes. We assessed the degree of adhesions and the feasibility of the 2nd and 3rd operation by using an established adhesion score (Zühlke) and a feasibility score. The severity of the adhesions and the pro-inflammatory cellular response were further evaluated by morphometry of thickness (HE) of the adhesion layer and quantification of infiltrating neutrophils (ASDCL) in the adhesion layer on the liver surface. RESULTS: The planned liver resection as the third procedure was only feasible when a mechanical barrier was placed. Extent of cholestasis or time interval between the operations had no significant impact on adhesions score or feasibility of the whole sequence. CONCLUSION: A sequence of three hepato-biliary operations in a small animal model (rat) is feasible. It should be considered to implant a mechanical barrier in a sequence of more than two surgical interventions in an experimental model in order to assure the feasibility of the final operation.

[Liver engineering as a new source of donor organs : A systematic review]. / "Liver engineering" als neue Quelle von Spenderorganen : Eine systematische Übersichtsarbeit.

BACKGROUND: Organ engineering is a new strategy to cope with the shortage of donor organs. A functional scaffold from explanted organs is prepared by removing all cellular components (decellularization) and the reseeding (repopulation) of the organ scaffold to generate a functional organ in vitro for transplantation. This technique was also applied to the liver (liver engineering). OBJECTIVES: Outline of the current state of the art and resulting approaches for future research strategies. MATERIAL AND METHODS: Systematic review according to the PRISMA guidelines: a PubMed-based literature search (search terms liver, decellularization), selection of relevant articles based on predetermined criteria for relevance (e.g. decellularization, repopulation and transplantation), extraction and critical appraisal of data and results concerning the conditions for decellularization, repopulation and transplantation. RESULTS: Decellularization was successfully performed in small and large animal models. Hepatocytes as well as stem cells and hepatic cell lines were applied for repopulation and 7 publications could show the successful transplantation of acellular and repopulated organ scaffolds. The current scientific need for further studies concerning the source of donor organs, optimization of the decellularization process, the cell type for the reseeding process and the establishment of the optimal conditions for the repopulation of the scaffold is still tremendous. For successful recellularization of the liver three goals need to be achieved: (1) reseeding of the organ scaffold with a sufficient amount of parenchymal cells, (2) endothelialization of the vascular tree to ensure the supply of oxygen and nutrients to parenchymal cells and (3) an appropriate epithelialization of the biliary tree. In order to progress to clinical trials a suitable transplantation model to verify the function of the organ constructs must be established. CONCLUSION: Liver engineering using biological cell-free organ scaffolds represents a scientific and ethical challenge. The existing results emphasize the potential of this new and promising strategy to create organs for transplantation in the future.