Splenic artery steal syndrome (SASS) has only recently been recognized as a potential threat to transplanted livers. We report a case of SASS with progressive liver dysfunction that developed after living donor right lobe liver transplantation. SASS suspected by serial pre- and postoperative computed tomographic (CT) scans was diagnosed by celiac trunk angiography. It was successfully salvaged by splenic artery embolization. In this case, serial examinations of CT scans were useful to diagnose SASS. This case showed that portal hyperperfusion injury is a cause of liver graft dysfunction in SASS. The splenic artery embolization technique is a safe procedure that can be applied to treat such injury.
Splenic Artery , Subclavian Steal Syndrome/diagnosis , Ascites/pathology , Aspartate Aminotransferases/blood , Balloon Occlusion , Bilirubin/blood , Female , Hepatic Artery/diagnostic imaging , Humans , Liver Function Tests , Middle Aged , Splenic Artery/diagnostic imaging , Splenic Artery/surgery , Subclavian Steal Syndrome/therapy , Tomography, X-Ray Computed , Treatment Outcome
Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.
Carcinoma, Hepatocellular/physiopathology , Immunosuppressive Agents/pharmacology , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Liver Neoplasms, Experimental/physiopathology , Liver Transplantation , Protein Serine-Threonine Kinases/antagonists & inhibitors , Tacrolimus/pharmacology , Amides/pharmacology , Animals , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/physiology , Cell Proliferation/drug effects , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Intracellular Signaling Peptides and Proteins/physiology , Liver Neoplasms, Experimental/therapy , Male , Neoplasm Invasiveness/physiopathology , Neoplasm Recurrence, Local/physiopathology , Neoplasm Recurrence, Local/prevention & control , Protein Serine-Threonine Kinases/physiology , Pyridines/pharmacology , Rats , Rats, Inbred BUF , Signal Transduction/drug effects , Signal Transduction/physiology , rho-Associated Kinases
