Toshiyuki Takeishi

Impaired splenic erythropoiesis in phlebotomized mice injected with CL2MDP-liposome: an experimental model for studying the role of stromal macrophages in erythropoiesis.

Erythropoiesis occurs in the presence of erythropoietin (EPO) without macrophages in vitro. In hematopoietic tissues, however, erythroid cells associate closely with stromal macrophages, forming erythroblastic islands via interactions with adhesion molecules. To elucidate the role of macrophages in erythropoiesis, we selectively abrogated stromal macrophages of splenic red pulp of phlebotomized mice by injection with dichloromethylene diphosphonate encapsulated in multilamellar liposomes (CL2MDP‐liposome). In the spleen, no erythropoietic activity occurred until 5 days after the treatment. Colony assay revealed that the erythropoiesis was suppressed at the level of CFU‐E. The splenic erythropoietic activity gradually developed from day 6 after the treatment, when F4/80+ macrophages began to appear in the red pulp. EPO mRNA was expressed in kidney but not in liver or spleen of phlebotomized mice injected with CL2MDP‐liposome, and the serum EPO concentration in these mice was higher than that in phlebotomized mice. These findings suggest that abrogation of stromal macrophages by injection with CL2MDP‐liposome impairs the splenic microenvironment for erythropoiesis induced by hypoxic stress, and this may be an excellent experimental model for further characterization of the in vivo role of splenic macrophages in erythropoiesis.

Sclerosing encapsulating peritonitis in two patients with liver cirrhosis.

Sclerosing encapsulating peritonitis (SEP) has been reported in a wide variety of patients, including those who have undergone peritoneal dialysis (PD), young adolescent girls, cirrhotic patients after peritoneal-venous shunting (PVS), and patients treated with Β-blockers. Nevertheless, the etiology of SEP remains obscure. In this article, we report on two patients with severe liver cirrhosis who were diagnosed as having SEP. The association of SEP with liver cirrhosis in patients who have not undergone PVS has previously been reported only rarely. Neither of our two patients had received PD or PVS, and neither had been treated with Β-blockers, but both had suffered persistent intraabdominal infection. In one patient, we performed therapy combining total enterolysis with the oral administration of prednisolone, at 5 mg/day. The patient recovered and is currently free of symptoms at approximately 15 months after surgery. We believe that SEP may produce complications in cirrhotic patients with persistent intraabdominal infection, and that a combination therapy of surgical and immunosuppressive treatment may be effective for alleviating the small-intestinal obstruction due to SEP.

Management of major portosystemic shunting in small-for-size adult living-related donor liver transplantation with a left-sided graft liver

PurposeWe investigated the mechanisms of small-for-size graft syndrome by time-lag ligation, a novel approach to treating major portosystemic shunts in small-for-size adult living-related donor liver transplantation (LRDLT) using left-sided graft liver.MethodsFive patients with end-stage liver failure and major splenorenal shunting underwent LRDLT using left lobe grafts. The average graft volume to recipient body weight (GV/RBW) ratio was 0.68 ± 0.14. Two patients underwent time-lag ligation of their splenorenal (SR) shunts on postoperative days (PODs) 8 and 14, respectively. The shunts of the other three patients were untreated.ResultsThe portal pressures in the first patient who underwent time-lag ligation rose above 300 mmH2O and remained there for 2 weeks. Thus, we ligated the SR shunt in the second patient on POD 14, resulting in an increase from 177 mmH2O to 258 mmH2O, but it decreased again thereafter. In the other three patients, the SR shunt was not ligated because portal blood flow volumes remained sufficient. Total bilirubin levels in the first time-lag ligation patient rose to 16 mg/dl, paralleling the rise in portal pressures. Although they increased after ligation in the second patient, they did not exceed 10 mg/dl.ConclusionsWe recommend time-lag ligation if portal venous blood flow decreases in the early post-transplant period, but not until at least 2 weeks after transplantation. If the portal venous blood flow does not decrease, early postoperative ligation is unnecessary. If there are no major portosystemic shunts, making a portosystemic shunt might decompress excessive portal hypertension. With donor safety priority in LRDLT, novel approaches must be developed to enable the use of smaller donor grafts. We describe a potential means of using left lobe grafts in adult LRDLT.

Auxiliary partial orthotopic living donor liver transplantation for fulminant hepatic failure with flat electroencephalogram: a case report.

A 54-year-old woman with hepatic encephalopathy grade IV (coma) and flat electroencephalogram (EEG) due to fulminant liver failure (FHF) due to hepatitis B virus infection was admitted to our hospital on May 24, 2002. We performed a living donor auxiliary partial orthotopic liver transplantation (APOLT) emergently on the day of admission. The donor was the patients son, whose ABO blood group was identical. The immunosuppressant regimen consisted of tacrolimus and low-dose steroids. The left lobe (260 g) of the recipient, which was removed using a Pringle maneuver, was reconstructed with a left lobe (417 g) graft from the donor, which was orthotopically positioned as an auxiliary support. The patient remained in a coma for the first 5 days but on day 6 her eyes opened and followed objects. Finally, she recovered an almost normal appearance. Abdominal compartment syndrome, bile leak, and a mild rejection episode occurred during the postoperative course; all were treated successfully. The patient was discharged on the postoperative day 142. Computed tomography (CT) scan and biopsy were used to follow the changes in the graft and the native liver. On postoperative day 520, a CT scan showed a remarkable improvement in native liver size (493 cm3). Immunosuppression was tapered off and stopped on the postoperative day 635 to surrender the grafted liver. The graft liver biopsy specimen showed severe chronic rejection. The present status of the patient, who is now more than 7 years after transplantation, is an absence of neurological findings with normal liver function.

Temporary Cardiac Pacing for Fatal Arrhythmia in Living-Donor Liver Transplantation: Three Case Reports

Cardiac pacing often turns out to be the only effective treatment of severe, life-threatening arrhythmias. We performed 77 living-donor liver transplantations (LDLT) from 1999 to 2007. In these cases, three recipients experienced fatal arrhythmia and required temporary cardiac pacing during the perioperative period. The first case was a 68-year-old woman diagnosed with liver cirrhosis and hepatocellular carcinoma (HCC). Her Model for End-Stage Liver Disease (MELD) score was 34. We performed LDLT using a right lobe graft. She showed complete atrioventricular block with cardiac arrest at postoperative day (POD) 42 after a bacterial infection. We performed a resuscitation and instituted temporary cardiac pacing. However, she was dead at POD 43. Pathologic findings at autopsy showed a diffuse myocardial abscess, which caused the fatal arrhythmia. The second case was a 58-year-old man diagnosed with HCC and liver cirrhosis; his MELD score was 9. We performed LDLT using a right lobe graft. He showed atrial fibrillation after septic shock. He also showed sinus bradycardia with a cardiac arrest at POD 10. We performed resuscitation and emergent temporary pacing. He recovered and was alive without recurrence of arrhythmia or infection. The third case was a 58-year-old woman diagnosed with multiple HCC. During preoperative regular check-up, she was diagnosed to have cardiac hypertrophy and was started on beta-blockers as treatment for cardiac hypertrophy. However, severe bradycardia necessitated temporary cardiac pacing. LDLT was performed safely after implantation of a pacemaker. Early use of temporary cardiac pacing for severe arrhythmias may be effective to maintain the hemodynamic state in LDLT.