K. Asonuma

Auxiliary partial orthotopic liver transplantation from living donors : Significance of portal blood flow

BACKGROUND Auxiliary liver transplantation has several advantages over standard orthotopic liver transplantation. However, functional competition has been reported even in auxiliary partial orthotopic liver transplantation (APOLT). We evaluated herein the interaction in APOLT between the native liver and the graft in terms of portal blood flow and regeneration. The need for diversion of the portal blood flow to the graft was also assessed. METHODS A total of 15 patients received APOLT from living donors. Portal blood flow to the native liver was preserved in 6 patients, and the portal vein to the native liver was preemptively transected at the time of transplantation in 9 patients. RESULTS Of the patients with preservation of the portal blood flow to the native liver, two showed inadequate graft portal blood flow just after operation, and in the other three patients the graft portal blood flow decreased or the graft atrophied after deterioration of the graft function. In the patients with preemptive transection of the portal vein to the native liver, optimal graft portal blood flow was obtained, and the native liver, supplied only by arterial inflow, supported a small-for-size graft until the graft regenerated. The damage to the native liver was minimal. CONCLUSIONS Functional competition may occur in APOLT with preservation of the portal blood flow to the native liver, whereas preemptive transection of the native liver portal vein is a safe procedure and effectively prevents the portal steal phenomenon.

One‐way donor‐recipient HLA‐matching as a risk factor for graft‐versus‐host disease in living‐related liver transplantation

Abstract Although one‐way matching between an HLA‐homozygous donor and a haploidentical recipient is a recognized risk factor in transfusion‐associated graft‐versus‐host disease (GVHD), its impact in living‐related liver transplantation (LRLT) has so far not been investigated. We present a case of fatal acute GVHD in our LRLT program that was attributed to one‐way HLA matching between donor and recipient. Although the disappearance of donor cells in peripheral blood was suggested by genetic analysis, severe septicemia led to a fatal outcome. We further reviewed 280 LRLT cases and correlated one‐way HLA matching with outcome. A total of 8 out of 280 donors (2.9%) and 11 out of 278 recipients (4.0%) were completely HLA homozygous in our LRLT program. Complete one‐way HLA matching linked to GVHD was observed in four cases, including the present case. Although other contributing factors also need to be clarified, one‐way HLA matching is a definite risk factor for GVHD in LRLT. We advocate caution before proceeding with one‐way HLA donor‐recipient combinations.

Living related liver transplantation from donors with the left-sided gallbladder/portal vein anomaly.

The presence of a left-sided gallbladder poses a unique challenge for living related liver donation. Associated anomalies include segment IV atrophy, absence of portal vein bifurcation, and abnormal intrahepatic portal branches to segments II and III. The complex is rare, but is more frequent in Japan. Of 379 living related liver transplants from our institution, the complex has been encountered on four occasions (incidence: 1.1%), and we herein review our experience. Anomalies were identified preoperatively (by computed tomography and ultrasound) in all instances. One donor was turned down because there was no common portal trunk to segment II and III branches. Three donors underwent successful retrieval using a modified technique. There were no complications in the donors or recipients relating to the complex. Thus, living related liver retrieval can be achieved safely in the presence of the left-sided gallbladder/portal anomaly complex, but technical modifications are required.

Small bowel transplantation using grafts from living-related donors. Two case reports

Abstract A living‐related small bowel transplantation (SBT) was performed in two pediatric patients with short bowel syndrome. In both cases, the donor was the patients mother. The distal ileum (100 cm, 120 cm) was harvested and the ileocolic vessels, ileocecal valve, and terminal ileum were left intact. The two donors were discharged from the hospital on postoperative days 15 and 6, respectively. Recipient 1 was a 2 year 6 month‐old boy with short bowel syndrome who underwent SBT due to loss of venous access. The graft vein was anastomosed to the recipients infrarenal inferior vena cava. Despite triple immunosuppression (tacrolimus, steroid, and azathioprine), there were four episodes of rejection. The patient had been on total parenteral nutrition for almost his entire post‐transplant course. He died from Pneumocystis carinii pneumonia 16 months after the transplantation. Recipient 2 was a 4 year 5 month‐old girl with short bowel syndrome who underwent an isolated small bowel transplantation because of recurrent line sepsis. Her pretransplant bilirubin was 8.0 mg/dl and a biopsy showed severe fibrosis. The graft vein was anastomosed to the recipients inferior mesenteric vein. After transplantation, her bilirubin level became normal within 10 days. Triple immunosuppression (tacrolimus, steroid, and cyclophosphamide) together with a 3‐day course of OKT‐3 made her post‐transplant course feasible. After overcoming a single episode of rejection she left the hospital 4 months after SBT. The patient is currently (10 months after transplantation) hospitalized due to rejection, which is being successfully controlled, and she is off total parenteral nutrition. From our experience, harvesting of the distal ileum for use as a bowel graft can be safely performed. The advantages of living‐related grafts, optimal graft length, and choice of vascular reconstruction in SBT are yet to be explored.

Serotonin as a useful parameter for cold and warm ischemic injury in small bowel transplantation

We investigated serotonin as a parameter of cold and warm ischemic injury prior to transplantation. Lewis rats were used as both donors and recipients, and the proximal 20 cm of jejunum served as the graft. The grafts were preserved in 4 degrees C lactated Ringers solution for 0, 6, 12, 18, and 24 hr after harvest for cold ischemia (n=7/group). The superior mesenteric artery was clamped for 0, 15, 30, 60, and 120 min before harvest for warm ischemia (n=7/group). The serotonin concentration was measured in the luminal effluent and the preservation solution before transplantation, and total serotonin was calculated as the sum of these amounts. Finally, transplantation was performed heterotopically. Total serotonin increased significantly with both cold and warm ischemic time (P<0.01 by analysis of variance, Fishers PLSD); however, between 18 hr and 24 hr of cold ischemic time only, there were no significant changes. Total serotonin levels correlated well with cold and warm ischemic time, as shown by linear regression analysis (cold ischemia: R2=80.2%, P<0.01; warm ischemia: R2=92.8%, P<0.01). We established the cutoff level of total serotonin to predict the graft survival at 2200 ng, and using this critical level, graft survival was predicted by total serotonin with a sensitivity of 71.4% and a specificity of 89.8%. Immunohistochemical staining with the serotonin antibody revealed that the number of serotonin-positive cells decreased with both cold and warm ischemic time. In conclusion, serotonin is a useful parameter of cold and warm ischemic injury before transplantation and can assist in predicting graft survival.

Portal Blood Flow and Liver Regeneration in Auxiliary Partial Orthotopic Liver Transplantation in a Canine Model

Functional competition has been shown to lead to a detrimental outcome in auxiliary liver transplantation. We evaluated the interaction in auxiliary partial orthotopic liver transplantation between the native liver and the graft in terms of portal flow and regeneration. The need for diversion of the portal flow to the graft was also assessed. Reduced-size liver grafts were transplanted orthotopically after partial hepatectomy in beagles. There were two groups: the preserved group, where portal inflow to the native liver was preserved, and the ligated group, where it was interrupted. Portal flow was measured serially and liver regeneration was evaluated on postoperative day 5. Functional competition was not observed in the preserved group. On the other hand, ligation of the native liver portal vein had no obviously detrimental effects on the remnant native liver. This leads to the conclusion that the portal vein to the native liver can be safely ligated to prevent functional competition.

Immunological Treatment with Low Dosage Ciclosporin in Rat Liver Allotransplantation

Ciclosporin (CsA) was administered subcutaneously at a dose of 3 mg/kg body weight/day from the day of operation to 14 days of liver allotransplantation in ACI rat (RT1a) to LEW rat (RT1(l) strain combination. All LEW recipients of ACI liver transplants without immunosuppressive treatment had severe rejection and expired within 12 days. In contrast, 7 out of 9 recipients in the same strain combination with temporary CsA treatment survived indefinitely. Histologically, widespread cellular infiltration and massive hepatocyte necrosis were evident upon autopsy of the recipients without CsA treatment. In contrast, in the surviving rats of the CsA-treated group, mononuclear cell infiltration was restricted to the periportal field and hepatocytes appeared to be normal at 14 days posttransplant. CsA concentrations in whole blood were determined by high-performance liquid chromatography. The trough levels were 788 +/- 48, 621 +/- 76 and 546 +/- 52 ng/ml, at 5, 10 and 14 days posttransplant, respectively. We concluded that this relatively low-dose subcutaneous administration of CsA offered adequate immunosuppression in rat liver allotransplantation in this strain combination.

Effect of cyclosporine on oxidative phosphorylation and adenylate energy charge of regenerating rat liver

SummaryThe effect of cyclosporin A (CyA) on regenerating liver was investigated in subtotal hepatectomized rats treated with CyA in terms of mitochondrial phosphorylative activity, hepatic energy charge, and serum bilirubin levels. In the CyA-treated hepatectomized group, the energy charge decreased from normal control value of 0.857 to 0.782 at 6 h after hepatectomy. The decreased energy charge, however, gradually increased and returned to 0.842 at 48 h after hepatectomy with no significant changes being observed between CyA-treated and untreated hepatectomized groups. Phosphorylation rate in the CyA-untreated group increased to 142% of the normal control at 24 h and then decreased to 114% at 48 h after hepatectomy. By contrast, phosphorylation rate in the CyA-treated group increased to 144% of the normal control at 24 h, but remained at the high value of 132% (P < 0.01; compared to the CyA-untreated group) even at 48 h after hepatectomy. Serum total bilirubin levels in the CyA-treated group were significantly higher than those in the CyA-untreated group during all experimental periods. We conclude that CyA does not exert a direct detrimental effect on mitochondrial function and that, despite the marked hyperbilirubinemia induced by CyA, the mitochondrial phosphorylative activity increases adaptively to provide sufficient energy for enhanced ATPutilizing reactions in an early process of liver regeneration.

An improved technique for liver transection using a new device for soft coagulation in living donor hepatectomy.

BACKGROUND/AIMS In LDLT, parechymal resection is the most invasive process in the donor procedure. The control of bleeding is crucial for donor safety without the occlusion of hepatic inflow. Therefore, a reliable coagulation device is necessary for the transection of the hepatic parenchyma. This study evaluated a newly developed monopolar applicator, SOFT COAG (ERBE Elektromedizin, Tübingen) for rapid soft coagulation with regulated power output. Our objective was to assess an improved hepatic resection technique using a the SOFT COAG device for LDLT. METHODOLOGY Between July 1999 and May 2008, 195 consecutive donors underwent a hepatic resection for LDLT. For graft extraction, 50 patients had a left lateral sectionectomy (LLS), 65 had a left hemihepatectomy (LHH), and 80 had a right hemihepatectomy (RHH). RESULTS In 125 donors, the control of parenchymal bleeding was performed by coagulation with bipolar forceps and in 70 donors it was controlled by soft coagulation with a monopolar electrode. The intraoperative blood loss was 763.9±494.4 mL and 435.2±424.7mL in RHH with bipolar and soft coagulation, respectively, with a statistically significant difference. Regarding postoperative liver function, most of the laboratory data showed no significant difference according to coagulation device. There was no significant difference in the incidence of postoperative complications. CONCLUSIONS It is evident that the new soft coagulation device represents a safe and feasible technique for donor hepatic parenchymal transection without inflow occlusion.

A New Bioabsorbable Material for Rat Orthotopic Liver Transplantation

Rat orthotopic liver transplantation was performed using a newly synthesized bioabsorbable material (LA-GA copolymer) cuffs and the ordinary polyethylene cuffs. The LA-GA copolymer cuff which anastomosed the portal vein was patent and developed no collateral veins even after 6 months, keeping the transplanted liver normal. By contrast, the polyethylene cuff-anastomosed portal vein was completely occluded and the collateral veins were highly developed, with the transplanted liver showing the fatty degeneration of hepatocytes and numerous regenerative nodules. It is concluded that the LA-GA copolymer cuff is a suitable material for the short- and long-term study of rat orthotopic liver transplantation.