The outcome of primary liver transplantation from deceased donors in children with body weight < or =10 kg.

Between November 1982 and March 2006, 67 children with body weight < or =10 kg had a primary liver transplantation from deceased donors in our unit. The aim of this study was to analyze the outcome in terms of patient and graft survival and to search for factors affecting this outcome. Overall, one-, three-, five-, and 10-yr primary patient and graft survival rates were 73%, 71%, 66%, 63% and 59%, 56%, 53%, 48%, respectively. Twenty-four of 67 (36%) children died and in the remaining 22 (33%), the first grafts failed and they were retransplanted. Cox regression analysis revealed that a need for retransplantation and urgent transplantation were important predictors for patient survival (p = 0.04 and p = 0.001, respectively). To assess whether the need for retransplantation can be influenced, all study variables were compared between surviving grafts and failed grafts. Cox regression analysis showed that only donor/recipient (D/R) weight ratio proved to be independent predictor for graft survival (p = 0.004). After comparison of graft survival with the long rank test according to different D/R weight ratios (3.0-7.0), the cut-off point for significantly different graft survival approached 4.0. The one-, three-, five-, and 10-yr graft survival for technical variant grafts with a D/R weight ratio <4.0 was 85%, 68%, 68%, and 68% compared with a D/R weight ratio >4.0 was 44%, 38%, 38%, and 30%, respectively (p = 0.02). In summary, patient survival in children with body weight < or =10 kg is determined by urgent transplantation and the need for retransplantation. Graft loss and retransplantation in small children can be prevented by adequate size matching of donor and recipient whereby a D/R weight ratio <4.0 seems to offer the favorable outcome.

Metabolism for cyclosporin A during liver regeneration after partial hepatectomy in rats.

AIM: To elucidate the metabolism and the effect of the cyclosporin A (CyA) as a representative immunosuppressive drug used in transplantation in a partially hepatectomized rat model. METHODS: CyA was administered to rats that underwent a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; (group 1) water, (group 2) 5 mg/kg CyA, (group 3) 10 mg/kg CyA. On postoperative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver regeneration ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-polymerase chain reaction method to determine albumin and cytochrome p450 expression. RESULTS: The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associated with CyA metabolism was significantly decreased on day 14, while preserving the albumin producing activity. CONCLUSION: These data indicate that the p-450 activity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepatectomy, which may, therefore, be linked to difficulty in controlling the optimal dose of CyA during early period of LDLT.

Simplified technique for middle hepatic vein tributary reconstruction of a right hepatic graft in adult living donor liver transplantation.

A simple procedure of direct end-to-end anastomosis between the middle hepatic vein tributary of the right hepatic graft and the preserved recipient middle hepatic vein is described. During the final step of total hepatectomy in the recipient, the middle hepatic vein was preserved, while crushing the liver tissue for a sufficient length of middle hepatic vein to perform tension-free anastomosis with the middle hepatic vein tributary of the graft. This procedure enabled us to avoid using an interposition graft.

Destructive granuloma derived from a liver cyst: a case report.

We herein report the case of an idiopathic liver cystic mass which aggressively infiltrated the thoraco-abdominal wall. A 74-year-old woman who had a huge cystic lesion in her right hepatic lobe was transferred to our hospital for further examinations. Imaging studies revealed a simple liver cyst, and the cytological findings of intracystic fluid were negative. She was followed up periodically by computed tomography (CT) scans. Seven years later, she complained of a prominence and dull pain in her right thoraco-abdominal region. CT revealed an enlargement of the cystic lesion and infiltration into the intercostal subcutaneous tissue. We suspected the development of a malignancy inside the liver cyst such as cystadenocarcinoma, and she therefore underwent surgery. A tumor extirpation was performed, including the chest wall, from the 7th to the 10th rib, as well as a right hepatic lobectomy. Pathologically, the lesion consisted of severe inflammatory change with epithelioid cell granuloma and bone destruction without any malignant neoplasm. No specific pathogens were evident based on further histological and molecular examinations. Therefore the lesion was diagnosed to be a destructive granuloma associated with a long-standing hepatic cyst. Since undergoing surgery, the patient has been doing well without any signs of recurrence.

Changes in serum levels of hepatocyte growth factor in patients undergoing adult-to-adult living-donor liver transplantation.

Changes in the serum concentration of hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, were investigated in adult-to-adult living-donor liver transplantation (LDLT) in which liver regeneration is involved. Between August 2000 and November 2002, 15 consecutive adult-to-adult LDLTs were performed using the right lobe graft. The recipients were divided into two groups: acute liver failure (n=6) and chronic liver failure (n=9). In addition, right lobe donors (n=12) were evaluated. Measurement of HGF was performed on preoperative and postoperative days 1, 3, 7, and 14 after LDLT. The pretransplant levels of serum HGF were higher in the acute liver failure group than in the chronic liver failure group (P<0.05). After liver replacement, serum HGF levels normalized rapidly in both groups and remained rather low. Despite vigorous liver regeneration in all groups, serum HGF levels did not change significantly after adult-to-adult LDLT with right lobe graft.

Role of intrasplenic hepatocyte transplantation in improving survival and liver regeneration after hepatic resection in cirrhotic rats.

We studied the effect of preoperative hepatocyte transplantation on the prevention of liver failure in cirrhotic rats after hepatic resection. Two groups of Lewis rats were rendered cirrhotic by i.p. injection of 1% dimethylnitrosamine and were subjected to 33% hepatectomy. Two days before the resection, 36 rats in group I received intrasplenic hepatocyte transplantation, and 25 rats in group II were given intrasplenic injection of normal saline as a control. By the end of the third postoperative day, the rats in group I had better survival and a better biochemical profile than those in group II. The liver growth rate and the labeling index of proliferating cell nuclear antigen (PCNA-LI) showed a steady rise in group I. Compared with group II, group I had a significantly lower transforming growth factor (TGF-beta1) level (p < 0.05). We conclude that preoperative intrasplenic hepatocyte transplantation improves survival and facilitates regeneration in cirrhotic rats after hepatic resection.

Hepatic expression and serum levels of thrombomodulin reflect the extent of liver injury in rats with fulminant hepatic failure and extensive hepatectomy.

In order to evaluate the biological significance of thrombomodulin (TM) in the serum and its expression in the liver, changes in TM were investigated in rats with fulminant hepatic failure (FHF) or after extensive hepatectomy. Forty-two rats were divided into four groups as follows: control (sham, n=6), 70% hepatectomy (70% Hx, n=12), 90% hepatectomy (90% Hx, n=12) and fulminant hepatic failure (FHF, n=12). The soluble-TM levels in the 90% Hx and FHF groups were significantly higher than that in the 70% Hx group. In the FHF group, the soluble-TM level 24 h after induction was significantly higher than that at 12 h (P<0.05). Moreover, the level of soluble TM was significantly higher in the FHF group than that in the 90% Hx group, while hyaluronic acid was not increased at statistical significance. The expression of TM in the liver intensified with time in both FHF and 90% Hx groups, which was more pronounced in zone 3 of the liver in FHF group than in the 90% Hx group. In conclusion, elevation of s-TM in the serum and expression of TM in the sinusoidal endothelial cell are useful markers of hepatic failure and its sinusoidal endothelial injury, especially in the state of FHF, since the presence of necrotic liver tissue is the only difference between FHF and 90% Hx in the model of the rats.

End-to-side caval anastomosis in adult piggyback liver transplantation.

No consensus exists regarding the optimal reconstruction of the cavo-caval anastomosis in piggyback orthotopic liver transplantation (PB-LT). The aim of this study was to analyze our experience with end-to-side (ES) cavo-cavostomy. Outcome parameters were patient and graft survival and surgical complications. During the period 1995-2002 146 full-size PB-LT in 137 adult patients were performed with ES cavo-cavostomy without the routine use of temporary portocaval shunt (TPCS). In 12 patients (8%) this technique was used for implantation of second or third grafts. Veno-venous bypass was not used in any case and TPCS was performed only in eight patients (6%). One-, three- and five-yr patient and graft survival were 84%, 79% and 75%, and 81%, 74% and 69%, respectively. The median number of intraoperative transfusion of packed red blood cells (RBC) was 2.0 (range 0-33) and 30% of the patients (n = 43) did not require any RBC transfusion. Surgical complications of various types were observed after 49 LT (34%) and none of the complications was specifically related to the technique of ES cavo-cavostomy. Our experience indicates that PB-LT with ES cavo-cavostomy is a safe procedure, can safely be performed without the routine use of a TPCS, has a very low risk of venous outflow obstruction and can also be used effectively during retransplantations.

Sequential and simultaneous revascularization in adult orthotopic piggyback liver transplantation.

The aim of the study was to assess whether there is a difference in outcome after sequential or simultaneous revascularization during orthotopic liver transplantation (OLT) in terms of patient and graft survival, mortality, morbidity, and liver function. The study population consisted of 102 adult patients with primary full-size piggyback OLT transplanted between January 1998 and December 2001. In 71 patients (70%) the grafts were sequentially reperfused after completion of the portal vein anastomosis and subsequent arterial reconstruction was performed (sequential reperfusion [SeqR] group). In 31 patients (30%) the graft was reperfused simultaneously via the portal vein and hepatic artery (simultaneous reperfusion [SimR] group). Patient and graft survival at 1, 3, and 6 months and at 1 year did not differ between the SeqR group and the SimR group. The red blood cell (RBC) requirements were significantly higher in the SimR group (5.5 units; range 0-20) in comparison to the SeqR group (2 units; range 0-19) (P = 0.02). Apart from a higher number of biliary anastomotic complications and abdominal bleeding complications in the SimR group in comparison to the SeqR group (13% vs. 2% and 19% vs. 6%, respectively; P = 0.06), morbidity was not different between the groups. No differences between the groups were observed regarding the incidence of primary nonfunction (PNF), intensive care unit stay, and acute rejection. This was also true for the severity of rejections. Postoperative recuperation of liver function was not different between the groups. In conclusion, no advantage of either of the 2 reperfusion protocols could be observed in this analysis, especially with respect to the incidence of ischemic type biliary lesions (ITBL).

Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback techniques in adults.

The aim of this study is to analyse a single centre's experience with two techniques of liver transplantation (OLT), conventional (CON-OLT) and piggyback (PB-ES), and to compare outcome in terms of survival, morbidity, mortality and post-operative liver function as well as operative characteristics. A consecutive series (1994-2000) of 167 adult primary OLT were analysed. Ninety-six patients had CON-OLT and 71 patients had PB-ES. In PB-ES group two revascularization protocols were used. In the first protocol reperfusion of the graft was performed first via the portal vein followed by the arterial anastomosis (PB-seq). In the second protocol the graft was reperfused simultaneously via portal vein and hepatic artery (PB-sim). One-, 3- and 5-yr patient survival in the CON-OLT and PB-ES groups were 90, 83 and 80%, and 83, 78 and 78%, respectively (p = ns). Graft survival at the same time points was 81, 73 and 69%, and 78, 69 and 65%, respectively (p = ns). Apart from the higher number of patients with cholangitis and sepsis in CON-OLT group, morbidity, retransplantation rate and post-operative liver and kidney function were not different between the two groups. The total operation time was not different between both groups (9.4 h in PB-ES vs. 10.0 h in CON-OLT), but in PB-ES group cold and warm ischaemia time (CIT and WIT), revascularization time (REVT), functional and anatomic anhepatic phases (FAHP and AAHP) were significantly shorter (8.9 h vs. 10.7 h, 54 min vs. 63 min, 82 min vs. 114 min, 118 min vs. 160 min and 87 min vs. 114 min, respectively, p < 0.05). RBC use in the PB-ES group was lower compared to the CON-OLT group (4.0 min vs. 10.0 units, p < 0.05). Except for WIT and REVT there were no differences in operative characteristics between PB-Sim and PB-Seq groups. The WIT was significantly longer in PB-Sim group compared with PB-Seq group (64 min vs. 50 min, p < 0.05); however REVT was significantly shorter in PB-Sim group (64 min vs. 97 min, p < 0.05). Results of this study show that both techniques are comparable in survival and morbidity; however PB-ES results in shorter AAHP, FAHP, REVT and WIT as well as less RBC use. In the PB-ES group there seems to be no advantage for any of the revascularization protocols.