Continuous infusion of local anesthesia after living donor nephrectomy: a comparative analysis.

INTRODUCTION: Today local anesthetic wound infiltration is widely recognized as a useful adjunct in a multimodality approach to postoperative pain management. The effectiveness of continuous wound infusion of ropivacaine for postoperative pain relief after laparoscopic living donor nephrectomy was analyzed in this retrospective, comparative analysis. METHODS: Twenty patients undergoing living donor nephrectomy were divided into two groups: standard analgesic therapy (n=10) and ropivacaine continuous infusion group (n = 10). RESULTS: We observed a significant difference in term of visual analogue scale scores, use of morphine, hospital stay, and bowel recovery in favor of the ropivacaine group. The cost analysis demonstrated an overall savings of 985 Euros/patient. DISCUSSION: Surgical wound infusion with ropivacaine was safe and seemed to improve pain relief and accelerate recovery and discharge, reducing the overall costs of care. Postoperative pain control in the donor is of primary importance for better patient compliance and greater perceived quality of health care service.

Causes of sirolimus discontinuation in 97 liver transplant recipients.

INTRODUCTION: Sirolimus is a potent immunosuppressant with a mechanism of action different from calcineurin inhibitors (CNIs). It has increasing importance for liver transplant (OLT) patients, in particular if when there is decreased renal function. We evaluated the efficacy and the causes for discontinuation of sirolimus-based immunosuppression among OLT recipients. OBJECTIVE: We retrospectively analyzed 97 liver transplanted patients who were prescribed sirolimus as the principal immunosuppressant. Of these, 61 patients discontinued treatment. Herein we have reported the causes, the timing, and the effects of sirolimus discontinuation. RESULTS: The overall patient survival at 3 years follow-up was 89%. Hepatotoxicity and blood disorders were the most frequent, severe reported side effects. Acute cellular rejection episodes appeared in seven patients and was relieved in 1 to 2 weeks after the sirolimus administration. In 10 patients, the cholestasis associated with chronic rejection was sharply reduced after the introduction of sirolimus. No increase in vascular thrombosis and/or poor wound healing were reported. CONCLUSION: Sirolimus given alone or in combination with CNIs appears to be an effective primary immunosuppressant regimen for OLT patients. However, in the late postoperative period (>3 months) the drug is associated with a relatively high rate of side effects.

Incidence and clinical significance of bacterial and fungal contamination of the preservation solution in liver transplantation.

A perfusion fluid used in the preservation of the grafted liver represents a medium suitable for microorganism growth. In this observational study, a sample of 232 transplanted livers was collected. Perfusion fluid samples were stored for microbiological analysis from harvested donors. Bacteria were isolated in 91 out of 232 samples, post-operative infections related to contaminated perfusion solution occurred in 13 cases. The contamination rate of the preservation medium appears to be high, but postoperative infections occurs rarely. We suggest periodic detection and a protocol in place designed for antibiotic use for transplanted patients exposed to contaminated perfusion solution.

Does arterialisation time influence biliary tract complications after orthotopic liver transplantation?

BACKGROUND: In the cardiac death donor era, many reports deal with biliary tract complications and concerns about ischemic reperfusion injury owing to the exclusive arterial vascularization of the biliary tree, the warm ischemia time has been implicated as responsible for biliary lesions during organ procurement. We defined the arterialization time as the second warm ischemia time. Our purpose was to study the correlation between the arterialization time during liver implantation and the appearance of biliary lesions. METHODS: We retrospectively collected data from the last 5-years of orthotopic liver transplantation: namely, indications, cold perfusion fluid, cold ischemia time, operative procedure times, and acute rejection events. We excluded split-liver transplantations, retransplantations, pediatric patients, transplantations for cholestatic disease, cases where hepatic artery thrombosis happened before biliary complications, or patients with posttransplant cytomegalovirus infection. We defined 2 groups: A) without biliary complications; and B) with biliary complications. We compared the mean arterialization time using Student t test to define whether the warm ischemic time during implantation was responsible for biliary tract complications. A P value of <.05 was considered to be significant. RESULTS: Between 2004 and the end of 2008, we grafted 402 patients among whom 243 met the inclusion criteria: 198 in group A and 45 in group B. Only the cold ischemia time was significantly different between the 2 groups (P = .039). CONCLUSION: After the anhepatic time, the surgeon may take time for the arterial anastomosis without fearing increased biliary damage.

Laparoscopic ultrasound-guided radiofrequency ablation as a bridge to liver transplantation for hepatocellular carcinoma: preliminary results.

INTRODUCTION: The aim of this study was to assess the impact of laparoscopic thermoablation (LTA) as a neoadjuvant therapy prior to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). METHODS: Between January 2008 and January 2009, 12 consecutive patients, including 10 males and 2 females with unresectable HCC within liver cirrhosis, were treated with LTA under ultrasound (US) guidance. Most patients were in Child-Pugh class B (54.1%) with a mean age of 60.7 +/- 7.74 years (range, 45-69; median, 60). RESULTS: The LTA procedure was completed in all patients with thermoablation of 23 HCC nodules. LTA identified 4 new malignant lesions (20%) undetected by preoperative imaging (<0.5 cm). The mean length of surgery was 96 minutes (range, 45-118). Six procedures were performed in 4 patients. No postoperative hepatic insufficiency was reported. The mean hospital stay was 4.5 days; no postoperative morbidity was reported. Complete tumor necrosis was achieved in 19/23 thermoablated nodules (82.6%) as evidenced computed tomography (CT) scan by at 3 weeks after the treatment. All patients underwent OLT without complications. The histology of the native liver showed complete necrosis in 17/23 (74%) treated nodules. DISCUSSION: There is currently no convincing evidence that LTA allows one to expand the current selection criteria for OLT, nor that LTA decreases dropout rates on the waiting list. However, LTA does not increase the risk of postoperative complications. There is insufficient evidence that LTA offers any benefit when used prior to OLT either for early or for advanced HCC.

Incisional hernia repair after liver transplantation: role of the mesh.

BACKGROUND: Patients undergoing orthotopic liver transplantation (OLT) show a high risk of developing an incisional hernia. The aim of this retrospective study was to establish the incidence and the factors influencing the outcomes of this complication. METHODS: We reviewed 450 consecutive OLT performed in 422 adult recipient between January 2000 and December 2005. Herniae were analysed with aspect to localization, classification, repair technique, and recurrence. All treated herniae were followed for a median of 50.5 months. RESULTS: Incisional herniae occurred in 36 patients (8.5%, Group 1). Their mean age OLT was 51.4 years with 94.4% male subjects. No significant difference was observed between affects and unaffected individuals for age, OLT indication, Child-Pugh score, albumin, comorbidities, operative time, transfusions, immunosuppressant regimen, and graft rejection episodes as well as for the incisional approach and hospital stay. Gender, body mass index (BMI), preoperative ascites, and pulmonary complications after OLT were significantly different (P < .01). Herniae were small (<5 cm; n = 12), medium (5-10 cm; n = 28), or large (> 10 cm; n = 2). Herniorrhaphy techniques included primary suture repair in 5 (13.9%) and mesh repair in 31 (86.1%) cases. In 3 patients with a primary repair and 1 patient with a mesh repair there were recurrences. CONCLUSIONS: Preoperative ascites, gender, BMI, and pulmonary complications after OLT seemed to have significant influences on the formation of incisional herniae. Polypropylene mesh may be a first choice for the surgical treatment of there transplant recipients.

Hepatocyte ploidy in regenerating livers after partial hepatectomy, drug-induced necrosis, and cirrhosis.

The hepatocyte ploidy was investigated by flow cytometry in regenerating Sprague-Dawley rat livers following either drug-induced acute necrosis (single sublethal doses of D-galactosamine or thioacetamide) or drug-induced chronic cirrhosis (repeated thioacetamide injections for 10-18 weeks) and in regenerating livers following 70% partial hepatectomy and was compared with that of normal hepatocytes. Twenty-four hours after partial hepatectomy, a significant decrease in 2n (1 diploid nucleus) hepatocytes and a significant increase in 8n (1 octoploid nucleus) hepatocytes occurred. In contrast, 24 h following induction of acute hepatic failure by single D-galactosamine or thioacetamide injections, a significant increase in 2n hepatocytes was observed, whereas the proportion of 8n hepatocytes remained unchanged. The liver ploidy returned to basal values within 21 days in all cases. In cirrhotic livers induced by chronic thioacetamide injections, the rate of 2n hepatocytes was about ten times that of the controls having the same age, while 4n (1 tetraploid nucleus) and 8n hepatocytes were one third of controls. The binucleation rate was also significantly decreased.

A surgical solution to extrahepatic portal thrombosis and portal cavernoma: the splanchnic-intrahepatic portal bypass.

Three cases of prehepatic portal vein thrombosis, complicated by the clinical manifestations of portal hypertension, were successfully treated by surgically created splanchnic-intrahepatic portal bypass. Two out of three patients had been previously submitted to liver transplantation. No significant morbidity was observed and long-term Doppler evaluations proved the patency of the venous grafts. Together with the technical aspects of the procedures, the possible role of this technique, primarily proposed by De Ville de Goyet in 1992, is discussed in relation to the available therapies for the extrahepatic portal vein thrombosis.

Influence of pre-, intra- and post-operative parameters of donor liver on the outcome of isolated human hepatocytes.

The aim of the present study was to analyse, retrospectively on a large panel of patients (149), the influence of the donor liver characteristics on the outcome of human hepatocyte isolation obtained from resected liver biopsies from surgical waste after hepatectomy. Among the pre-operative parameters, the type of disease, age and sex of the patient, previous chemotherapy, alcohol or tobacco consumption did not affect the yield, viability, attachment rate and function of the isolated human hepatocytes. Pre-operative biological and anatomopathological data indicated that, while mild steatosis (10% steatotic hepatocytes) tended to decrease hepatocyte yield. Cholestasis, as assessed by gamma-glutamyl transferase serum values, significantly negatively correlated with the percentage of digested liver and the yield of viable cells. Intra-operative clamping time, that is, warm ischaemia, longer than 30 min was found to decrease both the percentage of digested liver and cell yield. Among the post-operative parameters, the percentage of digested liver decreased when biopsy weights were higher than 100 g, the use of glue tended to increase both the percentage of digested tissue and the yield of viable cells.In conclusion, human diseased livers appear to be a valuable source of isolated functional human hepatocytes. We recommend, for an optimal isolation, to use liver biopsies weighing less than 100 g, to glue the section surfaces of the biopsies and to avoid the use of moderate steatotic livers (>10% steatotic hepatocytes) and cholestatic livers, as well as livers undergoing warm ischaemia or clamping during resection due to the decrease in cell yield.

Comparative evaluation of Celsior solution versus Viaspan in a pig liver transplantation model.

BACKGROUND: In a pig liver transplantation model, we compared the effects of Celsior solution (CS), an extracellular preservation solution, with Viaspan (University of Wisconsin solution, UW) on graft function and animal survival. METHODS: Pig livers were flushed with either CS or UW solution and cold-stored for 12 hr (group 1) or for 8 to 10 hr (group 2). Grafts were transplanted orthotopically. Intrahepatic reduced and oxidized glutathione and adenine nucleotides were evaluated 1 hr after reperfusion. Liver function of transplanted animals was monitored for up to 6 days by serum transaminases, total bilirubin, purine nucleoside phosphorylase, and prothrombin levels. RESULTS: In group 1, all animals died within 24 hr after reperfusion regardless of the preservation solution used. In group 2, no significant difference was seen in survival between the CS (72%) and the UW (67%) groups 6 days after transplantation, and there were no statistically significant differences in the biochemical data. There were no differences in histological evaluation of the livers at the time of death or killing of the animals between the CS and UW groups. CONCLUSION: Within the limits of this pilot study, CS is equivalent to UW in terms of graft function and animal survival.

Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.

Organ perfusion is one of the possible strategies to attenuate rejection of discordant xenografts by reducing the levels of the recipient's xenoreactive natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in models of primate blood or plasma perfusion through porcine kidneys or livers, with special attention to haematological consequences and potential side-effects. We first perfused the blood of rhesus monkeys through pig kidneys and livers, and demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we normalized for the weight of the perfused organs and for levels of natural antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of rejection were observed in perfused kidneys, but not in perfused livers. A major drawback of the perfusion of blood through livers was a considerable decrease in the primates' haemoglobin and platelet levels. To avoid this, we developed a plasma liver perfusion device. This method allowed a significant improvement in the haemodynamic state of primates and was particularly effective in preventing anaemia. Moreover, plasma liver perfusion was as effective as blood liver perfusion to remove natural antibodies and, resulted in a marked decrease in their functional activity as assessed by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other plasma proteins was not significantly affected, apart from a dilution effect. After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and ADCC between days 7 and 14 and then decreased progressively. We conclude that the separation of blood to allow the perfusion of plasma through a pig organ is safer than the perfusion of unseparated blood and is associated with efficient natural antibody removal. However, organ perfusion is limited by a rebound in antibody levels after a few days, and thus will have to be associated with anti-B cell immunosuppressive therapy for long-term or repeated applications.

Comparative study of target antigens for primate xenoreactive natural antibodies in pig and rat endothelial cells.

BACKGROUND: A rat-to-primate cardiac xenograft model has been proposed as an alternative to the clinically relevant but more cumbersome pig-to-primate model for assessing the efficacy of strategies aimed at preventing xenograft hyperacute rejection. As in pig xenografts, the rejection of rat hearts was mediated by the binding of xenoreactive natural antibodies (XNA) and complement activation. The present study was conducted to identify target antigens recognized by cynomolgus and rhesus monkey IgM XNA on rat tissues and cells in comparison with pig cells. METHODS: The reactivity of rhesus or cynomolgus serum on pig and rat endothelial cells (ECs) was studied by flow cytometry, ELISA, and complement-dependent cytotoxicity, after removal of primate XNA by perfusion of pig livers, immunoadsorption on a Gal alpha(1,3)Gal affinity column, and enzymatic removal of alpha-galactosyl epitopes from the cell surface. Rat and pig EC extracts were also immunoprecipitated with primate serum and resolved in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The expression of the Gal alpha(1,3)Gal epitope was analyzed on rat tissues and ECs by immunohistochemistry, flow cytometry, and Western blot, using the isolectin B4 from Griffonia simplicifolia. RESULTS: Removal of primate XNA or of alphaGal epitopes resulted in a decrease in XNA binding to pig and rat cells, leaving a similar degree of residual reactivity in the two species. At least five proteins of 260, 210, 110, 56, and 50 kDa were immunoprecipitated on rat ECs, with molecular weight similar to several proteins identified on pig ECs. These results suggest that primate XNA recognize similar antigens on rat and pig ECs. Rat cells expressed lower levels of the Gal alpha(1,3)Gal epitope than pig cells. A large proportion, but not all, of primate XNA react with this epitope on pig and rat ECs. CONCLUSION: This study suggests that the rat is a valuable species for the evaluation of genetic engineering strategies on the vascular endothelium aimed at preventing hyperacute xenograft rejection.