HCC influence on patient survival after liver transplantation for HDV cirrhosis.

BACKGROUND/AIMS: The effect of hepatocellular cancer (HCC) in patients transplanted for hepatitis B and D virus (HB/DV) cirrhosis is not well studied. Our aim was to study the long-term survival outcomes of patients who underwent liver transplantation for HB/DV cirrhosis with and without HCC. METHODOLOGY: A total of 231 primary, adult, single- organ liver transplants were performed from 1990 to 2007. HB/DV was the cause of cirrhosis in 36 patients. Nine patients died during the first 3 postoperative months from surgical complications. The study group comprised the remaining 27 patients. The median follow-up was 1515 days. RESULTS: The mean patient survival was 3760 days (95% CI: 3013-4507). Six patients were diagnosed with HCC. The mean patient survival was 3011 days (95% CI: 2344-3679) and 4036 days (95% CI: 3002-5070) for recipients without and with HCC, respectively. For the same groups, the incidence of microbial infections was 61.9% and 33.3%, respectively (p=0.219). HCC has not recurred in any of the six patients. CONCLUSIONS: The mean long-term survival after liver transplantation for HB/DV and HCC surpassed 11 years. The superior survival of HCC patients is difficult to explain. The increased number (almost double) of microbial infections in the non- HCC population might be held accountable.

Successful, combined long-term treatment of cerebral aspergillosis in a liver transplant patient.

Invasive aspergillosis has long been recognized as one of the most significant and often fatal opportunistic fungal infections in liver transplant recipients. We report a case of a liver transplant recipient who developed an Aspergillus fumigatus brain abscess that produced significant neurologic symptoms. The patient was managed successfully with a combination of surgery and medical treatment with Voriconazole. To our knowledge, this is the second such case reported in the literature.

Liver transplantation in Greek children: 15 years experience.

Liver transplantation (LT) is the only available live-saving procedure for children with irreversible liver failure. This paper reports our experience from the follow-up of 16 Greek children with end-stage liver failure who underwent a LT. Over a period of 15 years, 16 pediatric liver recipients received follow up after being subjected to OLT (orthotopic liver transplantation) due to end-stage liver failure. Nine children initially presented with extrahepatic biliary atresia, 2 with acute liver failure after toxic mushroom ingestion, 2 with intrahepatic cholestasis, 2 with metabolic diseases and one with hepatoblastoma. Ten children received a liver transplant in the Organ Transplantation Unit of Aristotle University of Thessaloniki and the rest in other transplant centers. Three transplants came from a living-related donor and 13 from a deceased donor. Six children underwent immunosuppressive treatment with cyclosporine, mycophenolate mofetil and corticosteroids, and 7 with tacrolimus, mycophenolate mofetil and corticosteroids. Three out of 16 children died within the first month after the transplantation due to post-transplant complications. Three children presented with acute rejection and one with chronic organ rejection which was successfully managed. Five children presented with cytomegalovirus infection, 5 with Epstein-Barr virus, 2 with HSV(1,2), 2 with ParvoB19 virus, 2 with varicella-zoster virus and one with C. Albicans infection. One child presented with upper gastrointestinal hemorrhage and one with small biliary paucity. A satisfying outcome was achieved in most cases, with good graft function, except for the patient with small biliary paucity who required re-transplantation.The long-term clinical course of liver transplanted children is good under the condition that they are attended in specialized centers.

Attenuation of liver ischemia/reperfusion induced apoptosis by epigallocatechin-3-gallate via down-regulation of NF-kappaB and c-Jun expression.

INTRODUCTION: Hepatic ischemia/reperfusion (I/R) activates Kupffer cells and initiates severe oxidative stress with enhanced production of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha). ROS and TNF-alpha mediate the expression of nuclear factors and kinases, activating the signal transduction pathway, and triggering apoptosis. The aim of our study was to evaluate the potential protective effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kappaB, c-Jun, and caspase-3 in a model of severe hepatic I/R. MATERIALS AND METHODS: Thirty Wistar rats were allocated into three groups. Sham operation, I/R, and I/R-EGCG 50mg/kg. Hepatic ischemia was induced for 60min by Pringle's maneuver. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, scanning electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry for NF-kappaB, c-Jun, caspase-3, analysis on liver specimens and aspartate (AST), and alanine (ALT) transferases analysis in serum, were performed 120min after reperfusion. RESULTS: Apoptosis as indicated by TUNEL and caspase-3 was widely expressed in the I/R group but very limited in the EGCG treated group. Liver was stained positive for NF-kappaB and c-Jun in the I/R group but failed to be stained positive in the EGCG treated group. MDA, MPO, AST, and ALT showed marked increase in the I/R group and significant decrease in EGCG treated group. Significant alterations of liver specimens were observed by light histology and transmission electron microscopy whilst pretreatment with EGCG resulted in parenchymal preservation. CONCLUSIONS: Administration of EGCG is likely to inhibit I/R-induced apoptosis and protect liver by down-regulating NF-kappaB and c-Jun signal transduction pathways.

The natural history of vascular access for hemodialysis: a single center study of 2,422 patients.

BACKGROUND: Our objective is to provide provision of primary and secondary patency rates data and incidence of complications. Despite the publication of some review articles and small prospective trials about vascular accesses, controversy still exists regarding the choice of the outflow conduit and especially the choice of the fistula to be formed in secondary and tertiary access procedures. METHODS: This is a retrospective study of 2,422 consecutive patients who underwent 3,685 vascular access procedures in a tertiary care hospital, including radial-cephalic (RCAVF), brachial-cephalic (BCAVF), brachial-basilic (BBAVF), and prosthetic graft (PTFE) fistulas. Maximum follow-up period was 20 years. Actuarial patency rates were obtained by Kaplan-Meier analysis. RESULTS: The median primary patency (days) of the most common 1st choices for vascular access were 712 (95% CI: 606, 818), 1,009 (95% CI: 823, 1,195), and 384 (95% CI: 273, 945) days for RCAVF, BCAVF, and PTFE, respectively. The median secondary patency was 1809 days (95% CI: 1,692, 1,926) for the RCAVF. The median primary patency of BBAVF (2nd or 3rd choice for vascular access) was 1,582 days (95% CI: 415, 2,749). The cumulative incidence of clinically important complications for the patients who received a RCAVF, BCAVF, BBAVF, and u-PTFE was 0.25, 0.57, 0.33, and 0.61 per patient-year, respectively. CONCLUSION: We advocate maximal use of autogenous conduits, except probably the case of the older diabetic patient, in whom access at the antecubital fossa should be the first choice. BBAVF is an excellent fistula and should probably be constructed before prosthetic graft placement.

Inhibition of intestinal ischemia/repurfusion induced apoptosis and necrosis via down-regulation of the NF-kB, c-Jun and caspace-3 expression by epigallocatechin-3-gallate administration.

Intestinal ischemia/reperfusion (I/R) produces reactive oxygen species (ROS) activating signal transduction and apoptosis. The aim of this study was to evaluate the effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kB, c-Jun and caspace-3 in intestinal I/R. Thirty male wistar rats were used. Group A sham operation, B I/R, C I/R-EGCG 50 mg/kg ip. Intestinal ischemia was induced for 60 min by clamping the superior mesenteric artery. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, Fragment End Labelling of DNA (TUNEL), immunocytochemistry for NF-kB, c-Jun and caspace-3 analysis in intestinal specimens were performed 120 min after reperfusion. Apoptosis as indicated by TUNEL and Caspace-3, NF-kB and c-Jun was widely expressed in I/R group but only slightly expressed in EGCG treated groups. MDA and MPO showed a marked increase in the I/R group and a significant decrease in the EGCG treated group. Light histology showed preservation of architecture in the EGCG treated group. In conclusion, EGCG pre-treatment is likely to inhibit intestinal I/R-induced apoptosis by down-regulating the expression of NF-kB, c-Jun and caspase-3.

Papillomatosis of intra- and extrahepatic biliary tree: Successful treatment with liver transplantation.

Approximately 60 cases of biliary papillomatosis have been reported in the world literature, while only 6 cases have been reported to be treated with liver transplantation. This rare disease, which is characterized by relapsing episodes of obstructive jaundice and cholangitis that lead to secondary cirrhosis and death from sepsis or liver failure, it is also considered premalignant because of its frequent malignant transformation (25-50%). We present a case of a 43-year-old white man with papillomatosis of intra- and extrahepatic biliary tree who sought care for repeated episodes of obstructive jaundice and cholangitis. The diagnosis was suspected after endoscopic retrograde cholangiopancreatography and confirmed by liver and common bile duct biopsies. The patient underwent orthotopic liver transplantation with Roux-en-Y hepatico-jejunostomy to treat end-stage liver cirrhosis. Fifteen months' follow-up revealed a patient with normal graft function and with no clinically or laboratory findings of disease recurrence or cancer development.

Living-related transplantation of an ectopic pelvic kidney.

Ectopic kidneys are usually contraindicated for transplantation as a result of anomalous vascular and drainage system. Graft shortage increases the need of expanding the donor pool and the use of ectopic pelvic kidneys might provide a small but useful source. Transplantation of an ectopic pelvic kidney is a technically demanding procedure and very few cases have been published. We present a case of a living-related kidney transplantation of an ectopic pelvic kidney. The donor was a healthy 65-year-old lady and preoperative work-up had showed a left ectopic pelvic kidney. The recipient was a 34-year-old male with a history of end-stage renal disease secondary to chronic glomerulonephritis. After the transplantation, there was an immediate function of the allograft and the donor's postoperative course was uneventful. The donor was discharged on the fifth postoperative day.

The protective effect of alpha-tocopherol and GdCl3 against hepatic ischemia/reperfusion injury.

PURPOSE: To evaluate the combined effect of alpha-tocopherol and gadolinium chloride (GdCl3) in reducing lipid peroxidation after severe hepatic ischemia/reperfusion (IR) injury. METHODS: Sixty male Wistar rats, 200-250 g, were randomly divided into six equal groups. There were two sham operation (SHAM) groups, two untreated IR groups, and two IR groups treated with GdCl3 and alpha-tocopherol (IRGT). After 60 min of total hepatic ischemia and 120 min reperfusion, one of each group was killed, liver samples were taken for malondialdehyde (MDA) and myeloperoxidase (MPO) analysis and light microscopy examination, and blood samples were analyzed for aspartate (AST) and alanine (ALT) transaminase, lactate dehydrogenase (LDH), and alpha-tocopherol content. The remaining groups were monitored for survival rate determination. RESULTS: The mean MDA and MPO values in the SHAM, IR, and IRGT groups, respectively, were 1.117, 1.476, and 0.978 nmol/g wet tissue and 1.49, 6.26, and 1.78 (U/g). The mean alpha-tocopherol values in the SHAM, IR, and IRGT groups, respectively, were 10.4, 1.9, and 12 micromol/l. The mean serum AST, ALT, and LDH values were significantly higher in the IR group than in the SHAM group (P < 0.001), and significantly lower in the IRGT group than in the IR group (P < 0.001). Light microscopy examination revealed more severe congestion and vacuolization in the IR group than in the SHAM group, and minimal congestion and vacuolization in the IRGT group. Survival was significantly higher in the IRGT group than in the IR group. CONCLUSION: The administration of GdCl3 and alpha-tocopherol is likely to protect the liver against lipid peroxidation by suppressing Kupffer cell and polymorphonuclear leukocyte activation and enhancing endogenous antioxidant activity.

Mycophenolate mofetil impairs the integrity of colonic anastomosis.

BACKGROUND: The aim of this experimental study was to investigate the effect of mycophenolate mofetil (MMF) during the three phases of colonic anastomosis healing and specifically to check the effect of MMF on the expression of transforming growth factor-beta1 (TGF-beta1), one of the most important growth factors contributing to mechanical stability of colonic anastomosis. MATERIALS AND METHODS: Sixty male Wistar rats underwent colonic resection and end-to-end anastomosis. The animals were divided into two groups, a study group given MMF 40 mg/kg, intraduodenally and a control group given vehicle. The rats were sacrificed at 3, 7, and 14 days (10 animals in each group). The anastomoses were tested by measuring bursting pressure and hydroxyproline content. Histological examination and immunohistochemical expression of TGF-beta1 also were assessed. RESULTS: The mean bursting pressure in the study group was significantly lower on day 3 and 7, but there was no statistical significance on day 14. The mean hydroxyproline content was lower in the study group on days 3, 7, and 14. Histology showed decreased number of macrophages and fibroblasts on days 3 and 7 but no difference on day 14. The expression of TGF-beta1 was significantly reduced in the study group, with the difference being more pronounced on days 3 and 7. CONCLUSION: MMF weakens the integrity of colonic anastomosis, and this effect is more significant during the inflammatory phase of healing. MMF has a negative effect on macrophages and TGF-beta1 expression, resulting in decreased collagen accumulation at the anastomosis.

Intramuscular administration of very high dose of alpha-tocopherol protects liver from severe ischemia/reperfusion injury.

The effect of intramuscular administration of high (30 mg/kg body weight for 3 days) or very high (300 mg/kg body weight for 3 days) doses of a-tocopherol to Wistar rats subjected to total severe warm hepatic ischemia and reperfusion was investigated. After a 60-minute period of total hepatic ischemia and 120 minutes of reperfusion, animals were killed, and liver samples were taken for determination of malondialdehyde (MDA) and histological examinations. Blood samples were also taken for assay of serum a-tocopherol, alanine transaminase (ALT), aspartate transaminase (AST), and lactic dehydrogenase (LDH). Additional animals were followed for a 7-day survival rate determination. Results showed that ischemia and reperfusion decreased the survival rate to 10%, whereas the levels of AST, ALT, and LDH in serum were increased compared with levels in animals that were sham operated. The MDA concentrations in liver were also increased, from 1.142 to 1.567 nmoles/g, whereas the levels of a-tocopherol in serum were decreased from 10.20 to 1.80 mmol/L. Pretreatment with a-tocopherol increased the viability to 50% and 70%, for the high and very high doses, respectively, and decreased the levels of AST, ALT, and LDH in serum. It also decreased the MDA concentrations in liver to 0.975 and 0.774 nmoles/g for the high and very high doses of a-tocopherol, respectively, whereas it increased the level of a-tocopherol in serum to 11.25 and 13.02 mmol/L for the high and very high doses, respectively. Histological examinations showed protection of the liver parenchyma in the animals treated with a-tocopherol.