[Show abstract][Hide abstract] ABSTRACT: Aim:
To investigate whether amifostine contributes to the antioxidant and cytoprotective effects of histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions.
Forty-eight Sprague Dawley male rats were equally divided into six groups: (1) ringer Lactate (RL) group; (2) RL + amifostine (RL + A) group; (3) HTK group; (4) HTK + A group; (5) UW group; and (6) UW + A group. Rats in the RL + A, HTK + A and UW + A groups were administered amifostine intraperitoneally at a dose of 200 mg/kg prior to laparotomy. The RL group was perfused with RL into the portal vein. The RL + A group were perfused with RL into the portal vein after amifostine administration. The HTK group received an HTK perfusion while the HTK + A group received an HTK perfusion after administration of amifostine. The UW group received a perfusion of UW, while the UW + A group received a UW perfusion after amifostine administration. Liver biopsy was performed to investigate histopathological, immunochemical [transferase mediated dUTP nick end labeling (TUNEL), inducible nitric oxide syntetase (iNOS)] and ultrastructural alterations. Biochemical alterations were determined by examining levels of alanine aminotransferase, alkaline phosphatase and nitric oxide in the perfusion fluid.
Pathological sinusoidal dilatation and centrilobular hydropic alteration were significantly lower in the groups that received amifostine prior to preservation solution perfusion. Although the best results were obtained in the UW + A group, we did not observe a statistically significant difference between the UW + A and HTK + A groups. iNOS grades were significantly lower in the amifostine groups 12 h after treatment. When the amifostine groups were compared against each other, the iNOS grades obtained from the UW + A and HTK + A groups were similar while the RL + A group had a much poorer score. TUNEL assays demonstrated a lower apoptosis ratio in the amifostine groups than in the non-amifostine groups 12 h after treatment. No statistically significant difference was observed between the UW + A and HTK + A groups for apoptosis. Cellular ultrastructure was best preserved in the UW + A and HTK + A groups.
Here, we show that preoperative administration of a single dose of amifostine is sufficient to minimize the preservation damage in hepatic cells.
World Journal of Gastroenterology 09/2014; 20(34):12292-300. DOI:10.3748/wjg.v20.i34.12292 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antibody-mediated rejection is a rare complication that often results in the loss of the kidney graft. Treatment options include plasmapheresis, intravenous immunoglobulin, and use of rituximab.
We retrospectively evaluated the data files from 86 pediatric renal transplant patients over the last 5 years. A biopsy was taken for each rejection episode.
Seven patients (7.7%) developed antibody-mediated rejection. All patients with antibody-mediated rejection had histologic evidence of severe acute humoral rejection and extensive C4d staining in peritubular capillaries. Staining was diffuse (involving > 50% of peritubular capillaries) for 4 biopsies, and it was focal (involving < 50% of peritubular capillaries) for 3 biopsies. Twelve biopsies demonstrated at least 1 histologic feature associated with acute humoral rejection. Donor-specific antibodies were evaluated in recipients. The mean peak panel reactive antibody class 1 was 7.16% (range, 0%-86%). The mean time between rejection episodes and the transplant was 16.9 ± 13.5 months. All patients were treated with high-dose intravenous methylprednisolone and intravenous immunoglobulin. Three patients recovered renal function rapidly after this treatment. Donor-specific antibodies were negative in these patients. Five sessions of plasmapheresis were used simultaneously in these 4 patients. In 3 resistant patients, rituximab was prescribed after plasmapheresis and intravenous immunoglobulin. The presence of donor-specific antibodies was demonstrated in 4 patients. Two patients were refractory to antibody-mediated rejection treatment and lost their transplants. One patient had interstitial fibrosis and tubular atrophy during the 16th month after her antibody-mediated rejection. Graft survival in patients with antibody-mediated rejection at the end of 1 year was 71.4%.
Early diagnosis and treatment with plasmapheresis, intravenous immunoglobulin, and rituximab may resolve antibody-mediated rejection. Although effective therapy is available for acute antibody-mediated rejection, the allograft remains at risk for chronic antibody-mediated rejection and shortened survival.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the effects of prostaglandin E-1 (PGE-1) on preservation injury in livers perfused with the University of Wisconsin (UW) or histidine-tryptophan-ketoglutarate (HTK) solutions.
Five groups each including six rats included. Ringer's lactate RL (group 1), HTK (group 2), HTK + PGE-1 (group 3), UW (group 4), or UW PGE-1 (group 5). Liver tissue and preservation fluid samples were obtained from the perfused lives for pathological and biochemical examinations respectively at 0, 6 and 12 hours.
Upon biochemical examination, aspartate aminotrasnferase and alanine aminotransferase values were highest among the group with RL solution and lowest with PGE-1. Liver structure was found to be damaged immediately after RL solution, whereas it was preserved in the other four groups. Fewer cellular changes were reported at the end of 12 hours in the groups administered PGE-1 compared with the other groups.
PGE-1 when applied before preservation protected liver functions, decreased pathologic injury, and delayed changes that occur under cold ischemic conditions.
[Show abstract][Hide abstract] ABSTRACT: The current study sought to examine the interactions between inflammatory and immune events in the lung and circulating interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) levels at different burn depths with concomitant smoke inhalation in the rat model. Forty-eight female Sprague-Dawley rats were divided into six groups: S, sham; P, partial-thickness burns; F, full-thickness burns; I, inhalation; Pi, partial-thickness burns + inhalation; and Fi, full-thickness burns + inhalation. Blood samples and lung biopsies were obtained 24 hours later. Blood levels of IL-6, TNF-α, and IF-γ were measured with enzyme-linked immunosorbent assay. The proportions of CD3(+) lymphocytes and CD68(+) macrophages in the biopsies were studied immunohistochemically. The most severe inflammatory changes, except the neutrophil sequestration, were observed in the Fi group. A dense amount of neutrophils was observed in the F group. Edema and massive alveolar bleeding were seen in the I, Pi, and Fi groups. The amount of CD3(+) lymphocytes were dense in the P, F, and Pi groups. The amount of CD68(+) macrophages were significantly dense in Pi, F, I, and Fi groups. IL-6, TNF-α, and IF-γ increased in all groups when compared to the S group. The highest IL-6 level was seen in the Fi group. TNF-α significantly increased in the F, Pi, I, and Fi groups. Increase in IFN-γ levels in the Pi and Fi groups was significantly higher than in the P and F groups. In concomitant smoke inhalation and skin burns, pulmonary damage and systemic inflammatory response are related and may be evaluated by blood levels of IL-6, TNF-α, and IFN-γ cytokines.
Journal of burn care & research: official publication of the American Burn Association 11/2012; 34(3). DOI:10.1097/BCR.0b013e3182644e9b · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Splenic arterial steal syndrome is an important cause of morbidity and mortality after orthotopic liver transplant. Splenic arterial steal syndrome is characterized by arterial hypoperfusion of the graft; and if left untreated, causes ischemic biliary tract injury. Selective arterial embolization is important when treating splenic arterial steal syndrome. Doppler ultrasound has been used to follow-up liver transplant patients. This study sought to analyze alterations in portal vein velocity, peak systolic velocity, and resistivity index of the hepatic artery before diagnosis and after treatment of splenic arterial steal syndrome.
We analyzed the Duplex Doppler ultrasonography results of 20 liver transplant recipients who developed angiographically proven splenic arterial steal syndrome between January 2005 and March 2009. Peak systolic velocity and resistivity index of the hepatic artery were noted during transplant surgery, before selective arterial embolization, and after embolization procedures.
A statistically significant decrease was found in peak systolic velocity and resistivity index of the hepatic artery between the intraoperative and pre-embolization values. In contrast to the statistically significant increase in peak systolic velocity of the hepatic artery, there were no significant changes in resistivity index after the selective arterial embolization. Portal vein velocity did not show a statistically significant change between intraoperative and preprocedure values. Portal vein velocity did show a tendency to decrease after coil embolization, but this was not significant.
Doppler ultrasound surveillance is a valuable tool in early detection of hepatic arterial complications. A decrease in peak systolic velocity and resistivity index compared to the corresponding intraoperative data should raise suspicion of splenic arterial steal syndrome. Also Doppler ultrasound can be effectively used to examine the hepatic arterial inflow after selective arterial embolization.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the frequency, type, and predictors of intraoperative adverse events during donor hepatectomy for living-donor liver transplant.
Retrospective analyses of the data from 182 consecutive living-donor liver transplant donors between May 2002 and September 2008.
Ninety-one patients (50%) had at least 1 intraoperative adverse event including hypothermia (39%), hypotension (26%), need for transfusions (17%), and hypertension (7%). Patients with an adverse event were older (P = .001), had a larger graft weight (P = .023), more frequently underwent a right hepatectomy (P = .019), and were more frequently classified as American Society of Anesthesiologists physical status class II (P = .027) than those who did not have these adverse events. Logistic regression analysis revealed that only age (95% confidence interval 1.018-1.099; P = .001) was a risk factor for intraoperative adverse events. Patients with these adverse events more frequently required admission to the intensive care unit and were hospitalized longer postoperatively. A before and after analysis showed that after introduction of in-line fluid warmers and more frequent use of acute normovolemic hemodilution, the frequency of intraoperative adverse events was significantly lower (80% vs 29%; P < .001).
Intraoperative adverse events such as hypothermia and hypotension were common in living-donor liver transplant donors, and older age was associated with an increased risk of these adverse events. However, the effect of these adverse events on postoperative recovery is not clear.
[Show abstract][Hide abstract] ABSTRACT: We investigated the prognostic factors affecting recurrence including Ki-67 among patients who underwent liver transplantation for hepatocellular carcinoma.
The 50 patients with a diagnosis of hepatocellular carcinoma and cirrhosis included those with expanded criteria for hepatocellular carcinoma excluding subjects with major vascular invasion and metastases but not taking into account tumor size and number of tumor nodules.
Twenty-eight patients had hepatocellular carcinoma characteristics outside the Milan criteria. Nineteen patients had unifocal; 31, multifocal hepatocellular carcinomas. Mean tumor size was 3.2 cm; mean tumor number was 5.06 lesions. Over a mean follow-up of 45.3±22.6 months, we diagnosed, respectively 2 recurrences. Overall 1-, 3-, and 5-year patient survival rates were 95.6%, 88.4%, and 84.8% and disease-free survival rates, 92%, 78.4%, and 71%, respectively. The independent prognostic factors by multivariate analyses were the number of tumors and Ki-67 with a cutoff value of 10%.
Ki-67 staining percentage represent a marker to select recipients and to follow posttransplant recurrence.
[Show abstract][Hide abstract] ABSTRACT: One consequence of chronic kidney disease (CKD) is an elevated risk for cancer. There is sufficient evidence to conclude that there is an increased incidence of at least some cancers in kidney-dialysis patients. Cancer risk after kidney transplantation has mainly been attributed to immunosuppressive therapy. There are no data evaluating DNA damage in children with CKD, in dialysis patients, or following kidney transplantation. In this study, the comet assay and the enzyme-modified comet assay - with the use of endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) enzymes - were conducted to investigate the basal damage and the oxidative DNA damage as a result of treatment in peripheral blood lymphocytes of children. Children at various stages of treatment for kidney disease, including pre-dialysis patients (PreD) (n=17), regular hemodialysis patients (HD) (n=15), and those that received kidney transplants (Tx) (n=17), comprised the study group. They were compared with age- and gender-matched healthy children (n=20) as a control group. Our results show that the %DNA intensity, a measure of basal damage, was significantly increased in children with CKD (mean ± SD) (5.22 ± 1.57) and also in each of the PreD, HD, and Tx groups [(4.92 ± 1.23), (4.91 ± 1.35), and (5.79 ± 1.94), respectively, vs the healthy children (2.74 ± 2.91) (p<0.001). Significant increases in oxidative DNA damage were only found in the FPG-sensitive sites for the PreD and Tx groups, compared with control and HD groups (p<0.05), suggesting that basal DNA damage was more evident for the PreD, HD, and Tx groups. The findings of the present study indicate a critical need for further research on genomic damage with different endpoints and also for preventive measures and improvements in treatment of pediatric patients, in order to improve their life expectancy.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 07/2011; 725(1-2):22-8. DOI:10.1016/j.mrgentox.2011.07.005 · 3.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: One of the crucial adverse effects of chronic kidney disease (CKD) and its treatment is an elevated cancer risk. There are no data on cytogenetic effects in children with CKD or children undergoing dialysis or those who have received a transplant. In this study, cytogenetic effects in children with CKD in pre-dialysis (PreD) stage, on regular haemodialysis (HD) and transplanted (Tx) compared with a control group of healthy children has been investigated using the cytokinesis-blocked micronucleus (CBMN) assay and fluorescence in situ hybridisation (FISH) combined with CBMN (CBMN-FISH) in peripheral blood lymphocytes. The results revealed a significant increase (P < 0.001) in micronucleus (MN) frequencies [mean ± SD (n)] in the PreD, HD and Tx groups versus the control group [CBMN assay; 9.19 ± 2.61 (16), 9.07 ± 4.86 (15), 6.12 ± 5.33 (17) versus 1.60 ± 0.99 (20), respectively]. Moreover, centromere negative micronucleus (C- MN) and centromere positive micronucleus (C+ MN) frequencies were significantly higher in each subgroup children (PreD, HD and Tx) than in the control group (P < 0.01) although children in Tx group had lower C- MN frequencies than PreD and lower C+ MN frequencies than PreD and HD groups (P < 0.05). Additionally, MN frequencies in mononuclear cells, nucleoplasmic bridges and nuclear buds in binucleated cells were increased in children with CKD (P < 0.001, P < 0.001, P > 0.05, respectively). The nuclear division index significantly decreased in Tx group relative to the control, PreD and HD groups (P < 0.001). Associations between cytogenetic parameters and creatinine or blood urea nitrogen were found (P < 0.05). To provide longer and better life expectancy of children with CKD and treatment modes, further research is needed to better understand and avoid these effects.
[Show abstract][Hide abstract] ABSTRACT: The incidence of detecting hepatocellular carcinoma in a removed recipient liver after a liver transplant is not rare. Here, we sought to evaluate incidental hepatocellular carcinoma at our center.
Among 296 patients who had undergone a liver transplant between September 2001 and November 2010, we retrospectively analyzed the outcomes of 6 patients with incidental hepatocellular carcinoma. The proportion of incidental hepatocellular carcinoma was 2%. The rate of incidental hepatocellular carcinoma among all hepatocellular carcinoma patients is 11.5%. There were 3 children and 3 adults (mean age, 28.3 ± 26 years; age range, 1-57 years). Two of the 6 patients were 1 year old. Alpha-fetoprotein levels were mildly elevated in 3 patients.
The results of preoperative imaging studies in all patients were normal, except for those that demonstrated regenerative or dysplastic nodules. One of the grafts was from a deceased donor, the remaining 5 were from living-related donors. We encountered no complications after the transplants. Pathology findings showed a mean tumor size of 0.8 ± 0.3 cm (range, 0.5-1.2 cm) and multiplicity in 1 patient. One patient with multiple tumors had microvascular invasion. According to the Tumor Node Metastasis staging system, 5 patients had Stage I, and the remaining patient had Stage II carcinoma. There were no recurrences of hepatocellular carcinoma, and no deaths occurred during a mean follow-up of 63 ± 16.5 months (range, 33-79 months).
The incidence of hepatocellular carcinoma in patients with cirrhosis who have undergone a liver transplant at our hospital is similar to those reported in other studies. Incidentally found hepatocellular carcinomas showed less-invasive pathologic features and better prognoses than did preoperatively found hepatocellular carcinomas.
[Show abstract][Hide abstract] ABSTRACT: Hepatitis B immune globulin use for preventing hepatitis B virus recurrence after liver transplant has changed our behavior radically, and it now seems that hepatitis B immune globulin has a vital role in preventing recurrence. New nucleotide or nucleoside analogues have promising results in treating chronic hepatitis and in posttransplant hepatitis B virus-infected patients. Hepatitis B immune globulin and other antivirals act on different pathways, so it is logical to combine these drugs to achieve maximum response in suppressing hepatitis B virus (HBV)-replication.
[Show abstract][Hide abstract] ABSTRACT: Portal vein stenosis is a relatively rare complication after living-donor liver transplantation, which sometimes leads to a life-threatening event owing to gastrointestinal bleeding or graft failure. This study sought to evaluate the diagnoses and management of late-onset portal vein stenosis in pediatric living-donor liver transplants.
Since September 2001, we performed 123 living-donor liver transplant procedures in 120 children, among which 109 children with a functioning graft at 6 months after living-donor liver transplant are included in this analysis. Seven instances of portal vein stenosis were diagnosed and were analyzed retrospectively.
The median age of the children was 5.3 years, and the median body weight was 19.2 kg. Portal vein stenosis was diagnosed at 11.2±3.1 months after living-donor liver transplantation. Whereas 3 children were asymptomatic, splenomegaly and/or massive ascites were observed in the remaining 4. Additionally, platelet counts were below the normal limit in 4 children. All children were treated with transhepatic balloon dilatation except 1. Intraluminal stent placement was needed in 1 child owing to resistance of balloon dilatation. The mean pressure gradient decreased from 12.4 to 3.2 mmHg after successful treatment. We did not observe any treatment-related complications. Portal venous patency was maintained in all children during posttreatment follow-up of 43.2±20.4 months. There were no recurrences of portal vein stenosis. One child died; the remaining 6 children are alive with good graft function at 49.8±23.9 months of follow-up.
Although most portal vein stenosis is asymptomatic, splenomegaly and platelet counts are 2 important markers for portal vein stenosis. Early detection of portal vein stenosis with these 2 markers can lead to successful interventional percutaneous approaches and avoid graft loss.
[Show abstract][Hide abstract] ABSTRACT: In pediatric liver transplantation, Roux-en-Y hepaticojejunostomy is often preferred for biliary reconstruction, especially in living-donor liver transplantation (LDLT). Limited numbers of duct-to-duct biliary reconstructions have been presented in pediatric recipients. We retrospectively reviewed our experiences with duct-to-duct biliary reconstruction without a stent in pediatric LDLT recipients.
Since September 2006, 32 LDLTs were performed using a duct-to-duct biliary reconstruction without a stent in 31 children (16 boys and 15 girls; overall mean age, 8.3±5.1 years). We transplanted 19 left lobe grafts, 11 left lateral segments, 1 monosegment, and 1 reduced-size right lobe graft. Twenty-eight grafts had a single bile duct; the remaining 4, two bile ducts. We created a single orifice at the back table for the grafts that had 2 bile ducts.
Two recipients developed bile leakage in the early postoperative period; 3 bile duct stenoses occurred in the late postoperative period. All biliary complications were successfully treated with interventional radiologic or endoscopic approaches. There was no morbidity and no graft loss owing to biliary complications. During a mean follow-up of 23.5±13.6 months (range, 4-44), 4 children died and the remaining 27 (88%) are doing well with satisfactory liver function.
Our results showed that duct-to-duct biliary reconstruction without a stent was a safe technique for biliary reconstruction even among pediatric cases.
[Show abstract][Hide abstract] ABSTRACT: Recurrence of hepatitis B virus after a liver transplantation (OLT) is a risk factor affecting graft and patient survivals. Short-term hepatitis B virus reactivation rates after OLT range between 3% and 15%. Using combination prophylaxis, the outcomes of OLT among patients with liver disease related to hepatitis B virus have improved to levels comparable to those whose disease is not related to hepatitis B virus.
Since September 2001, we performed 288 OLT in 282 patients including 74 who had liver failure related to hepatitis B virus among whom 58 were followed for >12 months and analyzed retrospectively. Our protocol included lamivudine (100 mg orally per day beginning the day after surgery) and hepatitis B immunoglobulin (10,000 IU IV during the anhepatic phase, 2000 IU/d IV during the first week after surgery, 2000 IU IV/month from postoperative months 1 to 12). Using our protocol, the anti-hepatitis B surface antibodies (HBsAb) serum titer was maintained up to 100 IU/mL. The female:male ratio was 11:47. The mean age of patients was 43±12.8 years.
Five patients died of causes unrelated to hepatitis B virus. At the time of death, their hepatitis B surface antigens were negative, and serum titers of anti-HBsAb were 45, 35.3, 56.4, 79.6, and 123 IU/mL. Mean follow-up was 46.5±18.9 months (range, 12-79). The hepatitis B surface antigen became positive in 4 patients; the remaining 49 had no evidence of hepatitis B surface antigen. In 18 patients, serum titer of anti-hepatitis B surface antigen was 0; in the remaining 31 patients, it was 69.2±133 IU/mL.
Our combination protocol with hepatitis B immunoglobulin and lamivudine is a safe, cost-saving, and effective treatment for hepatitis B virus prophylaxis after liver transplantation.
[Show abstract][Hide abstract] ABSTRACT: Increased serum bilirubin levels are common after living-donor hepatectomy. Little information is available on the characteristics and clinical significance of serum bilirubin levels soon after donor hepatectomy.
Since September 2001, we performed 229 living donor hepatectomies for living-donor liver transplantations. The 128 men and 101 women had a mean age of 34.4±8.9 years (range, 19-66). Most donors were parents (n=110; 48%). We transplanted 110 right lobes, 46 left lobes, and 73 left lateral segments. Donors were divided into 2 groups: Group 1 consisted of 181 donors who showed total bilirubin levels of <3 mg/dL, and group 2, 48 donors with levels of ≥3 mg/dL on postoperative day 3. Preoperative total bilirubin level, ratio of preoperatively estimated remnant liver volume, surgical duration, gender, age, graft type, blood transfusions, and preoperative liver biopsy findings were evaluated as risk factors for hyperbilirubinemia.
The mean postoperative maximum total bilirubin level was 2.26±1.49 mg/dL (range, 0.36-9.9). Remnant liver volume<40%, preoperative bilirubin levels>1 mg/dL, right lobe donor hepatectomy, male donor, and abnormal liver biopsy findings were significant risk factors for postoperative hyperbilirubinemia (P=.015, P=.02, P<.01, P=.008, and P=.023 respectively). Also donor age>50 years showed a slight effect on hyperbilirubinemia (P=.052). Blood transfusions and surgical times were not significant factors.
Donor safety is paramount, requiring thorough donor evaluation. Extensive liver resection may result in transient functional impairment. Several factors are believed to play roles in the development of postoperative hyperbilirubinemia after living-donor hepatectomy.