M.I. Leonardi

Intraoperative Massive Transfusion Decreases Survival After Liver Transplantation

Patients undergoing liver transplantation often experience coagulopathy and massive intraoperative blood loss that can lead to morbidity and reduced survival. The aim of this study was to verify the survival rate and discover predictive factors for death among liver transplant patients who received massive intraoperative blood transfusions. This cohort study was based on prospective data collected retrospectively from January 2004 to July 2006. The 232 patients were distributed according to their blood requirements, (namely, more or less than 6 units), including red blood cell saver. The statistical analyses were performed using Student t test, Cox hazard regression, and the Kaplan-Meier method (log-rank test). The massively transfused cohort displayed higher Child-Pugh classifications (10.2 vs 9.6; P = .03); model for end-stage liver disease (MELD) scores (19 vs 17; P = .02); recipient weights (75.4 vs 71 kg; P = .03); as well as warm ischemia times (70.7 vs 56.4 minutes; P < .001) and surgery times (584.6 vs 503.4 minutes; P < .05). The proportional hazard (Cox) regression analysis showed that the risk of death increased 2.1% for each unit of donor sodium and 1.6% for each additional year of donors age over 50. The survival rates at 6, 12, 60, and 120 months for > or = 6 vs <6 U of blood transfusion of 63.8% vs 83.3%; 53.9% vs 76.3%; 40% vs 60%; 34.5% vs 49.2%. In conclusion, we observed that patients receiving over 6 red blood cell units intraoperatively displayed reduced survival. Predictive factors for this risk factor were high donor level of sodium and of age.

Elderly Donors for HCV+ Versus Non-HCV Recipients: Patient Survival Following Liver Transplantation

INTRODUCTION Chronic liver failure due to hepatitis C virus (HCV)-related cirrhosis is the leading indication for liver transplantation. Inferior long-term results have been reported for liver transplantation in HCV(+) patients, especially when marginal donor livers are utilized. AIM The aim of this study was to analyze retrospectively the outcome of liver transplantation patients from elderly donors in the case of HCV(+) versus non-HCV recipients. METHODS Among 330 liver transplantations performed from January 1994 to December 2006, we selected 244 excluding acute hepatic failure, children, and retransplants. Among these patients we analyzed 232 subjects who underwent the piggyback technique. Donor risk index (DRI) as described by Feng et al was applied using 1.7 as a cutoff value. We used Kaplan-Meier survival and Cox hazard regression analyses. We studied 14 donor variables using descriptive statistical tests. RESULTS There were 148 (63.8%) HCV(+) recipients and 84 (36.2%) non-HCV liver transplant recipients. Among HCV(+) recipients, 130/148 (87.8%) patients received livers, from donors less than 50 years old, and 18/148 (12.2%), over 50 years. The descriptive statistics of patient categorical variables are shown in Table 1, and continuous variables in Table 2. The cumulative proportional survival curves are shown in Figs 1 and 2. Mortality predictive factors in HCV(+) liver transplant recipients with donor age > 50 years old as determined by Cox hazard regression showed that death risk was increased with hazard ratios for warm ischemia = 1.01 (P = .001); for red blood cell intraoperative requirements = 2.63 (P = .003); for Child-Turcotte-Pugh classification points = 2.25 (P = .04), and for DRI > 1.7 = 2.19 (P = .03). In conclusion, advancing donor age, as well as the use of nonideal donors, intraoperative bleeding, and prolonged warm ischemia, had an adverse influence on patient survival for HCV(+) recipients.

Extragastrointestinal Stromal Tumor and Liver Transplantation : Case Report and Review

The occurrence of de novo malignant neoplasias has been shown in postransplant patients under imunosuppression. It is the second leading cause of late death in liver transplant recipients. The greatest incidence is seen in cancers associated with chronic infection by human papilloma virus, skin cancers, oropharyngeal, and gastrointestinal (GI) malignancies. GI stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract. Rare cases are identified outside the GI tract are collectively known as extragastrointestinal stromal tumors (EGISTs). We present an EGIST case in a liver transplantation patient. A 64-year-old man underwent liver transplantation because of cirrhosis (hepatitis B virus and alcoholism) and hepatocellular carcinoma. Histopathologic findings revealed 2 trabecular hepatocellular carcinomas: a 3.5-cm-diameter lesion located at segment VIII and another 2-cm one at segment V. Seven months later, he noticed a hardened, mobile, painless, 3-cm subcutaneous nodule in the perineum localized in the right lateral quadrant 2 cm distant from the anus. A surgical resection with 1 cm margin yielded a histopathology report of a 5.0 x 3.0 cm spindle cell stromal tumor. The immunohistochemical profile was compatible with a GIST, with 5 mitosis per 50 high-powered fields. This tumor is extremely rare after liver transplantation but has shown a good outcome up to now.

Human herpesvirus-7 in Brazilian liver transplant recipients: a follow-up comparison between molecular and immunological assays.

Abstract: Human herpesvirus‐6 and ‐7 (HHV‐6, HHV‐7) remain latent after primary infection and can reactivate after transplantation. HHV‐6 active infection has been related to some clinical manifestation, but the role of HHV‐7 remains unclear. The clinical significance of HHV‐7 DNAemia is not completely known and the immune response against HHV‐7 has been poorly studied in transplantation. In this study, we investigated HHV‐7 DNAemia in liver transplant recipients and evaluated the immunoglobulin (Ig) G and IgM response against HHV‐7. A total of 22 adult liver transplant recipients were followed up for 90 days. HHV‐7 DNAemia was detected by nested polymerase chain reaction (PCR) in DNA extracted from sera. IgG and IgM detection was performed by immunofluorescent assay using HHV‐7‐infected cord blood mononuclear cells. A significant virus antibody response was defined as either a positive IgM or a ≥4‐fold rise in the virus IgG antibody. All patients had pre‐transplant HHV‐7‐positive serostatus. Nine of 22 (40.9%) patients presented HHV‐7 DNAemia during follow‐up. All these patients had anti‐HHV‐7‐positive IgM and/or significant increase in IgG titers with concurrent or subsequent DNAemia. In patients without DNAemia and low persistent IgG antibody titers, IgM was not detected. Correlation between nested PCR and IgM detection was statistically significant (P=0.01). Our study indicates that nested PCR in DNA extraction from serum can be useful to detect and monitor HHV‐7 active infection in liver transplant recipients. IgM antibody detection also can be useful as a first immunological technique to detect active infection, especially if combined with PCR.

Prospective analysis between the therapy of immunosuppressive medication and allogeneic microchimerism after liver transplantation

After liver transplantation, migration of donor-derived hematopoietic cells to recipient can be detected in peripheral blood. This state is termed microchimerism. The aim of this study was to investigate prospectively the presence of allogeneic microchimerism, the occurrence of acute cellular rejection and the level of immunosuppression in transplanted patients. Microchimerism occurrence between 10 days and 12 months after liver transplantation was analyzed in 47 patients aged between 15 and 65 by a two-stage nested PCR/SSP technique to detect donor MHC HLA-DR gene specifically. A pre-transplant blood sample was collected from each patient to serve as individual negative control. Microchimerism was demonstrated in 32 (68%) of the 47 patients; of these, only 10 patients (31.2%) presented rejection. Early microchimerism was observed in 25 patients (78.12%) and late microchimerism in 7 patients (21.8%). Among the patients with microchimerism, 14 were given CyA and 18 were given FK506. In the group without microchimerism, 12 patients were given CyA and 03 were given FK506. There was a significant association between the presence of microchimerism and the absence of rejection (p=0.02) and also between microchimerism and the type of immunosuppression used. Our data indicate that microchimerism and probably differentiation of donor-derived leukocytes can have relevant immunologic effects both in terms of sensitization of recipient and in terms of immunomodulation toward tolerance induction.

Expanded Milan Criteria on Pathological Examination After Liver Transplantation: Analysis of Preoperative Data

BACKGROUND We sought to evaluate the accuracy of imaging techniques related to the Milan criteria (MC) compared with the explant histology and the survival of these patients. METHODS Between 1997 and 2006, we selected 45 cirrhotic patients with hepatocellular carcinoma distributed into two groups according to explant histology: MC and Expanded Milan Criteria (EMC). Age, gender, preoperative imaging (ultrasound [US] and/or computed tomography [CT]), maximal tumor dimension, number of tumors, explanted histology, histology degree, alpha-fetoprotein (AFP) level and vascular invasion were compared among the patients to evaluate the value of these prognostic factors for survival after liver transplantation. RESULTS By histology 42.2% explants were identified as EMC. The mean AFP level was 204.5 ng/mL. Vascular invasion was detected in 31.5% of explants and 68.4% showed incidental tumors. The survival rates after 10 years were 47.4% whereas MC patients showed 57.77%. The mean AFP level among MC patients was 150.2 ng/mL with vascular invasion detected in 7.7% of explants, and 47.4% with incidental tumors. The overall sensitivity of the imaging techniques was 83.3% for CT and 75% for US. The specificity was 96% for CT and 80.1% for US. CONCLUSION Scan examinations in the preoperative evaluation underestimated about 42.2% of tumors. Those patients had vascular invasion but the survival after 10 years was similar between the ECM and MC groups.

Red Blood Cell Antigen Alloimmunization in Liver Transplant Recipients

Orthotopic liver transplantation (OLT) is a life-saving procedure for patients with end-stage liver disease. Transfusion support is an important part of OLT. Intraoperative transfusion of large volumes of blood products is recognized to be a poor prognostic factor, probably due to the negative effects of blood transfusions, such as transfusion reactions, infectious contamination of blood products, or immune modulation of the transfused patient. The aim of this study was to evaluate the frequency of alloimmunization and its specificity to red blood cell (RBC) antigens among patients undergoing OLT. We identified 74 RBC alloantibodies in 70 (23%) patients when the indirect antiglobulin test (IAT) was performed. The most common RBC alloantibodies were against Rh system antigens. The majority (41.9%) were directed against the E antigen. Despite the ethnic heterogeneity of our population there were no cases of intravascular hemolysis. The incidence of alloimmunization (23%) was slightly higher among patients than in the literature, most probably as a consequence of our ethnic heterogeneity.

Ascites After Liver Transplantation and Inferior Vena Cava Reconstruction in the Piggyback Technique

we have used the piggyback technique byperforming an end-to-side cavocaval anastomosis betweenthe suprahepatic donor vena cava and the recipient venacava, as described by Starzl. The donor suprahepatic venacava is anastomosed to the vascular cuff formed by combin-ing the lumina of the three suprahepatic veins of therecipient.

No Protective Function Found in Wistar Rats Submitted to Long Ischemia Time and Reperfusion After Intermittent Clamping of the Total Hepatic Pedicle

BACKGROUND Although the intermittent Pringle maneuver is used for major transplant surgery, traumas, and hepatic protection, long ischemia time and reperfusion may limit some protection in Wistar rats. The aim of the study was to evaluate the protection effects of intermittent clamping in the total hepatic pedicle after a long period of ischemia and reperfusion in Wistar rats. METHODS Forty-two male Wistar rats, weighing ± 327.7 g, were anesthetized intravenously with sodium thiopental and given a U-shaped incision in the abdomen. The total hepatic pedicle was isolated and subjected to clamping with a microvascular clamp. Groups included were the continuous group (CG, n = 14, 40 minutes of ischemia/40 minutes of reperfusion); the intermittent group (IG, n = 14, 4 cycles a 10 minute ischemia/reperfusion 10 minutes); and the sham group (SG, n = 14, 80 minutes of observation time). Blood collection for transaminase dosage was carried out, and hepatic biopsy specimens were taken for mitochondrial respiration and histological evaluation. RESULTS In groups CG and IG, aspartate aminotransferase and alanine aminotransferase enzymes were elevated in comparison to group SG (P < .008); mitochondrias, when stimulated by use of adenosine diphosphate or carbonylcyanide p-trifluoromethoxyphenylhydrazone, had a significant decrease in mitochondrial respiration (P < .05), and the respiratory control ratio in the ischemic groups was lower (P < .03) when compared with the GS. On histological examination, 100% of the GC had lesions: 33% focal hemorrhagic necrosis, 17% sinuzoidal congestion and/or vacuolization, and 50% venous congestion; in the IG, 100% had lesions: 43% sinusoidal congestion and/or vacuolization and 57% venous congestion. CONCLUSIONS The intermittent total hepatic pedicle clamping for a long period of time in the Wistar rats had no efficacy in protection of liver injury.

Indicações e resultados da ressecção cirúrgica do hemangioma hepático: indications and results

OBJETIVO: Apresentar os resultados do tratamento cirurgico em pacientes portadores de hemangioma hepatico. METODO: Foram estudados 20 pacientes portadores de hemangioma hepatico cavernoso, operados entre fevereiro de 1991 e fevereiro de 2005. A idade dos pacientes variou de 16 a 72 anos (media de 42 anos) com predominio do sexo feminino (80%), sendo que 85% deles eram sintomaticos. Todos os pacientes foram submetidos a ultrassonografia abdominal (US) e a tomografia computadorizada contrastada (TC). Utilizou-se incisao abdominal subcostal bilateral associada a incisao mediana. RESULTADOS: Durante o periodo de seguimento clinico nao se constataram recidiva de sintomas ou de hemangioma. A morbidade pos-operatoria representada por infeccao da ferida cirurgica foi observada em um (5%) paciente, insuficiencia hepatica leve em 40% e moderada em 15% que apresentaram evolucao clinica satisfatoria com o tratamento clinico instituido; em um (5%) verificou-se a ocorrencia de bilioma que necessitou drenagem por puncao abdominal. A maioria dos pacientes retornou as atividades habituais ate o 3o. mes de pos-operatorio. Nao ocorreram obitos nesta serie de pacientes. CONCLUSAO: A resseccao cirurgica do hemangioma hepatico, gigante ou sintomatico, e opcao de tratamento segura e eficaz, sendo que a extensao da resseccao varia de acordo com a localizacao e tamanho.