Does Additional Doxorubicin Chemotherapy Improve Outcome in Patients with Hepatocellular Carcinoma Treated by Liver Transplantation?

The aim of this prospective randomized study was to determine whether additional doxorubicin chemotherapy improves outcome in patients with hepatocellular carcinoma (HCCA) treated by liver transplantation. Stratification parameters were tumor stage (UICC I-IVa), gender, age 50 years, α-fetoprotein 20 ng/mL, cirrhosis and HbsAg status. For pre-operative chemotherapy doxorubicin (15 mg/m²) was given biweekly, intra-operative chemotherapy was a single dose administered before surgical manipulation. Post-operative chemotherapy from day 10 was as given preoperatively for a total dosage of 300 mg/m². Outcome parameters were overall survival (OS) and disease-free survival. Of the 75 consecutive patients who received liver transplantation for treatment of HCCA, 62 patients were enrolled. Thirty-four patients were randomized in the chemotherapy group; 28 patients were in the control group and transplanted only. OS rates at 5 years were 38% in the chemotherapy group and 40% in the control group, disease-free survival rates at 5 years 43% and 53%, respectively. Tumor stage and vascular invasion were identified as independent risk factors for recurrence of disease. Doxorubicin chemotherapy did not improve organ survival and disease-free survival in patients undergoing liver transplantation for HCCA.     

Adult Liver Transplant Candidate Attitudes Toward Graft Sharing Are Not Obstacles to Split Liver Transplantation

Split liver transplantation (SLT) benefits society by increasing the total number of transplants that can be performed, but it is yet unknown if a decreased post-transplant survival (in comparison to whole liver transplantation) would make participation in SLT less appealing to adult liver transplant candidates. A 20-item questionnaire was administered to 50 adult candidates to assess attitudes toward SLT and organ sharing. The overall attitudes of 60% of participants were classified as utilitarian (maximizing benefit to greatest number of candidates), while 26% were classified as self-preserving (maximizing individual benefit) and 14% were undecided. Ninety percent of participants would be willing to share even if expected survival was less than that of whole liver transplantation, and 69% felt that pediatric candidates should have priority over adult candidates. In conclusion, attitudes toward graft sharing and the possibility of compromised survival benefit are not barriers to SLT for most adult liver transplant candidates.     

Randomized Trial of Basiliximab Induction versus Steroid Therapy in Pediatric Liver Allograft Recipients Under Tacrolimus Immunosuppression

Avoidance of corticosteroids could be beneficial after pediatric liver transplantation (LTx). To test this hypothesis, we performed a randomized prospective study to compare immunosuppression with tacrolimus (TAC) and steroids versus TAC and basiliximab (BAS) after pediatric LTx. Seventy-two patients were recruited, 36 receiving TAC and steroids and 36 TAC and BAS. The primary endpoint was the occurrence of the first rejection episode. Secondary endpoints were the cumulative incidence and severity of rejection, patient and graft survival, and incidence of adverse events. Overall 1-year patient and graft survival rates were 91.4% and 85.5% in the steroid group, and 88.6% and 80% in the BAS group (p = NS). Patients free from rejection were 87.7% in the BAS group and 67.7% in the steroid group (p = 0.036). The use of BAS was associated with a 63.6% reduction in incidence of acute rejection episodes. Overall incidence of infection was 72.3% in the steroid group and 50% in the BAS group (p = 0.035). We conclude that the combination of TAC with BAS is an alternative to TAC and steroid immunosuppression in pediatric LTx, which allows for a significant reduction in the incidence of acute rejection and infectious complications.     

Segmental Liver Transplantation from Non-Heart Beating Donors—An Early Experience with Implications for the Future

We report our experience of pediatric liver transplantation with partial grafts from non-heart beating donors (NHBD). Controlled donors less than 40 years of age with a warm ischemia time (WI) of less than 30 min were considered for pediatric recipients. Death was declared 5 min after asystole. A super-rapid recovery technique with aortic and portal perfusion was utilized. Mean donor age was 29 years and WI 14.6 min (range 11–18). Seven children, mean age 4.9 years (0.7–11), median weight 20 kg (8.4–53) received NHBD segmental liver grafts. Diagnoses included seronegative hepatitis, neonatal sclerosing cholangitis, familial intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII deficiency (n = 2).The grafts included four reduced and one split left lateral segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3 h (6.2–8.8). Complications included one pleural effusion and one biliary collection drained percutaneously. At 20 months (10–36) follow-up all children are alive and well with functioning grafts.
Donation after cardiac death is a significant source of liver grafts for adults and children with careful donor selection and short cold ischemic times.     

Genes or environment to determine alcoholic liver disease and non-alcoholic fatty liver disease.

While the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome will have steatosis, only a minority will ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of fibrosis. For ALD, the dose and pattern of alcohol intake, along with obesity are the most important environmental factors determining disease risk. For NAFLD, dietary saturated fat and antioxidant intake and small bowel bacterial overgrowth may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the alcohol dehydrogenases and aldehyde dehydrogenase alcohol metabolising genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, TNF-alpha, transforming growth factor-beta, and angiotensinogen may be associated with steatohepatitis and/or fibrosis.     

In vivo detection of single cells by MRI.

The use of high-relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double-labeled with green fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases.     

肝移植术后胆道并发症的介入治疗

目的 探讨原位肝移植术后胆道并发症的介入治疗疗效。方法 回顾性分析我院2002年6月至2005年9月诊治的173例原位肝移植患者的临床资料。结果 术后出现胆道并发症14例（8．1％），其中胆管狭窄6例．胆管狭窄合并胆漏1例，胆泥淤积或结石3例，肝断面胆漏2例（劈离式肝移植患者），T管拔除后胆漏1例，Oddi括约肌功能失常1例。除1例胆道狭窄再次行肝移植，因发生严重感染导致肝功能衰竭死亡外．其余患者经介入治疗均获得满意的效果。结论 介入治疗是诊断和治疗肝移植术后胆道并发症的首选方法。     

肝移植围手术期出凝血功能障碍的防治

目的　探讨肝移植围手术期出凝血功能障碍的防治。方法　回顾性分析我院 2 0 0 2年 6月～ 2 0 0 3年 12月施行的 6 1例肝移植病例。结果　 6 1例肝移植术前肝功能ChildC级 35例 (5 7 4 % ) ,ChildB级 2 6例 (4 2 6 % ) ,ChildC组的患者术中凝血指标 (INR)的变化程度大于ChildB组 (P <0 0 5 )。与凝血有关的并发症中大出血 5例 (8 2 % ) ,肾衰 6例 (9 8% ) ,肝动脉血栓形成 5例 (8 2 % ) ,手术开展两阶段对比 ,第二阶段主要因限制了大量凝血药及血制品的使用 ,并发症明显减少。结论　掌握好不同时期、不同患者出血和血栓形成的平衡是防治肝移植围手术期出凝血功能障碍的关键     

Serial CT findings of Paragonimus infested dogs and the Micro-CT findings of the worm cysts.

OBJECTIVE: To investigate the serial CT findings of Paragonimus westermani infected dogs and the microscopic structures of the worm cysts using Micro-CT. MATERIALS AND METHODS: This study was approved by the committee on animal research at our institution. Fifteen dogs infected with P. westermani underwent serial contrast-enhanced CT scans at pre-infection, after 10 days of infection, and monthly thereafter until six months for determining the radiologic-pathologic correlation. Three dogs (one dog each time) were sacrificed at 1, 3 and 6 months, respectively. After fixation of the lungs, both multi-detector CT and Micro-CT were performed for examining the worm cysts. RESULTS: The initial findings were pleural effusion and/or subpleural ground-glass opacities or linear opacities at day 10. At day 30, subpleural and peribronchial nodules appeared with hydropneumothorax and abdominal or chest wall air bubbles. Cavitary change and bronchial dilatation began to be seen on CT scan at day 30 and this was mostly seen together with mediastinal lymphadenopathy at day 60. Thereafter, subpleural ground-glass opacities and nodules with or without cavitary changes were persistently observed until day 180. After cavitary change of the nodules, the migratory features of the subpleural or peribronchial nodules were seen on all the serial CT scans. Micro-CT showed that the cyst wall contained dilated interconnected tubular structures, which had communications with the cavity and the adjacent distal bronchus. CONCLUSION: The CT findings of paragonimiasis depend on the migratory stage of the worms. The worm cyst can have numerous interconnected tubular channels within its own wall and these channels have connections with the cavity and the adjacent distal bronchus.