Role of [18F] fludeoxyglucose positron emission tomography in the selection of liver transplantation candidates in patients with hepatocellular carcinoma

BACKGROUND： The Milan criteria are widely accepted among many centers. However, patients with hepatocellular carcinoma beyond the Milan criteria might still benefit from liver transplantation （LT） when tumor itself is not aggressive. [18F] fluorodeoxyglucose positron emission tomography/computed tomography imaging could provide useful information of tumor behaviors, which is helpful to predict the prognosis for many tumors. METHOD： In order to determine its role in candidate selection for LT, we therefore retrospectively analyzed 103 recipients with preoperative positron emission tomography （PET） findings. RESULTS： Positive PET findings （PET＋） were significantly associated with tumor nodule numbers （P=0.013）, tumor grade （P=0.025）, macro- （P=0.002） and micro-vascular invasion （P=0.002）, as well as the Milan criteria （P=0.018）. PET＋ patients had significantly increased risk of tumor recurrence post-LT compared to PET negative （PET-） patients （P=0.007）. The 1-, 3-, and 5-year overall survival rate of PET- patients were 96.0%, 87.2% and 76.2%, compared to 74.7%, 55.4% and 49.9% in PET＋ patients, respectively （P〈0.05）. The 1-, 3-, and 5-year recurrence-free survival rate of PET- patients were 91.8%,81.9% and 76.0%, compared to 70.1%, 39.3% and 21.9% in PET＋ patients, respectively （P〈0.05）. Recipients within the Milan criteria showed comparable 1-, 3-, and 5-year survival rates in comparison with those beyond the Milan criteria with a PET- findings （1-, 3-, and 5-year overall survival rates, 97.5%, 83.3%, and 83.3% vs 90.0%, 80.0%, and 66.7%, P= 0.123; 1-, 3-, and 5-year recurrence-free survival rates, 95.1%, 73.1%, and 73.1% vs 90.0%, 78.8%, and 65.6%, P=0.148）. CONCLUSIONS： Certain patients with hepatocellular carcinoma and negative PET findings, who have exceeded the Milan criteria, are also eligible candidates for LT. Preoperative PET/CT imaging is an important marker, which should be incorporated in extended candidate selection criteria for LT.

Lack of association between genetic polymorphisms in cytokine genes and tumor recurrence in patients with hepatocellular carcinoma undergoing transplantation

BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after liver transplantation(LT) remains one of the most common causes of poor long-term survival.However,the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated.The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC.METHODS:Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes,i.e.,the IL-1 family(IL-1α and IL-1β),IL-6,IL-8,IL-10,TNF-α,and TGF-β1,were genotyped in 93 HCC patients treated with LT using DNA sequencing.The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables.RESULTS:The genotype frequency of IL-10-1082 A/G in patients with and without recurrence of HCC was AA 83.3%,GA 16.7% and AA 97.6%,GA 2.4%,respectively.The association between IL-10-1082 GA and recurrence was significant(P=0.033).No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence.Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients(23.5 vs 5.7 months,P=0.001).However,multivariate analysis failed to reveal that the GA genotype of IL-10-1082 A/G was an independent indicator of recurrence.CONCLUSIONS:This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population.The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.

Oncogenic role of microRNA-423-5p in hepatocellular carcinoma

BACKGROUND： It has been found that microRNA-423-5p （miR423-Sp） is an oncogenic factor and frequently upregulated in gastric carcinoma. However, the involvement of miR423- 5p in hepatocellular carcinoma （HCC） has been rarely reported. The aim of this study was to assess whether miR423-Sp is aberrantly expressed in HCC tissues, and to characterize its roles in the cancerous biology of HCC.

Machine perfusion for liver transplantation:A concise review of clinical trials

Background: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications Machine perfusion(MP) is a beneficial alternative preservation strategy for donor livers, particularly fo those considered to be of suboptimal quality, and could expand the limited donor pool. Data sources: A comprehensive search in Pub Med, EMBASE, Ovid databases and Clinical Trials.gov website was conducted using the medical subject heading terms "machine perfusion", "machine preservation""liver transplantation", combined with free text terms such as "hypothermic", "normothermic" and "sub normothermic". The deadline for the search was September 30, 2017. Results: MP can be classified as hypothermic, subnormothermic, and normothermic with the tempera ture maintained at 0–12 °C, 25–34 °C and 35–38 °C, respectively. Twelve clinical trials of MP have been reported in recent years. MP effectively decreased AST/ALT level and the incidence of early allograft dys function. However, the graft and patient survival rate after MP were similar to static cold storage. The detailed clinical characteristics such as liver function, graft survival, patient survival and early allograf dysfunction were reviewed.Conclusions: Clinical trial results showed that MP improves delayed graft function, primary non-function and biliary strictures. However, MP still requires validation in large clinical trials and the key parameters during MP still require optimization.

A modified protocol with rituximab and intravenous immunoglobulin in emergent ABO-incompatible liver transplantation for acute liver failure

BACKGROUND： The established procedure for ABO-incompatible liver transplantation（ABO-I LT） was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin（IVIG） for ABO-I LT in patients with acute liver failure（ALF）.METHODS： The data from 101 patients who had undergone liver transplantation（LT） for ALF were retrospectively analyzed.The patients were divided into two groups： ABO-compatible liver transplantation group（ABO-C LT, n=66） and ABO-I LT group（n=35）. All the patients in the ABO-I LT group received a single dose of rituximab（375 mg/m2） and IVIG（0.4 g/kg per day） at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol.Quadruple immunosuppressive therapy including basiliximab,corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression.RESULTS： The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%,respectively（P〉0.05）, and the graft survival rates were 80.0%and 86.3%, respectively（P〉0.05）. Two patients（5.7%） suffered from antibody-mediated rejection in the ABO-I LT group.Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups.CONCLUSIONS： The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.

Current strategies for preventing the recurrence of hepatocellular carcinoma after liver transplantation

BACKGROUND：Liver transplantation is the optimal treatment for a selected group of patients with moderate to severe cirrhosis and hepatocellular carcinoma（HCC）.Despite the strict selection of candidates,post-transplant recurrence often occurs and markedly reduces the long-term survival of patients with HCC.The present review focuses on the current strategies on preventing the recurrence of HCC after liver transplantation.DATA SOURCES： Relevant articles were identified by exten- sive searching of PubMed using the keywords ＂hepatocellular carcinoma＂, ＂recurrence＂ and ＂liver transplantation＂ between January 1996 and January 2014. Additional papers were searched manually from the references in key articles. RESULTS： The current theories of HCC recurrence after liver transplantation are： （i） the growth of pre-transplant occult metastases; （ii） the engraftment of circulating tumor cells released at the time of transplantation. Pre-transplant treatment aims to control local tumor by radiofrequency ablation, transarterial embolization and transarterial chemoembolization. The main objective during the operation is to prevent tumor cell dissemination. Post-transplant treatment includes systemic anticancer therapy, antiviral therapy, and most recently, immunotherapy. These strategies concentrate on the control of the tumor when the patients are waiting for transplant, to reduce the release of HCC cells during surgical procedures and to dear the occult HCC cells after transplantation.CONCLUSIONS： Much can be done to prevent HCC recurrence after liver transplantation. In future, effort is likely to be di- rected towards combining multidisciplinary approaches and various treatment modalities.

Middle hepatic vein reconstruction in adult right lobe living donor liver transplantation improves recipient survival

Background: The efficacy and necessity of middle hepatic vein(MHV) reconstruction in adult-to-adult right lobe living donor liver transplantation(LDLT) remain controversial. The present study aimed to evaluate the survival beneficiary of MHV reconstructions in LDLT. Methods: We compared the clinical outcomes of liver recipients with MHV reconstruction( n = 101) and without MHV reconstruction( n = 43) who underwent LDLT using right lobe grafts at our institution from January 2006 to May 2017. Results: The overall survival(OS) rate of recipients with MHV reconstruction was significantly higher than that of those without MHV reconstruction in liver transplantation( P = 0.022; 5-yr OS: 76.2% vs 58.1%). The survival of two segments(segments 5 and 8) hepatic vein reconstruction was better than that of the only one segment(segment 5 or segment 8) hepatic vein reconstruction( P = 0.034; 5-yr OS: 83.6% vs 67.4%). The survival of using two straight vascular reconstructions was better than that using Y-shaped vascular reconstruction in liver transplantation with two segments hepatic vein reconstruction( P = 0.020; 5-yr OS: 100% vs 75.0%). The multivariate analysis demonstrated that MHV tributary reconstructions were an independent beneficiary prognostic factor for OS(hazard ratio = 0.519, 95% CI: 0.282–0.954, P = 0.035). Biliary complications were significantly increased in recipients with MHV reconstruction(28.7% vs 11.6%, P = 0.027). Conclusions: MHV reconstruction ensured excellent outflow drainage and favored recipient outcome. The MHV tributaries(segments 5 and 8) should be reconstructed as much as possible to enlarge the hepatic vein anastomosis and reduce congestion.