Gastroduodenal artery disconnection during liver transplantation decreases non-anastomotic stricture incidence

Background:The hepatic artery is the only blood source nourishing the biliary duct and associated with biliary complication after liver transplantation(LT).Gastroduodenal artery(GDA)disconnection increased proper hepatic artery flow.Whether this procedure attenuates biliary non-anastomotic stricture(NAS)is not clear.Methods:A total of 241 patients with LT were retrospectively analyzed.The patients were divided into the GDA disconnection(GDA-)and GDA preservation(GDA+)groups.Propensity score matching(PSM)was administrated to reduce bias.Logistic regression was conducted to analyze risk factors for biliary NAS before and after PSM.Postoperative complications were compared.Kaplan-Meier survival analysis and log-rank tests were performed to compare overall survival.Results:In all,99 patients(41.1%)underwent GDA disconnection,and 49(20.3%)developed NAS.Multivariate logistic regression revealed that GDA preservation(OR=2.24,95%CI:1.11-4.53;P=0.025)and model for end-stage liver disease(MELD)score>15(OR=2.14,95%CI:1.12-4.11;P=0.022)were risk factors for biliary NAS.PSM provided 66 pairs using 1:2 matching method,including 66 GDA disconnection and 99 GDA preservation patients.Multivariate logistic regression after PSM also showed that GDA preservation(OR=3.15,95%CI:1.26-7.89;P=0.014)and MELD score>15(OR=2.41,95%CI:1.08-5.36;P=0.031)were risk factors for NAS.When comparing complications between the two groups,GDA preservation was associated with a higher incidence of biliary NAS before and after PSM(P=0.031 and 0.017,respectively).In contrast,other complications including early allograft dysfunction(P=0.620),small-for-size graft syndrome(P=0.441),abdominal hemorrhage(P=1.000),major complications(Clavien-Dindo grade≥3,P=0.318),and overall survival(P=0.088)were not significantly different between the two groups.Conclusions:GDA disconnection during LT ameliorates biliary NAS incidence and may be recommended for application in clinical practice.

Ex vivo liver resection followed by autotransplantation in radical resection of gastric cancer liver metastases:A case report

BACKGROUND Radical resection of gastric cancer liver metastases(GCLM)can increase the 5-year survival rate of GCLM patients.However,patients may lose the theoretical feasibility of surgery due to the critical location of liver metastasis in some cases.CASE SUMMARY A 29-year-old woman had a chief complaint of chronic abdominal pain for 1 year.Abdominal computed tomography and magnetic resonance imaging examinations suggested a mass of unknown pathological nature located between the first and second hila and the margin of the lower segment of the right lobe of the liver.The anterior wall of the gastric antrum was unevenly thickened.The diagnosis of(gastric antrum)intramucosal well-differentiated adenocarcinoma was histopathologically confirmed by puncture biopsy with gastroscopy guidance.She underwent radical resection(excision of both gastric tumors and ex vivo liver resection followed by autotransplantation simultaneously)followed by XELOX adjuvant chemotherapy.Without serious postoperative complications,the patient was successfully discharged on the 20th day after the operation.Pathological examination of the excised specimen indicated that gastrectomy with D2 lymph node dissection for primary gastric tumors and R0 resection for liver metastases were achieved.The resected mass was confirmed to be poorly differentiated gastric carcinoma(hepatoid adenocarcinoma with neuroendocrine differentiation)with liver metastases in segments VIII.No recurrence or metastasis within the liver was found during a 7.5-year follow-up review that began 1 mo after surgery.CONCLUSION Application of ex vivo liver resection followed by autotransplantation in radical resection for GCLM can help selected patients with intrahepatic metastases located in complex sites obtain a favorable clinical outcome.

Neuron-glial antigen 2 overexpression in hepatocellular carcinoma predicts poor prognosis

AIM:To investigate whether neuron-glial antigen 2(NG2) could be an effective prognostic marker in hepatocellular carcinoma(HCC).METHODS:NG2 expression was semi-quantitatively scored from the immunohistochemistry(IHC) data based on the number of positive cells and the staining intensity.A total of 132 HCC specimens and 96 adjacent noncancerous tissue samples were analyzed by IHC for NG2 protein expression.To confirm the NG2 expression levels observed by IHC,we measured NG2 expression in 30 randomly selected tumor and adjacent noncancerous tissue samples by quantitative real-time polymerase chain reaction and Western blot.The correlations between NG2 protein expression and the clinicopathological features of HCC patients were analyzed using the χ2 test.To assess the prognostic value of NG2 for HCC,the association between NG2 expression and survival was analyzed using the KaplanMeier method with the log-rank test.To further evaluate the prognostic value of NG2 expression,a Cox multivariate proportional hazards regression analysis was performed with all the variables to derive risk estimates related to disease-free and overall survival and to control for confounders.RESULTS:High NG2 expression was observed in significantly more primary tumor samples(63.6%; 84/132) compared with the adjacent noncancerous tissue samples(28.1%; 27/96)(P < 0.0001).Moreover,high NG2 protein expression was closely associated with tumor differentiation(χ2 = 9.436,P = 0.0089),recurrence(χ2 = 5.769,P = 0.0163),tumor-nodemetastasis(TNM) stage(χ2 = 8.976,P = 0.0027),and invasion(χ2 = 5.476,P = 0.0193).However,no significant relationship was observed between NG2 protein expression in HCC and other parameters,such as age,sex,tumor size,serum alpha fetoprotein(AFP),tumor number,or tumor capsule.The log-rank test indicated a significant difference in the overall survival of HCC patients with high NG2 expression compared with those with low NG2 expression(29.2% vs 9.5%,P < 0.001).Moreover,NG2 expression in HCC tissue significantly correlated with disease-free survival(15.2% vs 6.7%,P < 0.001).Multivariate analysis showed that NG2 expression(HR = 2.035,P = 0.002),serum AFP(HR = 1.903,P = 0.003),TNM stage(HR = 2.039,P = 0.001),and portal vein invasion(HR = 1.938,P = 0.002) were independent prognostic indicators for OS in HCC patients.Furthermore,NG2 expression(HR = 1.974,P = 0.003),serum AFP(HR = 1.767,P = 0.008),TNM stage(HR = 2.078,P = 0.001),tumor capsule(HR = 0.652,P = 0.045),and portal vein invasion(HR = 1.941,P = 0.002) were independent prognostic indicators for DFS in HCC patients.CONCLUSION:The up-regulation of NG2 is associated with poor prognosis in HCC.Therefore,NG2 could be useful as an additional prognostic marker to increase the resolution of traditional approaches.

Hepatic sinusoidal obstruction syndrome induced by tacrolimus following liver transplantation:Three case reports

BACKGROUND Hepatic sinusoidal obstruction syndrome(HSOS)is a rare complication in solid organ transplant recipients,especially in liver transplantation recipients.However,the consequences of HSOS occurrence are pernicious,which could result in severe liver or renal failure,and even death.In addition to previously reported azathioprine and acute rejection,tacrolimus is also considered as one predisposing factor to induce HSOS after liver transplantation,although the underlying mechanism remains unclear.CASE SUMMARY In this study,we reported three cases of tacrolimus-related HSOS after liver transplantation.The diagnosis of HSOS was firstly based on the typical symptoms including ascites,painful hepatomegaly and jaundice.Furthermore,the features of patchy enhancement on portal vein and delayed phase of abdominal enhanced computed tomography were suspected of HSOS and ultimately confirmed by liver biopsy and histological examination in two patients.A significant decrease in ascites and remission of clinical symptoms of abdominal distention and pain were observed after withdrawal of tacrolimus.CONCLUSION Tacrolimus-induced HSOS is a scarce but severe complication after liver transplantation.It lacks specific symptoms and diagnostic criteria.Timely diagnosis of HSOS is based on clinical symptoms,radiological and histological examinations.Discontinuation of tacrolimus is the only effective treatment.Transplantation physicians should be aware of this rare complication potentially induced by tacrolimus.

Degradation of helicase-like transcription factor(HLTF)byβ-TrCP promotes hepatocarcinogenesis via activation of the p62/mTOR axis

Helicase-like transcription factor (HLTF) has been found to be involved in the maintenance of genome stability and tumoursuppression, but whether its downregulation in cancers is associated with posttranslational regulation remains unclear. Here, weobserved that HLTF was significantly downregulated in hepatocellular carcinoma (HCC) tissues and positively associated with thesurvival of HCC patients. Mechanistically, the decreased expression of HLTF in HCC was attributed to elevated β-TrCP-mediated ubiquitination and degradation. Knockdown of HLTF enhanced p62 transcriptional activity and mammalian target of rapamycin (mTOR)activation, leading to HCC tumourigenesis. Inhibition of mTOR effectively blocked β-TrCP overexpression- or HLTF knockdownmediated HCC tumourigenesis and metastasis. Furthermore, in clinical tissues, decreased HLTF expression was positively correlatedwith elevated expression of β-TrCP, p62, or p-mTOR in HCC patients. Overall, our data not only uncover new roles of HLTF in HCCcell proliferation and metastasis, but also reveal a novel posttranslational modification of HLTF by β-TrCP, indicating that theβ-TrCP/HLTF/p62/mTOR axis may be a new oncogenic driver involved in HCC development. This finding provides a potentialtherapeutic strategy for HCC patients by targeting the β-TrCP/HLTF/p62/mTOR axis.