Risk factor analysis of perioperative mortality after ruptured bleeding in hepatocellular carcinoma

AIM:To discuss strategies and prognosis for the emergency treatment of ruptured bleeding in primary hepatocellular carcinoma.METHODS:The retrospective analysis was performed by examining the emergency treatment experiences of60 cases of ruptured bleeding in primary hepatocellular carcinoma.The treatment methods included surgical tumour resection,transcatheter arterial embolization(TAE)and non-surgical treatment.Univariate and multivariate analyses were performed to identify the risk factors that impacted 30-d mortality in the research groups.RESULTS:The 30-d mortality of all patients was 28.3%(n=17).The univariate analysis showed that ChildPugh C level liver function,shock,massive blood transfusion and large tumour volume were risk factors thatinfluenced 30-d mortality.The multivariate analysis showed that shock and massive blood transfusion were independent risk factors that impacted the 30-d mortality of surgical resection.As for the TAE patients,larger tumour volume was a risk factor towards prognosis.CONCLUSION:Radical resection and TAE therapy would achieve better results in carefully selected ruptured hepatocellular tumours.

High incidence of biliary complications in rat liver transplantation:Can we avoid it?

AIM:To investigate how to reduce the incidence of biliary complications in rat orthotopic liver transplantation.METHODS:A total of 165 male Wistar rats were randomly divided into three groups:Group A,orthotropic liver transplantation with modified "two-cuff" technique;Group B,bile duct was cut and reconstructed without transplantation;and Group C,only laparotomy was performed.Based on the approaches used for biliary reconstruction,Group A was divided into two sub-groups:A1(n = 30),duct-duct reconstruction,and A2(n = 30),duct-duodenum reconstruction.To study the influence of artery reconstruction on bile duct complication,Group Bwas divided into four sub-groups:B1(n = 10),duct-duct reconstruction with hepatic artery ligation,B2(n = 10),duct-duct reconstruction without hepatic artery ligation,B3(n = 10),duct-duodenum reconstruction with hepatic artery ligation,and B4(n = 10),duct-duodenum reconstruction without hepatic artery ligation.The samples were harvested 14 d after operation or at the time when significant biliary complication was found.RESULTS:In Group A,the anhepatic phase was 13.7 ± 1.06 min,and cold ischemia time was 50.5 ± 8.6 min.There was no significant difference between A1 and A2 in the operation duration.The time for biliary reconstruction was almost the same among all groups.The success rate for transplantation was 98.3%(59/60).Significant differences were found in the incidence of biliary complications in Groups A(41.7%),B(27.5%) and C(0%).A2 was more likely to have biliary complications than A1(50% vs 33.3%).B3 had the highest incidence of biliary complications in Group B.CONCLUSION:Biliary complications are almost inevitable using the classical "two cuff" techniques,and duct-duodenum reconstruction is not an ideal option in rat orthotopic liver transplantation.

Anti-programmed cell death ligand 1-based immunotherapy in recurrent hepatocellular carcinoma with inferior vena cava tumor thrombus and metastasis:Three case reports

BACKGROUND Recurrent hepatocellular carcinoma(HCC)with inferior vena cava tumor thrombus is a great challenge for oncologists and has a poor prognosis.To date,the safety and efficacy of programmed cell death ligand 1(PD-L1)inhibitors are still unknown.CASE SUMMARY A 59-year-old male was identified as having a tumor thrombus in the inferior vena cava 3 years after surgery.The patient underwent a second surgery and adjuvant chemotherapy.However,the level of alpha-fetoprotein was elevated after 2 mo,and lung metastases and mediastinal lymph node metastases were identified.The expression of PD-L1 in HCC and inferior vena cava tumor thrombus tissues was analyzed by immunohistochemistry.Then,the patient received atezolizumab immunotherapy.The level of alpha-fetoprotein dropped to normal,the mediastinal lymph node metastases decreased in size and the lung metastases disappeared after 3 mo of immunotherapy.The patient had no signs of recurrence at 21 mo of follow-up.A 60-year-old male underwent left hepatic tumor resection,inferior vena cava incision and thrombus removal,followed by regular chemotherapy.The patient developed lung and splenic metastases after surgery.Pembrolizumab was used for six courses,and the splenic metastasis shrank,after which splenectomy was performed.The patient continued to receive pembrolizumab for thirteen courses,and the lung metastases showed no progression.A 34-year-old male was diagnosed with liver cancer with inferior vena cava tumor thrombus.The patient underwent right hepatectomy and received tislelizumab for three courses.He is still receiving immunotherapy and in good condition.CONCLUSION Anti-PD-L1 therapy in HCC patients with inferior vena cava tumor thrombus and metastasis is associated with relatively good patient outcomes.

Retraction Note:Dickkopf-1 contributes to hepatocellular carcinoma tumorigenesis by activating the Wnt/β-catenin signaling pathway

Retraction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-019-0082-5,published online 06 December 2019 The authors have retracted this article.After publication,concerns were raised regarding suspected overlap in the cell images in Figs.2 and 3.Specifically.

Dickkopf-1 contributes to hepatocellular carcinoma tumorigenesis by activating the Wnt/β-catenin signaling pathway

Dysregulation of dickkopf-related protein 1(DKK1)expression has been reported in a variety of human cancers.We previously reported that DKK1 was upregulated in hepatocellular carcinoma(HCC).However,the role of DKK1 in HCC remains unclear.This study aimed to investigate the clinical significance and biological functions of DKK1 in HCC.The expression of DKK1 was examined in cirrhotic and HCC tissues by immunohistochemistry and quantitative real-time polymerase chain reaction(qRT-PCR).DKK1 was silenced or overexpressed in HCC cell lines,and in vitro and in vivo studies were performed.Immunohistochemistry revealed that DKK1 was weakly expressed in cirrhotic tissues(8/22,36.4%)but upregulated in HCC tissues(48/53,90.6%,cohort 1).Significant upregulation of DKK1 was observed in 57.6%(19/33,cohort 2)of HCC tissues by qRT-PCR,and the expression of DKK1 was associated with tumor size(P=0.024)and tumor number(P=0.019).Genetic depletion of DKK1 impaired the proliferation,colony-forming ability,invasion,and tumor formation of HCC cells(HepG2 and HUH-7).Conversely,forced expression of DKK1 increased the proliferation,colony-forming ability,and invasion of HepG2 and HUH-7 cells in vitro and enhanced tumor formation in vivo.Subsequent investigation revealed that the DKK1-mediated proliferation and tumorigenicity of HepG2 and HUH-7 cells is dependent on the Wnt/β-catenin signaling pathway.These findings indicate that DKK1 plays an oncogenic role in HCC by activating the Wnt/β-catenin signaling pathway.

Clinical strategies for differentiating IgG4-related cholecystitis from gallbladder carcinoma to avoid unnecessary surgical resection

Immunoglobulin G4(IgG4)-related cholecystitis(IgG4-C)is often difficult to distinguish from gallbladder carcinoma(GBC).This study aimed to determine a practical strategy for differentiating between IgG4-C and GBC to avoid unnecessary surgical resection.The expression of IgG4 in the gallbladder was detected by immunohistochemistry.The clinicopathological and radiological characteristics of IgG4-C patients and GBC patients were analyzed retrospectively.Immunohistochemistry revealed that IgG4 was upregulated in the plasma cells of IgG4-C tissues.The median serum total bilirubin levels were significantly higher in the patients with IgG4-C than in those with GBC(45.8μmol L^-1 vs.29.9μmol L^-1).The serumγ-GGT levels were higher in IgG4-C patients than in GBC patients,whereas the serum levels of CA125 were significantly higher in GBC patients than in IgG4-C patients.The imaging scans were helpful for differentiating IgG4-C from GBC based on the presence of a layered pattern and Rokitansky-Aschoff sinuses in the gallbladder wall.There were no statistically significant differences in age,presence of abdominal pain,level of emaciation between the two groups.Our study demonstrated that the combination of imaging with serum total bilirubin,γ-GGTand CA125 levels can offer added preoperative diagnostic value and reduce the rate of IgG4-C misdiagnosis.

Hepatitis B Virus Surface Antigen Promotes Stemness of Hepatocellular Carcinoma through Regulating MicroRNA-203a

Background and Aims:Patients with persistent positive hepatitis B surface antigen(HBsAg),even with a low HBVDNA load,have a higher risk of hepatocellular carcinoma(HCC)than those without HBV infection.Given that tumor stemness has a critical role in the occurrence and maintenance of neoplasms,this study aimed to explore whether HBsAg affects biological function and stemness of HCC by regulating microRNA,and to explore underlying mechanisms.Methods:We screened out miR-203a,the most significant down-regulated microRNA in the microarray analysis of HBsAg-positive samples and focused on that miRNA in the ensuing study.In vitro and in vivo functional experiments were performed to assess its regulatory function.The effect of miR-203a on stemness and the possible correlation with BMI1 were analyzed in this study.Results:MiR-203a was significantly down-regulated in HBsAg-positive HCC with the sharpest decrease shown in microarray analysis.The negative correlation between miR-203a and HBsAg expression was confirmed by quantitative real-time PCR after stimulation or overexpression/knockdown of HBsAg in cells.We demonstrated the function of miR-203a in inhibiting HCC cell proliferation,migration,clonogenic capacity,and tumor development in vivo.Furthermore,the overexpression of miR-203a remarkably increases the sensitivity of tumor cells to 5-FU treatment and decreases the proportion of HCC cells with stem markers.In concordance with our study,the survival analysis of both The Cancer Genome Atlas database and samples in our center indicated a worse prognosis in patients with low level of miR-203a.We also found that BMI1,a gene maintains the self-renewal capacity of stem cells,showed a significant negative correlation with miR-203a in HCC specimen(p<0.001).Similarly,opposite BMI1 changes after overexpression/knockdown of miR203a were also confirmed in vitro.Dual luciferase reporting assay suggested that miR-203a may regulate BMI1 expression by direct binding.Conclusions:HBsAg may promote the development of HCC and tumor stemness by inhibiting miR-203a,resulting in poor prognosis.miR-203a may serve as a crucial treatment target in HBsAg-positive HCC.More explicit mechanistic studies and animal experiments need to be conducted as a next step.

利用剪切黏弹性模量对大鼠肝纤维化流变特性进行分析和建模(英文)

研究目的:肝脏的纤维化进程改变肝脏组织的流变属性。创新要点:本文利用剪切黏弹性模量描绘并比较了大鼠肝脏F0期到F4期的纤维化过程。研究方法:两个黏弹性模型,即Zener模型和Voigt模型用于解释流变力学测试得到的实验数据,由此得到每个纤维化分期的肝脏弹性和黏性值。重要结论:肝脏中度纤维化(≤F2期)与黏弹性值密切相关。Zener模型的弹性均值E1从F0期的(0.452±0.094)kPa增加到F2期的(1.311±0.717)kPa,而Voigt模型的弹性均值E从F0期的(0.618±0.089)kPa增加到F2期的(1.701±0.844)kPa。Zener模型的黏性均值从F0期的(3.499±0.186)Pa·s增加到F2期的(4.947±1.811)Pa·s,而Voigt模型的黏性均值从F0期的(3.379±0.316)Pa·s增加到F2期的(4.625±1.296)Pa·s。无论选用哪个黏弹性模型,在F1期和F2期,肝脏弹性值的标准差比黏性值的标准差变化要小。因此,测得的弹性比黏性更有效地区分肝纤维化F0期到F2期。