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.

Primary duct closure versus T-tube drainage after laparoscopic common bile duct exploration:a meta-analysis

Background and aims:Laparoscopic common bile duct exploration(LCBDE)is considered a safe and effective method for the removal of bile duct stones.However,the choice of primary duct closure(PDC)or T-tube drainage(TTD)technique after LCBDE is still controversial.This study aimed to compare the safety and effectiveness of PDC and TTD after LCBDE.Methods:Studies published before May 1,2021 in Pub Med,Web of Science,and Cochrane Library databases were searched to screen out randomized controlled trials(RCTs)and cohort studies to compare PDC with TTD.Meta-analyses of fixed effect and random effect models were performed using Rev Man 5.3.Results:A total of 1865 patients were enrolled in six RCTs and ten cohort studies.Regarding RCTs,the PDC group was significantly better than the TTD group in terms of operation time,total postoperative complications,postoperative hospital stay,and hospitalization expenses(all P<0.05).Based on cohort studies of the subgroup,the PDC group had shorter operation time,shorter postoperative hospital stay,less intraoperative blood loss,and limited total postoperative complications.Statistically,there were no significant differences in bile leakage,retained stones,stone recurrence,bile duct stricture,postoperative pancreatitis,other complications,or postoperative exhaust time between the TTD and PDC groups.Conclusions:Based on the available evidence,compared with TTD,PDC is safe and effective,and can be used as the first choice after transductal LCBDE in patients with choledocholithiasis.

Clinicopathological and Prognostic Value of Programmed Cell Death 1 Expression in Hepatitis B Virus-related Hepatocellular Carcinoma:A Meta-analysis

Background and Aims:The efficacy of targeted programmed cell death 1/programmed death ligand 1(PD-1/PD-L1)monoclonal antibodies(mAbs)has been confirmed in many solid malignant tumors.The overexpression of PD-1/PD-L1 serves as a biomarker to predict prognosis and clinical progression.However,the role of PD-1 in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC)remains indeterminate.Given that HBV is the most important cause for HCC,this study aimed to investigate the prognostic and clinicopathological value of PD-1 in HBV-HCC via a meta-analysis.Methods:We searched PubMed,Embase,Scopus,the Cochrane Library,Web of Science and Google Scholar up to January 2021 for studies on the correlation between clinicopathology/prognosis and PD-1 in patients with HBV-HCC.The pooled hazard ratios(HRs)and 95%confidence intervals(CIs)were calculated to investigate the prognostic significance of PD-1 expression.The odds ratios(ORs)and 95%CIs were determined to explore the association between PD-1 expression and clinico-pathological features.Results:Our analysis included seven studies with 658 patients,which showed that high PD-1 expression was statistically correlated with poorer overall survival(HR=2.188,95%CI:[1.262-3.115],p<0.001)and disease-free survival(HR=2.743,95%CI:[1.980-3.506],p<0.001).PD-1 overexpression was correlated with multi-ple tumors(OR=2.268,95%CI:[1.209-4.257],p=0.011),high level of alpha fetoprotein(AFP;OR=1.495,95%CI:[1.005-2.223],p=0.047)and advanced Barcelona Clinic Liver Cancer(BCLC)stage(OR=3.738,95%CI:[2.101-6.651],p<0.001).Conclusions:Our meta-analysis revealed that the high level of PD-1 expression was associated with multiple tumors,high level of AFP and advanced BCLC stage.It significantly predicted a poor prognosis of HBV-HCC,which suggests that anti-PD-1 therapy for HBV-HCC patients is plausible.