Glutamine synthetase-negative hepatocellular carcinoma has better prognosis and response to sorafenib treatment after hepatectomy

Background:Glutamine synthetase(GS)and arginase 1(Arg1)are widely used pathological markers that discriminate hepatocellular carcinoma(HCC)from intrahepatic cholangiocarcinoma;however,their clinical significance in HCC remains unclear.Methods:We retrospectively analyzed 431 HCC patients:251 received hepatectomy alone,and the other 180 received sorafenib as adjuvant treatment after hepatectomy.Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining.mRNA sequencing and immunostaining to detect progenitor markers(cytokeratin 19[CK19]and epithelial cell adhesion molecule[EpCAM])and mutant TP53 were also conducted.Results:Up to 72.4%(312/431)of HCC tumors were GS positive(GS+).Of the patients receiving hepatectomy alone,GS negative(GS-)patients had significantly better overall survival(OS)and recurrence-free survival(RFS)than GS+patients;negative expression of Arg1,which is exclusively expressed in GS-hepatocytes in the healthy liver,had a negative effect on prognosis.Of the patients with a high risk of recurrence who received additional sorafenib treatment,GS-patients tended to have better RFS than GS+patients,regardless of the expression status of Arg1.GS+HCC tumors exhibit many features of the established proliferation molecular stratification subtype,including poor differentiation,high alpha-fetoprotein levels,increased progenitor tumor cells,TP53 mutation,and upregulation of multiple tumor-related signaling pathways.Conclusions:GS-HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy.Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.

Can a laparoscopic surgery be an alternative to transjugular intrahepatic portosystemic shunts (TIPS) for the treatment of portal hypertensive bleeding?

We read with great confusion the guidance written by Garcia-Tsao et al.(1).In the practice guidance developed by the American Association for the Study of Liver Diseases(AASLD),there is no trail of surgical operation for the treatment of portal hypertensive bleeding in cirrhosis at all.However,it is well known that surgical shunts played an important role in this setting before the emergence of transjugular intrahepatic portosystemic shunts(TIPS),existing studies have shown that surgical shunt still has better long-term patency and survival than TIPS(2),and surgical portoazygous devascularization is still considered as the most direct and effective way of hemostasis in some countries(3).

Chinese expert consensus on conversion therapy for hepatocellular carcinoma(2021 edition)

Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.

Tenofovir vs.entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy

Background:Hepatectomy for hepatocellular carcinoma(HCC)beyond the Milan criteria is shown to be beneficial.However,a high rate of post-operative HCC recurrence hinders the long-term survival of the patients.This study aimed to investigate and compare the impacts of tenofovir(TDF)and entecavir(ETV)on the recurrence of hepatitis B viral(HBV)-related HCC beyond the Milan criteria.Methods:Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers.Recurrence-free survival(RFS)analysis was performed using the Kaplan-Meier method.Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence.Results:The analysis incorporates 595 HBV-related HCC patients.The overall 5-year RFS was 21.3%.Among them,533 and 62 patients received ETV and TDF treatment,respectively.The 1-,3-,and 5-year RFS rates were 46.3%,27.4%,and 19.6%,respectively,in the ETV group compared with 65.1%,41.8%,and 37.2%,respectively,in the TDF group(P<0.001).Multivariate analysis showed that TDF treatment(hazard ratio[HR]:0.604,P=0.005),cirrhosis(HR:1.557,P=0.004),tumor size(HR:1.037,P=0.008),microvascular invasion(MVI)(HR:1.403,P=0.002),portal vein tumor thrombus(PVTT)(HR:1.358,P=0.012),capsular invasion(HR:1.228,P=0.040),and creatinine levels(CREA)(HR:0.993,P=0.031)were statistically significant prognostic factors associated with RFS.Conclusions:Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy.Compared to the ETV therapy,TDF administration significantly lowered the risk of HCC recurrence.

Multidisciplinary management of recurrent and metastatic hepatocellular carcinoma after resection: an international expert consensus

Hepatocellular carcinoma (HCC) is the sixth-most common cancer and the third leading cause of cancer-related death in the world. However, 40–70% patients eventually suffer from postoperative recurrence within 5 years. HCC recurrence after surgery severely affects prognosis of the patients. Nevertheless, there is an opportunity to improve patients' prognosis if doctors and researchers can recognize the importance of a standardized perioperative management and study it in clinical and pre-clinical settings. Hence, based on our own experience and published studies from other researchers, we develop this consensus regarding multidisciplinary management of locally recurrent and metastatic hepatocellular carcinoma after resection. This consensus consists of the entire course of recurrent hepatocellular carcinoma (RHCC) management, including prediction of recurrence, prevention, diagnosis, treatment and surveillance of RHCC. Consensus recommendations are presented with grades of evidences (Ia, Ib, IIa, IIb, III and IV), and strength ofrecommendations (A, B, C, D and E). We also develop a decision-making path for RHCC treatment, which can intuitively demonstrate the management for RHCC. It is hoped that we may make some effort to standardize the management of RHCC and ultimately understand how to improve outcomes.

Use of donor-specific red blood cell transfusions for patients undergoing liver transplantation during the COVID-19 pandemic

Background:Increased risks have been found for patients undergoing liver transplantation due to the blood supply shortage following the ongoing coronavirus disease 2019(COVID-19)pandemic.Hence,exploring a method to alleviate this dilemma is urgent.This phase I,nonrandomized,prospective trial aimed to evaluate the safety and feasibility of using donor-specific red blood cell transfusion(DRBCT)as an urgent measurement to alleviate the blood supply shortage in deceased donor liver transplantation(DDLT).Methods:The outcomes of 26 patients who received DRBCT and 37 patients in the control group who only received 3rd party packed red blood cells(pRBCs)transfusion between May 2020 and January 2021 were compared.Results:Patients receiving DRBCT did not develop transfusion-related complications,and the incidence of postoperative infection was similar to that in the control group(23.1%vs.18.9%,P=0.688).Because the patients received the red blood cells from organ donors,the median volume of intraoperative allogeneic red blood cell transfusion from blood bank was 4.0 U(IQR 1.1-8.0 U)in the DRBCT group,which is significantly lower than that(7.5 U,IQR 4.0-10.0 U)in the control group(P=0.018).The peak aspartate aminotransferase(AST)level was significantly lower in the DRBCT group than in the control group(P=0.008)and so were the AST levels in the first two days after the operation(P=0.006 and P=0.033).Conclusions:DRBCT is a safe and effective procedure to lower the need for blood supply and is associated with a reduction in AST levels after transplantation.DRBCT is beneficial to patients receiving life-saving transplantation without sufficient blood supply during the COVID-19 pandemic.

Conversion resection for patients with hepatocellular carcinoma and inferior vena cava tumor thrombus: a consecutive case series

To the Editor:The incidence of hepatocellular carcinoma(HCC)with inferior vena cava tumor thrombus(IVCTT)is.approximately 1.4%.Owing to direct cancercll dissemination into the systemic circulation,HCC-IVCTT is frequently associated with synchronous and metachronous extrahepatic metastasis.Without treatment,the median survival time is only 3 months for patients with HCC-IVCTT.

Reducing biliary complications in adult-to-adult living donor liver transplantation using right lobe graft:experience of 124 cases

The aim of this paper is to summarize our experience of using right lobe liver grafts to reduce biliary complications in adult-to-adult(A-A)living donor liver transplantation(LDLT).From January 2002 to October 2007,124 adult patients underwent living donor liver transplantation using right lobe grafts at the West China Hospital,Sichuan University Medical School,China.There was no death in all donors.Biliary reconstruction for 178 hepatic duct orifices from 124 donor grafts was performed which included 106 reconstructions of duct-to-duct anastomoses and 72 cholangiojejunostomy.Nine recipients had biliary complications including six bile lea-kages(four from the anastomotic site and two from the cut surface of the liver graft)and three biliary strictures.With the improved techniques for biliary reconstruction,we have achieved good results in 124 recipients of A-A LDLT.We ascribe our success to the introduction of microsurgical techniques and the use of fixed operators which help in decreasing the biliary complications of LDLT.

Safety of elective hepatectomy performed on weekend for patients with hepatocellular carcinoma

The incidence of hepatocellular carcinoma(HCC)is increasing year by year.The International Agency for Research on Cancer(IARC)reported that more than 630,000 people were diagnosed with HCC in 2020 and more than half of new cases of HCC were in China.The increasing number of patients overburdens the medical system and the waiting time before the surgery becomes longer and longer.This poses a new challenge to the applicability of traditional surgical management model.The elective surgery performed on weekend could provide an efficient solution to the problem.However,the safety of weekend surgery is controversial because surgical patients have a higher severe complication incidence and postoperative mortality on the weekend compared to the weekday(ie,weekend effect).