Impact of human leukocyte antigen mismatching on outcomes of liver transplantation:A meta-analysis

AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies.METHODS:Articles in PubMed/MEDLINE,EMBASE and the Cochrane database from January 1970 to June 2009,including non-English literature identified in these databases,were searched.Only studies comparing HLA or sub-phenotype matching with mismatching were extracted.The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed.A meta-analysis was performed when at least 3 studies provided data.RESULTS:Sixteen studies met the inclusion criteria.A lower number of HLA mismatches(0-2 vs 3-6) did reduce the incidence of acute rejection(relative risk:0.77,P = 0.03).The degree of HLA mismatching(0-2 vs 3-6) had no significant effect on 1-year [hazard ratio(HR):1.04,P = 0.68] and 5-year(HR:1.09,P = 0.38) graft survival.In sub-phenotype analysis,the degree of HLA-A,B and DR mismatching(0 vs 1-2) had no significant effect on 1-year and 5-year graft survival,either.The HRs and P-values were 0.95,0.71(HLA-A,1-year);1.06,0.60(HLA-A,5-year);0.77,0.16(HLA-B,1-year);1.07,0.56(HLA-DR,1-year);1.18,0.23(HLADR,5-year),respectively.CONCLUSION:The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes.To obtain a short recovery time and minimize rejection post transplantation,HLA matching studies should be considered before the operation.

Malaria after living donor liver transplantation:report of two cases

BACKGROUND:Infectious complications are common during the postoperative course of a liver transplant recipient. Malaria, however, is a rare complication in such a setting. METHOD:We report post-transplantation malaria causing elevation of liver enzymes in two recipients. RESULTS:Both patients who had undergone living donor liver transplantation showed elevated levels of liver enzymes and fever during the postoperative course. Investigations (including liver biopsy in one patient) were initially inconclusive in determining the cause of liver dysfunction. The diagnosis of malaria was established in both cases by peripheral blood smear. Liver function transiently worsened with antimalarial treatment but subsequently became normal. CONCLUSION:This report highlights the importance of excluding such uncommon causes of post-transplantation liver dysfunction, especially when either the recipient or the donor comes from a region endemic for malaria.

Impact of neoadjuvant multimodal therapy in the setting of locally advanced hepatocellular carcinoma

Immunotherapy and the implementation of more aggressive treatment schemes for locally advanced hepatocellular carcinomas have expanded the boundaries of curative options.Because of these advancements,patients who were once considered beyond the aim of a cure are now eligible for liver transplantation and resection.

Helicobacter species sequences in liver samples from patients with and without hepatocellular carcinoma

AIM:Only a minority of patients carrying a defined viral aetiologic agent develop cirrhosis and ultimately hepatocellular carcinoma (HCC), the mechanism underlying the worsening is still undefined. Experimental infection by Helicobacter hepaticusin mice causes chronic hepatitis and HCC and recently, more Helicobacter species (Helicobacter spp.) have been detected in the liver of patients suffering from cholestatic diseases and HCC arising from non-cirrhotic liver. We investigated whether Helicobacter spp. sequences could be detected in the liver of patients with cirrhosis and HCC compared to subjects with metastasis to liver from colon cancer.METHODS:Twenty-three liver samples from patients operated upon for HCC superimposed on hepatitis C virus (HCV)-related cirrhosis and 6 from patients with resected metastases from colorectal cancer, were tested by polymerase chain reaction for presence of genomic 16S rRNA of Helicobacter genus using specific primers. DNA sequencing and cagA gene analysis were also performed.RESULTS:Genomic sequences of Helicobacter spp. were found in 17 of 20 (85%) liver samples from patients with HCC and in 2 of 6 samples from patients with liver metastasis.In three samples of the first group the result was uncertain.Hpyloriwas revealed in 16 out of 17 positive samples and Helicobacter pullorum in the other.CONCLUSION: Helicobacter spp., carcinogenic in mice,were found at a higher frequency in the liver of patients with HCV-related cirrhosis and HCC than those in patients without primary liver disease.

Embolization of liver tumors:Past,present and future

Curative therapies for hepatocellular carcinoma(HCC),such as resection and liver transplantation,can only be applied in selected patients with early tumors.More advanced stages require local or systemic therapies.Resection of HCC offers the only hope for cure.Even in patients undergoing resection,recurrences are common.Chemoembolization,a technique combining intraarterial chemotherapy with selective tumor ischemia,has been shown by randomized controlled trials to be efficacious in the palliative setting.There is now renewed interest in transarterial embolization/transarterial chemoembolization(TACE) with regards to its use as a palliative tool in a combined modality approach,as a neoadjuvant therapy,in bridging therapy before transplantation,for symptomatic indications,and even as an alternative to resection.There have also been rapid advances in the agents being embolized trans-arterially(genes,biological response modifiers,etc.).The current review provides an evidence-based overview of the past,present and future trends of TACE in patients with HCC.

Surgical management of liver diseases invading the hepatocaval confluence based on IH classification: The surgical guideline in our center

AIM To investigate the short-term outcomes and risk factors indicating postoperative death of patients with lesions adjacent to the hepatocaval confluence.METHODS We retrospectively analyzed 54 consecutive patients who underwent hepatectomy combined with inferior vena cava(IVC)and/or hepatic vein reconstruction(HVR)from January 2012 to January 2016 at our liver surgery center.The patients were divided into5 groups according to the range of IVC and hepatic vein involvement.The patient details,indications for surgery,operative techniques,intra-and postoperative outcomes were compared among the 5 groups.Univariate and multivariate analyses were performed to explore factors predictive of overall operative death.RESULTS IVC replacement was carried out in 37(68.5%)patients and HVR in 17(31.5%)patients.Type I2H2 had the longest operative blood loss,operative duration and overall liver ischemic time(all,p<0.05).Three patients of Type I3H1 with totally occluded IVC did not need IVC reconstruction.Total postoperative morbidity rate was40.7%(22 patients)and the operative mortality rate was 16.7%(9 patients).Factors predictive of operative death included IVC replacement(p=0.048),duration of liver ischemia(p=0.005)and preoperative liver function being Child-pugh B(p=0.025). CONCLUSION IVC replacement,duration of liver ischemia and preoperative poor liver function were risk factors predictive of postoperative death.We should be cautious about IVC replacement,especially in Type I2H2.For Type I3H1,it was unnecessary to replace IVC when the collateral circulation was established.

Standard liver weight model in adult deceased donors with fatty liver: A prospective cohort study

BACKGROUND Standard liver weight(SLW)is frequently used in deceased donor liver transplantation to avoid size mismatches with the recipient.However,some deceased donors(DDs)have fatty liver(FL).A few studies have reported that FL could impact liver size.To the best of our knowledge,there are no relevant SLW models for predicting liver size.AIM To demonstrate the relationship between FL and total liver weight(TLW)in detail and present a related SLW formula.METHODS We prospectively enrolled 212 adult DDs from West China Hospital of Sichuan University from June 2019 to February 2021,recorded their basic information,such as sex,age,body height(BH)and body weight(BW),and performed abdominal ultrasound(US)and pathological biopsy(PB).The chi-square test and kappa consistency score were used to assess the consistency in terms of FL diagnosed by US relative to PB.Simple linear regression analysis was used to explore the variables related to TLW.Multiple linear regression analysis was used to formulate SLW models,and the root mean standard error and interclass correlation coefficient were used to test the fitting efficiency and accuracy of the model,respectively.Furthermore,the optimal formula was compared with previous formulas.RESULTS Approximately 28.8%of DDs had FL.US had a high diagnostic ability(sensitivity and specificity were 86.2%and 92.9%,respectively;kappa value was 0.70,P<0.001)for livers with more than a 5%fatty change.Simple linear regression analysis showed that sex(R2,0.226;P<0.001),BH(R2,0.241;P<0.001),BW(R2,0.441;P<0.001),BMI(R2,0.224;P<0.001),BSA(R2,0.454;P<0.001)and FL(R2,0.130;P<0.001)significantly impacted TLW.In addition,multiple linear regression analysis showed that there was no significant difference in liver weight between the DDs with no steatosis and those with steatosis within 5%.Furthermore,in the context of hepatic steatosis,TLW increased positively(nonlinear);compared with the TLW of the non-FL group,the TLW of the groups with hepatic steatosis within 5%,between 5%and 20%and more than 20%increased by 0 g,90 g,and 340 g,respectively.A novel formula,namely,-348.6+(110.7 x Sex[0=Female,1=Male])+958.0 x BSA+(179.8 x FLUS[0=No,1=Yes]),where FL was diagnosed by US,was more convenient and accurate than any other formula for predicting SLW.CONCLUSION FL is positively correlated with TLW.The novel formula deduced using sex,BSA and FLUS is the optimal formula for predicting SLW in adult DDs.

Synchronous splenectomy and hepatectomy for patients with hepatocellular carcinoma and hypersplenism:A casecontrol study

AIM:To investigate whether the use of synchronoushepatectomy and splenectomy(HS)is more effective than hepatectomy alone(HA)for patients with hepatocellular carcinoma(HCC)and hypersplenism.METHODS:From January 2007 to March 2013,84consecutive patients with HCC and hypersplenism who underwent synchronous hepatectomy and splenectomy in our center were compared with 84 well-matched patients from a pool of 268 patients who underwent hepatectomy alone.The short-term and longterm outcomes of the two groups were analyzed and compared.RESULTS:The mean time to recurrence was 21.11±12.04 mo in the HS group and 11.23±8.73 mo in the HA group,and these values were significantly different(P=0.001).The 1-,3-,5-,and 7-year disease-free survival rates for the patients in the HS group and the HA group were 86.7%,70.9%,52.7%,and 45.9%and 88.1%,59.4%,43.3%,and 39.5%,respectively(P=0.008).Platelet and white blood cell counts in the HS group were significantly increased compared with the HA group one day,one week,one month and one year postoperatively(P<0.001).Splenectomy and micro-vascular invasion were significant independent prognostic factors for disease-free survival.Gender,tumor number,and recurrence were independent prognostic factors for overall survival.CONCLUSION:Synchronous hepatectomy and hepatectomy potentially improves disease-free survival rates and alleviates hypersplenism without increasing the surgical risks for patients with HCC and hypersplenism.

A gist of gastrointestinal stromal tumors: A review

Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.

Contrast-enhanced ultrasound:Improving the preoperative staging of hepatocellular carcinoma and guiding individual treatment

AIM:To investigate the clinical role of contrast-enhanced ultrasound(CEUS) combined with contrast-enhanced computed tomography(CE-CT) or magnetic resonance imaging to improve the preoperative staging of hepatocellular carcinoma(HCC) and guide surgical decisionmaking.METHODS:Sixty-nine patients who underwent liver resection for HCC in our center were enrolled prospectively in the study.CEUS and CE-CT/MRI were performed before surgery.Intraoperative ultrasound(IOUS)wascarried out after liver mobilization.Lesions depicted by each imaging modality were counted and mapped.To investigate the impact of tumor size on the study,we divided the patients into two groups,the"Smaller group"(S-group,≤5 cm in diameter)and the"Largergroup"(L-group,>5 cm in diameter).The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of CE-CT/MRI,CEUS,IOUS,CEUS+CE-CT/MRI and the tumor node metastasis staging of tumors were calculated and compared.Changes in the surgical strategy as a result of CEUS and IOUS were analyzed.RESULTS:One hundred and twenty-seven nodules,comprising 94 HCCs confirmed by histopathology and33 benign lesions confirmed by histopathology and follow-up,were identified in 69 patients.The overall diagnostic sensitivity rates of CE-CT/MRI,CEUS,IOUS and CEUS+CE-CT/MRI were 78.7%,89.4%,89.4%and 89.4%,respectively.There was a significant difference between CEUS+CE-CT/MRI and CE-CT/MRI(P=0.046).Combining CEUS with CT or MRI increased,the diagnostic specificity compared with CT/MRI,CEUS and IOUS,and this difference was statistically significant(100%,72.7%,97.0%,and 69.7%,P=0.004,P=0.002,P=0.002,respectively).The diagnostic accuracy was significantly higher for CEUS+CT/MRI compared with CT/MRI(92.1%vs 77.2%,P=0.001).The TNM staging of tumors based on CEUS+CE-CT/MRI approximated to the final pathological TNM staging(P=0.977).There was a significant difference in the accuracy of TNM staging when comparing CEUS+CECT/MRI with CE-CT/MRI(P=0.002).Before surgery,strategies were changed in 15.9%(11/69)of patients as a result of CEUS.Finally,only 5.7%(4/69)of surgical strategies were changed because of IOUS findings.In the S-group,CEUS revealed 12 false positive lesions,including seven false positive lesions that were diagnosedby preoperative imaging examinations and five by IOUS.In contrast,in the L-group,IUOS revealed eight new malignant lesions;six of these lesions were true HCCs that were also identified by preoperative CEUS.CONCLUSION:CEUS combined with CT or MRI improves the accuracy of preoperative staging for hepatocellular carcinoma and may help to guide individualized treatment for patients with HCC.CEUS may better identify non-malignant lesions in patients with small tumors and discover new malignant lesions in patients with large tumors.

p53-expressing conditionally replicative adenovirus CNHK500-p53 against hepatocellular carcinoma in vitro

AIM: To develop a conditionally replicative gene-viral vector system called CNHK500-p53, which contains dual promoters within the E1 region, and combines the advantages of oncolytic virus and gene therapies for hepatocellular carcinoma (HCC). METHODS: CNHK500-p53 was constructed by using human telomerase reverse transcriptase (hTERT) promoter to drive adenovirus E1 a gene and hypoxia response element (HRE) promoter to drive adenovirus E1b gene. p53 gene expressing cassette was inserted into the genome of replicative virus. Viral replication experiments, cytopathic effect (CPE) and methyl thiazolyl tetrazolium (MTT) assay were performed to test the selective replication and oncolytic efficacy of CNHK500-p53.RESULTS: Immunohistochemistry verified that infection with CNHK500-p53 was associated with selective replication of adenovirus and production of p53 protein in telomerase-positive and hypoxia-inducible factor-dependent HCC cells. p53 protein secreted from HepG2, infected with CNHK500-p53 was significantly higher than that infected with nonreplicative adenovirus Ad-p53 in vitro (388 ± 34.6 μg/L vs 76.3 ± 13.17 μg/L). Viral replication experiments showed that replication of CNHK500-p53 and CNHK500 or WtAd5, was much stronger than that of Ad-p53 in tested HCC cell lines. CPE and MTT assay indicated that CNHK500-p53 selectively replicated in and killed HCC cells while leaving normal cells unaffected. CONCLUSION: A more efficient gene-viral system is developed by combining selective oncolysis with exogenous expression of p53 against HCC cells.

Misdiagnosis of left supraclavicular lymph node metastasis of hepatocellular carcinoma:A case report

Left supraclavicular lymph node metastasis is a rare presentation of hepatocellular carcinoma (HCC).This phenomenon is easily neglected in the clinic.A 56-yearold man presented with HCC.On examination,a 1cm long left supraclavicular lymph node was palpated.Auxiliary examination indicated a lesion located in the right lobe of the liver.Fine needle aspiration cytology (FNAC) of the enlarged lymph node was performed;however,only necrosis was found.Hepatectomy was performed and HCC was confirmed by Hematoxylin-Eosin staining.However,14 d after surgery,significantly enlarged left supraclavicular lymph nodes,a new intrahepatic lesion,and pulmonary and mediastinal metastasis appeared.An excisional biopsy of the left supraclavicular lymph node was performed,and its findings confirmed metastatic HCC.The patient's HCC rapidly progressed and he died one month later.It is possible for HCC tometastasize to the left supraclavicular lymph node.Surgeons should always consider an overall physical examination.When left supraclavicular lymphadenopathy of unknown origin is encountered,FNAC should be performed initially.If the results are negative,an excisional biopsy and subsequent Positron emission tomography computed tomography scanning should be performed.These are very important for making the correct diagnosis and for selecting reasonable therapies.

Incidental gall bladder cancers:Are they truly incidental?

AIM: To seek and analyze features suggestive of gallbladder cancer(GBC) on preoperative imaging and intraoperative findings in patients diagnosed as having incidental GBC(IGBC). METHODS: The study was conducted on 79 patients of IGBC managed in our department over a 10-year period(2003-2012). Review of preoperative imaging and operative notes was done to ascertain any suspicion of malignancy-in-retrospect.RESULTS: Of the 79 patients, Ultrasound abdomen showed diffuse thickening, not suspicious of malignancy in 5 patients, and diffuse suspicious thickening was seen in 4 patients. Focal thickening suspicious of malignancy was present in 24 patients. Preoperative computed tomography/magnetic resonance imaging was done in 9 patients for suspicion of malignancy. In 5 patients, dif-ficult Cholecystectomy was encountered due to dense/inflammatory adhesions. Intraoperative findings showed focal thickening of the gallbladder and a gallbladder mass in 9 and 17 patients respectively. On overall analysis, 37 patients had preoperative imaging or intraoperative findings suggestive of malignancy, which was either a missed GBC or an unsuspected/unexpected GBC. In 42(53.2%) patients, there was no evidence suggestive of malignancy and was an unanticipated diagnosis.CONCLUSION: Our study highlights a potential and not-so-rare pitfall of Laparoscopic Cholecystectomy. A greater awareness of this clinical entity along with a high index of suspicion and a low threshold for conversion to open procedure, especially in endemic areas may avert avoidable patient morbidity and mortality.

Implications of the presence of an aberrant right hepatic artery in patients undergoing pancreaticoduodenectomy

AIM:To analyze the differences in outcomes and the clinical impact following pancreatoduodenectomy(PD)in patients with and without aberrant right hepatic artery(aRHA).METHODS:All patients undergoing PD between January 2008 and December 2012 were divided into two groups,one with aRHA and the other without.These groups were compared to identify differences in the intraoperative variables,the oncological clearance and the postoperative morbidity,mortality and hospital stay.RESULTS:A total of 225 patients underwent PD,of which 43(19.1%)patients were found to have eitheraccessory or replaced right hepatic arteries(aRHA group).The aRHA was preserved in 79%of the patients.There was no significant difference in the intraoperative blood loss but operative time was prolonged,reflecting the complexity of the procedure[420±44(240-540)min vs 480±45(300-600)min,P<0.05)].There were no differences in the incidence of postoperative complications(pancreatic leak,pancreatic fistula,delayed gastric emptying and mortality)and hospital stay.Oncological clearance in the form of positive resection margins[13(7.1%)vs 3(6.9%)]and lymph node yield were also similar in the two groups.CONCLUSION:An aRHA is found in approximately one fifth of patients undergoing PD.Preservation is technically possible in most patients and can increase the operative complexity but does not negatively affect the safety or oncological outcomes of the procedure.

Occurrence of cGMP/nitric oxide-sensitive store-operated calcium entry in fibroblasts and its effect on matrix metalloproteinase secretion

AIM: To examine the existence of Nitric oxide/ cGMP sensitive store-operated Ca2+ entry in mouse fibroblast NIH/3T3 cells and its influence on matrix metalloproteinase (MMP) production and adhesion ability of fi broblasts. METHODS: NIH/3T3 cells were cultured. Confocal laser scanning microscopy was used to examine the existence of thapsigargin-induced store-operated Ca2+ entry in fibroblasts. Gelatin zymography and semiquantitative reverse transcriptase-polymerase chain reaction (RT- PCR) were employed to detect the involvement of [Ca2+]i and NO/cGMP in MMP secretion. The involvement of NO/ cGMP-sensitive Ca2+ entry in adhesion was determined using matrigel-coated culture plates. RESULTS: 8-bromo-cGMP inhibited the thapsigargin- induced Ca2+ entry in 3T3 cells. The cGMP-induced inhibition was abolished by an inhibitor of protein kinase G, KT5823 (1μmol/L). A similar effect on the Ca2+ entry was observed in 3T3 cells in response to a NO donor, (±)-S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin-induced Ca2+ entry was also observed, indicating NO/cGMP- regulated Ca2+ entry in 3T3 cells. Results of gelatin zymography assay showed that addition of extracellular Ca2+ concentration induced MMP release and activation in a dose-dependent manner. RT-PCR also showed that cGMP and SNAP reduced the production of MMP mRNA in 3T3 cells. Experiments investigating adhesion potentials demonstrated that cGMP and SNAP could upgrade 3T3 cell attachment rate to the matrigel-coated culture plates.CONCLUSION: NO/cGMP sensitive store-operated Ca2+ entry occurs in fi broblasts, and attenuates their adhesion potentials through its in? uence on MMP secretion.

Development and validation of an artificial intelligence model for predicting post-transplant hepatocellular cancer recurrence

Dear Editor,In recent years,criteria based on the combinationof morphology and biology have been proposed forimproving the selection of hepatocellular cancer(HCC)patients waiting for liver transplantation(LT)[1,2].Since all the proposed models showed suboptimalresults in predicting the risk of postLT recurrence,aprediction model constructed using artificial intelligence(Al)could be an attractive way to surpass this limit[3,4].Therefore,the Time_Radiological-response_Alpha-fetoproteIN_Artificial-Intelligence(TRAIN-AI)modelwas developed,combining morphology and biology tumorvariables.

Establishment of hepatocellular carcinoma multidrug resistant monoclone cell line HepG2/mdr1

Background The multidrug resistance （MDR） associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell （HCC） patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1. Methods The 4.5-kb mdrl cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCl-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein （Pgp） in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated. Results The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of mdrl cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were （59.7±7.9）% and （12.28±2.09）%, respectively, compared with （16.9±3.2）% and （3.07±1.06）% in HepG2 cells. In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours. Conclusion The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the experimental basis of MDR research.

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.