Selective internal radiation therapy segmentectomy:A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long periods.Locoregional therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting LT.Although largely used in the past,transarterial embolization(TAE)has been replaced by transarterial chemoembolization(TACE).However,the superiority of TACE over TAE has not been consistently shown in the literature.AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT.METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included.All patients underwent LRT with either TACE or TAE.Some patients also underwent percutaneous ethanol injection(PEI),concom-itantly or in different treatment sessions.The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus.The primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse events.In the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also assessed.RESULTS Twelve(18.5%)patients in the TACE group(only TACE and TACE+PEI;n=65)and 3(7.9%)patients in the TAE group(only TAE and TAE+PEI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACE and TAE groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACE group and 29(76.3%)of the 38 patients in the TAE group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACE and TAE groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACE and TAE groups,respectively(P=0.756).Posttransplant recurrence-free survival was similar between the groups(P log-rank test=0.71).CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC.Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

Conversion therapy in liver transplantation for hepatocellular carcinoma:What's new in the era of molecular and immune therapy?

Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic treatments,fast development of targeted drugs,the success of immunotherapy,as well as the emergence of the therapeutic alliance,conversion therapy has recently become more well developed and an effective therapeutic strategy.This article aimed to review recent developments in conversion therapy in liver transplantation(LT)for HCC.Data sources:We searched for relevant publications on Pub Med before September 2022,using the terms“HCC”,“liver transplantation”,“downstaging”,“bridging treatment”and“conversion therapy.”Results:Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT.Although combining various local and systematic treatments in conversion therapy is still controversial,growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time,which ultimately increases the opportunities for LT.Moreover,the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors.Conclusions:In the era of targeted therapy and immunotherapy,applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients.With the expansion of conversion therapy concepts,further investigation and research is required to realize the full potential of conversion treatment strategies,including accurately selecting candidates,determining the timing of surgery,improving the conversion rate,and guaranteeing the safety and long-term efficacy of treatment.

Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature

BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.

Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions

Clinically,it is highly challenging to promote recovery in patients with acute liver failure(ALF)and acute-on-chronic liver failure(ACLF).Despite recent advances in understanding the underlying mechanisms of ALF and ACLF,standard medical therapy remains the primary therapeutic approach.Liver transplantation(LT)is considered the last option,and in several cases,it is the only intervention that can be lifesaving.Unfortunately,this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant.Another option is to restore impaired liver function with artificial extracorporeal blood purification systems.The first such systems were developed at the end of the 20th century,providing solutions as bridging therapy,either for liver recovery or LT.They enhance the elimination of metabolites and substances that accumulate due to compromised liver function.In addition,they aid in clearance of molecules released during acute liver decompensation,which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy,multiple-organ failure,and other complications of liver failure.As compared to renal replacement therapies,we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems.Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging.The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins.Furthermore,conventional methods such as plasma exchange are being re-evaluated,and novel adsorption filters are increasingly being used for liver indications.These strategies are very promising for the treatment of liver failure.Nevertheless,the best method,system,or device has not been developed yet,and its probability of getting developed in the near future is also low.Furthermore,little is known about the effects of liver support systems on the overall and transplant-free survival of these patients,and further investigation using randomized controlled trials and meta-analyses is needed.This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy.It focuses on general principles of their function,and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF.In addition,we have outlined the basic advantages and disadvantages of each system.

Comprehensive Treatment Uncertainty Analysis and PTV Margin Estimation for Fiducial Tracking in Robotic Liver Stereotactic Body Radiation Therapy

Objective This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy(SBRT)cases,and evaluate the required planning target volume(PTV)margins.Methods A total of 11 liver tumor patients with a total of 57 fractions,who underwent SBRT with synchronous fiducial tracking,were enrolled for the present study.The correlation/prediction model error,geometric error,and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties.The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment.Results The correlation model error-related uncertainty was 4.3±1.8,1.4±0.5 and 1.8±0.7 mm in the superior-inferior(SI),left-right,and anterior-posterior directions,respectively.These were the primary contributors among all uncertainty sources.The geometric error significantly increased for treatments without rotation correction.The fraction-level composite uncertainties had a long tail distribution.Furthermore,the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions,and only 75%of uncertainties in the SI direction.In order to cover 90%of uncertainties in the SI direction,an 8-mm margin would be needed.For scenarios without rotation correction,additional safety margins should be added,especially in the superior-inferior and anterior-posterior directions.Conclusion The present study revealed that the correlation model error contributes to most of the uncertainties in the results.Most patients/fractions can be covered by a 5-mm margin.Patients with large treatment uncertainties might need a patient-specific margin.

The AGH score is a predictor of disease-free survival and targeted therapy efficacy after liver transplantation in patients with hepatocellular carcinoma

Background:Liver transplantation(LT)is the“cure”therapy for patients with hepatocellular carcinoma(HCC).However,some patients encounter HCC recurrence after LT.Unfortunately,there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy.The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population,and to evaluate whether these patients are suitable for adjuvant targeted therapy.Methods:Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed.Results:A total of 201 patients were included in the study.The multivariate Cox analysis suggested that preoperative alpha-fetoprotein(AFP)>200μg/L(HR=2.666,95%CI:1.515-4.690;P=0.001),glutamyl transferase(GGT)>96 U/L(HR=1.807,95%CI:1.012-3.224;P=0.045),and exceeding the Hangzhou criteria(HR=2.129,95%CI:1.158-3.914;P=0.015)were independent risk factors for poor disease-free survival(DFS)in patients with HCC who underwent LT.We established an AFP-GGT-Hangzhou(AGH)scoring system based on these factors,and divided cases into high-,moderate-,and low-risk groups.The differences in overall survival(OS)and disease-free survival(DFS)rates among the three groups were significant(P<0.05).The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria,UCSF criteria,Milan criteria,and TNM stage.Only in the high-risk group,we found that lenvatinib significantly improved prognosis compared with that of the control group(P<0.05).Conclusions:The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China.Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy

BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer resection.However,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further investigation.AIM To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal strategy.METHODS This study involved network meta-analyses and followed the PRISMA guidelines.The data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane Library.We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints.The magnitudes of the effects were determined using risk ratios with 95%confidential intervals.The results were analyzed using R software and STATA software.RESULTS A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this study.There was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and transitivity.OS analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS.Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT.CONCLUSION HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT.IMRT,a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT,may be a preferred option.

Successful multidisciplinary therapy for a patient with liver metastasis from ascending colon adenocarcinoma:A case report and review of literature

BACKGROUND Liver metastasis is the most common form of distant metastasis in colorectal cancer,and the only possible curative treatment for patients with colorectal liver metastases(CRLM)is hepatectomy.However,approximately 25%of patients with CRLM have indications for liver resection at the initial diagnosis.Strategies aimed at downstaging large or multifocal tumors to enable curative resection are appealing.CASE SUMMARY A 42-year-old man was diagnosed with ascending colon cancer and liver metastases.Due to the huge lesion size and compression of the right portal vein,the liver metastases were initially diagnosed as unresectable lesions.The patient was treated with preoperative transcatheter arterial chemoembolization(TACE)consisting of 5-fluorouracil/Leucovorin/oxaliplatin/Endostar®.After four courses,radical right-sided colectomy and ileum transverse colon anastomosis were performed.Postoperatively,the pathological analysis revealed moderately differentiated adenocarcinoma with necrosis and negative margins.Thereafter,S7/S8 partial hepatectomy was performed after two courses of neoadjuvant chemotherapy.Pathological examination of the resected specimen revealed a pathologically complete response(pCR).Intrahepatic recurrence was detected more than two months after the operation,and the patient was then treated with TACE consisting of irinotecan/Leucovorin/fluorouracil therapy plus Endostar®.Subsequently,the patient was treated with aγ-knife to enhance local control.Notably,a pCR was reached,and the patient's overall survival time was>9 years.CONCLUSION Multidisciplinary treatment can promote the conversion of initially unresectable colorectal liver metastasis and facilitate complete pathological remission of liver lesions.

Options and survival benefits of conversion therapy for unresectable hepatocellular carcinoma

In the study by Wu et al,patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization(TACE)as a conversion therapy in order to render their tumors suitable for resection.A nomogram was devised and shown to be effective in predicting the survival of these patients.Generalization of the results,however,is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for TACE.Immunotherapy can be considered to be an option for conversion therapy.However,markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking.The question of whether effective conversion therapy can truly enhance overall survival remains unanswered.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation:Where do we stand?

Liver transplantation (LT) for hepatocellular carcinoma (HCC) within Milan criteria is a widely accepted optimal therapy. Neo-adjuvant therapy before transplantation has been used as a bridging therapy to prevent dropout during the waiting period and as a down-staging method for the patient with intermediate HCC to qualify for liver transplantation. Transarterial chemoembolization and radiofrequency ablation are the most commonly used method for locoregional therapy. The data associated with newer modalities including drug-eluting beads, radioembolization with Y90, stereotactic radiation therapy and sorafenib will be discussed as a tool for converting advanced HCC to LT candidates. The concept &#x0201c;ablate and wait&#x0201d; has gained the popularity where mandated observation period after neo-adjuvant therapy allows for tumor biology to become apparent, thus has been recommended after down-staging. The role of neo-adjuvant therapy with conjunction of &#x0201c;ablate and wait&#x0201d; in living donor liver transplantation for intermediate stage HCC is also discussed in the paper.

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.

Targeted IL-24 gene therapy inhibits cancer recurrence after liver tumor resection by inducing tumor cell apoptosis in nude mice

BACKGROUND: Interleukin-24 (IL-24) is a novel candidate tumor suppressor that induces tumor cell apoptosis experimentally in a variety of human malignant cells including liver cancer cells. The present study was conducted to investigate the potential effect of recombinant adeno-associated virus (rAAV)-mediated IL-24 gene therapy on tumor recurrence and metastasis by inducing tumor cell apoptosis in a hepatocellular carcinoma (HCC) model in nude mice. METHODS: We established a recurrent and metastatic HCC model in nude mice and constructed an rAAV vector carrying alpha-fetoprotein (AFP) promoter for expressing the IL-24 gene (rAVV/AFP/IL-24). The vector was administered by regional injection (liver incisal margin). AFP was detected by radiation immunoassay. Histological evaluation of tumor recurrence and metastasis was performed for the liver and lung. The effect of tumor cell apoptosis was confirmed by TUNEL analysis. RESULTS: IL-24 gene therapy prevented tumor recurrence and metastasis, as evidenced by marked decreases in the number of metastatic tumor nodules and tumor volume in the liver and lung. At the same time, serum AFP concentration decreased markedly in the IL-24 group compared with the control or rAAV groups (P<0.05). IL-24 gene therapy inhibited tumor recurrence and metastasis as evidenced by the induction of tumor cell apoptosis. CONCLUSION: The results demonstrated that targeted IL-24 gene therapy was effective in the prevention of postoperative recurrence and metastasis in an HCC nude mice model by induction of tumor cells apoptosis with potential minimum tumor burden.

Advances in postoperative adjuvant therapy for primary liver cancer

Hepatocellular carcinoma(HCC)is a highly heterogeneous,invasive,and conventional chemotherapy-insensitive tumor with unique biological characteristics.The main methods for the radical treatment of HCC are surgical resection or liver transplantation.However,recurrence rates are as high as 50%and 70%at 3 and 5 years after liver resection,respectively,and even in Milan-eligible recipients,the recurrence rate is approximately 20%at 5 years after liver transplantation.Therefore,reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer.This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival,including local adjuvant therapy(e.g.,transcatheter arterial chemoembolization),adjuvant systemic therapy(e.g.,molecular targeted agents and immunotherapy),and other adjuvant therapies(e.g.,antiviral and herbal therapy).Finally,potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.

Molecular Therapy and Prevention of Liver Diseases

Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts: (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.

Progress of transformational therapy in colorectal liver metastases

Colorectal cancer liver metastases （CLM） treatment is very important given the high incidence of colorectal cancer with liver metastases, which are primarily treated by surgical resection. Transformational therapy such as systemic chemotherapy, hepatic arterial infusion （HAl）, portal vein embolization （PVE）, ablation therapy, and targeted therapy, should be applied to CLM patients who are unable to undergo immediate surgery to improve patients＇ survival and quality of life.

Application of interventional therapy via hepatic artery in pancreatic neuroendocrine neoplasms liver metastases

Pancreatic neuroendocrine neoplasm(PNEN)is the second most common malignant tumor of the pancreas.It has the characteristic of high metastases rate,and the liver is the most common site for metastasis.Metastasis affects prognosis and survival seriously.A number of earlier studies have shown that the interventional therapy via hepatic artery could reduce hepatic tumor burden and hormone secretion safely and rapidly,significantly improve objective response rate(ORR),and enhance the efficacy and prolong the survival time when combined with system therapy.The interventional therapy via hepatic artery plays an important role in the treatment of PNEN liver metastases.Interventional therapy via hepatic artery could possibly increase ORR,prolong progression-free survival,and even overall survival for appropriate patients.