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.

Hotspots and trends in stem cell therapy for liver fibrosis and cirrhosis: A bibliometric analysis

BACKGROUND Liver fibrosis and cirrhosis are global medical challenges that require safe and effective treatments.In the past two decades,there has been a surge in research on stem cell therapy for liver fibrosis and cirrhosis.This study aimed to conduct a comprehensive analysis of the research hotspots and trends in this field through bibliometrics.sters was conducted.RESULTS As of September 20,2024,a total of 1935 documents were retrieved dating from 2004 to 2024,with 1186 strongly relevant publications obtained after screening.China,the United States,and Japan were the major contributors in this field.Cairo University,Zhejiang University and Yamaguchi University were the major institution in this field.The journal Stem Cell Research&Therapy published the most papers.There were 686 authors,with Shuji Terai,Isao Sakaida,Soon Koo Baik,and Lanjuan Li publishing the most papers.The research focused on alcoholic cirrhosis and nonalcoholic fatty liver disease.The emerging areas of interest were extracellular vesicles,exosomes,and their enriched microRNAs.The field is experiencing rapid growth due to the changing research trends and increasing literature.CONCLUSION These findings provide a thorough overview of stem cell therapy in the field of liver fibrosis and cirrhosis.

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.

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 “ablate and wait” 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 “ablate and wait” in living donor liver transplantation for intermediate stage HCC is also discussed in the paper.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Conversion therapy for unresectable hepatocellular carcinoma:Advances and challenges

Recently,the World Journal of Gastrointestinal Oncology published an article entitled“Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of the literature”,in which the authors shared their successful experience with complete surgical resection after multidisciplinary conversion therapy.The study by Chu et al demonstrates the great challenges that the advanced hepatocellular carcinoma(HCC)poses to surgical oncology,reveals the complexity of conversion therapy for unresectable HCC,emphasizes the important role of a multidisciplinary management model in conversion therapy,and enriches our understanding of the dynamics of personalized treatment for different patients.At present,conversion therapy is a hot research topic in the treatment of unresectable HCC,which has brought new hope to many patients with moderately advanced HCC.However,there are still many urgent problems to be solved in conversion therapy.Here,we would like to further discuss the advances and challenges of conversion therapy for unresectable HCC with the authors and the general readers.

Exploring combination therapy centered on targeted immunotherapy for advanced hepatocellular carcinoma:a beacon of hope

Hepatocellular carcinoma(HCC)is an aggressive malignancy that is highly prevalent worldwide.It is often diagnosed at an advanced stage,which poses challenges for curative treatment and leads to an unfavorable prognosis.The introduction of targeted therapy drugs,such as tyrosine kinase inhibitors,and immunotherapeutic drugs,including immune checkpoint inhibitors,has substantially improved the thera-peutic effectiveness for advanced HCC.However,their efficacy remains suboptimal,owing to challenges related to patient responsiveness and drug resistance.To address these challenges,researchers have investigated combination therapies,including targeted immunother-apy,and triple therapies based on targeted immunotherapy,such as a combination of radiotherapy and targeted immunotherapy.In ad-dition,they conducted a comprehensive investigation of potential new targets and drugs,yielding a series of significant findings.This re-view presents an outline of the treatment mechanisms and associated clinical research findings on mainstream targeted therapies,immu-notherapies,and combination therapies.It also summarizes the current status of combination therapies for advanced HCC and anticipates future developments and trends in this field.

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.

Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

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.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

High-intensity focused ultrasound ablation as a bridging therapy for hepatocellular carcinoma patients awaiting liver transplantation

The scarcity of liver grafts in Asia leads to a significant dropout of patients from liver transplant waiting lists, particularly patients with hepatocellular carcinoma and a low model for end-stage liver disease score. In order to reduce dropping out, different bridging therapies are employed. We report the use of high-intensity focused ultrasound ablation as a bridging therapy for a patient with hepatocellular carcinoma of stage two and an extremely low platelet count (20×10 9 /L). The ablation was successful. Blood tests showed that his liver function was similar before and after the treatment. No adhesion was encountered in the liver transplantation performed six months later.

Outcomes of loco-regional therapy for down-staging of hepatocellular carcinoma prior to liver transplantation

BACKGROUND: The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade. Many patients with HCC who were beyond the Milan criteria were allowed to receive a liver transplantation (LT) once the HCC was successfully down-staged. This retrospective study aimed to analyze the outcomes of LRTs prior to LT in patients with HCC beyond the Milan criteria. METHODS: We analyzed 56 patients treated from June 2006 to March 2010: 22 met the Milan criteria (T1+T2, 39.3%), 16 had T3 tumors (28.6%), and 11 had T4a tumors (19.6%), while 7 were suspected of tumor vascular invasion (T4b, 12.5%). All patients underwent preoperative LRTs, including transcatheter arterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, liver resection, and/or microwave coagulation therapy. The number of the patients who were successfully down-staged before LT, the types of LRTs used before LT, and their outcomes after LT were recorded. RESULTS: Eleven patients had necrotic tumors (pT0, 19.6%); 6 had pT1 tumors (10.7%), 22 had pT2 tumors (39.3%), 6 had pT3 tumors (10.7%), 5 had pT4a tumors (8.9%), and 6 had pT4b tumors (10.7%). The histopathologic tumors of 39 patients (69.6%) were down-staged and met the established Milan criteria (pT0-2). Imaging-proven under-staging was present in 5 HCC patients (8.9%) who had tumors involving the intrahepatic venous system. Twenty-three patients (41.1%) had stable HCC and 10 (17.9%) died. The 1-, 3- and 4-year survival rates were 96%, 73% and 61%, respectively, with a mean survival time of 22.29±1.63 months. Six patients died of tumorrecurrence. The 1-, 3- and 4-year recurrence-free survival (RFS) rates were 88%, 75% and 66%, respectively. The 3-year RFS of patients with pT0-2 tumors was 82%, which was markedly greater than that of patients with pT3 tumors (63%, P=0.018) or pT4 tumors (17%, P=0.000). Although the 3-year RFS of patients with pT3 tumors was greater than that of patients with pT4 tumors, the difference was not significant. CONCLUSIONS: Successful down-staging of HCCs can be achieved in the majority of carefully selected patients by LRTs. Importantly, patients who are successfully down-staged and undergo LT may have a higher RFS rate.

High-risk esophageal varices in patients treated with locoregional therapy for hepatocellular carcinoma:Assessment with liver computed tomography

AIM： To assess the diagnostic performance of follow- up liver computed tomography （CT） for the detection of high-risk esophageal varices in patients treated with Io- coregional therapy for hepatocellular carcinoma （HCC）. METHODS： We prospectively enrolled 100 patients with cirrhosis who underwent transcatheter arterial chemoembolization, radiofrequency ablation or both procedures for HCCs. All patients underwent upper endoscopy and subsequently liver CT. Three radiolo- gists independently evaluated the presence of high-riskesophageal varices with transverse images alone and with three orthogonal multiplanar reformation （MPR） images, respectively. With endoscopic grading as the reference standard, diagnostic performance was as- sessed by using receiver operating characteristic （ROC） curve analysis. RESULTS： The diagnostic performances （areas under the ROC curve） of three observers with transverse im- ages alone were 0.947 ± 0.031, 0.969 ± 0.024, and 0.916 ＋ 0.038, respectively. The mean sensitivity, spec- ificity, positive predicative value （PPV）, and negative predicative value （NPV） with transverse images alone were 90.1%, 86.39%, 70.9%, and 95.9%, respectively. The diagnostic performances, mean sensitivity, specific- ity, PPV, and NPV with three orthogonal MPR images （0.965 ± 0.025, 0.959 ± 0.027, 0.938 ± 0.033, 91.4%, 89.5%, 76.3%, and 96.6%, respectively） were not su- perior to corresponding values with transverse images alone （P 〉 0.05）, except for the mean specificity （P = 0.039）. CONCLUSION： Our results showed excellent diagnos- tic performance, sensitivity and NPV to detect high-risk esophageal varices on follow-up liver CT after Iocore- gional therapy for HCC,

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.

Low-dose intermittent interferon-alpha therapy for HCV-related liver cirrhosis after curative treatment of hepatocellular carcinoma

AIM: To assess the efficacy of low-dose intermittent interferon (IFN) therapy in patients with hepatitis C virus (HCV)-related compensated cirrhosis who had received curative treatment for primary hepatocellular carcinoma (HCC). METHODS: We performed a prospective case controlled study. Sixteen patients received 3 MIU of natural IFN- alpha intramuscularly 3 times weekly for at least 48 wk (IFN group). They were compared with 16 matched historical controls (non-IFN group). RESULTS: The cumulative rate of first recurrence of HCC was not significantly different between the IFN group and the non-IFN group (0% vs 6.7% and 68.6% vs 80% at 1- and 3-year, P = 0.157, respectively). The cumulative rate of second recurrence was not also significantly different between the IFN group and the non-IFN group (0% vs 6.7% and 35.9% vs 67% at 1- and 3-year, P = 0.056, respectively). Although the difference in the Child-Pugh classification score between the groups at initial treatment of HCC was not signifi cant, the score was signifi cantly worse at the time of data analysis in the non-IFN group than IFN group (7.19 ± 1.42 vs 5.81 ± 0.75, P = 0.0008). The cumulative rate of deviation from objects of any treatment for recurrentHCC was also higher in the non-IFN group than IFN group (6.7% and 27% vs 0 and 0% at 1- and 3-year, P = 0.048, respectively). CONCLUSION: Low-dose intermittent IFN-alpha therapy for patients with HCV-related compensated cirrhosis after curative HCC treatment was effective by making patients tolerant to medical or surgical treatment for recurrent HCC in the later period of observation.

Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing

AIM: To explore the impact of prolonged fraction dosedelivery time modeling intensity-modulated radiation therapy (IMRT) on cell killing of human hepatocellular carcinoma (HCC) HepG2 and Hep3B cell lines.METHODS: The radiobiological characteristics of human HCC HepG2 and Hep3b cell lines were studied with standard clonogenic assays, using standard linear-quadratic model and incomplete repair model to fit the dose-survival curves. The identical methods were also employed to investigate the biological effectiveness of irradiation protocols modeling clinical conventional fractionated external beam radiotherapy (EBRT, fraction delivery time 3 min) and IMRT with different prolonged fraction delivery time (15, 30, and 45 min). The differences of cell surviving fraction irradiated with different fraction delivery time were tested with paired t-test. Factors determining the impact of prolonged fraction delivery time on cell killing were analyzed.RESULTS: The α/β and repair half-time (T1/2) of HepG2and Hep3b were 3.1 and 7.4 Gy, and 22 and 19 min respectively. The surviving fraction of HepG2 irradiated modeling IMRT with different fraction delivery time was significantly higher than irradiated modeling EBRT and the cell survival increased more pronouncedly with the fraction delivery time prolonged from 15 to 45 min,while no significant differences of cell survival in Hep3b were found between different fraction delivery time protocols.CONCLUSION: The prolonged fraction delivery time modeling IMRT significantly decreased the cell killing in HepG2 but not in Hep3b. The capability of sub-lethal damage repair was the predominant factor determining the cell killing decrease. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments for HCC.

Improving clinical outcomes of patients with hepatocellular carcinoma:Role of antiviral therapy,conversion therapy,and palliative therapy

In this editorial,I comment on three articles published in the recent issue of the World Journal of Gastrointestinal Oncology.Hepatocellular carcinoma(HCC)is an important public health concern,and there are three articles on the theme of HCC in this issue.I focus on the articles by Mu et al,Chu et al,and Ma et al for this editorial.While these articles may be considered as low-quality evidence,and the results cannot be generalized to non-hepatitis-B or C virus patients,the discussion of the results is important.In addition,though all the articles are from China,the relevance of the results is not minuscule.As resection is the main form of curative treatment modality owing to a donor liver shortage,surgeons need to be aware that preoperative long-course antiviral therapy can improve clinical outcomes by reducing postoperative liver dysfunction and recurrence of HCC following resection.Similarly,patients with super-giant HCC(defined as≥15 cm diameter)should also be carefully considered for liver resection,and if it is unresectable upfront,then a combination of liver-directed therapy and systemic therapy may downstage HCC.If,following downstaging,the patient qualifies for liver resection based on locally prevalent resectability criteria,then such therapy is labelled as conversion(from unresectable to resectable)therapy.In unresectable patients treated by a combination of treatment options,serological markers like neutrophil-to-lymphocyte ratio and alpha-fetoprotein are reported to predict treatment responses,thus enabling personalized medicine.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.