Harnessing the prognostic power of preoperative systemic immuneinflammation index/albumin ratio in hepatocellular carcinoma resection

The recent study by Chen et al,published in the World Journal of Gastroenterology,introduces a groundbreaking assessment tool-the preoperative systemic immuneinflammation index/albumin(SII/ALB)ratio-for patients with hepatocellular carcinoma(HCC)undergoing curative resection.This study not only establishes the independent prognostic significance of the SII/ALB ratio but also incorporates it into a predictive nomogram,enhancing its utility for clinical decision-making.The SII/ALB ratio,by integrating inflammatory and nutritional biomarkers,offers a novel lens through which the prognosis of HCC patients can be viewed,suggesting a more tailored approach to patient management.The development of the nomogram,validated for its accuracy in predicting patient outcomes,marks a pivotal advance,potentially guiding surgical decisions and postoperative care.However,the study's focus on a single-center cohort prompts the need for validation in a broader,more diverse patient population to ensure its applicability across various clinical settings.Moreover,longitudinal studies could elucidate the dynamic changes in SII/ALB post-surgery,offering insights into its potential as a continuous monitor for recurrence and long-term survival.This abstract aim to underscore the critical findings of Chen et al's study while calling for further research to explore the full potential of the SII/ALB ratio in the global management of hepatocellular carcinoma.

Radiomics and molecular analysis:Bridging the gap for predicting hepatocellular carcinoma prognosis

This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the survival of patients with hepatocellular carcinoma(HCC).By integrating radiomics with molecular analysis,the study presented a strategy for accurately predicting the expression of EZH2 from CT scans.The findings demonstrated a strong link between the radiomics model,EZH2 expression,and patient prognosis.This noninvasive approach provides valuable insights into the therapeutic management of HCC.

Gamma-glutamyl transferase-to-lymphocyte ratio as a prognostic marker in patients with hepatocellular carcinoma undergoing hepatectomy

BACKGROUND We investigated the utility of gamma-glutamyl transferase-to-lymphocyte ratio(GLR)as a predictive indicator for postoperative survival in patients with hepatocellular carcinoma(HCC)across different time periods and developed a predictive model based on this.AIM To evaluate the prognostic accuracy of GLR for overall survival(OS)in patients with HCC and its impact over time.METHODS This study enrolled 301 patients with HCC treated with curative hepatectomy.Exclusion criteria included non-HCC hepatic malignancies,inadequate records,and prior cancer treatments.Baseline demographics,clinical features,and hematological parameters were recorded.Time-dependent receiver operating characteristic curve analysis was used to determine the optimal GLR threshold for survival prediction at 13 months.Statistical analyses included the Kaplan-Meier method,multivariate Cox regression,and the creation of a prognostic nomogram.RESULTS Out of 301 patients,293 were eligible for analysis,with a male predominance(84.6%).High preoperative GLR correlated with several adverse clinical features.Optimal cutoff values for GLR were significantly associated with stratification of 13-month OS.Multivariate analysis identified age,liver enzymes,postoperative transarterial chemoembolization,Child-Pugh grade,and inflammatory markers as independent predictors of OS.Notably,GLR had a significant impact on long-term postoperative OS,with its influence becoming more pronounced over time.CONCLUSION GLR can serve as a potent prognostic tool for postoperative HCC management,particularly in predicting long-term outcomes.

Therapeutic potential of kakkatin derivatives against hepatocellular carcinoma

In this article,we commented on the work done by Jiang et al,where they syn-thesized a kakkatin derivative,6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-me-thoxy-4H-chromen-4-one(HK),and investigated its antitumor activities and me-chanism in gastric cancer MGC803 and hepatocellular carcinoma(HCC)SMMC-7721 cells.HK was evaluated for its antitumor activity as compared to kakkatin and cisplatin.This article focused on various risk factors of HCC,the mechanism of HCC progression and molecular targets of the kakkatin derivative,and limi-tations of available treatment options.HCC is a predominant form of primary liver cancer characterized by the accumulation of multiple gene modifications,overexpression of protooncogenes,altered immune microenvironment,and infilt-ration by immune cells.Puerariae flos(PF)has been used in traditional medicine in China,Korea,and Japan for lung clearing,spleen awakening,and relieving alcohol hangovers.PF exerts antitumor activity by inhibiting cancer cell prolif-eration,invasion,and migration.PF induces apoptosis in alcoholic HCC via the estrogen-receptor 1-extracellular signal-regulated kinases 1/2 signaling pathway.Kakkatin isolated from PF is known as a hepatoprotective bioflavonoid.The ka-kkatin derivative,HK,exhibited anticancer activity against HCC cell lines by in-hibiting cell proliferation and upregulating nuclear factor kappa B subunit 1 and phosphodiesterase 3B.However,further preclinical and clinical studies are required to establish its therapeutic potential against HCC.

Five-year complete remission of super-giant hepatocellular carcinoma with hepatectomy followed by sorafenib plus camrelizumab:A case report

BACKGROUND Cirrhotic patients with super-giant hepatocellular carcinoma(HCC)and portal vein invasion generally have a poor prognosis.This paper presents a patient with super-giant HCC and portal vein invasion,who underwent hepatectomy followed by a combination of sorafenib and camrelizumab,resulting in complete remission(CR)for 5 years.CASE SUMMARY A 40-year-old male with compensated hepatitis B-related cirrhosis was diagnosed with HCC,Barcelona Clinic Liver Cancer stage C.Enhanced computed tomography imaging revealed a 152 mm×171 mm tumor in the right liver,invading the portal vein and hepatic vein.Liver function was normal.The patient successfully underwent hepatectomy on July 18,2019.However,by December 2019,HCC recurrence with lung metastases and portal vein invasion were detected.He started treatment with sorafenib(200 mg twice daily)and camrelizumab(200 mg every 3 weeks).By May 12,2020,the patient was confirmed to have CR.Camrelizumab was adjusted to 200 mg every 12 weeks from June 16,2021,with the last infusion on March 29,2024.Although no further tumor recurrence was observed,he experienced two episodes of gastrointestinal bleeding due to esophagogastric varices,which were managed with endoscopic therapy.To date,the patient has remained in CR for 5 years.CONCLUSION The combination of hepatectomy with sorafenib and camrelizumab can achieve durable CR in patients with supergiant HCC and portal vein invasion.Further research is necessary to address these challenges and improve patient outcomes.

Efficacy of sorafenib combined with transarterial chemoembolization in the treatment of advanced hepatocellular carcinoma:A metaanalysis

BACKGROUND The combination of sorafenib with transarterial chemoembolization(TACE)is being investigated for its potential to improve outcomes in advanced hepatocellular carcinoma(HCC).AIM To evaluate the efficacy of this combined treatment strategy in enhancing overall survival(OS)and progression-free survival(PFS)compared to monotherapies.METHODS A systematic review was conducted following the PRISMA guidelines.A comprehensive search was performed across PubMed,EMBASE,Web of Science,and the Cochrane Library up to May 8,2024.Studies were included if they compared sorafenib plus TACE to sorafenib alone or TACE alone in adults with advanced HCC.Primary outcomes were OS,PFS,response rates,and safety profiles.Data extraction and quality assessment were independently performed by two reviewers.Heterogeneity was assessed using the I²statistic,and a random-effects model was applied for pooling data.Sensitivity analysis and publication bias assessment were also conducted.RESULTS A total of twelve studies involving 1174 patients met the inclusion criteria.Significant heterogeneity was observed for both OS(I²=72.6%,P<0.001)and PFS(I²=83.7%,P<0.001).The combined treatment of sorafenib with TACE significantly improved OS[hazard ratio(HR)=0.60,95%confidence interval(CI):0.44-0.76]and PFS(HR=0.54,95%CI:0.38-0.69).Sensitivity analysis confirmed the robustness of these findings.Funnel plots and Egger's test indicated no significant publication bias.CONCLUSION Sorafenib combined with TACE significantly enhances both OS and PFS in patients with advanced HCC compared to monotherapy.This combination therapy represents a promising approach to improving clinical outcomes in advanced liver cancer.

CRAFITY score and nomogram predict the clinical efficacy of lenvatinib combined with immune checkpoint inhibitors in hepatocellular carcinoma

BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.

Anticipation for hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcinoma

Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in managingadvanced HCC, particularly in regions with high prevalence rates. Despite itspromise, several challenges and areas for future research remain. Clinical studieshave substantiated the efficacy of HAIC in enhancing survival outcomes forpatients with advanced hepatic carcinoma. Notably, combination therapiesinvolving immune checkpoint inhibitors, such as lenvatinib and programmeddeath-1 inhibitors, have shown substantial improvements in median overallsurvival and progression-free survival compared to systemic chemotherapy.These combination therapies have also exhibited superior response rates anddisease control, with manageable and often less severe adverse events relative tosystemic treatments. This article is based on the review by Zhou et al and aims todiscuss the current status and future directions in the treatment of HCC, emphasizingthe role of HAIC and its integration with novel therapeutic agents.

Transmembrane channel-like 5 drives hepatocellular carcinoma progression by regulating epithelial-mesenchymal transition

BACKGROUND Hepatocellular carcinoma(HCC)is a difficult cancer to manage due to its highly invasive and metastatic nature.AIM To investigate the molecular function of transmembrane channel-like 5(TMC5)in vitro and in vivo,with the objective of identifying novel diagnosis and treatment targets for HCC.METHODS The expression of TMC in cancer and normal tissues,along with its correlation with HCC prognosis,was analyzed using the GENT2,GEPIA database,and Human Protein Atlas.COX analysis was conducted to assess the relationship between TMC5 expression and overall survival in TCGA-LIHC patients.Further experiments were conducted to investigate the effect of TMC5 in cancer progression through loss-and gain-of-function assays in vitro and in vivo.RESULTS Bioinformatics revealed that TMC5 expression was generally higher in tumors than in normal tissues,and its expression was associated with poorer patient survival outcomes.TMC5 expression in HCC tissues and cells was consistent with the results of the bioinformatics analysis.Suppression of TMC5 expression reduced migration,invasion,and proliferation,while also decreasing the expression of epithelial-mesenchymal transition(EMT)-associated molecules in MHCC97-LM3 cells.Conversely,higher TMC5 expression significantly increased cell migration,invasion,proliferation,and EMT in MHCC97 L cells.TMC5 knockdown significantly decreased both the formation and spread of nodules in liver tissue,whereas TMC5 overexpression promoted them.CONCLUSION Our study provides compelling evidence that TMC5 is highly expressed in HCC and drives cancer progression through the activation of EMT-mediated invasion.TMC5 could represent a valuable molecular target for the diagnosis and treatment of HCC.

Histopathological diagnosis of microvascular invasion in hepatocellular carcinoma:Is it reliable?

BACKGROUND Microvascular invasion(MVI)is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence,but the reliability of its current pathological diagnosis remains uncertain.AIM To evaluate the accuracy of current 7-point sampling methods and propose an optimal pathological protocol using whole-mount slide imaging(WSI)for better MVI detection.METHODS We utilized 40 New Zealand white rabbits to establish VX2 liver tumor models.The entire tumor-containing liver lobe was subsequently obtained,following which five different sampling protocols(A-E)were employed to evaluate the detection rate,accuracy,quantity,and distribution of MVI,with the aim of identifying the optimal sampling method.RESULTS VX2 liver tumor models were successfully established in 37 rabbits,with an incidence of MVI of 81.1%(30/37).The detection rates[27%(10/37),43%(16/37),62%(23/37),68%(25/37),and 93%(14/15)]and quantity(15,36,107,125,and 395)of MVI increased significantly from protocols A to E.The distribution of MVI showed fewer MVIs farther away from the tumor,but the percentage of MVI detected quantity gradually increased from 6.7%to 48.3%in the distant nonneoplastic liver tissue from protocols A to E.Protocol C was identified as the optimal sampling method by comparing them in sequence.The sampling protocol of three consecutive interval WSIs at the tumor center(WSI3)was further screened to determine the optimal number of WSIs.Protocol A(7-point sampling method)exhibited only 46%accuracy and a high false-negative rate of 67%.Notably,the WSI3 protocol improved the accuracy to 78%and decreased the false-negative rate to 27%.CONCLUSION The current 7-point sampling method has a high false-negative rate in MVI detection.In contrast,the WSI3 protocol provides a practical and effective approach to improve MVI diagnostic accuracy,which is crucial for hepatocellular carcinoma diagnosis and treatment planning.

Prediction of posthepatectomy liver failure in patients withhepatocellular carcinoma through ultrasound elastography

In this article,we comment on the article by Cheng et al published in recently.Posthepatectomy liver failure(PHLF)remains a leading cause of hepatectomyrelated mortality and can be evaluated according to liver reserve function.Liver stiffness(LS)measured by ultrasonic elastography and spleen area demonstrate a strong correlation with hepatic proliferation,fibrosis,and portal vein congestion,thus indirectly reflecting liver reserve function.This article highlights a meticulous study aimed at investigating the potential of two-dimensional shear wave elastography in assessing LS,as well as its integration with spleen area,surgical factors,and laboratory indicators,for predicting the risk of PHLF in hepatocellular carcinoma patients.In this article,we discussed the non-invasive elastography modality by ultrasound and magnetic resonance imaging to assess LS.Based on literature data,we subsequently suggested that several risk factors may contribute to PHLF,including excessive intrahepatic neutrophil accumulation,the formation of neutrophil extracellular traps,end-stage liver disease scores,and albumin-bilirubin scores.Therefore,a more comprehensive study incor-porating detailed information requires further investigation.

Unveiling expression patterns,mechanisms,and therapeutic opportunities of transmembrane protein 106C:From pan-cancers to hepatocellular carcinoma

BACKGROUND Although transmembrane protein 106C(TMEM106C)has been elucidated to be overexpressed in cancers,its underlying mechanisms have not yet been fully understood.AIM To investigate the expression levels and molecular mechanisms of TMEM106C across 34 different cancer types,including liver hepatocellular carcinoma(LIHC).METHODS We analyzed TMEM106C expression patterns in pan-cancers using microenvironment cell populations counter to evaluate its association with the tumor microenvironment.Gene set enrichment analysis was conducted to identify molecular pathways related to TMEM106C.Chromatin immunoprecipitation followed by sequencing(ChIP-seq)analysis was conducted to identify upstream transcriptional regulators of TMEM106C.In LIHC,we examined mRNA profiles,performed in-house quantitative polymerase chain reaction,immunohistochemistry,and constructed a co-expression gene network.Functional assays,including cell counting kit-8,cell cycle,apoptosis,migration,and invasion,were conducted.The effect of nitidine chloride(NC)on LIHC xenograft was evaluated through RNA sequencing and molecular docking.Finally,potential therapeutic agents targeting TMEM106C were predicted.RESULTS TMEM106C was significantly overexpressed in 27 different cancer types and presaged poor prognosis in four of these types,including LIHC.Across pan-cancers,TMEM106C was inversely correlated to the abundances of immune and stromal cells.Furthermore,TMEM106C was significantly linked to cell cycle and DNA replication pathways in pan-cancers.ChIP-seq analysis predicted CCCTC-binding factor as a pivotal transcriptional factor targeting the TMEM106C gene in pan-cancers.Integrated analysis showed that TMEM106C was upregulated in 4657 LIHC compared with 3652 normal liver tissue[combined standardized mean difference=1.31(1.09,1.52)].Inhouse LIHC samples verified the expression status of TMEM106C.Higher TMEM106C expression signified worse survival conditions in LIHC patients treated with sorafenib,a tyrosine kinase inhibitor(TKI).Co-expressed analysis revealed that TMEM106C were significantly enriched in the cell cycle pathway.Knockout experiments demonstrated that TMEM106C plays a crucial role in LIHC cell proliferation,migration,and invasion,with cell cycle arrest occurring at the DNA synthesis phase,and increased apoptosis.Notably,TMEM106C upregulation was attenuated by NC treatment.Finally,TMEM106C expression levels were significantly correlated with the drug sensitivity of anti-hepatocellular carcinoma agents,including JNJ-42756493,a TKI agent.CONCLUSION Overexpressed TMEM106C was predicted as an oncogene in pan-cancers,which may serve as a promising therapeutic target for various cancers,including LIHC.Targeting TMEM106C could potentially offer a novel direction in overcoming TKI resistance specifically in LIHC.Future research directions include in-depth experimental validation and exploration of TMEM106C’s role in other cancer types.

Innovative applications and research progress of hepatic arterial infusion chemotherapy in the treatment of advanced hepatocellular carcinoma

This article provides an in-depth analysis of the study conducted by Wang et al,which explores hepatic arterial infusion chemotherapy and its synergistic strategies in managing advanced hepatocellular carcinoma(HCC).HCC ranks as the fourth most common cause of cancer-related mortality globally and is frequently associated with portal vein tumor thrombus(PVTT).The approach to managing HCC,particularly when PVTT is present,diverges markedly between Eastern and Western practices.These differences are rooted in variations in epidemiology,etiology,pathology,comorbidities,and prognosis.The paper delves into the diagnosis,classification,and treatment strategies for HCC with PVTT,as well as the evolving role and advancements of hepatic arterial infusion chemotherapy in the therapeutic landscape of HCC.

Laparoscopic hepatectomy using indocyanine green attenuates postoperative inflammatory response for hepatocellular carcinoma:A propensity score matching analysis

BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver surgeons.AIM To determine the benefits of indocyanine green(ICG)fluorescence imaging in patients with hepatocellular carcinoma(HCC)who underwent laparoscopic hepatectomy during and after surgery.METHODS We retrospectively collected the clinicopathological data of 107 patients who successfully underwent laparoscopic hepatectomy at Zhongshan Hospital(Xiamen),Fudan University from June 2022 to June 2023.Whether using the ICG fluorescence imaging technique,we divided them into the ICG and non-ICG groups.To eliminate statistical bias,a 1:1 propensity score matching analysis was conducted.The comparison of perioperative outcomes,including inflammationrelated markers and progression-free survival,was analyzed statistically.RESULTS Intraoperatively,the ICG group exhibited lower blood loss,a shorter surgical time,lower hepatic inflow occlusion(HIO)frequency,and a shorter total HIO time.Postoperatively,the participation of ICG resulted in a shorter duration of hospitalization(6.5 vs 7.6 days,P=0.03)and postoperative inflammatory response attenuation(lower neutrophil-lymphocyte ratio on the first day after surgery and platelet-lymphocyte ratio on the third day,P<0.05).Although the differences were not significant,the levels of all inflammation-related markers were lower in the ICG group.The rates of postoperative complications and the survival analyses,including progression-free and overall survivals showed no significant difference between the groups.CONCLUSION The involvement of ICG fluorescence imaging may lead to improved perioperative outcomes,especially postoperative inflammatory response attenuation,and ultimately improve HCC patients’recovery after surgery.

Mechanistic link between long noncoding RNA and stability of oncogene reveals stemness and chemoresistance of hepatocellular carcinoma

This letter comments on the recently published manuscript by Yu et al,in which the authors revealed a novel mechanism by which the m6A-modified long noncoding RNA kinesin family member 9-antisense RNA 1 promotes stemness and sorafenib resistance of hepatocellular carcinoma(HCC)through ubiquitinspecific peptidase 1-mediated deubiquitination of oncogene short stature homeobox 2.Given the high mortality rate and poor prognosis of HCC,the findings by Yu et al open a new avenue for overcoming HCC burden by focusing on kinesin family member 9-antisense RNA 1 and short stature homeobox 2 as prognostic markers and therapeutic targets.

Bidirectional regulation of the cyclic guanosine monophosphateadenosine monophosphate synthase-stimulator of interferon gene pathway and its impact on hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are limited.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)activates the stimulator of interferon gene(STING)signaling pathway as a crucial immune response pathway in the cytoplasm,which detects cytoplasmic DNA to regulate innate and adaptive immune responses.As a potential therapeutic target,cGASSTING pathway markedly inhibits tumor cell proliferation and metastasis,with its activation being particularly relevant in HCC.However,prolonged pathway activation may lead to an immunosuppressive tumor microenvironment,which fostering the invasion or metastasis of liver tumor cells.AIM To investigate the dual-regulation mechanism of cGAS-STING in HCC.METHODS This review was conducted according to the PRISMA guidelines.The study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science databases.Through rigorous screening and meticulous analysis of the retrieved literature,the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC tumors.RESULTS All authors collaboratively selected studies for inclusion,extracted data,and the initial search of online databases yielded 1445 studies.After removing duplicates,remaining 964 records were screened.Ultimately,55 articles met the inclusion criteria and were included in this review.CONCLUSION Acute inflammation can have a few inhibitory effects on cancer,while chronic inflammation generally promotes its progression.Extended cGAS-STING pathway activation will result in a suppressive tumor microenvironment.

Clinicopathological features and surgical outcome of patients with fibrolamellar hepatocellular carcinoma(experience with 22 patients over a 15-year period)

AIM To evaluate the clinicopathological features and the surgical outcomes of patients with fibrolamellar hepato-cellular carcinoma(FL-HCC)over a 15-year period. METHODS This is a retrospective study including 22 patients with a pathologic diagnosis of FL-HCC who underwent hepatectomy over a 15-year period. Tumor characteristics,survival and recurrence were evaluated. RESULTS There were 11 male and 11 female with a median age of 29 years(range from 21 to 58 years). Two(9%)patients had hepatitis C viral infection and only 2(9%)patients had alpha-fetoprotein level > 200 ng/m L. The median size of the tumors was 12 cm(range from 5-20 cm). Vascular invasion was detected in 5(23%)patients. Four(18%)patients had lymph node metastases. The median follow up period was 42 mo and the 5-year survival was 65%. Five(23%)patients had a recurrent disease,4 of them had a second surgery with 36 mo median time interval. Vascular invasion is the only significant negative prognostic factor CONCLUSION FL-HCC has a favorable prognosis than common HCC and should be suspected in young patients with non cirrhotic liver. Aggressive surgical resection should be done for all patients. Repeated hepatectomy should be considered for these patients as it has a relatively indolent course.

Downstaging strategies for unresectable hepatocellular carcinoma

A significant number of patients with hepatocellular carcinoma(HCC)are usually diagnosed in advanced stages,that leads to inability to achieve cure.Palliative options are focusing on downstaging a locally advanced disease.It is wellsupported in the literature that patients with HCC who undergo successful conversion therapy followed by curative-intent surgery may achieve a significant survival benefit compared to those who receive chemotherapy alone or those who are successfully downstaged with conversion therapy but not treated with surgery.Hepatic artery infusion chemotherapy can be a potential downstaging strategy,since recent studies have demonstrated excellent outcomes in patients with colorectal liver metastatic disease as well as primary liver malignancies.

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.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.