Epidemiology,therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont,Italy

BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide.It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate.HCC patients have increasingly complex and constantly changing characteristics,thus up-to-date and comprehensive data are fundamental.AIM To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019.METHODS In this retrospective study,we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at"Santa Croce e Carle"Hospital in Cuneo(Italy)between 1 January 2010 and 31 December 2019.To highlight possible changes in HCC patterns over the 10-year period,we split the population into two 5-year groups,according to the diagnosis period(2010-2014 and 2015-2019).RESULTS Of the 328 HCC patients who were included(M/F 255/73;mean age 68.9±11.3 years),154 in the first period,and 174 in the second.Hepatitis C virus infection was the most common HCC risk factor(41%,135 patients).The alcoholic etiology rate was 18%,the hepatitis B virus infection etiology was 5%,and the non-viral/non-alcoholic etiology rate was 22%.The Child-Pugh score distribution of the patients was:class A 75%,class B 21%and class C 4%.The average Mayo end-stage liver disease score was 10.6±3.7.A total of 55 patients(17%)were affected by portal vein thrombosis and 158(48%)by portal hypertension.The average nodule size of the HCC was 4.6±3.1 cm.A total of 204 patients(63%)had more than one nodule<3,and 92%(305 patients)had a non-metastatic stage of the disease.The Barcelona Clinic Liver Cancer(BCLC)staging distribution of all patients was:4%very early,32%early,23%intermediate,34%advanced,and 7%terminal.Average survival rate was 1.6±0.3 years.Only 20%of the patients underwent treatment.Age,presence of ascites,BCLC stage and therapy were predictors of a better prognosis(P<0.01).A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology(P<0.05)and alpha-fetoprotein(AFP)levels(P<0.01).CONCLUSION In this study analyzing patients with a new diagnosis of HCC between 2010-2019,hepatitis C virus infection was the most common etiology.Most patients presented with an advanced stage disease and a poor prognosis.When comparing the two 5-year groups,we observed a statistically significant difference only in global etiology(P<0.05)and AFP levels(P<0.01).

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.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.

Molecular pathological epidemiology in diabetes mellitus and risk of hepatocellular carcinoma

Molecular pathological epidemiology(MPE) is a multidisciplinary and transdisciplinary study field,which has emerged as an integrated approach of molecular patho-logy and epidemiology,and investigates the relationship between exogenous and endogenous exposure factors,tumor molecular signatures,and tumor initiation,progression,and response to treatment.Molecular epidemiology broadly encompasses MPE and conventional-type molecular epidemiology.Hepatocellular carcinoma(HCC) is the third most common cause of cancer-associated death worldwide and remains as a major public health challenge.Over the past few decades,a number of epidemiological studies have demonstrated that diabetes mellitus(DM) is an established independent risk factor for HCC.However,how DM affects the occurrence and development of HCC remains as yet unclearly understood.MPE may be a promising approach to investigate the molecular mechanisms of carcinogenesis of DM in HCC,and provide some useful insights for this pathological process,although a few challenges must be overcome.This review highlights the recent advances in this field,including:(1) introduction of MPE;(2) HCC,risk factors,and DM as an established independent risk factor for HCC;(3) molecular pathology,molecular epidemiology,and MPE in DM and HCC;and(4) MPE studies in DM and risk of HCC.More MPE studies are expected to be performed in future and I believe that this field can provide some very important insights on the molecular mechanisms,diagnosis,personalized prevention and treatment for DM and risk of HCC.

Epidemiology, clinical-treatment patterns and outcome in 256 hepatocellular carcinoma cases

AIM: To analyze the epidemiology, clinical characteristics, treatment patterns and outcome in hepatocellular carcinoma (HCC) patients. METHODS: We analyzed clinical, pathological and therapeutic data from 256 consecutive patients, examined at S. Croce Hospital in Cuneo-Piedmont, with a diagnosis of HCC between 30th June 2000 and 1st July 2010. We analyzed the hospital imaging database and examined all medical records, including the diagnosis code for HCC (155.0 according to the ICD-9M classification system), both for inpatients and outpatients, and discovered 576 relevant clinical records. After the exclusion of reports relating to multiple admissions for the same patient, we identified 282 HCC patients. Moreover, from this HCC series, we excluded 26 patients: 1 patient because of an alternative final diagnosis, 8 patients because of a lack of complete clinical data in the medical record and 17 patients because they were admitted to different health care facilities, leaving 256 HCC patients. To highlight possible changes in HCC patterns over the ten-year period, we split the population into two five-year groups, according to the diagnosis period: 30 th June 2000-30th June 2005 and 1st July 2005-1st July 2010. Patients underwent a 6-mo follow up. RESULTS: Two hundred and fifty-six HCC patients were included (male/female 182/74; mean age 70 years), 133 in the first period and 123 in the second. Hepatitis C virus (HCV) infection was the most common HCC risk factor (54.1% in the first period, 50.4% in the second;P = 0.63); in the first period, 21.8% of patients were alcoholics and 15.5% were alcoholics in the second period (P > 0.05); the non-viral/non-alcoholic etiology rate was 3.7% in the first period and 20.3% in the second period (P < 0.001). Child class A patients increased significantly in the second period (P < 0.001). Adjusting for age, gender and etiology, there was a significant increase in HCC surveillance during the second period (P = 0.01). Differences between the two periods were seen in tumor parameters: there was an increase in the number of unifocal HCC patients, from 53 to 69 (P = 0.01), as well as an increase in the number of cases where the HCC was < 3 cm [from 22 to 37 (P = 0.01)]. The combined incidence of stage Barcelona Clinic Liver Cancer 0 (very-early) and A (early) HCC was 46 (34.6%) between 2000-2005, increasing to 62 (50.4%) between 2005-2010 (P = 0.01). Of the patients, 62.4% underwent specific treatment in the first group, which increased to 90.2% in the second group (P < 0.001). Diagnosis period (P < 0.01), Barcelona-Clinic Liver Cancer stage (P < 0.01) and treatment per se (P < 0.05) were predictors of better prognosis; surveillance was not related to survival (P = 0.20).CONCLUSION: This study showed that, between 2000-2005 and 2005-2010, the number of HCV-related HCC decreased, non-viral/non alcoholic etiologies increased and of surveillance programs were more frequently applied.

Unique situation of hepatocellular carcinoma in Egypt:A review of epidemiology and control measures

Hepatocellular carcinoma(HCC)is the sixth most common primary malignancy worldwide,and the third most common cause of death among cancers worldwide.HCC occurs in several pre-existing conditions,including hepatitis C,hepatitis B virus,and non-alcoholic cirrhosis.Egypt used to be the country with the heaviest hepatitis C virus(HCV)burden.The relationship between HCV and HCC is an important research area.In Egypt,HCC is a significant public health problem.A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV.A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt.Different treatment modalities are available in Egypt,with success rates comparable to global rates.The Egyptian health authorities have made the elimination of HCV from Egypt a special priority,and this approach should lead to a decrease in number of HCC cases in the near future.In this article we review the current situation of HCC in Egypt,including epidemiological aspects,relevant risk factors for HCC development,strategies,and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt.We highlight the different modalities for HCC treatment.

Combined hepatocellular cholangiocarcinoma: A clinicopathological update

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists alike.The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored recently.With a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease.In this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

Survival characteristics of fibrolamellar hepatocellular carcinoma:A Surveillance,Epidemiology,and End Results database study

BACKGROUND Fibrolamellar hepatocellular carcinoma(FL-HCC)is a rare and distinct type of hepatocellular carcinoma that frequently presents in an advanced stage in younger patients with no underlying liver disease.Currently,there is a limited understanding of factors that impact outcomes in FL-HCC.AIM To characterize the survival of FL-HCC by age,race,and surgical intervention.METHODS This is a retrospective study of The Surveillance,Epidemiology,and End Results database.We identified patients with FL-HCC between 2000-2018 by using an ICD-O-3 site code C22.0 and a histology code 8171/3:Hepatocellular carcinoma,fibrolamellar.In addition,demographics,tumor characteristics,types of surgical procedure,stages,and survival data were obtained.We conducted three separate survival analyses by age groups;≤19,20-59,and≥60-year-old,and race;White,Black,Hispanic,Asian and Pacific islanders(API),and surgical types;Wedge resection or segmental resection,lobectomy,extended lobectomy(lobectomy+locoregional therapy or resection of the other lobe),and transplant.The Chi-Square test analyzed categorical variables,and continuous variables were examined using the Mann-Whitney U test.The Kaplan-Meier survival curve was used to compare survival.Multivariate analysis was done with Cox regression analysis.RESULTS We identified 225 FL-HCC patients with a mean age of 36.9.Overall median survival was 34(95%CI:27-41)mo.Patients≤19-years-old had more advanced disease with positive lymph nodes status.However,they received more surgical interventions such as a wedge,segmental resection,lobectomy,extended lobectomy,and transplant.Survival for≤19 was 85(95%CI:37-137)mo,age 20-59 was 29(95%CI:18-41)mo,and age≥60 years was 12(95%CI:7-31)mo(P<0.001).There were no differences in stage,lymph node status,metastasis status,and surgical treatment among races.The median survival were;Whites had 39(95%CI:29-63),Blacks 26(95%CI:5-92),Hispanics 31(95%CI:11-54),and APIs 28(95%CI:5-39)mo(P=0.28).Of 225 patients,111 FL-HCC patients had surgical procedures.Median survivals for a wedge or segmental resection was 112(95%CI:78-NA),lobectomy was 92(95%CI:57-NA),extended lobectomy was 54(95%CI:23-NA),and a transplant was 63(95%CI:20-NA)mo(P<0.001).The median survival was better in patients who had surgical treatments regardless of lymph nodes or metastasis status(P<0.001).CONCLUSION FL-HCC occurs in a primarily younger population,but survival can be prolonged despite the aggressive disease.There were no racial differences in the survival of FL-HCC;however,Asians with FL-HCC tended to be older than in other races.Surgical treatment provided better survival even in those patients with nodal disease or metastases.Although future studies are needed to explore other therapies for FL-HCC,surgical options should be considered in all cases of FL-HCC unless contraindicated.

Prognostic Factors of Liver Transplantation for Hepatocellular Carcinoma: A Surveillance, Epidemiology, and End Results (SEER) Database Analysis

Objective We aimed to identify new,more accurate risk factors of liver transplantation for liver cancer through using the Surveillance,Epidemiology,and End Results(SEER)database.Methods Using the SEER database,we identified patients that had undergone surgical resection for non-metastatic hepatocellular carcinoma(HCC)and subsequent liver transplantation between 2010 and 2017.Overall survival(OS)was estimated using Kaplan-Meier plotter.Cox proportional hazards regression modelling was used to identify factors independently associated with recurrent disease[presented as adjusted hazard ratios(HR)with 95%CIs].Results Totally,1530 eligible patients were included in the analysis.There were significant differences in ethnicity(P=0.04),cancer stage(P<0.001),vascular invasion(P<0.001)and gall bladder involvement(P<0.001)between the groups that survived,died due to cancer,or died due to other causes.In the Cox regression model,there were no significant differences in OS at 5 years with different operative strategies(autotransplantation versus allotransplantation),nor at survival at 1 year with neoadjuvant radiotherapy.However,neoadjuvant radiotherapy did appear to improve survival at both 3 years(HR:0.540,95%CI:0.326–0.896,P=0.017)and 5 years(HR:0.338,95%CI:0.153–0.747,P=0.007)from diagnosis.Conclusion This study demonstrated differences in patient characteristics between prognostic groups after liver resection and transplantation for HCC.These criteria can be used to inform patient selection and consent in this setting.Preoperative radiotherapy may improve long-term survival post-transplantation.

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.

Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus–Di?erences in Etiology, Epidemiology and Prevention

In Germany, esophageal carcinoma is one of the ten most frequent causes of death. Normally the disease is found in men over the age of 50. Although squamous cell carcinoma (SCC) of the esophagus has been more commonly diagnosed over the past 30 years, there is increasing incidence of esophageal adenocarcinoma (AC) in Western industrialized countries. For SCC the known etiological risk factors are nicotine and alcohol abuse. For AC, they are moderate nicotine and alcohol consumption as well as gastro-esophageal re?ux and obesity.

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.

Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND Non-invasive differential diagnosis between hepatocellular carcinoma(HCC)and other liver cancer(i.e.cholangiocarcinoma or metastasis)is highly challenging and definitive diagnosis still relies on histological exam.The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features.Dynamic contrast-enhanced ultrasound(DCEUS)with standardized software could help to overcome these obstacles,providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion.AIM To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules.METHODS A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS Rise time was significantly higher in HCC patients with a standardized mean difference(SMD)of 0.83(95%CI:0.48-1.18).Similarly,other statistically significant parameters were mean transit time local with a SMD of 0.73(95%CI:0.20-1.27),peak enhancement with a SMD of 0.37(95%CI:0.03-0.70),area wash-in area under the curve with a SMD of 0.47(95%CI:0.13-0.81),wash-out area under the curve with a SMD of 0.55(95%CI:0.21-0.89)and wash-in and wash-out area under the curve with SMD of 0.51(95%CI:0.17-0.85).SMD resulted not significant in fall time and wash-in rate,but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma.CONCLUSION DCEUS could improve non-invasive diagnosis of HCC,leading to less liver biopsy and early treatment.This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound

BACKGROUND Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC)represent the predominant histological types of primary liver cancer,comprising over 99%of cases.Given their differing biological behaviors,prognoses,and treatment strategies,accurately differentiating between HCC and ICC is crucial for effective clinical management.Radiomics,an emerging image processing technology,can automatically extract various quantitative image features that may elude the human eye.Reports on the application of ultrasound(US)-based radiomics methods in distinguishing HCC from ICC are limited.METHODS In our retrospective study,we included a total of 280 patients who were diagnosed with ICC(n=140)and HCC(n=140)between 1999 and 2019.These patients were divided into training(n=224)and testing(n=56)groups for analysis.US images and relevant clinical characteristics were collected.We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models.We compared the diagnostic performances of these ultrasomics models with that of radiologists.RESULTS Four distinct ultrasomics models were constructed,with the number of selected features varying between models:13 features for the US model;15 for the contrast-enhanced ultrasound(CEUS)model;13 for the combined US+CEUS model;and 21 for the US+CEUS+clinical data model.The US+CEUS+clinical data model yielded the highest area under the receiver operating characteristic curve(AUC)among all models,achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort.This performance exceeded even the most experienced radiologist(AUC=0.964).The AUC for the US+CEUS model(training cohort AUC=0.964,test cohort AUC=0.955)was significantly higher than that of the US model alone(training cohort AUC=0.822,test cohort AUC=0.816).This finding underscored the significant benefit of incorporating CEUS information in accurately distin-guishing ICC from HCC.CONCLUSION We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC,which outperformed experienced radiologists.

Three-in-one incidence of hepatocellular carcinoma,cholangiocellular carcinoma,and neuroendocrine carcinoma:A case report

BACKGROUND Primary hepatic neuroendocrine carcinoma(NEC)is rare,and a combination with hepatocellular carcinoma(HCC)and cholangiocarcinoma(CCA)is extremely rare.To date,only four combination cases have been reported.The present paper describes the fifth patient.CASE SUMMARY A 32-year-old Chinese man with chronic hepatitis B was hospitalized for persistent upper abdominal pain.Abdominal computed tomography(CT)examination revealed a liver mass.The tumor was located in the 7th and 8th segments of the liver,and CT and magnetic resonance imaging findings were consistent with the diagnosis of HCC.Laboratory examinations revealed the following:Alanine aminotransferase,243 U/L;aspartate aminotransferase,167 U/L;alpha-fetoprotein,4519μg/L.Laparoscopic right lobe hepatectomy was performed on the liver mass.Postoperative pathology showed low differentiation HCC plus medium and low differentiation CCA combined with NEC.One month after the surgery,the patient suffered from epigastric pain again.Liver metastasis was detected by CT,and tumor transcatheter arterial chemoembolization was performed.Unfortunately,the liver tumor was progressively increased and enlarged,and after 1 mo,the patient died of liver failure.CONCLUSION This is a rare case,wherein the tumor is highly aggressive,grows rapidly,and metastasizes in a short period.Imaging and laboratory tests can easily misdiagnose or miss such cases;thus,the final diagnosis relies on pathology.

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice

Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated mortality.This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease.This makes the management of patients more challenging,since physicians must take into consideration two different conditions,the chronic liver disease and the tumor.The underlying liver disease has several implications in clinical practice,because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC,obstacles in surveillance,and differences in the efficacy of the treatment against HCC.A shift in the prevalence of liver diseases has been evident over the last few years,with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance.Therefore,in an era of personalized medicine,it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

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.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.