Background:Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma(HCC).Based on age,sex,alpha-fetoprote...Background:Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma(HCC).Based on age,sex,alpha-fetoprotein(AFP),and protein induced by vitamin K absence II(PIVKA-II)with/without AFP-L3,ASAP and GALAD models are potential diagnostic panels.The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases(CLDs).Methods:A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chi-nese hospitals.The etiologies of CLDs included hepatitis B virus(HBV),hepatitis C virus(HCV),alcoholic liver disease(ALD),and nonalcoholic fatty liver disease(NAFLD).Using area under the receiver operating characteristic curve(AUC)values,the diagnostic performances of ASAP and GALAD models were com-pared to detect HCC among patients with various etiologies of CLDs.Results:Among 248 HCC patients and 722 CLD controls,the ASAP model demonstrated the highest AUC(0.886)to detect HCC at any stage,outperforming the GALAD model(0.853,P=0.001),as well as any individual biomarker(0.687-0.799,all P<0.001).In the subgroup analysis of various CLDs etiologies,the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology.In addition,the ASAP model performed better in detecting early-stage(BCLC stage 0/A)HCC versus the GALAD model.Conclusions:Despite using one less laboratory variable(AFP-L3),the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various eti-ologies of CLDs-related HCC.展开更多
Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and...Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.展开更多
Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths worldwide.The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments.Despite be...Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths worldwide.The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments.Despite being widely used,alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC.The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins,metabolites,circulating tumor deoxyribonucleic acid,and circulating non-coding ribonucleic acid.Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment,thus prolonging survival outcomes.Currently,multiple clinical trials involving locoregional,systemic therapies,and combinations of these modalities are changing therapeutic strategies for different stage HCC.Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future.This review summarizes the most recent advances in noninvasive early molecular detection,current therapy strategies,and potential immunotherapeutic innovations of HCC.展开更多
Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma(HCC).Overwhelming evidence from publishe...Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma(HCC).Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis,predicting responses to specific therapies,evaluating prognosis before or after therapy,as well as serving as novel therapeutic targets.Detection and analysis of proteins,metabolites,circulating nucleic acids,circulating tumor cells,and extracellular vesicles in body fluids(e.g.,blood and urine)and gut microbiota(e.g.,in feces)have excellent capabilities to improve different aspects of management of HCC.Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis,treatment,and monitoring responses of HCC to conventional therapies,most of which may improve diagnosis and management of HCC in the future.This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.展开更多
To the Editor:We read with great interest the recent article by Chang et al.[1].By analyzing the data of 1350 cirrhotic patients,the authors concluded that statin significantly decreases the risk of decompensation of ...To the Editor:We read with great interest the recent article by Chang et al.[1].By analyzing the data of 1350 cirrhotic patients,the authors concluded that statin significantly decreases the risk of decompensation of cirrhosis,mortality and hepatocellular carcinoma(HCC)incidence,and these effects are dose dependent.展开更多
Hepatocellular carcinoma(HCC)is still one of the most challenging malignancies worldwide,ranked as the third leading cause of cancer-related mortality with over 830,000 deaths annually(1).Although hepatic resection of...Hepatocellular carcinoma(HCC)is still one of the most challenging malignancies worldwide,ranked as the third leading cause of cancer-related mortality with over 830,000 deaths annually(1).Although hepatic resection offers potential cure chance for patients with resectable HCC,the recurrence rate attains 70%within 5 years after surgery(2).This very high recurrence rate underscores the urgent need for more effective perioperative management against recurrence.The recent success of immune checkpoint inhibitors(ICIs)in advanced-stage HCC,exemplified by combination regimens like atezolizumab-bevacizumab and durvalumab-tremelimumab,has sparked interest in their application in the neoadjuvant and adjuvant setting(3,4).展开更多
Liver diseases continue to pose formidable challenges to global health in 2025,characterized by their broad disease spectrum and therapeutic complexity.Among the diverse array of hepatic disorders,hepatocellular carci...Liver diseases continue to pose formidable challenges to global health in 2025,characterized by their broad disease spectrum and therapeutic complexity.Among the diverse array of hepatic disorders,hepatocellular carcinoma(HCC)ranks as the sixth most common cancer and third leading cause of cancer-related mortality worldwide.1 Reflecting changing global health patterns and lifestyle factors,the landscape of liver diseases is experiencing profound changes:while successful viral hepatitis control programs in many regions have led to a gradual decline in virus-related HCC incidence.展开更多
Background:Hepatectomy is the preferred treatment for solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,but long-term survival remains unsatisfactory in certain patients.We so...Background:Hepatectomy is the preferred treatment for solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,but long-term survival remains unsatisfactory in certain patients.We sought to identify whether the grading severity of microscopic vascular invasion(MVI)was associated with recurrence and survival among patients with solitary HCC.Methods:Consecutive patients who underwent hepatectomy for solitary HCC were identified from a multicenter prospectively-collected database.Patients were categorized into three groups according to the MVI grading system proposed by the Liver Cancer Pathology Group of China:M0(no MVI),M1(1-5 sites of MVI occurring≤1.0 cm away from the tumor),and M2(>5 sites occurring≤1.0 cm or any site occurring>1 cm away from the tumor).Recurrence-free survival(RFS)and overall survival(OS)were compared among the groups.Results:Among 227 patients,97(42.7%),83(36.6%),and 47(20.7%)patients had M0,M1,and M2,respectively.Median RFS rates among patients with M0,M1,and M2 were 38.3,35.1,11.6 months,respectively,while OS rates were 66.8,62.3,30.6 months,respectively(both P<0.001).Multivariate Cox-regression analyses demonstrated that both M1 and M2 were independent risk factors for RFS(hazard ratio 1.20,95%CI:1.03-1.89,P=0.040;and hazard ratio 1.67,95%CI:1.06-2.64,P=0.027)and OS(hazard ratio 1.28,95%CI:1.05-2.07,P=0.035;and hazard ratio 1.97,95%CI:1.15-3.38,P=0.013).Conclusions:Grading severity of MVI was independently associated with RFS and OS after hepatectomy for solitary HCC.Enhanced surveillance for recurrence and potentially adjuvant therapy may be considered for patients with MVI,especially individuals with more severe MVI grading(M2).展开更多
Background:The application of Pringle maneuver(PM)during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion,but its effect on long-term recurrence and survival for patients with h...Background:The application of Pringle maneuver(PM)during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion,but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma(HCC)remains controversial.We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC.Methods:Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified.Using two propensity score methods[propensity score matching(PSM)and inverse probability of treatment weight(IPTW)],cumulative recurrence rate and cancer-specific mortality(CSM)were compared between the patients in the PM and non-PM groups.Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors.Results:Of the 2,798 included patients,2,404 and 394 did and did not adopt PM(the PM and non-PM groups),respectively.The rates of intraoperative blood transfusion,postoperative 30-day mortality and morbidity were comparable between the two groups(all P>0.05).In the PSM cohort by the 1:3 ratio,compared to 382 patients in the non-PM group,1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM(63.9%and 39.1%vs.55.3%and 31.6%,both P<0.05).Similar results were also yielded in the entire cohort and the IPTW cohort.Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts[hazard ratio(HR),0.82 and 0.77 in the adjusted entire cohort,HR 0.80 and 0.73 in the PSM cohort,and HR 0.80 and 0.76 in the IPTW cohort,respectively].Conclusions:The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20–25%.展开更多
Hepatocellular carcinoma(HCC)is a prevalent malignancy worldwide,ranking as the sixth most common malignancy and the third leading cause of cancer-related mortality.Late diagnosis,limited management options,and its co...Hepatocellular carcinoma(HCC)is a prevalent malignancy worldwide,ranking as the sixth most common malignancy and the third leading cause of cancer-related mortality.Late diagnosis,limited management options,and its complex etiology contribute to the poor prognosis and high mortality rates.Recent advances in understanding the molecular mechanisms of HCC and innovations in high-throughput sequencing technologies have led to the development of molecular diagnostics and personalized therapies for this challenging malignancy.This review provides a comprehensive overview of research on the molecular diagnosis and individualized treatment for HCC.We highlight key advances and potential future directions and discuss the application of next-generation sequencing technologies to identify and characterize genetic and epigenetic alterations in HCC patients.These technologies may aid in the selection of targeted therapies,prediction of treatment response,and monitoring disease progression.Furthermore,we explore the role of liquid biopsy in HCC diagnosis,prognosis prediction,and treatment monitoring,focusing on circulating tumor cells,circulating tumor DNA,and extracellular vesicles.We also explore the evolving landscape of personalized therapy for HCC,including targeted therapies against key oncogenic signaling pathways,immune checkpoint inhibitors,tumor-agnostic therapies,and innovative cellbased therapies.We discuss the challenges and opportunities that lie ahead in the quest to improve HCC patient outcomes through the integration of molecular diagnostics and individualized precision therapies.We emphasize the need for multi-interdisciplinary collaboration,refinement of predictive and prognostic biomarkers,and the development of more effective combination strategies for HCC management in the new area of precision medicine.展开更多
The rising global impact of liver disorders,such as non-alcoholic fatty liver disease(NAFLD),viral hepatitis,and hepatocellular carcinoma(HCC),stands as a daunting hurdle in modern healthcare.These ailments,now major ...The rising global impact of liver disorders,such as non-alcoholic fatty liver disease(NAFLD),viral hepatitis,and hepatocellular carcinoma(HCC),stands as a daunting hurdle in modern healthcare.These ailments,now major causes of global morbidity and mortality,exert a profound strain on health systems and affect the life quality of patients.The World Health Organization's estimates reveal liver conditions lead to around 2 million deaths annually,with viral hepatitis contributing to 1.34 million of these,underscoring the critical need for enhanced research and novel therapeutic interventions.Additionally,the escalating incidence of NAFLD,intertwined with the worldwide obesity crisis,is swiftly rising,affecting about 25%of the global population[1].This surge underscores an urgent call for extensive investigative work across molecular science,clinical applications,and public health initiatives.展开更多
Background and aims:The ASAP and GALAD scores are widely used diagnostic models for detecting hepatocellular carcinoma(HCC),incorporating factors such as sex,age,alpha-fetoprotein(AFP),protein induced by vitamin K abs...Background and aims:The ASAP and GALAD scores are widely used diagnostic models for detecting hepatocellular carcinoma(HCC),incorporating factors such as sex,age,alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ),and lens culinaris agglutinin-reactive fraction of AFP(AFP-L3%).This study compares the diagnostic efficacy of the ASAP and GALAD scores in the early detection of HCC in patients with non-alcoholic fatty liver disease(NAFLD).Methods:NAFLD patients with and without HCC were recruited from 12 Chinese tertiary hospitals.Serum levels of AFP,PIVKA-II,and AFP-L3%were measured.The diagnostic accuracy of individual biomarkers,the ASAP score,and the GALAD score in detecting NAFLD-HCC at various stages was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC)values.Results:In a cohort of 147 NAFLD-HCC cases and 460 NAFLD controls,both the ASAP and GALAD scores outperformed individual biomarkers in detecting NAFLD-HCC.The ASAP score demonstrated a high AUC of 0.910(sensitivity:80.3%,specificity:92.8%)for identifying NAFLD-HCC at all stages,surpassing AFP(AUC:0.716,P<0.001),PIVKA-II(AUC:0.849,P<0.001),AFP-L3%(AUC:0.663,P<0.001),and the GALAD score(AUC:0.882,P?0.014).Comparable results were observed for early-stage NAFLD-HCC and for detecting HCC in NAFLD patients with or without cirrhosis.Conclusion:The ASAP score,which excludes the AFP-L3%indicator,demonstrated superior performance in differentiating NAFLD-HCC compared to the GALAD score,suggesting its potential for early screening of HCC in NAFLD patients.展开更多
Introduction:Gallbladder polyps(GPs)are protrusions of the gallbladder wall into the lumen,and are commonly detected during ultrasound examinations.Traditional management of multiple GPs(MGPs)has been conservative,inc...Introduction:Gallbladder polyps(GPs)are protrusions of the gallbladder wall into the lumen,and are commonly detected during ultrasound examinations.Traditional management of multiple GPs(MGPs)has been conservative,including lifestyle interventions,regular monitoring,and surgical intervention in certain cases,but this approach poses risks of polyps enlargement and increase of number,as well as patients’psychological burdens.Danning Tablets,a traditional Chinese medicine,have emerged as a potential non-surgical treatment for GPs,showing promise in reducing polyp size and alleviating symptoms,backed by their anti-inflammatory and antitumor properties demonstrated in preclinical studies.This suggests the need for further research into Danning Tablets as an alternative treatment for MGPs.Methods and analysis:The study is designed as a prospective,randomized,controlled,open-label trial.The study will be conducted across multiple centres specializing in gastroenterology and hepatology.Participants will be recruited from these centres,ensuring a diverse patient demographic.Adult patients diagnosed with MGPs,based on ultrasound findings,will be included.Exclusion criteria include patients with a history of gallbladder cancer,previous gallbladder surgery,or serious comorbid conditions.The control group will receive standard care,including dietary and lifestyle advice,while the intervention group will receive Danning Tablets and standard care.The dosage and administration of Danning Tablets will follow established clinical guidelines.The primary outcome will be the change in size of the largest gallbladder polyps on week 24±1,measured by ultrasound.The secondary outcomes will include symptom improvement and recording of any adverse events.The study will span over a period of 6 months,with periodic assessments at baseline,4,8,12,and 24 weeks.展开更多
Objective This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy(SIC)in sepsis patients.Methods We conducted a retrospective study of septic patients admitted to the Intensive...Objective This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy(SIC)in sepsis patients.Methods We conducted a retrospective study of septic patients admitted to the Intensive Care Units of Shandong Provincial Hospital(Central Campus and East Campus),and Shenxian People’s Hospital from January 2019 to September 2024.We used Kaplan-Meier analysis to assess survival outcomes.LASSO regression identified predictive variables,and logistic regression was employed to analyze risk factors for pre-SIC.A nomogram prediction model was developed via R software and evaluated via receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).Results Among 309 patients,236 were in the training set,and 73 were in the test set.The pre-SIC group had higher mortality(44.8%vs.21.3%)and disseminated intravascular coagulation(DIC)incidence(56.3%vs.29.1%)than the non-SIC group.LASSO regression identified lactate,coagulation index,creatinine,and SIC scores as predictors of pre-SIC.The nomogram model demonstrated good calibration,with an AUC of 0.766 in the development cohort and 0.776 in the validation cohort.DCA confirmed the model’s clinical utility.Conclusion SIC is associated with increased mortality,with pre-SIC further increasing the risk of death.The nomogram-based prediction model provides a reliable tool for early SIC identification,potentially improving sepsis management and outcomes.展开更多
Recurrence is common among patients undergoing hepatic resection for hepatocellular carcinoma(HCC),which greatly limits long-term survival.We aimed to identify predictors and long-term prognosis of early and late recu...Recurrence is common among patients undergoing hepatic resection for hepatocellular carcinoma(HCC),which greatly limits long-term survival.We aimed to identify predictors and long-term prognosis of early and late recurrence after HCC resection.Methods:Multicenter data of patients who underwent HCC resection between 2002 and 2016 were analyzed.Recurrence was divided into early(≤2 years)and late recurrence(>2 years after surgery).Predictors of early and late recurrence,and prognostic factors of post-recurrence survival(PRS)were identified by univariate and multivariate analyses.Results:Among 1,426 patients,554(38.8%)and 348(24.4%)developed early and late recurrence,respectively.Independent predictors associated with early recurrence included preoperative alpha-fetoprotein level>400μg/L,resection margin<1 cm,and tumor size>5.0 cm,multiplicity,macrovascular and microvascular invasion,and satellites of the initial tumor at the first diagnosis of HCC;independent predictors associated with late recurrence included male,cirrhosis,and tumor size>5.0 cm,multiplicity,macrovascular and microvascular invasion,and satellites of the initial tumor.Patients with early recurrence had a lower likelihood of undergoing potentially curative treatments for recurrence(37.2%vs.48.0%,P<0.001)and a worse median PRS(13.5 vs.36.6 months,P<0.001)vs.patients who had late recurrence.Multivariate analysis revealed that early recurrence and irregular postoperative surveillance were independently associated with worse PRS[hazard ratio(HR)=1.250,95%CI:1.016-1.538,P=0.035;and HR=1.983,95%CI:1.677-2.345,P<0.001].Conclusions:Predictors associated with early and late recurrence after curative resection for patients with HCC were generally same,although several did differ.Patients with late recurrence had better long-term survival than patients with early recurrence.展开更多
Background:A solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,regardless of tumor size,is currently classified as early-stage disease by the latest Barcelona Clinic Liver Can...Background:A solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,regardless of tumor size,is currently classified as early-stage disease by the latest Barcelona Clinic Liver Cancer(BCLC)staging system.While the preferred treatment is surgical resection,the association of tumor morphology with long-term survival outcomes after liver resection for a solitary huge HCC of≥10 cm has not been defined.Methods:Patients who underwent curative liver resection for a solitary huge HCC were identified from a multicenter database.Preoperative imaging findings were used to define spherical-or ellipsoidal-shaped lesions with smooth edges as balloon-shaped HCCs(BS-HCCs);out-of-shape lesions or lesions of any shape with matt edges were defined as non-balloon-shaped HCCs(NBS-HCCs).The two groups of patients with BS-HCCs and NBS-HCCs were matched in a 1:1 ratio using propensity score matching(PSM).Clinicopathologic characteristics,long-term overall survival(OS)and recurrence-free survival(RFS)were assessed.Results:Among patients with a solitary huge HCC,74 pairs of patients with BS-HCC and NBS-HCC were matched.Tumor pathological features including proportions of microvascular invasion,satellite nodules,and incomplete tumor encapsulation in the BS-HCC group were lower than the NBS-HCC group.At a median follow-up of 50.7 months,median OS and RFS of all patients with a solitary huge HCC after PSM were 27.8 and 10.1 months,respectively.The BS-HCC group had better median OS and RFS than the NBS-HCC group(31.9 vs.21.0 months,P=0.01;and 19.7 vs.6.4 months,P=0.015).Multivariate analyses identified BS-HCC as independently associated with better OS(HR=0.592,P=0.009)and RFS(HR=0.633,P=0.013).Conclusions:For a solitary huge HCC,preoperative imaging on tumor morphology was associated with prognosis following resection.In particular,patients with BS-HCCs had better long-term survival following liver resection versus patients with large NBS-HCCs.展开更多
Background:Family history is a risk factor for the development of hepatocellular carcinoma(HCC).The aim of the current study was to investigate the association between family history of HCC and long-term oncologic pro...Background:Family history is a risk factor for the development of hepatocellular carcinoma(HCC).The aim of the current study was to investigate the association between family history of HCC and long-term oncologic prognosis among patients undergoing curative liver resection for hepatitis B virus(HBV)-related HCC.Methods:Patients who underwent curative liver resection of HBV-related HCC between 2003 and 2013 were consecutively enrolled.Family history was defined as a self-reported history of HCC in a first-degree relative.Propensity score matching(PSM)and multivariable Cox-regression analyses were performed to compare overall survival(OS)and recurrence-free survival(RFS)among patients with and without a family history.Results:Among 1,112 patients,183(16.5%)patients had a family history of HCC.Using PSM,179 pairs of patients with and without a family history were created that had no differences in the baseline characteristics and operative variables.On matched analysis,family history was associated with decreased OS and RFS after curative-intent resection of HBV-related HCC in the propensity matching cohort(P=0.042 and 0.006,respectively).On multivariable Cox-regression analyses,a family history of HCC was associated with decreased OS(HR:1.574;95%CI:1.171–2.116;P=0.003)and RFS(HR:1.534;95%CI:1.176–2.002;P=0.002)after adjusting for other prognostic risk factors.Conclusions:Family history was associated with decreased OS and RFS rates among patients undergoing curative liver resection of HBV-related HCC.展开更多
Background The role of adjuvant transarterial chemoembolisation(TACE)to reduce postoperative recurrence varies widely among patients undergoing hepatectomy with curative intent for hepatocellular carcinoma(HCC).Person...Background The role of adjuvant transarterial chemoembolisation(TACE)to reduce postoperative recurrence varies widely among patients undergoing hepatectomy with curative intent for hepatocellular carcinoma(HCC).Personalised predictive tool to select which patients may benefit from adjuvant TACE is lacking.This study aimed to develop and validate an online calculator for estimating the reduced risk of early recurrence from adjuvant TACE for patients with HCC.Methods From a multi-institutional database,2590 eligible patients undergoing curative-intent hepatectomy for HCC were enrolled,and randomly assigned to the training and validation cohorts.Independent predictors of early recurrence within 1 year of surgery were identified in the training cohort,and subsequently used to construct a model and corresponding prediction calculator.The predictive performance of the model was validated using concordance indexes(C-indexes)and calibration curves,and compared with conventional HCC staging systems.The reduced risk of early recurrence when receiving adjuvant TACE was used to estimate the expected benefit from adjuvant TACE.Results The prediction model was developed by integrating eight factors that were independently associated with risk of early recurrence:alpha-fetoprotein level,maximum tumour size,tumour number,macrovascular and microvascular invasion,satellite nodules,resection margin and adjuvant TACE.The model demonstrated good calibration and discrimination in the training and validation cohorts(C-indexes:0.799 and 0.778,respectively),and performed better among the whole cohort than four conventional HCC staging systems(C-indexes:0.797 vs 0.562–0.673,all p<0.001).An online calculator was built to estimate the reduced risk of early recurrence from adjuvant TACE for patients with resected HCC.Conclusions The proposed calculator can be adopted to assist decision-making for clinicians and patients to determine which patients with resected HCC can significantly benefit from adjuvant TACE.WHAT IS ALREADY KNOWN ON THIS TOPIC⇒Previous studies have indicated that adjuvant transarterial chemoembolisation(TACE)may im-prove long-term survival in certain subgroups of patients with hepatocellular carcinoma(HCC)after hepatectomy.⇒However,these studies did not provide personalised risk assessment or net benefit estimation for indi-vidual patients,highlighting the need for a more refined prediction model.WHAT THIS STUDY ADDS⇒This study developed a risk prediction model in-corporating eight independent factors associat-ed with early recurrence after hepatectomy for HCC,demonstrating good predictive accuracy and discrimination.⇒The model outperformed four commonly used con-ventional HCC staging systems and facilitated the development of an online calculator to estimate in-dividual patient’s reduced risk of early recurrence using adjuvant TACE.HOW THIS STUDY MIGHT AFFECT RESEARCH,PRACTICE OR POLICY⇒The study’s findings may assist clinicians in decid-ing whether to use adjuvant TACE after hepatectomy for HCC,potentially improving patient outcomes.⇒Further research should validate the model with larger cohorts or those from other centres to assess its broader applicability.展开更多
Hepatocellular carcinoma(HCC),a typical inflammatory-related cancer,mainly occurs in patients with chronic liver diseases.Moreover,the liver is an immunologically privileged apparatus with multiple immunosuppressive c...Hepatocellular carcinoma(HCC),a typical inflammatory-related cancer,mainly occurs in patients with chronic liver diseases.Moreover,the liver is an immunologically privileged apparatus with multiple immunosuppressive cell groups.The long process of inflammation-mediated carcinogenesis turns the HCC tumor microenvironment(TME)into one with strong immunosuppression,facilitating the immune escape of HCC cells.Accumulated data have manifested that tumor-associated cell-derived exosomes carry diverse molecular cargoes(e.g.,proteins and nucleic acids)for mediating cell-to-cell communication and are implicated in TME remodeling to promote tumor-infiltrating immune cell reprogramming,ultimately creating a tumor-friendly microenvironment.Characterized by several intrinsic attributes,such as good stability(bilayer-like structure)and high biocompatibility(cell secretion),exosomes can be modified or engineered as nanocarriers to deliver tumor-specific antigens or antitumor drugs to targeted cells or organs,thus effectively triggering the HCC cell elimination by the immune system.This review aimed to highlight the pivotal role of exosomes in regulating immune escape mechanisms in HCC and recent advances in exosome-mediated immunotherapy for HCC.展开更多
China is a big nation primarily affected by liver cancer with the number of patients with liver cancer accounting more than 50%worldwide.1,2 Dr.Wu Mengchao(August 1922-May 2021;Fig.1)has devoted almost all his energy ...China is a big nation primarily affected by liver cancer with the number of patients with liver cancer accounting more than 50%worldwide.1,2 Dr.Wu Mengchao(August 1922-May 2021;Fig.1)has devoted almost all his energy and wisdom to fighting against liver cancer for more than half a century.Dr.Wu graduated from the Tongji University School of Medicine in 1949.In 1960,Dr.Wu worked as the chief surgeon completing the first case of surgical resection for liver cancer in China.展开更多
基金supported by grants from the National Natural Science Foundation of China(81972726 and 82273074)Abbott Diagnostics(ADD-China-2016).
文摘Background:Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma(HCC).Based on age,sex,alpha-fetoprotein(AFP),and protein induced by vitamin K absence II(PIVKA-II)with/without AFP-L3,ASAP and GALAD models are potential diagnostic panels.The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases(CLDs).Methods:A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chi-nese hospitals.The etiologies of CLDs included hepatitis B virus(HBV),hepatitis C virus(HCV),alcoholic liver disease(ALD),and nonalcoholic fatty liver disease(NAFLD).Using area under the receiver operating characteristic curve(AUC)values,the diagnostic performances of ASAP and GALAD models were com-pared to detect HCC among patients with various etiologies of CLDs.Results:Among 248 HCC patients and 722 CLD controls,the ASAP model demonstrated the highest AUC(0.886)to detect HCC at any stage,outperforming the GALAD model(0.853,P=0.001),as well as any individual biomarker(0.687-0.799,all P<0.001).In the subgroup analysis of various CLDs etiologies,the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology.In addition,the ASAP model performed better in detecting early-stage(BCLC stage 0/A)HCC versus the GALAD model.Conclusions:Despite using one less laboratory variable(AFP-L3),the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various eti-ologies of CLDs-related HCC.
基金This study was supported by grants from the National Natural Science Foundation of China(81972726,82273074 and 82372813)Dawn Project Foundation of Shanghai(21SG36)+2 种基金Shanghai Health Academic Leader Program(2022XD001)the Natural Science Foundation of Shanghai(22ZR1477900)Adjunct Talent Fund of Zhejiang Provincial People’s Hospital(2021-YT).
文摘Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.
基金Supported by the National Natural Science Foundation of China(General Program),No.81972726.
文摘Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths worldwide.The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments.Despite being widely used,alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC.The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins,metabolites,circulating tumor deoxyribonucleic acid,and circulating non-coding ribonucleic acid.Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment,thus prolonging survival outcomes.Currently,multiple clinical trials involving locoregional,systemic therapies,and combinations of these modalities are changing therapeutic strategies for different stage HCC.Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future.This review summarizes the most recent advances in noninvasive early molecular detection,current therapy strategies,and potential immunotherapeutic innovations of HCC.
基金Supported by National Natural Science Foundation of China,No.81972726,No.81871949 and No.81572345.
文摘Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma(HCC).Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis,predicting responses to specific therapies,evaluating prognosis before or after therapy,as well as serving as novel therapeutic targets.Detection and analysis of proteins,metabolites,circulating nucleic acids,circulating tumor cells,and extracellular vesicles in body fluids(e.g.,blood and urine)and gut microbiota(e.g.,in feces)have excellent capabilities to improve different aspects of management of HCC.Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis,treatment,and monitoring responses of HCC to conventional therapies,most of which may improve diagnosis and management of HCC in the future.This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.
文摘To the Editor:We read with great interest the recent article by Chang et al.[1].By analyzing the data of 1350 cirrhotic patients,the authors concluded that statin significantly decreases the risk of decompensation of cirrhosis,mortality and hepatocellular carcinoma(HCC)incidence,and these effects are dose dependent.
基金funded by the Chongqing Technology Innovation and Application Development Special Key Project(No.CSTB2023TIAD-KPX0049-4).
文摘Hepatocellular carcinoma(HCC)is still one of the most challenging malignancies worldwide,ranked as the third leading cause of cancer-related mortality with over 830,000 deaths annually(1).Although hepatic resection offers potential cure chance for patients with resectable HCC,the recurrence rate attains 70%within 5 years after surgery(2).This very high recurrence rate underscores the urgent need for more effective perioperative management against recurrence.The recent success of immune checkpoint inhibitors(ICIs)in advanced-stage HCC,exemplified by combination regimens like atezolizumab-bevacizumab and durvalumab-tremelimumab,has sparked interest in their application in the neoadjuvant and adjuvant setting(3,4).
文摘Liver diseases continue to pose formidable challenges to global health in 2025,characterized by their broad disease spectrum and therapeutic complexity.Among the diverse array of hepatic disorders,hepatocellular carcinoma(HCC)ranks as the sixth most common cancer and third leading cause of cancer-related mortality worldwide.1 Reflecting changing global health patterns and lifestyle factors,the landscape of liver diseases is experiencing profound changes:while successful viral hepatitis control programs in many regions have led to a gradual decline in virus-related HCC incidence.
基金supported by the National Natural Science Foundation of China(Nos.81972726 and 82273074)Dawn Project Foundation of Shanghai(No.21SG36)+3 种基金Adjunct Talent Fund of Zhejiang Provincial People’s Hospital(No.2021-YT)Shanghai Health and Hygiene Discipline Leader Project(No.2022XD001)the Natural Science Foundation of Shanghai(No.22ZR1477900)Shanghai Science and Technology Committee Rising-Star Program(No.22QA1411600).
文摘Background:Hepatectomy is the preferred treatment for solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,but long-term survival remains unsatisfactory in certain patients.We sought to identify whether the grading severity of microscopic vascular invasion(MVI)was associated with recurrence and survival among patients with solitary HCC.Methods:Consecutive patients who underwent hepatectomy for solitary HCC were identified from a multicenter prospectively-collected database.Patients were categorized into three groups according to the MVI grading system proposed by the Liver Cancer Pathology Group of China:M0(no MVI),M1(1-5 sites of MVI occurring≤1.0 cm away from the tumor),and M2(>5 sites occurring≤1.0 cm or any site occurring>1 cm away from the tumor).Recurrence-free survival(RFS)and overall survival(OS)were compared among the groups.Results:Among 227 patients,97(42.7%),83(36.6%),and 47(20.7%)patients had M0,M1,and M2,respectively.Median RFS rates among patients with M0,M1,and M2 were 38.3,35.1,11.6 months,respectively,while OS rates were 66.8,62.3,30.6 months,respectively(both P<0.001).Multivariate Cox-regression analyses demonstrated that both M1 and M2 were independent risk factors for RFS(hazard ratio 1.20,95%CI:1.03-1.89,P=0.040;and hazard ratio 1.67,95%CI:1.06-2.64,P=0.027)and OS(hazard ratio 1.28,95%CI:1.05-2.07,P=0.035;and hazard ratio 1.97,95%CI:1.15-3.38,P=0.013).Conclusions:Grading severity of MVI was independently associated with RFS and OS after hepatectomy for solitary HCC.Enhanced surveillance for recurrence and potentially adjuvant therapy may be considered for patients with MVI,especially individuals with more severe MVI grading(M2).
基金Key Clinical Specialty Discipline Construction Program of Fuzhou,Fujian(No.201912002)Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic Tumors(No.2020Y2013)+4 种基金Scientific Foundation of Fuzhou Municipal Health commission(No.2021-S-wp1)National Natural Science Foundation of China(No.62275050)Major Research Projects for Young and Middle-aged Talent of Fujian Provincial Health Commission(No.2021ZQNZD013)Dawn Project Foundation of Shanghai(No.21SG36)Adjunct Talent Fund of Zhejiang Provincial People’s Hospital(No.2021-YT).
文摘Background:The application of Pringle maneuver(PM)during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion,but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma(HCC)remains controversial.We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC.Methods:Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified.Using two propensity score methods[propensity score matching(PSM)and inverse probability of treatment weight(IPTW)],cumulative recurrence rate and cancer-specific mortality(CSM)were compared between the patients in the PM and non-PM groups.Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors.Results:Of the 2,798 included patients,2,404 and 394 did and did not adopt PM(the PM and non-PM groups),respectively.The rates of intraoperative blood transfusion,postoperative 30-day mortality and morbidity were comparable between the two groups(all P>0.05).In the PSM cohort by the 1:3 ratio,compared to 382 patients in the non-PM group,1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM(63.9%and 39.1%vs.55.3%and 31.6%,both P<0.05).Similar results were also yielded in the entire cohort and the IPTW cohort.Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts[hazard ratio(HR),0.82 and 0.77 in the adjusted entire cohort,HR 0.80 and 0.73 in the PSM cohort,and HR 0.80 and 0.76 in the IPTW cohort,respectively].Conclusions:The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20–25%.
基金supported by the National Natural Science Foundation of China(Nos 81972726 and 82273074 for Yang T,No.82372813 for Wang MD,Nos 82241223 and U20A20360 for Lv GY),Dawn Project Foundation of Shanghai(No.21SG36 for Yang T)Shanghai Health and Hygiene Discipline Leader Project(No.2022XD001 for Yang T)+2 种基金Shanghai Outstanding Academic Leader Program(No.23XD1424900 for Yang T)the Natural Science Foundation of Shanghai(No.22ZR1477900 for Wang MD)Shanghai Science and Technology Committee Rising-Star Program(No.22QA1411600 for Wang MD).
文摘Hepatocellular carcinoma(HCC)is a prevalent malignancy worldwide,ranking as the sixth most common malignancy and the third leading cause of cancer-related mortality.Late diagnosis,limited management options,and its complex etiology contribute to the poor prognosis and high mortality rates.Recent advances in understanding the molecular mechanisms of HCC and innovations in high-throughput sequencing technologies have led to the development of molecular diagnostics and personalized therapies for this challenging malignancy.This review provides a comprehensive overview of research on the molecular diagnosis and individualized treatment for HCC.We highlight key advances and potential future directions and discuss the application of next-generation sequencing technologies to identify and characterize genetic and epigenetic alterations in HCC patients.These technologies may aid in the selection of targeted therapies,prediction of treatment response,and monitoring disease progression.Furthermore,we explore the role of liquid biopsy in HCC diagnosis,prognosis prediction,and treatment monitoring,focusing on circulating tumor cells,circulating tumor DNA,and extracellular vesicles.We also explore the evolving landscape of personalized therapy for HCC,including targeted therapies against key oncogenic signaling pathways,immune checkpoint inhibitors,tumor-agnostic therapies,and innovative cellbased therapies.We discuss the challenges and opportunities that lie ahead in the quest to improve HCC patient outcomes through the integration of molecular diagnostics and individualized precision therapies.We emphasize the need for multi-interdisciplinary collaboration,refinement of predictive and prognostic biomarkers,and the development of more effective combination strategies for HCC management in the new area of precision medicine.
文摘The rising global impact of liver disorders,such as non-alcoholic fatty liver disease(NAFLD),viral hepatitis,and hepatocellular carcinoma(HCC),stands as a daunting hurdle in modern healthcare.These ailments,now major causes of global morbidity and mortality,exert a profound strain on health systems and affect the life quality of patients.The World Health Organization's estimates reveal liver conditions lead to around 2 million deaths annually,with viral hepatitis contributing to 1.34 million of these,underscoring the critical need for enhanced research and novel therapeutic interventions.Additionally,the escalating incidence of NAFLD,intertwined with the worldwide obesity crisis,is swiftly rising,affecting about 25%of the global population[1].This surge underscores an urgent call for extensive investigative work across molecular science,clinical applications,and public health initiatives.
基金supported by the National Natural Science Foundation of China(Nos 81871949 and 82171834 to H.Z.,No.82273074 to T.Y.)the Jiangsu Six Talent Peaks Project(No.WSN-102 to H.Z.)+1 种基金the Key Research and Development Program of Social Development of Jiangsu Province(No.BE2022725 to H.Z.)the Dawn Project Foundation of Shanghai(No.21SG36 to T.Y.).
文摘Background and aims:The ASAP and GALAD scores are widely used diagnostic models for detecting hepatocellular carcinoma(HCC),incorporating factors such as sex,age,alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ),and lens culinaris agglutinin-reactive fraction of AFP(AFP-L3%).This study compares the diagnostic efficacy of the ASAP and GALAD scores in the early detection of HCC in patients with non-alcoholic fatty liver disease(NAFLD).Methods:NAFLD patients with and without HCC were recruited from 12 Chinese tertiary hospitals.Serum levels of AFP,PIVKA-II,and AFP-L3%were measured.The diagnostic accuracy of individual biomarkers,the ASAP score,and the GALAD score in detecting NAFLD-HCC at various stages was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC)values.Results:In a cohort of 147 NAFLD-HCC cases and 460 NAFLD controls,both the ASAP and GALAD scores outperformed individual biomarkers in detecting NAFLD-HCC.The ASAP score demonstrated a high AUC of 0.910(sensitivity:80.3%,specificity:92.8%)for identifying NAFLD-HCC at all stages,surpassing AFP(AUC:0.716,P<0.001),PIVKA-II(AUC:0.849,P<0.001),AFP-L3%(AUC:0.663,P<0.001),and the GALAD score(AUC:0.882,P?0.014).Comparable results were observed for early-stage NAFLD-HCC and for detecting HCC in NAFLD patients with or without cirrhosis.Conclusion:The ASAP score,which excludes the AFP-L3%indicator,demonstrated superior performance in differentiating NAFLD-HCC compared to the GALAD score,suggesting its potential for early screening of HCC in NAFLD patients.
基金funding from Shanghai Hutchison Pharmaceuticals Company.
文摘Introduction:Gallbladder polyps(GPs)are protrusions of the gallbladder wall into the lumen,and are commonly detected during ultrasound examinations.Traditional management of multiple GPs(MGPs)has been conservative,including lifestyle interventions,regular monitoring,and surgical intervention in certain cases,but this approach poses risks of polyps enlargement and increase of number,as well as patients’psychological burdens.Danning Tablets,a traditional Chinese medicine,have emerged as a potential non-surgical treatment for GPs,showing promise in reducing polyp size and alleviating symptoms,backed by their anti-inflammatory and antitumor properties demonstrated in preclinical studies.This suggests the need for further research into Danning Tablets as an alternative treatment for MGPs.Methods and analysis:The study is designed as a prospective,randomized,controlled,open-label trial.The study will be conducted across multiple centres specializing in gastroenterology and hepatology.Participants will be recruited from these centres,ensuring a diverse patient demographic.Adult patients diagnosed with MGPs,based on ultrasound findings,will be included.Exclusion criteria include patients with a history of gallbladder cancer,previous gallbladder surgery,or serious comorbid conditions.The control group will receive standard care,including dietary and lifestyle advice,while the intervention group will receive Danning Tablets and standard care.The dosage and administration of Danning Tablets will follow established clinical guidelines.The primary outcome will be the change in size of the largest gallbladder polyps on week 24±1,measured by ultrasound.The secondary outcomes will include symptom improvement and recording of any adverse events.The study will span over a period of 6 months,with periodic assessments at baseline,4,8,12,and 24 weeks.
基金funded by the Shandong Provincial Natural Science Foundation(No.ZR2024MH008)Postdoctoral Innovation Program of Shandong Province(No.SDCX-ZG-202400043)Beijing iGandan Foundation(No.iGandanF-1082022-RGG007).
文摘Objective This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy(SIC)in sepsis patients.Methods We conducted a retrospective study of septic patients admitted to the Intensive Care Units of Shandong Provincial Hospital(Central Campus and East Campus),and Shenxian People’s Hospital from January 2019 to September 2024.We used Kaplan-Meier analysis to assess survival outcomes.LASSO regression identified predictive variables,and logistic regression was employed to analyze risk factors for pre-SIC.A nomogram prediction model was developed via R software and evaluated via receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).Results Among 309 patients,236 were in the training set,and 73 were in the test set.The pre-SIC group had higher mortality(44.8%vs.21.3%)and disseminated intravascular coagulation(DIC)incidence(56.3%vs.29.1%)than the non-SIC group.LASSO regression identified lactate,coagulation index,creatinine,and SIC scores as predictors of pre-SIC.The nomogram model demonstrated good calibration,with an AUC of 0.766 in the development cohort and 0.776 in the validation cohort.DCA confirmed the model’s clinical utility.Conclusion SIC is associated with increased mortality,with pre-SIC further increasing the risk of death.The nomogram-based prediction model provides a reliable tool for early SIC identification,potentially improving sepsis management and outcomes.
基金Funding for the study was provided by the National Natural Science Foundation of China(Nos.81672699 and 81972726,to Dr.T Yang).
文摘Recurrence is common among patients undergoing hepatic resection for hepatocellular carcinoma(HCC),which greatly limits long-term survival.We aimed to identify predictors and long-term prognosis of early and late recurrence after HCC resection.Methods:Multicenter data of patients who underwent HCC resection between 2002 and 2016 were analyzed.Recurrence was divided into early(≤2 years)and late recurrence(>2 years after surgery).Predictors of early and late recurrence,and prognostic factors of post-recurrence survival(PRS)were identified by univariate and multivariate analyses.Results:Among 1,426 patients,554(38.8%)and 348(24.4%)developed early and late recurrence,respectively.Independent predictors associated with early recurrence included preoperative alpha-fetoprotein level>400μg/L,resection margin<1 cm,and tumor size>5.0 cm,multiplicity,macrovascular and microvascular invasion,and satellites of the initial tumor at the first diagnosis of HCC;independent predictors associated with late recurrence included male,cirrhosis,and tumor size>5.0 cm,multiplicity,macrovascular and microvascular invasion,and satellites of the initial tumor.Patients with early recurrence had a lower likelihood of undergoing potentially curative treatments for recurrence(37.2%vs.48.0%,P<0.001)and a worse median PRS(13.5 vs.36.6 months,P<0.001)vs.patients who had late recurrence.Multivariate analysis revealed that early recurrence and irregular postoperative surveillance were independently associated with worse PRS[hazard ratio(HR)=1.250,95%CI:1.016-1.538,P=0.035;and HR=1.983,95%CI:1.677-2.345,P<0.001].Conclusions:Predictors associated with early and late recurrence after curative resection for patients with HCC were generally same,although several did differ.Patients with late recurrence had better long-term survival than patients with early recurrence.
基金supported by National Natural Science Foundation of China(No.81972726).
文摘Background:A solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,regardless of tumor size,is currently classified as early-stage disease by the latest Barcelona Clinic Liver Cancer(BCLC)staging system.While the preferred treatment is surgical resection,the association of tumor morphology with long-term survival outcomes after liver resection for a solitary huge HCC of≥10 cm has not been defined.Methods:Patients who underwent curative liver resection for a solitary huge HCC were identified from a multicenter database.Preoperative imaging findings were used to define spherical-or ellipsoidal-shaped lesions with smooth edges as balloon-shaped HCCs(BS-HCCs);out-of-shape lesions or lesions of any shape with matt edges were defined as non-balloon-shaped HCCs(NBS-HCCs).The two groups of patients with BS-HCCs and NBS-HCCs were matched in a 1:1 ratio using propensity score matching(PSM).Clinicopathologic characteristics,long-term overall survival(OS)and recurrence-free survival(RFS)were assessed.Results:Among patients with a solitary huge HCC,74 pairs of patients with BS-HCC and NBS-HCC were matched.Tumor pathological features including proportions of microvascular invasion,satellite nodules,and incomplete tumor encapsulation in the BS-HCC group were lower than the NBS-HCC group.At a median follow-up of 50.7 months,median OS and RFS of all patients with a solitary huge HCC after PSM were 27.8 and 10.1 months,respectively.The BS-HCC group had better median OS and RFS than the NBS-HCC group(31.9 vs.21.0 months,P=0.01;and 19.7 vs.6.4 months,P=0.015).Multivariate analyses identified BS-HCC as independently associated with better OS(HR=0.592,P=0.009)and RFS(HR=0.633,P=0.013).Conclusions:For a solitary huge HCC,preoperative imaging on tumor morphology was associated with prognosis following resection.In particular,patients with BS-HCCs had better long-term survival following liver resection versus patients with large NBS-HCCs.
基金This work was supported in part by the National Natural Science Foundation of China(81472284 and 81672699 for T Yang).
文摘Background:Family history is a risk factor for the development of hepatocellular carcinoma(HCC).The aim of the current study was to investigate the association between family history of HCC and long-term oncologic prognosis among patients undergoing curative liver resection for hepatitis B virus(HBV)-related HCC.Methods:Patients who underwent curative liver resection of HBV-related HCC between 2003 and 2013 were consecutively enrolled.Family history was defined as a self-reported history of HCC in a first-degree relative.Propensity score matching(PSM)and multivariable Cox-regression analyses were performed to compare overall survival(OS)and recurrence-free survival(RFS)among patients with and without a family history.Results:Among 1,112 patients,183(16.5%)patients had a family history of HCC.Using PSM,179 pairs of patients with and without a family history were created that had no differences in the baseline characteristics and operative variables.On matched analysis,family history was associated with decreased OS and RFS after curative-intent resection of HBV-related HCC in the propensity matching cohort(P=0.042 and 0.006,respectively).On multivariable Cox-regression analyses,a family history of HCC was associated with decreased OS(HR:1.574;95%CI:1.171–2.116;P=0.003)and RFS(HR:1.534;95%CI:1.176–2.002;P=0.002)after adjusting for other prognostic risk factors.Conclusions:Family history was associated with decreased OS and RFS rates among patients undergoing curative liver resection of HBV-related HCC.
基金supported by the National Natural Science Foundation of China(no.82273074)Dawn Project Foundation of Shanghai(no.21SG36)+2 种基金Adjunct Talent Fund of Zhejiang Provincial People’s Hospital(no.2021-YT)the Natural Science Foundation of Shanghai(no.22ZR1477900)Shanghai Science and Technology Committee Rising-Star Programme(no.22QA1411600).
文摘Background The role of adjuvant transarterial chemoembolisation(TACE)to reduce postoperative recurrence varies widely among patients undergoing hepatectomy with curative intent for hepatocellular carcinoma(HCC).Personalised predictive tool to select which patients may benefit from adjuvant TACE is lacking.This study aimed to develop and validate an online calculator for estimating the reduced risk of early recurrence from adjuvant TACE for patients with HCC.Methods From a multi-institutional database,2590 eligible patients undergoing curative-intent hepatectomy for HCC were enrolled,and randomly assigned to the training and validation cohorts.Independent predictors of early recurrence within 1 year of surgery were identified in the training cohort,and subsequently used to construct a model and corresponding prediction calculator.The predictive performance of the model was validated using concordance indexes(C-indexes)and calibration curves,and compared with conventional HCC staging systems.The reduced risk of early recurrence when receiving adjuvant TACE was used to estimate the expected benefit from adjuvant TACE.Results The prediction model was developed by integrating eight factors that were independently associated with risk of early recurrence:alpha-fetoprotein level,maximum tumour size,tumour number,macrovascular and microvascular invasion,satellite nodules,resection margin and adjuvant TACE.The model demonstrated good calibration and discrimination in the training and validation cohorts(C-indexes:0.799 and 0.778,respectively),and performed better among the whole cohort than four conventional HCC staging systems(C-indexes:0.797 vs 0.562–0.673,all p<0.001).An online calculator was built to estimate the reduced risk of early recurrence from adjuvant TACE for patients with resected HCC.Conclusions The proposed calculator can be adopted to assist decision-making for clinicians and patients to determine which patients with resected HCC can significantly benefit from adjuvant TACE.WHAT IS ALREADY KNOWN ON THIS TOPIC⇒Previous studies have indicated that adjuvant transarterial chemoembolisation(TACE)may im-prove long-term survival in certain subgroups of patients with hepatocellular carcinoma(HCC)after hepatectomy.⇒However,these studies did not provide personalised risk assessment or net benefit estimation for indi-vidual patients,highlighting the need for a more refined prediction model.WHAT THIS STUDY ADDS⇒This study developed a risk prediction model in-corporating eight independent factors associat-ed with early recurrence after hepatectomy for HCC,demonstrating good predictive accuracy and discrimination.⇒The model outperformed four commonly used con-ventional HCC staging systems and facilitated the development of an online calculator to estimate in-dividual patient’s reduced risk of early recurrence using adjuvant TACE.HOW THIS STUDY MIGHT AFFECT RESEARCH,PRACTICE OR POLICY⇒The study’s findings may assist clinicians in decid-ing whether to use adjuvant TACE after hepatectomy for HCC,potentially improving patient outcomes.⇒Further research should validate the model with larger cohorts or those from other centres to assess its broader applicability.
基金This work was supported in part by the National Natural Science Foundation of China(No.81871949 and 82171834 to H.Zhu)Jiangsu Six Talent Peaks Project(WSN-102 to H.Zhu)+1 种基金Dawn Project Foundation of Shanghai(No.21SG36 to T.Yang)Adjunct Talent Fund of Zhejiang Provincial People's Hospital(No.2021-YT to T.Yang).
文摘Hepatocellular carcinoma(HCC),a typical inflammatory-related cancer,mainly occurs in patients with chronic liver diseases.Moreover,the liver is an immunologically privileged apparatus with multiple immunosuppressive cell groups.The long process of inflammation-mediated carcinogenesis turns the HCC tumor microenvironment(TME)into one with strong immunosuppression,facilitating the immune escape of HCC cells.Accumulated data have manifested that tumor-associated cell-derived exosomes carry diverse molecular cargoes(e.g.,proteins and nucleic acids)for mediating cell-to-cell communication and are implicated in TME remodeling to promote tumor-infiltrating immune cell reprogramming,ultimately creating a tumor-friendly microenvironment.Characterized by several intrinsic attributes,such as good stability(bilayer-like structure)and high biocompatibility(cell secretion),exosomes can be modified or engineered as nanocarriers to deliver tumor-specific antigens or antitumor drugs to targeted cells or organs,thus effectively triggering the HCC cell elimination by the immune system.This review aimed to highlight the pivotal role of exosomes in regulating immune escape mechanisms in HCC and recent advances in exosome-mediated immunotherapy for HCC.
基金This work was supported in part by the National Natural Science Foundation of China(No.81972726 to T.Yang).We thank Prof.Shun-Xing Zhang from Department of English Teaching of Naval Medical University for providing suggestive advice on manuscript drafting.
文摘China is a big nation primarily affected by liver cancer with the number of patients with liver cancer accounting more than 50%worldwide.1,2 Dr.Wu Mengchao(August 1922-May 2021;Fig.1)has devoted almost all his energy and wisdom to fighting against liver cancer for more than half a century.Dr.Wu graduated from the Tongji University School of Medicine in 1949.In 1960,Dr.Wu worked as the chief surgeon completing the first case of surgical resection for liver cancer in China.
