Background:It remains unclear what the antiviral therapy affects disease-free survival(DFS) and overall survival(OS)of patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) at different tumor stag...Background:It remains unclear what the antiviral therapy affects disease-free survival(DFS) and overall survival(OS)of patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) at different tumor stages and baseline HBV DNA levels.In this study,we analyzed the association of antiviral treatment with DFS and OS based on the stratification of baseline HBV DNA load in early-stage(stages Ⅰ and Ⅱ) HCC patients.Methods:We included 445 patients with early-stage HBV-related HCC who underwent curative resection,and then classified them into four subgroups based on baseline HBV DNA load and antiviral therapy stratification.The KaplanMeier and Cox regression analyses were performed to determine the association of clinical characteristics with survival.Results:The median follow-up period was 74 months.For all patients,cumulative OS rates in the antiviral group were significantly higher than those in the non-antiviral group(log-rank test,P = 0.023),whereas no significant differences in DFS rates were observed.High baseline HBV DNA level was a risk factor associated with short DFS and OS in all patients.In patients with baseline HBV DNA levels ≥2000 lU/mL,antiviral treatment was significantly associated with prolonged DFS and OS(log-rank test,P = 0.041 and 0.001,respectively).In patients with HBV DNA levels <2000 lU/mL or undetectable,antiviral treatment did not show a significant benefit in prolonging DFS and OS.Conclusions:High baseline HBV DNA levels are associated with poor prognosis in the patients with early-stage HCC,and the antiviral treatment could generate survival benefits for the patients.Therefore,antiviral treatment should be given for these patients.However,the effect of antiviral treatment on the patients with low viral load remains unclear,and further investigation is warranted.展开更多
Background:Laparoscopic hepatectomy is increasingly being used to treat hepatocellular carcinoma(HCC).However,few studies have examined the treatment of recurrent HCC in patients who received a prior hepatectomy.The p...Background:Laparoscopic hepatectomy is increasingly being used to treat hepatocellular carcinoma(HCC).However,few studies have examined the treatment of recurrent HCC in patients who received a prior hepatectomy.The present prospective study compared the clinical efficacy of laparoscopic surgery with conventional open surgery in HCC patients with postoperative tumor recurrence.Methods:We conducted a prospective study of 64 patients,all of whom had undergone open surgery once before,who were diagnosed with recurrent HCC between June 2014 and November 2014.The laparoscopic group(n = 31)underwent laparoscopic hepatectomy,and the control group(n = 33) underwent conventional open surgery.Operation time,intraoperative blood loss,surgical margins,postoperative pain scores,postoperative time until the patient could walk,anal exsufflation time,length of hospital stay,and inpatient costs were compared between the two groups.The patients were followed up for 1 year after surgery,and relapse-free survival was compared between the two groups.Results:All surgeries were successfully completed.No conversion to open surgery occurred in the laparoscopic group,and no serious postoperative complications occurred in either group.No significant difference in inpatient costs was found between the laparoscopic group and the control group(P = 0.079),but significant differences between the two groups were observed for operation time(116.7 ± 37.5 vs.148.2 ± 46.7 min,P = 0.031),intraoperative blood loss(117.5 ± 35.5 vs.265.9 ± 70.3 mL,P = 0.012),postoperative time until the patient could walk(1.6 ± 0.6vs.2.2 ± 0.8 days,P < 0.05),anal exsufflation time(2.1 ± 0.3 vs.2.8 ± 0.7 days,P = 0.041),visual analogue scale pain score(P < 0.05),postoperative hepatic function(P < 0.05),and length of hospital stay(4.5 ± 1.3 vs.6.0 ± 1.2 days,P = 0.014).During the 1-year postoperative follow-up period,6 patients in each group had recurrent HCC on the side of the initial operation,but no significant difference between groups was observed in the recurrence rate or relapse-free survival.In the laparoscopic group,operation time,postoperative time until the patient could walk,anal exsufflation time,and inpatient costs were not different(P > 0.05) between the patients with contralateral HCC recurrence(n=18) and those with ipsilateral HCC recurrence(n = 13).However,intraoperative blood loss was significantly less(97.7 ± 14.0 vs.186.3 ± 125.6 mL,P = 0.012) and the hospital stay was significantly shorter(4.2 ± 0.7 vs.6.1 ± 1.7 days,P = 0.021) for the patients with contralateral recurrence than for those with ipsilateral recurrence.Conclusions:For the patients who previously underwent conventional open surgical resection of HCC,complete laparoscopic resection was safe and effective for recurrent HCC and resulted in a shorter operation time,less intraoperative blood loss,and a faster postoperative recovery than conventional open surgery.Laparoscopic resection was especially advantageous for the patients with contralateral HCC recurrence.展开更多
Background: Patients with intermediate to advanced hepatocellular carcinoma(HCC) are most commonly treated with transarterial chemoembolization(TACE). Previous studies showed that TACE combined with recombinant human ...Background: Patients with intermediate to advanced hepatocellular carcinoma(HCC) are most commonly treated with transarterial chemoembolization(TACE). Previous studies showed that TACE combined with recombinant human adenovirus type 5(H101) may provide a clinical survival benefit. In the present study, we aimed to determine the survival benefit of TACE with or without H101 for patients with intermediate to advanced HCC and to develop an e ective nomogram for predicting individual survival outcomes of these patients.Methods: We retrospectively collected data from 590 patients with intermediate to advanced HCC who were treated at Sun Yat?sen University Cancer Center between January 2007 and July 2015. After propensity score matching, 238 patients who received TACE with H101(TACE with H101 group) and 238 patients who received TACE without H101(TACE group) were analyzed. Overall survival(OS) was evaluated using the Kaplan–Meier method; the nomogram was developed based on Cox regression analysis. Discrimination and calibration were measured using the concordance index(c?index) and calibration plots.Results: Clinical and radiologic features were similar between the two groups. OS rates were significantly lower in the TACE group than in the TACE with H101 group(1?year OS rate, 53.8% vs. 61.3%; 2?year OS rate, 33.4% vs. 44.2%; 3?year OS rate, 22.4% vs. 40.5%; all P < 0.05). Multivariate Cox regression analysis for the entire cohort showed that alpha?fetoprotein level, alkaline phosphatase level, tumor size, metastasis, vascular invasion, and TACE with or without H101 were independent factors for OS, all of which were included in the nomogram. Calibration curves showed good agreement between nomogram?predicted survival and observed survival. The c?index of the nomogram for predict?ing OS was 0.716(95% confidence interval 0.686–0.746).Conclusions: TACE plus H101 extends the survival of patients with intermediate to advanced HCC. Our proposed nomogram provides individual survival prediction and stratification for patients with intermediate to advanced HCC who receive TACE with or without H101.展开更多
Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepa...Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus(HBV)-related HCC treated with chemoembolization is unclear.This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC.Methods:A total of 224 HCC patients who successfully underwent chemoembolization were identified,and their survival and other relevant clinical data were reviewed.Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival(OS).Results:The median survival time(MST) was 15.9(95%confidence interval[CI],9.5-27.7) months in the antiviral group and 9.6(95%CI,7.8-13.7) months in the non-antiviral group(log-rank test,P = 0.044).Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS(P = 0.008).Additionally,a further analysis was based on the stratification of the TNM tumor stages.In the subgroup of early stages,MST was significantly longer in the antiviral-treatment group than in the non-antiviral group(61.8 months[95%CI,34.8 months to beyond the follow-up period]versus 26.2[95%CI,14.5-37.7]months,P= 0.012).Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup(P = 0.006).However,in the subgroup of advanced stages,MST of the antiviral-treated group was comparable to that of the non-antiviral group(8.4[95%CI,5.2-13.5]months versus 7.4[95%CI,5.9-9.3]months,P = 0.219).Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup.Conclusion:Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC,especially in patients with early-stage tumors.展开更多
Littoral-cell angioma(LCA), a primary angioma which clinically belongs to splenic hemangioma, can be mostly found in normal spleen red sinus shore cells of reticuloendothelial cell system. The cells of LCA strongly ex...Littoral-cell angioma(LCA), a primary angioma which clinically belongs to splenic hemangioma, can be mostly found in normal spleen red sinus shore cells of reticuloendothelial cell system. The cells of LCA strongly express endothelial and tissue cell associated antigens that indicate a dual differentiation characteristic; whereas only endothelial cell markers are positive in normal spleen red sinus shore cells. Diagnosis of LCA relies on histopathology. Regular follow-up is needed to monitor recurrence and metastasis.展开更多
Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related...Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.展开更多
Non-parasitic hepatic cysts with biliary communication are rare. qhe clinical symptoms involved are not specific to this condition, thereby making diagnosis difficult and treatment controversial. Here, we report a cas...Non-parasitic hepatic cysts with biliary communication are rare. qhe clinical symptoms involved are not specific to this condition, thereby making diagnosis difficult and treatment controversial. Here, we report a case of 70-year-old woman complaining of abdominal satiety, combined with non-specific pain in the right upper quadrant, qhe abdominal contrast-enhanced MR.I-scan revealed a large and thick-walled septus cystic lesion in the liver. During operation, the biliary fistula was confirmed in the cyst cavity. A silica gel tube was inserted via the cystic duct for cholangiography, which demonstrated communication between the cyst and biliary tract. We performed wide-scale cyst wall resection; the biliary fistula was completely repaired by the closure of communicated bile ducts. The postoperative course was uneventful, and the patient was discharged with no sign ofcholangitis or any other symptoms. The novel surgical management via wide resection of the cyst wall and closure of biliary communication proved to be an adequate and effective procedure for treating nonparasitic hepatic cysts with biliary communication.展开更多
Patients with late-stage cancer commonly have distant lymph node metastasis;however,poor health often contraindicates surgical treatment.Although the quality of life and overall survival for these patients are low,the...Patients with late-stage cancer commonly have distant lymph node metastasis;however,poor health often contraindicates surgical treatment.Although the quality of life and overall survival for these patients are low,there is neither a consensus nor a guide for treatment.Ablation technique and surrounding tissue damage are two possible reasons for limited study of radiofrequency ablation in patients with superficial distant lymph node metastasis.Here,we report two patients treated successfully with ultrasound-guided radiofrequency ablation for superficial distant lymph node metastasis.In these patients,deionized water was injected to the surrounding tissues of the lymph node to decrease heat injury.Results from these patients suggest that radiofrequency ablation may play an important role in the treatment of patients with distant lymph node metastasis.展开更多
Pancreatic cancer has a poor prognosis. Current therapies for pancreatic cancer have limited effects. In the past decade, precision medicine has shown great potential for clinical applications. In this review, differe...Pancreatic cancer has a poor prognosis. Current therapies for pancreatic cancer have limited effects. In the past decade, precision medicine has shown great potential for clinical applications. In this review, different strategies for applying precision medicine to the treatment of pancreatic cancer are described.展开更多
Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on l...Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.展开更多
Background: Laparoscopic hepatectomy for hepatocellular carcinoma(HCC) located in segment Ⅵ, Ⅶ, or Ⅷ of the liver is usually difficult because of poor operative exposure, due to the unique anatomical structure. In ...Background: Laparoscopic hepatectomy for hepatocellular carcinoma(HCC) located in segment Ⅵ, Ⅶ, or Ⅷ of the liver is usually difficult because of poor operative exposure, due to the unique anatomical structure. In this study, we evaluated the practice of laparoscopic hepatectomy with the left jackknife position for patients with HCC located in segment Ⅵ, Ⅶ, or Ⅷ.Methods: A total of 10 patients were enrolled to undergo laparoscopic hepatectomy with the left jackknife position.Tumors located in segment Ⅵ, Ⅶ, or Ⅷ were assessed by preoperative dynamic computed tomography or magnetic resonance imaging. Operation time, intraoperative blood loss, postoperative fasting time, postoperative drainage time, major postoperative complications, and duration of postoperative hospital stay were recorded.Results: All surgeries were successfully completed. None of the patients required conversion to open surgery during the procedure, and no serious postoperative complications were observed.The median tumor size was 31 mm(range 23-41 mm) in diameter, the mean operation time was 166 ± 38 min, the mean intraoperative blood loss was220 ± 135 mL, and the median postoperative hospital stay was 4 days(range 2-7 days).Conclusions: For HCC located in segment Ⅵ, Ⅶ, or Ⅷ, laparoscopic hepatectomy with this novel position—the left jackknife position—is safe and effective during tumor resection by exposing a sufficient operating field.Trial registration ClinicalTrials.gov ID:展开更多
Stem cell marker LIN28,related closely with SOX2 and OCT4,has been studied as a biomarker for the maintainance of pluripotent cells in several malignancies.Our previous study showed that SOX2 and OCT4 were negative pr...Stem cell marker LIN28,related closely with SOX2 and OCT4,has been studied as a biomarker for the maintainance of pluripotent cells in several malignancies.Our previous study showed that SOX2 and OCT4 were negative predictors for hepatocellular carcinoma(HCC).However,the predictive value of LIN28 in HCC outcome is still undetermined.We hypothesized that LIN28 may also play a role as a biomarker for HCC.To test this hypothesis,we examined the expression of LIN28 in 129 radically resected HCC tissues using reverse transcription-polymerase chain reaction and analyzed the association of LIN28 expression with clinicopathologic features and prognosis.Our study showed that LIN28 was expressed at a higher frequency in tumor tissues than in non-HCC tissues(45.0% vs.21.7%,P = 0.020).Moreover,LIN28 expression was significantly increased in cases with large tumor size(P = 0.010).Univariate analysis did not reveal a significant correlation between LIN28 expression and overall survival or recurrence-free survival.For HCC patients who met the Milan criteria,stratified analysis revealed shorter overall survival(P = 0.007) and recurrence-free survival(P < 0.001) in those with detectable LIN28 expression compared to those with no detectable LIN28 expression.Furthermore,multivariate analysis revealed that LIN28 was a negative independent predictor for both overall survival(hazard ratio= 7.093,P = 0.017) and recurrence-free survival(hazard ratio=5.518,P = 0.004) in patients who met the Milan criteria.Taken together,our results suggest that LIN28 identifies low-risk and high-risk subsets of HCC patients meeting the Milan criteria who undergo hepatectomy.展开更多
Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a re...Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a retrospective,single-center trial.Between April 3,2017 and July 2,2018,104 patients with Child-Pugh A and advanced HCC received either 400 mg of sorafenib orally twice daily plus HAIC with oxaliplatin(oxaliplatin 85 mg/m^2,every 3 weeks via repetitive catheterization)(n=46,soraOXA group)or 400 mg of only sorafenib orally twice daily(n=58,sorafenib group).Overall survival,progression-free survival,objective response rate,and treatment-related adverse events were compared.Results:The median overall survival was 9.37 months(95%CI,7.05-11.68)in the soraOXA group versus 4.8 months(95%CI,2.98-6.62)in the sorafenib group(HR 0.46[95%CI,0.29-0.72];P<0.001).The soraOXA group also showed a higher objective response rate(16[34.8%]vs 1[1.7%];P<0.001)and a longer progressionfree survival rate(5.5 months[95%CI,2.32-8.68]vs 2.4 months[95%CI,1.65-3.15],HR 0.54[95%CI,0.36-0.81],P=0.003)than the sorafenib group.There was no significant difference in the overall incidence of any grade adverse events,grade 3/4 adverse events,serious adverse events,or incidence of treatment termination due to adverse events between the two groups.Conclusion:Compared with sorafenib alone,sorafenib plus HAIC with oxaliplatin showed favorable treatment outcomes in patients with advanced HCC.The merits of this approach need to be established with a prospective trial.展开更多
Objective：This study proposed a modified Blumgart anastomosis（m-BA）that uses a firm ligation of the main pancreatic duct with a supporting tube to replace the pancreatic duct-to-jejunum mucosa anastomosis,with the ...Objective：This study proposed a modified Blumgart anastomosis（m-BA）that uses a firm ligation of the main pancreatic duct with a supporting tube to replace the pancreatic duct-to-jejunum mucosa anastomosis,with the aim of simplifying the complicated steps of the conventional BA（c-BA）.Thus,we observe if a difference in the risk of postoperative pancreatic fistula（POPF）exists between the two methods.Methods：The m-BA anastomosis method has been used since 2010.From October 2011 to October 2015,147 patients who underwent pancreatoduodenectomy（PD）using BA in Tianjin Medical University Cancer Institute and Hospital were enrolled in this study.According to the type of pancreatojejunostomy（PJ）,50 patients underwent m-BA and 97 received c-BA.The two patient cohorts were compared prospectively to some extent but not randomized,and the evaluated variables were operation time,the incidence rate of POPF,and other perioperative complications.Results：The operation time showed no significant difference（P〉0.05）between the two groups,but the time of duct-to-mucosa anastomosis in the m-BA group was much shorter than that in the c-BA group（P〈0.001）.The incidence rate of clinically relevant POPF was 12.0%（6/50）in the modified group and 10.3%（10/97）in the conventional group（P〉0.05）,which means that the modified anastomosis method did not cause additional pancreatic leakage.The mean length of postoperative hospital stay of the m-BA group was 23 days,and that of the c-BA group was 22 days（P〉0.05）.Conclusions：Compared with the conventional BA,we suggest that the modified BA is a feasible,safe,and effective operation method for P J of PD with no sacrifice of surgical quality.In the multivariate analysis,we also found that body mass index（≥25展开更多
Objective:This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection.Methods:From March 1...Objective:This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection.Methods:From March 1,2020 to July 31,2021,80 patients were enrolled,including 40 undergoing intraperitoneal Pringle maneuver(IPM)and 40 extraperitoneal Pringle maneuver(EPM).The observation indices included basic preoperative clinical characteristics and intraoperative and postoperative liver function indices.Results:There were no significant differences in the basic characteristics or types of hepatectomy,intraoperative blood loss,intraoperative blood transfusion,or hepatectomy time between the IPM and EPM groups.However,the blocking and operation time in the IPM group was shorter than that in the EPM group.There were no significant differences in alanine aminotransferase(ALT)or aspartate aminotransferase(AST)levels on the first day after surgery or in total bilirubin(TBIL)or albumin(ALB)levels on the first,third,or fifth days after surgery.However,C-reactive protein(CRP)levels on the first and third days,ALT and AST levels on the third and fifth days were lower,and hospital stay after surgery was shorter in the IPM group than in the EPM group.Conclusion:IPM using bulldog clamps is simple,safe,and effective.The inflammatory reaction is less severe,the degree of liver function injury is lower,and recovery is faster.展开更多
OBJECTIVE To investigate the effect of proteasome inhibition on the sensitivity of carcinoma cells to TRAIL-inducing apoptosis, and to study the mechanism of the response. METHODS Human hepatocellular carcinoma cells,...OBJECTIVE To investigate the effect of proteasome inhibition on the sensitivity of carcinoma cells to TRAIL-inducing apoptosis, and to study the mechanism of the response. METHODS Human hepatocellular carcinoma cells, pretreated with the proteasome inhibitor, MG132, were cotreated with TRAIL. Western blot assays, immunoprecipitation and RT-PCR were performed to test the expression of the Bcl-2 family proteins and Bax mRNA. RESULTS We found that (i) proteasome inhibition sensitized the human hepatocellular carcinoma cells to TRAIL; and (ii) resulted in Bax accumulation before release of cytochrome C and induction of apoptosis. These results were associated with the ability of proteasome inhibitors to overcome Bcl-2-mediated antiapoptotic function; (iii) Bax is regulated by an ubiquitin/proteasome-dependent degradation pathway. CONCLUSION Proteasome inhibition sensitized hepatocellular carcinoma cells to TRAIL by the inhibition of the ubiquitin/proteasome-mediated Bax degradation pathway.展开更多
Background Antitumor drugs(such as chemotherapy,targeted therapy,immunotherapy,etc.)and local treatments like surgery and radiotherapy are widely used in cancer treatment,but they often carry the risk of liver injury,...Background Antitumor drugs(such as chemotherapy,targeted therapy,immunotherapy,etc.)and local treatments like surgery and radiotherapy are widely used in cancer treatment,but they often carry the risk of liver injury,which seriously affects the prognosis and quality of life of patients.Therefore,liver protection is of crucial importance in cancer treatment.Methods Relevant experts organized by the Oncology Hepatology Committee of China Anti-Cancer Association Association formulated this guideline based on the latest research achievements and clinical practice experience at home and abroad,aiming to provide comprehensive and systematic guidance for clinicians on liver protection.Results This guideline elaborates on the importance of liver protection during cancer treatment,comprehensively introduces the pathophysiological mechanisms,diagnosis,treatment,and preventive measures of antitumor treatment-related liver injury.Conclusion This guideline is helpful for clinicians to formulate individualized treatment plans,improve the treatment outcome and quality of life of cancer patients,and provides an important reference for the clinical practice of liver protection in cancer treatment.展开更多
Background:Average postoperative follow-up intervals vary in patients undergoing hepatocellular carcinoma(HCC)resection because of limited evidence regarding the optimal interval.We aimed to compare the associations o...Background:Average postoperative follow-up intervals vary in patients undergoing hepatocellular carcinoma(HCC)resection because of limited evidence regarding the optimal interval.We aimed to compare the associations of long-versus short-interval follow-up with survival and recurrence in risk-stratified HCC patients.Methods:We performed a retrospective cohort study between 2007 and 2014.In total,1227 patients treated by curative resection of Barcelona Clinic Liver Cancer stage A or B HCC were stratified as having a low(n=865)or high(n=362)risk of early recurrence(within the first 2 years after resection)based on prognostic factors identified by the least absolute shrinkage and selection operation algorithm.Patients were further classified into long-interval(every 4-6 months)and short-interval(every 2-4 months)follow-up subgroups based on follow-up within 2 years after resection(low risk,long vs.short:n=390 vs.n=475;high-risk,long vs.short:n=149 vs.n=213).Results:The short-interval follow-up did not prolong overall survival in either the low-risk(hazard ratio[HR]=1.152;95%confidence interval[CI]0.720-1.843)or high-risk(HR=1.213;95%CI 0.702-2.094)patients.Early recurrence occurred in 401 patients.For high-risk patients,the short-interval follow-up subgroup exhibited smaller intrahepatic recurrence than did the long-interval group(2.6 vs.3.5 cm,respectively,P=0.045).However,no significant difference in the rate of Barcelona Clinic Liver Cancer stage 0/A recurrence was found between the long-and short-interval follow-up groups in either low-or high-risk patients(63.1%vs.68.2%,respectively,P=0.580;31.3%vs.41.5%,respec-tively,P=0.280).The rate of curative intent treatment for recurrence(34.5%vs.39.7%,respectively,P=0.430;14.6%vs.20.3%,respectively,P=0.388)was also similar between the follow-up groups for low-and high-risk patients.Conclusions:Shortening the postoperative follow-up interval from every 4-6 months to every 2-4 months within the first 2 years after resection did not increase the rate of curative intent treatment or prolong the overall survival of patients with Barcelona Clinic Liver Cancer stage A or B HCC.展开更多
Aim:To evaluate the perioperative outcomes and postoperative survival of applying staging laparoscopy(SL)in intrahepatic cholangiocarcinoma(ICC)patients undergoing surgical resection.Methods:A retrospective analysis w...Aim:To evaluate the perioperative outcomes and postoperative survival of applying staging laparoscopy(SL)in intrahepatic cholangiocarcinoma(ICC)patients undergoing surgical resection.Methods:A retrospective analysis was performed on all selected ICC patients who underwent curative-intent resection with/without applying staging laparoscopy from January 2010 to August December 2021.Perioperative outcomes and postoperative survival were analyzed.Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were performed to reduce the bias due to confounding variables in the SL group and the non-SL group.Multivariate Cox analysis was used to ascertain the independent predictor of survival for ICC patients.Results:A total of 279 patients(24.1%)were included in the SL group,while 881 patients(75.9%)were included in the non-SL group.Compared with the non-SL group,the SL group had lower blood loss,smaller tumor size,higher R0 resection rate,and shorter hospital stay,but a higher incidence of postoperative complications.The OS of the SL group was better than that of the non-SL group(Median OS:31 months vs.20 months).The 1-,3-,and 5-year overall survival rates of the SL group were 77.9%,45.1%,and 32.9%,respectively,while the non-SL group had rates of 63.9%,31.3%,and 18.4%.SL was confirmed as an independent predictor of survival by multivariate Cox analysis.Conclusion:ICC patients receiving SL had better perioperative outcomes and significantly prolonged overall survival after resection surgery.The subgroup analysis results support the use of routine SL.展开更多
Protein arginine methyltransferase 5(PRMT5)acts as an oncogene in liver cancer,yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined.Here,we demonstrat...Protein arginine methyltransferase 5(PRMT5)acts as an oncogene in liver cancer,yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined.Here,we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8^(+)T-cell-mediated antitumor immunity both in vivo and in vitro.Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule,fibrinogen-like protein 1(FGL1).Mechanistically,PRMT5 catalyzed symmetric dimethylation of transcription factor 12(TCF12)at arginine 554(R554),prompting the binding of TCF12 to FGL1 promoter region,which transcriptionally activated FGL1 in tumor cells.Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression,which promoted CD8^(+)T-cell-mediated antitumor immunity.Notably,combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice.Collectively,our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.展开更多
基金supported by project grants from the National Natural Science Foundation of China(no.81201603 for Dr.XML)the Guangdong Natural Science Funds(No.S2012010009631 for Dr.XML)the International Program for Ph.D.Candidates from Sun Yat-sen University(for Dr.JLC)
文摘Background:It remains unclear what the antiviral therapy affects disease-free survival(DFS) and overall survival(OS)of patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) at different tumor stages and baseline HBV DNA levels.In this study,we analyzed the association of antiviral treatment with DFS and OS based on the stratification of baseline HBV DNA load in early-stage(stages Ⅰ and Ⅱ) HCC patients.Methods:We included 445 patients with early-stage HBV-related HCC who underwent curative resection,and then classified them into four subgroups based on baseline HBV DNA load and antiviral therapy stratification.The KaplanMeier and Cox regression analyses were performed to determine the association of clinical characteristics with survival.Results:The median follow-up period was 74 months.For all patients,cumulative OS rates in the antiviral group were significantly higher than those in the non-antiviral group(log-rank test,P = 0.023),whereas no significant differences in DFS rates were observed.High baseline HBV DNA level was a risk factor associated with short DFS and OS in all patients.In patients with baseline HBV DNA levels ≥2000 lU/mL,antiviral treatment was significantly associated with prolonged DFS and OS(log-rank test,P = 0.041 and 0.001,respectively).In patients with HBV DNA levels <2000 lU/mL or undetectable,antiviral treatment did not show a significant benefit in prolonging DFS and OS.Conclusions:High baseline HBV DNA levels are associated with poor prognosis in the patients with early-stage HCC,and the antiviral treatment could generate survival benefits for the patients.Therefore,antiviral treatment should be given for these patients.However,the effect of antiviral treatment on the patients with low viral load remains unclear,and further investigation is warranted.
基金supported by the Foundation for Guangdong Medical Science and Technology(No.B2012137)
文摘Background:Laparoscopic hepatectomy is increasingly being used to treat hepatocellular carcinoma(HCC).However,few studies have examined the treatment of recurrent HCC in patients who received a prior hepatectomy.The present prospective study compared the clinical efficacy of laparoscopic surgery with conventional open surgery in HCC patients with postoperative tumor recurrence.Methods:We conducted a prospective study of 64 patients,all of whom had undergone open surgery once before,who were diagnosed with recurrent HCC between June 2014 and November 2014.The laparoscopic group(n = 31)underwent laparoscopic hepatectomy,and the control group(n = 33) underwent conventional open surgery.Operation time,intraoperative blood loss,surgical margins,postoperative pain scores,postoperative time until the patient could walk,anal exsufflation time,length of hospital stay,and inpatient costs were compared between the two groups.The patients were followed up for 1 year after surgery,and relapse-free survival was compared between the two groups.Results:All surgeries were successfully completed.No conversion to open surgery occurred in the laparoscopic group,and no serious postoperative complications occurred in either group.No significant difference in inpatient costs was found between the laparoscopic group and the control group(P = 0.079),but significant differences between the two groups were observed for operation time(116.7 ± 37.5 vs.148.2 ± 46.7 min,P = 0.031),intraoperative blood loss(117.5 ± 35.5 vs.265.9 ± 70.3 mL,P = 0.012),postoperative time until the patient could walk(1.6 ± 0.6vs.2.2 ± 0.8 days,P < 0.05),anal exsufflation time(2.1 ± 0.3 vs.2.8 ± 0.7 days,P = 0.041),visual analogue scale pain score(P < 0.05),postoperative hepatic function(P < 0.05),and length of hospital stay(4.5 ± 1.3 vs.6.0 ± 1.2 days,P = 0.014).During the 1-year postoperative follow-up period,6 patients in each group had recurrent HCC on the side of the initial operation,but no significant difference between groups was observed in the recurrence rate or relapse-free survival.In the laparoscopic group,operation time,postoperative time until the patient could walk,anal exsufflation time,and inpatient costs were not different(P > 0.05) between the patients with contralateral HCC recurrence(n=18) and those with ipsilateral HCC recurrence(n = 13).However,intraoperative blood loss was significantly less(97.7 ± 14.0 vs.186.3 ± 125.6 mL,P = 0.012) and the hospital stay was significantly shorter(4.2 ± 0.7 vs.6.1 ± 1.7 days,P = 0.021) for the patients with contralateral recurrence than for those with ipsilateral recurrence.Conclusions:For the patients who previously underwent conventional open surgical resection of HCC,complete laparoscopic resection was safe and effective for recurrent HCC and resulted in a shorter operation time,less intraoperative blood loss,and a faster postoperative recovery than conventional open surgery.Laparoscopic resection was especially advantageous for the patients with contralateral HCC recurrence.
文摘Background: Patients with intermediate to advanced hepatocellular carcinoma(HCC) are most commonly treated with transarterial chemoembolization(TACE). Previous studies showed that TACE combined with recombinant human adenovirus type 5(H101) may provide a clinical survival benefit. In the present study, we aimed to determine the survival benefit of TACE with or without H101 for patients with intermediate to advanced HCC and to develop an e ective nomogram for predicting individual survival outcomes of these patients.Methods: We retrospectively collected data from 590 patients with intermediate to advanced HCC who were treated at Sun Yat?sen University Cancer Center between January 2007 and July 2015. After propensity score matching, 238 patients who received TACE with H101(TACE with H101 group) and 238 patients who received TACE without H101(TACE group) were analyzed. Overall survival(OS) was evaluated using the Kaplan–Meier method; the nomogram was developed based on Cox regression analysis. Discrimination and calibration were measured using the concordance index(c?index) and calibration plots.Results: Clinical and radiologic features were similar between the two groups. OS rates were significantly lower in the TACE group than in the TACE with H101 group(1?year OS rate, 53.8% vs. 61.3%; 2?year OS rate, 33.4% vs. 44.2%; 3?year OS rate, 22.4% vs. 40.5%; all P < 0.05). Multivariate Cox regression analysis for the entire cohort showed that alpha?fetoprotein level, alkaline phosphatase level, tumor size, metastasis, vascular invasion, and TACE with or without H101 were independent factors for OS, all of which were included in the nomogram. Calibration curves showed good agreement between nomogram?predicted survival and observed survival. The c?index of the nomogram for predict?ing OS was 0.716(95% confidence interval 0.686–0.746).Conclusions: TACE plus H101 extends the survival of patients with intermediate to advanced HCC. Our proposed nomogram provides individual survival prediction and stratification for patients with intermediate to advanced HCC who receive TACE with or without H101.
基金partly supported by the Foundation for the Outstanding Young Scholar Award(Dr.Xiang-Ming Lao) from Sun Yat-sen University Cancer Center
文摘Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus(HBV)-related HCC treated with chemoembolization is unclear.This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC.Methods:A total of 224 HCC patients who successfully underwent chemoembolization were identified,and their survival and other relevant clinical data were reviewed.Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival(OS).Results:The median survival time(MST) was 15.9(95%confidence interval[CI],9.5-27.7) months in the antiviral group and 9.6(95%CI,7.8-13.7) months in the non-antiviral group(log-rank test,P = 0.044).Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS(P = 0.008).Additionally,a further analysis was based on the stratification of the TNM tumor stages.In the subgroup of early stages,MST was significantly longer in the antiviral-treatment group than in the non-antiviral group(61.8 months[95%CI,34.8 months to beyond the follow-up period]versus 26.2[95%CI,14.5-37.7]months,P= 0.012).Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup(P = 0.006).However,in the subgroup of advanced stages,MST of the antiviral-treated group was comparable to that of the non-antiviral group(8.4[95%CI,5.2-13.5]months versus 7.4[95%CI,5.9-9.3]months,P = 0.219).Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup.Conclusion:Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC,especially in patients with early-stage tumors.
文摘Littoral-cell angioma(LCA), a primary angioma which clinically belongs to splenic hemangioma, can be mostly found in normal spleen red sinus shore cells of reticuloendothelial cell system. The cells of LCA strongly express endothelial and tissue cell associated antigens that indicate a dual differentiation characteristic; whereas only endothelial cell markers are positive in normal spleen red sinus shore cells. Diagnosis of LCA relies on histopathology. Regular follow-up is needed to monitor recurrence and metastasis.
基金supported by the National Natural Science Foundation of China (Grant No. 62375202)Natural Science Foundation of Tianjin (Grant No. 23JCYBJC00950)+2 种基金Tianjin Health Science and Technology Project Key Discipline Special (Grant No. TJWJ2022XK034)Tianjin Key Medical Discipline (Specialty) Construction Project (Grant No.TJYXZDXK-059B)Research Project in Key Areas of TCM in 2024 (Grant No. 2024022)
文摘Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.
文摘Non-parasitic hepatic cysts with biliary communication are rare. qhe clinical symptoms involved are not specific to this condition, thereby making diagnosis difficult and treatment controversial. Here, we report a case of 70-year-old woman complaining of abdominal satiety, combined with non-specific pain in the right upper quadrant, qhe abdominal contrast-enhanced MR.I-scan revealed a large and thick-walled septus cystic lesion in the liver. During operation, the biliary fistula was confirmed in the cyst cavity. A silica gel tube was inserted via the cystic duct for cholangiography, which demonstrated communication between the cyst and biliary tract. We performed wide-scale cyst wall resection; the biliary fistula was completely repaired by the closure of communicated bile ducts. The postoperative course was uneventful, and the patient was discharged with no sign ofcholangitis or any other symptoms. The novel surgical management via wide resection of the cyst wall and closure of biliary communication proved to be an adequate and effective procedure for treating nonparasitic hepatic cysts with biliary communication.
文摘Patients with late-stage cancer commonly have distant lymph node metastasis;however,poor health often contraindicates surgical treatment.Although the quality of life and overall survival for these patients are low,there is neither a consensus nor a guide for treatment.Ablation technique and surrounding tissue damage are two possible reasons for limited study of radiofrequency ablation in patients with superficial distant lymph node metastasis.Here,we report two patients treated successfully with ultrasound-guided radiofrequency ablation for superficial distant lymph node metastasis.In these patients,deionized water was injected to the surrounding tissues of the lymph node to decrease heat injury.Results from these patients suggest that radiofrequency ablation may play an important role in the treatment of patients with distant lymph node metastasis.
文摘Pancreatic cancer has a poor prognosis. Current therapies for pancreatic cancer have limited effects. In the past decade, precision medicine has shown great potential for clinical applications. In this review, different strategies for applying precision medicine to the treatment of pancreatic cancer are described.
基金supported by the National Natural Science Foundation of China(No.81625017 and No.81572385)the Fundamental Research Funds for the Central Universities of China(No.16ykjc36)
文摘Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.
基金supported by the National Natural Science Foundation of China(No:81602143)
文摘Background: Laparoscopic hepatectomy for hepatocellular carcinoma(HCC) located in segment Ⅵ, Ⅶ, or Ⅷ of the liver is usually difficult because of poor operative exposure, due to the unique anatomical structure. In this study, we evaluated the practice of laparoscopic hepatectomy with the left jackknife position for patients with HCC located in segment Ⅵ, Ⅶ, or Ⅷ.Methods: A total of 10 patients were enrolled to undergo laparoscopic hepatectomy with the left jackknife position.Tumors located in segment Ⅵ, Ⅶ, or Ⅷ were assessed by preoperative dynamic computed tomography or magnetic resonance imaging. Operation time, intraoperative blood loss, postoperative fasting time, postoperative drainage time, major postoperative complications, and duration of postoperative hospital stay were recorded.Results: All surgeries were successfully completed. None of the patients required conversion to open surgery during the procedure, and no serious postoperative complications were observed.The median tumor size was 31 mm(range 23-41 mm) in diameter, the mean operation time was 166 ± 38 min, the mean intraoperative blood loss was220 ± 135 mL, and the median postoperative hospital stay was 4 days(range 2-7 days).Conclusions: For HCC located in segment Ⅵ, Ⅶ, or Ⅷ, laparoscopic hepatectomy with this novel position—the left jackknife position—is safe and effective during tumor resection by exposing a sufficient operating field.Trial registration ClinicalTrials.gov ID:
基金supported by grants from the National Natural Science Foundation of China(30872489and30972916)
文摘Stem cell marker LIN28,related closely with SOX2 and OCT4,has been studied as a biomarker for the maintainance of pluripotent cells in several malignancies.Our previous study showed that SOX2 and OCT4 were negative predictors for hepatocellular carcinoma(HCC).However,the predictive value of LIN28 in HCC outcome is still undetermined.We hypothesized that LIN28 may also play a role as a biomarker for HCC.To test this hypothesis,we examined the expression of LIN28 in 129 radically resected HCC tissues using reverse transcription-polymerase chain reaction and analyzed the association of LIN28 expression with clinicopathologic features and prognosis.Our study showed that LIN28 was expressed at a higher frequency in tumor tissues than in non-HCC tissues(45.0% vs.21.7%,P = 0.020).Moreover,LIN28 expression was significantly increased in cases with large tumor size(P = 0.010).Univariate analysis did not reveal a significant correlation between LIN28 expression and overall survival or recurrence-free survival.For HCC patients who met the Milan criteria,stratified analysis revealed shorter overall survival(P = 0.007) and recurrence-free survival(P < 0.001) in those with detectable LIN28 expression compared to those with no detectable LIN28 expression.Furthermore,multivariate analysis revealed that LIN28 was a negative independent predictor for both overall survival(hazard ratio= 7.093,P = 0.017) and recurrence-free survival(hazard ratio=5.518,P = 0.004) in patients who met the Milan criteria.Taken together,our results suggest that LIN28 identifies low-risk and high-risk subsets of HCC patients meeting the Milan criteria who undergo hepatectomy.
基金supported by National Key R&D Program of China(2017YFA0505803)National Natural Science Foundation of China(No.81625017,No.81572385)National Science and Technology Major Project of China(2018ZX10302205).
文摘Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a retrospective,single-center trial.Between April 3,2017 and July 2,2018,104 patients with Child-Pugh A and advanced HCC received either 400 mg of sorafenib orally twice daily plus HAIC with oxaliplatin(oxaliplatin 85 mg/m^2,every 3 weeks via repetitive catheterization)(n=46,soraOXA group)or 400 mg of only sorafenib orally twice daily(n=58,sorafenib group).Overall survival,progression-free survival,objective response rate,and treatment-related adverse events were compared.Results:The median overall survival was 9.37 months(95%CI,7.05-11.68)in the soraOXA group versus 4.8 months(95%CI,2.98-6.62)in the sorafenib group(HR 0.46[95%CI,0.29-0.72];P<0.001).The soraOXA group also showed a higher objective response rate(16[34.8%]vs 1[1.7%];P<0.001)and a longer progressionfree survival rate(5.5 months[95%CI,2.32-8.68]vs 2.4 months[95%CI,1.65-3.15],HR 0.54[95%CI,0.36-0.81],P=0.003)than the sorafenib group.There was no significant difference in the overall incidence of any grade adverse events,grade 3/4 adverse events,serious adverse events,or incidence of treatment termination due to adverse events between the two groups.Conclusion:Compared with sorafenib alone,sorafenib plus HAIC with oxaliplatin showed favorable treatment outcomes in patients with advanced HCC.The merits of this approach need to be established with a prospective trial.
文摘Objective：This study proposed a modified Blumgart anastomosis（m-BA）that uses a firm ligation of the main pancreatic duct with a supporting tube to replace the pancreatic duct-to-jejunum mucosa anastomosis,with the aim of simplifying the complicated steps of the conventional BA（c-BA）.Thus,we observe if a difference in the risk of postoperative pancreatic fistula（POPF）exists between the two methods.Methods：The m-BA anastomosis method has been used since 2010.From October 2011 to October 2015,147 patients who underwent pancreatoduodenectomy（PD）using BA in Tianjin Medical University Cancer Institute and Hospital were enrolled in this study.According to the type of pancreatojejunostomy（PJ）,50 patients underwent m-BA and 97 received c-BA.The two patient cohorts were compared prospectively to some extent but not randomized,and the evaluated variables were operation time,the incidence rate of POPF,and other perioperative complications.Results：The operation time showed no significant difference（P〉0.05）between the two groups,but the time of duct-to-mucosa anastomosis in the m-BA group was much shorter than that in the c-BA group（P〈0.001）.The incidence rate of clinically relevant POPF was 12.0%（6/50）in the modified group and 10.3%（10/97）in the conventional group（P〉0.05）,which means that the modified anastomosis method did not cause additional pancreatic leakage.The mean length of postoperative hospital stay of the m-BA group was 23 days,and that of the c-BA group was 22 days（P〉0.05）.Conclusions：Compared with the conventional BA,we suggest that the modified BA is a feasible,safe,and effective operation method for P J of PD with no sacrifice of surgical quality.In the multivariate analysis,we also found that body mass index（≥25
基金supported by grants from Scientific Research Fund of Anhui Medical University(No.2021xkj034)Clinical Research Cultivation Program of the Second Affiliated Hospital of Anhui Medical University(No.2020LCYB18)Anhui Institute of Translational Medicine(No.2023zhyx-C84).
文摘Objective:This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection.Methods:From March 1,2020 to July 31,2021,80 patients were enrolled,including 40 undergoing intraperitoneal Pringle maneuver(IPM)and 40 extraperitoneal Pringle maneuver(EPM).The observation indices included basic preoperative clinical characteristics and intraoperative and postoperative liver function indices.Results:There were no significant differences in the basic characteristics or types of hepatectomy,intraoperative blood loss,intraoperative blood transfusion,or hepatectomy time between the IPM and EPM groups.However,the blocking and operation time in the IPM group was shorter than that in the EPM group.There were no significant differences in alanine aminotransferase(ALT)or aspartate aminotransferase(AST)levels on the first day after surgery or in total bilirubin(TBIL)or albumin(ALB)levels on the first,third,or fifth days after surgery.However,C-reactive protein(CRP)levels on the first and third days,ALT and AST levels on the third and fifth days were lower,and hospital stay after surgery was shorter in the IPM group than in the EPM group.Conclusion:IPM using bulldog clamps is simple,safe,and effective.The inflammatory reaction is less severe,the degree of liver function injury is lower,and recovery is faster.
基金This work was supported by grants fromTianjin Education Commission, China(No.20040217).
文摘OBJECTIVE To investigate the effect of proteasome inhibition on the sensitivity of carcinoma cells to TRAIL-inducing apoptosis, and to study the mechanism of the response. METHODS Human hepatocellular carcinoma cells, pretreated with the proteasome inhibitor, MG132, were cotreated with TRAIL. Western blot assays, immunoprecipitation and RT-PCR were performed to test the expression of the Bcl-2 family proteins and Bax mRNA. RESULTS We found that (i) proteasome inhibition sensitized the human hepatocellular carcinoma cells to TRAIL; and (ii) resulted in Bax accumulation before release of cytochrome C and induction of apoptosis. These results were associated with the ability of proteasome inhibitors to overcome Bcl-2-mediated antiapoptotic function; (iii) Bax is regulated by an ubiquitin/proteasome-dependent degradation pathway. CONCLUSION Proteasome inhibition sensitized hepatocellular carcinoma cells to TRAIL by the inhibition of the ubiquitin/proteasome-mediated Bax degradation pathway.
文摘Background Antitumor drugs(such as chemotherapy,targeted therapy,immunotherapy,etc.)and local treatments like surgery and radiotherapy are widely used in cancer treatment,but they often carry the risk of liver injury,which seriously affects the prognosis and quality of life of patients.Therefore,liver protection is of crucial importance in cancer treatment.Methods Relevant experts organized by the Oncology Hepatology Committee of China Anti-Cancer Association Association formulated this guideline based on the latest research achievements and clinical practice experience at home and abroad,aiming to provide comprehensive and systematic guidance for clinicians on liver protection.Results This guideline elaborates on the importance of liver protection during cancer treatment,comprehensively introduces the pathophysiological mechanisms,diagnosis,treatment,and preventive measures of antitumor treatment-related liver injury.Conclusion This guideline is helpful for clinicians to formulate individualized treatment plans,improve the treatment outcome and quality of life of cancer patients,and provides an important reference for the clinical practice of liver protection in cancer treatment.
基金supported by grants from the National Natural Science Foundation of China(No.81372571 and 81772598)the Sun Yat-sen University Clinical Research 5010 Program(No.2012010)+1 种基金the State“973 Program”of China(2014CB542005)the Fundamental Research Funds for the Central Universities(17ykzd34).
文摘Background:Average postoperative follow-up intervals vary in patients undergoing hepatocellular carcinoma(HCC)resection because of limited evidence regarding the optimal interval.We aimed to compare the associations of long-versus short-interval follow-up with survival and recurrence in risk-stratified HCC patients.Methods:We performed a retrospective cohort study between 2007 and 2014.In total,1227 patients treated by curative resection of Barcelona Clinic Liver Cancer stage A or B HCC were stratified as having a low(n=865)or high(n=362)risk of early recurrence(within the first 2 years after resection)based on prognostic factors identified by the least absolute shrinkage and selection operation algorithm.Patients were further classified into long-interval(every 4-6 months)and short-interval(every 2-4 months)follow-up subgroups based on follow-up within 2 years after resection(low risk,long vs.short:n=390 vs.n=475;high-risk,long vs.short:n=149 vs.n=213).Results:The short-interval follow-up did not prolong overall survival in either the low-risk(hazard ratio[HR]=1.152;95%confidence interval[CI]0.720-1.843)or high-risk(HR=1.213;95%CI 0.702-2.094)patients.Early recurrence occurred in 401 patients.For high-risk patients,the short-interval follow-up subgroup exhibited smaller intrahepatic recurrence than did the long-interval group(2.6 vs.3.5 cm,respectively,P=0.045).However,no significant difference in the rate of Barcelona Clinic Liver Cancer stage 0/A recurrence was found between the long-and short-interval follow-up groups in either low-or high-risk patients(63.1%vs.68.2%,respectively,P=0.580;31.3%vs.41.5%,respec-tively,P=0.280).The rate of curative intent treatment for recurrence(34.5%vs.39.7%,respectively,P=0.430;14.6%vs.20.3%,respectively,P=0.388)was also similar between the follow-up groups for low-and high-risk patients.Conclusions:Shortening the postoperative follow-up interval from every 4-6 months to every 2-4 months within the first 2 years after resection did not increase the rate of curative intent treatment or prolong the overall survival of patients with Barcelona Clinic Liver Cancer stage A or B HCC.
基金supported by the National Science Foundation of China(No.81772521)Multicenter Clinical Research Project of Shanghai Jiaotong University School of Medicine(No.DLY201807)Clinical Training Program of Shanghai Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine(No.17CSK06).
文摘Aim:To evaluate the perioperative outcomes and postoperative survival of applying staging laparoscopy(SL)in intrahepatic cholangiocarcinoma(ICC)patients undergoing surgical resection.Methods:A retrospective analysis was performed on all selected ICC patients who underwent curative-intent resection with/without applying staging laparoscopy from January 2010 to August December 2021.Perioperative outcomes and postoperative survival were analyzed.Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were performed to reduce the bias due to confounding variables in the SL group and the non-SL group.Multivariate Cox analysis was used to ascertain the independent predictor of survival for ICC patients.Results:A total of 279 patients(24.1%)were included in the SL group,while 881 patients(75.9%)were included in the non-SL group.Compared with the non-SL group,the SL group had lower blood loss,smaller tumor size,higher R0 resection rate,and shorter hospital stay,but a higher incidence of postoperative complications.The OS of the SL group was better than that of the non-SL group(Median OS:31 months vs.20 months).The 1-,3-,and 5-year overall survival rates of the SL group were 77.9%,45.1%,and 32.9%,respectively,while the non-SL group had rates of 63.9%,31.3%,and 18.4%.SL was confirmed as an independent predictor of survival by multivariate Cox analysis.Conclusion:ICC patients receiving SL had better perioperative outcomes and significantly prolonged overall survival after resection surgery.The subgroup analysis results support the use of routine SL.
基金supported by the National Natural Science Foundation of China(Nos.82372818 to Xiaodong Zhang,82103066 to Guang Yang,82302887 to Hongfeng Yuan,82303210 to Yufei Wang)The China Postdoctoral Science Foundation(No.2022M712389 to Hongfeng Yuan,No.2023M732624 to Yufei Wang,No.2023M742621 to Lina Zhao)+1 种基金Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-009A to W.Lu,China)“14th Five-Year Plan”Tumor Prevention and Treatment Research Project of Tianjin Medical University Cancer Institute and Hospital(No.YZ-03,China).
文摘Protein arginine methyltransferase 5(PRMT5)acts as an oncogene in liver cancer,yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined.Here,we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8^(+)T-cell-mediated antitumor immunity both in vivo and in vitro.Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule,fibrinogen-like protein 1(FGL1).Mechanistically,PRMT5 catalyzed symmetric dimethylation of transcription factor 12(TCF12)at arginine 554(R554),prompting the binding of TCF12 to FGL1 promoter region,which transcriptionally activated FGL1 in tumor cells.Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression,which promoted CD8^(+)T-cell-mediated antitumor immunity.Notably,combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice.Collectively,our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.
