Objective: To discuss the methods and effects of serial therapies oriented by surgery in the treatment of pri- mary large liver cancers. Methods: From January 1993 to June 1999, 191 pa- tients with large liver carcino...Objective: To discuss the methods and effects of serial therapies oriented by surgery in the treatment of pri- mary large liver cancers. Methods: From January 1993 to June 1999, 191 pa- tients with large liver carcinoma were treated surgi- cally. The size of tumors varied from 5.2 to 19.7 cm (mean 9.4 cm). Several types of liver resections were made in 121 patients and as a supplement, cry- osurgery was carried out for the remaining 70 pa- tients. Importable drug delivery system was institu- ted intraoperatively. Transcatheter arterial chemo- embolization (THP 30-60 mg, E-ADM 20-40 mg, CDDP 40-80 mg, MMC 10-20 mg, iodin oil 5-30 ml), percutaneous ethanol injection, bioimmunother- apy and traditional Chinese medicine were used pre- and post-operatively. CT angiography and CT dur- ing arterial portography were used to find satellite nodules. Early stage recurrences were predicted by AFPmRNA in peripheral blood. Child-Pugh's classi- fication plus branch chain amino acid/aromatic ami- no acid ratio (BCAA/AAA) was adopted in evalua- ting pre-operative liver functions. Results: Marked results were observed after serial treatments oriented by surgery. The 1-, 3- and 5- year survival rates in resection group were 75.8 %, 45.6% and 30.4%. respectively. The 1- and 3-year survival rates in cryosurgery group were 63.2 % and 37.0 %. The operative mortality was 1.57 %. Recur- rence rates were 69.2 % in AFPmRNA positive group and 33.3% in AFPmRNA negative group (P< 0.05). The BCAA/AAA ratio was lower than 1.5 in two patients who died of hepatic failure after resec- tion. Conclusions: Serial treatments with surgery as the chief modality gives satisfactory results in patients with large primary liver carcinoma. This regimen should be regarded as a main strategy to deal with large liver carcinoma. AFPmRNA in the peripheral blood, signifying a recurrence, may become a new clinical parameter. The BCAA/AAA ratio plus Child-Pugh's classification is able to evaluate more accurately liver function reserve before surgery.展开更多
A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared wi...A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared with the control cell clone JX-0 transferred with the vector plasmid and the parent BEL-7404 cells, the antisense EGFR transferred cell clone JX-1 showed a decreased EGFR gene expression and reduced significantly the growth potential either in anchorage-dependent or anchorage-independent growth. Furthermore. JX-1 cells appeared to be distinctly dependent on serum concentration for monolayer growth. The results suggested that antisense EGFR could partly block the EGFR gene ex-pression and reverse the malignant growth properties of human liver carcinoma cells in vitro.展开更多
The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2...The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up- regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.展开更多
Objective Liver transplantation is a current treatment option for hepatocellular carcinoma(HCC).The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of ...Objective Liver transplantation is a current treatment option for hepatocellular carcinoma(HCC).The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of liver transplantation,including locoregional recurrence,distant metastasis,and in-hospital mortality,in HCC patients with concurrent hepatitis B infection,hepatitis C infection,or alcoholic cirrhosis.Methods This retrospective cohort study included HCC patients(n=2391)from the National Inpatient Sample database who underwent liver transplantation and were diagnosed with hepatitis B or C virus infection,co-infection with hepatitis B and C,or alcoholic cirrhosis of the liver between 2005 and 2014.Associations between HCC etiology and post-transplant outcomes were examined with multivariate analysis models.Results Liver cirrhosis was due to alcohol in 10.5%of patients,hepatitis B in 6.6%,hepatitis C in 10.8%,and combined hepatitis B and C infection in 24.3%.Distant metastasis was found in 16.7%of patients infected with hepatitis B and 9%of hepatitis C patients.Local recurrence of HCC was significantly more likely to occur in patients with hepatitis B than in those with alcohol-induced disease.Conclusion After liver transplantation,patients with hepatitis B infection have a higher risk of local recurrence and distant metastasis.Postoperative care and patient tracking are essential for liver transplant patients with hepatitis B infection.展开更多
Context/Objectives: Hepatocellular carcinoma occurs mainly and increasingly in developing countries, where the prognosis is particularly poor. The Barcelona Clinic Liver Cancer classification is used to guide the trea...Context/Objectives: Hepatocellular carcinoma occurs mainly and increasingly in developing countries, where the prognosis is particularly poor. The Barcelona Clinic Liver Cancer classification is used to guide the treatment of hepatocellular carcinoma. The aim of this retrospective study was to describe the Barcelona Clinic Liver Cancer classification and the treatment of hepatocellular carcinoma in a University Hospital in Côte d’Ivoire. Methods: Patients with hepatocellular carcinoma hospitalized in the hepato-gastroenterology unit of the University Hospital of Yopougon from 01 January 2012 to 30 June 2017 were included. The diagnosis of hepatocellular carcinoma was based on the presence of hepatic nodules on the abdominal ultrasound scan, typical images with the helical scanner associated or not with an increase of the α-fetoprotein higher than 200 ng/ml or with histology. Demographic, clinical, biological and radiological data were determined at the time of diagnosis. Patients were classified according to the Barcelona Clinic Liver Cancer classification. Their treatment was specified. Results: There were 258 patients whose median age was 48.1 years. Viral hepatitis B virus was the primary cause of hepatocellular carcinoma in 64.7% of cases. The severity of the underlying cirrhosis was Child-Pugh A in 12.1%, B in 63.6% and C in 24.3% of cases. The median size of the tumor was 63 mm. The α-fetoprotein level was higher than 200 mg/ml in 56.03% of cases. The Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) system was ≥2 in 82.9%. The Barcelona Clinic Liver Cancer classification was A in 1.3%, B in 0%, C in 55.2% and D in 43.5% of patients. There was no transplantation or hepatic resection. Very few patients (1.9%) received radio-frequency curative therapy. The treatment was predominantly symptomatic in 97.8% of patients. During hospitalization 43.7% of patients died. Conclusion: Hepatocellular carcinoma occurs on a liver with severe cirrhosis at a late stage. This does not allow cure treatment and explains a high mortality rate during hospitalization. Hepatitis B virus is the main risk factor and immunization at birth will reduce the incidence of this cancer in Africa.展开更多
Objective To investigate the antitumor effects of intrasplenically transplanted interleukin-18 (IL-18) gene-modified hepatocytes on murine implanted liver carcinoma. Methods Embryonic murine hepatocyte cell line (BNL-...Objective To investigate the antitumor effects of intrasplenically transplanted interleukin-18 (IL-18) gene-modified hepatocytes on murine implanted liver carcinoma. Methods Embryonic murine hepatocyte cell line (BNL-CL2) was transfected with a recombinant adenovirus encoding IL-18 and used as delivery cells for IL-18 gene transfer. Two cell lines,BNL-LacZ and BNL-CL2, were used as controls. One week after intrasplenic injection of C26 cells (colon carcinoma line),tumor-bearing syngeneic mice underwent the intrasplenic transplantation of IL-18 gene-modified hepatocyte cell line and were divided into treatment group (BNL IL-18) and control groups (BNL-LacZ and BNL-CL2 ). Two weeks later,the serum levels of IL-18,interferon-γ (IFN-γ),tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in the implanted liver carcinoma-bearing mice were assayed,the cytotoxicity of murine splenic cytotoxic T-lymphocytes (CTLs) was measured,and the morphology of the hepatic tumors was studied to evaluate the antitumor effects of the approach. Results In the treatment group,the serum levels of IL-18,IFN-γ,TNF-α and NO increased significantly. The splenic CTL activity increased markedly ( P <0.01) ,accompanied by a substantial decrease in tumor volume and the percentage of tumor area and prolonged survival of liver carcinomo-being mice. Conclusions In vivo IL-18 expression by ex vivo manipulated cells with IL-18 recombinant adenovirus is able to exert potent antitumor effects by inducing a predominantly T-cell-helper type 1 (Th1) immune response. Intrasplenic transplantation of adenovirus-mediated IL-18 gene-modified hepatocytes could be used as a targeting treatment for implanted liver carcinoma.展开更多
OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effe...OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effect of interventional hyperthermia and interventional thermochemotherapy on VX2 carcinoma in rabbit liver. METHODS VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups (15 per group). The 4 groups (designated as 1, 2, 3, 4 respectively) were injected with 10 ml of the following via the hepatic artery: physiological saline (37℃); adriamycin (37℃); physiological saline (60℃); adriamycin (60℃). One week later, the tumor volume, serum level of aspartate transaminase (AST) and the survival of the rabbits bearing VX2 were observed and compared among the different treated groups. RESULTS The tumor growth rate in group 4 (ADM 60℃) (0.53±0.21)% was significantly lower than that in group 1 (3.48±1.17)%, in group 2 (1.09±0.26)% and group 3 (3.32±1.28)% (P<0.05, P<0.05, P<0.01, respectively). The days of survival days for group 4 (87.0±2.0) were significantly more than that in group 1 (40.0±3.0). Group 4 showed a significantly higher increase in serum AST compared to group 1 (P<0.05), but without significant differences compared to the other groups (P>0.05). CONCLUSION Adriamycin treatment at 60℃ significantly deceased the tumor growth, prolonged the survival period and resulted in reversible liver damage.展开更多
Introduction: Acute hemoperitoneum due to the spontaneous rupture of hepatocellular carcinoma (HCC) is a rare case of non-traumatic intra-abdomen bleeding that requires a high index of suspicion to approach, especiall...Introduction: Acute hemoperitoneum due to the spontaneous rupture of hepatocellular carcinoma (HCC) is a rare case of non-traumatic intra-abdomen bleeding that requires a high index of suspicion to approach, especially if no known history of HCC. It can mislead the physicians when the patient presents in an atypical way. Case Presentation: In this case report, we describe a fortuitous rupture of hepatocellular carcinoma in a 58-year-old male who was not previously diagnosed as having HCC and who came with atypical symptoms and signs of hemoperitoneum. He was then treated by trans-arterial embolectomy. Discussion: Diagnosis of hemoperitoneum in a case with bradycardia and hypotension is uncommon, as it goes more towards cardiogenic shock than hypovolemic shock, especially in a patient who is previously not symptomatic and has no risk factor for hepatocellular carcinoma. Conclusion: physicians should be alert to the possibility of encountering a hemorrhagic shock, although no trauma injury in any hypotensive patient with no clear reason for his condition.展开更多
Objective:To identify potential early diagnostic markers for hepatitis B progression to primary liver carcinoma using routine immunological tests based on 6 cytokine combinations.Methods:Eight hundred and ninety-nine ...Objective:To identify potential early diagnostic markers for hepatitis B progression to primary liver carcinoma using routine immunological tests based on 6 cytokine combinations.Methods:Eight hundred and ninety-nine patients with hepatitis B progressing to early primary liver carcinoma admitted to and treated at Changhai Hospital,Naval Military Medical University,Shanghai,China between March 2015 and June 2017 were included in this observational study,including 666 patients with HBsAg^(+),HBeAb^(+),HBcAb^(+)liver carcinoma and 233 patients with HBsAg+,HBeAg+,HBcAb+liver carcinoma.Receiver operating characteristic(ROC)curves were used to evaluate the efficiency of the different cytokine in the diagnosis of hepatocellular carcinoma in patients with hepatitis B.This study was approved by the Institutional Review Board of Changhai Hospital,Naval Military Medical University,China(approval No.CHEC2020-080)on June 6,2020.Results:Changed levels of interleukin(IL)-1β,IL-2R,IL-8,and tumor necrosis factor(TNF)-a were statistically significant(P<0.05).The area under the ROC curve,sensitivity,specificity,positive predictive value,negative predictive value,and Youden index for the diagnosis of primary liver carcinoma using the combination of IL-1β,IL-2R,IL-8,and TNF-α were 0.938,79.2%,96.7%,96%,82.0%,0.759,respectively.The serum alpha-fetoprotein level in patients with primary liver carcinoma was positively correlated with IL-2R(r=0.3502,P<0.001),IL-8(r=0.1558,P=0.0273),and TNF-α(r=0.2544,P<0.001)levels.The equation fitted to the results was logit(P)=0.086+0.01IL-2R–0.001IL-8–0.033TNF-α–0.041IL-1β.Conclusion:Our study establishes a novel,potentially valuable diagnostic model based on four cytokines related to the early stages of liver carcinoma.展开更多
Objective：We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation（LT）for hepatocellular carcinoma（HCC）.Methods：We retrospectively analyzed HCC recipients withou...Objective：We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation（LT）for hepatocellular carcinoma（HCC）.Methods：We retrospectively analyzed HCC recipients without steroids after LT（SF group,n=368）based on the China Liver Transplant Registry（CLTR）database.These recipients were matched 1：2 with patients using steroids（S group,n=736）for the same period after LT for HCC,according to propensity scores.Results：Multivariate analysis indicates that recipients with younger age[odds ratio（OR）,1.053;P=0.011],preoperative hepatitis B virus（HBV）DNA≥1,000 copies/mL（OR,2.597;P=0.004）and beyond Milan criteria（OR,4.255;P〈0.001）were identified as the risk factors associated with tumor recurrence in steroid avoidance recipients after LT.The patients fulfilling the Milan criteria in the SF group presented higher overall and tumor-free survival rates than those in the S group（P〈0.05）.Multivariate analysis revealed that recipient beyond Milan criteria was an independent prognostic factor for overall survival（OR,1.690;P〈0.001）and tumor-free survival（OR,2.066;P〈0.001）.The incidences of new-onset diabetes mellitus（21.20% vs.33.29%,P〈0.001）,new-onset hypertension（10.05%vs.18.61%,P〈0.001）and hyperlipidemia（4.08% vs.7.20%,P=0.042）were significantly lower in the SF group.Conclusions：Steroid-free immunosuppression could be safe and feasible for HBV-related HCC patients in LT.Age,HBV DNA level and Milan criteria maybe risk factors associated with tumor recurrence in steroid avoidance recipients.Recipient beyond Milan criteria was an independent prognostic factor and recipient fulfilling Milan criteria can benefit the most from steroid-free immunosuppression.展开更多
AIM: To investigate the efficacy(survival) and safety of treatments for recurrent hepatocellular carcinoma(HCC) in liver transplantation(LT) patients.METHODS: Literature search was performed on available online databa...AIM: To investigate the efficacy(survival) and safety of treatments for recurrent hepatocellular carcinoma(HCC) in liver transplantation(LT) patients.METHODS: Literature search was performed on available online databases without a time limit until January 2015. Clinical studies describing survival after HCC recurrence in LT patients were retrieved for a fulltext evaluation. A total of 61 studies were selected: 13 case reports, 41 retrospective case series, and 7 retrospective comparative studies.RESULTS: Based on all included studies, the mean HCC recurrence rate was 16% of all LTs for HCC. A total of 1021 LT patients experienced HCC recurrence. The median time from LT to HCC recurrence was 13 mo(range 2-132 mo). The majority of patients(67%) presented with HCC extra-hepatic recurrences, involving lung, bone, adrenal gland, peritoneal lymph nodes, and rarely the brain. Overall survival after HCC recurrence was 12.97 mo. Surgical resection of localized HCC recurrence and Sorafenib for controlling systemic spread of HCC recurrence were associated with the higher survival rates(42 and 18 mo, res-pectively). However, Sorafenib, especially when combined with m TOR, was frequently associated with severe side effects that required dose reduction or discontinuation CONCLUSION: Management of recurrent HCC in LT patients is challenging and associated with poor prognosis independently of the type of treatment.展开更多
The barcelona clinic liver cancer(BCLC)staging system has been approved as guidance for hepatocellular carcinoma(HCC)treatment guidelines by the main Western clinical liver associations.According to the BCLC classific...The barcelona clinic liver cancer(BCLC)staging system has been approved as guidance for hepatocellular carcinoma(HCC)treatment guidelines by the main Western clinical liver associations.According to the BCLC classification,only patients with a small single HCC nodule without signs of portal hypertension or hyperbilirubinemia should undergo liver resection.In contrast,patients with intermediate-advanced HCC should be scheduled for palliative therapies,even if the lesion is resectable.Recent studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by liver resection.Therefore,this classification has been criticised because it excludes many patients who could benefit from curative resection.The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations.Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function with a 5-year survival rate of 50%.Surgery also offers good long-term result in selected patients with multiple or large HCCs with a reported 5-year survival rate of over 50%and 40%,respectively.Although macrovascular invasion is associated with a poor prognosis,liver resection provides better long-term results than palliative therapies or best supportive care.Recently,researchers have identified several genes whose altered expression influences the prognosis of patients with HCC.These genes may be useful for classifying the biological behaviour of different tumours.A revision of the BCLC classification should be introduced to provide the best treatment strategy and to ensure the best prognosis in patients with HCC.展开更多
BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with multiple etiologies, high incidence, and high mortality. The standard surgical management for patients with HCC consists of locoregional ab...BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with multiple etiologies, high incidence, and high mortality. The standard surgical management for patients with HCC consists of locoregional ablation, surgical resection, or liver transplantation, depending on the background state of the liver. Eighty percent of patients initially presenting with HCC are unresectable, either due to the extent of tumor or the level of underlying hepatic dysfunction. While in patients with no evidence of cirrhosis and good hepatic function resection has been the surgical treatment of choice, it is contraindicated in patients with moderate to severe cirrhosis. Liver transplantation is the optimal surgical treatment. DATA SOURCES: PubMed search of recent articles (from January 2000 to March 2011) was performed looking for relevant articles about hepatocellular carcinoma and its treatment. Additional articles were identified by evaluating references from selected articles. RESULTS: Here we review criteria for transplantation, the types, indications, and role of locoregional therapy in treating the cancer and in downstaging for possible later transplantation. We also summarize the contribution of immunosuppression and adjuvant chemotherapy in the management and prevention of HCC recurrence. Finally we discuss recent advances in imaging, tumor biology, and genomics as we delineate the remaining challenges for the diagnosis and treatment of this disease. CONCLUSIONS: Much can be improved in the diagnosis and treatment of HCC. A great challenge will be to improve patient selection to criteria based on tumor biology. Another will be to incorporate systemic agents post-operatively in patients at high risk for recurrence, paying close attention to efficacy and safety. The future direction of the effort in treating HCC will be to stimulate prospective trials, develop molecular imaging of lymphovascular invasion, to improve recipient selection, and to investigate biomarkers of tumor biology.展开更多
OBJECTIVE: To study the changes of immune function in liver cirrhosis patients after splenectomy combined with resection of hepatocellular carcinoma (HCC). METHODS: Sixteen patients with HCC associated with liver cirr...OBJECTIVE: To study the changes of immune function in liver cirrhosis patients after splenectomy combined with resection of hepatocellular carcinoma (HCC). METHODS: Sixteen patients with HCC associated with liver cirrhosis were divided into two groups: splenectomy combined with hepatectomy (splenectomy group n=7) and hepatectomy (non-splenectomy group, n=9). T lymphocyte subsets such as CD4, CD8, CD4/CD8 and Th lymphocyte cytokines such as interferon γ (IFN-γ), IL-2, IL-10 in 7 ml peripheral venous blood before operation and 2 months after operation were examined and compared between the two groups. RESULTS: There was no significant difference in pre-operative CD4, CD8, CD4/CD8, IL-2, IFN-γ, IL-10 levels in the two groups. Two months after operation, the levels of CD4 (38.2%±3.7%), CD4/CD8 (1.7±0.3), IFN-γ (104.4±14.9 pg/ml), 1L-2 (98.6±18.6 pg/ml) were increased and those of CD8 (23.7±3.7 pg/ml), IL-10 (55.5±11.2 pg/ml) levels were decreased in the splenectomy group. The levels of CD4 (32.5%±4.0%), CD4/CD8 (1.1±0.1), IFN-γ(70.5±12.6 pg/ml), IL-2(80.9±13.5 pg/ml) in the non-splenectomy group were much lower than those in the splenectomy group, but the levels of CD8 (29.4%±4.0%), IL-10 (89.4±10.0 pg/ml) in the non-splenectomy group were significantly higher than those in the splenectomy group (P<0.05). CONCLUSIONS: Splenectomy combined with hepatectomy for HCC patients associated with liver cirrhosis does not decrease but promote the recovery of T lymphocyte subsets and Th1/Th2 cytokines from imbalance and improve anti-tumor immune function of the patients.展开更多
BACKGROUND：Early recurrence of hepatocellular carcinoma（HCC）is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early...BACKGROUND：Early recurrence of hepatocellular carcinoma（HCC）is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early recurrence after cu rative hepatectomy and to establish a simple predictive model for HCC early recurrence.METHODS： A total of 200 patients who had undergone curative resection for HCC were retrospectively analyzed. The patients were divided into early recurrence （within 2 years） and non-early recurrence groups. Demographical characteristics, preopera- tive liver function parameters, surgical factors and tumor related factors of the patients were assessed by univariate analysis to identify potential significant predictors for early recurrence after resection of HCC. Parameters with statisti- cal significance were entered into a Cox proportional hazard model to find independent risk factors. Receiver operating characteristic analysis was done to determine optimal cut-off values and the number of combined factors in multi-factor predictive model. RESULTS： Of 13 potential risk factors for early recurrence identified by univariate analysis, high lactate dehydrogenase （LDH〉206 U/L, HR=1.711, P=0.006）, high aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio （AST/ ALT〉0.96, HR=1.769, P=0.006）, elevated alpha-fetoprotein （AFP〉8.6 ng/mL, HR=2.079, P=0.007）, small resection margin （〈1 cm, HR=2.354, P〈0.001） and advanced TNM stage （TNM III-IV, HR=2.164, P〈0.001） were independent risk factors for early recurrence of HCC shown by multivariate analysis. Patients with three or more concurrent independent risk factors had significantly higher risk for early recurrence than those with low risk factors. The sensitivity and specificity of this predictive model are 53.6% and 80.7%, respectively （area under curve=0.741, 95% CI 0.674-0.800, P〈0.0001）. CONCLUSIONS： Preoperative common fiver enzyme markers, LDH and AST/ALT ratio, were independently associated with early recurrence of HCC. The combination of serum liver enzyme markers with AFP, resection margin and TNM stage bet- ter predicted early recurrence of HCC after curative resection in a simple multi-factor model.展开更多
Liver resection for hepatocellular carcinoma(HCC)is currently known to be a safer procedure than it was before because of technical advances and improvement in postoperative patient management and remains the first-li...Liver resection for hepatocellular carcinoma(HCC)is currently known to be a safer procedure than it was before because of technical advances and improvement in postoperative patient management and remains the first-line treatment for HCC in compensated cirrhosis.The aim of this review is to assess current indications,advantages and limits of laparoscopic surgery for HCC resections.We also discussed the possible evolution of this surgical approach in parallel with new technologies.展开更多
BACKGROUND: With the maturation and popularization of skills in liver transplantation (LT), patients with hepatocellular carcinoma (HCC) have an alternative choice. LT as a curative treatment for HCC provides good liv...BACKGROUND: With the maturation and popularization of skills in liver transplantation (LT), patients with hepatocellular carcinoma (HCC) have an alternative choice. LT as a curative treatment for HCC provides good liver function and systemic condition to recipients. Preoperative tumor characteristics are critical in selecting optimal candidates for LT to optimize the use of donor livers and to achieve a long-term survival. The present study aimed to elucidate the risk factors of HCC involved in fatal recurrence in the first year after LT and to investigate their utility in selecting suitable candidates for LT. METHODS: From April 2002 to October 2005, 303 patients who had received orthotopic LT for HCC were reviewed. Of these patients, those with diffuse intrahepatic or multiple systemic recurrent lesions who died within I year after surgery were investigated as fatal recurrence group (48 patients) and the remaining patients including those who were disease-free without recurrence, those who were alive with recurrence in the first year, or those who died in the first year of other causes, served as control group (255). The two groups were compared by demographics, tumor, and histopathological characteristics for their prognostic significance by logistic regression analysis. RESULTS: Multivariate analysis between the fatal recurrence group and the control group showed that the presence of vascular invasion, a tumor size greater than 6.5 cm, and a preoperative serum alpha-fetoprotein (AFP) level greater than 1000 mu g/L were risk factors for fatal recurrence. Increased risk factors reduced the suitability of candidates for LT and diminished survival in the first year. 85.71% of the patients with all three risk factors, 37.84% of those with two factors, 13.64% of those with one factor, and 6.71% of those without risk factors died from tumor recurrence within I year after transplantation. CONCLUSIONS: Vascular invasion, tumor size >= 16.5 cm, and preoperative serum AFP level >= 1000 mu g/L, were significant predictors of fatal recurrence after LT for HCC. Patients with two or more risk factors should not be candidates for LT.展开更多
A large number of liver transplants have been performed for hepatocellular carcinoma(HCC), and recurrence is increasingly encountered. The recurrence of HCC after liver transplantation is notoriously difficult to mana...A large number of liver transplants have been performed for hepatocellular carcinoma(HCC), and recurrence is increasingly encountered. The recurrence of HCC after liver transplantation is notoriously difficult to manage. We hereby propose multi-disciplinary management with a systematic approach. The patient is jointly managed by the transplant surgeon, physician, oncologist and radiologist. Immunosuppressants should be tapered to the lowest effective dose to protect against rejection. The combination of a mammalian target of rapamycin inhibitor with a reduced calcineurin inhibitor could be considered with close monitoring of graft function and toxicity. Comprehensive staging can be performed by dual-tracer positron emission tomography-computed tomography or the combination of contrast computed tomography and a bone scan. In patients with disseminated recurrence, sorafenib confers survival benefits but is associated with significant drug toxicity. Oligo-recurrence encompasses recurrent disease that is limited in number and location so that loco-regional treatments convey disease control and survival benefits. Intra-hepatic recurrence can be managed with graft resection, but significant operative morbidity is expected. Radiofrequency ablation and stereotactic body radiation therapy(SBRT) are effective alternative strategies. In patients with more advanced hepatic disease, regional treatment with trans-arterial chemoembolization or intra-arterial Yttrium-90 can be considered. For patients with extra-hepatic oligorecurrence, loco-regional treatment can be considered if practical. Patients with more than one site of recurrence are not always contraindicated for curative treatments. Surgical resection is effective for patients with pulmonary oligo-recurrence, but adequate lung function is a prerequisite. SBRT is a non-invasive and effective modality that conveys local control to pulmonary and skeletal oligo-recurrences.展开更多
Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma(HCC) with annual cumulative incidence...Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma(HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3. Current literature describes NAFLD-HCC mostly as a disease of late presentation with lower rates of receipt of curative therapy and worse prognosis. However, a growing body of evidence has reported comparable and potentially more favorable disease-free and overall survival rates among patients with NAFLD-HCC after receipt of curative treatment. This review summarizes current evidence of epidemiology, pathophysiology, disease presentation, demand and receipt of curative therapy, post-treatment outcomes, and overall survival of NAFLD-associated HCC.展开更多
文摘Objective: To discuss the methods and effects of serial therapies oriented by surgery in the treatment of pri- mary large liver cancers. Methods: From January 1993 to June 1999, 191 pa- tients with large liver carcinoma were treated surgi- cally. The size of tumors varied from 5.2 to 19.7 cm (mean 9.4 cm). Several types of liver resections were made in 121 patients and as a supplement, cry- osurgery was carried out for the remaining 70 pa- tients. Importable drug delivery system was institu- ted intraoperatively. Transcatheter arterial chemo- embolization (THP 30-60 mg, E-ADM 20-40 mg, CDDP 40-80 mg, MMC 10-20 mg, iodin oil 5-30 ml), percutaneous ethanol injection, bioimmunother- apy and traditional Chinese medicine were used pre- and post-operatively. CT angiography and CT dur- ing arterial portography were used to find satellite nodules. Early stage recurrences were predicted by AFPmRNA in peripheral blood. Child-Pugh's classi- fication plus branch chain amino acid/aromatic ami- no acid ratio (BCAA/AAA) was adopted in evalua- ting pre-operative liver functions. Results: Marked results were observed after serial treatments oriented by surgery. The 1-, 3- and 5- year survival rates in resection group were 75.8 %, 45.6% and 30.4%. respectively. The 1- and 3-year survival rates in cryosurgery group were 63.2 % and 37.0 %. The operative mortality was 1.57 %. Recur- rence rates were 69.2 % in AFPmRNA positive group and 33.3% in AFPmRNA negative group (P< 0.05). The BCAA/AAA ratio was lower than 1.5 in two patients who died of hepatic failure after resec- tion. Conclusions: Serial treatments with surgery as the chief modality gives satisfactory results in patients with large primary liver carcinoma. This regimen should be regarded as a main strategy to deal with large liver carcinoma. AFPmRNA in the peripheral blood, signifying a recurrence, may become a new clinical parameter. The BCAA/AAA ratio plus Child-Pugh's classification is able to evaluate more accurately liver function reserve before surgery.
文摘A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared with the control cell clone JX-0 transferred with the vector plasmid and the parent BEL-7404 cells, the antisense EGFR transferred cell clone JX-1 showed a decreased EGFR gene expression and reduced significantly the growth potential either in anchorage-dependent or anchorage-independent growth. Furthermore. JX-1 cells appeared to be distinctly dependent on serum concentration for monolayer growth. The results suggested that antisense EGFR could partly block the EGFR gene ex-pression and reverse the malignant growth properties of human liver carcinoma cells in vitro.
文摘The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up- regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.
基金This study was supported by the Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province(No.CXPJJH11900001-2019210).
文摘Objective Liver transplantation is a current treatment option for hepatocellular carcinoma(HCC).The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of liver transplantation,including locoregional recurrence,distant metastasis,and in-hospital mortality,in HCC patients with concurrent hepatitis B infection,hepatitis C infection,or alcoholic cirrhosis.Methods This retrospective cohort study included HCC patients(n=2391)from the National Inpatient Sample database who underwent liver transplantation and were diagnosed with hepatitis B or C virus infection,co-infection with hepatitis B and C,or alcoholic cirrhosis of the liver between 2005 and 2014.Associations between HCC etiology and post-transplant outcomes were examined with multivariate analysis models.Results Liver cirrhosis was due to alcohol in 10.5%of patients,hepatitis B in 6.6%,hepatitis C in 10.8%,and combined hepatitis B and C infection in 24.3%.Distant metastasis was found in 16.7%of patients infected with hepatitis B and 9%of hepatitis C patients.Local recurrence of HCC was significantly more likely to occur in patients with hepatitis B than in those with alcohol-induced disease.Conclusion After liver transplantation,patients with hepatitis B infection have a higher risk of local recurrence and distant metastasis.Postoperative care and patient tracking are essential for liver transplant patients with hepatitis B infection.
文摘Context/Objectives: Hepatocellular carcinoma occurs mainly and increasingly in developing countries, where the prognosis is particularly poor. The Barcelona Clinic Liver Cancer classification is used to guide the treatment of hepatocellular carcinoma. The aim of this retrospective study was to describe the Barcelona Clinic Liver Cancer classification and the treatment of hepatocellular carcinoma in a University Hospital in Côte d’Ivoire. Methods: Patients with hepatocellular carcinoma hospitalized in the hepato-gastroenterology unit of the University Hospital of Yopougon from 01 January 2012 to 30 June 2017 were included. The diagnosis of hepatocellular carcinoma was based on the presence of hepatic nodules on the abdominal ultrasound scan, typical images with the helical scanner associated or not with an increase of the α-fetoprotein higher than 200 ng/ml or with histology. Demographic, clinical, biological and radiological data were determined at the time of diagnosis. Patients were classified according to the Barcelona Clinic Liver Cancer classification. Their treatment was specified. Results: There were 258 patients whose median age was 48.1 years. Viral hepatitis B virus was the primary cause of hepatocellular carcinoma in 64.7% of cases. The severity of the underlying cirrhosis was Child-Pugh A in 12.1%, B in 63.6% and C in 24.3% of cases. The median size of the tumor was 63 mm. The α-fetoprotein level was higher than 200 mg/ml in 56.03% of cases. The Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) system was ≥2 in 82.9%. The Barcelona Clinic Liver Cancer classification was A in 1.3%, B in 0%, C in 55.2% and D in 43.5% of patients. There was no transplantation or hepatic resection. Very few patients (1.9%) received radio-frequency curative therapy. The treatment was predominantly symptomatic in 97.8% of patients. During hospitalization 43.7% of patients died. Conclusion: Hepatocellular carcinoma occurs on a liver with severe cirrhosis at a late stage. This does not allow cure treatment and explains a high mortality rate during hospitalization. Hepatitis B virus is the main risk factor and immunization at birth will reduce the incidence of this cancer in Africa.
基金Thisstudywassupportedby grantsfromtheNationalNaturalScienceFoundationofChina (No 3 0 12 10 0 2 )andNationalKeyBasicResearchProgramofChina (No .2 0 0 1CB5 10 0 0 2 )
文摘Objective To investigate the antitumor effects of intrasplenically transplanted interleukin-18 (IL-18) gene-modified hepatocytes on murine implanted liver carcinoma. Methods Embryonic murine hepatocyte cell line (BNL-CL2) was transfected with a recombinant adenovirus encoding IL-18 and used as delivery cells for IL-18 gene transfer. Two cell lines,BNL-LacZ and BNL-CL2, were used as controls. One week after intrasplenic injection of C26 cells (colon carcinoma line),tumor-bearing syngeneic mice underwent the intrasplenic transplantation of IL-18 gene-modified hepatocyte cell line and were divided into treatment group (BNL IL-18) and control groups (BNL-LacZ and BNL-CL2 ). Two weeks later,the serum levels of IL-18,interferon-γ (IFN-γ),tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in the implanted liver carcinoma-bearing mice were assayed,the cytotoxicity of murine splenic cytotoxic T-lymphocytes (CTLs) was measured,and the morphology of the hepatic tumors was studied to evaluate the antitumor effects of the approach. Results In the treatment group,the serum levels of IL-18,IFN-γ,TNF-α and NO increased significantly. The splenic CTL activity increased markedly ( P <0.01) ,accompanied by a substantial decrease in tumor volume and the percentage of tumor area and prolonged survival of liver carcinomo-being mice. Conclusions In vivo IL-18 expression by ex vivo manipulated cells with IL-18 recombinant adenovirus is able to exert potent antitumor effects by inducing a predominantly T-cell-helper type 1 (Th1) immune response. Intrasplenic transplantation of adenovirus-mediated IL-18 gene-modified hepatocytes could be used as a targeting treatment for implanted liver carcinoma.
文摘OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effect of interventional hyperthermia and interventional thermochemotherapy on VX2 carcinoma in rabbit liver. METHODS VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups (15 per group). The 4 groups (designated as 1, 2, 3, 4 respectively) were injected with 10 ml of the following via the hepatic artery: physiological saline (37℃); adriamycin (37℃); physiological saline (60℃); adriamycin (60℃). One week later, the tumor volume, serum level of aspartate transaminase (AST) and the survival of the rabbits bearing VX2 were observed and compared among the different treated groups. RESULTS The tumor growth rate in group 4 (ADM 60℃) (0.53±0.21)% was significantly lower than that in group 1 (3.48±1.17)%, in group 2 (1.09±0.26)% and group 3 (3.32±1.28)% (P<0.05, P<0.05, P<0.01, respectively). The days of survival days for group 4 (87.0±2.0) were significantly more than that in group 1 (40.0±3.0). Group 4 showed a significantly higher increase in serum AST compared to group 1 (P<0.05), but without significant differences compared to the other groups (P>0.05). CONCLUSION Adriamycin treatment at 60℃ significantly deceased the tumor growth, prolonged the survival period and resulted in reversible liver damage.
文摘Introduction: Acute hemoperitoneum due to the spontaneous rupture of hepatocellular carcinoma (HCC) is a rare case of non-traumatic intra-abdomen bleeding that requires a high index of suspicion to approach, especially if no known history of HCC. It can mislead the physicians when the patient presents in an atypical way. Case Presentation: In this case report, we describe a fortuitous rupture of hepatocellular carcinoma in a 58-year-old male who was not previously diagnosed as having HCC and who came with atypical symptoms and signs of hemoperitoneum. He was then treated by trans-arterial embolectomy. Discussion: Diagnosis of hemoperitoneum in a case with bradycardia and hypotension is uncommon, as it goes more towards cardiogenic shock than hypovolemic shock, especially in a patient who is previously not symptomatic and has no risk factor for hepatocellular carcinoma. Conclusion: physicians should be alert to the possibility of encountering a hemorrhagic shock, although no trauma injury in any hypotensive patient with no clear reason for his condition.
基金This work was supported by the State Key Program of National Natural Science Foundation of China(No.82030073,to SL)the National Natural Science Foundation of China(No.81501401,to CH)Shanghai Science and Technology Committee(No.18XD1405300,to SL).
文摘Objective:To identify potential early diagnostic markers for hepatitis B progression to primary liver carcinoma using routine immunological tests based on 6 cytokine combinations.Methods:Eight hundred and ninety-nine patients with hepatitis B progressing to early primary liver carcinoma admitted to and treated at Changhai Hospital,Naval Military Medical University,Shanghai,China between March 2015 and June 2017 were included in this observational study,including 666 patients with HBsAg^(+),HBeAb^(+),HBcAb^(+)liver carcinoma and 233 patients with HBsAg+,HBeAg+,HBcAb+liver carcinoma.Receiver operating characteristic(ROC)curves were used to evaluate the efficiency of the different cytokine in the diagnosis of hepatocellular carcinoma in patients with hepatitis B.This study was approved by the Institutional Review Board of Changhai Hospital,Naval Military Medical University,China(approval No.CHEC2020-080)on June 6,2020.Results:Changed levels of interleukin(IL)-1β,IL-2R,IL-8,and tumor necrosis factor(TNF)-a were statistically significant(P<0.05).The area under the ROC curve,sensitivity,specificity,positive predictive value,negative predictive value,and Youden index for the diagnosis of primary liver carcinoma using the combination of IL-1β,IL-2R,IL-8,and TNF-α were 0.938,79.2%,96.7%,96%,82.0%,0.759,respectively.The serum alpha-fetoprotein level in patients with primary liver carcinoma was positively correlated with IL-2R(r=0.3502,P<0.001),IL-8(r=0.1558,P=0.0273),and TNF-α(r=0.2544,P<0.001)levels.The equation fitted to the results was logit(P)=0.086+0.01IL-2R–0.001IL-8–0.033TNF-α–0.041IL-1β.Conclusion:Our study establishes a novel,potentially valuable diagnostic model based on four cytokines related to the early stages of liver carcinoma.
基金supported by the Cheung Kong Scholars Programthe Zhejiang Provincial Program for the Cultivation of Highlevel Innovative Health Talentsthe Projects of Medical and Health Technology Program in Zhejiang Province (No. 2015KYB151 and 2017RC002)
文摘Objective：We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation（LT）for hepatocellular carcinoma（HCC）.Methods：We retrospectively analyzed HCC recipients without steroids after LT（SF group,n=368）based on the China Liver Transplant Registry（CLTR）database.These recipients were matched 1：2 with patients using steroids（S group,n=736）for the same period after LT for HCC,according to propensity scores.Results：Multivariate analysis indicates that recipients with younger age[odds ratio（OR）,1.053;P=0.011],preoperative hepatitis B virus（HBV）DNA≥1,000 copies/mL（OR,2.597;P=0.004）and beyond Milan criteria（OR,4.255;P〈0.001）were identified as the risk factors associated with tumor recurrence in steroid avoidance recipients after LT.The patients fulfilling the Milan criteria in the SF group presented higher overall and tumor-free survival rates than those in the S group（P〈0.05）.Multivariate analysis revealed that recipient beyond Milan criteria was an independent prognostic factor for overall survival（OR,1.690;P〈0.001）and tumor-free survival（OR,2.066;P〈0.001）.The incidences of new-onset diabetes mellitus（21.20% vs.33.29%,P〈0.001）,new-onset hypertension（10.05%vs.18.61%,P〈0.001）and hyperlipidemia（4.08% vs.7.20%,P=0.042）were significantly lower in the SF group.Conclusions：Steroid-free immunosuppression could be safe and feasible for HBV-related HCC patients in LT.Age,HBV DNA level and Milan criteria maybe risk factors associated with tumor recurrence in steroid avoidance recipients.Recipient beyond Milan criteria was an independent prognostic factor and recipient fulfilling Milan criteria can benefit the most from steroid-free immunosuppression.
文摘AIM: To investigate the efficacy(survival) and safety of treatments for recurrent hepatocellular carcinoma(HCC) in liver transplantation(LT) patients.METHODS: Literature search was performed on available online databases without a time limit until January 2015. Clinical studies describing survival after HCC recurrence in LT patients were retrieved for a fulltext evaluation. A total of 61 studies were selected: 13 case reports, 41 retrospective case series, and 7 retrospective comparative studies.RESULTS: Based on all included studies, the mean HCC recurrence rate was 16% of all LTs for HCC. A total of 1021 LT patients experienced HCC recurrence. The median time from LT to HCC recurrence was 13 mo(range 2-132 mo). The majority of patients(67%) presented with HCC extra-hepatic recurrences, involving lung, bone, adrenal gland, peritoneal lymph nodes, and rarely the brain. Overall survival after HCC recurrence was 12.97 mo. Surgical resection of localized HCC recurrence and Sorafenib for controlling systemic spread of HCC recurrence were associated with the higher survival rates(42 and 18 mo, res-pectively). However, Sorafenib, especially when combined with m TOR, was frequently associated with severe side effects that required dose reduction or discontinuation CONCLUSION: Management of recurrent HCC in LT patients is challenging and associated with poor prognosis independently of the type of treatment.
文摘The barcelona clinic liver cancer(BCLC)staging system has been approved as guidance for hepatocellular carcinoma(HCC)treatment guidelines by the main Western clinical liver associations.According to the BCLC classification,only patients with a small single HCC nodule without signs of portal hypertension or hyperbilirubinemia should undergo liver resection.In contrast,patients with intermediate-advanced HCC should be scheduled for palliative therapies,even if the lesion is resectable.Recent studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by liver resection.Therefore,this classification has been criticised because it excludes many patients who could benefit from curative resection.The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations.Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function with a 5-year survival rate of 50%.Surgery also offers good long-term result in selected patients with multiple or large HCCs with a reported 5-year survival rate of over 50%and 40%,respectively.Although macrovascular invasion is associated with a poor prognosis,liver resection provides better long-term results than palliative therapies or best supportive care.Recently,researchers have identified several genes whose altered expression influences the prognosis of patients with HCC.These genes may be useful for classifying the biological behaviour of different tumours.A revision of the BCLC classification should be introduced to provide the best treatment strategy and to ensure the best prognosis in patients with HCC.
文摘BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with multiple etiologies, high incidence, and high mortality. The standard surgical management for patients with HCC consists of locoregional ablation, surgical resection, or liver transplantation, depending on the background state of the liver. Eighty percent of patients initially presenting with HCC are unresectable, either due to the extent of tumor or the level of underlying hepatic dysfunction. While in patients with no evidence of cirrhosis and good hepatic function resection has been the surgical treatment of choice, it is contraindicated in patients with moderate to severe cirrhosis. Liver transplantation is the optimal surgical treatment. DATA SOURCES: PubMed search of recent articles (from January 2000 to March 2011) was performed looking for relevant articles about hepatocellular carcinoma and its treatment. Additional articles were identified by evaluating references from selected articles. RESULTS: Here we review criteria for transplantation, the types, indications, and role of locoregional therapy in treating the cancer and in downstaging for possible later transplantation. We also summarize the contribution of immunosuppression and adjuvant chemotherapy in the management and prevention of HCC recurrence. Finally we discuss recent advances in imaging, tumor biology, and genomics as we delineate the remaining challenges for the diagnosis and treatment of this disease. CONCLUSIONS: Much can be improved in the diagnosis and treatment of HCC. A great challenge will be to improve patient selection to criteria based on tumor biology. Another will be to incorporate systemic agents post-operatively in patients at high risk for recurrence, paying close attention to efficacy and safety. The future direction of the effort in treating HCC will be to stimulate prospective trials, develop molecular imaging of lymphovascular invasion, to improve recipient selection, and to investigate biomarkers of tumor biology.
文摘OBJECTIVE: To study the changes of immune function in liver cirrhosis patients after splenectomy combined with resection of hepatocellular carcinoma (HCC). METHODS: Sixteen patients with HCC associated with liver cirrhosis were divided into two groups: splenectomy combined with hepatectomy (splenectomy group n=7) and hepatectomy (non-splenectomy group, n=9). T lymphocyte subsets such as CD4, CD8, CD4/CD8 and Th lymphocyte cytokines such as interferon γ (IFN-γ), IL-2, IL-10 in 7 ml peripheral venous blood before operation and 2 months after operation were examined and compared between the two groups. RESULTS: There was no significant difference in pre-operative CD4, CD8, CD4/CD8, IL-2, IFN-γ, IL-10 levels in the two groups. Two months after operation, the levels of CD4 (38.2%±3.7%), CD4/CD8 (1.7±0.3), IFN-γ (104.4±14.9 pg/ml), 1L-2 (98.6±18.6 pg/ml) were increased and those of CD8 (23.7±3.7 pg/ml), IL-10 (55.5±11.2 pg/ml) levels were decreased in the splenectomy group. The levels of CD4 (32.5%±4.0%), CD4/CD8 (1.1±0.1), IFN-γ(70.5±12.6 pg/ml), IL-2(80.9±13.5 pg/ml) in the non-splenectomy group were much lower than those in the splenectomy group, but the levels of CD8 (29.4%±4.0%), IL-10 (89.4±10.0 pg/ml) in the non-splenectomy group were significantly higher than those in the splenectomy group (P<0.05). CONCLUSIONS: Splenectomy combined with hepatectomy for HCC patients associated with liver cirrhosis does not decrease but promote the recovery of T lymphocyte subsets and Th1/Th2 cytokines from imbalance and improve anti-tumor immune function of the patients.
基金supported by grants from the Key Project of Medical Science and Technology Development FoundationNanjing Municipality Health Bureau(ZKX12011)+1 种基金Jiangsu Provincial Innovation Program for Ph D Candidates(KYLX_0058)Scientific Research Foundation of Graduate School of Nanjing University(2013CL14)
文摘BACKGROUND：Early recurrence of hepatocellular carcinoma（HCC）is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early recurrence after cu rative hepatectomy and to establish a simple predictive model for HCC early recurrence.METHODS： A total of 200 patients who had undergone curative resection for HCC were retrospectively analyzed. The patients were divided into early recurrence （within 2 years） and non-early recurrence groups. Demographical characteristics, preopera- tive liver function parameters, surgical factors and tumor related factors of the patients were assessed by univariate analysis to identify potential significant predictors for early recurrence after resection of HCC. Parameters with statisti- cal significance were entered into a Cox proportional hazard model to find independent risk factors. Receiver operating characteristic analysis was done to determine optimal cut-off values and the number of combined factors in multi-factor predictive model. RESULTS： Of 13 potential risk factors for early recurrence identified by univariate analysis, high lactate dehydrogenase （LDH〉206 U/L, HR=1.711, P=0.006）, high aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio （AST/ ALT〉0.96, HR=1.769, P=0.006）, elevated alpha-fetoprotein （AFP〉8.6 ng/mL, HR=2.079, P=0.007）, small resection margin （〈1 cm, HR=2.354, P〈0.001） and advanced TNM stage （TNM III-IV, HR=2.164, P〈0.001） were independent risk factors for early recurrence of HCC shown by multivariate analysis. Patients with three or more concurrent independent risk factors had significantly higher risk for early recurrence than those with low risk factors. The sensitivity and specificity of this predictive model are 53.6% and 80.7%, respectively （area under curve=0.741, 95% CI 0.674-0.800, P〈0.0001）. CONCLUSIONS： Preoperative common fiver enzyme markers, LDH and AST/ALT ratio, were independently associated with early recurrence of HCC. The combination of serum liver enzyme markers with AFP, resection margin and TNM stage bet- ter predicted early recurrence of HCC after curative resection in a simple multi-factor model.
文摘Liver resection for hepatocellular carcinoma(HCC)is currently known to be a safer procedure than it was before because of technical advances and improvement in postoperative patient management and remains the first-line treatment for HCC in compensated cirrhosis.The aim of this review is to assess current indications,advantages and limits of laparoscopic surgery for HCC resections.We also discussed the possible evolution of this surgical approach in parallel with new technologies.
文摘BACKGROUND: With the maturation and popularization of skills in liver transplantation (LT), patients with hepatocellular carcinoma (HCC) have an alternative choice. LT as a curative treatment for HCC provides good liver function and systemic condition to recipients. Preoperative tumor characteristics are critical in selecting optimal candidates for LT to optimize the use of donor livers and to achieve a long-term survival. The present study aimed to elucidate the risk factors of HCC involved in fatal recurrence in the first year after LT and to investigate their utility in selecting suitable candidates for LT. METHODS: From April 2002 to October 2005, 303 patients who had received orthotopic LT for HCC were reviewed. Of these patients, those with diffuse intrahepatic or multiple systemic recurrent lesions who died within I year after surgery were investigated as fatal recurrence group (48 patients) and the remaining patients including those who were disease-free without recurrence, those who were alive with recurrence in the first year, or those who died in the first year of other causes, served as control group (255). The two groups were compared by demographics, tumor, and histopathological characteristics for their prognostic significance by logistic regression analysis. RESULTS: Multivariate analysis between the fatal recurrence group and the control group showed that the presence of vascular invasion, a tumor size greater than 6.5 cm, and a preoperative serum alpha-fetoprotein (AFP) level greater than 1000 mu g/L were risk factors for fatal recurrence. Increased risk factors reduced the suitability of candidates for LT and diminished survival in the first year. 85.71% of the patients with all three risk factors, 37.84% of those with two factors, 13.64% of those with one factor, and 6.71% of those without risk factors died from tumor recurrence within I year after transplantation. CONCLUSIONS: Vascular invasion, tumor size >= 16.5 cm, and preoperative serum AFP level >= 1000 mu g/L, were significant predictors of fatal recurrence after LT for HCC. Patients with two or more risk factors should not be candidates for LT.
文摘A large number of liver transplants have been performed for hepatocellular carcinoma(HCC), and recurrence is increasingly encountered. The recurrence of HCC after liver transplantation is notoriously difficult to manage. We hereby propose multi-disciplinary management with a systematic approach. The patient is jointly managed by the transplant surgeon, physician, oncologist and radiologist. Immunosuppressants should be tapered to the lowest effective dose to protect against rejection. The combination of a mammalian target of rapamycin inhibitor with a reduced calcineurin inhibitor could be considered with close monitoring of graft function and toxicity. Comprehensive staging can be performed by dual-tracer positron emission tomography-computed tomography or the combination of contrast computed tomography and a bone scan. In patients with disseminated recurrence, sorafenib confers survival benefits but is associated with significant drug toxicity. Oligo-recurrence encompasses recurrent disease that is limited in number and location so that loco-regional treatments convey disease control and survival benefits. Intra-hepatic recurrence can be managed with graft resection, but significant operative morbidity is expected. Radiofrequency ablation and stereotactic body radiation therapy(SBRT) are effective alternative strategies. In patients with more advanced hepatic disease, regional treatment with trans-arterial chemoembolization or intra-arterial Yttrium-90 can be considered. For patients with extra-hepatic oligorecurrence, loco-regional treatment can be considered if practical. Patients with more than one site of recurrence are not always contraindicated for curative treatments. Surgical resection is effective for patients with pulmonary oligo-recurrence, but adequate lung function is a prerequisite. SBRT is a non-invasive and effective modality that conveys local control to pulmonary and skeletal oligo-recurrences.
文摘Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma(HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3. Current literature describes NAFLD-HCC mostly as a disease of late presentation with lower rates of receipt of curative therapy and worse prognosis. However, a growing body of evidence has reported comparable and potentially more favorable disease-free and overall survival rates among patients with NAFLD-HCC after receipt of curative treatment. This review summarizes current evidence of epidemiology, pathophysiology, disease presentation, demand and receipt of curative therapy, post-treatment outcomes, and overall survival of NAFLD-associated HCC.
