Short-term efficacy assessment of transarterial chemoembolization combined with radioactive iodine therapy in primary hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)is an effective treatment for primary hepatocellular carcinoma(PHC).Radioactive iodine therapy has been used in the treatment of advanced PHC,especially in patients with portal vein tumor thrombosis.However,data on the therapeutic effect of TACE combined with radioactive iodine therapy in PHC are scarce.AIM To investigate the clinical efficacy of TACE combined with radioactive iodine implantation therapy in advanced PHC via perfusion computed tomography(CT).METHODS For this study,98 advanced PHC patients were recruited and divided randomly into the study and control groups.Patients in the study group were treated with TACE combined radioactive iodine implantation therapy.Patients in the control group were treated with only TACE.The tumor lesion length,clinical effect,serum alpha-fetoprotein(AFP)and CT perfusion parameters were compared before and after therapy,and statistical analysis was performed.RESULTS There was no significant difference in tumor length and serum AFP between the study and control groups(P>0.05)before treatment.However,the tumor length and serum AFP in the study group were lower than those in the control group 1 mo and 3 mo after therapy.After 3 mo of treatment,the complete and partial remission rate of the study group was 93.88%,which was significantly higher than the control group(77.55%)(P<0.05).Before treatment,there were no significant differences between the two groups on the perfusion CT variables,including the lesion blood volume,permeability surface,blood flow,hepatic artery flow and mean transit time(P>0.05).After 3 mo of treatment,all perfusion CT variables were lower in the study group compared to the control group(P<0.05).The survival time of patients in the study group was 22 mo compared to 18 mo in the control group,which was significantly different[log rank(Mantel-Cox)=4.318,P=0.038].CONCLUSION TACE combined with radioactive iodine implantation in the treatment of advanced PHC can inhibit the formation of blood vessels in tumor tissue and reduce the perfusion level of tumor lesions,thereby improving the clinical efficacy and prolonging the survival time of patients.

Combination of serum tumor markers dickkopf-1,DCP and AFP for the diagnosis of primary hepatocellular carcinoma

Objective:To evaluate the detection accuracy of the biomarkers dickkopf-1,DCP and AFP as a serum biomarker panel by comparing the sensitivity of the panel with those of the individual biomarkers.Methods:The study was composed of three groups,one with HCC patients,one with non-HCC liver diseases and one with healthy controls.Serum AFP was measured using a chemiluminescence assay and serum dickkopf-1 and DCP were measured with ELISA.The sensitivity and specificity of the biomarkers were analyzed as single parameters and as a serum panel.Results:The HCC group showed higher levels of dickkopf-1,DCP and AFP than the other two groups(P<0.05).Dickkopf-1 showed better sensitivity(73.26%vx.58.13%.P<0.05) and better specificity(44.00%vs.29.00%,P>0.05) than AFP.DCP also had better sensitivity(74.42%vs.58.13%.P<0.05) than AFP,but their specificity was similar(30.00%vs.29.00%.P>0.05).The combination of the biomarkers as a scrum panel produced much better sensitivity(93.02%) and specificity(78.00%) than each of the markers individually(P<0.05).Conclusion:The combination of AFP.DCP and dickkopf-1 as a biomarker panel can significantly improve the detection power with much higher sensitivity and specificity for HCC than any of the biomarkers alone.The tests are convenient and inexpensive,and may serve as a valuable addition to current options for the diagnosis of HCC.

Patients with advanced primary hepatocellular carcinoma treated by melatonin and transcatheter arterial chemoembolization: a prospective study

Objective: To observe the clinical efficacy of tran- scatheter arterial chemoembolization (TACE) and TACE+MLT (melatonin) on inoperable advanced primary hepatocellular carcinoma. Methods: From January 1997 to January 1998, one hundred patients with inoperable advanced primary hepatocellular carcinoma were treated separately by TACE (50) and TACE+MLT (20 mg/d at 8:00 PM orally, 7 days before TACE) (50). Results: The effective rates (WHO standards) of TACE and TACE+MLT were 16% and 28% respec- tively (P<0.05). After TACE or TACE+MLT, the resection rate at two-stage of TACE was 4% or 14% (P<0. 01). The 0.5-, 1- and 2-year survival rates in the TACE group were 82%, 54% and 26% respectively; in the TACE+MLT group 100%, 68% and 40% respectively. The results were significantly better in the TACE+MLT group than in the TACE group. MLT could protect liver function from the damage caused by TACE. The IL-2 levels of all pa- tients significantly increased, whereas sIL-2R expres- sions decreased after TACE+MLT as compared with the TACE group (P<0.01). Conclusions: With definite protection and treatment effect on the liver function damage caused by TACE, MLT can enhance the immunological activities of pa- tients. It also can improve the effect of TACE by in- creasing the survival and resection rate after two- stage operation.

Thirty-one patients with primary hepatocellular carcinoma survived for more than 5 years after hepatectomy

Objective: To investigate the factors affecting progno- sis of patients with primary hepatocellular carcinoma (PHC) after resection. Methods: From 1976 to 1992, 213 patients with PHC treated with hepatectomy were followed up for more than 5 years. Thirty-one of the patients who had sur- vived for more than 5 years were compared with 56 patients who had survived for less than 5 years. Results: Early detection of tumor, radical resection, number of tumors, capsule formation, operation safe distance, presence of portal tumor embolus, pre- sence of cirrhosis and tumor size were important fac- tors affecting the prognosis of patients with PHC. The proportion of small liver cancer in the patients who had survived for more than 5 years was greatly larger than that in the control group. Conclusions: Early detection of tumor and radical re- section are of value in raising the 5-year survival rate. Much remains to be investigated about the rela- tionship between safe margin distance and prognosis of patients with PHC.

EXPRESSION OF CELLULAR ONCOGENES IN HUMAN PRIMARY HEPATOCELLULAR CARCINOMA

With DNA-mRNA hybridization in situ technique, the expression of five oncogenes, c-N-ras, c-Ki-ras. c-Ha-ras, c-myc and c-fos, was observed in two cases of human hepatocellular carcinoma. The expression of c-N-ras & c-fos was greatly enhanced in tumor tissues of the two cases, and about 25% -50% of the tumor cells showed positive expression. The other three oncogenes namely c-Ki-ras, c-Ha-ras & c-myc, were not detected in these two carcinomas or in the non-cancerous liver tissues adjacent to the carcinomas. It is surmised that c-N-ras and c-fos may play coordinative role in maintaining the malignant phenotype of human primary hepatocellular carcinoma.

EXPRESSION OF FcγR AND REGULATION OF rIFNγ ON FcγR EXPRESSION ON PATIENTS WITH PRIMARY HEPATOCELLULAR CARCINOMA

The level of FcγR on peripheral blood mononuclear cells (PBMC) was determined by ABC-ELIsA in 43 patients with primary hepatocellular carcinoma (PHC) and in 8 patients with space-occupying benign lesion (BL) in liver, twelve patients who received carcinomaectomy were followed up to detect their FcγR.Nine PBMC samples from PHC were treated with rIFNγ-The results showed that: 1. the level of FcγR in PHC patients was significantly lower than that in BL and In normal control; 2. the expression of FcγR was enhanced in postoperated PHC patients; and 3. the production of IFNγ in PHC patients was defective. The level of FcγR on PBMC was increased obviously in PHC after PBMC being treated with rIFNγ but was still lower than that in control. These results suggested; (1) FcyR detection is helpful tor distinguishing malignant liver lesion from benign; (2) the inhibited expression of FcγR in PHC could be related to some factors secreted by cancer tissues and also to low level of IFNγ; and (3) IFNγstimulates the expression of FcyR in vitro as one of the anti-tumor mechanism forIFNγ.

Dual fluorescence in situ hybridization in detection of HER-2 oncogene amplification in primary hepatocellular carcinoma

BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.

CT guided ^125iodine seed implantation for portal vein tumor thrombus in primary hepatocellular carcinoma

Background This study evaluated the clinical application of CT guided ^125iodine implantation in patients with portal vein tumor thrombus in primary hepatocellular carcinoma. Methods The ten patients （9 males and 1 female, aged from 36 to 72 years） with portal vein tumor thrombus accompanying hepatocellular carcinoma had been treated with comprehensive therapy including surgery, transcatheter arterial chemoembolization, radiotherapy ablation, microwave ablation or percutaneous ethanol injection. The average diameter of each tumor thrombus was 21.5 mm × 30.5 mm. Seeds of 30 MBq ^125I were implanted 5 mm apart within the portal vein tumor thrombus. The follow-up after 4 months included enhanced spiral CT. Results CT screening of the tumours indicated that 4 out of 10 patients showed complete response to the therapy, 5 partial response and 1 stable disease. Adverse effects included aggravated abdominal dropsy and temporarily increased transaminase, which were controlled by medical management. Severe complications such as haemorrhage, biliary fistula hepatic abscess, pancreatic fistula and hepatic function failure were not observed. Implanted seeds migrated to lung and left hepatic lobe in 1 case. Conclusion CT guided implantation of ^125iodine seeds, can effectively treat portal vein tumor thrombus accompanying hepatocellular carcinoma with minimal damage and few complications.

Effect of Maotai liquor on P53 gene in primary hepatocellular carcinoma induced by compound factors in rats

In China, the morbidity of alcoholic liver diseases （ALD） is increasing, which is the second cause of liver diseases after viral hepatitis. An epidemiological survey of 99 subjects in Kweichow Maotai Distillery who have drunk a lot of Maotai liquor for a long time showed that fatty livers were predominate and the incidence of hepatic fibrosis and cirrhosis was relatively low. Now, we carried out an animal experiment to investigate the mutation of P53 gene in liver tissues of primary hepatocellular carcinoma （HCC） induced by compound factors.

The value of PIVKA-Ⅱversus AFP for the diagnosis and detection of postoperative changes in hepatocellular carcinoma

Objective:To explore the diagnostic value of abnormal prothrombinⅡ(PIVKA-Ⅱ)and alpha-fetoprotein(AFP)in primary hepatocellular carcinoma(HCC).Methods:From 20180.01 to 2020.01,there were 158 patients with primary liver cancer caused by chronic hepatitis B(male 116,women 42)and 62 patients with chronic hepatitis B(male 34,female 28).The levels of serum PIVKA-Ⅱand AFP were measured,and the results were statistically analyzed.Results:The value of PIVKA-Ⅱin liver cancer group was distinctly higher than that in chronic viral hepatitis B group,the difference is statistically significant(P<0.05).So does the value of AFP.Draw the subject working characteristic curve(ROC curve),the area under the curve of AFP and PIVKA-Ⅱis 0.799 and 0.836,and that of the combination of AFP and PIVKA-Ⅱis 0.854,the sensitivity is 57.6%,68.4%,72.2%,respectively,the specificity is93.5%,98.4%,96.8%,respectively.After operation or interventional therapy,the value of PIVKA-Ⅱin liver cancer group was clearly lower than that before treatment,and the difference was statistically significant.Conclusion:In the diagnostic value of primary liver cancer,PIVKA-Ⅱcombined with AFP is higher than PIVKA-Ⅱ,while AFP has the lowest benefit.We also find that PIVKA-Ⅱhas higher disease monitoring value than AFP.

Pre-sarcopenia and Mac-2 binding protein glycosylation isomer as predictors of recurrence and prognosis of early-stage hepatocellular carcinoma

BACKGROUND The Mac-2 binding protein glycosylation isomer(M2BPGi),a fibrosis marker in various liver diseases,is reportedly a prognostic marker in patients with hepatocellular carcinoma(HCC)who underwent hepatectomy.AIM To evaluate whether the M2BPGi value,M2BP,and pre-sarcopenia before radiofrequency ablation(RFA)could be useful recurrence and prognostic markers in patients with early-stage HCC.METHODS In total,160 patients with early-stage primary HCC treated with RFA were separately analyzed as hepatitis C virus(HCV)-positive and HCV-negative.Factors contributing to recurrence and liver-related death,including M2BP,M2BPGi,and skeletal muscle mass index,were statistically analyzed.Eighty-three patients were HCV-positive and 77 were HCV-negative.RESULTS In HCV-positive patients,only des-γ-carboxy-prothrombin≥23 mAU/mL was a significant poor prognostic factor affecting survival after RFA.In HCV-negative patients,M2BPGi≥1.86 cutoff index was significantly associated with tumor recurrence,while M2BP was not.M2BPGi≥1.86 cutoff index(hazard ratio,4.89;95%confidence interval:1.97-12.18;P<0.001)and pre-sarcopenia(hazard ratio,3.34,95%confidence interval:1.19-9.37;P=0.022)were independent significant poor prognostic factors in HCV-negative patients.CONCLUSION In HCV-negative patients with primary HCC treated with RFA,lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period.Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients.These factors might be useful recurrence and prognostic markers for early-stage primary HCC.

Cryoablation combined with radiotherapy for hepatic malignancy:Five case reports

BACKGROUND The survival of patients treated with monotherapy for hepatic malignancies is not ideal.A comprehensive program of cryoablation combined with radiotherapy for the treatment of hepatic malignancies results in less trauma to the patients.It may provide an option for the treatment of patients with advanced hepatic malignancies.CASE SUMMARY We reported 5 cases of advanced-stage hepatic malignancies treated in our hospital from 2017-2018,including 3 cases of primary hepatocellular carcinoma and 2 cases of metastatic hepatic carcinoma.They first received cryoablation therapy on their liver lesions.The procedure consisted of 2 freeze-thaw cycles,and for each session,the duration of freezing was 13-15 min,and the natural rewarming period was 2-8 min.Depending on the tumor size,the appropriate cryoprobes were selected to achieve complete tumor ablation to the greatest extent possible.After cryoablation surgery,intensity-modulated radiotherapy(IMRT)for liver lesions was performed,and the radiotherapy regimen was 5400 cGy/18f and 300 cGy/f.None of the 5 patients had adverse events above grade II,and their quality of life was significantly improved.Among them,4 patients were free of disease progression in the liver lesions under local control,and their survival was prolonged;3 patients are still alive.CONCLUSION Our clinical practice demonstrated that cryoablation combined with IMRT could be implemented safely.The definitive efficacy for hepatic malignancies needs to be confirmed in larger-size sample prospective studies.

EVALUATION ON FACTORS INFLUENCING LIVER CANCER METASTASIS AFTER LIVER SURGERY BY A MOUSE MODEL

Objective: To evaluate the influence of surgical trauma on liver cancer metastasis. Methods: A mouse model of experimental liver cancer metastasis was established by subcapsule injecting hepatoma ascites tumor cells (H22) into spleen of NIH mice. Simple intrasplenic inoculation, with sham operation, partial hepatectomy, total occlusion of hepatic blood inflow and blood loss and re-perfusion were performed and metastatic effects were observed. Results: There were significant higher metastasis-augmenting effects in sham operation and partial hepatectomy groups. Compared with no-blood transfusion, blood transfusion group was found to be potent to increase intrahepatic metastases. But, neither inhibition nor enhancement with total occlusion of hepatic blood inflow for 20 and 30 minutes was seen. Conclusions: Surgical trauma, especially partial hepatectomy and blood transfusion, are involved in enhancing metastasis, but total occlusion of hepatic blood inflow is not responsible for enhanced liver metastasis in the experimental metastasis model.

Analysis of Significance of Unite Examination of AFP and DNA Polymorphism of P3 Promoter of IGF-Ⅱ Gene

The DNA of P3 promoter region of IGF-Ⅱ gene was obtained by means of PCR technique. The examination of DNA polymorphism by restriction endonuclease BstE Ⅱ and the examination of AFP by bioluminescence immunoassay technique were carried out. The results have a significant difference( P <0.005). But the positive rate of AFP is higher than that of DNA polymorphism. The experimental result shows that the change of the DNA polymorphism of IGF-Ⅱis not the only carcinogenic factor. The suggested unite examination is the best method for the diagnosis of the primary hepatocellular carcinoma.