Analysis of the efficacy and safety of proton radiotherapy for primary hepatocellular carcinoma / 国际生物医学工程杂志

Objective:To study the efficacy, safety and prognostic factors affecting survival of proton radiation therapy for primary hepatocellular carcinoma (HCC).Methods:Forty-four patients with primary hepatocellular carcinoma treated at Zibo Wanjie Cancer Hospital in Shandong Province from June 15, 2005 to September 12, 2018 were enrolled and given proton radiation therapy with a single dose of 2-5 Gy and a total dose of 25-75 Gy. The overall and local control rates, factors influencing survival, and adverse effects were observed during a follow-up period of 12 to 120 months.Results:The overall survival rates of all patients were 79.5% at 1 year, 68.2% at 2 years, 50.0% at 3 years, and 45.5% at 5 years. The overall local control rate was 95.5%. Patients older than 50 years had a longer overall survival (Log Rank Chi-Square of 4.787, P = 0.029). Child-Pugh A classification had better overall survival compared with B classification (Log Rank Chi-Square 4.077, P = 0.043). The main adverse reactions were skin reactions and gastrointestinal reactions. Among the patients with adverse reactions, 23 patients had skin reactions and 9 patients had mild gastrointestinal reactions, and no serious adverse events were found. Conclusions:Proton radiation therapy has good efficacy and high safety in patients with HCC. Age and Child-Pugh classification are prognostic factors affecting survival after proton radiation therapy.

Clinical significance of LAG-3 on microvessel density in primary hepatocellular carcinoma

Aims: We aimed to determine whether lymphocyte activation gene 3 (LAG-3), also known as CD223, is associated with microvessel density (MVD) in primary hepatocellular carcinoma (HCC), as well as their clinical significance in predicting survival. Materials and methods: One hundred and twenty-seven patients were enrolled in the study. Samples were obtained on resection at the Department of Hepatobiliary Surgery of the Qingdao Municipal Hospital from June 2014 to June 2016. Immunohistochemistry was used to determine vessel density and LAG-3 abundance. Statistical analyses were performed to test for correlation of LAG-3 density and other clinicopathological variables with overall survival (OS). Results: High LAG-3 abundance was significantly correlated with increased MVD in primary HCC (P < 0.05). The ?2 test revealed a significant association of LAG-3 with preoperative AFP level, tumor diameter, N stage, and the presence of HBV infection (P < 0.05). Patients with high LAG-3 expression had shorter OS compared to those with low LAG-3 expression (P < 0.05). The Cox proportional hazards model showed that both higher LAG-3 and MVD density, age, the number of tumors, preoperative AFP level, tissue differentiation, Child–Pugh grade, and lymph node metastasis correlated with survival. Conclusions: High expression of LAG-3 is associated with angiogenesis and poor prognosis in HCC patients. With the deepening of research, LAG-3 is likely to become a novel biomarker for clinical diagnosis and prognosis and can even be a therapeutic target of HCC.

Effect of symptom management theory-based nursing care on postoperative abdominal distension in patients with primary hepatocellular carcinoma / 中国实用护理杂志

Objective:To investigate the effect of symptom management theory(SMT)-based nursing care for the prevention of postoperative abdominal distension in patients with primary hepatocellular carcinoma.Methods:A total of 80 primary hepatocellular carcinoma patients in the Second Affiliated Hospital of Wenzhou Medical University from May 2016 to May 2019 were assigned to the experimental group and the control group according to the admission time, there were 40 cases in each group. The patients in the control group received routine postoperative nursing care, while the patients in the experimental group added SMT-based intervention. The postoperative first exhaust time and defecation time were recorded; the abdominal distension degree after 1, 3, 7 days of surgery were evaluated. In addition, the symptom distress was assessed by The Symptom Module Specific to Primary Liver Cancer (TSM-PLC).Results:The postoperative first exhaust time and defecation time were (69.08±11.44), (78.80±15.54) h in the experimental group, which were significantly lower than those in the control group (76.03±12.26), (86.03±13.48) h, the differences were statistically significant ( t=2.62, 2.22, both P<0.05). After 3, 7 days of surgery, the abdominal distension degrees were significantly alleviated in the experimental group compared to the control group, the differences were statistically significant ( Z =2.31, 2.34, both P<0.05). After 7 days of surgery, the abdominal distension, weight loss, fever symptom scores in TSM-PLC were 1.80±0.28, 0.76±0.21, 0.48±0.19 in the experimental group, which were significantly lower than those in the control group 2.16±0.31, 0.93±0.25, 0.74±0.20, the differences were statistically significant ( t=5.38, 3.27, 5.90, all P<0.05). Conclusions:SMT-based intervention can promote the recovery of postoperative gastrointestinal function and alleviate abdominal distension symptom distress of patients with primary hepatocellular carcinoma.

Mechanism of Chemotherapy Resistance of Hepatocellular Carcinoma and Intervention with Chinese Medicine： A Review / 中国实验方剂学杂志

Multidrug resistance （MDR） has been a main culprit behind the failure of chemotherapy in patients with malignant tumors and a major obstacle to improving the life quality and prolonging the survival of patients. Hepatocellular carcinoma cells， the innate drug-resistant cells， are generally insensitive to radiotherapy and chemotherapy. Moreover， as the early symptoms of hepatocellular carcinoma are atypical， most patients are diagnosed at the advanced stage， with short survival period and high recurrence rate. Thus， the sensitivity to chemotherapy drugs is decreased. This explains how MDR becomes one of the important reasons for the failure of primary hepatocellular carcinoma （PHC） treatment. Therefore， it is an urgent task to search for safe and effective chemosensitizers with little adverse effect in the research on the drug resistance of hepatocellular carcinoma. As Chinese medicine has been widely applied in the treatment of tumors， the mechanisms of compound Chinese medicine prescriptions， Chinese medicine injections， and single Chinese medicinal in reversing chemotherapy resistance in liver cancer have attracted the interest of scholars. According to previous reports， the mechanisms can be summarized as increasing intracellular drug concentration， influencing changes in enzyme activity， inducing apoptosis， reversing abnormalities in cellular signaling pathways， and regulating the tumor microenvironment. Traditional Chinese medicine reduces the chemotherapy resistance of hepatocellular carcinoma cells through multiple targets and multiple pathways， thereby improving the chemotherapy sensitivity of the cancer cells and enhancing the toxicity of chemotherapeutic drugs to hepatocellular carcinoma cells. Therefore， exploring the mechanism of MDR of hepatocellular carcinoma from the perspective of traditional Chinese medicine is important for reversing the MDR and is of great reference value for clinical treatment of hepatocellular carcinoma. However， there are few experimental types and adverse effects available. Thus， the multi-mechanism and multi-target experiments and clinical research should be carried out in the future.

Clinical Study of Jiawei Xiaochaihutang Combined with Microwave Ablation in Treatment of Primary Hepatocellular Carcinoma / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Jiawei Xiaochaihutang combined with microwave ablation （MWA） in the treatment of primary hepatocellular carcinoma （HCC） and its influence on tumor microenvironment. MethodA total of 128 patients were randomly divided into control group （64 cases： 2 cases of dropout，2 cases of elimination，and 60 cases of completion） and observation group （64 cases： 3 cases of dropout，2 cases of elimination，and 59 cases of completion）. Both groups were given comprehensive treatment after MWA surgery. Patients in control group took Biejiajian Wan orally （3 g/time，3 times/d）， and those in observation group took Jiawei Xiaochaihutang （1 dose/d）. The treatment lasted for 3 consecutive months. The size of solid tumor before and after treatment was evaluated to record the progression-free survival （PFS）. The alpha-fetoprotein-L13 （AFP-L3），des-γ-carboxy prothrombin （DCP），Golgi protein 73 （GP73），tumor necrosis factor-α （TNF-α），transforming growth factor-β （TGF-β），vascular endothelial growth factor （VEGF） and matrix metalloproteinase-2 （MMP-2） levels，as well as performance status （PS），liver function and syndrome of liver depression and Qi stagnation scores were also detected before and after treatment. In addition， the incidence of side effects of grade Ⅲ and above was compared. ResultThe total effective rate of solid tumor in observation group was 91.53% （54/59），higher than that （76.67%， 46/60） in control group（χ2=4.895，P<0.05）. The PFS in observation group was （7.16±0.95） months， longer than that （6.24±0.89 months） in control group （P<0.01）. The effective rate of traditional Chinese medicine （TCM） syndrome in observation and control groups were 88.14% （52/59）and 70.00% （42/60）， respectively （χ2=5.897，P<0.05）. The observation group （57.63%，34/59） had higher marked effective rate of TCM syndrome than control group （31.67%，19/60） （χ2=8.116，P<0.01）. The AFP-13，DCP，GP73，TNF-α，TGF-β，VEGF and MMP-2 levels and the PS，liver function and syndrome of liver depression and Qi stagnation scores in observation group were lower than those in control group （both P<0.01）. The cumulative incidence of side effects of grade Ⅲ and above in observation and control groups was 16.95% and 33.33%， respectively（χ2=4.261，P<0.05）. ConclusionConsolidation treatment of HCC after MWA surgery with Jiawei Xiaochaihutang relieved symptoms and side effects，improved PS and liver function，regulated tumor microenvironment，inhibited tumor markers and prolonged survival time. The clinical effect was better than that of Biejia decoction pill， and thus it was worthy of clinical use.

Three-dimensional visualization combined with indocyanine green fluorescence imaging in diagnosis and treatment of primary hepatocellular carcinoma / 南方医科大学学报

OBJECTIVE@#To explore the value of three-dimensional visualization technology (3DVT) combined with indocyanine green (ICG) fluorescence imaging in the diagnosis and treatment of primary hepatocellular carcinoma (HCC).@*METHODS@#We retrospectively analyzed the clinical data of 154 patients with HCC admitted to the Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University between January, 2016 and November, 2018. In 57 of the patients (3DVT group), preoperative CT and Gd-EOB-DTPA-enhanced MRI were performed and 3D visualization and surgical planning was carried out before the operation; intraoperative ICG florescence imaging was performed for real-time detection of the tumor location and demarcation, intrahepatic satellite lesions and metastases. According to the intraoperative fluorescent signals and 3D visualization-based surgical planning, the final surgical plan was determined. In the other 97 patients (control group), conventional surgical assessment and surgical resection of the tumor was carried out. The preoperative imaging findings, intraoperative tumor detection, postoperative laboratory results, pathological reports, and follow-up data of the patients were analyzed.@*RESULTS@#In 3DVT group, 63 and 70 lesions were detected by preoperative CT and MRI, respectively; compared with CT examination, intraoperative ICG florescence imaging revealed additional 17 lesions, among which 10 were pathologically confirmed as HCC and 7 as cirrhosis nodules. The median volume of bleeding was 300 mL in 3DVT group, significantly less than that in the control group (400 mL; Z=2.291, =0.022). In both groups, serious complications or perioperative death occurred in none of the patients. The incidence of postoperative complications was significantly lowed in 3DVT group than in the control group [21% (12/57) 48.4% (47/97); =11.406, =0.001]. The overall disease-free survival rate at 2 years after the operation was significantly higher in 3DVT group than in the control group (74.9% 28.9%, =0.022).@*CONCLUSIONS@#3DVT combined with ICG fluorescence imaging allows precise preoperative diagnosis, surgical planning and implementation, intraoperative detection of small liver cancers and precise navigation for HCC treatment, thereby helping to reduce postoperative complications and improve the disease-free survival rate of the patients.

Transarterial chemoembolization by using CalliSpheres drug-eluting beads combined with 8Spheres microsphere for the treatment of advanced hepatocellular carcinoma: study on its short-term efficacy and safety / 介入放射学杂志

Objective To investigate the clinical short-term efficacy and safety of transarterial chemoembolization (TACE) by using CalliSpheres drug-eluting beads combined with blank microspheres (8 Spheres) in treating advanced hepatocellular carcinoma (HCC) . Methods The clinical data of 98 HCC patients, who were treated at authors′ hospital during the period from July 2016 to November 2017, were retrospectively analyzed. The patients were divided into DEB-TACE group (receiving TACE by using CalliSpheres drug-eluting beads combined with 8 Spheres embolic microspheres, n =50) and cTACE group (receiving TACE by using opium poppy ethyl iodized oil together with 8 Spheres embolic microspheres, n =48) . The disease remission rate, control rate and incidence of complications as well as preoperative and 3-day postoperative hepatic function indexes were collected, and the results were compared between the two groups. Results No statistically significant differences in baseline data existed between the two groups (P>0.05) . Both the 3-month and the 6-month disease remission rates in DEB-TACE group were remarkably higher than those in cTACE group (P<0.05), besides, the 6-month disease progression rate and the incidence of elevated serum AFP in DEB-TACE group were lower than those in cTACE group, the short-term efficacy of DEB-TACE group was better than that of cTACE group (P<0.05) . Three days after treatment, the levels of ALT and AST in cTACE group were strikingly higher than those in DEB-TACE group (P<0.05) . No serious adverse reactions occurred in both groups. Conclusion In treating advanced HCC with TACE, the short-term efficacy and safety of CalliSpheres drug-eluting beads combined with 8 Spheres embolic microspheres are superior to those of opium poppy ethyl iodized oil together with 8 Spheres embolic microspheres.

TACE by using arsenic trioxide drug-bearing CalliSpheres beads for the treatment of BCLC stage B HCC: preliminary results in 13 patients / 介入放射学杂志

Objective To evaluate the clinic effect of transcatheter arterial chemoembolization (TACE) by using arsenic trioxide (ATO) drug-bearing CalliSpheres beads (CB) in treating BCLC stage B hepatocellular carcinoma (HCC) . Methods The clinical data of 13 patients with advanced HCC, who received TACE by using CB loaded with ATO (CBATO) during the period from January 2017 to September 2017, were retrospectively analyzed. The clinical data, imaging materials, laboratory examinations, interventional complications, prognosis, etc., were summarized and evaluated. Results The patients were followed up for9-15 months, with a median period of 11 months. The survival rate was 100％. One, 3, 6 and 9 months after treatment, the disease remission (CR+PR) rates were 76.9％, 76.9％, 69.2％ and 61.5％ respectively, and the disease control rates were 92.3％, 92.3％, 92.3％ and 84.6％ respectively. In all 13 patients, no severe complications such as hepatic failure, renal insufficiency, bone marrow suppression, liver abscess, bile leakage complicated by infection and gastrointestinal bleeding occurred. Conclusion For the treatment of BCLC stage B HCC, TACE by using CBATO is safe and effective with reliable short-term effect.

Role of miRNA expression and its correlation with immune cytokines in early diagnosis and prognosis of primary hepatocellular carcinoma / 中国免疫学杂志

Objective:To detect the expression of six miRNAs for miR-146a,miR-224,miR-34c,miR-200a,miR-148b,miR-375 level in primary hepatocellular carcinoma patients tissues and serum,and to explore the correlation between the expression of miRNA and inflammatory factors,in the hope of verification whether circulating miRNA could be used as an ideal blood borne biomarker for early detection of primary liver cancer.Methods:Venous blood samples were collected from patients with primary liver cancer,hepatitis,cirrhosis and healthy controls,cancer tissues and para cancerous tissues were collected from patients with cancer.After the total RNA was extracted,the relative expression levels of miRNA were detected by real-time quantitative PCR,and the relationship between the expression level of miRNA and the expression of serum tumor markers AFP,CEA,CA19-9 and CA125 was detected.The correlation between the expression level of miRNAs and the expression of HBsAg,anti-HBs,HBeAg,anti-HBe,anti-HBc and inflammatory factors IL-12,IL-4,IL-6,IL-10,IFN-γ,TNF-α was detected as well.Results:Compared with the healthy group,the expression of miR-34c,miR-224 and miR-146a in serum and tissues of PHC group was significantly up-regulated,and the expression of miR-200a,miR-148b and miR-375 in serum and tissues of PHC group was significantly down regulated.The difference was statistically significant.There was a regression relationship between HBsAg and serum miR-375 and miR-146a,and miR-375 decreased with the increase of HBsAg expression,while miR-146a increased with the increase of HBsAg.There was a regression relationship between IFN-γ and miR-146a,miR-146a increased with the decrease of IFN-γ expression.The diagnostic ability of miR-375 and miR-146a was greater than that of CA19-9 and AFP.Conclusion:MiR-146a,miR-224,miR-34c,miR-200a,miR-148b,miR-375 in serum and tissue of primary hepatocellular carcinoma are differentially express,among them,the diagnostic ability of miR-375 and miR-146a is better than that of AFP and CA19-9,and serum miR-375 and miR-146a may be the new markers for early diagnosis of PHC.

Clinical significance of the expression of serum microRNA-21, microRNA-122 and microRNA-145 in patients with primary hepatocellular carcinoma / 新乡医学院学报

Objective To investigate the clinical significance of the expression of serum microRNA-21 (miR-21),microRNA-122(miR-122) and microRNA-145 (miR-145) in patients with primary hepatocellular carcinoma(HCC).Methods A total of 100 patients with HCC who hospitalized in the Central Hospital of Tongchuan Mining Bureau from September 2014 to September 2016 were selected as HCC group,and 100 healthy subjects were selected as the control group.The expression of serum miR-21,miR-122 and miR-145 was detected by real-time quantitative fluorescence polymerase chain reaction.The relationship between the expression of serum miR-21,miR-122,miR-145 and the clinical characteristics of HCC patients was analyzed.Results The expression of serum miR-21 and miR-122 in HCC group was significantly higher than that in the control group(P ＜0.05),and the expression of serum miR-145 in HCC group was significantly lower than that in the control group (P ＜0.05).The expression of serum miR-21,miR-122 and miR-145 in HCC patients was significantly correlated with histological differentiation,clinical stage,tumor size and liver cirrhosis (P ＜ 0.05),but the expression of serum miR-21,miR-122 and miR-145 in HCC patients was not correlated with gender,age,hepatitis B virus antigen and hepatitis C virus antibody(P ＜0.05).The expression of serum miR-21 and miR-122 in the patients with poorly differentiated tissue,high clinical stage,tumor diameter ≥5 cm and liver cirrhosis was significantly higher than that in the patients with medium and high differentiated tissue,low clinical staging,tumor diameter ＜ 5 cm and no cirrhosis (P ＜ 0.05).The expression of serum miR-21 and miR-122 after operation was significantly lower than that before operation(P ＜ 0.05),and the expression of miR-145 after operation was significantly higher than that before operation in HCC patients(P ＜ 0.05).Conclusion The up-regulated expression of miR21 and miR-122 and the down-regulation of miR-145 may be related to the occurrence and development of HCC.The combined detection of serum miR-21,miR-122 and miR-145 is helpful for the diagnosis and evaluation of HCC.

Comparison of Tissue-Link combined with Cusa and Pringle in hepatectomy for primary hepatocellular carcinoma / 中国综合临床

Objective To evaluate the clinical effect of Tissue-Link combined with Cusa and Pringle in hepatectomy for primary hepatocellular carcinoma. Methods From January 2013 to January 2017,the clinical data of ninety-six primary hepatocellular carcinoma patients who had received hepatectomy were collected. 45 cases of hepatectomy (control group) were performed by Pringle. The other 51 cases (observation group) were treated with Tissue-Link combined with Cusa. The indexes and survival rates were compared between the two groups during and after operation. Results Compared with the control group, the operation time of the observation group was prolonged ((189. 2±45. 8) min vs. (151. 6±34. 7) min,t = -5. 101),the intraoperative blood loss ((273. 5±141. 6) ml vs. (371. 3±127. 2) ml,t = 7. 396),total bilirubin at seventh days after the operation (( 15. 7 ± 8. 9 ) μmol/ L vs. ( 26. 5 ± 10. 8 ) μmol/ L, t = 5. 320 ) and postoperative albumin supplementation((61. 0±9. 7) g vs. (84. 6±9. 3) g,t = 7. 698) of the observation group decreased. The tumor recurrence rate ( 0 vs. 8. 9% ( 4/ 45)), intrahepatic metastasis rate ( 7. 8% ( 4/ 51) vs. 20% ( 9/ 45)), extrahepatic metastasis rate (3. 9% (2/ 51) vs. 17. 8% (8/ 45)) (χ2 =. 031,6. 315,6. 746) decreased and the differences were statistically significant (P< 0. 05) . The 2 year and 3 year tumor free survival rate (88. 2%, 76. 5%) of the observation group was higher than those of the control group (64. 4%,44. 4%,χ2 = 5. 468, 8. 902),and the total survival rate of 3 year after operation (80. 4%) in the observation group was significantly, higher than that of the control group (51. 1%,χ2 = 4. 896),the difference was statistically significant (P<0. 05) . Conclusion Tissue-Link combined with Cusa is superior to Tissue-Link combined with Pringle in hepatectomy for primary hepatocellular carolnoma. It has less intraoperative blood loss, less damage to liver function and a lower relapse rate of ineisional margin,and the disease-free survival rate and overall survival rate are improved significantly.

Effect of high expression of Zwint on the proliferation of hepatoma cells and the prognosis of liver transplantation for hepatocellular carcinoma / 器官移植

Objective To investigate the expression of zeste white 10 interactor (Zwint) in primary hepatocellular carcinoma (HCC) and its effect on the prognosis of liver transplantation for HCC. Methods HCC tissues, paracancerous tissues and clinical data of 50 liver transplant recipients for HCC were collected. The expression levels of Zwint messenger RNA (mRNA) and Zwint protein in 20 pairs of HCC tissues and paracancerous tissues of 20 liver transplant recipients for HCC were compared using real-time fluorescence quantitative polymerase chain reaction (PCR), Western Blot and immunohistochemistry (IHC). Two HCC cell lines HepG-2 which interfered with the expression of Zwint successfully were selected as si-Zwint-1 group and si-Zwint-2 group, and the blank control was taken as si-NC group. The cell proliferation and cell cycle of various groups were compared using cell counting kit (CCK) -8 experiment, flat-cloning assay and cell cycle experiment. The consistency of the expression of Zwint and cyclin D1 in HCC tissues and cells was analyzed using Western Blot and IHC. The enrolled patients were divided into high expression group (22 cases) and low expression group (28 cases) based on the median of Zwint protein expression level, and the relationship of the expression level of Zwint protein and clinical characteristics, overall survival rate and disease free survival rate of liver transplant recipients for HCC was analyzed. Results The results of real-time fluorescence quantitative PCR showed that the expression level of Zwint mRNA in HCC tissues was higher than that of paracancerous tissues (P=0.03). The results of Western Blot and IHC showed that the expression level of Zwint protein in HCC tissues was higher than that of paracancerous tissues(both P<0.05).After the Zwint gene of HCC cell line HepG-2 was interfered,CCK-8 and flat-cloning assay showed that the cell proliferation potential was significantly weakened (all P<0.01), and the cell cycle arrested at stage G1(all P<0.05). The expression level of Zwint protein was closely related to tumor diameter and tumor, node, metastasis (TNM) staging (all P<0.05). The overall survival rate of liver transplant recipients for HCC in the high Zwint expression group was lower than that of the low expression group (P=0.02). Conclusions Zwint is highly expressed in HCC tissues, and it can promote the proliferation of HCC cells through regulating cell cycle. The expression level of Zwint is negatively correlated with the prognosis of liver transplantation for HCC.

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). The combination of the biomarkers as a serum 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.

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). The combination of the biomarkers as a serum 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.

Role of emergency and staged hepatectomy in peritoneal metastasis associated with spontaneous rupture of resectable hepatocellular carcinoma patients / 中华肝胆外科杂志

Objective To evaluate the role of emergency and staged hepatectomy in peritoneal metastasis associated with ruptured hemorrhage of resectable hepatocellular carcinoma (HCC) patients,and investigate the impact of surgery timing-selecting on peritoneal metastasis of postoperative HCC patients.Methods A retrospective analysis was conduct on the pooled data from 38 HCC patients with spontaneously ruptured hemorrhage treated in our hospital from August 2011 to January 2016.These patients were divided into emergency group who underwent hepatectomy within 24 hours at admission,and staged group who underwent the procedure one week after admission.Perioperative events,overall survival (OS) and disease-freesurvival (DFS) rates,incidence of recurrent and metastatic disease were compared between the two groups.Results The perioperative blood loss and transfusion were much more in emergency group than staged group (both P ＜ 0.05).Nevertheless,the incidence of postoperative mortality was not significantly different (6.0％ vs 0％,P ＞ 0.05).The median survival was 22.5 months in emergency group versus 14.2 months in staged group.The 6-month,1-year,3-year OS rates in emergency group were 88.2％,82.4％ and 30.3％ respectively,and 6-month,1-year,3-year DFS rates were 81.3％,54.7％ and 27.3％.The 1-year OS and 6-month DFS rates were higher than those of staged group (both P ＜ 0.05).The incidence of peritoneal metastasis in staged group was higher than that in emergency group,but it was not significantly different (38.1％ vs 29.4％,P ＞ 0.05).Univariate and multivariate analysis indicated that tumor diameter ≥ 10 cm and AFP ＞ 10 000 μg/L were the risk factors for peritoneal metastasis after hepatectomy for HCC patients with spontaneously ruptured hemorrhage.Conclusions Emergency hepatectomy would warrant a better short-term prognosis compared with staged hepatectomy for the HCC patients with spontaneously ruptured hemorrhage.Staged hepatectomy would not raise the possibility of postoperative peritoneal metastasis.The predictors of tumor diameter ≥ 10 cm and AFP ＞ 10 000 μg/L were risk factors for peritoneal metastasis after hepatectomy for spontaneously ruptured HCC patients.

The effects of saikosaponin-d on the expression of human hepatocellular carcinoma cell BECN1 and autophagic function / 西安交通大学学报(医学版)

ABSTRACT:Objective To observe the influence of saikosaponin-d (SSd)on the proliferation and the function of autophagy of human hepatocellular carcinoma (HCC)cell line SMMC-7721 to explore the possible mechanisms. Methods SMMC-7721 was cultured invitro and then treated with SSd of various concentrations (5.0,7.5,10.0, 12.5,15.0 and 17.5 mg/L)for 24,48 and 72 h.We used MTT to detect cell proliferation,selected the optimal concentration and time,and detected the expressions of BECN1 at mRNA and protein levels by PCR and Western blot.Results The inhibition rate of the proliferation of SMMC-7721 cell line increased with the increase of the concentration of SSd,and the highest inhibition rate (60%)appeared when the concentration reached 12.5 mg/L. The expression of BECN1 in the group with SSd was obviously higher than that in the control group (P<0.05). 3-MA decreased not only the expressions of BECN1 at mRNA and protein levels but also the expression of BECN1 when used in conjunction with SSd.Conclusion The inhibiting function of SSd on SMMC-7721 presents a dependency between drug concentration and function time,basically in line with the drug dose-effect relationship. SSd induces the occurrence of autophagic cell death through up-regulating the expression of BECN1 ,thus inhibiting the proliferation of SMMC-7 7 2 1 .

TACE combined with radiofrequency ablation for primary hepatocellular carcinoma exceeding Milan liver transplantation standard: comparative study of therapeutic evaluation between mRECIST criterion and RECIST criterion / 介入放射学杂志

Objective To investigate the consistency of mRECIST criterion and RECIST criterion in evaluating the curative effect of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) for primary hepatocellular carcinoma (PHC) which condition exceeds Milan liver transplantation standard in order to determine which criterion can evaluate the curative effect better.Methods A total of 78 PHC patients,whose lesion's extent exceeded Milan standard and who had received TACE combined with RFA therapy,were included in this study.The curative effect was separately evaluated by mRECIST criterion and RECIST criterion.KAPPA coefficient was calculated to determine the consistency of the evaluation results by the two criteria.By using Kaplan-Mier method,the median survival time (MST) of patients achieving different remission degree was calculated.Log-rank test was used to draw survival curve.The MST and the survival curve of patients with different remission degree were statistically compared between the two criteria.Results By using SPSS19.0 software,the KAPPA coefficient of the evaluation results of the two criteria was 0.243 (x2=5.250,P＜0.01).The MST of patients,which was calculated by Kaplan-Mier method,had multiple overlapping parts with SD and PR curves that were drawn by log-rank test based on RECIST criterion,the difference between the two was not statistically significant (P＞0.05).When mRECIST criterion was based on,the survival curve of patients with different remission degree was relatively balanced and showed no overlapping parts,the difference between the two was statistically significant (P＜0.01).Conclusion (1) The mRECIST criterion is not suitable for the evaluation of the curative effect of PHC patients whose lesion's extent exceeds Milan standard,and mRECIST criterion can not apply to make evaluation of the curative effect for PHC when the lesion's border is unclear and its enhancement is not obvious.(2) mRECIST criterion can more accurately evaluate the curative effect of TACE combined with PRA in treating PHC which extent exceeds Milan liver transplantation standard.

Accuracy of des-γ-carboxy prothrombin(DCP) for diagnosis of primary hepatocellular cancer: a Meta-analysis / 临床检验杂志

Objective To carry out a systematic evaluation for the diagnostic accuracy of Des-γ-carboxy-prothrombin(DCP) in primary hepatocellular cancer(PHC) by Meta-analysis.Methods The published international and domestic studies on DCP in the diagnosis of PHC were searched in multiple databases from its inception until December 2016.A total of seventeen studies were finally selected,among which 1 970 cases of PHC group and 2 588 cases of control group were included.The control group was composed of chronic hepatitis,cirrhosis,tumors in other systems and healthy subjects with physical examination.A meta-analysis was performed using Stata 12.0.Results The overall pooled results of the analysis and the 95％ confidence intervals were as follows:the sensitivity(SEN) was 0.79 (0.74 to 0.83),the specificity (SPE) was 0.90 (0.87 to 0.93),the positive likelihood ratio(PLR) was 8.1 (5.8 to 11.1),the negative likelihood ratio(NLR) was 0.24(0.19 to 0.29),the diagnostic odds ratio(DOR) was 34(21 to 55) and the area under the summary receiver operator characteristic curve (SROC) was 0.91 (0.89 to 0.93).The sensitivity combined the detections of AFP and DCP in the diagnosis of PHC was 0.90 with 0.94 of AUCROC and 56 of DOR.Conclusion The serum DCP may exhibit a relatively higher diagnostic specificity for PHC.The combined detections of AFP and DCP could improve the sensitivity and diagnostic accuracy.

The clinical application of raltitrexed in TACE for primary hepatocellular carcinoma / 介入放射学杂志

Objective To investigate the curative effect and safety of transcatheter arterial chemoembo -lization (TACE) containing raltitrexed scheme for primary hepatocellular carcinoma (PHCC).Methods From May 2013 to June 2014,a total of 90 patients with inoperable PHCC were treated with TACE containing raltitrexed scheme.The short-term effect,long-term effect and adverse reactions were analyzed.Results Of the 90 patients,complete response was obtained in 23,partial response in 36,stable disease in 24 and progressive disease in 7,the effective rate was 65.6％.The one-year survival rate was 72.2％,the median survival time was 15.9 months,and the progression free survival was 9.1 months.Single factor analysis showed that the statistically significant differences in survival rate existed among the patients with different BCLC staging,combination therapy,lipiodol deposit pattern and vascular tumor thrombus (P＜0.05).Multivariate analysis of Cox model indicated that BCLC staging (x2=9.83,P=0.002) and combined therapy (x2=6.40,P=0.011) were independent prognostic factors.The main adverse reactions were fever,pain,vomiting and bone marrow suppression.Grade Ⅲ-Ⅳ adverse reactions were rare and no treatment-related death occurred.Conclusion For the treatment of inoperable PHCC,TACE containing raltitrexed scheme is effective and safe,and this therapy can be well tolerated by patients.

TACE for the treatment of primary hepatocellular carcinoma associated with portal vein tumor thrombus: recent progress in research / 介入放射学杂志

At present,the combined interventional therapy that is based on transcatheter arterial chemoembolization (TACE) technique can control the progression of primary hepatocellular carcinoma (PHC)in different degrees,at the same time the clinical objectives,such as relieving portal hypertension,eliminating portal vein occlusion,controlling refractory ascites and lowering upper gastrointestinal bleeding probability,can be reliably achieved.Thus,the quality of life of the patients can be effectively improved and the survival time will be reliably prolonged.This paper aims to make a comprehensive review about the medical articles concerning TACE combined with other interventional therapies for PHC complicated by portal vein tumor thrombus,which have been published both at home and abroad in recent years,in order to provide practical help for clinical diagnosis and treatment of PHC.