Effect of microvascular invasion on long-term prognosis of liver resection for multiple hepatocellular carcinomas / 医学研究生学报

ObjectiveOnly few studies have been published of the effect of microvascular invasion (MVI) on long-term prognosis of liver resection (LR) for multiple hepatocellular carcinomas (mHCCs). Therefore, we investigate the efficacy of MVI on long-term prognosis of the patients undergoing LR formHCCs.MethodsThe clinical data of 505 patients undergoing LR for mHCCs in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University between March 2009 and March 2015 were retrospectively analyzed. Patients were divided into the MVI(+) group （n=279）and MVI (-) group (n=226), and146 patients in MVI (+) group and 124 patients in MVI (-) group received adjuvant transarterial chemoembolization (TACE). The Kaplan-Meier approach was used for survival analysis and the Cox proportional-hazards regression model was used forthe risk factors of long-term survival rate.ResultsThe early recurrence rate of MVI (+) group was significantly higher than that of MVI (-) group (60.4% vs 40.5%, P<0.01), and the 1-, 3-, 5-year overall survival rate of MVI (+) group was significantly lower than those in MVI (-) group (70.5%, 47.4%, 33.4% vs 86.6%, 66.8%, 50.1%, P<0.05). Among MVI (+) patients, the early recurrence rate and 1-, 3-, 5-year overall survival rate in the adjuvant TACE group were better than those in the control group (early recurrence rate 41.3% vs 39.3%, P<0.05; 1, 3, 5 year overall survival rate 92.8%, 72.5%, 53.1% vs 78.6%, 59.5%, 47.3%, P<0.05). Multivariate Cox model indicated that the Alpha-foetoprotein (AFP) level, maximum tumor diameter/minimum tumor diameter, MVI and adjuvant TACE were independent risk factors for early recurrence (HR=1.48, 1.51, 1.34, 0.76, P<0.05); maximum tumor diameter, intraoperative blood transfusion, MVI and adjuvant TACE were independent risk factors for postoperative overall survival (HR=1.75, 1.75, 1.36, 0.68, P<0.05).ConclusionMVI is a risk factor for early recurrence and poor long-term prognosis after LR for mHCCs. For mHCCs with MVI, adjuvant TACE after LR could reduce the early recurrence rate and improve the long-term survival rate.

Recent Advances in the Image-Guided Tumor Ablation of Liver Malignancies: Radiofrequency Ablation with Multiple Electrodes, Real-Time Multimodality Fusion Imaging, and New Energy Sources

Radiofrequency ablation (RFA) has emerged as an effective loco-regional treatment modality for malignant hepatic tumors. Indeed, studies have demonstrated that RFA of early stage hepatocellular carcinomas can provide comparable overall survival to surgical resection. However, the incidence of local tumor progression (LTP) after RFA is significantly higher than that of surgical resection. Thus, to overcome this limitation, multiple electrode radiofrequency (RF) systems that use a multi-channel RF generator have been developed, and they demonstrate better efficiency in creating larger ablation zones than that using the conventional RFA with a single electrode. Furthermore, RFA with multiple electrodes can allow the “no-touch” ablation technique which may also help to reduce LTP. Another technique that would be helpful in this regard is multi-modality-ultrasound fusion imaging, which helps to not only more accurately determine the target lesion by enabling the RFA of small, poorly visible or invisible tumors, but also improve the monitoring of procedures and determine the appropriateness of the ablation margin. In addition, new energy sources, including microwave and cryoablation, have been introduced in imaging-guided tumor ablation. In this review, these recently introduced ablation techniques and the results of the most current animal and clinical studies are discussed.

A prospective pilot study of combined intra-operative radiotherapy for centrally located hepatocellular carcinomas / 中华肿瘤杂志

Objective@#To carry out a prospective cohort study of combined intra-operative radiotherapy for centrally located hepatocellular carcinomas (HCC) and to observe the safety and postoperative complications.@*Methods@#A total of 79 patients with centrally located HCC who underwent hepatectomy were divided into two groups: experimental group (combined with targeted intra-operative radiotherapy, 32 cases) and control group (single surgical operation, 47 cases). Patients in the experimental group received intra-operative electron radiotherapy after tumor resection, while patients in the control group received to intra-operative electron radiotherapy.The haemorrhagia amount and operation time during the operation, intra-operative liver function and the recovery of liver and gastrointestinal tract of patients in these two groups were compared.@*Results@#No postoperative 30-day mortality was observed in all of the patients. The average total operation time of patients in the experimental group was (319±76) min, significantly longer than (233±76) min of the control group (P<0.001). The average aspartate transaminase (AST) level of patients in the experimental group at postoperative day 1 was 562.5 U/L, significantly higher than 347.0 U/L of control group (P=0.031). However, the average prothrombin activity levels of patients in the experimental group at postoperative day 3 and day 7 were (68.3±17.9)% and (73.4±10.2)%, respectively, significantly lower than (78.9±15.9)% and (80.0±10.6)% of control group (both P<0.05). There were no significant differences of tumor volume, differentiation degree, satellite lesion, dorsal membrane invasion, microvascular invasion between these two groups (all P>0.05). There were no significant differences of hospital stay, ventilation time, the incidence of hepatic insufficiency, ascites, pleural effusion, infection, biliary fistula between these two groups (all P>0.05). There were no significant differences of alanine aminotransferase (ALT), albumin, total bilirubin between these two groups at postoperative day 1, 3, 5 and 7 (all of P>0.05).@*Conclusion@#The resection of centrally located HCC combined with intra-operative radiotherapy may increase the total operation time, delay the early postoperative recovery of liver function, but it is still safe and feasible.@*Trial registration@#National Cancer Centre /Cancer Hospital, Chinese Academy of Medical Sciences, ChiCTR-TRC-12002802.

Interventional chemoembolization with drug-eluting microspheres of domestic CalliSpheres for the treatment of primary hepatocellular carcinomas: preliminary results in 12 patients / 介入放射学杂志

Objective To evaluate the clinical safety and efficacy of CalliSpheres,a domestic drugeluting microspheres,in treating primary hepatocellular carcinoma (HCC).Methods A total of 12 HCC patients were enrolled in this study.Interventional chemoembolization with CalliSpheres was carried out in all patients.The preoperative and postoperative clinical data,laboratory results and imaging findings were retrospectively analyzed.Results The success rate of initial interventional chemoembolization in 12 patients was 100％,the median follow-up time was 7.5 months (6-9 months).One week after the treatment,both AST and ALT levels were obviously increased when compared with preoperative ones,the differences were statistically significant (P＜0.05),although their mean values did not exceed the normal upper limit of 40 U/L.No statistically significant differences in Child-Pugh grading,creatinine level,hemoglobin,white blood cell count and platelet count existed between preoperative data and postoperative ones (P＞0.05).At 3 months and 6 months after treatment,the disease remission rates (CR+PR) were 75.00％ and 66.67％ respectively,the disease control rates (CR+PR+SD) were 91.67％ and 83.33％ respectively.In 10 HCC patients whose preoperative AFP was ≥ 200 μg/L,the postoperative AFP levels showed a significant decrease.Three months after the treatment,the complete remission rate,disease remission rate and disease control rate in the CalliSpheres combined with Lipiodol sequential transarterial chemoembolization group were better than those in the simple CalliSpheres embolization group,but the differences were not statistically significant (P＞0.05).Postoperative complications were mainly abdominal pain and fever.During follow-up period,the complications included pleural effusion (n=2),liver abscess (n=l) and lung metastasis (n=l).Conclusion The use of domestic CalliSpheres,as a drug-eluting microspheres,for the treatment of primary HCC is safe and feasible with satisfactory short-term efficacy.Its long-term efficacy and the effect of combination use of CalliSpheres and Lipiodol need to be further clarified with multicenter and large sample researches.

Prognostic factors after curative resection hepatocellular carcinoma and the surgeon's role

PURPOSE: Patient, surgical, and tumor factors affect the outcome after surgical resection for hepatocellular carcinoma (HCC). The surgical factors are only modifiable by the surgeon. We reviewed our experience with curative resection for HCC in terms of surgical factors. METHODS: After analyses of the prospectively collected clinical data of 256 consecutive patients undergoing surgical resection for HCC, prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified; all patients were stratified by tumor diameters > or 5 cm. CONCLUSION: Tumor recurrence after liver resection for HCC depends on tumor status, bleeding, and transfusions, which subsequently lead to poor patient survival. Surgeons can help improve the prognosis of patients by minimizing blood loss and transfusion, particularly in patients with larger tumors.

Synthesis of hydroxycinnamic acid derivatives as mitochondria-targeted antioxidants and cytotoxic agents

In order to develop agents with superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas, mitochondria-targeted hydroxycinnamic acids (MitoHCAs) were synthesized by conjugation with a triphenylphosphonium cation. These synthetic compounds were evaluated for their antioxidant activities in hepatic mitochondria, including against OHand ROOinduced lipid peroxidation. HOproduction was decreased significantly by increasing glutathione peroxidase and catalase activities. In addition, cell proliferation data from three cell lines (HepG2, L02 and WI38) indicated that the MitoHCAs were selective for cancer cells. Interestingly, the MitoHCAs both with or without Catriggered mitochondrial dysfunction by inducing mitochondrial swelling, collapsing the mitochondrial membrane potential and causing cytochromerelease. In particular, an inhibitor of the mitochondrial permeability transition pore (mPTP), cyclosporin A, attenuated mitochondrial damage and cell apoptosis, indicating that mPTP may be involved in the antiproliferative activity of MitoHCAs. Further studies focused on structural optimization of these compounds are onging.

Efficacy and Safety of Radiofrequency Ablation Combined with Transcatheter Arterial Chemoembolization for Hepatocellular Carcinomas Compared with Radiofrequency Ablation Alone: A Time-to-Event Meta-Analysis

OBJECTIVE: To compare the efficacy and safety of combined radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA alone for hepatocellular carcinomas (HCC). MATERIALS AND METHODS: Randomized controlled trial (RCT) studies that compared the clinical or oncologic outcomes of combination therapy of TACE and RFA versus RFA for the treatment of HCC were identified through literature searches of electronic databases (Pubmed, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, and Google Scholar). Hazard ratios (HRs) or odds ratios (ORs) with their corresponding 95% confidence interval (CI) were combined as the effective value to assess the summary effects. The strength of evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: Six RCTs with 534 patients were eligible for inclusion in this meta-analysis. The meta-analysis showed that the combination of TACE and RFA is associated with a significantly longer overall survival (HR = 0.62, 95% CI: 0.49-0.78, p < 0.001) and recurrence-free survival (HR = 0.55, 95% CI: 0.40-0.76, p < 0.001) in contrast with RFA monotherapy. The seemingly higher incidence of major complications in the combination group compared with RFA group did not reach statistical significance (OR = 1.17, 95% CI: 0.39-3.55, p = 0.78). CONCLUSION: In patients with HCC, the combination of TACE and RFA is associated with significantly higher overall survival and recurrence-free survival, as compared with RFA monotherapy, without significant difference in major complications.

The influence of down-regulation of Tspan 8 by shRNA on metastasis and invasion of hepatocellular carcinomas / 中华肝胆外科杂志

Objective To study the effect of Tspan 8 on metastasis and invasion of human hepatocellular carcinomas(HCC).Methods RT-PCR and western blot were used to detect the expressions of Tspan 8 in HCC cell lines,HCC and matched nontumorous tissues.The expression of Tspan 8 was then down-regulated by LV/GFP/Tspan 8 in HCC cells.The expressions of Tspan 8 mRNA and protein were determined by RT-PCR and Western blot assay,respectively.The proliferation was examined by MTT,the expression of AMDM12 was assessed by Western blot,and the invasion ability of HCC cells was evaluated by transwells.Results A high level of Tspan 8 was found in high metastatic potential HCC cells,and the expression of Tspan 8 in HCC tissues was much higher than that in the matched nontumorous tissues. Down-regulation of Tspan 8 had no influence on the proliferation of HCC cells (P＞0.05),while it inhibited the expression of ADAM12 and the invasive ability of HCC cells (P＜0.01,P＜0.01 respectively).Conclusion Tspan 8 played an important role in invasion and metastasis of human hepatocellular carcinomas and down-regulation by LV/GFP/Tspan 8 inhibited the invasiveness of human hepatocellular carcinoma cells.

Consensus Report of the 4th International Forum for Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid Magnetic Resonance Imaging

This paper reports on issues relating to the optimal use of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA MR imaging) together with the generation of consensus statements from a working group meeting, which was held in Seoul, Korea (2010). Gd-EOB-DTPA has been shown to improve the detection and characterization of liver lesions, and the information provided by the hepatobiliary phase is proving particularly useful in differential diagnoses and in the characterization of small lesions (around 1-1.5 cm). Discussion also focused on advances in the role of organic anion-transporting polypeptide 8 (OATP8) transporters. Gd-EOB-DTPA is also emerging as a promising tool for functional analysis, enabling the calculation of post-surgical liver function in the remaining segments. Updates to current algorithms were also discussed.

Study of using ?-cyanoacrylate to establish the orthotopic transplantation tumor model from the subcutaneous model of human hepatocellular carcinoma in nude mice / 肿瘤研究与临床

Objective Using ?-cyanoacrylate to establish the orthotopic transplantation tumor model from the subcutaneous model of human hepatocellular carcinomas(HCC)in nude mice. Methods The subcutaneous animal tumor model was established by transplanting BEL-7402 cell into the subcutaneous of nude mice. Then the orthotopic transplantation tumor model was established by injecting the subcutaneous transplanted tumor into liver(indirect orthotopic model). Results Using ?-cyanoacrylate to establish the indirect orthotopic model successfully and the survival rates of the transplantation tumor were 95.8 %. Conclusion It was compared with the traditional methods that the indirect orthotopic transplantation tumor model by using ?-cyanoacrylate to establish is an easy method with high successful rate and easy to spread.

The Relation Between Tumor Blood Vessels Around Hepatocellular Carcinomas and Metastases / 实用放射学杂志

Objective To study relation between tumor blood vessels around hepatocellular carcinomas and metastases and try to find out probability to predict potential metastases of hepatocellular carcinomas according to CT manifestation.Methods Both CT plain scans and dynamic contrast scans were taken in 134 cases of patients with hepatocellular carcinomas.The tumor blood vessels around and in cancers were counted.CT appearances,pathology results and patient follow-up were compared and analyzed.Results 1.The possibilty to happen metastases was much higher in carcinomas with heavy enhancement than that with gently or middle.2.Those with tumor blood vessel around neoplasm were greater metastasis rate than those without them.3.The enhancement degree in tumor border is positive correlation with blood count.Conclusion The latent metastases can be estimated according to the enhancing degree and tumor blood vessels around carcinomas.

Expression of TGF-?_2,TNF-? and its relationship with HBV infection in liver cirrhosis and hepatocellular carcinomas / 重庆医科大学学报

Objective:To study the expession of TGF-? 2,TNF-? and its relationship with hepatitis B(HBV) infection in chronic hepatitis B,liver cirrhosis,paratumor cirrhosis and hepatocellular carcinomas(HCC).Methods:HBsAg,HBcAg,TGF-? 2 and TNF-? were detected by immunohistochemical staining among total 63 cases of liver cirrhosis,HCC,paratumor cirrhosis and normal liver tissues.Results:TGF-? 2 and TNF-? were expressed in liver cirrhosis,HCC and paratumor cirrhosis,and they showed significant difference from normal control liver( P c

Expression and significance of P27 in hepatocellular carcinomas / 重庆医科大学学报

Objective:To study the expression and its significance of P27 protein in hcpatocellular carcinomas(HCC).Methods:Expression of P27 protein is investigated by immunohistochemistry technique(SP) in 50 cases of hepatocellular carcinoma who had undergone surgery for HCC,22 cases of their adjacent noncancerous lesions and 9 cases normal liver control specimens.Results:The P27 LI in hepatocellular carcinomas was higher than that in the adjacent noncancerous lesions (P=0.002).Furthermore,the P27LI in adjacent noncancerous lesions was significantly highter than that in normal liver lesions (P=0.007).The expression of P27 was significantly correlated with tumor differentiation,stage,size,portal invasion,and intrahepatic metastasis.The post-operation survival time for patients with P27LI≥50% was longer than those with P27 LI

Nodular hepatocellular carcinoma on three phases spiral CT scanning:Emphasis on evaluating the detected rate of the lesions / 重庆医科大学学报

Objective:To compare the detected rate of nodular hepatocellular carcinomas (HCC)on spiral CT enhanced scanning of arterial-, portal-, and delay phase. Methods: Spiral CT scanning was performed in 30 cases of nodular HCC. After plain CT examination, arterial phase(25s after injection) and portal venous phase (60～70s after injection), delay phase (4～6min after injection) were performed with a 150ml bolus injection of contrast material at 3ml/s. The morphology and characteristics on enhanced scans were analyzed and the numbers of the detected lesions were calculated on each phase.Results: 51 nodular HCC of total 30 cases were found.The detected rate on plain scan,arterial phase,portal venous phase and delay phase were 23.5%,84.3%,66.7% and 72.5% respectively.Conclusion: Spiral CT enhanced scanning can fully show the enhanced characteristics of HCC, and combination of three phases could improve the detectrate.