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1.
The diagnostic performance of gadoxetic acid disodium-enhanced magnetic resonance imaging and contrast-enhanced ultrasound in detecting hepatocellular carcinoma: A meta-analysis.
Wang, J, Ye, X, Li, J, He, S
Medicine. 2021;(6):e24602
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Abstract
The purpose of this study was to identify and compare the diagnostic performance of gadolinium-ethoxybenzyl-diethyltriethylenetriacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in hepatocellular carcinoma (HCC).Two researchers searched PubMed, EMBASE, and Cochrane Library databases from the inception of each database to 10 February 2020, to find comparative studies of Gd-EOB-DTPA-MRI and CEUS in detection of HCC.The study included eight studies (374 patients). MRI is superior to CEUS in diagnostic sensitivity of HCC, P = .03. The diagnostic sensitivity of MRI in lesions with a diameter of less than 30 mm was significantly higher than that of CEUS, P = .04. MRI and CEUS had no significant difference in diagnostic specificity of HCC, P = .95. Summary Receiver Operating Characteristics (SROC) of MRI showed a larger than that of CEUS, but with P > .05.Gd-EOB-DTPA-MRI showed higher sensitivity than CEUS for hepatocellular carcinoma lesions, especially for lesions of less than 30 mm across.
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Is transcatheter arterial chemoembolization plus sorafenib better than chemoembolization plus placebo in the treatment of hepatocellular carcinoma?
Xie, Y, Tian, H, Xiang, H
Tumori. 2021;(4):292-303
Abstract
OBJECTIVE To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus sorafenib compared with TACE plus placebo for hepatocellular carcinoma (HCC) using meta-analytical techniques. METHODS A search of PubMed, EMBASE, and Cochrane Library databases were done from inception to December 27, 2019. Published trials including a treatment group receiving TACE + sorafenib and a control group receiving TACE + placebo with data for at least 1-year survival or tumor response or time to progression were included. RESULTS Our study suggested that there was no evidence that TACE plus sorafenib was associated with a lower risk of disease progression compared with TACE plus placebo for treatment of HCC (hazard ratio 0.94 [95% confidence interval (CI), 0.84-1.05]), and no significant difference for treatment of HCC compared with TACE plus placebo in terms of 0.5-, 1-, 1.5-, and 2-year survival rates (risk ratio [RR] 1.01 [95% CI, 0.97-1.05]; RR 1.00 [95% CI, 0.92-1.08], RR 1.04 [95% CI, 0.89-1.23], RR 0.98 [95% CI, 0.72-1.34], respectively). The meta-analysis also showed that TACE + sorafenib seemed to have no significant difference for treatment of HCC compared with TACE + placebo in terms of complete response, partial response, stable disease, progressive disease, overall response rate, and disease control rate. There was an increased incidence of fatigue of grade 3/4 and elevation of aspartate aminotransferase and alanine aminotransferase of grade 3/4 in patients receiving TACE plus sorafenib compared with those receiving TACE plus placebo. CONCLUSIONS There is no additive benefit of TACE plus sorafenib compared to TACE plus placebo for HCC.
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Sorafenib versus hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis.
Zhuang, BW, Li, W, Xie, XH, Hu, HT, Lu, MD, Xie, XY
Japanese journal of clinical oncology. 2019;(9):845-855
Abstract
BACKGROUND The clinical benefits and safety of Sorafenib versus hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) are inconsistent in some studies. This meta-analysis aims to evaluate the effectiveness and safety of Sorafenib versus HAIC for patients with advanced HCC. METHODS An electronic search was performed from PubMed, Embase, the Cochrane Library and Web of Science to identify comparative studies evaluating Sorafenib versus HAIC for HCC. Objective response rate, disease control rate, overall survival, progression-free survival and adverse events were evaluated using meta-analytical techniques. RESULTS Fourteen retrospective studies with 1779 patients (Sorafenib = 773, HAIC = 1006) were included in the meta-analysis. HAIC delivered favorable outcomes in objective response rate (odds ratio 0.13; 95%CI, 0.07-0.24) and disease control rate (odds ratio 0.48; 95%CI 0.26-0.87) assessed by the Response Evaluation Criteria in Solid Tumors. The pooled hazard ratio for overall survival at 0.60 (95% CI 0.39-0.91) and the pooled hazard ratio for progression-free survival at 0.69(95% CI 0.51-0.95), further indicates that HAIC was superior to Sorafenib. There was a higher incidence of adverse events, including hypertension (odds ratio 13.07; 95% CI 2.37-71.67), fatigue (odds ratio 6.72; 95% CI 2.14-21.13), dermatological disorders (odds ratio 15.87; 95% CI 5.58-45.16) and gastrointestinal disorders (odds ratio 3.20; 95% CI 2.02-5.07) in patients receiving Sorafenib than in those receiving HAIC. CONCLUSION HAIC offers a safe and effective alternative to Sorafenib with better tumor response and longer overall survival and progression-free survival, hence HAIC should be recommended for the patients with advanced HCC.
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Transcatheter arterial chemoembolization plus sorafenib versus transcatheter arterial chemoembolization alone to treat advanced hepatocellular carcinoma: a meta-analysis.
Cai, R, Song, R, Pang, P, Yan, Y, Liao, Y, Zhou, C, Wang, S, Zhou, X, Wang, H, Zhang, H, et al
BMC cancer. 2017;(1):714
Abstract
BACKGROUND Many studies have combined sorafenib with transcatheter arterial chemoembolization (TACE) to treat patients with advanced hepatocellular carcinoma (HCC), but the results are disputable. Thus, we conducted this meta-analysis to assess the efficacy and safety of the combination treatment in patients with advanced HCC. METHODS Clinical data were collected from a computer search of literature published from January 2009 to June 2016 in PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang and the China Science and Technology Journal Database (CSTJ). The final analysis included 14 studies and 1670 patients. The primary endpoints were overall survival (OS), the objective response rate (ORR) and the disease control rate (DCR). RESULTS The combination group exhibited significantly more improvement than the group treated with TACE alone in ORR (RR =1.62, 95% confidence interval (CI) = 1.34-1.94, p < 0.00001), DCR (RR = 1.43, 95% CI = 1.26-1.62, p < 0.00001), 0.5-year OS (OR = 2.60, 95% CI = 1.57-4.29, p = 0.0002) and 1-year OS (OR = 1.88, 95% CI =1.39-2.53, p < 0.0001). The incidence of adverse events from combination therapy was increased compared to that from treatment with TACE alone, and the most commonly reported adverse events were fatigue, hand-foot skin reaction and diarrhoea, which were bearable. CONCLUSIONS The meta-analysis indicated that combination therapy is safe and efficient for clinical application.
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Prospective Study of Transcatheter Arterial Chemoembolization (TACE) with Ginsenoside Rg3 versus TACE Alone for the Treatment of Patients with Advanced Hepatocellular Carcinoma.
Zhou, B, Yan, Z, Liu, R, Shi, P, Qian, S, Qu, X, Zhu, L, Zhang, W, Wang, J
Radiology. 2016;(2):630-9
Abstract
Purpose To conduct a single-center, open-label, randomized, controlled trial to compare the effectiveness and safety of (a) ginsenoside Rg3 combined with transcatheter arterial chemoembolization (TACE) and (b) TACE alone in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001643). After informed consent was obtained, 228 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) were randomly assigned to receive an Rg3 capsule and undergo TACE (n = 152; mean age ± standard deviation, 52.4 years ± 11.8; 84.2% men) or undergo TACE alone (n = 76; mean age, 52.4 years ± 10.4; 82.9% men). TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused. The primary end point was overall survival. Secondary end points included time to progression, time to untreatable progression, disease control rate, and safety. Data were compared with the log-rank test, and survival curves were generated with the Kaplan-Meier method. Results Median overall survival was 13.2 months (95% confidence interval [CI]: 11.15, 15.26) in the TACE with Rg3 group and 10.1 months (95% CI: 9.14, 11.06) in the control group (hazard ratio, 0.63 [95% CI: 0.46, 0.85]; P = .002). Median time to progression (4.3 vs 3.2 months, respectively; P = .151) and median time to untreatable progression (8.3 vs 7.3 months, respectively; P = .063) were similar in the two groups. Disease control rate was 69.7% in the TACE with Rg3 group versus 51.3% in the control group (P = .012). Constipation and epistaxis were more frequent in the Rg3 with TACE group (P < .05). Importantly, Rg3 alleviated some TACE-related adverse syndromes and blood anomalies. Conclusion In patients with advanced HCC and adequate liver function, the combination of TACE and ginsenoside Rg3 may prolong overall survival when compared with TACE alone. (©) RSNA, 2016.
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Preoperative Enteral Nutritional Support in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma: A Strengthening the Reporting of Observational Studies in Epidemiology Article.
Yao, H, Bian, X, Mao, L, Zi, X, Yan, X, Qiu, Y
Medicine. 2015;(46):e2006
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Abstract
To compare the short-term outcomes between hepatocellular carcinoma (HCC) patients with and those without preoperative nutrition on the basis of postoperative enteral nutrition.HCC patients with postoperative enteral nutrition who underwent liver resection between February 2010 and December 2014 in Nanjing Drum Tower Hospital were considered for the study: 43 patients with and 36 patients without preoperative nutrition. Primary endpoint was the incidence of overall complications. Secondary endpoints were infectious and major complications.In the preoperative enteral nutrition group, shorter length of postoperative hospital stay (10.5 ± 2.7 versus 13.7 ± 6.3 days, P = 0.007), less exogenous albumin infusion (10.2 ± 22.4 versus 47.8 ± 97.7 g, P = 0.030), earlier first exhaust time (2.7 ± 0.8 versus 3.0 ± 0.9 days, P = 0.043), and first defection time (3.5 ± 0.9 versus 4.4 ± 1.4 days, P = 0.001) were observed. No significant differences were observed in the incidence of overall complications (32.6% versus 52.8%, P = 0.070), infectious complications (7.0% versus 8.3%, P = 1), and major complications (14.0% versus 11.1%, P = 0.969) between the preoperative enteral nutrition and control group.Preoperative enteral nutrition could improve short-term outcomes of HCC patients via accelerating the recovery of gastrointestinal function and shortening the length of postoperative hospital stay.
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Comparative Metabolomic Profiling of Hepatocellular Carcinoma Cells Treated with Sorafenib Monotherapy vs. Sorafenib-Everolimus Combination Therapy.
Zheng, JF, Lu, J, Wang, XZ, Guo, WH, Zhang, JX
Medical science monitor : international medical journal of experimental and clinical research. 2015;:1781-91
Abstract
BACKGROUND Sorafenib-everolimus combination therapy may be more effective than sorafenib monotherapy for hepatocellular carcinoma (HCC). To better understand this effect, we comparatively profiled the metabolite composition of HepG2 cells treated with sorafenib, everolimus, and sorafenib-everolimus combination therapy. MATERIAL AND METHODS A 2D HRMAS 1H-NMR metabolomic approach was applied to identify the key differential metabolites in 3 experimental groups: sorafenib (5 µM), everolimus (5 µM), and combination therapy (5 µM sorafenib +5 µM everolimus). MetaboAnalyst 3.0 was used to perform pathway analysis. RESULTS All OPLS-DA models displayed good separation between experimental groups, high-quality goodness of fit (R2), and high-quality goodness of predication (Q2). Sorafenib and everolimus have differential effects with respect to amino acid, methane, pyruvate, pyrimidine, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism. The addition of everolimus to sorafenib resulted in differential effects with respect to pyruvate, amino acid, methane, glyoxylate and dicarboxylate, glycolysis or gluconeogenesis, glycerophospholipid, and purine metabolism. CONCLUSIONS Sorafenib and everolimus have differential effects on HepG2 cells. Sorafenib preferentially affects glycerophospholipid and purine metabolism, while the addition of everolimus preferentially affects pyruvate, amino acid, and glucose metabolism. This phenomenon may explain (in part) the synergistic effects of sorafenib-everolimus combination therapy observed in vivo.
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CT versus MR imaging of hepatocellular carcinoma: toward improved treatment decisions.
Murakami, T, Okada, M, Hyodo, T
Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine. 2012;(2):75-81
Abstract
Detection, characterization, staging, and treatment monitoring are major roles of diagnostic imaging of liver cancers. Developments in multidetector-row computed tomography (MDCT) technology have increased the spatial and temporal resolution of CT to allow more precise evaluation of the hemodynamics of liver tumors and improve the diagnostic accuracy of dynamic MDCT. The high spatial and temporal resolutions of dynamic MDCT enable us to reconstruct 3-dimensional (3D) images that are very useful for pretreatment evaluation. Dynamic MR imaging with fast 3D T(1)-weighted gradient echo imaging sequence using nonspecific contrast medium can be highly sensitive for detecting hypervascular HCC. However, the use of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), a contrast medium specific to hepatic tissue, offers greater diagnostic ability and, so, has become essential to liver imaging. MR imaging with Gd-EOB-DTPA may replace CT during hepatic arteriography and CT during arterioportography.
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Comparison of Kupffer-phase Sonazoid-enhanced sonography and hepatobiliary-phase gadoxetic acid-enhanced magnetic resonance imaging of hepatocellular carcinoma and correlation with histologic grading.
Sugimoto, K, Moriyasu, F, Saito, K, Taira, J, Saguchi, T, Yoshimura, N, Oshiro, H, Imai, Y, Shiraishi, J
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2012;(4):529-38
Abstract
OBJECTIVES To determine the relative wash-out of hepatocellular carcinomas and dysplastic nodules using Kupffer-phase sonography with Sonazoid (Daiichi-Sankyo, Tokyo, Japan) enhancement and hepatobiliary-phase gadoxetic acid-enhanced magnetic resonance imaging (MRI) in the evaluation of the histopathologic grades of individual nodules. METHODS This retrospective study included 66 consecutive patients with 78 histologically confirmed hepatocellular carcinomas and dysplastic nodules. In patients with carcinomas, 33 were well differentiated; 29 were moderately differentiated; and 11 were poorly differentiated; and there were 5 dysplastic nodules. All patients underwent both gadoxetic acid-enhanced MRI and Sonazoid-enhanced sonography. The interval between the two imaging examinations was less than 30 days. Six radiologists independently reviewed both images and rated the degree of relative wash-out between the tumorous and nontumorous areas on Kupffer- and hepatobiliary-phase images using a continuous rating scale. We compared these results with the histopathologic grade of each nodule, and the results were then analyzed with multireader multicase receiver operating characteristic analysis. RESULTS The average Kupffer-phase (P < .001) and hepatobiliary-phase (P = .004) rating scores increased as the carcinomas became less differentiated (Kruskal-Wallis test). The diagnostic accuracies of the average area under the receiver operating characteristic curve, which were estimated using the confidence levels of the relative wash-out of the Kupffer- and hepatobiliary-phase images, were 0.705 and 0.785 for dysplastic nodules versus well-, moderately, and poorly differentiated carcinomas (P = .517), 0.791 and 0.687 for dysplastic nodules and well-differentiated carcinomas versus moderately and poorly differentiated carcinomas (P = .093), and 0.871 and 0.716 for dysplastic nodules and well-and moderately differentiated carcinomas versus poorly differentiated carcinomas (P = .005), respectively. CONCLUSIONS Kupffer-phase Sonazoid-enhanced sonography and hepatobiliary-phase gadoxetic acid-enhanced MRI may be useful in estimating the histologic grade, although Kupffer-phase Sonazoid-enhanced sonography may be more accurate in distinguishing hepatocellular carcinomas, especially moderately and poorly differentiated types.
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Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma.
Kudo, M, Imanaka, K, Chida, N, Nakachi, K, Tak, WY, Takayama, T, Yoon, JH, Hori, T, Kumada, H, Hayashi, N, et al
European journal of cancer (Oxford, England : 1990). 2011;(14):2117-27
Abstract
BACKGROUND In Japan and South Korea, transarterial chemoembolisation (TACE) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown effective and safe in patients with advanced HCC. This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE. METHODS Patients (n=458) with unresectable HCC, Child-Pugh class A cirrhosis and ≥25% tumour necrosis/shrinkage 1-3 months after 1 or 2 TACE sessions were randomised 1:1 to sorafenib 400mg bid or placebo and treated until progression/recurrence or unacceptable toxicity. Primary end-point was time to progression/recurrence (TTP). Secondary end-point was overall survival (OS). FINDINGS Baseline characteristics in the two groups were similar; >50% of patients started sorafenib>9 weeks after TACE. Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months, respectively (hazard ratio (HR), 0.87; 95% confidence interval (CI), 0.70-1.09; P=0.252). HR (sorafenib/placebo) for OS was 1.06 (95% CI, 0.69-1.64; P=0.790). Median daily dose of sorafenib was 386 mg, with 73% of patients having dose reductions and 91% having dose interruptions. Median administration of sorafenib and placebo was 17.1 and 20.1 weeks, respectively. No unexpected adverse events were observed. INTERPRETATION This trial, conducted prior to the reporting of registrational phase III trials, found that sorafenib did not significantly prolong TTP in patients who responded to TACE. This may have been due to delays in starting sorafenib after TACE and/or low daily sorafenib doses.