Antibiotic prophylaxis in transarterial chemoembolization of hepatocellular carcinoma

Background and study aims

Transarterial chemoembolization remains a common treatment option in unresectable hepatocellular carcinoma. However, protocols for pre- and post-procedure care and the role of antibiotic prophylaxis have not been evaluated. The aim of this work was to compare 3 different groups of prophylactic antibiotics in patients undergoing chemoembolization and to compare the efficacy of intravenous versus oral route.

中药治疗原发性肝癌介入术后发热的疗效分析

目的：观察中药对原发性肝癌（HCC）患者肝动脉灌注化疗栓塞（TACE）术后出现发热、腹水的治疗效果。方法：采用随机入组的方式,将拟行TACE初治的原发性肝癌患者随机分为中药加常规治疗组和常规治疗组,观察两组患者的体温变化及腹水发生情况。结果：两组患者的最高体温及发热持续时间比较差异有统计学意义,腹水发生率无统计学差异。结论：中药可以减轻肝癌患者介入术后出现的发热症状。     

Review of preoperative transarterial chemoembolization for resectable hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the few cancers whose incidence has been continually increasing over recent years.Resection of HCC offers the only hope for cure.However,recurrences are common in patients who have undergone resection.In our opinion,the effectiveness with which transarterial chemoembolization(TACE) as a neoadjuvant therapy for resectable HCC prevents recurrence and prolongs survival has not been conclusively demonstrated.All published meta-analyses have consistently failed to demonstrate that preoperative TACE improves the prognosis of resectable HCC.We believe that these published articles have several limitations and have our own views about the results of meta-analyses.It is very important that the scientific community shed more light on the pathogenesis of HCC and relate this to choice of therapy.This review mainly concerns our understanding of preoperative TACE for resectable HCC and briefly addresses desirable directions for future studies.     

经肝动脉化疗栓塞术联合索拉非尼治疗中晚期肝细胞癌研究进展

经肝动脉化疗栓塞术(TACE)联合索拉非尼是目前治疗失去手术机会的中晚期肝细胞癌(HCC)最常用的策略,但具体治疗模式还未形成共识。分析了TACE联合索拉非尼治疗HCC的治疗模式及其有效性和安全性。认为不同的治疗模式均具有其利弊,还需要进行更多的临床研究,为中晚期肝癌患者的治疗提供一定参考。     

Conventional vs drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma

Transarterial chemoembolization(TACE) is the current standard of therapy for patients with intermediatestage hepatocellular carcinoma(HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE(cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drugeluting beads(DEBs) have been imposed as novel drugdelivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEBTACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.     

Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion

Background and Aim:  This study aimed to evaluate the therapeutic efficacy and safety of repeated transarterial chemoembolization (TACE) with additional radiation therapy (RT) in hepatocellular carcinoma (HCC) with portal vein (PV) invasion.
Methods:  We performed survival analysis of consecutive HCC patients with PV invasion according to the treatment modalities after stratification by the degree of PV invasion and liver function retrospectively.
Results:  During 2005, 281 patients were newly diagnosed to have HCC with PV invasion at our institution. Repeated TACE or transarterial chemoinfusion (TACI) was performed in 202 (71.9%) patients and additional RT was performed for PV invasion in 43 of them. A total of 281 patients had a median survival of 5.2 months and a 2-year survival rate (YSR) of 19.2%. Repeated TACE showed significant survival benefits compared with conservative management in patients with PV branch invasion; median survival and 2-YSR was 10.2 vs 2.3 months and 33.7% vs 0% in Child–Pugh A categorized patients and 5.5 vs 1.3 months and 10.3 vs 0% in Child–Pugh B categorized patients, respectively ( P  < 0.001). In patients with PV branch invasion, the survival rate was significantly longer with TACE/TACI plus RT than with TACE/TACI alone both in Child–Pugh A categorized patients (1-YSR: 63.6 vs 35.6%, P  = 0.031) and Child–Pugh B categorized patients (1-YSR: 66.7 vs 7.7%, P  = 0.007). Repeated TACE was well tolerated in our patients, with only one dying within one month after TACE.
Conclusion:  Repeated TACE with additional RT can be performed safely and showed a significant survival benefit in HCC patients with PV branch invasion with conserved liver function.     

Lipiodolized transarterial chemoembolization in hepatocellular carcinoma patients after curative resection

Purpose

To explore the effect of lipiodolized transarterial chemoembolization (lip-TACE) in hepatocellular carcinoma (HCC) patients at different risk of recurrence after curative resection.

Methods

One thousand nine hundred and twenty-four consecutive HCC patients who underwent curative resection were retrospectively analyzed. Patients who underwent resection only were classified into control group, while those received adjuvant lip-TACE were classified into intervention group. Patients were further stratified into 4 groups, that is, tumor ≤5 cm with low or high risk factors, as well as tumor >5 cm with low or high risk factors for recurrence. Tumor number and microscopic tumor thrombus were defined as risk factors for recurrence. The effect of adjuvant lip-TACE on early (<2 year) or late (≥2 year) recurrence was evaluated.

Results

There was no significant difference in recurrence curve between intervention group and control group in each stratum. Adjuvant lip-TACE showed an overall survival benefit in patients with tumor >5 cm and presenting high risk factors, mainly for those with time to recurrence (TTR) <2 years after operation. For them, the median survival was 17 months in the intervention group and 11 months in the control group (P = 0.010). For patients who were confirmed to be recurrence-free at 2 years after operation, it had the negative effect for survival (HR = 1.75, P = 0.004).

Conclusion

Adjuvant lip-TACE had no preventive effect on recurrence, but may be of benefit to detect early recurrence.     

经肝动脉化疗栓塞后联合索拉非尼治疗肝癌患者临床观察

目的探讨索拉非尼联合经肝动脉化疗栓塞术（TACE）治疗肝癌患者的效果。方法选取142例肝癌患者,其中57例接受TACE治疗,47例接受索拉非尼治疗,38例接受索拉非尼联合TACE治疗。在治疗后12 w,评估治疗效果、总生存期（OS）和疾病进展时间（TTP）。结果联合治疗组有效率为26.32%,显著高于TACE组的17.54%或索拉非尼组的19.15%（P<0.05）;联合治疗组疾病控制率为71.05%,显著高于TACE组的57.89%或索拉非尼组的53.19%（P<0.01）;联合治疗组患者OS为8.6 m,显著高于索拉非尼组的6.2 m或TACE组的7.3 m（P<0.05）;联合治疗组TTP为6.7 m,显著高于索拉非尼组的5.1m或TACE组的 5.6 m（P<0.01）。结论索拉非尼联合TACE治疗肝癌患者具有较好的临床效果。     

Chemotherapy for transarterial chemoembolization in patients with unresectable hepatocellular carcinoma

AIM: To compare the efficacy of different chemotherapeutic agents during conventional transarterial chemoembolization (cTACE) in the treatment of unresectable hepatocellular carcinoma (HCC).METHODS: A retrospective review was undertaken of patients with unresectable HCC undergoing cTACE from May 2003 to November 2011. A total of 107 patients were treated with at least one cTACE session. Irinotecan (CPT-11) was used as a chemotherapeutic agent in 24 patients, gemcitabine (GEM) in 24 and doxorubicin in 59.RESULTS: The time to progression and overall survival rates were significantly superior in patients treated with CPT-11 compared with the GEM or doxorubicin treated groups (11.4, 8.2, 9.5 mo, P = 0.02 and 21.7, 12.7, 14.5 mo, P = 0.004, respectively). Subgroup analysis showed that for intermediate-stage HCC, CPT-11 resulted in a significantly longer time to progression and overall survival compared with the GEM or doxorubicin treated groups (P = 0.022; P = 0.003, respectively). There were no significant differences in adverse events among the three groups (P > 0.05).CONCLUSION: For patients treated with cTACE, the chemotherapeutic agent CPT-11 was significantly associated with improved overall survival and delayed tumor progression compared with GEM or doxorubicin. There were no significant differences in clinical adverse events between the three agents. CPT-11 thus appears to be a promising agent when combined with cTACE for the treatment of HCC.     

Transarterial chemoembolization versus transarterial radioembolization in hepatocellular carcinoma: optimization of selecting treatment modality

Hepatocellular carcinoma (HCC) of intermediate stage consists of diverse tumor and patient factors in terms of tumor number, size and liver function resulting in various outcomes given by transarterial chemoembolization (TACE). Transarterial radioembolization (TARE) using radioactive isotope, β-ray emitting Yttrium-90 with a short half-life and penetration depth, is an emerging intra-arterial brachytherapy characterized by potent anti-cancer effect given by radiation but minimal embolic effect. Although there is lack of study directly comparing the efficacy and safety between TACE and TARE in patients with unresectable HCC, several retrospective or small-scaled studies suggest that overall efficacy indicated by overall survival and time to progression is similar between two modalities and TARE has a superiority in the safety including postembolization syndrome, hospitalization days and outpatient-based therapy. In advanced HCC with portal vein (PV) invasion, TACE is not consistently recommended due to risk of hepatic decompensation or failure after procedure. On the contrary, available data suggest that TARE might be a promising treatment option in HCC with PV thrombosis if patient’s liver function is preserved and the level of PV invasion is less than main trunk. Ongoing trials comparing TARE and sorafenib in advanced HCC would elucidate the role of this locoregional therapy. The need of a multidisciplinary team, complex steps of procedure and high cost of TARE are the hurdles to widespread recommendation of this therapy in intermediate or advanced HCC. The optimization of selection between TACE and TARE might be dependent on availability, experience, tumor factors and patient factors.     

Effect of camrelizumab plus transarterial chemoembolization on massive hepatocellular carcinoma

ObjectiveTo investigate the efficacy of camrelizumab plus transarterial chemoembolization (TACE) on massive hepatocellular carcinoma (HCC) patients.MethodsA total of 92 cases with massive HCC from October 2019 to January 2021 were prospectively enrolled and randomly divided into the study group (n = 46) and the control group (n = 46). The control group received TACE while the study group were treated with camrelizumab plus TACE. The primary end points were clinical efficacy and adverse events. And the secondary end points were liver function, and alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), carbohydrate antigen 19–9 (CA19–9) levels before and after treatment.ResultsAll participants were followed-up for 7 to 24 months, with a median of 12 months. Patients in the study group received TACE for 1–3 times, with an average of (2.01 ± 0.09) times, while patients in the control group receive TACE for 2–4 times, with an average of (3.78 ± 0.12) times, and the control group received significantly more TACEs (χ² = 5.518, P = 0.019). During the follow-up, the response rate and disease control rate of the study group were significantly higher than those of the control group (χ² = 5.518, P = 0.019; χ² = 4.467, P = 0.041). Before treatment, the levels of total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP), CEA, and CA19–9 were comparable between the groups (P > 0.05). After treatment, the levels of TBIL, ALT, AST, AFP, CEA, and CA19–9 decreased, and the above indicators in the study group were significantly lower than those in the control group (P < 0.05). All patients showed transient liver damage, vomiting, nausea, fever and abdominal pain after surgery, and their symptoms were relieved after symptomatic treatment. Adverse events occurred in 9 cases in the study group, and 3 cases in the control group (χ² = 3.419, P = 0.064).ConclusionCompared with TACE alone, camrelizumab plus TACE treatment can significantly improve the liver function of patients with massive HCC and enhance the treatment effect, which is worthy of clinical promotion.     

Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization

AIM To investigate novel predictors of survival in hepatocellular carcinoma(HCC) patients following transarterial chemoembolization(TACE).METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results(total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index(AgI). We used The Wilcoxon ranksum(Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival. RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI or 4 was 42.4% vs 61.8%; P 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56(95%CI: 1.120-5.863 P 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase(GGTP) had ORs of 1.01(95%CI: 1.003-1.026, P 0.017) and 0.99(95%CI: 0.99-1.00, P 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI 4 had HR for mortality of 2.18(95%CI: 1.108-4.310, P 0.024). GGTP's single unit change had a HR for mortality of 1.003(95%CI: 1.001-1.006, P 0.016). These were considered in the final multivariate model with the total cohort. An AgI 4 had a HR for mortality of 2.26(95%CI: 1.184-4.327, P 0.016). GGTP had a HR of 1.003(95%CI: 1.001-1.004, P 0.001).CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.     

Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma

Resection of hepatocellular carcinoma (HCC) offers the only hope for cure. However, in patients undergoing resection, recurrences, in particular, intrahepatic recurrence are common. The effectiveness of transarterial chemoembolization (TACE) as a neoadjuvant therapy for unresectable HCC was exploited by numerous liver units and employed preoperatively in the setting of resectable HCC with an aim to prevent recurrence and prolong survival. A systematic literature search of databases (Medline and PubMed) to identify published studies of TACE administered preoperatively as a neoadjuvant treatment for resectable HCC was undertaken. A systematic review by tabulation of the results was performed with disease‐free survival (DFS) as the primary endpoint. Overall survival (OS), rate of pathological response, impact on surgical morbidity and mortality and pattern of recurrences were secondary endpoints of this review. Eighteen studies; three randomized trials and 15 observational studies were evaluated. This comprised of 3927 patients, of which, 1293 underwent neoadjuvant TACE. The median DFS in the TACE and non‐TACE group ranged from 10 to 46 and 8 to 52 months, respectively, with 67% of studies reporting similar DFS between groups despite higher extent of tumour necrosis from the resected specimens indicating a higher rate of pathological response (partial TACE 27–72% vs. non‐TACE 23–52%; complete TACE 0–28% vs. non‐TACE zero), with no difference in surgical morbidity and mortality outcome. No conclusion could be drawn with respect to OS. Both randomized and non‐randomized trials suggest the use of TACE preoperatively as a neoadjuvant treatment in resectable HCC is a safe and efficacious procedure with high rates of pathological responses. However, it does not appear to improve DFS.