Clinical outcomes of radiofrequency ablation and surgical resection for small hepatocellular carcinoma: a meta-analysis

Background and Aim: To evaluate the evidence comparing radiofrequency ablation (RFA) and surgical resection (RES) on the treatment of hepatocellular carcinoma (HCC) using meta‐analytical techniques. Methods: Literature search was undertaken until March 2011 to identify comparative studies evaluating survival rates, recurrence rates, and complications. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with either the fixed or random effect model. Results: These studies included a total of 877 patients: 441 treated with RFA and 436 treated with RES. The overall survival was significantly higher in patients treated with RES than RFA at 1, 3 and 5 years (respectively: OR: 0.50, 95% CI: 0.29–0.86; OR: 0.51, 95% CI: 0.28–0.94; OR: 0.62, 95% CI: 0.45–0.84). In the RES group the 1, 3, and 5 years recurrence‐free survival rates were significantly higher than the RFA group (respectively: OR: 0.65, 95% CI: 0.44–0.97; OR: 0.65, 95% CI: 0.47–0.89; OR: 0.52, 95% CI: 0.35–0.77). RFA had a higher rate of local recurrence (OR: 4.08, 95% CI: 2.03–8.20). For tumors ≤ 3 cm RES was better than RFA in the 3‐year overall survival rates (OR: 0.38, 95% CI: 0.16–0.89). Conclusions: Surgical resection was superior to RFA in the treatment of HCC. However, the findings have to be carefully interpreted due to the lower level of evidence.     

肝切除术和肝移植术治疗的肝细胞癌患者3年随访结局比较

目的比较肝切除术(LR)和肝移植术(LT)两种方法治疗的肝细胞癌(HCC)患者3年的随访结局。方法回顾性分析2009年3月—2014年3月于首都医科大学附属北京佑安医院接受手术治疗的171例HCC患者临床资料,根据治疗方法分为LR组(n=83)和LT组(n=88),比较两组患者的临床资料差异。分类资料组间比较使用χ^2检验。采用Kaplan-Meier生存曲线和log-rank检验分析两组之间无瘤生存期和总生存期的差异;用Cox比例风险模型分别对无瘤生存期和总生存期进行单因素和多因素分析。结果与LR组对比,LT组的单发肿瘤比例(45.78%vs 85.23%)、直径<3 cm的肿瘤比例(15.66%vs 67.05%)、高Child-Pugh分期比例(9.64%vs 26.14%)明显偏高,LT组的肿瘤复发率明显偏低(48.19%vs 32.95%),且差异具有统计学意义(χ^2值分别为29.649、46.383、7.833、4.121,P值分别为<0.001、<0.001、0.005、0.042);LR治疗患者的无瘤生存率是46.02%,而LT治疗患者的无瘤生存率为80.71%,两者比较具有统计学差异(P=0.006);LR治疗患者的总生存率是76.44%,而LT治疗患者的总生存率为86.99%,差异无统计学意义(P=0.219);Cox单因素和多因素分析均显示治疗方法是无瘤生存期的独立危险因素[RR(95%CI)分别为3.383(1.334~8.579)、0.239(0.093~0.612),P值均<0.05],而治疗方法对于总生存期的预测未达到统计学差异(P=0.232)。结论LT更倾向于选择肝功能储备较差的早期肝癌患者,3年无瘤生存率较好。     

Surgical treatment for early hepatocellular carcinoma: comparison of resection and liver transplantation

Purpose  

The optimum strategy, hepatic resection (HR) or liver transplantation (LT), for treatment of early hepatocellular carcinoma (HCC) associated with liver diseases of Child–Pugh A is far from established. The aim of this study was to compare and determine which strategy is optimal for HCC fulfilling the Milan criteria.     

Adjuvant transarterial chemoembolization for patients after curative resection of hepatocellular carcinoma: a meta-analysis

Objective: To evaluate the efficacy and safety of adjuvant transarterial chemoembolization (TACE) after curative hepatectomy in improving the survival of patients with primary hepatocellular carcinoma (HCC).

Methods: MEDLINE, Embase and the Cochrane Library were searched for randomized or nonrandomized studies comparing postoperative adjuvant TACE with curative resection alone. Meta-analysis was performed after converting time-event data into a hazard ratio (HR), using an inverse diversity model.

Results: Eight randomized controlled trials (RCTs) and 12 retrospective studies matched the selection criteria, thereby including 3191 patients (779 in RCT, 2412 in observational studies) for the meta-analysis. The meta-analysis showed that receiving adjuvant TACE was associated with improved overall survival (OS, ln[HR]?=?0.70, 95%CI: 0.63–0.78, p?<?.001) and recurrence-free survival (RFS, ln[HR]?=?0.69, 95%CI: 0.63–0.76, p?<?.001) after curative hepatectomies. The results of observational studies were consistent with those of RCTs. Furthermore, meta-regression was utilized to detect study-level factors associated with treatment outcome. It revealed that overall survival was similar among patients treated with various combinations of chemotherapeutic drugs. Subgroup analyses demonstrated that repeated TACE interventions do not provide a higher survival benefit compared with a single course, and patients with a single tumor or tumor size?≥5cm might stand to benefit the most from adjuvant TACE therapy.

Conclusions: This meta-analysis demonstrated that postoperative adjuvant TACE could achieve higher OS and RFS than surgical resection alone. However, these results need to be validated through further high-quality clinical studies.     

Comparative analysis of outcomes after liver resection and liver transplantation for early stages hepatocellular carcinoma in HIV-infected patients. An intention-to-treat analysis

BackgroundTo address the results of resection for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers, and to compare them against survival after liver transplantation (LT).MethodsAll patients with HIV and HCC listed for LT (candidates = LTc+) or resection (LR+) between 2000 and 2017 in our centre were analysed and compared for overall survival (OS) and disease-free survival (DFS).ResultsThe LTc + group (n = 43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than LR + group (n = 15). One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR + groups, respectively (p = 0.746). Eleven LTc + patients dropped out. After LT, OS was 81%, 68% and 59% (no difference with LR + group; p = 0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR + group (p = 0.062).ConclusionThis was the largest series of resections for HCC in HIV + patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of higher recurrence rate, resection could be integrated in the global armoury of liver surgeons.     

Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation

Liver transplantation is proposed as the best therapy for early hepatocellular carcinoma in cirrhotic patients. However, the confrontation with the results obtained by surgical resection has never been done on an intention-to-treat basis. Between 1989 and 1997, 164 out of 1,265 patients with hepatocellular carcinoma were evaluated for surgery. Seventy-seven (48 men, mean 61 years of age, 74 Child-Pugh class A, size 33 +/- 18 mm) were resected (first line option) and 87 (65 men, mean 55 years of age, 50 Child-Pugh class B/C, size 24 +/- 14 mm) were selected for transplantation. The 1-, 3-, and 5-year "intention-to-treat" survival was 85%, 62%, and 51% for resection and 84%, 69%, and 69% for transplantation (8 drop-outs on waiting list). Bilirubin and clinically relevant portal hypertension were independent survival predictors after resection. Thereby, the 5-year survival of the best candidates (absence of clinically relevant portal hypertension, n = 35) was 74%, whereas it was 25% for the worst candidates (portal hypertension and bilirubin >/=1 mg/dL, n = 27) (P <.00001). The variable "drop-out on waiting list" was the sole survival predictor after transplantation. The 2-year survival rate of patients evaluated for transplantation was 84% in the 1989 to 1995 period (mean waiting time, 62 days; no drop-outs) and 54% during 1996 to 1997 (mean waiting time, 162 days; 8 drop-outs)(P <.003). This outcome was significantly lower than that of the best candidates for resection (P =.002). In conclusion, a proper selection of candidates for resection promotes better results than transplantation, in which the results are significantly hampered by the growing incidence of drop-outs because of the increasing waiting time.     

Comparison of surgical resection and transcatheter arterial chemoembolization for large hepatocellular carcinoma: a systematic review and meta-analysis

Introduction and ObjectivesLarge primary hepatocellular carcinoma (HCC) has a high mortality rate and a variety of treatments. Surgery and transcatheter arterial chemoembolization (TACE) are important treatments. Which could be better remain debatable. The objective of the study is to compare the long-term overall survival of surgical resection (SR) and the use of TACE in patients with large hepatocellular carcinoma.Materials and MethodsWe assessed clinical trials through PubMed, Medline, Embase, and the Cochrane Library up to March 2022. Two researchers independently screened articles, extracted data, and assessed the study quality according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)guidelines. The primary outcome was overall survival (OS). The secondary outcomes were OS after propensity scores matching (PSM) and progression-free survival (PFS).ResultsA total of 14 studies, including 3609 patients, were enrolled in the meta-analysis. The meta-analysis indicated a significant improvement in the 1-year OS, 3-year OS, and 5-year OS favoring SR over TACE (OR = 2.19, 95% CI 1,60–3.00; OR = 3.47, 95% CI 2.47–4.88; OR = 2.72, 95% CI 2.03–3.64, p < 0.001, random model). The results were consistent across subgroups of tumor size and tumor numbers (p > 0.05). The pooled outcome indicated that 1-year OS, 3-year OS, and 5-year OS after PSM were higher in the SR group than in the TACE group (p < 0.001).ConclusionsThis meta-analysis indicates that among patients with large primary hepatocellular carcinoma, the overall survival rate of patients undergoing surgical resection was higher than that of patients undergoing TACE.     

Surgical and oncologic outcomes following laparoscopic versus open liver resection for hepatocellular carcinoma: A meta-analysis

Aim: Laparoscopic hepatectomy has become a common method for treatment of hepatocellular carcinoma (HCC) nowadays, but the oncologic risks of laparoscopic liver resection for HCC are still under investigation. We performed a meta‐analysis to quantitatively compare surgical and oncologic outcomes of patients with HCC undergoing laparoscopic versus open hepatectomy. Methods: Systematic review and meta‐analysis of studies comparing laparoscopic with open liver resection for HCC. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5. Results: Ten studies comprising 627 patients were eligible for inclusion. The overall rate of conversion to open surgery was 6.6%. The laparoscopic group had significantly less blood loss by 223.17 mL (95% confidence interval [CI]: ?331.81, ?114.54; P < 0.0001), fewer need for transfusions (odds ratio [OR]: 0.42, 95% CI: 0.22, .079; P = 0.007), shorter hospital stay by 5.05 days (95% CI: ?7.84, ?2.25; P = 0.0004) and fewer postoperative complications (OR: 0.50; 95% CI: 0.32, 0.77; P = 0.002). No significant differences were found concerning surgery margin (weighted mean differences [WMD], 0.55; 95% CI: ?0.71, 1.80; P = 0.39), resection margin positive rate (OR, 0.63; 95% CI: 0.25, 1.54; P = 0.31) and tumor recurrence (OR, 0.79; 95% CI: 0.49, 1.27; P = 0.33). In the 244 patients that underwent laparoscopic hepatectomy of all 10 studies included, no patients developed tumor recurrence at the site of resection margin, peritoneal dissemination or trocar‐site metastases. Conclusions: On currently available evidence, laparoscopic resection appears not to affect oncologic outcomes and increase tumor recurrence. It also offers less blood loss, decreased rate of intraoperative transfusion and shorter lengths of hospital stay. Laparoscopic resection is a safe and feasible choice for selected patients with HCC.     

Salvage liver transplantation in the treatment of hepatocellular carcinoma: a meta-analysis

AIM: To evaluate survival and recurrence after salvage liver transplantation (SLT) for the treatment of hepatocellular carcinoma (HCC) compared with primary liver transplantation (PLT) using a meta-analysis.METHODS: Literature on SLT versus PLT for the treatment of HCC published between 1966 and July 2011 was retrieved. A meta-analysis was conducted to estimate pooled survival and disease-free rates. A fixed or random-effect model was established to collect the data.RESULTS: The differences in overall survival and disease-free survival rates at 1-year, 3-year and 5-year survival rates were not statistically significant between SLT group and PLT group (P > 0.05). After stratifying the various studies by donor source and Milan criteria, we found that: (1) Living donor liver transplantation recipients had significantly higher 1-year survival rate, lower 3-year and 5-year survival rates compared with deceased-donor liver transplantation (DDLT) recipients. And in DDLT recipients they had better 1-year and 5-year disease-free survival rate in SLT group; and (2) No difference was seen in 1-year, 3-year and 5-year survival rates between two groups who beyond Milan criteria at the time of liver transplantation.CONCLUSION: SLT can be effectively performed for patients with recurrence or deterioration of liver function after hepatectomy for HCC. It does not increase the perioperative mortality and has a similar long-term survival rates compared to PLT.     

Systematic review and meta-analysis of outcomes after liver resection in patients with hepatocellular carcinoma (HCC) with and without bile duct thrombus

IntroductionThis meta-analysis aimed to compare perioperative and survival outcomes in patients who underwent hepatectomy with and without Bile Duct Tumour Thrombus (BDTT).MethodsA comprehensive search of Cochrane Library, PubMed, MEDLINE and EMBASE was performed to identify relevant articles. The perioperative, postoperative and long term outcomes were compared.ResultsEleven studies including 6051 patients met the inclusion criteria. The perioperative outcomes were comparable between the 2 groups. The BDTT group had higher proportion poorly differentiated tumours (OR = 1.87, X² = 10.00, df = 6, p = 0.002, I² = 40%), Lymphovascular invasion (LVI) (OR = 4.85, X² = 28.21, df = 9, p = <0.001, I² = 68%) and Macrovascular invasion (MVI) (OR = 5.41, X² = 8.73, df = 9, p = <0.001, I² = 0%). There was no difference in 1 and 3 year survival, however 5-yr survival was poorer in the BDTT group (OR = 0.37, X² = 37.04, df = 7, p = <0.001, I² = 81%). The mean difference (MD) in overall survival in the BDTT group was −20 months [−32.31, −7.06], p = 0.002, I² = 95%.ConclusionPatients with HCC with BDTT had more advanced stage HCC with adverse histological features including higher rates of MVI, LVI and poor differentiation. Hepatectomy in this group of patients offers similar survival at 3 years but inferior long-term survival and should be considered when feasible.Abbreviations: BDTT, bile duct tumour thrombus; HCC, hepatocellular carcinoma; BCLC, Barcelona clinical liver cancer; RR, risk ratio; CI, confidence interval; NOS, Newcastle–Ottawa score     

射频消融对比手术切除治疗小肝癌的Meta分析

目的:比较射频消融术与外科手术切除在治疗小肝癌中的疗效.方法:计算机检索1991-2011年发表的有关采用射频消融术(radiofrequency ablation,RFA)与外科手术肝切除(surgical hepatic resection,HR)治疗小肝癌的对照试验,按照Cochrane系统评价员手册4.2.2版所推荐的质量评价标准来筛选试验,评价纳入研究的方法学质量,用RevMan5.0.25版软件对研究进行系统评价及Meta分析.结果:共纳入2个随机对照试验,9个非随机对照试验,其中英文9篇,中文1篇,韩文1篇.所纳入的研究共包括2965例患者:其中射频消融组患者1459例、外科手术切除组患者1506例.Meta分析表明:外科手术组在3年、5年生存率及1、3、5年无瘤生存率上明显高于射频消融组,差异均有统计学意义(P<0.05),两者1年生存率相比无显著差异(P>0.05);术后严重并发症射频消融组明显低于外科手术组(P<0.05).结论:现有的证据表明,对于小肝癌,射频消融术后严重并发症明显少于外科手术切除,但是外科手术切除治疗小肝癌总体疗效仍明显优于射频消融治疗.     

Medicaid expansion is associated with a higher likelihood of early diagnosis,resection, transplantation,and overall survival in patients with hepatocellular carcinoma

BackgroundWe examined the association between Medicaid expansion (ME) and the diagnosis, treatment, and survival of patients with hepatocellular carcinoma (HCC).MethodsWe identified patients with HCC <65yrs with Medicaid or without insurance within the National Cancer Database before (2010–2013) or after (2015–2017) ME with early (cT1) or intermediate/advanced (cT2-T4 or M1) disease.ResultsWe identified 4848 patients with HCC before and 4526 after ME. Prior to ME, there was no association between future ME status and diagnosis of early HCC (34.5% vs. 32.9%). There was no association between future ME status and treating early HCC with ablation, resection, or transplantation. Patients with early HCC in future ME states were less likely to die (HR = 0.81, 95% CI: 0.67–0.98). After ME, patients in ME states were more likely to be diagnosed with early HCC (39.2% vs. 32.1%). Patients with early disease in ME states were more likely to undergo resection (OR=1.78, 95% CI: 1.16–2.75) or transplantation (OR=3.20, 95% CI: 1.40–7.33). There was a further associated decrease in the hazard of death (HR=0.68, 95% CI: 0.54–0.86).ConclusionME was associated with early diagnosis of HCC. For early HCC, ME was associated with increased utilization of resection and transplantation and improvement in survival.     

Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis

BackgroundOrgan allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT).MethodsThe National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vs LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan–Meier survival analyses and log-rank tests were performed.Results1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size.DiscussionHCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.     

Liver transplantation outcomes in 1,078 hepatocellular carcinoma patients: a multi-center experience in Shanghai, China

Purpose  To evaluate current selection criteria for patients undergoing liver transplantation (LT) in response to hepatocellular carcinoma (HCC), and to analyze the prognostic factors for successful transplantation. Methods  We evaluated the outcome of 1,078 consecutive patients with HCC from the Shanghai Multi-Center Collaborative LT Group who underwent LT over a 6-year period. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan–Meier survival estimates and log-rank tests. Multivariate study with Cox’s proportional hazard model was used to evaluate the prognosis-relative aspects. Results  We determined that expansion of Milan criteria to include: a solitary lesion ≤9 cm in diameter, no more than three lesions with the largest ≤5 cm, a total tumor diameter ≤9 cm without macrovascular invasion, lymph node invasion and extrahepatic metastasis (referred to as the “Shanghai criteria”), resulted in overall survival (OS) and disease-free survival (DFS) rates that were similar to the Milan criteria. Multivariate analysis using the Cox proportional hazards regression model showed that the Child-Pugh-Turcotte classification (P = 0.010, 0.000), tumor differentiation (P = 0.001, 0.000), tumor size (P = 0.000, 0.000) and number (P = 0.014, 0.016), macrovascular invasion (P = 0.022, 0.000) and alpha-fetoprotein (AFP) levels (P = 0.031, 0.003) were independent predictors of OS and DFS, while post-LT chemotherapy (OS, P = 0.000) and tumor encapsulation (DFS, P = 0.038) were independent predictors of OS or DFS. Conclusion  Shanghai criteria expanded the current criteria while maintaining similar survival. J. Fan, G.-S. Yang, Z.-R. Fu, Z.-H. Peng, Q. Xia, C.-H. Peng, J.-M. Qian, J. Zhou and Y. Xu contributed equally to this work. This is an original work by all the authors from the Shanghai Multi-center Collaborative Liver Transplantation Group.     

Survival and prognostic factors after transplantation,resection and ablation in a national cohort of early hepatocellular carcinoma

BackgroundIn patients with early hepatocellular cancer (HCC) and preserved liver function, the choice between transplantation, resection and ablation and which factors to consider is not obvious and guidelines differ. In this national cohort study, we aimed to compare posttreatment survival in patients fulfilling predefined criteria, and to analyse preoperative risk factors that could influence decision.MethodsWe used data from HCC-patients registered with primary transplantation, resection or ablation 2008–2016 in the SweLiv-registry. In Child A-subgroups, 18–75 years, we compared survival after transplantation or resection, with different tumour criteria; either corresponding to our transplantation criteria (N = 257) or stricter with single tumours ≤50 mm (N = 159). A subgroup with single tumours ≤30 mm, compared all three treatments (N = 193).ResultsWe included 1022 HCC-patients; transplantation n = 223, resection n = 438, ablation n = 361. In the transplant criteria subgroup, differences in five-year survival, adjusted for age and gender, were not significant, with 71.2% (CI 62.3–81.3) after transplantation (n = 109) and 63.5% (CI 54.9–73.5) after resection (n = 148). Good liver function (Child 5 vs. 6, Albumin ≥36), increased the risk after transplantation, but decreased the risk after resection and ablation.ConclusionEven within Child A, detailed liver function assessment is important before treatment decision, and for stratifying survival comparisons.     

Laparoscopic vs open approach to resection of hepatocellular carcinoma in patients with known cirrhosis: Systematic review and meta-analysis

AIM: To review the currently available literature comparing laparoscopic to open resection of hepatocellular carcinoma (HCC) in patients with known liver cirrhosis.METHODS: A literature search of MEDLINE, EMBASE, and Cochrane databases was conducted. The search terms used included (laparoscopic OR laparoscopy) AND (hepatic or liver) AND (surgery or resection) AND “hepatocellular carcinoma” AND (cirrhosis or cirrhotic). Furthermore, to widen the search, we also used the “related articles” section. Studies reporting a comparison of outcomes and methods of open vs laparoscopic hepatic resection for HCC in patients with liver cirrhosis were included. Meta-analysis of results was performed using a random effects model to compute relative risk (RR) and for dichotomous variables and standard mean differences (SMD) for continuous variables.RESULTS: A total of 420 patients from 4 cohort studies were included in final analysis. Patients undergoing laparoscopic procedures had statistically less blood loss compared to the open cohort, SMD of -1.01 (95%CI: -1.23-0.79), P < 0.001, with a reduced risk of transfusion, RR = 0.19 (95%CI: 0.09-0.38), P < 0.001. A wider clearance at tumour resection margins was achieved following a laparoscopic approach, SMD of 0.34 (95%CI: 0.08-0.60), P = 0.011. No significant difference was noted between laparoscopic and open resection operative times, SMD of -0.15 (95%CI: 0.35-0.05), P = 0.142. The overall RR of suffering from postoperative morbidity is 0.25 in favour of the open surgery cohort (95%CI: 0.17-0.37), P < 0.001. Patients under-going laparoscopic surgery had significantly shorter length of stays in hospital compared to the open cohort, SMD of -0.53 (95%CI: -0.73 to -0.32), P < 0.001.CONCLUSION: This review suggests that laparoscopic resection of hepatocellular carcinoma in patients with cirrhosis is safe and may provide improved patient outcomes when compared to the open technique.