Preoperative transarterial chemoembolization for barcelona clinic liver cancer stage A/B hepatocellular carcinoma beyond the milan criteria: a propensity score matching analysis

BackgroundDebate continues about the benefits of preoperative transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). This study aimed to assess the impact of preoperative TACE on long-term outcomes after curative resection for HCC beyond the Milan criteria.MethodsPatients who underwent HCC resection exceeding the Milan criteria without macrovascular invasion between 2015 and 2018 were identified (n = 393). Short- and long-term outcomes were compared between patients who underwent preoperative TACE and patients who did not before and after propensity score matching (PSM). Factors associated with recurrence after resection were analyzed.Results100 patients (25.4%) underwent preoperative TACE. Recurrence-free survival (RFS) and overall survival (OS) were comparable with patients who underwent primary liver resection. 7 patients (7.0%) achieved total necrosis with better RFS compared with patients who had an incomplete response to TACE (P=0.041). PSM created 73 matched patient pairs. In the PSM cohort, preoperative TACE improved RFS (P=0.002) and OS (P=0.003). The maximum preoperatively diagnosed tumor diameter (HR 3.230, 95% CI: 1.116–9.353; P=0.031) and hepatitis B infection (HR 2.905, 95%CI: 1.281–6.589; P=0.011) were independently associated with favorable RFS after HCC resection.ConclusionPreoperative TACE made no significant difference to perioperative complications and was correlated with an improved prognosis after surgical resection for patients with HCC beyond the Milan criteria.     

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: a propensity score matching analysis

BackgroundSurgical resection is a first-line curative option for hepatocellular carcinoma, but its role is still unclear in elderly patients. The aim of our study was to compare short- and long-term outcomes of laparoscopic and open liver resection in elderly patients with hepatocellular carcinoma.MethodsThe study included 665 consecutive hepatocellular carcinoma liver resection cases in patients with ≥70 years of age treated in eight European hospital centres. Patients were divided into laparoscopic and open liver resection groups. Perioperative and long-term outcomes were compared between these groups.ResultsAfter a 1:1 propensity score matching, 219 patients were included in each group. Clavien-Dindo grades III/IV (6 vs. 20%, p = 0.04) were lower in the laparoscopic than in the open matched group. Hospital stay was shorter in the laparoscopic than in the open matched group (5 vs. 7 days, p < 0.001). There were no significant differences between laparoscopic and open groups regarding overall survival and disease-free survival at 1-, 3- and 5- year periods.ConclusionLaparoscopic liver resection for hepatocellular carcinoma is associated with good short-term outcomes in patients with ≥70 years of age compared to open liver resection. Laparoscopic liver resection is safe and feasible in elderly patients with hepatocellular carcinoma.     

Transarterial chemoembolization can prolong survival for patients with metastatic hepatocellular carcinoma: a propensity score matching analysis

Background

In Asian countries, transarterial chemoembolization (TACE) is widely applied in hepatocellular carcinoma (HCC) patients with extra-hepatic metastasis in the absence of main portal vein thrombosis. However, its survival benefit is unclear. The study aimed to analyze the role of TACE in patients with metastatic HCC.

Methods

From 2002 to 2009, 2,165 consecutive HCC patients were retrospectively reviewed. Of the 893 Barcelona Clinic Liver Cancer stage C patients, 105 who had extra-hepatic metastasis on initial presentation without main portal vein thrombosis were enrolled, including 46 who received TACE (TACE group) and 59 who received supportive treatment (control group). Factors associated with survival were evaluated by multivariate analysis. Survival between the two groups was compared by propensity score matching analysis.

Results

Median survival in the TACE and control groups was 6.6 and 3.2?months, respectively (p?<?0.001). By multivariate analysis, TACE [hazard ratio (HR)?=?0.476, p?=?0.002], tumor size >10?cm (HR?=?1.606, p?=?0.045), and alpha-fetoprotein (AFP) >2,000?ng?ml^?1 (HR?=?1.599, p?=?0.037) were factors associated with survival. After propensity score matching analysis, a better survival was noted in the TACE group (median survival 4.0 vs. 3.0?months, p?=?0.029). Subgroup analysis showed that patients with tumor size ??10?cm and AFP levels ??2,000?ng?ml^?1 had the best survival from TACE. Smaller tumor size is the only independent predictor for survival longer than 6?months in patients receiving TACE.

Conclusions

TACE provides survival benefit for metastatic HCC patients. Prospective randomized controlled trials are warranted to delineate the role of combining TACE with sorafenib or other treatment for metastatic HCC.     

Medical treatment of unresectable hepatocellular carcinoma: Going beyond sorafenib

Even though Sorafenib has radically changed the natural history of those hepatocellular carcinoma patients who are not amenable for curative treatments, further therapeutic improvements are badly needed. As it was for Sorafenib, our increasingly refined understanding of the complex mechanisms underlying HCC carcinogenesis are the starting point for the future development of such treatments. Presently, a number of molecularly targeted agents are in different stages of development for this once orphan cancer. Indeed, several pathways are presently being explored to identify potentially active drugs, including epidermal growth factor receptor, vascular endothelial growth factor/vascular endothelial growth factor receptors, mammalian target of rapamycin, phosphatidyl-inositol-3-kinase/Akt, insulin growth factor, Aurora kinase, Wnt/β-catenin, retinoic acid receptor and hepatocyte growth factor/C-Met. This review is aimed at addressing the results obtained so far with these newer drugs, also considering the challenges we shall face in the near future, including the issue of response evaluation and identification of predictive/prognostic biomarkers.     

Hepatic resection compared to percutaneous ethanol injection for small hepatocellular carcinoma using propensity score matching

BACKGROUND: Several surgical and non-surgical therapeutic modalities have been used for the treatment of hepatocellular carcinoma (HCC). There have been several studies comparing hepatic resection (HR) and percutaneous ethanol injection (PEI) for the treatment of HCC. However, there is still disagreement about the best treatment modality. METHODS: From 130 patients undergoing HR, 116 patients were individually matched to 116 controls from 249 patients undergoing PEI using propensity score matching to overcome possible biases in non-randomized study. Survival analyses were undertaken to compare these propensity score-matched groups. RESULTS: After matching by propensity score, the major clinical outcomes in the HR (n = 116) and the PEI (n = 116) groups were found to be similar. The 1-, 3- and 5-year overall survival rates were higher in the HR group (94.8%, 76.5% and 65.6%) compared to the PEI group (95.7%, 73.5% and 49.3%) (P = 0.059). The cumulative 1-, 3- and 5-year disease-free survival rates showed the same trend (HR: 76.1%, 50.6% and 40.6%; PEI: 62.6%, 25.5% and 19.1%) (P < 0.001). However, when stratified by Child-Pugh classification, it was no longer the case in the Child B patients. Single intrahepatic recurrence was the most common pattern of tumor recurrence after both treatments. CONCLUSIONS: Patients undergoing HR had a better survival profile than those undergoing PEI. However, when considering which technique to use for optimal HCC management, the individual patient's hepatic function must be considered.     

Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: A review

Liver transplantation(LT) has been accepted as an effective therapy for hepatocellular carcinoma(HCC). The Milan criteria(MC) are widely used across the world to select LT candidates in HCC patients. However, the MC may be too strict because a substantial subset of patients who have HCC exceed the MC and who would benefit from LT may be unnecessarily excluded from the waiting list. In recent years, many extended criteria beyond the MC were raised, which were proved to be able to yield similar outcomes compared with those patients meeting the MC. Because the simple use of tumor size and number was insufficient to indicate HCC biological features and to predict the risk of tumor recurrence, some biological markers such as Alphafetoprotein, Des-Gamma-carboxy prothrombin and the neutrophil-to-lymphocyte ratio were useful in selecting LT candidates in HCC patients beyond the MC. For patients with advanced HCC, downstaging therapy is an effective way to reduce the tumor stage to fulfill the MC by using liver-directed therapy such as transarterial chemoembolization, radiofrequency ablation and percutaneous ethanol injection. This article reviews the recent advances in LT for HCC beyond the MC.     

Microwave ablation versus radiofrequency ablation for perivascular hepatocellular carcinoma: a propensity score analysis

BackgroundTo compare the efficacy and safety of microwave ablation (MWA) and radiofrequency ablation (RFA) as first-line treatments for perivascular HCC.MethodsThis multicentre study enrolled 170 patients with perivascular HCC who underwent MWA or RFA. The ablation response, progression-free survival (PFS), overall survival (OS), and complications between the treatment groups for the total and propensity score-matched (PSM) cohorts were compared.ResultsThe disease control rates for MWA and RFA were similar in total (94% vs. 91%, p = 0.492) and PSM (93% vs. 93%, p = 1.00) cohorts. The PFS rates at 1, 3, and 5 years were 71%, 55% and 52% in MWA group and 61%, 33% and 28% in RFA group (p = 0.017). The OS rates were comparable between two groups in total (p = 0.249) and PSM cohorts (p = 0.345). In subgroup analyses, the PFS of patients with periportal HCC (45 vs. 36 months, p = 0.048) and a single HCC nodule (51 vs. 42 months, p = 0.014) were significantly better in MWA group than RFA. Major complications were more frequent in the MWA group than in RFA (27% vs. 7%, p < 0.001).ConclusionCompared with RFA, MWA provides better control of tumour progression especially in periportal HCC or single-nodule perivascular HCC patients.     

Thymosin alpha-1 therapy improves postoperative survival after curative resection for solitary hepatitis B virus-related hepatocellular carcinoma: A propensity score matching analysis

Thymosin alpha-1 (Tα1) is an immunomodulatory and antiviral agent with potential effects on chronic hepatitis B and liver cancer. Its impact on solitary hepatocellular carcinoma (HCC) remains controversial, so we aimed to investigate the efficacy of Tα1 in solitary HBV-related HCC patients after curative resection.Between May 2010 and April 2016, 468 patients with solitary HBV-related HCC after curative resection were analyzed. Propensity score matching (PSM) was used to minimize confounding variables. Risk factors were identified by the Cox proportional hazards model. Recurrence-free survival (RFS) rates, overall survival (OS) rates, immunological, and virologic response were compared.The median follow up was 60.0 months. Immunological response improved in the Tα1 group compared with the control group (P < .001) but the virologic response was similar between 2 groups after 24 months. Patients with Tα1 therapy had better RFS and OS before (P = .018 and P < .001) and after (P = .006 and P < .001) propensity matching. Multivariate analysis revealed that Tα1 therapy was an independent prognostic factor for both OS (P < .001, HR = 0.308, 95% CI: 0.175–0.541) and RFS (P < .001, HR = 0.381, 95% CI: 0.229–0.633).Tα1 as an adjuvant therapy improves the prognosis of solitary HBV-related HCC patients after curative liver resection.     

Transarterial chemoembolization as initial treatment for unresectable hepatocellular carcinoma in southern China

AIM:To identify prognostic factors from pretreatment variables of the initial transarterial chemoembolization(TACE)procedure in unresectable hepatocellular carcinoma(HCC). METHODS:One thousand and five hundred and sixtynine patients with unresectable HCC underwent TACE as initial treatment were retrospectively studied.Pretreatment variables of the initial TACE procedure with a P value less than 0.05 by univariate analysis were subjected to Cox proportional hazards model. RESULTS:The median overall survival ...