Interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma after hepatectomy: a multicenter population-based study.

An interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma (ES-HHCC) after hepatectomy is still lacking. This study was aimed at exploring the independent risk parameters and developing an interactive model for predicting the cancer-specific survival (CSS) of ES-HHCC. Data from patients with ES-HHCC who underwent hepatectomy were collected. The dimensionality of the clinical features was reduced by least absolute shrinkage and selection operator regression and further screened as predictors of CSS by Cox regression. Then, an interactive prediction model was developed and validated. Among the 514 screened patients, 311 and 203 of them were assigned into the training and validation cohort, respectively. Six independent variables, including alpha-fetoprotein, cirrhosis, microvascular invasion, satellite, tumor morphology, and tumor diameter, were identified and incorporated into the prediction model for CSS. The model achieved C-indices of 0.724 and 0.711 in the training and validation cohorts, respectively. Calibration curves showed general consistency in both cohorts. Compared with single predictor, the model had a better performance and greater benefit according to the time-independent receiver operating characteristic curve and decision curve analysis (P < 0.05). The calculator owned satisfactory accuracy and flexible operability for predicting the CSS of ES-HHCC, which could serve as a practical tool to stratify patients with different risks, and guide decision-making.

Development of preoperative and postoperative machine learning models to predict the recurrence of huge hepatocellular carcinoma following surgical resection.

Resection has been commonly utilized for treating huge hepatocellular carcinoma (HCC) with a diameter of ≥10 cm; however, a high rate of mortality is reported due to recurrence. The present study was designed to predict the recurrence following resection based on preoperative and postoperative machine learning models. In total, 1,082 patients with HCC who underwent liver resection in the Eastern Hepatobiliary Surgery Hospital cohort between January 2008 and December 2016 were divided into a training cohort and an internal validation cohort. In addition, 164 patients from Mengchao Hepatobiliary Hospital cohort between January 2014 and December 2016 served as an external validation cohort. The demographic information, and serological, MRI, and pathological data were obtained from each patient prior to and following surgery, followed by evaluating the model performance using the concordance index, time-dependent receiver operating characteristic curves, prediction error cures, and a calibration curve. A preoperative random survival forest (RSF) model and a postoperative RSF model were constructed based on the training set, which outperformed the conventional models, such as the Barcelona Clinic Liver Cancer (BCLC), the 8th edition of the American Joint Committee on Cancer (AJCC 8th) staging systems, and the Chinese stage systems. In addition, the preoperative and postoperative RSF models could also re-stratify patients with BCLC stage A/B/C or AJCC 8th stage IB/II/IIIA/IIIB or Chinese stage IB/IIA/IIB/IIIA into low-risk, intermediate-risk, and high-risk groups in the training and the two validation cohorts. The preoperative and postoperative RSF models were effective for predicting recurrence in patients with huge HCC following hepatectomy.

Cirrhotic and non-cirrhotic huge hepatocellular carcinoma (≥ 10 cm): a comparative study of surgical management and follow-up treatment in a single institution.

PURPOSE: Liver resection (LR) of huge hepatocellular carcinoma (HCC) has increasingly been regarded as a viable option of enhanced efficacy for patients, but most studies have focused on comparing various tumor sizes and the outcomes of surgery. The study aim was to evaluate the clinicopathologic characteristics and surgical outcomes of huge HCC with and without cirrhosis that underwent LR, and to delineate the treatment for recurrence. METHODS: Sixty-three patients with huge HCC who underwent hepatectomy from 2010 to 2019 were enrolled and reviewed. Clinicopathological findings, surgical outcomes of the entire cohort, and differences between the cirrhotic and non-cirrhotic groups were analyzed. RESULTS: Forty patients (60.3%) had huge HCC with cirrhosis. Clinicopathological findings were not different between the two groups, except tumor size ≥ 15 cm (40% in cirrhosis vs 17.4% in non-cirrhosis, p = 0.024) and major portal vein tumor thrombus were detected only in the cirrhosis group (11 patients, p = 0.006). Extended LR was performed in 13 cirrhotic patients (32.5%) and in 1 non-cirrhotic patient (4.4%) (p = 0.010). Operative data, postoperative complications including postoperative liver failure, and pattern of recurrence were not different between the two groups. For the entire cohort, mortality rate was 1.5%. The 1-, 3-, and 5-year overall survival rates (OS) were 81%, 54%, and 39%. Multivariate analysis showed resection margin ≥ 0.1 cm was a good prognostic factor for OS (HR 0.247 (p = 0.017)). For tumor recurrence, local ablative treatment for liver recurrence and resection for lung recurrence provided good long-term outcomes. CONCLUSION: Although huge HCC with cirrhosis has been a more unfavorable tumor, LR still provided long-term survival with acceptable risk morbidity and mortality.

Liver resection for large and huge hepatocellular carcinoma: Predictors of failure, recurrence patterns, and prognoses.

BACKGROUND: Characteristic symptoms and signs are often absent in patients with hepatocellular carcinoma (HCC). As a result, many patients are not diagnosed until their tumors have grown to large (> 5cm) or huge sizes (> 10cm). Liver resection has traditionally been reserved for patients with small HCC, but more recently it is being used for patients with large and huge tumors. The aim of this study was to determine risk predictors of recurrence, patterns of recurrence, and survival rates for large and huge HCC patients who underwent curative liver resection. MATERIALS AND METHODS: We retrospectively identified a subgroup of patients who underwent liver resection for HCC with diameters 5 cm or larger. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to investigate potential risk factors for recurrence and death. RESULTS: Among 897 patients, the median follow-up was 48 (range, 5-140) months. The 1-, 3-, and 5-year RFS rates were 51.6%, 36.1%, and 30.1%, respectively, and OS rates were 80.2%, 55.4%, and 47.7%, respectively. Significant independent predictors of recurrence were preoperative satellite nodule (HR = 2.25; 95% CI, 1.17-4.31; p = .02), preoperative AFP levels above 400 ng/ml (HR = 1.23; 95% CI, 1.04-1.45; p = .01), resection margins of 1 cm or less (HR = 1.21; 95% CI, 1.00-1.46; p = .047), cirrhosis (HR = 2.64; 95% CI, 2.13-3.28; p < .001), and microvascular invasion (HR = 1.71; 95% CI, 1.45-2.20; p < .001). All of these except narrow resection margin were also independent risk factors of OS. CONCLUSIONS: Hepatic resection for patients with large and huge HCC without hepatic vascular invasion, extrahepatic metastases, or severe chronic liver disease results in acceptable long-term outcomes.

The Characteristics and Mortality of Chinese Herbal Medicine Users among Newly Diagnosed Inoperable Huge Hepatocellular Carcinoma (≥10 cm) Patients: A Retrospective Cohort Study with Exploration of Core Herbs.

For patients with inoperable huge hepatocellular carcinoma (H-HCC, tumor size ≥10 cm), treatment options are limited. This study aimed to evaluate the characteristics and outcomes of patients with H-HCC who use Chinese herbal medicine (CHM). Multi-institutional cohort data were obtained from the Chang Gung Research Database (CGRD) between 1 January 2002 and 31 December 2018. All patients were followed up for 3 years or until the occurrence of death. Characteristics of CHM users and risk of all-cause mortality were assessed, and core CHMs with potential pharmacologic pathways were explored. Among 1618 patients, clinical features of CHM users (88) and nonusers (1530) were similar except for lower serum α-fetoprotein (AFP) and higher serum albumin levels in CHM users. CHM users had significantly higher 3 year overall survival rates (15.0% vs. 9.7%) and 3 year liver-specific survival rates (13.4% vs. 10.7%), about 3 months longer median survival time, and lower risk of all-cause mortality. Core CHMs were discovered from the prescriptions, including Hedyotis diffusa Willd combined with Scutellaria barbata D.Don, Salvia miltiorrhiza Bunge., Curcuma longa L., Rheum palmatum L., and Astragalus mongholicus Bunge. CHM use appears safe and is possibly beneficial for inoperable H-HCC patients; however, further clinical trials are still required.

Benefits of step-by-step debulking microwave ablation for huge unresectable hepatocellular carcinoma patients after transcatheter arterial chemoembolization refractoriness.

OBJECTIVES: To compare the safety and efficacy of step-by-step debulking Microwave Ablation (MWA) with Transarterial Chemoembolization (TACE) monotherapy for huge (≥10 cm in diameter) unresectable hepatocellular carcinoma (HCC) after TACE refractoriness. METHODS: This is a multi-center retrospective study carried out on 599 patients with huge unresectable HCC who received TACE as first-line therapy at five hospitals from January 2009 to December 2018. A total of 103 patients with TACE refractoriness were divided into two cohorts: monthly step-by-step debulking MWA (n = 52) or continued TACE (n = 51). Overall survival (OS) and progression-free survival (PFS) after refractory TACE were evaluated. Residual liver and tumor volume were recorded for the MWA group. RESULTS: Median follow-up period was 24.3 months and median OS and PFS were significantly longer in the MWA group than in the TACE group (OS 21.0 vs. 11.7 months, PFS 6.1 vs. 3.0 months, both p < 0.001). The one-, two-, and three-year OS rates in the MWA and TACE groups were 73.1%, 46.6%, and 37.2% versus 43.1%, 15.5%, and 2.9%, respectively. Furthermore, the 0.5-, 1-, and 2-year PFS rates in the MWA and TACE groups were 51.9%, 36.5%, and 25.0% versus 27.5%, 11.8%, and 0, respectively. Multivariate analyses confirmed that switching to debulking MWA treatment was an independent favorable prognostic factor for PFS and OS. In the MWA group, the average additions of residual liver volume/total liver volume were 7.7% ± 6.7%, 7.2% ± 10.2%, and 10.1% ± 8.8% after the first, second, and third MWA procedure. CONCLUSION: Step-by-step debulking MWA can significantly improve long-term OS and PFS in patients with huge unresectable HCCs compared with repeated TACE after TACE refractoriness. Key PointThe debulking MWA therapy provides significantly longer OS and PFS than continued TACE for patients with huge unresectable HCCs after TACE-refractory, especially with complete tumor ablation.The most common complications were fever (48.1%) and pain (46.2%) in the MWA group. Two major complications (abdominal infection) were recorded in the MWA group, which recovered after symptomatic treatment.During the course of repeated MWAs, liver hyperplasia appeared mainly after the second MWA procedure and the average maximum increased RLV/TLV rate was 16.3%±12.7%.

An mALBI-Child-Pugh-based nomogram for predicting post-hepatectomy liver failure grade B-C in patients with huge hepatocellular carcinoma: a multi-institutional study.

OBJECTIVE: Post-hepatectomy liver failure (PHLF) is a severe complication in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. This study aims to develop a nomogram of PHLF grade B-C in patients with huge HCC (diameter ≥ 10 cm). METHODS: We retrospectively collected clinical information of 514 and 97 patients who underwent hepatectomy for huge HCC at two medical centers between 2016 and 2021. Univariate and multivariate analysis were carried out to screen the independent risk factors of PHLF grade B-C, which were visualized as a nomogram. RESULTS: Three Hundred Forty Three Thousand One Hundred Seventy One  and 97 HCC patients were included in the training cohort, internal validation cohort, and external validation cohort, with probabilities of PHLF grade B-C of 15.1%, 12.9%, and 22.7%, respectively. Pre-operative modified albumin-bilirubin (mALBI) grade (p < 0.001), Child-Pugh classification (p = 0.044), international normalized ratio (INR) (p = 0.005), cirrhosis (p = 0.019), and intraoperative blood loss (p = 0.004) were found to be independently associated with PHLF grade B-C in the training cohort. All the five independent factors were considered in the establishment of the nomogram model. In the internal validation cohort and external validation cohort, the area under receiver operating characteristic curve for the nomogram in PHLF grade B-C prediction reached 0.823 and 0.740, respectively. Divided into different risk groups according to the optimal cut-off value, patients in the high-risk group reported significantly higher frequency of PHLF grade B-C than those in the low-risk group, both in the training cohort and the validation cohort (p < 0.001). CONCLUSIONS: The proposed noninvasive nomogram based on mALBI-Child-Pugh and three other indicators achieved optimal prediction performance of PHLF grade B-C in patients with huge HCC.

Prognostic Significance of Tumor Growth Rate (TGR) in Patients with Huge Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization.

The prognostic value of the tumor growth rate (TGR) in huge hepatocellular carcinoma (HHCC) patients treated with transcatheter arterial chemoembolization (TACE) as an initial treatment remains unclear. This two-center retrospective study was conducted in 97 patients suffering from HHCC. Demographic characteristics, oncology characteristics, and some serological markers were collected for analysis. The TGR was significantly linear and associated with the risk of death when applied to restricted cubic splines. The optimal cut-off value of TGR was -8.6%/month, and patients were divided into two groups according to TGR. Kaplan-Meier analysis showed that the high-TGR group had a poorer prognosis. TGR (hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.23-3.43; p = 0.006), presence of portal vein tumor thrombus (PVTT) (HR, 1.93; 95% CI, 1.13-3.27; p = 0.016), and subsequent combination therapy (HR, 0.59; 95% CI, 0.35-0.99; p = 0.047) were independent predictors of OS in the multivariate analysis. The model with TGR was superior to the model without TGR in the DCA analysis. Patients who underwent subsequent combination therapy showed a longer survival in the high-TGR group. This study demonstrated that higher TGR was associated with a worse prognosis in patients with HHCC. These findings will distinguish patients who demand more personalized combination therapy and rigorous surveillance.

Efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization using CalliSpheres in treating huge hepatocellular carcinoma patients.

BACKGROUND: The treatment of huge hepatocellular carcinoma (HCC) is still challengeable due to its deteriorative heterogeneity, for which conventional transarterial chemoembolization (TACE) is proposed as an efficient therapy; however, drug-eluting beads TACE (DEB-TACE) is rarely reported in these patients. Thus, the current study aimed to explore the efficacy, prognostic factors, and safety of DEB-TACE using CalliSpheres in huge HCC patients. METHODS: Ninety-nine huge HCC patients treated by DEB-TACE using CalliSpheres were retrospectively reviewed. Treatment response, change of tumor markers, liver function indexes, progression-free survival (PFS), and adverse events were retrieved. RESULTS: Objective response rate (ORR) was 66.1%, 48.6%, and 23.8%, then disease control rate (DCR) was 85.5%, 67.6%, and 33.3% at month (M) 1, M3, and M6, respectively; furthermore, carcinoembryonic antigen (CEA) (p = 0.037), alpha fetoprotein (AFP) (p < 0.001), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) (p < 0.001) were all declined at 1 month after DEB-TACE. The median PFS was 8.3 (95% confidence interval: 6.0-10.6) months with 1-year and 2-year PFS rates of 38.5% and 15.5%, accordingly. Moreover, elevated China liver cancer (CNLC) stage (p = 0.036, hazard ratio (HR): 1.937) and abnormal cancer antigen 199 (p = 0.019, HR: 2.465) were correlated with unfavorable PFS. Besides, liver function indexes were not deteriorated after DEB-TACE. Lastly, main adverse events included pain (20.2%), fever (17.2%), nausea (14.1%), and vomit (9.1%), which were mild and manageable. CONCLUSION: DEB-TACE using CalliSpheres presents satisfying efficacy and tolerable safety in huge HCC patients, suggesting that it might be a good treatment option for these patients.

Efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) plus apatinib versus DEB-TACE alone in treating huge hepatocellular carcinoma patients.

BACKGROUND: Apatinib, a tyrosine kinase inhibitor, inhibits angiogenesis under the tumor hypoxic environment induced by drug-eluting bead transarterial chemoembolization (DEB-TACE), which is hypothesized to have synergic effect with DEB-TACE in treating hepatocellular carcinoma (HCC) patients. This study aimed to evaluate the efficacy and safety of DEB-TACE plus apatinib in treating huge HCC patients. METHODS: Totally, 73 huge HCC patients (tumor size > 10 cm) were screened and divided into DEB-TACE plus apatinib group (N = 34) or DEB-TACE group (N = 39) based on the treatment they received. Their clinical response and adverse events were retrieved. The progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: DEB-TACE plus apatinib achieved a trend of higher objective response rate (64.7% vs. 43.6%, P = 0.071), but similar disease control rate (88.2% vs. 79.5%, P = 0.314) than DEB-TACE alone. Moreover, DEB-TACE plus apatinib reached an improved PFS (median (95%CI): 19.0 months (15.5-22.5) vs. 10.9 months (8.0-13.8), P = 0.025) and OS (median (95%CI): 25.1 months (20.3-29.9) vs. 13.7 months (9.8-17.6), P = 0.042) than DEB-TACE alone. After adjustment by multivariate Cox's regression analyses, DEB-TACE plus apatinib (vs. DEB-TACE alone) was independently correlated with better PFS (HR: 0.420, P = 0.004) and OS (HR: 0.477, P = 0.022). Regarding safety, adverse events were mostly mild and manageable; also, they were of no difference between DEB-TACE plus apatinib and DEB-TACE alone (all P > 0.05). CONCLUSION: DEB-TACE plus apatinib achieves prolonged PFS and OS, while similar adverse events occurrence compared to DEB-TACE alone in huge HCC treatment.

Development and validation of prognostic nomograms for single large and huge hepatocellular carcinoma after curative resection.

AIM: The prediction model of postoperative survival for single large and huge hepatocellular carcinoma (SLH-HCC, diameter > 5.0 cm) without portal vein tumour thrombus has not been well established. This study aimed to develop novel nomograms to predict postoperative recurrence and survival of these patients. METHODS: Data from 2469 patients with SLH-HCC who underwent curative resection from January 2005 to December 2015 in China were retrospectively collected. Specifically, nomograms of recurrence-free survival (RFS) and overall survival (OS) using data from a training cohort were developed with the Cox regression model (n = 1012). The modes were verified in an internal validation cohort (n = 338) and an external cohort comprising four tertiary institutions (n = 1119). RESULTS: The nomograms of RFS and OS based on tumour clinicopathologic features (diameter, differentiation, microvascular invasion, α-fetoprotein), operative factors (preoperative transcatheter arterial chemoembolisation therapy, scope of liver resection and intraoperative blood transfusion), underlying liver function (albumin-bilirubin grade) and systemic inflammatory or immune status (neutrophil-to-lymphocyte ratio) achieved high C-indexes of 0.85 (95% confidence interval [CI], 0.79-0.91) and 0.86 (95% CI, 0.79-0.93) in the training cohort, respectively, which were significantly higher than those of the five conventional HCC staging systems (0.62-0.73 for RFS, 0.63-0.75 for OS). The nomograms were validated in the internal cohort (0.83 for RFS, 0.84 for OS) and external cohort (0.87 for RFS, 0.88 for OS) and had well-fitted calibration curves. Our nomograms accurately stratified patients with SLH-HCC into low-, intermediate- and high-risk groups of postsurgical recurrence and mortality. CONCLUSIONS: The two nomograms achieved optimal prediction for postsurgical recurrence and OS for patients with SLH-HCC after curative resection.

A novel preoperative predictive model of 90-day mortality after liver resection for huge hepatocellular carcinoma.

BACKGROUND: Hepatectomy for huge hepatocellular carcinoma (HCC) (diameter ≥10 cm) is characterized by high mortality. This study aimed to establish a preoperative model to evaluate the risk of postoperative 90-day mortality for huge HCC patients. METHODS: We retrospectively enrolled 1,127 consecutive patients and prospectively enrolled 93 patients with huge HCC who underwent hepatectomy (training cohort, n=798; validation cohort, n=329; prospective cohort, n=93) in our institute. Based on independent preoperative predictors of 90-day mortality, we established a logistic regression model and visualized the model by nomogram. RESULTS: The 90-day mortality rates were 9.6%, 9.2%, and 10.9% in the training, validation, and prospective cohort. The α-fetoprotein (AFP) level, the prealbumin levels, and the presence of portal vein tumor thrombosis (PVTT) were preoperative independent predictors of 90-day mortality. A logistic regression model, AFP-prealbumin-PVTT score (APP score), was subsequently established and showed good performance in predicting 90-day mortality (training cohort, AUC =0.87; validation cohort, AUC =0.91; prospective cohort, AUC =0.93). Using a cut-off of -1.96, the model could stratify patients into low risk (≤-1.96) and high risk (>-1.96) with different 90-day mortality rates (~30% vs. ~2%). Furthermore, the predictive performance for 90-day mortality and overall survival was significantly superior to the Child-Pugh score, the model of end-stage liver disease (MELD) score, and the albumin-bilirubin (ALBI) score. CONCLUSIONS: The APP score can precisely predict postoperative 90-day mortality as well as long-term survival for patients with huge HCC, assisting physician selection of suitable candidates for liver resection and improving the safety and efficacy of surgical treatment.

Efficacy of the association liver partition and portal vein ligation for staged hepatectomy for the treatment of solitary huge hepatocellular carcinoma: a retrospective single-center study.

BACKGROUND: The feasibility of association liver partition and portal vein ligation for staged hepatectomy (ALPPS) for solitary huge hepatocellular carcinoma (HCC, maximal diameter ≥ 10 cm) remains uncertain. This study aims to evaluate the safety and the efficacy of ALPPS for patients with solitary huge HCC. METHODS: Twenty patients with solitary huge HCC who received ALPPS during January 2017 and December 2019 were retrospectively analyzed. The oncological characteristics of contemporaneous patients who underwent one-stage resection and transcatheter arterial chemoembolization (TACE) were compared using propensity score matching (PSM). RESULTS: All patients underwent complete two-staged ALPPS. The median future liver remnant from the ALPPS-I stage to the ALPPS-II stage increased by 64.5% (range = 22.3-221.9%) with a median interval of 18 days (range = 10-54 days). The 90-day mortality rate after the ALPPS-II stage was 5%. The 1- and 3-year overall survival (OS) rates were 70.0% and 57.4%, respectively, whereas the 1- and 3-year progression-free survival (PFS) rates were 60.0% and 43.0%, respectively. In the one-to-one PSM analysis, the long-term survival of patients who received ALPPS was significantly better than those who received TACE (OS, P = 0.007; PFS, P = 0.011) but comparable with those who underwent one-stage resection (OS, P = 0.463; PFS, P = 0.786). CONCLUSION: The surgical outcomes of ALPPS were superior to those of TACE and similar to those of one-stage resection. ALPPS is a safe and effective treatment strategy for patients with unresectable solitary huge HCC.

Multi-institutional validation of novel models for predicting the prognosis of patients with huge hepatocellular carcinoma.

The population of patients with huge hepatocellular carcinoma (H-HCC diameter > 10.0 cm) is an odd group that is not well adjudicated in the current staging systems, whose prognosis after curative resection varies. We aimed to develop novel models to predict the long-term outcomes of patients with H-HCC without portal vein tumor thrombus after hepatectomy. There were 1076 H-HCC patients enrolled who underwent curative liver resection in five institutions in China. In total, 670 patients were recruited from our center and randomly divided into the training cohort (n = 502) and internal validation (n = 168) cohorts. Additionally, 406 patients selected from other four centers as the external validation cohort. Novel models were constructed based on independent preoperative and postoperative predictors of postsurgical recurrence (PSR) and postsurgical mortality (PSM) determined in multivariable cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell's concordance index (C index) and calibration curve and compared with five conventional HCC staging systems. PSR model and PSM model were constructed based on tumor number, microscopic vascular invasion, tumor differentiation, preoperative alpha-fetoprotein level, albumin-bilirubin grade, liver segment invasion, neutrophil-to-lymphocyte ratio or platelet-to-neutrophil ratio, and surgical margin or intraoperative blood transfusion. The C-indexes were 0.84 (95% CI, 0.78-0.90) and 0.85 (95% CI, 0.78-0.91) for the PSR and PSM models, respectively, which were substantially higher than those of the five conventional HCC staging systems (0.63-0.75 for PSR; 0.66-0.77 for PSM). The two novel models achieved more accurate prognostic predictions of PSR and PSM for H-HCC patients after curative liver resection.

Efficacy of combined bland embolization and chemoembolization for huge (≥10 cm) hepatocellular carcinoma.

INTRODUCTION: To assess the efficacy of combined therapy involving bland transarterial embolization using gelatin sponge particles (bland GS-TAE) followed by transarterial chemoembolization using lipiodol mixed with anticancer agents and GS particles (Lip-TACE) to reduce the adverse events and increase the therapeutic effect of Lip-TACE in the treatment of huge (≥10 cm) hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Twenty-one consecutive patients with huge HCCs (≥10 cm in diameter) were enrolled in this study. First, bland GS-TAE was performed to reduce the tumor volume, and then Lip-TACE was performed to control the remaining tumor at intervals of around three weeks. Tumor response, survival, and adverse events of this combined therapy were assessed. RESULTS: The tumor response was assessed three months after combined TACE, with complete response in 38.1% and partial response in 57.1% of cases. Severe adverse events were seen in two patients, acute cholecystitis and tumor rupture. The median survival time was 2.7 years, and the one-, two-, three-, and five-year overall survival rates were 76.2%, 66.7%, 42.9%, and 25.0%, respectively. CONCLUSION: Combined therapy involving bland GS-TAE followed by Lip-TACE can be performed safety and may improve survival in patients with huge HCCs.

Outcomes of conventional transarterial chemoembolization for hepatocellular carcinoma ≥10 cm.

AIM: To retrospectively evaluate the outcomes of conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) ≥10 cm. METHODS: Twenty-five patients with naïve HCC ≥10 cm (mean maximum tumor diameter, 130 ± 27.6 mm; single [n = 12], 2-9 [n = 6], and ≥10 [n = 7]) without extrahepatic spread treated with cTACE were eligible. Five (20%) had vascular invasion. Two to three stepwise cTACE sessions using iodized oil ≤10 mL in one cTACE session were scheduled. When the tumor recurred, additional cTACE was repeated on demand, if possible. Overall survival (OS) rates were calculated using the Kaplan-Meier method. The prognostic factors were evaluated using uni- and multivariate analyses. RESULTS: Stepwise cTACE sessions were completed for 20 (80%) patients, but could not be completed for four (16%). In the remaining (4%) patient, the whole tumor was embolized in one session. Additional treatment, mainly cTACE, was undertaken for 19 (76%) patients. The OS rates at 1, 3, and 5 years were 68, 34.7, and 23.1%, respectively. A tumor number of three was a significant prognostic factor (P = 0.020) and the 1-, 3-, and 4-year OS rates in patients with ≤3 and ≥4 tumors were 81.3 and 33.3, 55.6 and 11.1, and 38.9% and 0%, respectively. Whole tumor embolization and the serum level of protein induced by vitamin K absence or antagonist-II were also significant prognostic factors (P < 0.001 and P = 0.042, respectively). Bile duct complications requiring additional interventions developed in two (8%) patients. CONCLUSION: Conventional TACE is safe and effective for huge HCCs, but has limited effects in cases with four or more tumors.

Huge Hepatocellular Carcinoma Treated with Radical Hepatectomy after Drug-eluting Bead Transarterial Chemoembolization.

We performed split drug-eluting bead transarterial chemoembolization (DEB-TACE) in a patient with huge unresectable hepatocellular carcinoma and multiple intrahepatic metastases. However, TACE was discontinued at the fourth application because the tumor was fed by the cholecystic artery. As most intrahepatic metastases disappeared following DEB-TACE, the patient was able to undergo radical hepatectomy, and has maintained a complete response. DEB-TACE enables cancer treatment without reducing the liver or renal function. However, it is associated with a risk of ischemia in other organs in patients whose arteries feed both tumors and other organs; thus appropriate selection is required.

Efficacy of hepatic resection vs transarterial chemoembolization for solitary huge hepatocellular carcinoma.

AIM: To compare the efficacy of hepatic resection (HR) and transarterial chemoembolization (TACE) for patients with solitary huge (≥ 10 cm) hepatocellular carcinoma (HCC). METHODS: Records were retrospectively analyzed of 247 patients with solitary huge HCC, comprising 180 treated by HR and 67 by TACE. Long-term overall survival (OS) was compared between the two groups using the Kaplan-Meier method, and independent predictors of survival were identified by multivariate analysis. These analyses were performed using all patients in both groups and/or 61 pairs of propensity score-matched patients from the two groups. RESULTS: OS at 5 years was significantly higher in the HR group than the TACE group, across all patients (P = 0.002) and across propensity score-matched pairs (36.4% vs 18.2%, P = 0.039). The two groups showed similar postoperative mortality and morbidity. Multivariate analysis identified alpha-fetoprotein ≥ 400 ng/mL, presence of vascular invasion and TACE treatment as independent predictors of poor OS. CONCLUSION: Our findings suggest that HR can be safe and more effective than TACE for patients with solitary huge HCC.

Stereotactic body radiotherapy combined with transarterial chemoembolization for huge (≥10 cm) hepatocellular carcinomas: A clinical study.

This study was conducted to evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE) for huge (≥10 cm) hepatocellular carcinomas (HCCs). Between May, 2006 and December, 2012, 72 patients with huge HCCs were treated by SBRT following incomplete TACE. The median total dose of 35.6 Gy was delivered over 12-14 days with a fractional dose of 2.6-3.0 Gy and 6 fractions per week. The patients were classified into those with tumor encapsulation (group A, n=33) and those without tumor encapsulation (group B, n=39). The clinical outcomes of tumor response, overall cumulative survival and toxicities/complications were retrospectively analyzed. Among the 72 patients, CR, PR, SD and PD were achieved in 6 (8.3%), 51 (70.8%), 9 (12.5%) and 6 patients (8.3%), respectively, within a median follow-up of 18 months. The objective response rate was 79.1%. The overall cumulative 1-, 3- and 5-year survival rates and the median survival time were 38, 12 and 3% and 12.2 months, respectively. In group A, the overall cumulative 1-, 3- and 5-year survival rates were 56, 21 and 6%, respectively, with a median survival of 19 months; in group B, the overall cumulative 1-, 3- and 5-year survival rates were 23, 4 and 0%, respectively, with a median survival of 10.8 months (P=0.023). The treatment was well tolerated, with no severe radiation-induced liver disease and no reported > grade 3 toxicity. Tumor encapsulation was found to be a significant prognostic factor for survival. In conclusion, the combination of SBRT and TACE was shown to be a safe and effective treatment option for patients with unresectable huge HCC.

Long-term survival after surgical resection for huge hepatocellular carcinoma: comparison with transarterial chemoembolization after propensity score matching.

BACKGROUND AND AIMS: Surgical resection (SR) and transarterial chemoembolization (TACE) have been commonly applied for patients with huge hepatocellular carcinoma (HCC). However, optimal treatment has not been established. METHODS: Between 2000 and 2009, 267 patients with huge HCC (≥ 10 cm) underwent TACE and 84 underwent SR as the first treatment. Propensity score matching generated a matched cohort composed of 152 patients. We investigated overall survival and possible prognostic factors. RESULTS: At baseline, the surgery group showed a tendency to have solitary tumor (72.6% vs 39.3%, P < 0.001), less vessel invasion (29.8% vs 51.3%, P < 0.001), and unilobar tumor extent (77.4% vs 50.9%, P < 0.001) than TACE group. During median follow up of 10 months (range: 0-103), the surgery group showed higher 1-, 3-, and 5-year overall survival rates than TACE group (73.8%, 54.8%, and 39.8% vs 37.8%, 16.3%, and 9.7%, respectively, P < 0.001). In the propensity score-matched cohort, baseline characteristics did not differ between the two groups. Surgery group showed higher 1-, 2-, and 3-year overall survival rates than TACE group (69.7%, 58.6%, and 51.7% vs 40.2%, 33.9%, and 18.5%, respectively, P < 0.001) during median follow up of 14.5 months (range: 0-103). Multivariate analysis revealed that male (HR 1.90; 95% CI, 1.01-3.58; P = 0.048), albumin (HR 0.54; 95% CI, 0.34-0.85; P = 0.008), ascites (HR 1.77; 95% CI, 1.02-3.08; P = 0.044), and SR (HR 0.44; 95% CI, 0.28-0.70; P = 0.001) were the independent prognostic factors associated with survival. CONCLUSION: Comparing survival after SR and TACE, we showed that SR would be associated with better outcomes than TACE as the first treatment of huge HCC.