Renal failure in patients with hepatocellular carcinoma and ascites undergoing transarterial chemoembolization

Background: Ascites is often present in patients with hepatocellular carcinoma (HCC) with cirrhosis. Advanced cirrhosis may predispose to renal dysfunction. Acute renal failure (ARF) may occur after transarterial chemoembolization (TACE) for HCC because of radiocontrast agents. This study aimed to investigate the incidence and risk factors of ARF and prognostic predictors in HCC patients with ascites undergoing TACE. Methods: A total of 591 HCC patients receiving TACE were enrolled. Results: In a mean follow‐up duration of 19±17 months, 239 (40.4%) patients undergoing TACE died. Ascites, which was present in 91 (15.4%) patients at entry, independently predicted a poor prognosis in the Cox proportional hazard model [risk ratio (RR): 1.71, P=0.002]. Of these, 11 (12.6%) of 87 patients with complete follow‐up developed ARF after TACE. Serum albumin level <3.3 g/dl (odds ratio: 7.3, P=0.009) was the only independent risk factor associated with ARF in the logistic regression analysis. ARF (RR: 2.17, P=0.036), α‐fetoprotein >400 ng/ml (RR: 1.84, P=0.04), multiple tumours (RR: 2.11, P=0.013), tumour size ≥5 cm (RR: 2.32, P=0.006) and serum sodium level <139 mmol/L (RR: 2.4, P=0.005) were independent poor prognostic predictors for HCC patients with ascites receiving TACE. Conclusions: Pre‐existing ascites is associated with increased mortality in HCC patients receiving TACE. In HCC patients with ascites, hypoalbuminaemia is associated with the occurrence of post‐TACE ARF. Post‐TACE ARF is a poor prognostic predictor in this subset of HCC patients.     

Comparison between chemoembolization combined with radiotherapy and chemoembolization alone for large hepatocellular carcinoma

AIM: To investigate the efficacy of transcatheter arterial chemoembolization (TACE) combined with radiotherapy for unresectable large hepatocellular carcinoma (HCC). METHODS: From June 1994 to June 1999, a total of 76 patients with large unresectable HCC were treated with TACE followed by external-beam irradiation. 89 patients with large HCC, who underwent TACE alone during the same period, served as the control group. Clinical features, therapeutic modalities, acute effects and survival rates were analyzed and compared between TACE plus irradiation group and TACE alone group. A multivariate analysis of nine clinical variables and one treatment variable (irradiation) was performed by the Cox proportional hazards model. RESULTS: The clinical features and therapeutic modalities except irradiation between the two groups were comparable (P>0.05). The objective response rate (RR) in TACE plus irradiation group was higher than that in TACE alone group (47.4 % vs 28.1 %, P<0.05). The overall survival rates in TACE plus irradiation group (64.0 %, 28.6 %, and 19.3 % at 1, 3, 5 years, respectively) were significantly higher than those in TACE alone group (39.9 %, 9.5 %, and 7.2 %, respectively, P=0.0001). Cox proportional hazards model analysis showed that tumor extension and Child grade were significant and were independent negative predictors of survival, while irradiation was an independent positive predictor of survival. CONCLUSION: TACE combined with radiotherapy is more effective than TACE alone, and is a promising treatment for unresectable large HCC.     

Transarterial chemoembolization for inoperable,early stage hepatocellular carcinoma in patients with Child-Pugh grade A and B: results of a comparative study in 96 Chinese patients

OBJECTIVE: The efficacy of transarterial chemoembolization (TACE) in prolongation of survival is controversial. We conducted a comparative study to determine whether TACE treatment had any survival benefit for patients with unresectable hepatocellular carcinoma (HCC) and with relatively preserved liver function. METHODS: In all, 96 patients with unresectable HCC of Okuda stage I or II and Child-Pugh grade A or B were recruited. A total of 80 patients (group 1) who received TACE were compared to 16 patients (group 2) who were treated conservatively. RESULTS: The median survival time of group 1 patients was significantly longer than that of group 2 patients (31.2 vs 14.1 months respectively, p = 0.0126). The cumulative survival rates at 6 months, 1 yr, 2 yr, 3 yr, and 4 yr of group 1 compared to group 2 were as follows: 93.8% versus 62.5% (p = 0.002); 86.3% versus 62.5% (p = 0.023); 78.8% versus 50% (p = 0.017); 57.5% versus 50% (p = ns); and 51.3% versus 43.8% (p = ns), respectively. Tumor response was observed in 28% of patients receiving TACE. Patients with higher pretreatment albumin levels, lower pretreatment alpha-fetoprotein levels, and Okuda stage I disease were associated with a favorable response to TACE. CONCLUSION: TACE treatment improved survival in patients with unresectable HCC in the early stages and with relatively preserved liver function.     

Local radiotherapy as a complement to incomplete transcatheter arterial chemoembolization in locally advanced hepatocellular carcinoma.

PURPOSE: In order to determine the effect of additional radiotherapy (RT) after an incomplete transcatheter arterial chemoembolization (TACE) in an unresectable hepatocellular carcinoma (HCC), the treatment results of patients receiving TACE plus RT were analyzed and compared with those treated with TACE alone. MATERIALS AND METHODS: One hundred and five patients with an unresectable HCC were treated with TACE from January 1992 to December 2002. In 73 of these patients, the TACE was incomplete. Among them, TACE was repeatedly performed in 35 patients (TACE group), and the remaining 38 patients were also treated with local RT (TACERT group). The patients were either in stage III or IVa, Eastern Cooperative Oncology Group 2 or less, and Child-Pugh class A or B. The average frequency of TACE prior to RT was 2 and the RT was started within 7-10 days after the TACE. RESULTS: The 2-year survival rate was significantly higher in the TACERT than in the TACE group (36.8 % vs. 14.3%, P=0.001). According to the tumor size, the 2-year survival rates in the TACERT and TACE groups were 63% vs. 42% in 5-7 cm (P=0.22), 50% vs. 0% in 8-10 cm (P=0.03), and 17% vs. 0% in larger than 10 cm (P=0.0002) respectively. CONCLUSION: There was a significantly improved survival rate in the TACERT group of unresectable HCC patients than in the TACE group, particularly in case of tumors > or =8 cm in diameter. Therefore, RT in addition to TACE is strongly recommended for patients with an unresectable HCC.     

Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test

OBJECTIVES: Transcatheter arterial chemoembolization (TACE) is the major treatment modality for patients with unresectable hepatocellular carcinoma (HCC). Hepatic failure after TACE is relatively common in patients with preexisting liver dysfunction. The purpose of this study was to evaluate whether the monoethylglycinexylidide test and other parameters might predict hepatic failure after TACE in HCC patients. METHODS: One hundred forty-two HCC patients undergoing TACE were enrolled into this study. Before TACE, their venous blood was collected 15 min after a bolus injection of lidocaine (1 mg/kg body weight). A fluorescence polarization immunoassay was used to measure monoethylglycinexylidide oncentrations in their sera. Univariate and multivariate analyses were performed on the monoethylglycinexylidide test and other parameters between patients with and without hepatic failure after TACE. RESULTS: Nineteen patients (13.4%) suffered hepatic failure after TACE. Univariate analysis revealed that the monoethylglycinexylidide concentration (17.7+/-5.8 vs 43.9+/-13.2 ng/ml), Child-Pugh score (6.9+/-0.6 vs 6.0+/-0.7), indocyanine green retention ratio at 15 min (32.4+/-6.5% vs 15.7+/-5.8%), prolonged PT, and serum total bilirubin and albumin showed significant differences between patients with and without hepatic failure after TACE. After a multiple logistic regression, only the monoethylglycinexylidide test was an independent predictor of hepatic failure (OR = 1.68, 95% CI = 1.07-2.65, p = 0.026). Among the 19 hepatic failure patients, three (15.8%) died of hepatic failure associated with TACE within 1 month after this procedure. CONCLUSIONS: As a predictor of hepatic failure after TACE, the monoethylglycinexylidide test is better than conventional liver function tests and clinical parameters. The monoethylglycinexylidide test may be used to select patients with relatively good liver reserves for safe TACE treatment.     

Phase I/II study of a fine‐powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinoma

Aim: The clinical feasibility of transcatheter arterial chemoembolization (TACE) with fine‐powder cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC) has not been investigated. A phase I/II study was conducted to investigate the safety and tolerability of fine‐powder CDDP when it was used with lipiodol and gelatin sponge particles for TACE. Methods: Fine‐powder CDDP emulsified in lipiodol was injected into tumor arteries. Embolization was subsequently performed with gelatin sponge particles. The CDDP dose was started at 45 mg/m² (level 1) and increased to 65 mg/m² in 10 mg/m² increments. Results: Thirteen patients were enrolled in phase I study since no dose limiting toxicity was observed in any patients, even in seven patients at level 3 (65 mg/m²), the recommended dose was 65 mg/m². The major adverse event was grade 3 thrombocytopenia, which occurred in 8% of patients. The incidence of hematological toxicities was 15% for leukocytopenia, 84% for thrombocytopenia, and 84% for anemia. Increased serum total bilirubin was observed in 54% and increased aspartate aminotransferase or alanine aminotransferase in all patients. All digestive tract symptoms (nausea 77%, anorexia 84%, vomiting 31%) were grade 2 or lower. Total adverse events were grade 3 or higher in 44%. The response rate in 19 patients who received the recommended dose was 21%. Conclusions: TACE with a fine‐powder formulation of CDDP at a dose of 65 mg/m² is well tolerated in patients with unresectable HCC.     

Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients

BACKGROUND & AIMS: To elucidate the survival of the patients with unresectable hepatocellular carcinoma (HCC) who underwent transcatheter arterial lipiodol chemoembolization (TACE) and to analyze the factors affecting the survivals. METHODS: During the last 8 years, a nationwide prospective cohort study was performed in 8510 patients with unresectable HCC who underwent TACE using emulsion of lipiodol and anticancer agents followed by gelatin sponge particles as an initial treatment. Exclusion criteria were extrahepatic metastases and/or any previous treatment prior to the present TACE. The primary end point was survival. The survival rates were calculated by the Kaplan-Meier method. The multivariate analyses for the factors affecting survival were evaluated by the Cox proportional hazard model. The mean follow-up period was 1.77 years. RESULTS: For overall survival rates by TACE, median and 1-, 3-, 5-, and 7-year survivals were 34 months, 82%, 47%, 26%, and 16%, respectively. Both the degree of liver damage and the tumor-node-metastasis (TNM) system proposed by the Liver Cancer Study Group of Japan demonstrated good stratification of survivals (P = .0001). The multivariate analyses showed significant difference in degree of liver damage (P = .0001), alpha-fetoprotein value (P = .0001), maximum tumor size (P = .0001), number of lesions (P = .0001), and portal vein invasion (P = .0001). The last 3 factors could be replaced by TNM stage. The TACE-related mortality rate after the initial therapy was .5%. CONCLUSIONS: TACE showed safe therapeutic modality with a 5-year survival of 26% for unresectable HCC patients. The degrees of liver damage, TNM stage, and alpha-fetoprotein values were independent risk factors for patient survival.     

Postoperative adjuvant transarterial chemoembolization for participants with hepatocellular carcinoma: A meta‐analysis

Aim: The efficacy of transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC) is positive, but for postoperative HCC, many studies have reported controversial results. The present study aimed to evaluate the efficacy of postoperative adjuvant TACE for participants with HCC. Methods: Electronic and manual searches were conducted to identify randomized controlled trials (RCT) evaluating postoperative adjuvant TACE for participants with HCC. Results: Six RCT totaling 659 participants, of whom almost all were of stage IIIA HCC, were included. For the 1‐year tumor recurrence rate, hepatectomy plus TACE showed statistically significant less incidence of recurrence, with a pooled risk ratio (RR) of 0.68 (95% confidence interval [CI] = 0.55–0.84, P = 0.0003). For 1‐year mortality, the trials were favorable for TACE with a pooled risk ratio of 0.48 (95% CI = 0.35–0.65, P < 0.00001). For 3‐year mortality, the trials also revealed statistically significant less incidence, with a pooled risk ratio of 0.76 (95% CI = 0.64–0.90, P = 0.002). However, for 5‐year mortality, TACE did not demonstrate statistically significant less incidence (RR = 0.94, 95% CI = 0.81–1.08, P = 0.36). Transient fever and nausea/vomiting were reported as side‐effects of TACE but were well tolerated by most participants. Conclusion: Postoperative adjuvant TACE seems promising for participants with HCC with risk factors (multiple nodules of >5 cm or vascular invasion) but requires further trial.     

Incidence and risk factors of acute hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma]

BACKGROUND/AIMS: Although transcatheter arterial chemoembolization (TACE) is a major treatment modality for unresectable hepatocellular carcinoma (HCC), acute hepatic failure after TACE is not rare. However, reports dealing with this important complication are not good enough and results are often variable. The purpose of this study was to evaluate the incidence and associated risk factors of acute hepatic failure after TACE. METHODS: From January 2001 to November 2004, six hundred and thirty-two TACE sessions were performed in 377 patients (294 men and 83 women). Adriamycin mixed lipiodol solution and gelfoam were used for TACE. Various clinical and radiological factors before and after the procedure were reviewed retrospectively. Univariate and multivariate analyses were performed to evaluate the risk factors associated with the development of acute hepatic failure after TACE. RESULTS: Acute hepatic failure occurred in 76 (12.0%) of the 632 TACE sessions within 14 days. Univariate analysis revealed that Child-Pugh class, 1st TACE, total bilirubin level, number of involved segments, total size of tumor, presence of right portal vein thrombosis (PVT) or main PVT, involvement of segment 1, 5, 6, 7, modified UICC stage, and doses of chemotherapeutic agent were significantly different between the patients with or without hepatic failure after TACE. Among them, elevated total bilirubin (p=0.001, E (beta)=1.449), presence of right (p=0.035, E (beta)=2.109) or main (p=0.011, E (beta)=4.067) PVT were independently associated factors in multivariate analysis. CONCLUSIONS: The incidence of acute hepatic failure after TACE was 12.0%. Elevated bilirubin level and portal vein thrombosis could be considered as the predictive factors for acute hepatic failure after TACE in HCC patients.     

Transarterial chemoembolization in combination with percutaneous ablation therapy in unresectable hepatocellular carcinoma: a meta‐analysis

Background: Recent evidence suggests that transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) or a percutaneous ethanol injection (PEI) may have a synergistic effect in treating hepatocellular carcinoma (HCC). The aim of the current meta‐analysis was to identify the survival benefits of TACE combined with percutaneous ablation (PA) therapy (RFA or PEI) for unresectable HCC compared with those of TACE or PA alone. Methods: Randomized‐controlled trials (RCTs) published as full papers or abstracts were searched to assess the survival benefit or tumour recurrence for patients with unresectable HCC on electronic databases. The primary outcome was survival. The secondary outcomes were response to therapy and tumour recurrence. Results: Ten RCTs met the criteria to perform a meta‐analysis including 595 participants. TACE combined with PA therapy, respectively improved, 1‐, 2‐, and 3‐year overall survival compared with that of monotherapy [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.14–4.57; P=0.020], (OR=4.53, 95% CI 2.62–7.82, P<0.00001) and (OR=3.50, 95% CI 1.75–7.02, P=0.0004). Sensitivity analysis demonstrated a significant benefit in 1‐, 2‐ and 3‐year overall survival of TACE plus PEI compared with that of TACE alone for patients with large HCC lesions, but not in TACE plus RFA vs RFA for patients with small HCCs. The pooled result of five RCTs showed that combination therapy decreased tumour recurrence compared with that of monotherapy (OR=0.45, 95% CI 0.26–0.78, P=0.004). Conclusion: TACE combined with PA therapy especially PEI improved the overall survival status for large HCCs.     

Predictors of repeat transarterial chemoembolization in the treatment of hepatocellular carcinoma

ObjectivesRepeat transarterial chemoembolization (TACE) is a common intervention performed for hepatocellular carcinoma (HCC). The aim of this study was to identify predictors of the need for repeat TACE.MethodsBetween 2008 and 2012, data on patient and tumour variables were collected for 262 patients treated with a first TACE procedure for HCC. The decision to perform repeat TACE procedures was made at the completion of the first TACE or after follow-up imaging demonstrated the subtotal treatment of HCC tumours.ResultsRepeat TACE was performed in 67 of 262 (25.6%) patients. Necrosis of HCC, measured after the first TACE, was lower in patients who subsequently received repeat TACE (P = 0.042). On multivariable analysis, total tumour diameter of >5 cm [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.45–5.25; P = 0.002] and increasing age (OR 1.04/year, 95% CI 1.00–1.07; P = 0.030) were predictive of the need for repeat TACE. Measures of liver function and TACE approach (selective versus non-selective) were not predictive of repeat TACE. Median survival did not differ significantly between patients who did (median survival: 21.1 months) and did not (median survival: 26.1 months) receive a repeat TACE procedure (P = 0.574).ConclusionsThe requirement for repeat TACE is associated with older age, increased HCC tumour burden and subtotal TACE-induced HCC necrosis. Importantly, repeat TACE was not associated with reduced survival.     

Portal Vein Embolization can Prevent Intrahepatic Metastases to Non-Embolized Liver

Background/Aims: To determine the efficacy of portal vein embolization (PVE) against unresectable hepatocellular carcinoma (HCC). Methodology: We conducted a comparative study using 17 patients with HCC determined to be unresectable and who received a combination of PVE and transarterial chemoembolization (TACE) (PVE group) and 22 HCC patients with tumors in the unilateral lobe, which were treated only with repeated TACE (TACE group) from January 2000 to December 2008. Results: There were no significant differences in background factors except for gender between the two groups. The cumulative intrahepatic recurrence rates in the non-portal-embolized area (in the contralateral lobe for the TACE group) at 1 year and 3 years was 41.1% and 58.8% in the PVE group and 77.3% and 81.8% in the TACE group, respectively. The former was significantly lower (p<0.05). The cumulative overall survival rate at 1 year, 3 and 5 years was 88.2%, 38.2% and 38.2% in the PVE group, and 68.1%, 22.7% and 8.5% in the TACE group, respectively. The former was significantly higher (p<0.05). Conclusions: Although in patients with unresectable HCC, when HCC is localized in the portal-embolized area, PVE combined with TACE can prevent intrahepatic metastasis to the non-portal-embolized area and improve overall survival.     

Selecting a prognostic renal surrogate for patients with hepatocellular carcinoma undergoing transarterial chemoembolization

Background and Aim: Renal insufficiency (RI) often coexists with hepatocellular carcinoma (HCC) and predicts a poor outcome in patients receiving transarterial chemoembolization (TACE). The modification of diet in renal disease (MDRD) and chronic kidney disease epidemiology collaboration (CKD‐EPI) equations are used to provide estimated glomerular filtration rate (eGFR). This study aimed to determine a prognsotic renal surrogate for outcome prediction in HCC patients receiving TACE. Methods: A total of 684 patients with HCC undergoing TACE were retrospectively analyzed. The prognostic ability between the MDRD and CKD‐EPI equation was compared by the Akaike information criterion (AIC). Results: Patients were categorized by eGFR into > 60, 30–60 and < 30 mL/min per 1.73 m² (equivalent to CKD stages 1–2, 3, and 4–5, respectively) groups. The eGFR generated by the MDRD equation had a better predictive accuracy by having a lower AIC score (3234.5) compared to the CKD‐EPI equation (3236.7). The adjusted risk ratio for patients with eGFR 30–60 mL/min per 1.73 m² by the MDRD was 1.313 (P = 0.041) compared with patients with eGFR > 60 mL/min per 1.73 m² in the multivariate Cox model. The eGFR defined by the MDRD equation consistently had better prognostic ability when patients were stratified by the Child‐Turcotte‐Pugh score of 5 and > 5 and Cancer of the Liver Italian Program score 0 to 1 and > 1. Conclusions: The eGFR according the MDRD equation may provide better prognostic accuracy than the CKD‐EPI equation independent of liver functional reserve and tumor staging, and is a more feasible renal surrogate for outcome prediction in CKD stage 1–3 HCC patients receiving TACE.     

Best radiological response to trans‐arterial chemoembolization for hepatocellular carcinoma does not imply better outcomes

IntroductionRegional therapy with trans‐arterial chemoembolization (TACE) is a common treatment for unresectable hepatocellular carcinoma (HCC). Outcomes were examined in patients with the best radiological response (BR) after the initial TACE.MethodsThis was a retrospective cohort study of patients who underwent TACE as the initial treatment for HCC between the years 2000 and 2010. BR was defined as complete disappearance of the tumour or no enhancement with contrast on the first cross‐sectional imaging study after the initial TACE.ResultsSeventy‐eight out of 104 total consecutive patients were identified with the potential for a BR to TACE therapy for unresectable HCC, and 24 met the criteria for BR. Patients with BR had a median survival of 12.8 months (2.2–54.9) compared with 18.9 months(1.3–56.7) for the entire cohort (P= 0.313). The median time to progression was 10.6 months (1.2–24.3) in the BR group and 3.2 months (0.7–49.2) in the patients without a BR (P= 0.003).DiscussionBR to initial TACE for unresectable HCC is associated with comparable survival to those without BR in spite of a longer time to cancer progression. It may be reasonable to consider further therapy such as repeat TACE or biological/systemic therapy in patients with HCC even when the radiological response to the initial TACE is favourable.     

Combination therapy with transarterial chemoembolization and interferon-α compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma

Background and Aims:  The present study was carried out to test the hypothesis that interferon-α (IFN-α) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization (TACE) treatment of hepatitis B virus (HBV) related unresectable hepatocellular carcinoma (HCC).
Methods:  216 patients with unresectable HBV-related HCC were randomized into a TACE group and a TACE-IFN group, each group had 108 patients. In the TACE-IFN group, patients received IFN-α1b at a dose of 3 million units (mu) three times a week by intramuscular injection one week after/before TACE treatment, for 48 weeks.
Results:  The median disease-free survival in the TACE-IFN treatment group was 23.6 months (95% CI: 21.4–25.8) and 20.3 months (95% CI: 15.8–24.8) in the TACE group ( P  = 0.027). The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group (39.8% vs 59.3%, P  = 0.004). The median overall survival was 29 months (95% CI: 27.5–32.1) in the TACE-IFN group and 26 months (95% CI: 20.1–31.9) in the TACE group ( P  = 0.003). The 2-year overall survival in the TACE-IFN group was higher than in the TACE group (72.2% vs 52.8%, P  = 0.003).
Conclusions:  IFN-α treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC, with acceptable toxicities.     

Transcatheter arterial chemoembolization therapy for patients with hepatocellular carcinoma: a case-controlled study.

BACKGROUND & AIMS: Transcatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival. METHODS: Fifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care. RESULTS: The 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis. CONCLUSIONS: TACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.     

A comparative study of damage to liver function after TACE with use of low-dose versus conventional-dose of anticancer drugs in hepatocellular carcinoma

BACKGROUND/AIMS: To study liver function damage after transcatheter arterial chemoembolization (TACE) with use of low-dose versus conventional-dose anticancer drugs in patients with hepatocellular carcinoma (HCC). METHODOLOGY: One hundred and twelve patients with unresectable HCC were randomly divided into two groups to receive superselective TACE. Patients in group A (n=52) received low-dose anticancer drugs: mitomycin C (MMC) 2-8 mg, epirubicin (EPI) 5-10 mg and carboplatin (CBP) 100mg were used. Patients in group B (n=60) were given conventional-dose of anticancer drugs (MMC 10 mg, EPI 40 mg, CBP 300 mg). Lipiodol-anticancer drugs emulsion was injected into the feeding arteries of tumors followed by gelatin sponge (GS) or polyvinyl alcohol (PVA) particles embolization. Liver function was evaluated with Child-Pugh scores, total bilirubin (TBIL), albumin (ALB) and alanine aminotransferase (ALT) before TACE, three days, one week (wk) and four wk after procedures. RESULTS: In both groups, TBIL, ALT, and Child-Pugh scores increased (P < 0.001 or P < 0.05) and ALB decreased (P < 0.001 or P < 0.01) three days and one wk after TACE. The different between the parameters obtained four wk after the procedure and baseline parameters was not significant in group A (P > 0.05). In group B, however, significant difference (P < 0.05) was found in all parameters except ALT. CONCLUSIONS: Superselective TACE with use of low-dose anticancer drugs induces transient impairment in liver function, but use of conventional-dose anticancer drugs can cause lasting, more serious worsening of liver function.     

经动脉化学栓塞和经皮冷冻序贯治疗肝细胞癌

目的 评价经动脉化学栓塞(TACE)和经皮冷冻序贯治疗无法切除的肝细胞肝癌(HCC)的疗效.方法 将420例无法手术切除的HCC患者分为TACE-冷冻序贯治疗组290例(序贯组)和单纯冷冻组130例(冷冻组).TACE按常规操作,术后2～4周行经皮冷冻治疗.1个月及以后每2～3个月随访1次,包括肝脏超声和(或)腹部CT,并检测血清甲胎蛋白(AFP).结果 平均随访(42±17)个月(范围24～70个月),所有患者消融灶局部复发率为17%,序贯组和冷冻组分别为11%和24%(P=0.001).1、2、3、4和5年平均存活率分别为72%、57%、47%、39%和31%.序贯组1年和2年存活率(71%和61%)与冷冻组(73%和54%)相似(P值分别=0.69和0.147);而4年和5年存活率,序贯组(49%和39%)高于冷冻组(21%和23%,P=0.001).序贯组有18例肿瘤直径＞5cm的患者存活逾5年,而冷冻组无一例.全组并发症发生率为24%,序贯组和冷冻组分别为21%和26%(P=0.06).冷冻组肝出血的发生率显著高于序贯组(P=0.02),且有2例发生肝破裂.结论 冷冻治疗前先行TACE能提高冷冻消融的疗效,减少其并发症,特别是肝出血.TACE和冷冻序贯疗法可能是治疗不能切除性HCC,特别是大肝癌的较好方法 .     

Biliary phenotype of hepatocellular carcinoma after preoperative transcatheter arterial chemoembolization

Background and Aim: Transcatheter arterial chemoembolization (TACE) is now the mainstay of treatment for non‐curative hepatocellular carcinoma (HCC), and hoped to have chemotherapeutic and ischemic effects; however, the histopathological changes of HCC caused by TACE have not been sufficiently discussed so far. We aimed to assess the morphological and immunohistochemical features of HCC treated with TACE by immunostaining cytokeratin (CK) 7, CK14, CK19 and vimentin, and to correlate these data with observed clinicopathological characteristics. Methods: Eighty cases of surgically resected HCC with preoperative TACE and 146 cases of HCC resected without TACE as a control were analyzed. Results: The incidences of intrahepatic metastasis, poorly differentiated histology, multinucleated giant cells, mitotic figures and cytoplasmic inclusion bodies in the TACE group were significantly higher than those in the non‐TACE group. The TACE group showed reactivity for CK7 in 56.3% (45/80) of patients, CK14 in 12.5% (10/80), CK19 in 23.8% (19/80) and vimentin in 6.3% (5/80) of patients. CK19 expression in the TACE group was significantly higher than in the non‐TACE group (P = 0.0423). There was no correlation between immunoreactivity and the number of times TACE was carried out, but the expression of CK19 and vimentin in the massive necrotic group was higher than that in the mild necrotic group (P = 0.0197, P = 0.0229, respectively). Only TACE was an independent determinant of CK19 expression in all cases by multivariate analysis. Conclusions: These results suggest that preoperative TACE may have an impact on the biliary phenotype of HCC. Some post‐therapeutic HCC patients might develop HCC with a biliary phenotype indicating more aggressive malignancies.     

Comparative effectiveness of traditional chemoembolization with or without sorafenib for hepatocellular carcinoma

AIM: To compare the overall survival (OS) and progression-free survival (PFS) with associated adverse events (AE) in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) + sorafenib vs TACE alone. METHODS: In this retrospective cohort study we collected data on all consecutive patients with a diagnosis of unresectable HCC between 2007 and 2011 who had been treated with TACE + sorafenib or TACE alone. We hypothesized that the combination therapy is superior to TACE alone in improving the survival in these patients. Data extracted included patient’s demographics, etiology of liver disease, histology of HCC, stage of liver disease with respect to model of end stage liverdisease score and Child-Turcotte-Pugh (CTP) classification and Barcelona Clinic Liver Cancer (BCLC) staging for HCC. Computed tomography scan findings, alpha fetoprotein levels, number of treatments and related AE were also recorded and analyzed. RESULTS: Of the 43 patients who met inclusion criteria, 13 were treated with TACE + sorafenib and 30 with TACE alone. There was no significant difference in median survival: 20.6 mo (95%CI: 13.4-38.4) for the TACE + sorafenib and 18.3 mo (95%CI: 11.8-32.9) for the TACE alone (P = 0.72). There were also no statistically significant differences between groups in OS (HR = 0.82, 95%CI: 0.38-1.77; P = 0.61), PFS (HR = 0.93, 95%CI: 0.45-1.89; P = 0.83), and treatment-related toxicities (P = 0.554). CTP classification and BCLC staging for HCC were statistically significant (P = 0.001, P = 0.04 respectively) in predicting the survival in patients with HCC. The common AE observed were abdominal pain, nausea, vomiting and mild elevation of liver enzymes. CONCLUSION: Combination therapy with TACE + sorafenib is safe and equally effective as TACE alone in patients with unresectable HCC. CTP classification and BCLC staging were the significant predictors of survival. Future trials with large number of patients are needed to further validate this observation.