Unresectable hepatocellular carcinoma: Survival and prognostic factors after lipiodol chemoembolisation in 89 patients

BACKGROUND: The majority of patients with hepatocellular carcinoma are not eligible for surgical radical treatment (resection or liver transplantation) and lipiodol chemoembolisation is an efficient alternative procedure in this indication. AIMS: To identify prognostic factors in patients treated with lipiodol chemoembolisation. PATIENTS AND METHODS: During 10 years, 89 consecutive patients with unresectable hepatocellular carcinoma underwent lipiodol chemoembolisation as a single treatment. There were 80 males and 9 females, with a median age of 65 years. Treatment consisted of one to six courses of hepatic intra-arterial lipiodol with doxorubicine and gelatin sponge. RESULTS: The median survival was 13 months with a 13.6% survival rate at 4 years. Univariate analysis showed that serum levels of albumin, bilirubin, alkaline phosphatase and alpha-fetoprotein, Child's class, tumour type, tumour size and intensity of lipiodol capture after the first course of lipiodol chemoembolisation were significant prognostic factors of survival. In the multivariate analysis, four parameters remained associated with a significantly better outcome: Child's class A, largest lesion<5 cm, uninodular tumour and intense lipiodol capture. CONCLUSIONS: While lipiodol chemoembolisation is associated with good results only in some patients, in the absence of lipiodol capture, it should be ruled out.     

Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with Child's grade A or B cirrhosis: a multivariate analysis of prognostic factors.

We evaluated factors affecting long-term survival after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) complicating cirrhosis. One hundred eighty-two patients with Child's class A or B cirrhosis and an HCC, not amenable to surgery or percutaneous ethanol injection, underwent 346 TACEs (mean 1.9) with epirubicin, iodized oil, and gelatin sponge. Many prognostic factors were subjected to univariate analysis and thereafter, when significant, to the Cox's hazard proportional model. Finally, the significant indices in the Cox's model were used to estimate the accuracy of the probability of death with computation of the area under the receiving operative characteristic (ROC) curve. The cumulative survival rates at 1, 2, 3, and 5 years were 0.83, 0.52, 0.40, and 0.16, respectively. According to Cox's model, the factors associated with significantly worse survival were the presence of ascites (p = 0.0027), elevated bilirubin levels (p = 0.0163), elevated alpha-fetoprotein (alphaFP) values (p = 0.0067), a tumor greater than 5 cm in diameter (p = 0.0001), and the absence of a tumor capsule-like rim (p = 0.0278). According to these parameters, the accuracy of the probability of death estimated with ROC analysis was 0.63. Minor and major complications occurred in 82 patients (45%) and caused death in 2 patients. Long-term prognosis after TACE for HCCs in patients with Child's class A or B cirrhosis depends on the presence of ascites, the bilirubin level, the alphaFP value, the diameter of the tumor, and the presence of a tumor capsule-like rim. However, when considered altogether, these variables are poor predictors to evaluate survival, and other factors should be investigated to identify subjects more responsive to TACE. Complications occur in a high percentage of patients, but they do not affect long-term prognosis.     

Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with cirrhosis: evaluation of two kinds of dosages of anticancer drugs and analysis of prognostic factors

BACKGROUND/AIMS: To evaluate the efficacy of TACE (transcatheter arterial chemoembolization) with use of low-dose versus conventional-dose anticancer drugs in hepatocellular carcinoma patients with cirrhosis and to analyze their prognostic factors. METHODOLOGY: Eight-two patients with unresectable hepatocellular carcinoma underwent super-selective TACE. Patients in group A (n = 40) received low-dose anticancer drugs. Patients in group B (n = 42) were given conventional-dose of anticancer drugs. Tumor response and survival time in the two groups were compared. Cox proportion-hazards modeling was used to evaluate the relative importance of prognostic variables. RESULTS: There was no significant difference between the two groups in initial tumor response (P < 0.05). The median survival in all patients was 18 months (mo). The median survival in groups A and B were 20 mo and 16 mo respectively. The cumulative survival rates at 6, 12, 18, 24, 30 mo were 68.4%, 57.6%, 38.4%, 26.6%, 19.9% in group A, and 62.6%, 43.8%, 31.9%, 26.5%, 26.5% in group B. There was no significant difference in survival between the two groups (P > 0.05). The factors influencing prognosis were Child-Pugh scores (P < 0.0001), tumor thrombus in the portal vein (P < 0.0001), tumor size (P < 0.0001), method of embolization (P < 0.0001), TACE times (P < 0.001). The dosage of anticancer drugs employed in TACE was not relevant to the survival rates (P = 0.883). CONCLUSIONS: TACE with use of large-dose anticancer drugs does not significantly enhance the anticancer effects and survival compared that with lowdose anticancer drugs. The therapeutic effect of TACE was mainly attributed to embolization of the artery rather than to anticancer drugs.     

Transcatheter arterial embolization of ruptured hepatocellular carcinoma associated with liver cirrhosis

Four cases of hepatocellular carcinoma treated by transcatheter arterial embolization have been reported. In three patients, the bleeding stopped completely after the procedure. Embolized tumor appeared to be necrotized in two cases. Transcatheter arterial embolization should be considered the treatment of choice for the emergency therapy of ruptured hepatocellular carcinoma.     

Predictive factors of transarterial chemoembolisation toxicity in unresectable hepatocellular carcinoma

BackgroundTransarterial chemoembolisation (TACE) is an effective treatment for unresectable hepatocellular carcinoma (HCC), but can cause severe toxicity.AimTo identify predictive factors of severe TACE-related toxicity in patients with unresectable HCC.MethodsAll HCC patients who underwent TACE at the Dijon University Hospital between 2008 and 2011 were included in this retrospective study. Severe TACE-related toxicity was defined as the occurrence of any adverse event grade ≥4, or any adverse event that caused a prolongation of hospitalisation of >8 days, or any additional hospitalisation within 1 month after TACE. Factors predicting toxicity were identified using a logistic regression model. The robustness of the final model was confirmed using bootstrapping (500 replications).Results124 patients were included, median age was 67 years and 90% were male; 22 patients (18%) experienced severe TACE-related toxicity. Factors that independently predicted severe TACE-related toxicity in multivariate analysis were total tumour size (OR, 1.15 cm⁻¹; 95%CI, 1.04–1.26; p = 0.01), and high serum AST levels (OR, 1.10 per 10 IU/l; 95%CI, 1.01–1.21; p = 0.04). The results were confirmed by bootstrapping.ConclusionsTotal tumour size and high serum AST levels were predictive factors of severe TACE-related toxicity in this hospital-based series of patients with unresectable HCC.     

Transcatheter arterial chemo-embolization for humoral hypercalcemia of hepatocellular carcinoma

A 50-year-old male with unresectable hepatocellular carcinoma (HCC) had a hypercalcemic crisis with a serum calcium concentration of 7.8 mEq/zeta, without any evidence for bone metastases or parathyroid lesions. The hypercalcemia was thought to be due to increased renal reabsorption of calcium and increased bone resorption, which was probably caused by humoral factors derived from the HCC, some being parathyroid hormone-like factors. Since conservative therapy for hypercalcemia was not sufficiently effective and was accompanied by progressive exacerbation of ascites and leg edema, transcatheter arterial chemo-embolization (TACE) was performed. On the following day, serum calcium concentration decreased from 6.3 mEq/zeta to the normal range, although serum alpha-fetoprotein levels decreased only slightly. Thereafter hypercalcemia did not develop for about 4 weeks. The results demonstrated that TACE can be effective for humoral hypercalcemia of HCC.     

The radiological prognostic factors of transcatheter arterial chemoembolization to hepatocellular carcinoma

Transcatheter arterial chemoembolization (TACE) is the recommended treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the HCC radiological characteristics associated with prognosis of patients with intermediate stage HCC receiving TACE. Patients with HCC BCLC stage B from January 2005 to December 2009 were collected. According to mRECIST criteria, patients with complete response and partial response were assigned to the objective response (OR) group, while those with stable disease and progressive disease were assigned to the nonobjective response (non-OR) group. Among a total of 128 enrolled patients, there were 66 (51.6%) and 62 (48.4%) patients in the OR group and non-OR group, respectively. The clinical parameters in the two groups were similar, although HCC size was smaller in the OR group. Logistic analysis found combined radiological characteristics including complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush were significant correlated with achievement of OR (odds ratio 2.46, 95% CI 1.08–5.61, P = .032). However, no radiological characteristics had significant strength to predict overall survival. Patients with OR after TACE had significantly longer survival time than those with non-OR. Combined characteristics of complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush had a positive impact on OR in TACE. In patients receiving TACE, those who achieved OR had a better overall survival.     

Transcatheter arterial embolization for hepatocellular carcinoma with portal vein thrombosis

Abstract In order to evaluate the possible benefits of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients with peripheral portal vein thrombosis, 96 consecutive HCC cases with peripheral portal vein thrombosis were analysed. Of them, 35 cases received TAE and 61 cases did not. Most (77.8%) of the TAE-treated cases showed decreased α-fetoprotein (AFP) levels after treatment, but 57.1% of them suffered another rise in AFP levels and subsequently died. One patient (2.8%) developed progressive jaundice after TAE and died within 1 month, while four of the non-TAE cases died within 1 month after diagnosis. In general, TAE is safe for HCC patients with peripheral portal vein thrombosis. In addition, using Cox's regression model for multivariate survival analysis, serum total bilirubin (≤, > 2 mg/dL; P = 0.0254), AFP (≤ 3155 ng/mL, > 3155 ng/mL; P = 0.0002) and treatments (TAE, non-TAE; P = 0.0059) were found to affect their prognosis. There was significant difference in survival between TAE and non-TAE groups, the 6 month, 1 year and 2 year survival rates were 91.4 versus 62.3%, 51.4 versus 26.2% and 17.1 versus 4.9% ( P = 0.0017). The median survival times of TAE and non-TAE groups were 10.3 versus 3.7 months, respectively. Though TAE only provided palliative treatment, it did prolong survival in HCC patients with peripheral portal vein thrombosis.     

Transcatheter arterial chemoembolization of hepatocellular carcinoma: a Japanese experience

Hepatocellular carcinoma is one of the most common causes of cancer death in Japan and in 80% of cases is associated with chronic liver disease caused by hepatitis C virus. Poor hepatic function reserve due to underlying cirrhosis is the primary factor which limits extended surgical resection in many cases. Furthermore, in patients treated by curative resection, high incidence of recurrent tumors or/and newly developed tumor in the residual liver was reported. Therefore, the aim of various therapeutic options such as operation, percutaneous ethanol injection, radiofrequency coagulation therapy and transcatheter arterial chemoembolization should be the local control of hepatocellular carcinoma. Transcatheter hepatic arterial chemoembolization has a main role for the multidisciplinary treatment for hepatocellular carcinoma with this biological behavior.     

Poor prognostic factors of hepatectomy in patients with resectable small hepatocellular carcinoma and cirrhosis

Purpose Some patients with hepatocellular carcinoma (HCC) at an early stage cannot attain long-term survival after hepatectomy. The aim of the present study was to investigate the poor prognostic factors for hepatectomy in patients with resectable small HCC with cirrhosis.Methods We studied 95 patients with cirrhosis with HCC, which consisted of a single tumor 5 cm or smaller or two or three tumor nodules each 3 cm or less; an absence of extrahepatic metastasis; and an absence of radiological evidence of macroscopic portal vein or hepatic vein invasion. We used Coxs proportional hazard model to identify risk factors associated with prognosis to determine the contra-indications for hepatectomy in patients with resectable small HCC.Results Preoperative risk factors were: (1) serum AFP concentration of more than 400 ng/ml; (2) infiltrative-, massive-, or multinodular-type (multiple) HCC; and (3) the presence of intrahepatic metastasis. Patients who had had more than one of the three preoperative risk factors were poor candidates for hepatic resection, with a 4-year survival of 16.3%.Conclusion If patients with resectable small HCC are diagnosed as having more than one of three preoperative risk factors, they should not receive hepatectomy or should be considered for primary liver transplantation as a therapeutic option for HCC.     

Transcatheter partial splenic arterial embolization in patients with hypersplenism: a clinical evaluation as supporting therapy for hepatocellular carcinoma and liver cirrhosis

Eleven cases with hypersplenism, one with liver cirrhosis and ten with hepatocellular carcinoma (HCC) associated with liver cirrhosis, underwent transcatheter partial splenic arterial embolization. In four of ten HCC cases, the spleen was accidentally infarcted during the procedure of transcatheter hepatic arterial embolization (TAE). The mean infarcted area of the spleen was 55.7%. An increase in the peripheral platelet count was particularly remarkable and continued over one year after the embolization. High fever and abdominal pain were observed in all cases. The fever was seen for 18.0 days and pain was noted for an average of 12.8 days after the embolization. Other adverse effects such as pleural effusion and ascites were transitorily observed. Splenic embolization is an effective supporting therapy for hypersplenism in patients with cirrhosis or HCC.     

Transcatheter arterial embolization for gastrointestinal bleeding: Clinical outcomes and prognostic factors predicting mortality

We evaluated clinical outcome and prognostic factors predicting mortality of transcatheter arterial embolization (TAE) for acute gastrointestinal (GI) bleeding. Fifty-nine patients (42 men, 17 women; mean age 66.1 ± 17.0) who underwent 59 TAE procedures for GI bleeding during 2013–2018 were retrospectively evaluated. Clinical outcomes included technical success, adverse events, and rebleeding and mortality rate within 30 days. The technical success rate was 100%. Angiography showed contrast extravasation in 41 (69.5%) patients and indirect signs of bleeding in 16 (27.1%) patients. Two (3.4%) patients underwent prophylactic embolization. TAE-related adverse events occurred in 7 (11.9%) patients; adverse events were more common for mid GI or lower GI bleeding than for upper GI bleeding (22.6% vs 0%, P = 0.007). Rebleeding within 30 days was observed in 22 (37.3%) patients after TAE. Coagulopathy was a prognostic factor for rebleeding (odds ratio [OR] = 3.53, 95% confidence interval 1.07–11.67, P = .038). Mortality within 30 days occurred in 11 (18.6%) patients. Coagulopathy (OR = 24, 95% confidence interval 2.56–225.32, P = .005) was an independent prognostic factor for mortality within 30 days. TAE is an effective, safe, and potentially lifesaving procedure for GI bleeding. If possible, coagulopathy should be corrected before TAE as it may reduce rebleeding and mortality.     

Therapeutic effects and prognostic factors in three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

AIM: To evaluate the therapeutic efficacy of threedimensional conformal radiotherapy (3D-CRT) combined with transcatheter arterial chernoembolization (TACE) on the patients with hepatocellular carcinoma (HCC).METHODS: Between 1998 and 2001, 94 patients with HCC received 3D-CRT combined with TACE. A total 63 patients had a Okuda stage Ⅰ lesion and 31 patients had stage Ⅱ. The median tumor size was 10.7 cm (range 3.0-18 cm), and liver drrhosis was present in all the patients. There were 43 cases of class A and 51 dass B. TACE was performed using lipiodol,5-fluorouracil, cisplatin, doxorubicin hydrochloride and mitomycin, followed by gelatin sponge cubes. Fifty-nine patients received TACE only one time, while the others 2 to 3 times. 3D-CRT was started 3-4 wk after TACE. All patients were irradiated with a stereotactic body frame and received 4-8 Gy single high-dose radiation for 8-12 times at the isocenter during a period of 17-26 d (median 22 d).RESULTS: The median follow-up was 37 mo (range 10-48 mo) after diagnosis. The response rate was 90.5%. The overallsurvival rate at 1-, 2-, and 3- year was 93.6%, 53.8% and 26.0% respectively, with the median survival of 25 too. On univariate analysis, age (P=-0.026), Child-Pugh classification for cirrhosis of liver (P=0.010), Okuda stage (P=-0.026),tumor size (P=0.000), tumor type (P=0.029), albuminemia (P=0.035), and radiation dose (P=0.000) proved to be significant factors for survival. On multivariate analysis,age (P=-0.024), radiation dose(P=-0.001), and tumor size (P=0.000) were the significant factors.CONCLUSION: 3D-CRT combined with TACE is an effective and feasible approach for HCC. Age, radiation dose and tumor size were found to be significant prognostic factors for survival of patients with HCC treated by 3D-CRT combined with TACE. Further study for HCC is needed to improve the treatment efficacy.     

Postresection recurrence of hepatocellular carcinoma treated by arterial embolization: analysis of prognostic factors.

Of 270 consecutive patients with hepatocellular carcinoma who underwent surgery, 50 who had recurrence and were subsequently treated with transcatheter arterial embolization were analyzed. The longest interval between surgery and recurrence in the 50 patients who underwent transcatheter arterial embolization was 7 yr. Recurrence was initially found in the remnant liver in all patients but one; extrahepatic metastases were detected in 13 patients (26%) during follow-up. A "multiple" type was the most common (64%) hepatic recurrence pattern on angiography, followed by the "solitary" (16%) and "tumor thrombus" (12%) patterns. Hepatic recurrence was most frequently found in the ipsilateral lobe (48%) relative to the site of the primary hepatocellular carcinoma. Multivariate analysis of the factors affecting survival after transcatheter arterial embolization indicated that recurrence pattern (p = 0.025) and distant metastases (p = 0.011) were significant. Of 13 patients with distant metastases, 11 had the "multiple" pattern of hepatic recurrence. Survival rates for all 50 patients after initial surgery and after transcatheter arterial embolization were 90% and 64%, respectively, at 1 yr; 52% and 24%, respectively, at 3 yr; and 27% and 5%, respectively, at 5 yr. On analysis of survival rates after transcatheter arterial embolization in 37 patients with recurrence only in the liver and of the response of recurrent hepatocellular carcinoma to transcatheter arterial embolization, a significant difference was noted between those with "partial response" and "progressive disease" (p less than 0.05) and between those with "no change" and "progressive disease" (p less than 0.05).     

Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival.

We analyzed the growth pattern of tumor masses and the survival of 39 asymptomatic Italian patients with a total of 59 small (less than or equal to 5 cm in diameter) hepatocellular carcinomas arising from cirrhosis. The total length of the observation period ranged from 90 to 962 days, with an average of 364 +/- 229 (mean +/- S.D.). Doubling time ranged from 27.2 to 605.6 days (mean +/- S.D., 204.2 +/- 135; median = 171.6 days). Three different growth patterns were recognized: (a) tumors with no or very slow initial growth pattern (doubling time greater than 200 days), 10 cases (37%); (b) tumors with declining growth rate over time, 9 cases (33.4%); and (c) tumors with almost constant growth rate, 8 cases (29.6%). Using the stepwise discriminant analysis, we found a score based on albumin, alcohol intake, number of nodules, echo pattern and histological type that allowed a correct prediction of short doubling time (less than or equal to 150 days) in 55.6%, medium doubling time (151 to 300 days) in 60% and long doubling time (greater than 300 days) in 100% of cases. The estimated survival rate of the 39 patients, calculated by the Kaplan-Meier method was 81% at 1 yr, 55.7% at 2 yr and 21% at 3 yr. Stepwise discriminant analysis showed that a score based on sex, HBsAg status, alcohol consumption, ascites, gamma-glutamyltranspeptidase, prothrombin time, Child-Pugh class and all the sonographical parameters could predict 2-yr survival in 100% of cases. We conclude that great variability of growth patterns exists among and within small hepatocellular carcinomas. Prediction of subsequent growth rate is unreliable in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transcatheter arterial chemoembolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma

AIM:To evaluate the efficacy of transcatheter arterial chemoembolization(TACE) using a suspension of a fine-powder formulation of cisplatin(DDPH) for hepatocellular carcinoma(HCC).METHODS:The study population was comprised of 164 patients who were treated by TACE alone.Of these patients,76 underwent TACE using a suspension of DDPH in lipiodol(LPD)(DDPH group),and the remaining 88 underwent TACE with an emulsion of doxorubicin(ADM) with LPD(ADM group).We compared the DDPH group with the ADM group in terms of...