Varices on computed tomography as predictor of survival after hepatic resection in patients with single hepatocellular carcinoma.

BACKGROUND AND AIM: The aim of this study was to evaluate whether presence of varices on computed tomography (CT) could predict treatment outcome for hepatocellular carcinoma patients. METHODS: We enrolled 241 patients with single hepatocellular carcinoma ≤ 5 cm treated by surgery. With the use of preoperative CT/endoscopy, patients were classified into the following: presence of standard clinically significant portal hypertension (CSPH) surrogate, defined as varices on esophagogastroduodenoscopy and/or thrombocytopenia with splenomegaly (group 1, n = 47); varices on CT without standard CSPH surrogate (group 2, n = 45); and none of both (group 3, n = 149). Development of posthepatectomy liver failure and overall survival (OS) were evaluated for each patient group, and patients were re-classified into two groups according to presence of CT-enhanced CSPH surrogate, defined as standard surrogate and/or varices on CT. Predictive power of each survival model was compared using Harrell's C-index. RESULTS: Posthepatectomy liver failure rate in group 2 was similar to that in group 1 (53.3% [24/45] vs. 55.3% [26/47]; P = 1.000) but significantly higher than that in group 3 (53.3% [24/45] vs. 28.2% [42/149], P = 0.002). Seven-year OS rates in group 2 were similar to those in group 1 (55.6% vs. 60.8%, P = 0.988) but significantly lower than those in group 3 (55.6% vs. 83.3%, P = 0.001). Presence of standard CSPH surrogate (hazard ratio = 1.89 [1.08-3.30], P = 0.025) and CT-enhanced CSPH surrogate (hazard ratio = 2.60 [1.56-4.39], P < 0.001) were significant predicting factor for OS. However, CT-enhanced CSPH surrogate had significantly higher Harrell's C-index than standard surrogate (0.619 vs. 0.553, P = 0.034). CONCLUSION: The presence of CT-enhanced CSPH surrogate including varices on CT was the significant predictive of poor OS, providing better predictive power than standard surrogate.

Size discrepancy between sonographic and computed tomographic/magnetic resonance imaging measurement of hepatocellular carcinoma: the necessity of tumor size measurement standardization.

OBJECTIVES: There is no standardized method for size measurement of hepatocellular carcinoma. The purpose of this study was to evaluate whether the size and stage of hepatocellular carcinoma differ according to the imaging modality. METHODS: This retrospective study was approved by our Institutional Review Board, and written informed consent was waived. Patients with hepatocellular carcinoma who underwent either computed tomography (CT) or magnetic resonance imaging (MRI) along with planning sonography for radiofrequency ablation on the same day were included. A total of 113 patients with 127 hepatocellular carcinomas were included. The sizes of the tumors were measured and the tumor stages were assessed on CT/MRI and sonography. The results were compared by a t test, Bland-Altman limits of agreement, and a McNemar test. RESULTS: There was a significant difference in the hepatocellular carcinoma size between CT/MRI and sonographic measurements (mean difference, 0.26 cm; P < .0001). The sizes of 102 tumors (80.3%) were larger on sonography than on CT/MRI. Twelve tumors (9.5%) were the same size and 13 (10.2%) were smaller on sonography than on CT/MRI. There was also difference in the tumor stage (very early or not) between CT/MRI and sonography (P= .006, McNemar test). The stage was discordant in 16 of 127 tumors (12.6%). Among 69 tumors at the very early stage on CT/MRI, 14 (20.3%) were beyond the very early stage on sonography. CONCLUSIONS: The size of hepatocellular carcinoma measured on sonography tends to be larger than on CT/MRI; therefore, the tumor stage can differ between sonography and CT/MRI.

Radiofrequency ablation of high-grade dysplastic nodules.

UNLABELLED: High-grade dysplastic nodules (HGDNs) are known to be premalignant lesions of hepatocellular carcinoma (HCC). We devised a model to estimate the long-term survival benefit of treating HGDNs by radiofrequency ablation (RFA) (Group I), as compared with regular follow-up and timely treatment by resection (Group II). A hypothetical 60-year-old compensated patient with cirrhosis was assumed. The system being modeled was assumed to be a simple Markov process, and state transition probabilities were given as parameters. Data used for simulation were obtained by a systematic review of the literature. The reported overall malignant transformation rates of HGDNs ranged from 12.5% to 80.8%, and were assumed to be 20%, 50%, and 80% using the best, moderate, and worst scenarios for Group II, respectively. The 5-year overall survival benefit of Group I compared with Group II was calculated by summing the detrimental effect of overtreatment and the beneficial effects of avoiding operative mortality. When the overall malignant transformation rate was set at 20%, 50%, or 80% the expected additional 5-year overall survival benefits of Group I compared with Group II were -0.05%, 0.20%, and 0.47%, respectively, and the corresponding additional 10-year overall survival benefits were 0.03%, 0.33%, and 0.55%, respectively. One-way sensitivity analysis showed that Group I was preferable to Group II in terms of 5-year overall survival when the 5-year overall malignant transformation rate was greater than 25.9%. CONCLUSION: No definite evidence indicates that the treatment of HGDNs by RFA provides additional long-term overall survival benefit as compared with regular follow-up and timely treatment. The findings of the present study concur with the present American Association for the Study of Liver Diseases guidelines.

Hepatic resection versus radiofrequency ablation for very early stage hepatocellular carcinoma: a Markov model analysis.

UNLABELLED: No adequate randomized trials have been reported for a comparison between hepatic resection (HR) versus radiofrequency ablation (RFA) for the treatment of patients with very early stage hepatocellular carcinoma (HCC), defined as an asymptomatic solitary HCC <2 cm. For compensated cirrhotic patients with very early stage HCC, a Markov model was created to simulate a randomized trial between HR (group I) versus primary percutaneous RFA followed by HR for cases of initial local failure (group II) versus percutaneous RFA monotherapy (group III); each arm was allocated with a hypothetical cohort of 10,000 patients. The primary endpoint was overall survival. The estimates of the variables were extracted from published articles after a systematic review. In the parameter estimations, we assumed the best scenario for HR and the worst scenario for RFA. The mean expected survival was 7.577 years, 7.564 years, and 7.356 years for group I, group II, and group III, respectively. One-way sensitivity analysis demonstrated that group II was the preferred strategy if the perioperative mortality rate was greater than 1.0%, if the probability of local recurrence following an initial complete ablation was <1.9% or if the positive microscopic resection margin rate was >0.3%. The 95% confidence intervals for the difference in overall survival were -0.18-0.18 years between group I and II, 0.06-0.36 years between group I and III, and 0.13-0.30 years between group II and III, respectively. CONCLUSION: Primary percutaneous RFA followed by HR for cases of initial local failure was nearly identical to HR for the overall survival of compensated cirrhotic patients with very early stage HCC.

Radiofrequency ablation versus surgical resection as primary treatment of hepatocellular carcinoma meeting the Milan criteria: a systematic review.

BACKGROUND AND AIM: Surgery is the standard treatment option for hepatocellular carcinoma (HCC) meeting the Milan criteria, defined as single HCC ≤ 5 cm in maximum diameter or up to three nodules ≤ 3 cm. However, favorable survival outcomes have also been reported for these HCCs following radiofrequency ablation (RFA). METHODS: We performed a systematic review to compare the results of hepatic resection and percutaneous RFA as a primary treatment option of HCC meeting the Milan criteria. Studies were identified by searching MEDLINE on PubMed, the Cochrane Library database and CANCERLIT using appropriate key words. RESULTS: In all six identified observational studies, there were no statistically significant differences in overall survival rates between the two treatment modalities. The results of two randomized trials are controversial, while the power of these randomized trials is too limited to reach a reliable conclusion. In practice, the choice of treatment between surgery and RFA largely depends on the relationship between the local recurrence and perioperative mortality rates of HCC patients. Following RFA, local recurrence rates are low when a minimal safety margin ≥ 4-5 mm is achieved. A previous simulation study of overall survival for very early stage HCC, defined as an asymptomatic solitary small HCC ≤ 2 cm, showed that primary RFA with a 9% local recurrence rate is comparable to surgical resection with a 3% operative mortality rate. CONCLUSION: Acquisition of a sufficient safety margin seems to be a critical factor before recommending wider application of RFA as primary treatment for HCCs that meet the Milan criteria.

Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies.

UNLABELLED: According to the American Association for the Study of Liver Diseases guidelines, percutaneous ethanol injection (PEI) is a safe and highly effective treatment for small hepatocellular carcinomas (HCC) and should be the standard against which any new therapy is compared. The primary purpose of this study was to identify survival benefit of any percutaneous ablation therapy as compared with PEI in the treatment of patients with unresectable HCC. The secondary endpoints were initial tumor response, local tumor progression, and complications. Randomized controlled trials that compared pecutaneous ablative therapies with PEI were included. MEDLINE, the Cochrane Library, CANCERLIT, and manual search from 1978 to July 2008 were used. To control the potential heterogeneity, the random effects model of DerSimonian and Laird was used for a meta-analysis. Egger's test was performed to test a potential publication bias. We identified seven randomized controlled trials (RCTs), but only four RCTs including 652 patients that compared radiofrequency ablation (RFA) with PEI met the inclusion criteria to perform a meta-analysis assessing 3-year survival. A meta-analysis of the four RCTs demonstrated a significant improvement in 3-year survival favoring RFA over PEI (odds ratio 0.477, 95% confidence interval 0.340-0.670; P < 0.001). Heterogeneity among the four trials was not significant (Q = 4.586; P= 0.205). Egger's test revealed that the publication bias was not significant (P = 0.647). However, the number of patients included in the analysis was insufficient for a robust meta-analysis of initial tumor response. The definition of local tumor progression or major complication was not unified among the trials included in the meta-analysis. CONCLUSION: RFA demonstrated significantly improved 3-year survival status for patients with HCC, when compared to PEI.

Combined anomaly of the right hepatic lobe agenesis and absence of the inferior vena cava: a case report.

The absence of the inferior vena cava is an uncommon congenital anomaly that has recently been identified as an important risk factor contributing to the development of deep venous thrombosis. Congenital agenesis of the right hepatic lobe is a rare anomaly which is found incidentally in radiologic examinations. We present a case of a congenital absence of the infrarenal inferior vena cava, combined with agenesis of the right hepatic lobe in a 62-year-old man presented with symptoms of deep venous thrombosis.

Multivariate analysis of the predictors of survival for patients with hepatocellular carcinoma undergoing transarterial chemoembolization: focusing on superselective chemoembolization.

OBJECTIVE: While the prognostic factors of survival for patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE) are well known, the clinical significance of performing selective TACE for HCC patients has not been clearly documented. We tried to analyze the potential factors of disease-free survival for these patients, including the performance of selective TACE. MATERIALS AND METHODS: A total of 151 patients with HCC who underwent TACE were retrospectively analyzed for their disease-free survival (a median follow-up of 23 months, range: 1-88 months). Univariate and multivariate analyses were performed for 20 potential factors by using the Cox proportional hazard model, including 19 baseline factors and one procedure-related factor (conventional versus selective TACE). The parameters that proved to be significant on the univariate analysis were subsequently tested with the multivariate model. RESULTS: Conventional or selective TACE was performed for 40 and 111 patients, respectively. Univariate and multivariate analyses revealed that tumor multiplicity, venous tumor thrombosis and selective TACE were the only three independent significant prognostic factors of disease-free survival (p = 0.002, 0.015 and 0.019, respectively). CONCLUSION: In our study, selective TACE was a favorable prognostic factor for the disease-free survival of patients with HCC who underwent TACE.

Non-hypervascular Hypointense Nodules on Hepatocyte Phase Gadoxetic Acid-Enhanced MR Images: Transformation of MR Hepatobiliary Hypointense Nodules into Hypervascular Hepatocellular Carcinomas.

BACKGROUND/AIMS: The annual risk of transformation of non-hypervascular magnetic resonance (MR) hepatobiliary phase imaging (HBPI) hypointense nodules into hypervascular hepatocellular carcinomas (HCCs) was evaluated. METHODS: Cirrhotic patients with non-hypervascular HBPI hypointense nodules were retrospectively analyzed if they were diagnosed as HCC and MR followed up longer than 1 year during the period from January 2010 to October 2016 with regular intervals of 3 to 6 months. Risk factors for transformation into hypervascular HCCs were analyzed using the Cox proportional hazard model. RESULTS: Among the 103 non-hypervascular HBPI hypointense nodules meeting the inclusion criteria, transformation into hypervascular HCCs occurred in 44 tumors (42.7%). The median follow-up period was 24 months. Multivariate analysis revealed that hyperintensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI) were the two independent predictors of transformation into hypervascular HCCs (p=0.036 and p=0.041, respectively). Most tumors with hyperintensity on T2WI or DWI on the initial or follow-up MR were transformed into hypervascular HCCs within the first year. Among the 22 nodules (21.3%) showing a new change in dynamic phases during follow-up, 14 nodules (13.6%) showed malignant transformations. CONCLUSIONS: The transformation rates of HBPI hypointense nodules into hypervascular HCCs could be predicted according to the initial or serial MRI findings.

Local recurrence of hepatocellular carcinoma after segmental transarterial chemoembolization: risk estimates based on multiple prognostic factors.

OBJECTIVE: To determine the prognostic factors for local recurrence of nodular hepatocellular carcinoma after segmental transarterial chemoembolization. MATERIALS AND METHODS: Seventy-four nodular hepatocellular carcinoma tumors < or = 5 cm were retrospectively analyzed for local recurrence after segmental transarterial chemoembolization using follow-up CT images (median follow-up of 17 months, 4-77 months in range). The tumors were divided into four groups (IA, IB, IIA, and IIB) according to whether the one-month follow-up CT imaging, after segmental transarterial chemoembolization, showed homogeneous (Group I) or inhomogeneous (Group II) iodized oil accumulation, or whether the tumors were located within the liver segment (Group A) or in a segmental border zone (Group B). Comparison of tumor characteristics between Group IA and the other three groups was performed using the chi-square test. Local recurrence rates were compared among the groups using the Kaplan-Meier estimation and log rank test. RESULTS: Local tumor recurrence occurred in 19 hepatocellular carcinoma tumors (25.7%). There were: 28, 18, 17, and 11 tumors in Group IA, IB, IIA, and IIB, respectively. One of 28 (3.6%) tumors in Group IA, and 18 of 46 (39.1%) tumors in the other three groups showed local recurrence. Comparisons between Group IA and the other three groups showed that the tumor characteristics were similar. One-, two-, and three-year estimated local recurrence rates in Group IA were 0%, 11.1%, and 11.1%, respectively. The difference between Group IA and the other three groups was statistically significant (p = 0.000). CONCLUSION: An acceptably low rate of local recurrence was observed for small or intermediate nodular tumors located within the liver segment with homogeneous iodized oil accumulation.

Risk factors for local tumor recurrence after segmental transarterial chemoembolization for hepatocellular carcinoma: the importance of tumor located in the segmental border zone.

OBJECTIVE: We wanted to evaluate whether tumors located in a segmental border zone are predisposed to local recurrence after performing segmental transarterial chemoembolization for hepatocellular carcinoma. MATERIALS AND METHODS: Seventy-three hepatocellular carcinoma nodules were retrospectively analyzed for local tumor recurrence after performing segmental transarterial chemoembolization by using follow-up CT studies (median follow-up period: 20 months, range: 4-77 months). The tumors were divided into two groups according to whether the lesions were located at the segmental border zone (Group I) or not (Group II). Comparison of the tumor characteristics and chemoembolization methods between the two groups was performed using the chi-square test. The local recurrence rates were compared by Kaplan-Meyer method and analyzed with the log rank test. RESULT: Local tumor recurrence occurred for 25 hepatocellular carcinoma nodules (42.9%). The follow-up periods, tumor characteristics and chemoembolization methods between Groups l and ll were comparable. The local recurrence rate was 64.0% (16/25) in Group I and 18.8% (9/48) in Group II. The difference was statistically significant on the univariate and multivariate analyses (p = 0.000 for both). CONCLUSION: Tumor location in a segmental border zone was a significant risk factor for local tumor recurrence after performing segmental transarterial chemoembolization for hepatocellular carcinoma.

Transarterial Chemoembolization for Hepatocellular Carcinomas with Central Bile Duct Invasion: Safety, Prognosis, and Predictive Factors.

PURPOSE: To assess the safety and effectiveness of transarterial chemoembolization (TACE) of patients who have hepatocellular carcinomas (HCCs) with central bile duct invasion. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived informed consent. Fifty-three patients, initially treated with TACE for HCCs with central bile duct invasion from January 1999 to September 2012, were included. Clinical, laboratory, and survival data were reviewed. Complications and hospitalization length were evaluated using the χ(2) test, Fisher's exact test, and logistic regression analysis. Survival was analyzed using the Kaplan-Meier method with log-rank test and Cox proportional hazard model. RESULTS: Seven patients experienced TACE-related major complications (severe post-embolization syndrome in 3, non-fatal sepsis in 3, and secondary bacterial peritonitis in 1). The overall major complication rate was 13.2%, but there were no permanent adverse sequelae or deaths within 30 days. Serum total bilirubin ≥ 3.0 mg/dL was the only significant risk factor for long hospitalization [hazard ratio (HR) = 4.341, p = .022]. The median survival was 12.2 months. Extrahepatic metastasis (HR = 6.145, p < .001), international normalized ratio (PT-INR) ≥ 1.20 (HR = 4.564, p < .001), vascular invasion (HR = 3.484, p = .001), and intermediate tumor enhancement (HR = 2.417, p = .019) were significantly associated with shorter survival. CONCLUSION: TACE can be a safe and effective treatment for patients who have HCCs with central bile duct invasion. In particular, long-term survival can be expected if patients have strongly enhancing tumors without poor prognostic factors such as extrahepatic metastasis, PT-INR prolongation, and vascular invasion.

Detecting hepatocellular carcinoma in gadoxetic-acid-enhanced hepatobiliary-phase MR imaging at 3T: comparing high and low flip angle.

PURPOSE: We evaluated the diagnostic performance of fat-suppressed 3D T1-weighted gradient-echo magnetic resonance imaging (MRI) sequences for the hepatobiliary phase of gadoxetic-acid-enhanced liver MRI between low and high flip angle (FA) at 3T. MATERIALS AND METHODS: Forty-six patients with 62 HCCs were enrolled in this retrospective study from among 267 consecutive patients who underwent 3T MRI with low and high FA (10° and 25°) sequences at the hepatobiliary phase. A radiologist measured signal intensities and standard deviations (SD) of lesion, liver, and spleen and calculated signal-to-noise ratio, liver-spleen contrast, and liver-lesion contrast. Two reviewers assessed both image sequences using a five-point rating scale focusing on detecting hypointense lesions. RESULTS: The high FA sequence showed significantly higher liver-spleen and liver-lesion contrast compared with those of low FA (p < 0.05, p < 0.05, respectively). Per-lesion sensitivities of high FA were higher than those of low FA (p < 0.05, p < 0.05, respectively), and per-person sensitivities were elevated on high FA (p < 0.05 in a reviewer). There were statistically significant differences for detecting HCCs larger than 1 cm (p < 0.05, p < 0.05, respectively). CONCLUSION: Increasing FA in T1-weighted hepatobiliary-phase liver MRI may help in detecting HCC at 3T.