Predictors of Hepatocellular Carcinoma Early Recurrence in Patients Treated with Surgical Resection or Ablation Treatment: A Single-Center Experience.

Introduction: Hepatocellular carcinoma (HCC) is the sixth most diagnosed malignancy and the fourth leading cause of cancer-related death worldwide, with poor overall survival despite available curative treatments. One of the most crucial factors influencing survival in HCC is recurrence. The current study aims to determine factors associated with early recurrence of HCC in patients with BCLC Stage 0 or Stage A treated with surgical resection or local ablation. Materials and Methods: We retrospectively enrolled 58 consecutive patients diagnosed with HCC within BCLC Stage 0 or Stage A and treated either by surgical resection or local ablation with maximum nodule diameter < 50 mm. In the first year of follow-up after treatment, imaging was performed regularly one month after treatment and then every three months. Each case was discussed collectively by the Liver Multidisciplinary Group to decide diagnosis, treatment, follow-up, and disease recurrence. Variables resulting in statistically significant difference were then studied by Cox regression analysis; univariately and then multivariately based on forward stepwise Cox regression. Results are represented in hazard ratio (H.R.) with 95% confidence interval (C.I.). Results: There was no statistically significant difference in recurrence rates (34.8 vs. 45.7%, log-rank test, p = 0.274) between patients undergoing surgical resection and local ablation, respectively. Early recurrence was associated with male gender (HR 2.5, 95% C.I. 1.9−3.1), nodule diameter > 20 mm (HR 4.5, 95% C.I. 3.9−5.1), platelet count < 125 × 103 cell/mm3 (HR 1.6, 95% C.I. 1.2−1.9), platelet-lymphocyte ratio < 95 (HR 2.1, 95% C.I. 1.7−2.6), lymphocyte-monocyte ratio < 2.5 (HR 1.9, 95% C.I. 1.4−2.5), and neutrophil-lymphocyte ratio > 2 (HR 2.7, 95% C.I. 2.2−3.3). Discussion and Conclusions: Our results are in line with the current literature. Male gender and tumor nodule dimension are the main risk factors associated with early HCC recurrence. Platelet count and other combined scores can be used as predictive tools for early HCC recurrence, although more studies are needed to define cut-offs.

MicroRNAs Related to TACE Treatment Response: A Review of the Literature from a Radiological Point of View.

Hepatocellular Carcinoma (HCC) is the sixth most common cancer in the world. Patients with intermediate stage (Barcelona Clinic Liver Cancer, B stage) hepatocellular carcinoma (HCC) have been able to benefit from TACE (transarterial chemoembolization) as a treatment option. MicroRNAs (miRNAs), i.e., a subclass of non-coding RNAs (ncRNAs), participate in post-transcriptional gene regulation processes and miRNA dysfunction has been associated with apoptosis resistance, cellular proliferation, tumor genesis, and progression. Only a few studies have investigated the role of miRNAs as biomarkers predicting TACE treatment response in HCC. Here, we review the studies' characteristics from a radiological point of view, also correlating data with radiological images chosen from the cases of our institution.

Evidence of diagnostic enhancement pattern in hepatocellular carcinoma nodules ≤2 cm according to the AASLD/EASL revised criteria.

PURPOSE: To define the percentage of small (≤2 cm) hepatocellular carcinoma (HCC) nodules showing the diagnostic enhancement pattern at CEUS, computed tomography (CT), and gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance (MR) imaging. METHODS: 42 cirrhotic patients (26 male, 16 female; 67 ± 12 years) with 46 biopsy-proven HCCs ≤2 cm were included. Each HCC was scanned by CEUS, contrast-enhanced CT, and Gd-BOPTA-enhanced MR imaging. Nodule enhancement was evaluated by two readers. Independent analysis was followed by consensual analysis and the proportion of HCCs with the diagnostic enhancement pattern (nodule hyperenhancing on hepatic arterial phase and hypoenhancing on portal venous-late phase) on CEUS, CT, and MR imaging was compared by chi-square test. RESULTS: Very good inter-reader agreement was observed on hepatic arterial phase and portal venous-late phase: CEUS, k = 0.89 and 0.85; CT, k = 0.91 and 0.88; MR imaging, k = 0.96 and 0.94. CEUS and CT did not differ in the percentage of HCC nodules with a diagnostic enhancement pattern (18/46 and 16/46; P = 0.66), while MR imaging revealed the diagnostic pattern in higher percentage of nodules (29/46; P = 0.012) in comparison to CEUS and CT. CONCLUSIONS: CEUS and contrast-enhanced CT did not differ in the percentage of small HCC nodules with diagnostic enhancement pattern, while Gd-BOPTA-enhanced MR imaging revealed the diagnostic pattern in a higher nodule number in comparison to CEUS and CT.

Predictors of dysplastic nodule diagnosis in patients with liver cirrhosis on unenhanced and gadobenate dimeglumine-enhanced MRI with dynamic and hepatobiliary phase.

OBJECTIVE: The purpose of this article is to assess whether unenhanced and gadobenate dimeglumine-enhanced MRI with dynamic and hepatobiliary phase may predict the diagnosis of dysplastic nodules in patients with liver cirrhosis. MATERIALS AND METHODS: We retrospectively analyzed 75 cirrhotic patients (47 men and 28 women; mean [± SD] age, 55 ± 12 years) with 82 hepatocellular nodules, including histology-proven dysplastic nodules (n = 25; diameter, 1-3 cm) and hepatocellular carcinomas (n = 57; diameter, 2-3 cm) scanned by MRI before and after gadobenate dimeglumine injection during hepatic arterial phase (HAP), portal venous phase (PVP), equilibrium phase, and hepatobiliary phase. Nodule T1 and T2 intensities before contrast agent injection and nodule HAP, PVP, equilibrium phase, and hepatobiliary phase intensities were compared with the adjacent liver. Univariate and multivariate logistic regression analysis was conducted to assess how the nodule could predict dysplastic nodule diagnosis. RESULTS: Some imaging findings were independent predictors of dysplastic nodule diagnosis-namely, nodule T2 isohypointensity (odds ratio [OR], 12.28; 95% CI, 3.88-38.82), T1 isohyperintensity (OR, 26.74; 95% CI, 7.53-94.90), HAP isohypointensity (OR, 97.16; 95% CI, 20.06-470.49), PVP-equilibrium phase isohyperintensity (OR, 20.53; 95% CI, 5.36-78.62), and hepatobiliary phase isohyperintensity (OR, 119.6; 95% CI, 21.59-662.40). Nodule T2 and HAP isohypointensity (OR 31.47; 95% CI, 7.88-125.58), nodule T2 isohypointensity and hepatobiliary phase isohyperintensity (OR, 28.77; 95% CI, 7.79-106.19), nodule T1 isohyperintensity and HAP isohypointensity (OR, 17.22; 95% CI, 4.85-61.14), and nodule T1 and hepatobiliary phase isohyperintensity (OR, 19.39; 95% CI, 5.38-69.90) were also predictors of dysplastic nodule diagnosis. CONCLUSION: The combination of nodule appearance on T2-weighted MRI and nodule enhancement after gadobenate dimeglumine injection may predict dysplastic nodule diagnosis in patients with liver cirrhosis.

Arterial enhancing-only nodules less than 2 cm in diameter in patients with liver cirrhosis: predictors of hepatocellular carcinoma diagnosis on gadobenate dimeglumine-enhanced MR imaging.

PURPOSE: To assess whether gadobenate dimeglumine (Gd-BOPTA)-enhanced MR imaging could predict hepatocellular carcinoma (HCC) diagnosis in small arterial enhancing-only nodules detected by contrast-enhanced computed tomography (CT) in patients with liver cirrhosis. MATERIALS AND METHODS: We prospectively recruited 125 cirrhotic patients (67 males, and 58 females; age: 68 ± 12.36 years) with 151 small (<2 cm in diameter) arterial enhancing-only nodules identified by contrast-enhanced CT. All patients were scanned by MR imaging before and after Gd-BOPTA injection during the hepatic arterial phase (HAP), portal venous phase (PVP), equilibrium phase (EP), and hepatobiliary phase (HP). Nodule characterization was based on reference imaging criteria (n = 29 nodules), follow-up (n = 105), or histology (n = 17). Two radiologists (5 and 10 years experience) analyzed the MR images, and logistic regression was conducted to assess how well MR imaging findings could predict HCC diagnosis. RESULTS: Final diagnoses included 115 benign nodules and 36 HCCs. Nodule T2 hyperintensity, T1 hypointensity, PVP-EP hypointensity, and HP hypointensity were the best predictors of HCC on univariate analysis. Nodule T2 hyperintensity, T1 hypointensity, and HP hypointensity, were independent predictors of HCC on multivariate analysis. CONCLUSION: Gd-BOPTA-enhanced MR imaging provides imaging findings which may predict a diagnosis of HCC in small arterial enhancing-only nodules in cirrhotic patients.

Effect of observer experience in the differentiation between benign and malignant liver tumors after ultrasound contrast agent injection.

OBJECTIVE: The purpose of this study was to assess the impact of the observer level of experience on the diagnostic performance of contrast-enhanced ultrasound imaging (CEUS) for differentiation between benign and malignant liver tumors. METHODS: From a computerized search, we retrospectively identified 286 biopsy-proven liver tumors (105 hepatocellular carcinomas, 48 metastases, 7 intra-hepatic cholangiocarcinomas, 33 liver hemangiomas, and 93 nonhemangiomatous benign lesions) in 235 patients (140 male and 95 female; mean age +/- SD, 56 +/- 11 years) who underwent CEUS after sulfur hexafluoride-filled microbubble injection. The digital cine clips recorded during the arterial (10-35 seconds from injection), portal (50-120 seconds), and late (130-300 seconds) phases were analyzed by 6 independent observers without experience (group 1, observers 1-3) or with 2 to 10 years of experience in CEUS (group 2, observers 4-6). Specific training in the diagnostic and interpretative criteria was provided to the inexperienced observers. Each observer used a 5-point scale to grade diagnostic confidence: 1, definitely benign; 2, probably benign; 3, indeterminate; 4, probably malignant; or 5, definitely malignant on the basis of the enhancement pattern during the arterial phase and enhancement degree during the portal and late phases compared with the liver (hypoenhancement indicating malignant and isoenhancement to hyperenhancement indicating benign). RESULTS: The analysis of observer diagnostic confidence revealed higher intragroup (kappa = 0.63-0.83) than intergroup (kappa = 0.47-0.63) observer agreement. The experienced observers showed higher diagnostic performance in malignancy diagnosis than did inexperienced observers (overall accuracy: group 1, 63.3%-72.8%; group 2, 75.9%-93.1%; P < .05, chi(2) test). CONCLUSIONS: The diagnostic performance of CEUS in liver tumor characterization was dependant on the observer's level of experience.

The diagnostic value of small bowel wall vascularity after sulfur hexafluoride-filled microbubble injection in patients with Crohn's disease. Correlation with the therapeutic effectiveness of specific anti-inflammatory treatment.

PURPOSE: To assess the value of small bowel wall vascularity after microbubble contrast agent injection in evaluating the therapeutic effectiveness of specific anti-inflammatory treatment in patients with Crohn's disease. MATERIALS AND METHODS: Fifteen patients (7 male and 8 female; mean age+/-SD, 40 years+/-6) with a biopsy-proven diagnosis of Crohn's disease--Crohn's disease activity index (CDAI)>150 (n=12 patients) or <150 (n=3)--involving the terminal loop of the small bowel (wall thickness>5 mm) were included. In each patient the terminal loop was scanned by contrast-enhanced ultrasound (CEUS) after sulfur hexafluoride-filled microbubble injection before and after 6-month anti-inflammatory treatment. The vascularity of the terminal loop was quantified in gray-scale levels (0-255) by a manually drawn ROI encompassing the thickened bowel wall and it was correlated with CDAI. RESULT: Before the beginning of the specific treatment all patients revealed diffuse transparietal contrast enhancement after microbubble injection, except for 3 patients who revealed contrast enhancement limited to the submucosa. In 13 patients the slope of the first ascending tract and the area under the enhancement curve were significantly lower after anti-inflammatory treatment (P<0.05; Wilcoxon test) with a significant correlation with the CDAI score (rho=0.85, P<0.05). In 2 patients no significant vascularity changes were found even though a mild reduction of CDAI score was identified (from 200 to 150 gray-scale levels). CONCLUSION: CEUS is a useful method to assess the therapeutic effectiveness of specific medical anti-inflammatory treatment in patients with Crohn's disease.

Comparison of contrast-enhanced sonography with unenhanced sonography and contrast-enhanced CT in the diagnosis of malignancy in complex cystic renal masses.

OBJECTIVE: The objective of our study was to evaluate contrast-enhanced sonography in the diagnosis of malignancy in complex cystic renal masses. MATERIALS AND METHODS: We analyzed a series of 40 cystic renal masses (diameter, 2-8 cm) with a complex pattern at contrast-enhanced CT in 40 consecutive subjects (18 men, 22 women; mean age +/- SD, 62 +/- 11 years). Each renal mass was scanned using sonography without contrast material and after IV injection of sulfur hexafluoride-filled microbubbles during the arterial (15-40 seconds) and venous (40-120 seconds from injection) phases. Two radiologists in consensus assessed onsite the enhancement patterns in the peripheral wall and intracystic septa and the evidence of solid endocystic components. Three blinded readers with 2, 6, and 10 years of experience in renal imaging performed a retrospective off-site interpretation of unenhanced sonography, contrast-enhanced sonography, and CT images and made a benign or malignant diagnosis according to refer ence diagnostic criteria for contrast-enhanced sonography and to the Bosniak classification for CT. RESULTS: Final diagnoses comprised two multilocular cystic nephromas, two inflammatory and seven hemorrhagic cysts, and eight uncomplicated benign cysts and 21 cystic renal cell carcinomas. The overall diagnostic accuracy of contrast-enhanced sonography was better than unenhanced sonography and CT (contrast-enhanced sonography vs unenhanced sonography vs CT: reader 1, 83% vs 30% vs 75%; reader 2, 83% vs 30% vs 63%; reader 3, 80% vs 30% vs 70%; p < 0.05, McNemar test). CONCLUSION: Contrast-enhanced sonography was found to be better than unenhanced sonography and CT in the diagnosis of malignancy in complex cystic renal masses.