gadoxetic-acid-disodium and Cell-Transformation--Neoplastic

With the increasing use of gadoxetic acid-enhanced MRI for HCC surveillance, hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) are frequently encountered. We investigated the rate of these nodules with hypervascular transformation, which suggests hepatocarcinogenesis, by using a prospectively collected longitudinal surveillance cohort data.. This study included 382 prospectively enrolled patients at high risk for developing HCC who underwent 1-3 rounds of bi-annual surveillance gadoxetic acid-enhanced MRI. MRI was analyzed to detect HBP hypointense nodules without APHE. Follow-up dynamic CTs and MRIs were evaluated to detect hypervascular transformation of the nodules. Cox proportional hazards regression analyses were used to find predictors for hypervascular transformation.. A total of 76 HBP hypointense nodules without APHE were found in 48 patients, giving a prevalence of 12.6% (48/382). The mean nodule size was 10.8 mm, with 43.4% (33/76) being ≥ 10 mm. Over a median follow-up of 78.6 months, 19 nodules (25.0%) showed hypervascular transformation, all of which demonstrated typical imaging features of HCC. On multivariable Cox-regression analysis, size (≥ 10 mm) was the only independent predictor of hypervascular transformation (hazard ratio, 3.31; 95% confidence interval, 1.21-9.05). The cumulative incidence of hypervascular transformation at 12 and 60 months of nodules ≥ 10 mm was 12.3% and 50.4%, respectively, while that of nodules < 10 mm was 2.5% and 13.9%, respectively.. About half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC at 5 years of follow-up, indicating the necessity for cautious monitoring with an augmented and extended follow-up schedule for these nodules.. • The prevalence of HBP hypointense nodules without APHE was 12.6% in a prospectively recruited population at high risk of developing HCC. • Nodule size ≥ 10 mm was significantly associated with hypervascular transformation, and approximately half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC during 5 years of follow-up. • Given the risk of malignant transformation, HBP hypointense nodules ≥ 10 mm without APHE should be closely monitored.

Topics: Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Contrast Media; Follow-Up Studies; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Retrospective Studies

The annual risk of transformation of non-hypervascular magnetic resonance (MR) hepatobiliary phase imaging (HBPI) hypointense nodules into hypervascular hepatocellular carcinomas (HCCs) was evaluated.. 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.. 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.. The transformation rates of HBPI hypointense nodules into hypervascular HCCs could be predicted according to the initial or serial MRI findings.

Topics: Aged; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Contrast Media; Diffusion Magnetic Resonance Imaging; Female; Gadolinium DTPA; Hepatocytes; Humans; Liver; Liver Neoplasms; Male; Neovascularization, Pathologic; Retrospective Studies

Many improvements have been made in diagnosing hepatocellular carcinoma (HCC), but the radiological hallmarks of HCC have remained the same for many years. We prospectively evaluated the imaging criteria of HCC, early HCC and high-grade dysplastic nodules (HGDNs) in patients under surveillance for chronic liver disease, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and diffusion-weighted imaging.. Our study population included 420 nodules >1 cm in 228 patients. The MRI findings of each nodule were collected in all sequences/phases. The diagnosis of HCC was made according to the American Association for the Study of Liver Diseases (AASLD) criteria; all atypical nodules were diagnosed using histology.. A classification and regression tree was developed using three MRI findings which were independently significant correlated variables for early HCC/HCC, and the best sequence of their application in a new diagnostic algorithm (hepatobiliary hypointensity, arterial hyperintensity and diffusion restriction) was suggested. This algorithm demonstrated, both in the entire study population and for nodules ≤2 cm, higher sensitivity (96% [95% CI 93.5% to 97.6%] and 96.6% [95% CI 93.9% to 98.5%], P<0.001, respectively) and slightly lower specificity (91.8% [95% CI 88.6% to 94.1%], P=0.063, and 92.7% [95% CI 88.9% to 95.4%], P=0.125, respectively) than those of the AASLD criteria. Our new diagnostic algorithm also showed a very high sensitivity (94.7%; 95% CI 92% to 96.6%) and specificity (99.3%; 95% CI 97.7% to 99.8%) in classifying HGDN.. Our new diagnostic algorithm demonstrated significantly higher sensitivity and comparable specificity than those of the AASLD imaging criteria for HCC in patients with cirrhosis evaluated using Gd-EOB-DTPA MRI, even for lesions ≤2 cm. Moreover, this diagnostic algorithm allowed evaluating other lesions which could arise in a cirrhotic liver, such as early HCC and HGDN.

Topics: Aged; Algorithms; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Contrast Media; Disease Progression; Early Detection of Cancer; Female; Gadolinium DTPA; Humans; Liver Cirrhosis; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity

Incidental detection of nonenhancing tumors during imaging studies for patients with classical hepatocellular carcinoma is not unusual. These tumors are considered to have a high potential of malignant transformation. The aim of this study was to clarify the natural history of such tumors.. In 93 patients who underwent liver resection for hepatocellular carcinoma, 138 nonenhancing or enhancing nodules without washout were detected during dynamic computed tomography and observed without further treatments. We subsequently compared the cumulative occurrence of new hepatocellular carcinomas to that of the malignant transformation of these lesions. We additionally compared the appearance of new hepatocellular carcinomas between the patients with (n = 93) and without (n = 782) nonenhancing lesions or enhancing lesions without washout.. After a median follow-up period of 0.7 years (range, 0.2-6.8), the median intervals from resection to the appearance of new classical hepatocellular carcinoma and malignant transformation of nonenhancing lesions or enhancing lesions without washout were 1.6 years (95% confidence interval, 1.2-1.9) and 2.3 years (1.9-6.8 years; P = .002), respectively. On the other hand, the median intervals from resection to the appearance of new lesions in patients with and without nonenhancing lesions or enhancing lesions without washout were 1.6 years (95% confidence interval, 1.2-1.9) and 2.1 years (1.9-2.1 years; P = .031), respectively.. During the natural history of nonenhancing lesions and enhancing lesions without washout that coexist with hepatocellular carcinoma, new lesions often develop prior to the malignant transformation of these lesions. This should be considered a risk factor for the appearance of new hepatocellular carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Contrast Media; Female; Gadolinium DTPA; Hepatectomy; Humans; Incidental Findings; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Multidetector Computed Tomography; Multimodal Imaging

To establish a prognostic formula that distinguishes non-hypervascular hepatic nodules (NHNs) with higher aggressiveness from less hazardous one.. Seventy-three NHNs were detected in gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) study and confirmed to change 2 mm or more in size and/or to gain hypervascularity. All images were interpreted independently by an experienced, board-certified abdominal radiologist and hepatologist; both knew that the patients were at risk for hepatocellular carcinoma development but were blinded to the clinical information. A formula predicting NHN destiny was developed using a generalized estimating equation model with thirteen explanatory variables: age, gender, background liver diseases, Child-Pugh class, NHN diameter, T1-weighted imaging/T2-weighted imaging detectability, fat deposition, lower signal intensity in arterial phase, lower signal intensity in equilibrium phase, α-fetoprotein, des-γ-carboxy prothrombin, α-fetoprotein-L3, and coexistence of classical hepatocellular carcinoma. The accuracy of the formula was validated in bootstrap samples that were created by resampling of 1000 iterations.. During a median follow-up period of 504 d, 73 NHNs with a median diameter of 9 mm (interquartile range: 8-12 mm) grew or shrank by 68.5% (fifty nodules) or 20.5% (fifteen nodules), respectively, whereas hypervascularity developed in 38.4% (twenty eight nodules). In the fifteen shrank nodules, twelve nodules disappeared, while 11.0% (eight nodules) were stable in size but acquired vascularity. A generalized estimating equation analysis selected five explanatories from the thirteen variables as significant factors to predict NHN progression. The estimated regression coefficients were 0.36 for age, 6.51 for lower signal intensity in arterial phase, 8.70 or 6.03 for positivity of hepatitis B virus or hepatitis C virus, 9.37 for des-γ-carboxy prothrombin, and -4.05 for fat deposition. A formula incorporating the five coefficients revealed sensitivity, specificity, and accuracy of 88.0%, 86.7%, and 87.7% in the formulating cohort, whereas these of 87.2% ± 5.7%, 83.8% ± 13.6%, and 87.3% ± 4.5% in the bootstrap samples.. These data suggest that the formula helps Gd-EOB-DTPA-MRI detect a trend toward hepatocyte transformation by predicting NHN destiny.

Topics: Aged; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Chi-Square Distribution; Contrast Media; Decision Support Techniques; Diagnosis, Differential; Disease Progression; Early Detection of Cancer; Female; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Factors; Time Factors; Tumor Burden

To determine the pathologic nature of non-hypervascular hypointense nodules (≥1 cm) on the hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance (MR) imaging and to describe the chronological changes of their imaging features on follow-up MR imaging.. This retrospective study was approved by our Institutional Review Board and the requirement for informed consent was waived. 69 patients with 115 non-hypervascular HBP hypointense nodules (≥1 cm in diameter) in cirrhotic livers were enrolled. 67 nodules were histologically diagnosed (group 1) and 52 nodules were followed up with MR for at least 12 months (group 2); 4 nodules belonged to both groups. Two radiologists reviewed the initial and follow-up MR images to determine the size and signal intensities on unenhanced T1- and T2-weighted images, dynamic phases and HBP images in consensus. In addition, two pathologists reviewed the histologic findings including H&E staining and four kinds of immunohistochemical staining in group 1.. In group 1, 73.1% (49/67) of nodules were hepatocellular carcinomas. In group 2, 32.7% (17/52) of nodules developed arterial hypervascularity on follow-up, and 78.8% (41/52) showed at least one of the three imaging features considered to indicate malignant changes during follow-up (mean 19 ± 10 months): increase in diameter by ≥5 mm (23/52, 44.2%), arterialization (17/52, 32.7%) and hyperintensity on T2-weighted images (18/52, 34.6%).. Our study results demonstrate that a significant proportion of non-hypervascular HBP hypointense nodules (≥1 cm in diameter) in patients with cirrhosis showed either malignant features on pathology (73.1%) or developed hypervascularity (32.7%) during follow-up.

Topics: Aged; Biopsy, Needle; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Cohort Studies; Early Detection of Cancer; Female; Follow-Up Studies; Gadolinium DTPA; Humans; Immunohistochemistry; Liver; Liver Cirrhosis; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Neovascularization, Pathologic; Radiographic Image Enhancement; Retrospective Studies; Risk Assessment; ROC Curve; Time Factors

Hypovascular nodules that exhibit hypointensity in hepatocyte-phase images of gadoxetic acid-enhanced magnetic resonance (MR) imaging are frequently encountered in clinical practice. We investigated risk factors for the development of these nodules into hypervascular hepatocellular carcinoma (HCC).. We retrospectively reviewed our institutional database and identified 302 patients who underwent gadoxetic acid-enhanced MR imaging for suspected or confirmed HCC from February 1, 2008 to January 30, 2011. We excluded patients who were examined for metastasis of other malignancies or for other hepatic tumors, such as focal nodular hyperplasia. We identified hypovascular nodules that were hypointense in hepatocyte-phase images, recorded their characteristics, and calculated the cumulative hypervascularization rate for nodules that were followed up.. Of the 302 patients, 82 had hypovascular nodules (178 nodules; mean size, 9.3 mm). Sixty nodules were followed up for over 6 months, and eight progressed to hypervascular HCC. Hypervascularization occurred more frequently in nodules with fat than those without (P<0.01). The cumulative hypervascularization rate was 5.1% over a year.. The presence of intralesional fat was found to be a risk factor for hypervascularization of hypovascular nodules that exhibited hypointensity in the hepatocyte-phase images of gadoxetic acid-enhanced MR imaging.

Topics: Adipose Tissue; Aged; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Contrast Media; Female; Gadolinium DTPA; Hepatocytes; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Neovascularization, Pathologic; Reproducibility of Results; Risk Factors; Sensitivity and Specificity

To evaluate the incidence and predictive factors of hypervascular transformation during follow-up of "high-risk nodules" detected in the hepatobiliary phase of initial Gd-EOB-DTPA-enhanced MRI in chronic liver disease patients.. A total of 109 patients with chronic liver disease who underwent Gd-EOB-DTPA-enhanced MRI several times were investigated. Of these, 43 patients had 76 high-risk nodules with both hypointensity in the hepatobiliary phase and hypovascularity in the arterial phase of initial MRI. These nodules were observed until hypervascularity was detected. MRI and clinical findings were compared to assess the incidence and potential predictive factors for hypervascular transformation between the group showing hypervascular transformation and the group not showing hypervascularization.. The median observation period was 242.5 ± 203.2 days (range, 47-802 days). Overall, 24 of 76 high-risk nodules (31.6%) showed hypervascular transformation during follow-up (median observation period, 186.0 ± 190.3 days). The growth rate of the nodules (P < 0.001), the presence of fat within nodules (P = 0.037), and hyperintensity on T1-weighted images (P = 0.018) were significantly correlated with hypervascularization.. Subsets of high-risk nodules tended to show hypervascular transformation during follow-up, with an increased growth rate, the presence of fat, and hyperintensity on T1-weighted images as predictive factors.

Topics: Adult; Aged; Aged, 80 and over; Cell Transformation, Neoplastic; Comorbidity; Contrast Media; Female; Gadolinium DTPA; Hepatitis, Chronic; Humans; Incidence; Japan; Liver Cirrhosis; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Neovascularization, Pathologic; Pilot Projects; Prognosis; Reproducibility of Results; Risk Assessment; Sensitivity and Specificity

To investigate the predictive factors of malignant transformation of hypovascular hepatic nodule showing hypointensity in the hepatobiliary phase images of gadoxetic acid-enhanced MRI (HHN).. The clinical data and imaging findings of dynamic contrast-enhanced computed tomography (DCE-CT) and gadoxetic acid-enhanced MRI for a total of 103 HHNs in 24 patients with chronic liver disease were retrospectively investigated. After the results of follow-up examinations were investigated, HHNs were categorized into the three groups for each comparison: (1) nodules with enlargement and/or vascularization and others, (2) nodules with only enlargement and others, (3) nodules with only vascularization and others. Enlargement and/or vascularization during the follow-up period were defined as malignant transformation of HHN. The frequency of each clinical datum and imaging finding in each group was compared to identify the predictive factors for malignant transformation in HHN.. Multivariate analysis showed that a nodule size of 9 mm or more on the initial gadoxetic acid-enhanced MRI was a significant predictive factor for the enlargement and/or vascularization of HHN (P<0.05). On the other hand, the hypoattenuation on the delayed phase imaging of the initial DCE-CT was a significant predictive factor for the enlargement or vascularization of HHN (P<0.05).. A nodule size of 9 mm or more on the initial gadoxetic acid-enhanced MRI and hypoattenuation on the delayed phase imaging of initial DCE-CT would be helpful for predicting the outcome of HHN in patients with a risk of hepatocellular carcinoma.

Topics: Aged, 80 and over; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Contrast Media; Female; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Neovascularization, Pathologic; Reproducibility of Results; Sensitivity and Specificity