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Objective To investigate the distribution of traditional Chinese medicine (TCM) syndrome types and elements in liver cirrhosis patients with dysplastic nodules (DN), and to provide a basis for exploring the connotation and pattern of TCM syndrome types of DN in liver cirrhosis. Methods A total of 138 patients who attended The First Affiliated Hospital of Henan University of Chinese Medicine from March 2013 to January 2021 and were diagnosed with liver cirrhosis and DN were enrolled. General data such as age of onset and sex were collected, as well as the data on etiology, TCM syndrome types, and Child-Pugh class for liver function, and the distribution characteristics of TCM syndrome types and elements were summarized. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results The liver and the spleen were the main syndrome elements of disease location in liver cirrhosis patients with DN, accounting for 97.83% and 94.93%, respectively, followed by the kidney (23.91%); Qi deficiency and Qi stagnation were the main syndrome elements reflecting the nature of disease, accounting for 73.91% and 58.70%, respectively, followed by dampness (34.78%). The main TCM syndrome types included stagnation of liver Qi and spleen deficiency, damp-heat internal excess syndrome, blood stasis and toxin accumulation syndrome, and water-dampness retention syndrome, among which stagnation of liver Qi and spleen deficiency was more common and accounted for 58.70% ( P 0.05). There was a significant difference in Child-Pugh class between the liver cirrhosis DN patients with different TCM syndrome types ( χ 2 =34.320, P < 0.05), and Child-Pugh class A was more common in the patients with stagnation of liver Qi and spleen deficiency (59.8%), while Child-Pugh class C was more common in the patients with damp-heat internal excess syndrome (39.1%). Conclusion This article summarizes the distribution characteristics of common TCM syndrome types and elements of DN in liver cirrhosis, which provides a reference for the syndrome differentiation-based TCM treatment of DN in liver cirrhosis.
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Objective@#To investigate the risk factors for diagnosis of transformation of high-grade dysplastic nodules (HGDN) to hypervascular hepatocellular carcinoma (HCC) in patients with chronic liver disease with gadoxetate disodium-enhanced magnetic resonance imaging (MRI).@*Methods@#2 037 cases that underwent gadoxetate disodium-enhanced magnetic resonance imaging from January 2012 to December 2014 were retrospectively analyzed. 51 cases of HGDN with a background of chronic liver disease were screened and followed-up for at least 2 times with gadoxetate disodium-enhanced MRI scans and contrast enhanced CT scans was performed within 1 month before and after the first MRI. The endpoint of study was transformation of HGDN to hypervascular hepatocellular carcinoma, with a deadline of April 2019. Transformation was divided into transformed (group A) and untransformed (group B) group according to the presence or absence of hypervascularization. Linear regression was used to analyze the possible risk factors for hypervascular transformation.@*Results@#There were 36 nodules in group A and 79 nodules in group B, and hypervascular transformation rate was 31.3% (36/115). On univariate analysis, the length and diameter of nodule was > 10.2 mm (P = 0.034), with annual growth rate > 2% (P < 0.001), and lipid content (P = 0.007) was related to the occurrence of hypervascularity. On multivariate analysis, the annual growth rate of nodules was an independent risk factor for the occurrence of hypervascularity (P < 0.000 1).@*Conclusion@#The annual growth rate of HGDN in patients with chronic liver disease diagnosed with gadoxetate disodium-enhanced MRI imaging can be used as a potential predictor of hypervascularization.
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Hepatocarcinogenesis is a multi-step process in which detection of precancerous lesions and advanced hepatocellular carcinoma in its progressive stage is crucially important for predicting tumor behavior, estimating the extent of lesions, implementing the optimal treatment strategy, and improving the survival of patients. The rapid development and wide application of liver imaging technology, especially the application of hepatocyte-specific gadoxetate disodium MRI contrast agent (Gd-EOB-DTPA MRI), not only provide information on vascular changes of liver nodules and hepatocyte function, but also has become a precise diagnostic method for differentiating cirrhotic regenerative nodule (RN), low-grade dysplastic nodule (LGDN), high-grade dysplastic nodule (HGDN), early hepatocellular carcinoma and HCC. Hence, the risk for malignant progression is stratified. This review summarizes the value of Gd-EOB-DTPA MRI for early HCC diagnosis and analyzes the key concepts in the multi-step process of HCC development as well as the imaging manifestations of precancerous lesions that may eventually be transformed into typical HCC.
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The occurrence of hepatocellular carcinoma (HCC) is a multistep development process through precancerous lesions. A precancerous lesion of HCC is classified into hepatocyte dysplasia at the cytological level and dysplastic nodules at the histological level, and the corresponding lesion subtypes have different risks of canceration. Pathology is the "gold standard" for the diagnosis of early stage HCC and its precancerous lesions. However, it also faces many difficulties and challenges, such as the accumulation of experience in the pathological diagnosis, the understanding and grasp of key points of histopathological diagnosis and differential diagnosis, the combination application of immune and molecular diagnostic markers, and many others. This article briefly discusses the key points of pathological features and differential diagnosis of precancerous lesions of HCC.
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Objective@#To explore the value of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA) enhanced MRI T1 mapping in diagnosing and distinguishing dysplastic nodule (DN) and hepatocellular carcinoma (HCC) with different degrees of differentiation.@*Methods@#A retrospective study in the first affiliated Hospital of Guangxi Medical University from September 2015 to December 2017 was conducted. Seventy-one patients with HCC or DN (a total of 79 lesions) that confirmed by biopsy or surgical pathology findings. Seventy-nine lesions were divided into DN (n=10), well differentiated HCC (n=15), moderately differentiated HCC (n=36) and poorly differentiated HCC (n=18) according to histopathology. All the patients underwent plain MRI scan and Gd-EOB-DTPA-MRI T1 mapping before surgery or needle biopsy. The T1 values of each lesion and non-tumorous liver parenchyma were measured on 20 min hepatobiliary phase (HBP) T1 mapping after Gd-EOB-DTPA administration, respectively. The increment rate of T1 value in lesions relative to non-tumorous liver parenchyma were calculated. One-way ANOVA was used to compare the differences of T1 value and the increment rate of T1 value of DN and 3 groups of HCC with different degrees of differentiation. Spearman correlation was used to evaluate the correlation between T1 mapping parameters and the malignancy degree of DN and HCC. Area under the receiver operating characteristic (ROC) curves were used to evaluate the efficacy of T1 mapping parameters in the differential diagnosis of DN and HCC with different degree of differentiation.@*Results@#Significant differences were found in T1 value and increase rate of T1 value of DN and HCC with different degrees of differentiation (P< 0.05). The T1 value and increase rate of T1 value showed an increasing trend from DN to poorly differentiated HCC after enhancement. The T1 value and increase rate of T1 value were positively correlated with the malignancy of DN and HCC (r=0.418 and 0.634, P<0.01). There were significant differences in the increase rate of T1 value between well-differentiated HCC and moderately-differentiated, well-differentiated HCC and poorly-differentiated HCC, respectively (P<0.05). The area under ROC curve of T1 value and the increase rate of T1 value for differentiating DN from well-differentiated, moderately differentiated and poorly differentiated HCC was 0.933, 0.928, 0.939 and 0.867, 0.961, 0.961, respectively. The area under ROC curve of the increase rate of T1 value for differentiating well-differentiated HCC from moderately-differentiated, well-differentiated HCC from poorly-differentiated HCC was 0.770 and 0.844, respectively.@*Conclusions@#Gd-EOB-DTPA enhanced MRI combined with T1 mapping can provide valuable diagnostic information for identifying DN and HCC with different degrees of differentiation.
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Objective To investigate the features of low grade dysplastic nodule(LGDN)and high grade dysplastic nodule(HGDN)in cirrhotic liver on the baseline ultrasound(BUS)and contrast-enhanced ultrasound (CEUS).Methods Seventeen LGDNs and 16 HGDNs which were pathologically proved underwent baseline and CEUS examination.CEUS was performed with contrast pulse sequence(CPS)and contrast harmonic imaging (CHI)and used SonoVue as contrast agent.Results Significant differences(all P>0.05)were not shown between LGDN and HGDN for manifestations on both the BUS and CEUS.After contrast agent injected, hyperenhancement in arterial phase and hyper-or iso-enhancement in late phase,hypo-enhancement in early arterial phase and iso-enhancement through late arterial,portal and late phase,hyper-enhancement in arterial phase and hypo-enhancement in late phase,iso-enhancement in arterial,portal and late phase,iso-enhancement in arterial phase and hypo-enhancement in late phase were showed in 10(30.3%),10(30.3%),8(24.3%),4(12.1%),1(3.0%)cases of DN, respectively.Conclusions LGDN and HGDN displayed similar feature on both the BUS and CEUS.There were complicated manifestations of DN on the CEUS and the main contrast-enhanced sonographic feature of DN was,different from regenerative nodule and hepatocellular carcinoma.CEUS was helpful in diagnosing DN in cirrhotic liver.
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No abstract available.
Subject(s)
Adult , Humans , Male , Carcinoma, Hepatocellular/diagnosis , Cell Transformation, Neoplastic , Liver Neoplasms/diagnosis , Magnetic Resonance Imaging , Tomography, X-Ray ComputedABSTRACT
In recent years, growing number of literatures have supported the concept that large nodules usually found in cirrhotic livers represent premalignant lesions in the setting of chronic liver disease. With the use of advanced imaging techniques, nodules suspicious for malignancy have often been identified and resected. While some resected lesions were found to be small hepatocellular carcinomas (HCCs), others were not. Some of these non-malignant nodules were devoid of atypia, some had architectural or cytological atypia insufficient for a diagnosis of HCC though they are suggestive of a premalignant state, while others contained microscopic subnodules of HCC. In follow-up studies and series of explants from liver transplant centers, the occasional finding of microscopic foci of HCC in the nodules was confirmed and significant associations with HCC elsewhere in the same liver were established. Such findings suggested that these nodular lesions, which are referred as "dysplastic nodules" (or adenomatous hyerplasia), are probably a frequent pathway in human hepatocarcinogenesis. We discuss the pathological characteristics of dysplastic nodules and small HCCs.
Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , English Abstract , Liver Neoplasms/pathologyABSTRACT
In order to clarify the significance of E-cadherin methylation in multistep hepatocarcinogenesis, we examined the methylation status of the E-cadherin promoter region, using methylation-specific polymerase chain reaction in 64 hepatocellular carcinomas (HCCs) and 13 dysplastic nodules (DNs), and correlated these results with E-cadherin protein expression and clinicopathologic factors of HCCs. Promoter methylation was detected in 1 of 13 (7.7%) DNs, in 5 of 13 (38.5%) Edmondson and Steiner grade I HCCs, and in 27 of 51 (52.9%) grade II or III HCCs, and a significant correlation was observed between the methylation status and the stepwise progression of hepatocarcinogenesis (p=0.004). Reduced E-cadherin immunoreactivity was found in 18 of 64 (28%) HCCs, but in none of DNs. E-cadherin methylation status in HCCs was significantly correlated with microvascular invasion (p=0.02) and tumor recurrence (p=0.04), but not with reduced E-cadherin immunoreactivity. The Kaplan-Meier method showed that methylation status did not have a significant influence on the recurrence-free survival of HCC patients (p=0.15). Our results indicate that methylation of the E-cadherin promoter region is a frequent event in HCC, which may play an important role in the stepwise progression of hepatocarcinogenesis. And the promoter methylation of E-cadherin in HCC was found to be significantly correlated with microvascular invasion and recurrence.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Cadherins/genetics , Carcinoma, Hepatocellular/genetics , CpG Islands , Liver Neoplasms/genetics , Precancerous Conditions/genetics , Promoter Regions, GeneticABSTRACT
Deranged expression of cell cycle modulators has been reported to contribute to the development and progression of hepatocellular carcinoma (HCC). However, their expression patterns remain poorly understood in hepatitis B virus (HBV)-related HCC, which constitutes about 65-70% of HCC in Korea. The aims of this study were to evaluate the expressions of G1-S modulators in HBV-related HCCs and dysplastic nodules (DNs), and to correlate with the histopathologic features of HCCs. Immunohistochemical expressions of cyclin D1, cyclin E, p53, p27, p21, p16, Rb, and PCNA proteins were investigated in 80 HCCs and 22 DNs. Cyclin D1 overexpression showed positive relationships with advanced tumor stage, poor differentiation, larger tumor size, microvascular invasion, intrahepatic meta-stasis, no tumor capsule formation, infiltrative growth, aberrant p53 expression, and high PCNA labeling index (LI) of HCC (p<0.05). Aberrant p53 expression showed positive relationship with poor differentiation of HCC (p<0.01). Expression of cyclin D1 or p53 was not observed in DNs. The p27 LI and p16 LI were lower in HCCs with intrahepatic metastasis (p<0.05). Cyclin D1 overexpression and aberrant p53 expression could be associated with the progression of HBV-related HCC, and might have a less crucial role in the DN-HCC sequence. In addition, elevated expression of p27 and p16 proteins might have inhibitory action to the intrahepatic metastasis of HBV-related HCC.
Subject(s)
Adult , Aged , Female , Humans , Male , Carcinoma, Hepatocellular/chemistry , Cyclin D1/analysis , G1 Phase , Hepatitis B/complications , Immunohistochemistry , Liver Neoplasms/chemistry , Microfilament Proteins/analysis , Middle Aged , Precancerous Conditions/virology , Proliferating Cell Nuclear Antigen/analysis , Cyclin-Dependent Kinase Inhibitor p16/analysis , Tumor Suppressor Protein p53/analysis , Retinoblastoma Protein/analysis , S PhaseABSTRACT
Promyelocytic leukemia protein (PML) is a major component of PML nuclear bodies (PML NBs). Fusion of promyelocytic leukemia gene (PML) with retinoic acid receptor alpha gene with the t (15;17) translocation causes disassembly of PML NBs, leading to development of acute promyelocytic leukemia. In contrast, PML overexpression as well as different morphological changes of PML NBs were described in a few solid tumors. In this study, the expression of PML through the multistep hepatocarcinogenesis was analyzed in 95 cases of human hepatocellular carcinomas (HCCs) for comparison along with dysplastic nodules (DNs) and background liver cirrhosis (LC) or chronic hepatitis by immunohistochemistry and immunoblot. In addition, cases of HCCs were further evaluated according to their histologic grade and etiology. The amount of PML as well as the num-ber and size of PML NBs increased gradually through the progression from LC, DNs to HCCs. The overexpression of PML in HCCs was much more closely associated with HBV infection than HCV infection or alcoholic liver disease. The PML expression, however, was not correlated with histologic grade of HCCs. These results suggest that PML is involved in the early stage of multistep hepatocarcinogenesis, and HBV infection may be associated with the overexpression of PML and the morphological alteration of PML NBs.
Subject(s)
Humans , Carcinoma, Hepatocellular/chemistry , Cell Nucleus/chemistry , Liver/chemistry , Liver Neoplasms/chemistry , Neoplasm Proteins/analysis , Precancerous Conditions/chemistry , Transcription Factors/analysis , Tumor Cells, CulturedABSTRACT
p21 is a universal inhibitor of cyclin-dependent kinase (cdk) and of cell-cycle progression. p21 expression is variable according to the type of tissue and the pathologic condition. To study the role of p21 in the multistep hepatocarcinogenesis, the expression of p21, p53 and Ki-67 was investigated in 53 cases of inactive liver cirrhosis, 4 cases of low grade dysplastic nodules, 3 cases of high grade dysplastic nodules, 7 cases of early hepatocellular carcinomas (HCCs), 27 cases of small HCCs (3 cm). p21 expression was not detected in liver cirrhosis, low grade dysplastic nodules, high grade dysplastic nodules and early HCCs which were mitotically inactive. p21 expression was significantly increased in small HCCs and advanced HCCs which were mitotically active. p21 expression was significantly correlated with Ki-67 labelling indices. p53 protein was not expressed in liver cirrhosis, dysplastic nodules, and early HCCs. The expression of p53 protein was, however, significantly increased in small and advanced HCCs. The p21 expression was not correlated with p53 expression. Therefore, p21 is suggested to play a role in the mitotically active small and advanced HCCs, but not in the mitotically inactive lesion of dysplastic nodules and early HCC in multistep hepatocarcinogenesis. These findings suggest that homeostatic mechanism of growth control is not totally destroyed in HCC.
Subject(s)
Humans , Carcinoma, Hepatocellular , Cell Proliferation , Liver Cirrhosis , PhosphotransferasesABSTRACT
Dysplastic nodule (DN), which is nodular hepatocellular proliferation of at least 1mm in diameter, is detected most often through radiological and pathological observations in chronic advanced liver diseases. DNs characteristically contain portal tracts and they can be classified into low grade for mild atypia and high grade for at least moderate atypia that is insufficient for the diagnosis of malignancy. DNs are supplied portal venous blood and arterial blood supply. In unpaired arteries, new angiogenesis, shows stepwise increases in the following order of DN low grade, DN high grade, early hepatocellular carcinoma and hepatocellular carcinoma. There are convincing clinicopathological data to support the premise that DNs are considered to be precancerous lesions and early stages of multistep processes of hepatocellular carcinogenesis. Extensive clinicopathological and molecular study can provide a better understanding of the characteristics of DNs and new therapeutic approaches to DNs.