We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato- cellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 m...We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato- cellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven. US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia, and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia. Moreover, immunohistochemical staining of cyclase- associated protein 2, a new molecular marker of well- differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.展开更多
Contrast-enhanced ultrasound(CEUS)using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis.CEUS can be used as a problem-solving method for indeterminate nodules on computed tom...Contrast-enhanced ultrasound(CEUS)using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis.CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography(CT)or magnetic resonance imaging(MRI)or as an initial diagnostic test for small newly detected liver nodules.CEUS has unique advantages over CT and MRI including no renal excretion of contrast,real-time imaging capability,and purely intravascular contrast.Hepatocellular carcinoma(HCC)is characterized by arterial-phase hypervascularity and later washout(negative enhancement).Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase.However,there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout.Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rimlike or diffuse hypervascularity followed by rapid washout.Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS.CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance.CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC.展开更多
AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the d...AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)related HCC.METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucoseregulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r= 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.展开更多
AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver. METHODS: Two hundred and...AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver. METHODS: Two hundred and twelve hepatocellular nodules (106 HCC; 74 IRN, 32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA). RESULTS: HCA distributed HCC, DN, and HRN as defined by traditional histological evaluation as well as the individual histological variables, in a "malignancy scale". Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss, capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool classified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepandes were present for DN and MRN between the routine histological assignment and the dassification tool. Of 25 HCC assigned by routine assessment in the validation set, 8 were assigned to the DN category by the classification tool. CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this toolsystematically records histological features of diagnostic importance in the evaluation of small HCC.展开更多
AIM:To elucidate the variety of ways early-stage hepatocellular carcinoma(HCC)can appear on magnetic resonance(MR)imaging by analyzing T1-weighted,T2-weighted,and gadolinium-enhanced dynamic studies.METHODS:Seventy-th...AIM:To elucidate the variety of ways early-stage hepatocellular carcinoma(HCC)can appear on magnetic resonance(MR)imaging by analyzing T1-weighted,T2-weighted,and gadolinium-enhanced dynamic studies.METHODS:Seventy-three patients with well-differentiated HCC(wHCC)or dysplastic nodules were retrospectively identified from medical records,and new histological sections were prepared and reviewed.The tumor nodules were categorized into three groups:dysplastic nodule(DN),wHCC compatible with Edmondson-Steiner grade I HCC(w1-HCC),and wHCC compatible with Edmondson-Steiner gradeⅡHCC(w2-HCC).The signal intensity on pre-contrast MR imaging and the enhancing pattern for each tumor were recorded and compared between the three tumor groups.RESULTS:Among the 73 patients,14 were diagnosed as having DN,40 were diagnosed as having w1-HCC,and 19 were diagnosed as having w2-HCC.Hyperintensity measurements on T2-weighted axial images(T2WI)were statistically significant between DNs and wHCC(P=0.006)and between DN and w1-HCC(P=0.02).The other imaging features revealed no significant differences between DN and wHCC or between DN and w1-HCC.Hyperintensity on both T1W out-phase imaging(P=0.007)and arterial enhancement on dynamic study(P=0.005)showed statistically significant differences between w1-HCC and w2-HCC.The other imaging features revealed no significant differences between w1-HCC and w2-HCC.CONCLUSION:In the follow-up for a cirrhotic nodule,increased signal intensity on T2WI may be a sign of malignant transformation.Furthermore,a noted loss of hyperintensity on T1WI and the detection of arterial enhancement might indicate further progression of the histological grade.展开更多
Objective:To investigate the differences of apparent diffusion coefficient and transverse relaxation rate(R_(2)^(*))in magnetic resonance imaging(MRI)between micro hepatocellular carcinoma and nodules of cirrhosis.Met...Objective:To investigate the differences of apparent diffusion coefficient and transverse relaxation rate(R_(2)^(*))in magnetic resonance imaging(MRI)between micro hepatocellular carcinoma and nodules of cirrhosis.Method:The clinical data of 68 patients with micro hepatocellular carcinoma(76 lesions)and 45 patients with nodular cirrhosis(48 lesions)were retrospectively analyzed.Diffusion weighted imaging and R_(2)^(*)imaging were performed on all patients.The differences of apparent diffusion coefficient and R_(2)^(*)values in patients with micro hepatocellular carcinoma and nodular cirrhosis were compared.Receiver operating characteristic(ROC)curves were drawn to evaluate the diagnostic efficacy of apparent diffusion coefficient values and R_(2)^(*)values for microhepatocellular carcinoma.Result:Compared with nodules of cirrhosis,the mean apparent diffusion coefficient and R_(2)^(*)value of micro-hepatocellular carcinoma were significantly decreased(P<0.05).The diagnosis threshold of apparent diffusion coefficient is at 1.35×10^(-3)mm^(2)/s,and the sensitivity for the diagnosis of micro-hepatocellular carcinoma was 80.88%,and the specificity was 91.11%,and the corresponding area under the ROC curve was 0.88;The diagnostic threshold for R_(2)^(*)value was at 53.96 Hz,and the sensitivity for the diagnosis of small hepatocellular carcinoma was 91.18%,and the specificity was 77.78%,and the corresponding area under the ROC curve was 0.84.Conclusion:MRI apparent diffusion coefficient value and R_(2)^(*)value can be used to differentiate and diagnose micro hepatocellular carcinoma and nodules of cirrhosis,in which the apparent diffusion coefficient of nodules of cirrhosis was less than 1.35×10^(-3)mm^(2)/s,R_(2)^(*)values were lower than 53.96 Hz may indicate the occurrence of nodular canceration.展开更多
Hepatic regenerative nodules are reactive hepatocellular proliferations that develop in response to liver injury.Giant hepatic regenerative nodules of 10 cm or more are extremely rare and have only been reported in pa...Hepatic regenerative nodules are reactive hepatocellular proliferations that develop in response to liver injury.Giant hepatic regenerative nodules of 10 cm or more are extremely rare and have only been reported in patients with biliary atresia or Alagille syndrome.A 50-year-old man presented with a pathologically confirmed giant 11.3×9.4×11.2 cm hepatic regenerative nodule and hepatitis B virus-related cirrhosis.Imaging of intrahepatic nodule included mild hyperenhancement in the portal phase of contrast-enhanced CT and the hepatobiliary phase in the gadoxetic acid-enhanced MRI scan,as well as the portal vein crossing through sign in the setting of liver cirrhosis.This case highlights the imaging characteristics of giant hepatic regenerative nodules in hepatitis cirrhosis.展开更多
Objective: To assess if diffusion-weighted magnetic resonance (MR) imaging without apparent diffusion coefficient (ADC) values provides added diagnostic value in combination with conventional MR imaging in the de...Objective: To assess if diffusion-weighted magnetic resonance (MR) imaging without apparent diffusion coefficient (ADC) values provides added diagnostic value in combination with conventional MR imaging in the detection and characterization of small nodules in cirrhotic liver. Methods: Two observers retrospectively and independently analyzed 86 nodules (_〈3 em) certified pathologically in 33 patients with liver cirrhosis, including 48 hepatocellular carcinoma (HCC) nodules, 13 high-grade dysplastic nodules (HDN), 10 low-grade dysplastic nodules (LDNs) and 15 other benign nodules. All these focal nodules were evaluated with conventional MR images (Tl-weighted, T2-weighted and dynamic gadolinium-enhanced images) and breath-hold diffusion-weighted images (DWI) (b=500 s/mm2). The nodules were classified by using a scale of 1-3 (1, not seen; 3, well seen) on DWI for qualitative assessment. These small nodules were characterized by two radiologists. ADC values weren't measured. The diagnostic performance of the combined DWI-conventional images and the conventional images alone was evaluated using receiver operating characteristic (ROC) curves. The area under the curves (Az), sensitivity and specificity values for characterizing different small nodules were also calculated. Results: Among 48 HCC nodules, 33 (68.8%) were graded as 3 (well seen), 6 (12.5%) were graded as 2 (partially obscured), and 9 weren't seen on DWI. Among 13 HDNs, there were 3 (23.1%) and 4 (30.8%) graded as 3 and 2 respectively. Five (50%) of 10 benign nodules were partially obscured and slightly hyperintense. For 86 nodules, the average diagnostic accuracy of combined DWI-conventional images was 82.56%, which was increased significantly compared with conventional MR images with 76.17%. For HCC and HDN, the diagnostic accuracy of combined DWI-conventional images increased from 78.69% to 86.07 %. Conclusions: Diffusion-weighted MR imaging does provide added diagnostic value in the detection and characterization of HDN and HCC, and it may not be helpful for LDN and regenerative nodule (RN) in cirrhotic liver.展开更多
文摘We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato- cellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven. US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia, and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia. Moreover, immunohistochemical staining of cyclase- associated protein 2, a new molecular marker of well- differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.
文摘Contrast-enhanced ultrasound(CEUS)using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis.CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography(CT)or magnetic resonance imaging(MRI)or as an initial diagnostic test for small newly detected liver nodules.CEUS has unique advantages over CT and MRI including no renal excretion of contrast,real-time imaging capability,and purely intravascular contrast.Hepatocellular carcinoma(HCC)is characterized by arterial-phase hypervascularity and later washout(negative enhancement).Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase.However,there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout.Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rimlike or diffuse hypervascularity followed by rapid washout.Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS.CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance.CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC.
基金Supported by the fund from the Korea Science and Engineering Foundation (Grant No. R01-2001-00098). Seung Oe Lim was supported by BK21 Research Fellowship from the Ministry of Education and Human Resources Development
文摘AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)related HCC.METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucoseregulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r= 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.
文摘AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver. METHODS: Two hundred and twelve hepatocellular nodules (106 HCC; 74 IRN, 32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA). RESULTS: HCA distributed HCC, DN, and HRN as defined by traditional histological evaluation as well as the individual histological variables, in a "malignancy scale". Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss, capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool classified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepandes were present for DN and MRN between the routine histological assignment and the dassification tool. Of 25 HCC assigned by routine assessment in the validation set, 8 were assigned to the DN category by the classification tool. CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this toolsystematically records histological features of diagnostic importance in the evaluation of small HCC.
文摘AIM:To elucidate the variety of ways early-stage hepatocellular carcinoma(HCC)can appear on magnetic resonance(MR)imaging by analyzing T1-weighted,T2-weighted,and gadolinium-enhanced dynamic studies.METHODS:Seventy-three patients with well-differentiated HCC(wHCC)or dysplastic nodules were retrospectively identified from medical records,and new histological sections were prepared and reviewed.The tumor nodules were categorized into three groups:dysplastic nodule(DN),wHCC compatible with Edmondson-Steiner grade I HCC(w1-HCC),and wHCC compatible with Edmondson-Steiner gradeⅡHCC(w2-HCC).The signal intensity on pre-contrast MR imaging and the enhancing pattern for each tumor were recorded and compared between the three tumor groups.RESULTS:Among the 73 patients,14 were diagnosed as having DN,40 were diagnosed as having w1-HCC,and 19 were diagnosed as having w2-HCC.Hyperintensity measurements on T2-weighted axial images(T2WI)were statistically significant between DNs and wHCC(P=0.006)and between DN and w1-HCC(P=0.02).The other imaging features revealed no significant differences between DN and wHCC or between DN and w1-HCC.Hyperintensity on both T1W out-phase imaging(P=0.007)and arterial enhancement on dynamic study(P=0.005)showed statistically significant differences between w1-HCC and w2-HCC.The other imaging features revealed no significant differences between w1-HCC and w2-HCC.CONCLUSION:In the follow-up for a cirrhotic nodule,increased signal intensity on T2WI may be a sign of malignant transformation.Furthermore,a noted loss of hyperintensity on T1WI and the detection of arterial enhancement might indicate further progression of the histological grade.
文摘Objective:To investigate the differences of apparent diffusion coefficient and transverse relaxation rate(R_(2)^(*))in magnetic resonance imaging(MRI)between micro hepatocellular carcinoma and nodules of cirrhosis.Method:The clinical data of 68 patients with micro hepatocellular carcinoma(76 lesions)and 45 patients with nodular cirrhosis(48 lesions)were retrospectively analyzed.Diffusion weighted imaging and R_(2)^(*)imaging were performed on all patients.The differences of apparent diffusion coefficient and R_(2)^(*)values in patients with micro hepatocellular carcinoma and nodular cirrhosis were compared.Receiver operating characteristic(ROC)curves were drawn to evaluate the diagnostic efficacy of apparent diffusion coefficient values and R_(2)^(*)values for microhepatocellular carcinoma.Result:Compared with nodules of cirrhosis,the mean apparent diffusion coefficient and R_(2)^(*)value of micro-hepatocellular carcinoma were significantly decreased(P<0.05).The diagnosis threshold of apparent diffusion coefficient is at 1.35×10^(-3)mm^(2)/s,and the sensitivity for the diagnosis of micro-hepatocellular carcinoma was 80.88%,and the specificity was 91.11%,and the corresponding area under the ROC curve was 0.88;The diagnostic threshold for R_(2)^(*)value was at 53.96 Hz,and the sensitivity for the diagnosis of small hepatocellular carcinoma was 91.18%,and the specificity was 77.78%,and the corresponding area under the ROC curve was 0.84.Conclusion:MRI apparent diffusion coefficient value and R_(2)^(*)value can be used to differentiate and diagnose micro hepatocellular carcinoma and nodules of cirrhosis,in which the apparent diffusion coefficient of nodules of cirrhosis was less than 1.35×10^(-3)mm^(2)/s,R_(2)^(*)values were lower than 53.96 Hz may indicate the occurrence of nodular canceration.
文摘Hepatic regenerative nodules are reactive hepatocellular proliferations that develop in response to liver injury.Giant hepatic regenerative nodules of 10 cm or more are extremely rare and have only been reported in patients with biliary atresia or Alagille syndrome.A 50-year-old man presented with a pathologically confirmed giant 11.3×9.4×11.2 cm hepatic regenerative nodule and hepatitis B virus-related cirrhosis.Imaging of intrahepatic nodule included mild hyperenhancement in the portal phase of contrast-enhanced CT and the hepatobiliary phase in the gadoxetic acid-enhanced MRI scan,as well as the portal vein crossing through sign in the setting of liver cirrhosis.This case highlights the imaging characteristics of giant hepatic regenerative nodules in hepatitis cirrhosis.
基金supported by the Capital Medical Development Foundation(Grant No.2011-2015-02)the National Basic Research Program of China (973 Program)(Grant No.2011CB707705)the Capital Characteristic Clinical Application Research(Grant No.Z121107001012115)
文摘Objective: To assess if diffusion-weighted magnetic resonance (MR) imaging without apparent diffusion coefficient (ADC) values provides added diagnostic value in combination with conventional MR imaging in the detection and characterization of small nodules in cirrhotic liver. Methods: Two observers retrospectively and independently analyzed 86 nodules (_〈3 em) certified pathologically in 33 patients with liver cirrhosis, including 48 hepatocellular carcinoma (HCC) nodules, 13 high-grade dysplastic nodules (HDN), 10 low-grade dysplastic nodules (LDNs) and 15 other benign nodules. All these focal nodules were evaluated with conventional MR images (Tl-weighted, T2-weighted and dynamic gadolinium-enhanced images) and breath-hold diffusion-weighted images (DWI) (b=500 s/mm2). The nodules were classified by using a scale of 1-3 (1, not seen; 3, well seen) on DWI for qualitative assessment. These small nodules were characterized by two radiologists. ADC values weren't measured. The diagnostic performance of the combined DWI-conventional images and the conventional images alone was evaluated using receiver operating characteristic (ROC) curves. The area under the curves (Az), sensitivity and specificity values for characterizing different small nodules were also calculated. Results: Among 48 HCC nodules, 33 (68.8%) were graded as 3 (well seen), 6 (12.5%) were graded as 2 (partially obscured), and 9 weren't seen on DWI. Among 13 HDNs, there were 3 (23.1%) and 4 (30.8%) graded as 3 and 2 respectively. Five (50%) of 10 benign nodules were partially obscured and slightly hyperintense. For 86 nodules, the average diagnostic accuracy of combined DWI-conventional images was 82.56%, which was increased significantly compared with conventional MR images with 76.17%. For HCC and HDN, the diagnostic accuracy of combined DWI-conventional images increased from 78.69% to 86.07 %. Conclusions: Diffusion-weighted MR imaging does provide added diagnostic value in the detection and characterization of HDN and HCC, and it may not be helpful for LDN and regenerative nodule (RN) in cirrhotic liver.