Effect of acetylcysteine on prothrombin index in paracetamol poisoning without hepatocellular injury

DEFF Research Database (Denmark)

Schmidt, Lars E; Knudsen, Tore Tveit; Dalhoff, Kim

2002-01-01

Acetylcysteine treatment reduces liver damage after paracetamol overdose, but can affect the prothrombin index, which is used to assess the progress of overdose patients. We aimed to assess retrospectively the effect of intravenous acetylcysteine on the prothrombin index in patients with paraceta......Acetylcysteine treatment reduces liver damage after paracetamol overdose, but can affect the prothrombin index, which is used to assess the progress of overdose patients. We aimed to assess retrospectively the effect of intravenous acetylcysteine on the prothrombin index in patients...... with paracetamol poisoning without signs of hepatocellular injury. Prothrombin index had been recorded before, and serially during, acetylcysteine treatment in 87 patients. After initiation of treatment, prothrombin index decreased (mean 0.33, 95% CI 0.29-0.38) in all patients, and was strongly associated...... with the start of acetylcysteine infusion. In patients with uncomplicated paracetamol poisoning, a fall in this index might be misinterpreted as a sign of liver failure, leading to prolonged treatment time....

Detection of hepatocellular carcinoma: comparison of Gd-DTPA- and ferumoxides-enhanced MR imaging

International Nuclear Information System (INIS)

Simon, G.; Link, T.M.; Daldrup-Link, H.; Settles, M.; Woertler, K.; Doebereiner, F.; Schulte-Frohlinde, E.; Rummeny, E.J.

2005-01-01

The aim was to compare the diagnostic performance of dynamic Gd-DTPA- and ferumoxides-enhanced MRI for hepatocellular carcinoma (HCC). Twenty-five patients with chronic hepatitis or liver cirrhosis underwent both dynamic gadopentetate- and ferumoxides-enhanced MRI studies of the liver for HCC detection on the same day. MR data of both studies were retrospectively and independently analyzed. Two observers determined in consensus the grade of diffuse fibrotic liver changes (mild, moderate or severe) and the number of focal lesions. HCCs were confirmed by histology (n=22) and/or follow-up studies for at least six months (n=64). Differences in results obtained from both MR data sets were tested for significance with the McNemar's test (p 0.05) and Gd-DTPA-enhanced scans (94.2%). Gd-DTPA- and ferumoxides-enhanced MRI perform equally well for HCC detection. The majority of small hypervascular hepatic lesions, detected on dynamic Gd-DTPA-enhanced MRI but not on ferumoxides-enhanced MRI, represent no HCCs. (orig.)

Mangafodipir trisodium-enhanced MRI of hepatocellular carcinoma: correlation with histological characteristics

International Nuclear Information System (INIS)

Kim, J.H.; Kim, M.-J.; Park, Y.N.; Lee, J.T.; Kim, B.R.; Chung, J.B.; Choi, J.S.; Kim, K.S.; Kim, K.W.

2008-01-01

Aim: To define histopathological factors related to the degree of mangafodipir trisodium (MnDPDP) uptake in hepatocellular carcinomas (HCCs) on magnetic resonance imaging (MRI). Materials and methods: In-phase and opposed-phase gradient-echo MRI images were obtained preoperatively in 37 patients with 38 HCCs before and 15-30 min after intravenous injection of MnDPDP. Subjective ratings of the enhancement degree, the signal-to-noise ratio (SNR) of the lesion and the liver, and the contrast enhancement ratios (CER) were compared with histopathological factors. Results: The mean SNR of HCCs increased from 59.6 to 95.0 (CER = 59.5%), whereas that of the liver increased from 75.1 to 108.7 (CER = 45.2%). Eight HCCs showed mild enhancement, 11 moderate enhancement, and 15 strong enhancement. There was no visually perceptible enhancement in four HCCs (10.3%). The degree of MnDPDP enhancement was significantly related with the cell density ratio (p < .05) and monoclonal hepatocyte antibody positivity (p < 0.005), but not with size, growth type, cell type, histological type, cytokeratin 7, or cytokeratin 19. Well-differentiated HCC showed higher MnDPDP enhancement compared with higher grade HCCs, but the differences were not statistically significant. Conclusion: The uptake of MnDPDP by HCC was correlated with hepatocyte antibody expression and the cellular density ratio. Well-differentiated HCC tended to show higher MnDPDP enhancement

Computed tomography of liver tumors, 2. Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor by dynamic CT scanning

Energy Technology Data Exchange (ETDEWEB)

Naito, Akira; Fukuoka, Haruhito; Kashiwado, Kouzou; Ichiki, Toshio; Makidono, Yoko [Hiroshima Red Cross Hospital (Japan)

1984-02-01

Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor was attempted using dynamic CT scanning. Homogeneous and patchy types were peculiar to hepatocellular carcinoma, and ring-like type to metastatic hepatic tumor. However, with no enhancement, hepatocellular carcinoma could not be denied. Hepatocellular carcinoma was characterized by the enhancement shown on the early stage of dynamic CT. Ring enhancement was not visualized on dynamic CT but visualized on conventional contrast enhanced CT in hepatocellular carcinomas; it was visualized on conventional contrast enhanced CT and on dynamic CT in metastatic hepatic tumors.

Expression of toll-like receptors in hepatic cirrhosis and hepatocellular carcinoma.

Science.gov (United States)

Sun, L; Dai, J J; Hu, W F; Wang, J

2016-07-14

Toll-like receptors (TLRs) can specifically identify pathogen-associated molecular patterns (PAMPs) by recognizing structural patterns in diverse microbial molecules, and can provide an effective defense against multiple microbial infectious. A variety of TLRs can be expressed on the surface of liver parenchymal as well as nonparenchymal cells. Kupffer cells are a type of hepatic nonparenchymal macrophage, and are positively associated with the severity of liver fibrosis. They play an important role in the synthesis and deposition of the extracellular matrix by upregulating the expression of tissue inhibitor of metalloproteinases and downregulating the activity of matrix metalloproteinases. Cirrhosis, a chronic diffuse lesion usually accompanying extensive liver fibrosis and nodular regeneration, is caused by liver parenchymal cells repeating injury-repair following reconstruction of organizational structure in the hepatic lobules. Hepatocellular carcinoma is caused by repeated and persistent chronic severe liver injury, and partial hepatocytes can eventually transform into hepatoma cells. Multiple TLRs such as TLR2, TLR3, TLR4, and TLR9, as well as other receptors, can be expressed in cirrhosis and hepatocellular carcinoma. About 53 and 85% of hepatocellular carcinoma patients frequently express TLR3 and TLR9, respectively. The chronic and repeated liver injury caused by alcohol, and HBV, HCV, or other pathogens can be recognized by TLRs through the PAMP pathway, which directly increases the risk for hepatic cirrhosis and hepatocellular carcinoma. In this review, we briefly present evidence that the novel cellular molecular mechanisms of TLRs may provide more information about new therapeutics targets of the anti-inflammatory immune response.

Does Enhancement or Perfusion on Preprocedure CT Predict Outcomes After Embolization of Hepatocellular Carcinoma?

Science.gov (United States)

Borgheresi, Alessandra; Gonzalez-Aguirre, Adrian; Brown, Karen T; Getrajdman, George I; Erinjeri, Joseph P; Covey, Anne; Yarmohammadi, Hooman; Ziv, Etay; Sofocleous, Constantinos T; Boas, Franz Edward

2018-03-27

The objective of this study was to evaluate whether quantitative enhancement or perfusion measurements on preprocedure triphasic computed tomography (CT) can be used to predict response or overall survival after embolization of hepatocellular carcinoma. The institutional review board approved this retrospective review of 63 patients with hepatocellular carcinoma treated with particle embolization between March 2009 and December 2014. Quantitative enhancement and perfusion measurements were performed on the target tumor and the background liver on the triphasic CT performed before treatment. Microvascular invasion (MVI) and degree of differentiation were determined from a core biopsy specimen. Quantitative enhancement and perfusion values were then correlated with pathology (two-tailed t test), response to embolization on modified Response Evaluation Criteria In Solid Tumors (two-tailed t test), and overall survival after embolization (Cox proportional hazards model). Arterial enhancement did not predict immediate response or overall survival after embolization. The degree of differentiation or presence of MVI also did not predict immediate response or overall survival after embolization. However, high hepatic artery coefficient or low portal vein coefficient, both in the tumor (P = .011 and P = .004) and in the background liver (P = .015 and P = .009), were associated with worse survival. Hepatic artery coefficient, both in the tumor (P = .025) and in the background liver (P = .013), were independent predictors of survival in a multivariate model including the Child-Pugh score and the BCLC stage. Tumor and liver perfusion parameters estimated from preprocedure triphasic CT were predictive of survival after embolization. Arterial-phase enhancement and histology (degree of differentiation or MVI) did not predict immediate response or overall survival after particle embolization. Copyright © 2018 The Association of University Radiologists

Hepatocellular carcinoma with extensive hepatic artery injury: transcatheter arterial chemoembolization through collaterals after coil embolizatoin of gastric arteries

International Nuclear Information System (INIS)

Kim, Gab Choul; Yoon, Hyun Ki; Hwang, Jae Cheol; Lee, Duck Hee; Song, Ho Young; Suh, Dong Jin; Lee, Yung Sang; Chung, Young Hwa; Sung, Gyu Bo; Ko, Ki Young

1999-01-01

To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE) after coil embolization of the gastroduodenal artery in hepatocellular carcinoma cases with multiple collateral arteries caused by proper hepatic artery injury. Between March 1997 and November 1998, a prospective trial of transcatheter arterial chemoembolization (TACE) was performed through collaterals from the gastroduodenal artery of 31 hepatocellular carcinoma patients with extensive proper hepatic artery injury due to repeated TACE. Among this number, 16 (group A) underwent TACE after coil embolization of the right gastric and gastroduodenal artery. The other 15 patients (group B) underwent TACE without coil embolization. The two groups had the same TNM stage and Clild-Pugh status. During the follow-up period, group A underwent additional TACE 3.3 times, and group B 2.8 times. The therapeutic effect of TACE was evaluated with computed tomography and by measuring alpha-fetoprotein levels. Complications were evaluated by means of gastrofibroscopy, laboratory data, and evaluation of the patients' clinical symptoms. The results obtained after six months and one year were compared within and between each group. At six months follow-up, CT findings had improved or were unchanged in 11 patients(69 %) in group A, and four patients(27 %) in group B(p = 0.032). In ten patients in each group, the level of alpha-fetoprotein was above 200 ng/ml. Its level was decreased in five patients(50 %) and three patients(30 %), respectively. The six-month survival rate was 81 % (13/16) in group A and 67% (10/15) in group B (p 0.43), while the one-year survival figures for these two groups were 50 % (8/16) and 20 % (3/15), respectively(p = 0.135). In group A, the CT findings were steady in five out of eight patients(63 %), while in groupB, CT findings showed that tumors with increased alpha-fetoprotein levels had increased in size and/or number. In group A, it was found that in two (33 %) of six

Hepatocellular carcinoma with extensive hepatic artery injury: transcatheter arterial chemoembolization through collaterals after coil embolizatoin of gastric arteries

Energy Technology Data Exchange (ETDEWEB)

Kim, Gab Choul; Yoon, Hyun Ki; Hwang, Jae Cheol; Lee, Duck Hee; Song, Ho Young; Suh, Dong Jin; Lee, Yung Sang; Chung, Young Hwa; Sung, Gyu Bo [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Ko, Ki Young [Catholic Univ. College of Medicine, Seoul (Korea, Republic of)

1999-09-01

To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE) after coil embolization of the gastroduodenal artery in hepatocellular carcinoma cases with multiple collateral arteries caused by proper hepatic artery injury. Between March 1997 and November 1998, a prospective trial of transcatheter arterial chemoembolization (TACE) was performed through collaterals from the gastroduodenal artery of 31 hepatocellular carcinoma patients with extensive proper hepatic artery injury due to repeated TACE. Among this number, 16 (group A) underwent TACE after coil embolization of the right gastric and gastroduodenal artery. The other 15 patients (group B) underwent TACE without coil embolization. The two groups had the same TNM stage and Clild-Pugh status. During the follow-up period, group A underwent additional TACE 3.3 times, and group B 2.8 times. The therapeutic effect of TACE was evaluated with computed tomography and by measuring alpha-fetoprotein levels. Complications were evaluated by means of gastrofibroscopy, laboratory data, and evaluation of the patients' clinical symptoms. The results obtained after six months and one year were compared within and between each group. At six months follow-up, CT findings had improved or were unchanged in 11 patients(69 %) in group A, and four patients(27 %) in group B(p = 0.032). In ten patients in each group, the level of alpha-fetoprotein was above 200 ng/ml. Its level was decreased in five patients(50 %) and three patients(30 %), respectively. The six-month survival rate was 81 % (13/16) in group A and 67% (10/15) in group B (p 0.43), while the one-year survival figures for these two groups were 50 % (8/16) and 20 % (3/15), respectively(p = 0.135). In group A, the CT findings were steady in five out of eight patients(63 %), while in groupB, CT findings showed that tumors with increased alpha-fetoprotein levels had increased in size and/or number. In group A, it was found that in two (33 %) of six

Utility of Gd-EOB-DTPA-Enhanced MRI in Diagnosing Small Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Soo Ryang Kim

2009-07-01

Full Text Available We describe an 8-mm hepatocellular carcinoma (HCC with hepatitis C virus-related cirrhosis in a 74-year-old woman. Ultrasound (US revealed an 8-mm hyperechoic nodule in segment 6 of the liver. Contrast-enhanced computed tomography (CT and US revealed no hypervascularity in the early phase and no washout in the late phase and the Kupffer phase, respectively. CT during arteriography revealed no hypervascularity and CT during arterial portography disclosed no perfusion defect. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI revealed no hypervascularity in the early phase, but disclosed a defect in the hepatobiliary phase. Histologically, the nodule was diagnosed as well-differentiated HCC characterized by more than two-fold the cellularity of the non-tumorous area, with a high nuclear:cytoplasmic ratio, increased cytoplasmic eosinophilia, fatty change, and slight cell atypia with an irregular thin trabecular pattern. Our case demonstrates the utility of Gd-EOB-DTPA-enhanced MRI in the diagnosis of small HCC.

Placement of a covered self-expandable nitinol stent for bile duct stricture that caused by ischemic injury after transcatheter arterial chemoembolization in a patient with hepatocellular carcinoma: a case report

Energy Technology Data Exchange (ETDEWEB)

Yoo, Kweon; Seo, Tae Seok; Cha, In Ho; Huh, Sik; Byun, Kwan Soo [Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

2008-10-15

The authors report here on a case of focal stricture in the common hepatic duct that was caused by ischemic bile duct injury after repeat TACE procedures for hepatocellular carcinoma, and the patient was successfully treated with a covered self-expandable nitinol stent.

Hepatocellular carcinoma. Comparison between gadolinium and ironoxide enhanced MR imaging

International Nuclear Information System (INIS)

Castoldi, M.C.; Fauda, V.; Scaramuzza, D.; Vergnaghi, D.

2000-01-01

Purpose of this work is to compare prospectively dynamic gadolinium (Gd)-enhanced with superparamagnetic iron oxide (SPIO)-enhanced MRI for the detection of hepatocellular carcinoma (HCC). Twenty-five patients with histologically proven HCC and liver cirrhosis (28% of them in B or C Child class) underwent dynamic Gd-enhanced MRI and, a few days later, (mean interval: three days) SPIO-enhanced MRI. Only patients with availability of clinical and imaging follow-up for at least seven months were enrolled in this prospective study. MR images were reviewed by two independent radiologists. The readers scored each lesion for the presence of HCC and assigned confidence levels based on a five-grade scale: 1, definitely or almost definitely absent; 2, possibly present; 3, probably present; 4, definitely present; 5, definitely present with optimal liver/lesion contrast or good liver/lesion contrast and morphological signs (intact capsule, intranodular septa, extracapsular infiltration), useful for locoregional treatment planning. A positive diagnostic value was assessed for scores of 3 or higher. Gd-enhanced and SPIO-enhanced MRI found 44 lesions. Eight of twelve lesions visible with a single contrast agent measured less than 1 cm in diameter. HCC detectability was 75% with Gd-enhanced MRI and 97.7% with SPIO-enhanced MRI. SPIO-enhanced T2-weighted TSE images showed significantly higher diagnostic value than SPIO-enhanced T1-T2*GRE images only in three cases, while nodule morphological characteristics (capsule, septa, different cell differentiation components) were better depicted by TSE images. In thi study the combined use of SPIO-enhanced T2-weighted TSE and T1-T2*-weighted GRE sequences showed higher sensitivity than gadolinium-enhanced GRE dynamic imaging (97.7% versus 75%). These results are at least partly related to our study conditions, that is: 1)MRI was performed with a 1T system, 2) both axial and sagittal SPIO-enhanced imaging were performed with respiratory

Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma.

Science.gov (United States)

Minami, Yasunori; Kudo, Masatoshi

2009-12-31

The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.

Helical CT appearance of hypovascular small hepatocellular carcinoma with pathologic correlation

International Nuclear Information System (INIS)

Zheng Keguo; Xu Dasheng; Shen Jingxian

2003-01-01

Objective: To study the helical CT dual-phase enhancement manifestation of the hypodense small hepatocellular carcinoma, and to evaluate its correlation with the histopathology. Methods: The CT signs and its histopathologic changes were analyzed in 25 cases with 27 hypodense lesions in helical CT dual-phase enhancement. All the lesions were confirmed as small hepatocellular carcinoma by operation and histopathology. Results: (1) On unenhanced scan, 16 lesions were with obscure borders and 11 lesions were with well-delineated borders. On enhanced scan, only 7 lesions were with obscure borders and the other 20 lesions were with well-delineated borders, and their contours were slightly irregular. (2) On unenhanced scan, 18 lesions showed homogeneous hypodensity and 9 lesions showed heterogeneous hypodensity. On enhanced scan, only 6 lesions showed homogeneous hypodensity and the other 21 lesions showed heterogeneous hypodensity with multiple flecks of more hypodense areas. Conclusion: The helical CT dual-phase enhancement characteristic manifestations of hypodense small hepatocellular carcinoma were as follows: the border of the lesion was obscure on unenhanced scan, however the border of the lesion became well-delineated and slightly irregular, and there were multiple flecks of more hypodense areas in the lesions after enhancement. This might be an important character in distinguishing hypodense small hepatocellular carcinoma from other hypodense diseases in the liver

Hepatocellular carcinoma with neuroendocrine differentiation: clinical and imaging findings in five patients

International Nuclear Information System (INIS)

Park, Seong Hoon; Kang, Myeong Jin; Cho, Jin Han

2008-01-01

To describe the clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation, which is an extremely rare variant of hepatocellular carcinoma. We collected five patients who had histopathologically proven hepatocellular carcinoma with neuroendocrine differentiation, and described morphologic feature, enhancement pattern of tumors, extrahepatic manifestation and clinical findings. At CT, the tumor size ranged from 8 to 17 cm (mean: 12 cm) in maximum diameter. The tumor margin was well-defined and smooth in four patients and all tumors were heterogeneously hypoattenuating. Four tumor showed rim enhancement on arterial and portal phases. Local invasion to the portal vein, intrahepatic duct and gallbladder were seen. Extrahepatic manifestations included hepatic metastases, lymph node metastasis. At ultrasonography, the tumor showed heterogeneously hyperechoic in all patients and hypoechoic rim was found in four patients. Of four patients who were followed up, one survived for 16 months after initial diagnosis, while the other three died within 3 months after initial diagnosis. As described above, clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation were not specific. However, this rare variant of hepatocellular carcinoma could be considered when hepatic tumor is found in an advanced stage and shows persistent rim enhancement at CT

Magnetic Resonance Imaging Finding of Metastatic Hepatocellular Carcinoma in Ovary: A Case Report

International Nuclear Information System (INIS)

Kwak, Soon Hyuk; Cho, Bum Sang; Kang, Min Ho; Lee, Seung Young; Han, Gi Seok; Cha, Sang Hoon; Park, Kil Sun; Kim, Sung Jin; Choi, Song Yi

2011-01-01

Hepatocellular carcinoma is the most common primary malignant tumor of liver. Metastasis of hepatocellular carcinoma occurs in various organs, but metastasis to the ovary is extremely rare. We report MRI finding of metastatic hepatocellular carcinoma of the ovary in a 37-year-old woman who was treated hepatocellular carcinoma transarterial chemoembolization and radiofrequency ablation a year ago. Pelvic MRI revealed a mass in pelvic cavity with heterogeneous signal intensity and centripetal enhancement. Surgical excision and pathologic examination confirmed metastatic hepatocellular carcinoma in the ovary.

Detection of hepatocellular carcinoma with multi-slice spiral CT by ...

African Journals Online (AJOL)

STORAGESEVER

2010-06-07

Jun 7, 2010 ... The purpose of the study is to evaluate the effect of iodine concentration of contrast material on detection of hepatocellular carcinoma with multi-slice spiral computed tomography (CT) by using double-arterial phase and portal venous phase enhanced scanning. Ninety-four (94) patients with hepatocellular ...

Local ablation therapy with contrast-enhanced ultrasonography for hepatocellular carcinoma: a practical review

Directory of Open Access Journals (Sweden)

Tae Kyoung Kim

2015-10-01

Full Text Available A successful program for local ablation therapy for hepatocellular carcinoma (HCC requires extensive imaging support for diagnosis and localization of HCC, imaging guidance for the ablation procedures, and post-treatment monitoring. Contrast-enhanced ultrasonography (CEUS has several advantages over computed tomography/magnetic resonance imaging (CT/MRI, including real-time imaging capability, sensitive detection of arterial-phase hypervascularity and washout, no renal excretion, no ionizing radiation, repeatability, excellent patient compliance, and relatively low cost. CEUS is useful for image guidance for isoechoic lesions. While contrast-enhanced CT/MRI is the standard method for the diagnosis of HCC and post-ablation monitoring, CEUS is useful when CT/MRI findings are indeterminate or CT/MRI is contraindicated. This article provides a practical review of the role of CEUS in imaging algorithms for pre- and post-ablation therapy for HCC.

Gadoxetic acid-enhanced magnetic resonance imaging characteristics of hepatocellular carcinoma occurring in liver transplants

Energy Technology Data Exchange (ETDEWEB)

Kim, Mimi [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Hanyang University of Hospital, Department of Radiology, Seoul (Korea, Republic of); Kang, Tae Wook; Jeong, Woo Kyoung; Kim, Young Kon; Kim, Seong Hyun [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Jong Man [Sungkyunkwan University School of Medicine, Department of Surgery, Samsung Medical Center, Seoul (Korea, Republic of); Sinn, Dong Hyun [Sungkyunkwan University School of Medicine, Division of hepatology, Department of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Min-Ji; Jung, Sin-ho [Samsung Medical Center, Biostatics and Clinical Epidemiology Center, Seoul (Korea, Republic of)

2017-08-15

Characteristics of hepatocellular carcinoma (HCC) on magnetic resonance (MR) images were compared in patients who did or did not undergo liver transplantation (LT), and we evaluated the relationship of these findings with overall survival (OS) and time-to-tumour recurrence (TTR) after transplantation. The enhancement pattern of gadoxetic acid-enhanced MR images of 25 patients with recurrent HCCs (LT group) and 25 surgically confirmed HCC patients in the non-transplanted (control) group were compared. Typical enhancement was defined as 1) arterial enhancement and delayed wash-out and 2) absence of typical features of cholangiocarcinoma consisting of arterial rim enhancement and target appearance on hepatobiliary phase images. OS and TTR were analyzed in the LT group according to these patterns using the log-rank test. HCCs in the LT group significantly more often had an atypical enhancement pattern (16/25, 64.0%) than those in the control group (5/25, 20.0%; p = 0.004). However, OS and TTR did not differ significantly according to these enhancement patterns of recurrent HCC (p > 0.05). Although enhancement patterns of recurrent HCC in transplanted liver did not affect OS and TTR, these HCCs that arise after LT frequently revealed atypical enhancement on gadoxetic acid-enhanced MR imaging. (orig.)

Gadoxetic acid-enhanced magnetic resonance imaging characteristics of hepatocellular carcinoma occurring in liver transplants

International Nuclear Information System (INIS)

Kim, Mimi; Kang, Tae Wook; Jeong, Woo Kyoung; Kim, Young Kon; Kim, Seong Hyun; Kim, Jong Man; Sinn, Dong Hyun; Kim, Min-Ji; Jung, Sin-ho

2017-01-01

Characteristics of hepatocellular carcinoma (HCC) on magnetic resonance (MR) images were compared in patients who did or did not undergo liver transplantation (LT), and we evaluated the relationship of these findings with overall survival (OS) and time-to-tumour recurrence (TTR) after transplantation. The enhancement pattern of gadoxetic acid-enhanced MR images of 25 patients with recurrent HCCs (LT group) and 25 surgically confirmed HCC patients in the non-transplanted (control) group were compared. Typical enhancement was defined as 1) arterial enhancement and delayed wash-out and 2) absence of typical features of cholangiocarcinoma consisting of arterial rim enhancement and target appearance on hepatobiliary phase images. OS and TTR were analyzed in the LT group according to these patterns using the log-rank test. HCCs in the LT group significantly more often had an atypical enhancement pattern (16/25, 64.0%) than those in the control group (5/25, 20.0%; p = 0.004). However, OS and TTR did not differ significantly according to these enhancement patterns of recurrent HCC (p > 0.05). Although enhancement patterns of recurrent HCC in transplanted liver did not affect OS and TTR, these HCCs that arise after LT frequently revealed atypical enhancement on gadoxetic acid-enhanced MR imaging. (orig.)

CT of hepatocellular carcinoma. Analysis of contrast-enhanced CT using CT arteriography

Energy Technology Data Exchange (ETDEWEB)

Nakamura, H; Tanaka, T; Hori, S; Tokunaga, K; Yoshioka, H [Osaka Univ. (Japan). Faculty of Medicine

1981-02-01

Although changes in the CT appearance resulting from contrast enhancement (CE) for hepatocellular carcinoma have been considered in association with vascularity of tumors, no detailed studies have yet been made. We analyzed changes in the CT appearance following CE by comparing with hepatic arteriogram and CT arteriogram (CTA) performed during intraarterial infusion of contrast medium. When tumors showing low density in the plain CT were enhanced by contrast, the results were variable, ranging from intensification of the low density to replacement by high density, and the results were classified into L/sub 0/ to L/sub 3/ according to vascularity of tumors. The results after CE could also be classified into I/sub 0/ to I/sub 3/ when tumors showed isodensity in the plain CT. There was a correlation between vascularity presumed from CE and vascularity by CTA. It may be concluded that tumor vascularity could be estimated by the findings of CE which might indicate a possibility of qualitative diagnosis of tumors.

Is contrast-enhanced CT indicated in acute head injury

International Nuclear Information System (INIS)

Mauser, H.W.; Nieuwenhuizen, O. van; Veiga-Pires, J.A.

1984-01-01

The authors discuss the value of intravenous contrast enhancement in CT scanning in acute head injury. In a series of seventy consecutive patients they conclude that no incremental information was obtained by performing contrast-enhanced CT scans in the acute phase of the head injury. (orig.)

Evaluation of residual hepatocellular carcinoma after transcatheter arterial chemoembolization: Comparison between contrast-enhanced helical CT and contrast-enhanced power doppler ultrasonography

International Nuclear Information System (INIS)

Kim, Seung Hoon; Lim, Hyo Keun; Lee, Won Jae

2001-01-01

To evaluate the effectiveness of contrast-enhanced helical CT and contrast-enhanced power doppler ultrasonography (PDUS) in assessing the therapeutic effect of transcatheter arterial chemoembolization (TACE) in hepatocellular carcinomas (HCCs). The follow-up contrast-enhanced helical CT and contrast-enhanced PDUS were performed for twenty-nine nodular HCCs from twelve patients previously treated with TACE. We defined the residual HCCs as intratumoral enhancing area on contrast-enhanced helical CT and color signal on contrast-enhanced PDUS. The interval between two examinations was less than 2 weeks (mean, 9 days). Two radiologists evaluated two examinations by consensus, and the results of these two examination were compared with the findings of other examinations including CT, angiography, and/or pathology to calculate the sensitivity, specificity and accuracy of two examinations. Of the 29 HCCs, 20 had residual HCCs whereas no residual HCCs in 9 HCCs on pathologic examination and/or follow-up radiologic study. The sensitivity, sensitivity and accuracy of contrast-enhanced helical CT were 65 (13/20), 89 (8/9), and 72% (21/29) while those of contrast-enhanced PDUS were 100 (20/20), 89 (8/9) and 97% (28/29), respectively. A microbubble contrast-enhanced PDUS was more effective in the detection of residual tumor in HCCs following TACE than contrast-enhanced helical CT.

Clinical utility of imaging for evaluation of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Murakami T

2014-07-01

Full Text Available Takamichi Murakami,1 Masakatsu Tsurusaki,1 Tomoko Hyodo,1 Yasuharu Imai2 1Department of Radiology, Kinki University Faculty of Medicine, 2Department of Hepatology and Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan Abstract: The hemodynamics of a hepatocellular nodule is the most important imaging parameter used to characterize various hepatocellular nodules in liver cirrhosis, because sequential changes occur in the feeding vessels and hemodynamic status during hepatocarcinogenesis. Therefore, the imaging criteria for hepatocellular carcinoma (HCC are also usually based on vascular findings, eg, early arterial uptake followed by washout in the portal venous and equilibrium phases. Contrast-enhanced ultrasonography, dynamic multidetector-row computed tomography (MDCT, and dynamic magnetic resonance (MR imaging with gadopentetate dimeglumine (Gd-DTPA are useful for detecting hypervascular HCC on the basis of vascular criteria but are not as useful for hypovascular HCC. Contrast-enhanced MR imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA, a hepatocyte-specific MR contrast agent, is superior to dynamic MDCT and dynamic MR imaging with Gd-DTPA in detecting both hypervascular and hypovascular HCC. Moreover, Gd-EOB-DTPA-enhanced MR imaging can display each histologically differentiated HCC as hypointense relative to the liver parenchyma. 18F-fluorodeoxyglucose positron emission tomography imaging might not be suitable for the screening and detection of HCC, given its lower diagnostic performance. However, this technique plays an important role in determining whether HCC has spread beyond the liver. Keywords: hepatocellular carcinoma, evaluation, imaging, clinical utility

CD18 deficiency improves liver injury in the MCD model of steatohepatitis.

Science.gov (United States)

Pierce, Andrew A; Duwaerts, Caroline C; Siao, Kevin; Mattis, Aras N; Goodsell, Amanda; Baron, Jody L; Maher, Jacquelyn J

2017-01-01

Neutrophils and macrophages are important constituents of the hepatic inflammatory infiltrate in non-alcoholic steatohepatitis. These innate immune cells express CD18, an adhesion molecule that facilitates leukocyte activation. In the context of fatty liver, activation of infiltrated leukocytes is believed to enhance hepatocellular injury. The objective of this study was to determine the degree to which activated innate immune cells promote steatohepatitis by comparing hepatic outcomes in wild-type and CD18-mutant mice fed a methionine-choline-deficient (MCD) diet. After 3 weeks of MCD feeding, hepatocyte injury, based on serum ALT elevation, was 40% lower in CD18-mutant than wild-type mice. Leukocyte infiltration into the liver was not impaired in CD18-mutant mice, but leukocyte activation was markedly reduced, as shown by the lack of evidence of oxidant production. Despite having reduced hepatocellular injury, CD18-mutant mice developed significantly more hepatic steatosis than wild-type mice after MCD feeding. This coincided with greater hepatic induction of pro-inflammatory and lipogenic genes as well as a modest reduction in hepatic expression of adipose triglyceride lipase. Overall, the data indicate that CD18 deficiency curbs MCD-mediated liver injury by limiting the activation of innate immune cells in the liver without compromising intrahepatic cytokine activation. Reduced liver injury occurs at the expense of increased hepatic steatosis, which suggests that in addition to damaging hepatocytes, infiltrating leukocytes may influence lipid homeostasis in the liver.

Dynamic computed tomography of hepatocellular carcinoma with particular reference to capsule

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Otsuji, Hideaki [Nara Prefectural Hospital (Japan); Uchida, Hideo; Ohishi, H

1983-11-01

Dynamic CT of 117 hepatocellular carcinoma was analyzed about the capsule. Capsules were detected in 57 cases (49%) and they were classified into three types. The tumor showed high density during 15 to 26 sec after bolus injection of conrast medium, but the capsule was not enhanced. Incidence of the capsule enhanced as ring high density was 73% during 37 to 90 sec and over 90% after 4 min. Dynamic CT was very useful in the elucidation of hemodynamics of capsules of hepatocellular carcinoma.

Mechanisms of enhanced lung injury during sepsis

DEFF Research Database (Denmark)

Czermak, B J; Breckwoldt, M; Ravage, Z B

1999-01-01

. Enhanced lung injury was associated with increased accumulation of neutrophils in lung, enhanced production of CXC chemokines (but not tumor necrosis factor-alpha) in bronchoalveolar lavage fluids, and increased expression of lung vascular intercellular adhesion molecule-1 (ICAM-1). Complement depletion...

Novel fluorescence nanobubbles for contrast-enhanced ultrasound imaging in rabbit VX2 hepatocellular carcinoma model

Science.gov (United States)

Yu, Houqiang; Wang, Wei; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

2017-03-01

Ultrasound contrast agents (UCAs) such as SonoVue or Optison have been used widely in clinic for contrast-enhanced vascular imaging. However, microbubbles UCAs display limitations in tumor-targeted imaging due to the large sizes, nanoscaled UCAs has consequently attracted increasing attentions. In this work, we synthesized nanobubbles (NBs) by ultrasonic cavitation method, then a fluorescent marker of Alexa Fluor 680 was conjugated to the shell in order to observe the localization of NBs in tumor tissue. Measurement of fundamental characteristics showed that the NBs had homogeneous distribution of mean diameter of 267.9 +/- 19.2 nm and polydispersity index of 0.410 +/- 0.056. To assess in vivo tumor-selectivity of NBs, we established the rabbits VX2 hepatocellular carcinoma model though surgical implantation method. After the rabbits were intravenous administered of NBs, contrast-enhanced sonograms was observed in the surrounding of VX2 tumor, which showed there are rich capillaries in the tumor periphery. We additionally investigated the toxic of the NBs by hematoxylin-eosin staining. The results indicated that the NBs is a biocompatible non-toxic lipid system. Furthermore, the VX2 tumors and major organs were analyzed using ex vivo fluorescence imaging to confirm the targeted selectivity of NBs, and the results verified that the NBs were capable of targeting VX2 tumor. Confocal laser scanning microscopy examination showed that the NBs can traverse the VX2 tumor capillaries and target to the hepatocellular carcinoma tumor cells. All these results suggested that the newly prepared NBs have a potential application in molecular imaging and tumor-targeting therapy.

Overexpression of Cullin7 is associated with hepatocellular carcinoma progression and pathogenesis.

Science.gov (United States)

An, Jun; Zhang, Zhigang; Liu, Zhiyong; Wang, Ruizhi; Hui, Dayang; Jin, Yi

2017-12-06

Overexpression of Cullin7 is associated with some types of malignancies. However, the part of Cullin7 in hepatocellular carcinoma remains unclear. The aim of this study was to investigate the role of Cullin7 in pathogenesis and the progression of hepatocellular carcinoma. In the present study, the expression of Cullin7 in hepatocellular carcinoma cell lines and five surgical hepatocellular carcinoma specimens was detected with quantitative reverse transcription PCR and western blotting. In addition, the protein expression of Cullin7 was examined in 162 cases of archived hepatocellular carcinoma using immunohistochemistry. We found elevated expression of both mRNA and protein levels of Cullin7 in hepatocellular carcinoma cell lines, and Cullin7 protein was significantly upregulated in hepatocellular carcinoma compared with paired normal hepatic tissues. The immunohistochemistry analysis revealed that overexpression of Cullin7 occurred in 69.1% of hepatocellular carcinoma samples, which was a significantly higher rate than that in adjacent normal hepatic tissue (P hepatocellular carcinoma HepG2 cells, we revealed that Cullin7 could significantly enhance cell proliferation, growth, migration and invasion. Conversely, knocking down Cullin7 expression with short hairpin RNAi in hepatocellular carcinoma HepG2 cells inhibited cell proliferation, growth, migration and invasion. Our studies provide evidence that overexpression of Cullin7 plays an important role in the pathogenesis and progression of hepatocellular carcinoma and may be a valuable marker for hepatocellular carcinoma management.

Hepatocellular carcinoma: computed tomography assessment after invasive treatment

International Nuclear Information System (INIS)

Kozima, Shigeru; Larranaga, Nebil; Wulfson, Gabriela; Eisele, Guillermo; Ridruejo, Ezequiel; Mando, Oscar; Perazzo, Florencia

2008-01-01

Objective: To show the computed tomography (CT) usefulness after treatment with transcatheter arterial quimioembolization and radiofrequency ablation of hepatocellular carcinoma. Material and methods: In a period between march 2006 to april 2008 a total of 90 patient presenting 148 nodular lesions with diagnosis of hepatocellular carcinoma were controlled with triphasic CT. All the lesions were treated with minimally invasive procedure. For the treatment, the patients were classified in two groups following Milan criteria. The first group, constituted by 75 patients with 109 nodules, was treated with quimioembolization. The second group, of 15 patients with 25 nodules, was treated with radiofrequency ablation. In our population, a subgroup of 10 patients was treated with both methods. Results: Of 90 patients after CT control on a month, 3 months and for each 3 months during 2 years, on 63 cases (70%) was observed homogeneous accumulation of iodized oil, partial defect without enhancement or absence of enhancement on treated lesions. In these patients a new treatment after initial one was not performed. The remaining 27 patients (30%) underwent new treatment because we founded partial defect or absence of iodized oil with enhancement or peripheral enhancement on arterial phase in treated lesions. In this last group, 16 treated patients (17.7%) had new nodular enhancement on the remaining hepatic parenquimal. Conclusion: The CT unenhanced and the arterial phase on a month and for each 3 months, allow monitoring the effectiveness, residual disease and/or relapse of hepatocellular carcinoma after minimally invasive treatment. (authors) [es

CT of hepatocellular carcinoma

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Nakamura, H; Tanaka, T; Sai, H; Kawamoto, S; Morimoto, K [Osaka Univ. (Japan). Faculty of Medicine

1982-06-01

CT was investigated in 125 cases of hepatocelluar carcinoma and 47 cases of metastatic hepatic neoplasm. The entire contour of each tumor was traced and the average CT value in the tumor was estimated. As a result, the CT value for hepatocellular carcinoma tended to be higher on plain CT and also after contrast enhancement. The CT findings seen frequently were as follows: capsule in 76 cases (60.8%) and septum in 67 cases (53.6%); tumor thrombus in portal vein in 39 cases (31.2%) and that in inferior vena cava in 3 cases (2.4%); localized enlargement of hepatic bile duct in 24 cases (19.2%). These findings were rarely seen in the cases of metastatic hepatic neoplasm. As a relatively outstanding feature of hepatic metastases, a double contour, like concentric circles or contour lines, with a relatively large inner circle or contour line, was found in 21 cases (44.7%). By paying attention to the change of CT value on contrast enhancement and the characteristic image of each case, hepatocellular carcinoma could be differentiated from metastatic hepatic neoplasm with high probability.

Hepatobiliary effects of 90yttrium microsphere therapy for unresectable hepatocellular carcinoma.

Science.gov (United States)

Nalesnik, Michael A; Federle, Michael; Buck, David; Fontes, Paulo; Carr, Brian I

2009-01-01

(90)Yttrium (Therasphere) microspheres administered via hepatic artery are a valuable option for treatment of hepatocellular carcinoma. This therapy targets tumor nodules while largely sparing hepatic parenchyma. This retrospective study examines liver explants from 13 adult patients with hepatocellular carcinoma who received intrahepatic Theraspheres and subsequently underwent liver transplantation. Histopathologic and laboratory reviews are performed. Theraspheres preferentially migrated to the lobe(s) supplied by the injected artery branches and frequently localized to tumors. Tumors showed a chronology of changes beginning with confluent necrosis typically accompanied by hemorrhage and later by fibrinoid change. This was followed by fibrosis with regenerative activity at tumor peripheries. Adjacent hepatic parenchyma went through a similar sequence of injury and repair that could lead to markedly fibrotic cirrhotic nodules in the vicinity of treated tumors. No consistent pattern of thrombomodulin loss was seen in endothelial cells of the tumors or adjacent parenchyma, suggesting that direct endothelial cell injury was likely not a major contributor to the necrotic process. However, the pattern of injury and repair is suggestive of a localized and subclinical form of radiation-induced liver disease. The pathologist should be aware of these changes to distinguish them from the diffuse "radiation hepatitis" associated with older forms of radiotherapy.

Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development

International Nuclear Information System (INIS)

Nayeb-Hashemi, Hamed; Desai, Anal; Demchev, Valeriy; Bronson, Roderick T.; Hornick, Jason L.; Cohen, David E.; Ukomadu, Chinweike

2015-01-01

Fibrinogen like protein-1 (Fgl1) is a predominantly liver expressed protein that has been implicated as both a hepatoprotectant and a hepatocyte mitogen. Fgl1 expression is decreased in hepatocellular carcinoma (HCC) and its loss correlates with a poorly differentiated phenotype. To better elucidate the role of Fgl1 in hepatocarcinogenesis, we treated mice wild type or null for Fgl1 with diethyl nitrosamine and monitored for incidence of hepatocellular cancer. We find that mice lacking Fgl1 develop HCC at more than twice the rate of wild type mice. We show that hepatocellular cancers from Fgl1 null mice are molecularly distinct from those of the wild type mice. In tumors from Fgl1 null mice there is enhanced activation of Akt and downstream targets of the mammalian target of rapamycin (mTOR). In addition, there is paradoxical up regulation of putative hepatocellular cancer tumor suppressors; tripartite motif-containing protein 35 (Trim35) and tumor necrosis factor super family 10b (Tnfrsf10b). Taken together, these findings suggest that Fgl1 acts as a tumor suppressor in hepatocellular cancer through an Akt dependent mechanism and supports its role as a potential therapeutic target in HCC. - Highlights: • Fgl1 knockout mice (Fgl1KO) are more prone to carcinogen-induced liver cancer compared to wild type (WT) mates. • Tumors from the Fgl1KO are molecularly distinct with enhanced Akt and mTOR activity in comparison with Fgl1WT tumors. • Tumors from the Fgl1KO have enhanced expression of Trim35 and Tnfrsf10b, putative HCC tumor suppressors

Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development

Energy Technology Data Exchange (ETDEWEB)

Nayeb-Hashemi, Hamed; Desai, Anal; Demchev, Valeriy [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Bronson, Roderick T. [Department of Microbiology and Immunology, Harvard Medical School, Boston, MA 02115 (United States); Hornick, Jason L. [Department of Pathology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Cohen, David E. [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Ukomadu, Chinweike, E-mail: cukomadu@partners.org [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

2015-09-18

Fibrinogen like protein-1 (Fgl1) is a predominantly liver expressed protein that has been implicated as both a hepatoprotectant and a hepatocyte mitogen. Fgl1 expression is decreased in hepatocellular carcinoma (HCC) and its loss correlates with a poorly differentiated phenotype. To better elucidate the role of Fgl1 in hepatocarcinogenesis, we treated mice wild type or null for Fgl1 with diethyl nitrosamine and monitored for incidence of hepatocellular cancer. We find that mice lacking Fgl1 develop HCC at more than twice the rate of wild type mice. We show that hepatocellular cancers from Fgl1 null mice are molecularly distinct from those of the wild type mice. In tumors from Fgl1 null mice there is enhanced activation of Akt and downstream targets of the mammalian target of rapamycin (mTOR). In addition, there is paradoxical up regulation of putative hepatocellular cancer tumor suppressors; tripartite motif-containing protein 35 (Trim35) and tumor necrosis factor super family 10b (Tnfrsf10b). Taken together, these findings suggest that Fgl1 acts as a tumor suppressor in hepatocellular cancer through an Akt dependent mechanism and supports its role as a potential therapeutic target in HCC. - Highlights: • Fgl1 knockout mice (Fgl1KO) are more prone to carcinogen-induced liver cancer compared to wild type (WT) mates. • Tumors from the Fgl1KO are molecularly distinct with enhanced Akt and mTOR activity in comparison with Fgl1WT tumors. • Tumors from the Fgl1KO have enhanced expression of Trim35 and Tnfrsf10b, putative HCC tumor suppressors.

Liposomes equipped with cell penetrating peptide BR2 enhances chemotherapeutic effects of cantharidin against hepatocellular carcinoma.

Science.gov (United States)

Zhang, Xue; Lin, Congcong; Lu, Aiping; Lin, Ge; Chen, Huoji; Liu, Qiang; Yang, Zhijun; Zhang, Hongqi

2017-11-01

A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification. The cellular uptake results of HepG2 and Miha cells further confirmed the superior ability of BR2-modified liposomes to penetrate cancer cells. The colocalization study revealed that BR2-modified liposomes could enter tumor cells and subsequently release drugs. A higher efficiency of delivery by BR2 liposomes as compared to unmodified liposomes was evident by evaluation of the HepG2 tumor spheroids penetration and inhibition. The biodistribution studies and anticancer efficacy results in vivo showed the significant accumulation of BR2-modified liposomes into tumor sites and an enhanced tumor inhibition. In conclusion, BR2-modified liposomes improve the anticancer potency of drugs for HCC.

Diagnosis of small hepatocellular carcinoma by incremental dynamic CT

International Nuclear Information System (INIS)

Uchida, Masafumi; Kumabe, Tsutomu; Edamitsu, Osamu

1993-01-01

Thirty cases of pathologically confirmed small hepatocellular carcinoma were examined by Incremental Dynamic CT (ICT). ICT scanned the whole liver with single-breath-hold technique; therefore, effective early contrast enhancement could be obtained for diagnosis. Among the 30 tumors, 26 were detected. The detection rate was 87%. A high detection rate was obtained in tumors more than 20 mm in diameter. Twenty-two of 26 tumors could be diagnosed correctly. ICT examination was useful for detection of small hepatocellular carcinoma. (author)

SPIO-Enhanced MRI Findings of Well-Differentiated Hepatocellular Carcinomas: Correlation with MDCT Findings

International Nuclear Information System (INIS)

Kim, Seong Hyun; Lee, Won Jae; Lim, Hyo K.; Park, Cheol Keun

2009-01-01

This study was designed to assess superparamagnetic iron oxide (SPIO)-enhanced MRI findings of well-differentiated hepatocellular carcinomas (HCCs) correlated with their multidetector-row CT (MDCT) findings. Seventy-two patients with 84 pathologically proven well-differentiated HCCs underwent triple-phase MDCT and SPIO-enhanced MRI at a magnetic field strength of 1.5 Tesla (n = 49) and 3.0 Tesla (n = 23). Two radiologists in consensus retrospectively reviewed the CT and MR images for attenuation value and the signal intensity of each tumor. The proportion of hyperintense HCCs as depicted on SPIO-enhanced T2- or T2*-weighted images were compared in terms of tumor size ( 1 cm), five CT attenuation patterns based on arterial and equilibrium phases and magnetic field strength, by the use of univariate and multivariate analyses. Seventy-eight (93%) and 71 (85%) HCCs were identified by CT and on SPIO-enhanced T2- and T2*-weighted images, respectively. For the CT attenuation pattern, one (14%) of seven isodense-isodense, four (67%) of six hypodense- hypodense, four (80%) of five isodense-hypodense, 14 (88%) of 16 hyperdense- isodense and 48 (96%) of 50 hyperdense-hypodense HCCs were hyperintense (Cochran-Armitage test for trend, p 0.05). Most well-differentiated HCCs show hyperintensity on SPIOenhanced MRI, although the lesions show various CT attenuation patterns. The CT attenuation pattern is the main factor that affects the proportion of hyperintense well-differentiated HCCs as depicted on SPIO-enhanced MRI

Impact of gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance on the non-invasive diagnosis of small hepatocellular carcinoma: a prospective study.

Science.gov (United States)

Granito, A; Galassi, M; Piscaglia, F; Romanini, L; Lucidi, V; Renzulli, M; Borghi, A; Grazioli, L; Golfieri, R; Bolondi, L

2013-02-01

Gadoxetic acid (Gd-EOB-DTPA) is a 'hepatocyte-specific' contrast agent for magnetic resonance (MR) in both the vascular and the hepatobiliary phases. To evaluate the contribution of the hepatobiliary phase of Gd-EOB-DTPA MR in the diagnosis of small hepatocellular carcinoma (HCC) in cirrhotic patients under surveillance. Between 2008 and 2011, 48 consecutive small (10-30 mm) liver nodules were detected in 33 patients, who prospectively underwent contrast-enhanced ultrasound (CEUS), Gd-EOB-DTPA-enhanced MR and helical-computed tomography (CT) in a blind study. The diagnosis of HCC was established according to AASLD 2005 criteria. Of the 48 nodules, 38 (79%) were diagnosed as HCC, 24 (63%) of them based on AASLD non-invasive criteria, 11 diagnosed at histology and 3 during follow-up. The typical vascular pattern (arterial hypervascularisation and venous/late washout) was detected in 30 (79%) HCC nodules by MR, in 22 (58%) by CT and in 17 (45%) by CEUS. Hypointensity during the MR hepatobiliary phase was observed in all HCC nodules and in 3 nonmalignant nodules (sensitivity 100%, specificity 70%, positive predictive value 93%, negative predictive value 100%, positive likelihood ratio 3.33, negative likelihood ratio 0). Eight (21%) of the 38 HCC nodules, 7 of which lacked the typical vascular features at any of the imaging modalities, showed washout in the portal/venous phase and hypointensity in the hepatobiliary phase at MRI, while this pattern was not detected in any nonmalignant lesion. Gadoxetic acid magnetic resonance may enhance the sensitivity of the non-invasive diagnosis of small hepatocellular carcinoma nodules in cirrhotic patients under surveillance. Double hypointensity in the portal/venous and hepatobiliary phases could be considered a new magnetic resonance pattern, highly suggestive of hypovascular hepatocellular carcinoma. © 2012 Blackwell Publishing Ltd.

Chondroitin sulfate iron colloid-enhanced MR imaging in patients with hepatocellular carcinoma. Comparison with CT during arterial portography

Energy Technology Data Exchange (ETDEWEB)

Kamba, Masayuki [Dept. of Radiology, Tottori Univ., Yonago (Japan); Suto, Y. [Dept. of Radiology, Tottori Univ., Yonago (Japan); Kato, T. [Dept. of Radiology, Tottori Univ., Yonago (Japan)

1994-11-01

Chondroitin sulfate iron colloid (CSIC) was used as an MR contrast agent for the detection of hepatocellular carcinoma (HCC). The findings of 25 surgically confirmed HCCs in 19 patients were retrospectively analyzed. T1-, T2- and proton density-weighted spin echo MR images were obtained before and after i.v. injection of 23.6 {mu}M Fe/kg of CSIC. Unenhanced and CSIC-enhanced MR images and images obtained by CT during arterial protography (CT-AP) were correlated with surgical pathology findings. The sensitivities of CSIC-enhanced and unenhanced MR imaging, and CT-AP were 92%, 80%, and 88%, respectively. No significant differences were noted. Portal flow abnormalities demonstrated by CT-AP did not affect the detection of HCC by CSIC-enhanced MR imaging. CSIC-enhancement at MR imaging was a disadvantage in the detection of lesions less than 1 cm in diameter. CSIC-enhanced MR imaging is a supplemental method for the detection of HCC. (orig.).

Hepatocellular carcinoma on MR diffusion weighted imaging and dynamic contrast-enhanced imaging

International Nuclear Information System (INIS)

Dong Aisheng; Zuo Changjing; Tian Jianming; Lu Jianping; Wang Jian; Wang Li; Wang Fei

2009-01-01

Objective: To evaluate the findings of hepatocellular carcinoma (HCC) on DWI and dynamic Gd-DTPA-enhanced MR imaging. Methods: Eighty one patients with chronic hepatitis or liver cirrhosis underwent both DWI and dynamic Gd-DTPA-enhanced MRI studies of the liver for HCC detection. MR data of were retrospectively analyzed. Two observers determined in consensus the location and the number of focal lesions. The signal manifestation of the lesions on DWI and dynamic Gd-DTPA-enhanced MR imaging were analyzed. Results: DWI and Gd-DTPA-enhanced MR images detected 122 HCCs and 14 benign lesions. One hundred and sixteen HCCs (95.1%) showed hyperintensity on DWI and 6 HCCs in patients with severe cirrhosis showed isointensity. One hundred and five HCCs (86.1%) revealed hypointensity, 11 HCCs (9.0%) showed isointensity and 6 HCCs (4.9%) exhibited hyperintensity on T 1 weighted images. On Gd-DTPA-enhanced MR images, 101 HCCs(82.8%) were significantly enhanced on arterial phase and 99 HCCs showed hypointensity on portal and equilibrium phases. Twenty HCCs (16.4%), 18 of 20 less than 20 mm in diameter, showed isointensity on arterial phase and hyperintensity on DWI. Eight of 14 benign lesions showed hyperintensity and 6 isointensity on DWI. Five benign lesions with hypointensity on T 1 weighted images without contrast and hyperintensity on DWI showed no enhancement on Gd-DTPA-enhanced MR images; 6 benign lesions with isointensity on both T 1 weighted imaging without contrast and DWI exhibited avid enhancement on arterial phase and isointensty on portal and equilibrium phases; one of the two benign lesions, with isointensity before and after contrast images and hyperintentiy on DWI, was a regenerative nodule; another regenerative nodule with hyperintensity on both T 1 weighted images without contrast and DWI was greatly enhanced on arterial phase and showed isointensity on portal and equilibrium phases. Conclusions: Most of the HCCs were greatly enhanced on arterial phase on Gd-DTPA-enhanced

Diagnosis of hepatocellular carcinoma with gadoxetic acid-enhanced MRI: 2016 Consensus Recommendations of the Korean Society of Abdominal Radiology

International Nuclear Information System (INIS)

Park, Mi-Suk

2017-01-01

Diagnosis of hepatocellular carcinoma (HCC) with gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) poses certain unique challenges beyond the scope of current guidelines. The regional heterogeneity of HCC in demographic characteristics, prevalence, surveillance, and socioeconomic status necessitates different treatment approaches, leading to variations in survival outcomes. Considering the medical practices in Korea, the Korean Society of Abdominal Radiology (KSAR) study group for liver diseases has developed expert consensus recommendations for diagnosis of HCC by gadoxetic acid-enhanced MRI with updated perspectives, using a modified Delphi method. During the 39th Scientific Assembly and Annual Meeting of KSAR (2016), consensus was reached on 12 of 16 statements. These recommendations might serve to ensure a more standardized diagnosis of HCC by gadoxetic acid-enhanced MRI

Diagnosis of hepatocellular carcinoma with gadoxetic acid-enhanced MRI: 2016 Consensus Recommendations of the Korean Society of Abdominal Radiology

Energy Technology Data Exchange (ETDEWEB)

Park, Mi-Suk [Yonsei University College of Medicine, Severance Hospital, Seoul (Korea, Republic of)

2017-06-15

Diagnosis of hepatocellular carcinoma (HCC) with gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) poses certain unique challenges beyond the scope of current guidelines. The regional heterogeneity of HCC in demographic characteristics, prevalence, surveillance, and socioeconomic status necessitates different treatment approaches, leading to variations in survival outcomes. Considering the medical practices in Korea, the Korean Society of Abdominal Radiology (KSAR) study group for liver diseases has developed expert consensus recommendations for diagnosis of HCC by gadoxetic acid-enhanced MRI with updated perspectives, using a modified Delphi method. During the 39th Scientific Assembly and Annual Meeting of KSAR (2016), consensus was reached on 12 of 16 statements. These recommendations might serve to ensure a more standardized diagnosis of HCC by gadoxetic acid-enhanced MRI.

Pokemon promotes the invasiveness of hepatocellular carcinoma by enhancing MEF2D transcription.

Science.gov (United States)

Kong, Jing; Liu, Xiaoping; Li, Xiangqian; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

2016-05-01

Pokemon, a master oncogene crucial for the tumorigenicity and progression of a variety of cancers, has been demonstrated to enhance the proliferation and survival of hepatocellular carcinoma (HCC). However, the contribution of Pokemon to the invasiveness of HCC has not yet been studied. In this study, we employed HCC cells to investigate the role of Pokemon in the invasion of HCC with multidisciplinary approaches. Pokemon overexpression was found to be closely associated with invasion and intrahepatic metastasis of HCC in clinical specimens. Suppression of Pokemon attenuated the invasion of HCC cells by in vitro transwell and wound-healing assays. Myocyte enhancer factor 2D (MEF2D), an oncogene that can promote the invasiveness of HCC, was found to be underexpressed during Pokemon silencing in HCC cells. Restoration of MEF2D abolished the effect of Pokemon downregulation on the migration of HCC cells. Further experiments verified that Pokemon binds two putative recognition sites located within the upstream region of the MEF2D promoter and enhances its transcription. The association between Pokemon and MEF2D was further confirmed in HCC specimens. Animal experiments further confirmed that Pokemon downregulation attenuated the metastasis of HCC cells in mice. Collectively, Pokemon was found to enhance the migration and invasion of HCC by increasing MEF2D expression. Thus, targeting Pokemon and MEF2D may be an effective strategy to suppress the metastasis of HCC.

The antitumor effect of arsenic trioxide on hepatocellular carcinoma is enhanced by andrographolide.

Science.gov (United States)

Duan, Xuhua; Li, Tengfei; Han, Xinwei; Ren, Jianzhuang; Chen, Pengfei; Li, Hao; Gong, Shaojun

2017-10-31

High concentrations of arsenic trioxide (As 2 O 3 ) are used to treat acute promyelocytic leukemia and solid tumors, with negative side effects to normal cells. Andrographolide is a traditional Chinese medicine that exerts anti-cancer, anti-inflammatory, anti-virus, and anti-diabetic effects. Here, we tested the effects of combined andrographolide with As 2 O 3 against hepatocellular carcinoma (HCC). We found that by increasing apoptosis, andrographolide synergistically enhanced the anti-tumor effects of As2O3 in HepG2 cells in vitro and in vivo . Furthermore, results from our microarray assays and experiments with mouse xenografts showed that EphB4 was downregulated by the combination of As 2 O 3 plus andrographolide. These findings suggest that the combination of andrographolide and As 2 O 3 could yield therapeutic benefits in the treatment of HCC.

Gadoxetate disodium-enhanced MR imaging: Differentiation between early-enhancing non-tumorous lesions and hypervascular hepatocellular carcinomas

Energy Technology Data Exchange (ETDEWEB)

Goshima, Satoshi, E-mail: gossy@par.odn.ne.jp [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Kanematsu, Masayuki [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Department of Radiology Services, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Watanabe, Haruo; Kondo, Hiroshi; Mizuno, Nozomi; Kawada, Hiroshi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Shiratori, Yoshimune [Department of Medical Informatics, Gifu University School of Medicine, Gifu (Japan); Onozuka, Minoru [Department of Physiology and Neuroscience, Kanagawa Dental College, Yokosuka (Japan); Moriyama, Noriyuki [Research Center for Cancer Prevention and Screening, National Cancer Center Hospital, Tsukiji (Japan); Bae, Kyongtae T. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

2011-08-15

Purpose: To retrospectively assess imaging features that help differentiate early-enhancing non-tumorous (EN) hepatic lesions from hepatocellular carcinomas (HCCs) on gadoxetate disodium-enhanced MR imaging. Materials and methods: Our institutional review board approved this retrospective study. We reviewed the studies of 158 patients (92 men and 65 women; age range: 29-91; mean age: 65.6 years) with chronic liver damage, who underwent gadoxetate disodium-enhanced MR imaging at 3T MR scanner. Hypervascular lesions identified during the hepatic artery phase were selected for a study cohort. The location, shape, size (maximum diameter and maximum area), and contrast enhancement signal intensity characteristics of the lesions were evaluated, then compared between the EN and HCC lesions. Results: A total of 65 EN lesions (range: 3-60 mm, mean: 13.6 {+-} 10.6 mm) from 35 patients and 33 HCCs (range: 9-61 mm, mean: 19.3 {+-} 12.6 mm) from 20 patients were identified. Lesions were more frequently round or oval in shape for HCCs (n = 29; 88%) than ENs (n = 26; 40%) (P < 0.01). Unexpectedly, some ENs (n = 12; 18%) showed hypointensity on hepatocyte-phase, and 6 (50%) of them were T2 hyperintense. For lesions smaller than 2 cm (9 ENs and 21 HCCs) on hepatic arterial-phase images, the mean area of hypointensity in hepatocyte-phase (54.2 {+-} 33.1 mm{sup 2}) was significantly smaller than those of the corresponding hyperintensity in hepatic arterial-phase (97.1 {+-} 42.0 mm{sup 2}) for EN lesions (P = 0.019), whereas no significant difference in area was found for HCCs. Conclusion: EN lesions may occasionally present with hypointensity during the hepatocyte-phase; presenting a diagnostic dilemma. In this situation, EN lesions may be differentiated from HCCs when a hypointense area in hepatocyte-phase is smaller than the corresponding hypervascular area in hepatic-arterial phase.

Hepatocellular carcinoma localized in the bile duct lumen: two case report

Energy Technology Data Exchange (ETDEWEB)

Bae, Kyeung Kug; Chang, Jay Chun [Yeungnam Univ. School of Medicine, Seoul (Korea, Republic of)

1998-10-01

Intrabile duct tumor growth of hepatocellular carcinoma is an uncommon manifestation, but intraluminal bile duct hepatocellular carcinoma without primary hepatic parenchymal lesions is extremely rare. To our knowledge, only a few case reports have been published. We encountered two cases of primary hepatocellular carcinoma arising in the bile duct;serum alpha-fetoprotein levels were within the normal limits. Both showed the following characteristic radiologic features: (1) Cholangiography revealed filling defects within the dilated bile duct; (2) two-phase abdominal CT showed enhancement during the arterial-dominant phase and washout during the tissue equilibrium phase, as in typical HCC; and (3) hepateic arteriography revealed hypervascular tumor staining. Surgery was performed and the resected specimen showed no detectable primary hepatic parenchymal mass;on the basis of the pathologic finding, intraluminal bile duct hepatocellular carcinoma was confirmed. We cautiously assume that this peculiar type of HCC may arise primarily from bile duct mucosa.=20.

Imaging findings of mimickers of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Tae Kyoung Kim

2015-12-01

Full Text Available Radiological imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC as the noninvasive diagnosis of HCC in high-risk patients by typical imaging findings alone is widely adopted in major practice guidelines for HCC. While imaging techniques have markedly improved in detecting small liver lesions, they often detect incidental benign liver lesions and non-hepatocellular malignancy that can be misdiagnosed as HCC. The most common mimicker of HCC in cirrhotic liver is nontumorous arterioportal shunts that are seen as focal hypervascular liver lesions on dynamic contrast-enhanced cross-sectional imaging. Rapidly enhancing hemangiomas can be easily misdiagnosed as HCC especially on MR imaging with liver-specific contrast agent. Focal inflammatory liver lesions mimic HCC by demonstrating arterial-phase hypervascularity and subsequent washout on dynamic contrast-enhanced imaging. It is important to recognize the suggestive imaging findings for intrahepatic cholangiocarcinoma (CC as the management of CC is largely different from that of HCC. There are other benign mimickers of HCC such as angiomyolipomas and focal nodular hyperplasia-like nodules. Recognition of their typical imaging findings can reduce false-positive HCC diagnosis.

Contrast-enhanced ultrasound features of hepatocellular carcinoma not detected during the screening procedure.

Science.gov (United States)

Dong, Yi; Wang, Wen-Ping; Mao, Feng; Dietrich, Christoph

2017-08-01

Aim  The aim of this retrospective study is to report on the characteristics of contrast-enhanced ultrasound (CEUS) of primarily not detected hepatocellular carcinoma (HCC) during the screening procedure of patients at risk. Methods  Sixty-four patients with a finally solitary and histologically proven HCC not detected HCC during the screening procedure were retrospectively analyzed. Most of HCC lesions (90.6 %, 58/64) measured < 20 mm in diameter. All HCC lesions were not detected during the initial screening procedure but suspected using contrast-enhanced magnetic resonance imaging. The final gold standard was biopsy or surgery with histological examination. Results  On CEUS, 62/64 (96.8 %) of HCC were characterized as an obviously hyperenhanced lesion in arterial phase, and 41/64 (64.1 %) of HCC were characterized as hypoenhancing lesions in the portal venous and late phases. During the arterial phase of CEUS, 96.8 % of HCC displayed homogeneous hyperenhancement. Knowing the CEUS and magnetic resonance imaging findings, 45/64 (70.3 %) could have been detected using B-mode ultrasound (BMUS). Conclusion  BMUS as a screening procedure is generally accepted. Contrast-enhanced imaging modalities have improved detection and characterization of HCC. Homogeneous hyperenhancement during the arterial phase and mild washout are indicative for HCC in liver cirrhosis. © Georg Thieme Verlag KG Stuttgart · New York.

Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling

Science.gov (United States)

2015-01-01

Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients. PMID:26560447

Hypervascular hepatocellular carcinomas: detection with gadoxetate disodium-enhanced MR imaging and multiphasic multidetector CT

Energy Technology Data Exchange (ETDEWEB)

Onishi, Hiromitsu; Kim, Tonsok; Hori, Masatoshi; Nakaya, Yasuhiro; Tsuboyama, Takahiro; Nakamoto, Atsushi; Tatsumi, Mitsuaki; Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Radiology, Suita, Osaka (Japan); Imai, Yasuharu [Ikeda Municipal Hospital, Department of Gastroenterology, Ikeda, Osaka (Japan); Nagano, Hiroaki [Osaka University Graduate School of Medicine, Department of Surgery, Suita, Osaka (Japan); Kumano, Seishi; Okada, Masahiro; Murakami, Takamichi [Kinki University School of Medicine, Department of Radiology, Osakasayama, Osaka (Japan); Takamura, Manabu [Ikeda Municipal Hospital, Department of Radiology, Ikeda, Osaka (Japan); Wakasa, Kenichi [Osaka City University Graduate School of Medicine, Department of Diagnostic Pathology, Osaka, Osaka (Japan)

2012-04-15

To retrospectively compare the accuracy of detection of hypervascular hepatocellular carcinoma (HCC) by multiphasic multidetector CT and by gadoxetate disodium-enhanced MR imaging. After ethical approval, we analysed a total of 73 hypervascular HCC lesions from 31 patients suspected of having HCC, who underwent both gadoxetate disodium-enhanced MR imaging and multiphasic multidetector CT. Five blinded observers independently reviewed CT images, as well as dynamic MR images alone and combined with hepatobiliary phase MR images. Diagnostic accuracy (Az values), sensitivities and positive predictive values were compared by using the Scheffe post hoc test. The mean Az value for dynamic and hepatobiliary phase MR combined (0.81) or dynamic MR images alone (0.78) was significantly higher than that for CT images (0.67, P < 0.001, 0.005, respectively). The mean sensitivity of the combined MR images (0.67) was significantly higher than that of dynamic MR alone (0.52, P < 0.05) or CT images (0.44, P < 0.05). The mean positive predictive values were 0.96, 0.95 and 0.94, for CT, dynamic MR alone and combined MR images, respectively. Compared with multiphasic multidetector CT, gadoxetate disodium-enhanced MR imaging combining dynamic and hepatobiliary phase images results in significantly improved sensitivity and diagnostic accuracy for detection of hypervascular HCC. (orig.)

Subcentimeter hypervascular nodule with typical imaging findings of hepatocellular carcinoma in patients with history of hepatocellular carcinoma: natural course on serial gadoxetic acid-enhanced MRI and diffusion-weighted imaging

Energy Technology Data Exchange (ETDEWEB)

Song, Kyoung Doo; Kim, Seong Hyun; Lim, Hyo Keun [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Jung, Sin-Ho [Sungkyunkwan University School of Medicine, Center for Biostatistics and Clinical Epidemiology, Samsung Medical Center, Seoul (Korea, Republic of); Sungkyunkwan University School of Medicine, Samsung Advanced Institute for Health Sciences and Technology, Seoul (Korea, Republic of); Sohn, Insuk [Sungkyunkwan University School of Medicine, Center for Biostatistics and Clinical Epidemiology, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Hyung Sik [Gachon Medical School, Department of Radiology, Gil Medical Center, Incheon (Korea, Republic of)

2015-09-15

To evaluate the natural course of subcentimeter hypervascular nodules at high risk for developing into hepatocellular carcinomas (SHNHR) using serial magnetic resonance imaging (MRI) in patients with a history of hepatocellular carcinoma (HCC). An SHNHR was defined as a subcentimeter hypervascular nodule having typical imaging findings of HCC on gadoxetic acid-enhanced MRI and diffusion-weighted imaging. We included 39 patients with 46 SHNHRs (mean size ± standard deviation, 6.1 ± 1.6 mm; range, 3.2 - 9.0 mm). Overt HCC was defined as pathology proven HCC or a nodule larger than 1 cm with typical imaging findings of HCC. The cumulative rate and the independent predictive factors for progression to overt HCC were evaluated. The median follow-up period was 139 days (range, 64 - 392 days). The cumulative progression rate to overt HCC at 3, 6, 9, and 12 months was 13.9 %, 61.7 %, 83.2 %, and 89.9 %. The initial size of SHNHR was a significant predictor of progression to overt HCC, with an optimal cut-off value of 5.5 mm. The progression rate of SHNHR to overt HCC within 12 months was high (89.9 %) in patients with history of HCC. The initial size of SHNHR was an important predictor for progression to overt HCC. (orig.)

Correlation between chondroitin sulfate iron colloid - enhanced MR imaging and the histological grade of hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Suto, Y. [Dept. of Radiology, Tottori University School of Medcine, Yonago (Japan); Kodama, F. [Dept. of Radiology, Tottori University School of Medcine, Yonago (Japan); Kamba, M. [Dept. of Radiology, Tottori University School of Medcine, Yonago (Japan); Ohta, Y. [Dept. of Radiology, Tottori University School of Medcine, Yonago (Japan)

1995-01-01

The association between contrast enhancement by chondroitin sulfate iron colloid (CSIC) and the histological grade of hepatocellular carcinoma (HCC) was evaluated in 24 patients diagnosed by histological examination of surgical specimens (26 nodules: 11 well-differentiated and 15 poorly-moderately-differentiated nodules). In the well-differentiated HCC nodules, the tumor-liver contrast to noise ratio (CNR) was not significantly increased after i.v. CSIC injection on both T1-weighted and T2-weighted images. In the moderately-poorly-differentiated HCC, CNR was significantly increased after CSIC administration on both T1-weighted and T2-weighted images (p<0.01). MR imaging using CSIC may be useful for diagnosing the degree of HCC differentiation. (orig.).

Correlation between chondroitin sulfate iron colloid - enhanced MR imaging and the histological grade of hepatocellular carcinoma

International Nuclear Information System (INIS)

Suto, Y.; Kodama, F.; Kamba, M.; Ohta, Y.

1995-01-01

The association between contrast enhancement by chondroitin sulfate iron colloid (CSIC) and the histological grade of hepatocellular carcinoma (HCC) was evaluated in 24 patients diagnosed by histological examination of surgical specimens (26 nodules: 11 well-differentiated and 15 poorly-moderately-differentiated nodules). In the well-differentiated HCC nodules, the tumor-liver contrast to noise ratio (CNR) was not significantly increased after i.v. CSIC injection on both T1-weighted and T2-weighted images. In the moderately-poorly-differentiated HCC, CNR was significantly increased after CSIC administration on both T1-weighted and T2-weighted images (p<0.01). MR imaging using CSIC may be useful for diagnosing the degree of HCC differentiation. (orig.)

Hemorrhagic Cardiac Tamponade: Rare Complication of Radiofrequency Ablation of Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Loh, Kok Beng; Bux, Shaik Ismail; Abdullah, Basri Johan Jeet; Mokhtar, Raja Amin Raja; Mohamed, Rosmawati [Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia)

2012-09-15

Local treatment for hepatocellular carcinoma (HCC) has been widely used in clinical practice due to its minimal invasiveness and high rate of cure. Percutaneous radiofrequency ablation (RFA) is widely used because its treatment effectiveness. However, some serious complications can arise from percutaneous RFA. We present here a rare case of hemorrhagic cardiac tamponade secondary to an anterior cardiac vein (right marginal vein) injury during RFA for treatment of HCC.

Diagnostic performance of traditional hepatobiliary biomarkers of drug-induced liver injury in the rat.

Science.gov (United States)

Ennulat, Daniela; Magid-Slav, Michal; Rehm, Sabine; Tatsuoka, Kay S

2010-08-01

Nonclinical studies provide the opportunity to anchor biochemical with morphologic findings; however, liver injury is often complex and heterogeneous, confounding the ability to relate biochemical changes with specific patterns of injury. The aim of the current study was to compare diagnostic performance of hepatobiliary markers for specific manifestations of drug-induced liver injury in rat using data collected in a recent hepatic toxicogenomics initiative in which rats (n = 3205) were given 182 different treatments for 4 or 14 days. Diagnostic accuracy of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbili), serum bile acids (SBA), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total cholesterol (Chol), and triglycerides (Trig) was evaluated for specific types of liver histopathology by Receiver Operating Characteristic (ROC) analysis. To assess the relationship between biochemical and morphologic changes in the absence of hepatocellular necrosis, a second ROC analysis was performed on a subset of rats (n = 2504) given treatments (n = 152) that did not cause hepatocellular necrosis. In the initial analysis, ALT, AST, Tbili, and SBA had the greatest diagnostic utility for manifestations of hepatocellular necrosis and biliary injury, with comparable magnitude of area under the ROC curve and serum hepatobiliary marker changes for both. In the absence of hepatocellular necrosis, ALT increases were observed with biochemical or morphologic evidence of cholestasis. In both analyses, diagnostic utility of ALP and GGT for biliary injury was limited; however, ALP had modest diagnostic value for peroxisome proliferation, and ALT, AST, and total Chol had moderate diagnostic utility for phospholipidosis. None of the eight markers evaluated had diagnostic value for manifestations of hypertrophy, cytoplasmic rarefaction, inflammation, or lipidosis.

Cyclooxygenase-2 inhibitor is a robust enhancer of anticancer agents against hepatocellular carcinoma multicellular spheroids

Directory of Open Access Journals (Sweden)

Cui J

2014-02-01

Full Text Available Jie Cui,1,2 Ya-Huan Guo,3 Hong-Yi Zhang,4 Li-Li Jiang,1 Jie-Qun Ma,1 Wen-Juan Wang,1 Min-Cong Wang,1 Cheng-Cheng Yang,1 Ke-Jun Nan,1 Li-Ping Song5 1Department of Oncology, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, 2Department of Oncology, Yan'an University Affiliated Hospital, Yan'an, 3Department of Oncology, Shaanxi Province Cancer Hospital, Xi'an, 4Department of Urology, Yan'an University Affiliated Hospital, Yan'an, 5Department of Radiotherapy, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, People's Republic of China Purpose: Celecoxib, an inhibitor of cyclooxygenase-2 (COX2, was investigated for enhancement of chemotherapeutic efficacy in cancer clinical trials. This study aimed to determine whether celecoxib combined with 5-fluorouracil or sorafenib or gefitinib is beneficial in HepG2 multicellular spheroids (MCSs, as well as elucidate the underlying mechanisms. Methods: The human hepatocellular carcinoma cell line HepG2 MCSs were used as in vitro models to investigate the effects of celecoxib combined with 5-fluorouracil or sorafenib or gefitinib treatment on cell growth, apoptosis, and signaling pathway. Results: MCSs showed resistance to drugs compared with monolayer cells. Celecoxib combined with 5-fluorouracil or sorafenib exhibited a synergistic action. Exposure to celecoxib (21.8 µmol/L plus 5-fluorouracil (8.1 × 10-3 g/L or sorafenib (4.4 µmol/L increased apoptosis but exerted no effect on COX2, phosphorylated epidermal growth-factor receptor (p-EGFR and phosphorylated (p-AKT expression. Gefitinib (5 µmol/L, which exhibits no growth-inhibition activity as a single agent, increased the inhibitory effect of celecoxib. Gefitinib (5 µmol/L plus celecoxib (21.8 µmol/L increased apoptosis. COX2, p-EGFR, and p-AKT were inhibited. Conclusion: Celecoxib combined with 5-fluorouracil or sorafenib or gefitinib may be superior to single-agent therapy in HepG2

Differentiation of intrahepatic mass-forming cholangiocarcinoma from hepatocellular carcinoma on gadoxetic acid-enhanced liver MR imaging

Energy Technology Data Exchange (ETDEWEB)

Kim, Rihyeon; Shin, Cheong-Il; Yoon, Jeong Hee; Joo, Ijin; Kim, Seong Ho; Hwang, Inpyeong [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Lee, Jeong Min; Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Seoul (Korea, Republic of); Lee, Eun Sun; Choi, Byung Ihn [Chung-Ang University Hospital, Department of Radiology, Seoul (Korea, Republic of)

2016-06-15

To determine the different imaging features of intrahepatic mass-forming cholangiocarcinoma (IMCC) from hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). This retrospective study was institutional review board approved and the requirement for informed consent was waived. Patients who underwent gadoxetic acid-enhanced MRI with histologically confirmed IMCCs (n = 46) or HCCs (n = 58) were included. Imaging features of IMCCs and HCCs on gadoxetic acid-enhanced MRI including T2- and T1-weighted, diffusion weighted images, dynamic study and hepatobiliary phase (HBP) images were analyzed. Univariate and multivariate logistic regression analyses were performed to identify relevant differentiating features between IMCCs and HCCs. Multivariate analysis revealed heterogeneous T2 signal intensity and a hypointense rim on the HBP as suggestive findings of IMCCs and the wash-in and ''portal wash-out'' enhancement pattern as well as focal T1 high signal intensity foci as indicative of HCCs (all, p < 0.05). When we combined any three of the above four imaging features, we were able to diagnose IMCCs with 94 % (43/46) sensitivity and 86 % (50/58) specificity. Combined interpretation of enhancement characteristics including HBP images, morphologic features, and strict application of the ''portal wash-out'' pattern helped more accurate discrimination of IMCCs from HCCs. (orig.)

Radiosensitivity of hepatocellular carcinoma

International Nuclear Information System (INIS)

Hennequin, C.; Quero, L.; Rivera, S.

2011-01-01

The frequency of hepatocellular carcinoma (HCC) is increasing in the western world and the role of radiotherapy is more and more discussed. Classically, hepatocellular carcinoma was considered as a radioresistant tumour: in fact, modern radio-biologic studies, performed on cell lines directly established from patients, showed that hepatocellular carcinoma has the same radiosensitivity than the other epithelial tumours. From clinical studies, its α/β ratio has been estimated to be around 15 Gy. Radiosensitivity of normal hepatic parenchyma is now well evaluated and some accurate NTCP models are available to guide hepatic irradiation. The biology of hepatocellular carcinoma is also better described: the combination of radiotherapy and targeted therapies will be a promising approach in the near future. (authors)

Detection of hepatocellular carcinoma by Gd-EOB-DTPA-enhanced liver MRI: Comparison with triple phase 64 detector row helical CT

International Nuclear Information System (INIS)

Akai, Hiroyuki; Kiryu, Shigeru; Matsuda, Izuru; Satou, Jirou; Takao, Hidemasa; Tajima, Taku; Watanabe, Yasushi; Imamura, Hiroshi; Kokudo, Norihiro; Akahane, Masaaki; Ohtomo, Kuni

2011-01-01

Purpose: To compare the diagnostic performance of Gd-EOB-DTPA-enhanced MRI with that of triple phase 64-MDCT in the detection of hepatocellular carcinoma (HCC). Patients and methods: Thirty-four patients with 52 surgically proven lesions underwent Gd-EOB-DTPA-enhanced MRI and triple phase 64-MDCT. Two observers independently evaluated MR and CT imaging on a lesion-by-lesion basis. Sensitivity, positive and negative predictive values and reproducibility were evaluated. The diagnostic accuracy of each modality was assessed with alternative-free response receiver operating characteristic (ROC) analysis. Results: Both observers showed higher sensitivity in detecting lesions with MRI compared to CT, however, only the difference between the two imaging techniques for observer 2 was significant (P = 0.034). For lesions 1 cm or smaller, MRI and CT showed equal sensitivity (both 62.5%) with one observer, and MRI proved superior to CT with the other observer (MRI 75% vs. CT 56.3%), but the latter difference was not significant (P = 0.083). The difference in positive and negative predictive value between the two imaging techniques for each observer was not significant (P > 0.05). The areas under the ROC curve for each observer were 0.843 and 0.861 for MRI vs. 0.800 and 0.833 for CT and the differences were not significant. Reproducibility was higher using MRI for both observers, but the result was not significant (MRI 32/33 vs. CT 29/33, P = 0.083). Conclusion: Gd-EOB-DTPA-enhanced MRI tended to show higher diagnostic accuracy, sensitivity and reproducibility compared to triple phase 64-MDCT in the detection of hepatocellular carcinoma, however statistical significance was not achieved.

Dynamic CT of hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

1983-03-01

We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. Detecting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. The dynamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma.

Hepatocellular carcinoma: IVIM diffusion quantification for prediction of tumor necrosis compared to enhancement ratios

International Nuclear Information System (INIS)

Kakite, Suguru; Dyvorne, Hadrien A.; Lee, Karen M.; Jajamovich, Guido H.; Knight-Greenfield, Ashley; Taouli, Bachir

2015-01-01

To correlate intra voxel incoherent motion (IVIM) diffusion parameters of liver parenchyma and hepatocellular carcinoma (HCC) with degree of liver/tumor enhancement and necrosis; and to assess the diagnostic performance of diffusion parameters vs. enhancement ratios (ER) for prediction of complete tumor necrosis. In this IRB approved HIPAA compliant study, we included 46 patients with HCC who underwent IVIM diffusion-weighted (DW) MRI in addition to routine sequences at 3.0 T. True diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (PF) and apparent diffusion coefficient (ADC) were quantified in tumors and liver parenchyma. Tumor ER were calculated using contrast-enhanced imaging, and degree of tumor necrosis was assessed using post-contrast image subtraction. IVIM parameters and ER were compared between HCC and background liver and between necrotic and viable tumor components. ROC analysis for prediction of complete tumor necrosis was performed. 79 HCCs were assessed (mean size 2.5 cm). D, PF and ADC were significantly higher in HCC vs. liver (p < 0.0001). There were weak significant negative/positive correlations between D/PF and ER, and significant correlations between D/PF/ADC and tumor necrosis (for D, r 0.452, p < 0.001). Among diffusion parameters, D had the highest area under the curve (AUC 0.811) for predicting complete tumor necrosis. ER outperformed diffusion parameters for prediction of complete tumor necrosis (AUC > 0.95, p < 0.002). D has a reasonable diagnostic performance for predicting complete tumor necrosis, however lower than that of contrast-enhanced imaging

Cryotherapy for hepatocellular carcinoma

DEFF Research Database (Denmark)

Awad, Tahany; Thorlund, Kristian; Gluud, Christian

2009-01-01

BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy...... for the treatment of hepatocellular carcinoma. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by searching...... of benefit but included for the assessment of harm. Both severe and non-severe adverse events were reported, but the true nature and extent of harm was difficult to asses. AUTHORS' CONCLUSIONS: At present, there is no evidence to recommend or refute cryotherapy for patients with hepatocellular carcinoma...

The Impact of Liver Graft Injury on Cancer Recurrence Posttransplantation.

Science.gov (United States)

Li, Chang-Xian; Man, Kwan; Lo, Chung-Mau

2017-11-01

Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma. However, cancer recurrence, posttransplantation, remains to be the critical issue that affects the long-term outcome of hepatocellular carcinoma recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute-phase liver graft injury is a result of hepatic ischemia reperfusion injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation. The liver grafts from living donors, donors after cardiac death, and steatotic donors have been considered as promising sources of organs for liver transplantation and are associated with high incidence of liver graft injury. The acute-phase liver graft injury will trigger a series of inflammatory cascades, which may not only activate the cell signaling pathways regulating the tumor cell invasion and migration but also mobilize the circulating progenitor and immune cells to facilitate tumor recurrence and metastasis. The injured liver graft may also provide the favorable microenvironment for tumor cell growth, migration, and invasion through the disturbance of microcirculatory barrier function, induction of hypoxia and angiogenesis. This review aims to summarize the latest findings about the role and mechanisms of liver graft injury resulted from hepatic ischemia reperfusion injury on tumor recurrence posttransplantation, both in clinical and animal cohorts.

Dynamic CT of hepatocellular carcinoma

International Nuclear Information System (INIS)

Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

1983-01-01

We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. 1 Decting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. 2 The dinamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. 3 The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma. (author)

Mesenchymal stem cells enhance the metastasis of 3D-cultured hepatocellular carcinoma cells

International Nuclear Information System (INIS)

Liu, Chang; Liu, Yang; Xu, Xiao-xi; Guo, Xin; Sun, Guang-wei; Ma, Xiao-jun

2016-01-01

Accumulating evidences have demonstrated that mesenchymal stem cells (MSC) could be recruited to the tumor microenvironment. Umbilical cord mesenchymal stem cells (UCMSC) were attractive vehicles for delivering therapeutic agents against cancer. Nevertheless, the safety of UCMSC in the treatment of tumors including hepatocellular carcinoma (HCC) was still undetermined. In this study, an in vitro co-culture system was established to evaluate the effect of UCMSC on the cell growth, cancer stem cell (CSC) characteristics, drug resistance, metastasis of 3D-cultured HCC cells, and the underlying mechanism was also investigated. It was found that after co-cultured with UCMSC, the metastatic ability of 3D-cultured HCC cells was significantly enhanced as indicated by up-regulation of matrix metalloproteinase (MMP), epithelial-mesenchymal transition (EMT)-related genes, and migration ability. However, cell growth, drug resistance and CSC-related gene expression of HCC cells were not affected by UCMSC. Moreover, EMT was reversed, MMP-2 expression was down-regulated, and migration ability of HCC cell was significantly inhibited when TGF-β receptor inhibitor SB431542 was added into the co-culture system. Therefore, these data indicated that UCMSC could significantly enhance the tumor cell metastasis, which was due to the EMT of HCC cells induced by TGF-β. The online version of this article (doi:10.1186/s12885-016-2595-4) contains supplementary material, which is available to authorized users

Liver (Hepatocellular) Cancer Screening

Science.gov (United States)

... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

Ultrasound manifestation of hepatocellular carcinoma

International Nuclear Information System (INIS)

Hwang, M. S.; Yoo, H. S.; Park, C. Y.; Choi, H. J.; Moon, Y. M.; Lee, S. I.

1982-01-01

With the advent of gray scale ultrasonographic equipment, the parenchymal disease of liver is more easily evaluated. Ultrasonography is a non-invasive technique, different from angiography, and performed without discomfort to patient. And also ultrasonography can be used in assessing the liver in cases showing equivocal scintigraphy and in differentiation of solid and cystic masses, first detected on scintigrams. Therefore, the complementary use of ultrasonography, Tc-99m-sulfur colloid scan and angiography provides better diagnostic accuracy for the detection of hepatocellular carcinoma, and moreover, sequential ultrasonographic studies in the same patient are valuable of following the course of hepatocellular carcinoma and monitoring the effectiveness of therapy for hepatocellular carcinoma. In thirty patients with histologically proven hepatocellular carcinoma, an analysis of ultrasound manifestation is made and the results are as follows; 1. Ultrasound manifestation of hepatocellular carcinoma by gray scale showed four different sonographic patterns including discrete echo free, discrete echogenic, ill defined echogenic and mixed patterns. 2. The size of hepatocellular carcinoma by ultrasonographic measurement was larger than 5 cm in diameter in 28 cases. 3. In 7 cases performed with angiography, all echogenicities of hepatocellualr carcinoma were correlated with the findings of vascularity of angiography. 4. In cases combined with liver cirrhosis, the sonographic pattern of hepatocellular carcinoma appeared to be discrete or ill defined echogenic patterns

Ultrasound manifestation of hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Hwang, M S; Yoo, H S; Park, C Y; Choi, H J; Moon, Y M; Lee, S I [Yonsei University College of Medicine, Seoul (Korea, Republic of)

1982-06-15

With the advent of gray scale ultrasonographic equipment, the parenchymal disease of liver is more easily evaluated. Ultrasonography is a non-invasive technique, different from angiography, and performed without discomfort to patient. And also ultrasonography can be used in assessing the liver in cases showing equivocal scintigraphy and in differentiation of solid and cystic masses, first detected on scintigrams. Therefore, the complementary use of ultrasonography, Tc-99m-sulfur colloid scan and angiography provides better diagnostic accuracy for the detection of hepatocellular carcinoma, and moreover, sequential ultrasonographic studies in the same patient are valuable of following the course of hepatocellular carcinoma and monitoring the effectiveness of therapy for hepatocellular carcinoma. In thirty patients with histologically proven hepatocellular carcinoma, an analysis of ultrasound manifestation is made and the results are as follows; 1. Ultrasound manifestation of hepatocellular carcinoma by gray scale showed four different sonographic patterns including discrete echo free, discrete echogenic, ill defined echogenic and mixed patterns. 2. The size of hepatocellular carcinoma by ultrasonographic measurement was larger than 5 cm in diameter in 28 cases. 3. In 7 cases performed with angiography, all echogenicities of hepatocellualr carcinoma were correlated with the findings of vascularity of angiography. 4. In cases combined with liver cirrhosis, the sonographic pattern of hepatocellular carcinoma appeared to be discrete or ill defined echogenic patterns.

DNAJC6 promotes hepatocellular carcinoma progression through induction of epithelial–mesenchymal transition

International Nuclear Information System (INIS)

Yang, Tao; Li, Xiao-Na; Li, Xing-Guang; Li, Ming; Gao, Peng-Zhi

2014-01-01

Highlights: • DNAJC6 is up-regulated in hepatocellular carcinoma tissues. • DNAJC6 promotes hepatocellular carcinoma cell proliferation and invasion. • DNAJC6 induces epithelial–mesenchymal transition by activating transforming growth factor β signaling. - Abstract: Epithelial–mesenchymal transition (EMT) is a developmental program, which is associated with hepatocellular carcinoma (HCC) development and progression. DNAJC6 (DNA/HSP40 homolog subfamily C member 6) encodes auxilin, which is responsible for juvenile Parkinsonism with phenotypic variability. However, the role of DNAJC6 in HCC development and progression is limited. Here, we report that DNAJC6 is up-regulated in HCC tissues and up-regulation of DNAJC6 expression predicts poor outcome in patients with HCC. Furthermore, overexpression of DNAJC6 enhances the ability for acquisition of mesenchymal traits, enhanced cell proliferation and invasion. DNAJC6 positively regulated expression of EMT-related transcription factor, also activating transforming growth factor β (TGF-β) pathway to contribute to EMT. Our findings demonstrated an important function of DNAJC6 in the progression of HCC by induction of EMT, and they implicate DNAJC6 as a marker of poor outcome in HCC

DNAJC6 promotes hepatocellular carcinoma progression through induction of epithelial–mesenchymal transition

Energy Technology Data Exchange (ETDEWEB)

Yang, Tao [Hepatobiliary Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China); Li, Xiao-Na [General Surgery, Sports Science Institute of Hebei Province, Shijiazhuang 050011 (China); Li, Xing-Guang; Li, Ming [General Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China); Gao, Peng-Zhi, E-mail: pengzhigaovip@163.com [Hepatobiliary Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China)

2014-12-12

Highlights: • DNAJC6 is up-regulated in hepatocellular carcinoma tissues. • DNAJC6 promotes hepatocellular carcinoma cell proliferation and invasion. • DNAJC6 induces epithelial–mesenchymal transition by activating transforming growth factor β signaling. - Abstract: Epithelial–mesenchymal transition (EMT) is a developmental program, which is associated with hepatocellular carcinoma (HCC) development and progression. DNAJC6 (DNA/HSP40 homolog subfamily C member 6) encodes auxilin, which is responsible for juvenile Parkinsonism with phenotypic variability. However, the role of DNAJC6 in HCC development and progression is limited. Here, we report that DNAJC6 is up-regulated in HCC tissues and up-regulation of DNAJC6 expression predicts poor outcome in patients with HCC. Furthermore, overexpression of DNAJC6 enhances the ability for acquisition of mesenchymal traits, enhanced cell proliferation and invasion. DNAJC6 positively regulated expression of EMT-related transcription factor, also activating transforming growth factor β (TGF-β) pathway to contribute to EMT. Our findings demonstrated an important function of DNAJC6 in the progression of HCC by induction of EMT, and they implicate DNAJC6 as a marker of poor outcome in HCC.

Hepatocellular carcinoma treated with transarterial chemoembolization: Evaluation with parametric contrast-enhanced ultrasonography

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Moschouris, Hippocrates; Malagari, Katerina; Marinis, Athanasios; Kornezos, Ioannis; Stamatiou, Konstantinos; Nikas, Georgios; Papadaki, Marina Georgiou; Gkoutzios, Panagiotis

2012-01-01

AIM: To evaluate the response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) using a simplified protocol of parametric contrast-enhanced ultrasound (pCEUS). METHODS: Eighteen patients with HCC (18 target tumors, diameter: 2.8-12 cm) were evaluated before, and 20 d after TACE. The distribution and morphology of TACE-induced necrosis in these tumors precluded accurate evaluation by visual assessment or by simple measurements. For pCEUS, a 4.8 mL bolus of SonoVue (Bracco, Milan, Italy) was intravenously administered and analysis of tumor perfusion during the initial phase of enhancement (0-30 s post injection) was performed with dedicated software (Qontrast, Bracco, Milan, Italy). Time-intensity curves were plotted and three parameters were calculated: peak intensity (PI, in percentage %), time to peak (TTP in seconds, s) and area under the curve during wash-in (AUC-WI, in arbitrary units, a.u). Magnetic resonance imaging was the standard imaging modality for post-treatment evaluation. Changes in tumor size were recorded and response was assessed according to response evaluation criteria in solid tumors criteria. RESULTS: A statistically significant decrease in PI and AUC-WI was observed in the treated tumors post TACE; PIpre: 21.5% ± 8.7% (mean ± SD), PIpost: 12.7% ± 6.7%, P < 0.001, AUC-WI pre: 17493 ± 9563 a.u, AUC-WI post: 9585 ± 5494 a.u, P < 0.001. A slight increase in TTP was noted post TACE, but this was not statistically significant; TTP pre: 13.1 ± 4.3 s, TTP post: 13.6 ± 4.2 s , P = 0.058). The changes in the aforementioned parameters were not accompanied by significant tumor shrinkage. CONCLUSION: pCEUS, even when limited to the study of the arterial phase of tumoral enhancement, can detect and quantify early perfusional changes in HCC post TACE. PMID:22937217

MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model

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Vinh NQ

2015-06-01

Full Text Available Nguyen Quoc Vinh,1 Shigeyuki Naka,1 Horacio Cabral,2 Hiroyuki Murayama,1 Sachiko Kaida,1 Kazunori Kataoka,2 Shigehiro Morikawa,3 Tohru Tani4 1Department of Surgery, Shiga University of Medical Science, Shiga, Japan; 2Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan; 3Department of Nursing, Shiga University of Medical Science, Shiga, Japan; 4Biomedical Innovation Center, Shiga University of Medical Science, Shiga, Japan Abstract: Hepatocellular carcinoma (HCC is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexaneplatinum(II (DACHPt] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or

Clinical spectrum and therapeutic approach to hepatocellular injury in patients with hyperthyroidism

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Mazo DF

2013-02-01

Full Text Available Daniel Ferraz de Campos Mazo,1 Graciana Bandeira Salgado de Vasconcelos,1 Maria Adelaide Albergaria Pereira,2 Evandro Sobroza de Mello,3 Telesforo Bacchella,1 Flair Jose Carrilho,1 Eduardo Luiz Rachid Cançado1,41Department of Gastroenterology, 2Department of Internal Medicine, 3Department of Pathology, 4Laboratory of Immunopathology of Schistosomiasis (LIM 06, Institute of Tropical Medicine, University of São Paulo School of Medicine, São Paulo, BrazilAbstract: Liver dysfunction in patients with hyperthyroidism includes abnormalities associated with the effects of thyroid hormone excess, those secondary to drug-induced liver injury, and changes resulting from concomitant liver disease. Our goal was to describe clinical, biochemical, and histopathological patterns in patients suffering from hyperthyroidism and concomitant liver dysfunction and to propose an algorithm of procedures to facilitate diagnosis and management of such cases. This study describes seven patients with liver biochemistry abnormalities detected after diagnosis of hyperthyroidism and one with undiagnosed decompensated hyperthyroidism and acute hepatitis. Two patients showed autoantibody reactivity which, together with liver histology, suggested the diagnosis of classic autoimmune hepatitis. Three patients experienced hepatotoxicity induced by propylthiouracil, the manifestations of which ranged from a benign course after drug withdrawal in one, a longstanding course in another suggesting drug-induced autoimmune hepatitis, and a more severe clinical condition with acute liver failure in a third patient, requiring liver transplantation. The three remaining patients showed no precipitating factors other than thyroid hyperactivity itself. They could be interpreted as having a thyroid storm with different clinical presentations. In conclusion, this series of patients illustrates the most frequent patterns of hepatocellular damage associated with hyperthyroidism and provides an

Characteristic Uptake Pattern of Bone Scintigraphy in Patients with Hepatocellular Carcinoma Following Treatment with High-Intensity Focused Ultrasound

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Ma, Waihan; Ho, Waiyin; Lai, Andrew S. H.; Wong, Kwongkuen; Law, Martin [Queen Mary Hospital, Pokfulam (Hong Kong)

2013-12-15

This study retrospectively reviews the characteristic bone scintigraphic findings in 18 patients with hepatocellular carcinoma (HCC) following treatment with high-intensity focused ultrasound (HIFU). A potential complication of HIFU is damage to the tissues along the path of the ultrasound beam and structures superficial to the lesion of interest. Patients with hepatocellular carcinoma who underwent a bone scan between 1st December 2005 and 31st December 2011 were considered for this study. Among these patients, only those who had bone scans after the HIFU treatment were included. The time between HIFU treatment and bone scans, HIFU energy, HCC sites, tumour sizes and related radiological findings were evaluated. In total, 20 bone scans of 18 patients were reviewed. Of these scans, two patients were normal; three patients showed decreased uptake, four patients showed increased uptake and nine patients showed mixed uptakes of the bony tracer in their rib cages. The defects were located in the anterior, lateral, anterolateral or posterolateral aspects of the rib cage. The majority of those cold defects were in the right anterior rib cages. SPECT/CT was used to localise the decreased uptake in ribs. The magnetic resonance imaging in individual patients invariably showed ill-defined rim enhancement along the right chest wall, signifying chest wall injury. The results showed that tissue ablation using HIFU caused tissue injury along the pathway of high-intensity ultrasound beams. The harm to tissues is presented as photopenic area on the rib cages due to necrosis or hot spots due to rib fractures in the bone scan. Since these cold defects are subtle, they are easily overlooked or mistaken as aggressive bony metastasis.

Value of Gd-EOB-DTPA-enhanced MRI in diagnosis of hepatocellular carcinoma

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SUN Yu

2018-01-01

Full Text Available Objective To investigate the value of Gd-EOB-DTPA-enhanced MRI in the diagnosis of hepatocellular carcinoma (HCC. Methods A total of 40 patients with liver cirrhosis or suspected HCC who visited General Hospital of Shenyang Military Area Command from October 2016 to April 2017 were enrolled, and the data on three dynamic phases of Gd-EOB-DTPA-enhanced MRI (arterial phase, portal venous phase, and delayed phase, hepatobiliary phase (delayed for 20 minutes, and diffusion-weighted imaging (DWI (b=50,400, and 1000 s/mm2 were collected. Two radiologists made a diagnosis and gave diagnostic confidence scores based on the presence or absence of hepatobiliary phase images. Postoperative pathology or clinical diagnosis was used as the criteria for assessing the diagnostic accuracy of HCC. The t-test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. Results A total of 42 HCC lesions and 37 cirrhotic nodules were detected. There were significant differences between HCC lesions and cirrhotic nodules in signal intensity on hepatobiliary phase and DWI (χ2=64.503 and 67.855, both P＜0.001，as well as the apparent diffusion coefficient when the b-values of DWI were 400 s/mm2 and 1000 s/mm2 (t=62.75 and 75.36, both P＜0.001. There was a significant difference in diagnostic confidence score given by the radiologists between the images of three dynamic phases of Gd-EOB-DTPA-enhanced MRI and those of four dynamic phases (including hepatobiliary phase (3.260±0.521 vs 4.620±0.661, t=10.67, P＜0.001. With postoperative pathology and clinical diagnosis as criteria, the images of three dynamic phases of Gd-EOB-DTPA-enhanced MRI had a significantly higher diagnostic accuracy for HCC than those of four dynamic phases (including hepatobiliary phase ［76.19% (32/42 vs 95.24% (40/42, χ2=6.222, P=0.013］. Conclusion Gd-EOB-DTPA-enhanced MRI may improve diagnostic accuracy and confidence for HCC and has

Digital contrast enhancement of 18Fluorine-fluorodeoxyglucose positron emission tomography images in hepatocellular carcinoma

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Pandey, Anil Kumar; Sharma, Sanjay Kumar; Agarwal, Krishan Kant; Sharma, Punit; Bal, Chandrasekhar; Kumar, Rakesh

2016-01-01

The role of 18 fluorodeoxyglucose positron emission tomography (PET) is limited for detection of primary hepatocellular carcinoma (HCC) due to low contrast to the tumor, and normal hepatocytes (background). The aim of the present study was to improve the contrast between the tumor and background by standardizing the input parameters of a digital contrast enhancement technique. A transverse slice of PET image was adjusted for the best possible contrast, and saved in JPEG 2000 format. We processed this image with a contrast enhancement technique using 847 possible combinations of input parameters (threshold “m” and slope “e”). The input parameters which resulted in an image having a high value of 2 nd order entropy, and edge content, and low value of absolute mean brightness error, and saturation evaluation metrics, were considered as standardized input parameters. The same process was repeated for total nine PET-computed tomography studies, thus analyzing 7623 images. The selected digital contrast enhancement technique increased the contrast between the HCC tumor and background. In seven out of nine images, the standardized input parameters “m” had values between 150 and 160, and for other two images values were 138 and 175, respectively. The value of slope “e” was 4 in 4 images, 3 in 3 images and 1 in 2 images. It was found that it is important to optimize the input parameters for the best possible contrast for each image; a particular value was not sufficient for all the HCC images. The use of above digital contrast enhancement technique improves the tumor to background ratio in PET images of HCC and appears to be useful. Further clinical validation of this finding is warranted

Assessment of triple-phase CT findings for the differentiation of fat-deficient hepatic angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver

International Nuclear Information System (INIS)

Jeon, Tae Yeon; Kim, Seong Hyun; Lim, Hyo K.; Lee, Won Jae

2010-01-01

Background: To evaluate the triple-phase CT findings for the differentiation of fat-deficient angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver. Methods: We retrospectively reviewed contrast-enhanced triple-phase CT images of 10 patients with fat-deficient hepatic angiomyolipoma and 28 patients with 29 hepatocellular carcinomas in non-cirrhotic liver proved on histologic examination. The CT findings for the two types of tumors were compared using Fisher's exact test. Results: Early draining vein depicted on arterial or portal phases was seen in eight (80%) angiomyolipomas and two hepatocellular carcinomas (7%) (p < 0.001), in which the early draining vein was connected with tumoral vessels. The tumoral vessels in the angiomyolipoma were more prominent and ectatic, were distributed both centrally and peripherally, and were seen in smaller tumors than in the hepatocellular carcinoma. Tumor capsule enhancement was absent in all angiomyolipomas as compared with two (7%) hepatocellular carcinomas with no tumor capsule (p < 0.001). The other CT findings were not significantly different for the two different types of tumors. Conclusions: The presence of early draining vein connecting with prominent tumoral vessels and absent tumor capsule were useful CT findings for the differentiation of fat-deficient angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver.

Enhanced visuomotor processing of phobic images in blood-injury-injection fear.

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Haberkamp, Anke; Schmidt, Thomas

2014-04-01

Numerous studies have identified attentional biases and processing enhancements for fear-relevant stimuli in individuals with specific phobias. However, this has not been conclusively shown in blood-injury-injection (BII) phobia, which has rarely been investigated even though it has features distinct from all other specific phobias. The present study aims to fill that gap and compares the time-course of visuomotor processing of phobic stimuli (i.e., pictures of small injuries) in BII-fearful (n=19) and non-anxious control participants (n=23) by using a response priming paradigm. In BII-fearful participants, phobic stimuli produced larger priming effects and lower response times compared to neutral stimuli, whereas non-anxious control participants showed no such differences. Because these effects are fully present in the fastest responses, they indicate an enhancement in early visuomotor processing of injury pictures in BII-fearful participants. These results are comparable to the enhanced processing of phobic stimuli in other specific phobias (i.e., spider phobia). Copyright © 2014 Elsevier Ltd. All rights reserved.

Chondroitin sulfate iron colloid-enhanced MR imaging of hepatocellular carcinoma; Correlation between histologic grade and detectability

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Kamba, Masayuki; Suto, Yuji; Kodama, Fumiko; Kato, Terumi; Ohta, Yoshio; Horie, Yasushi; Hamazoe, Ryuichi; Kawasaki, Hironaka (Tottori Univ., Yonago (Japan). School of Medicine)

1994-03-01

We applied chondroitin sulfate iron colloid (CSIC) as an MR contrast agent to detect hepatocellular carcinoma (HCC). The MR and pathologic findings of 25 HCCs in 21 patients were analyzed. MR imaging was performed with a superconducting system operating at 1.5 T. Proton density-weighted (PDW), T[sub 2]-weighted (T[sub 2]W) and T[sub 1]-weighted (T[sub 1]W) images were obtained before and after an intravenous injection of 23.6 [mu]mol Fe/kg of CSIC. In moderately to poorly differentiated and moderately differentiated HCCs (n=15), all the lesions except a 5-mm satellite nodule were detectable with unenhanced T[sub 2]W images as well as CSIC-enhanced PDW, T[sub 2]W and T[sub 1]W images. In well to moderately differentiated HCCs (n=6), two to four lesions were detectable with unenhanced images. All the lesions except a 3-mm satellite nodule were detectable with CSIC-enhanced PDW, T[sub 2]W and T[sub 1]W images. In well differentiated HCCs (n=4), one or two lesions were detectable with unenhanced images. All the lesions were detectable with CSIC-enhanced T[sub 1]W images, while only two lesions were detectable with CSIC-enhanced PDW or T[sub 2]W images. CSIC administration improves detection rates, and is especially useful in detecting small foci of well to moderately or well differentiated HCC. (author).

Spinal cord injury after conducting transcatheter arterial chemoembolization for costal metastasis of hepatocellular carcinoma

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Sang Jung Park

2012-09-01

Full Text Available Transcatheter arterial chemoembolization (TACE has been used widely to treat patients with unresectable hepatocellular carcinoma. However, this method can induce various adverse events caused by necrosis of the tumor itself or damage to nontumor tissues. In particular, neurologic side effects such as cerebral infarction and paraplegia, although rare, may cause severe sequelae and permanent disability. Detailed information regarding the treatment process and prognosis associated with this procedure is not yet available. We experienced a case of paraplegia that occurred after conducting TACE through the intercostal artery to treat hepatocellular carcinoma that had metastasized to the rib. In this case, TACE was attempted to relieve severe bone pain, which had persisted even after palliative radiotherapy. A sudden impairment of sensory and motor functions after TACE developed in the trunk below the level of the sternum and in both lower extremities. The patient subsequently received steroid pulse therapy along with supportive care and continuous rehabilitation. At the time of discharge the patient had recovered sufficiently to enable him to walk by himself, although some paresthesia and spasticity remained.

FDG-avid portal vein tumor thrombosis from hepatocellular carcinoma in contrast-enhanced FDG PET/CT

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Canh Nguyen

2015-01-01

Full Text Available Objective(s: In this study, we aimed to describe the characteristics of portal vein tumor thrombosis (PVTT, complicating hepatocellular carcinoma (HCC in contrast-enhanced FDG PET/CT scan. Methods: In this retrospective study, 9 HCC patients with FDG-avid PVTT were diagnosed by contrast-enhanced fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT, which is a combination of dynamic liver CT scan, multiphase imaging, and whole-body PET scan. PET and CT DICOM images of patients were imported into the PET/CT imaging system for the re-analysis of contrast enhancement and FDG uptake in thrombus, the diameter of the involved portal vein, and characteristics of liver tumors and metastasis. Results: Two patients with previously untreated HCC and 7 cases with previously treated HCC had FDG-avid PVTT in contrast-enhanced FDG PET/CT scan. During the arterial phase of CT scan, portal vein thrombus showed contrast enhancement in 8 out of 9 patients (88.9%. PET scan showed an increased linear FDG uptake along the thrombosed portal vein in all patients. The mean greatest diameter of thrombosed portal veins was 1.8 ± 0.2 cm, which was significantly greater than that observed in normal portal veins (P<0.001. FDG uptake level in portal vein thrombus was significantly higher than that of blood pool in the reference normal portal vein (P=0.001. PVTT was caused by the direct extension of liver tumors. All patients had visible FDG-avid liver tumors in contrast-enhanced images. Five out of 9 patients (55.6% had no extrahepatic metastasis, 3 cases (33.3% had metastasis of regional lymph nodes, and 1 case (11.1% presented with distant metastasis. The median estimated survival time of patients was 5 months. Conclusion: The intraluminal filling defect consistent with thrombous within the portal vein, expansion of the involved portal vein, contrast enhancement, and linear increased FDG uptake of the thrombus extended from liver tumor are

The role of the hemostatic system in murine liver injury induced by coexposure to lipopolysaccharide and trovafloxacin, a drug with idiosyncratic liability

International Nuclear Information System (INIS)

Shaw, Patrick J.; Fullerton, Aaron M.; Scott, Michael A.; Ganey, Patricia E.; Roth, Robert A.

2009-01-01

The use of the fluoroquinolone antibiotic trovafloxacin (TVX) was severely restricted in 1999 due to its association with idiosyncratic hepatotoxicity. Previously, we reported that a nontoxic dose of TVX interacts with a nontoxic dose of lipopolysaccharide (LPS) to cause robust hepatocellular injury in mice. This interaction with LPS was not seen in mice treated with levofloxacin (LVX), a fluoroquinolone not associated with hepatotoxicity in people. TVX/LPS-coexposure caused an increase in plasma alanine aminotransferase (ALT) activity as early as 4.5 h after LPS administration which progressed through 15 h. We examined the role of the hemostatic system in TVX/LPS-induced liver injury. At the onset of liver injury, coexposure to TVX/LPS, but not exposure to TVX, LVX, LPS or LVX/LPS, caused increased plasma concentration of thrombin-antithrombin dimers and decreased plasma circulating fibrinogen. LPS treatment induced a small increase in plasma plasminogen activator inhibitor-1 (PAI-1) concentration, and TVX pretreatment enhanced this effect. TVX/LPS coexposure also resulted in hepatic fibrin deposition. Anticoagulant heparin administration reduced TVX/LPS-induced hepatic fibrin deposition and liver injury. PAI-1 -/- mice treated with TVX/LPS exhibited similar fibrin deposition to wild-type mice but had significantly reduced hepatocellular injury. PAI-1 -/- mice, but not heparin-treated mice, had reduced plasma concentrations of several cytokines compared to TVX/LPS-treated controls. In summary, TVX/LPS-coexposure caused an imbalance in the hemostatic system, resulting in thrombin activation increased, plasma concentration of PAI-1 and hepatic fibrin deposition. Both thrombin activation and PAI-1 play critical roles in the progression of TVX/LPS-induced liver injury, but through different modes of action.

Contrast-enhanced ultrasound-guided radiofrequency ablation in inconspicuous hepatocellular carcinoma on B-mode ultrasound.

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Kim, Eui Joo; Kim, Yun Soo; Shin, Seung Kak; Kwon, Oh Sang; Choi, Duck Joo; Kim, Ju Hyun

2017-11-01

B-mode ultrasound (US) has difficulty targeting small hepatocellular carcinomas (HCCs) with poor conspicuity during radiofrequency ablation (RFA). Contrast-enhanced ultrasound (CEUS) can improve visualization of small or inconspicuous HCCs. This study was conducted to evaluate the effectiveness of CEUS-guided RFA electrode insertion during the arterial phase in inconspicuous HCCs. Ninety-three treatment-naïve HCCs from 80 patients treated with RFA from August 2012 to December 2014 were retrospectively reviewed. Seventy-five HCCs from 65 patients underwent B-mode US-guided RFA, and 15 HCCs from 14 patients that were inconspicuous on B-mode US underwent CEUS-guided RFA during the arterial phase after injection of sulfur hexafluoride microbubbles (SonoVue®). Technical success was assessed by contrast-enhanced computed tomography within 1 week and 3 months after the procedure. The mean size of HCCs treated with CEUS-guided RFA was smaller than that of HCCs treated with B-mode US-guided RFA (1.17±0.36 vs. 1.63±0.55 cm, p=0.003). Technical success rates of CEUS-guided RFA within 1 week and 3 months were 100% (15/15) and 93.3% (14/15), respectively. Technical success rates of B-mode US-guided RFA were 97.3% (73/75) and 94.5% (69/73), respectively. CEUS-guided RFA is highly efficacious for ablation of very small and inconspicuous HCCs.

Chondroitin sulfate iron colloid-enhanced MR imaging in patients with small hepatocellular carcinomas. Correlations with hemodynamic and pathologic examinations

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Kamba, Masayuki; Suto, Yuji; Kodama, Fumiko; Sugihara, Shuji; Yoshida, Kotaro [Tottori Univ., Yonago (Japan). Faculty of Medicine

1997-07-01

To determine the usefulness of chondroitin sulfate iron colloid (CSIC)-enhanced magnetic resonance imaging (MRI) in evaluation of the histologic grade of hepatocellular carcinoma (HCC), we performed a comparative study with computed tomography during arterial portography (CTAP) and CT arteriography. Twenty-one surgically resected HCCs 3 cm or less in diameter were examined. There were five well-differentiated, six well- to moderately-differentiated and ten moderately- or poorly- differentiated HCCs. T2-weighted spin echo images (repetition time: 2,000 ms, echo time: 90 ms) were taken before and after intravenous injection of 23.6 {mu}molFe/kg of CSIC. The differences between precontrast and postcontrast contrast-to-noise ratios (enhancement index) was correlated with the findings of CTAP, CT arteriography and histological examination. The enhancement index increased with statistical significance as the intranodular arterial perfusion increased (p<0.01), and as the intranodular portal perfusion decreased (p<0.01). Though the enhancement index tended to increase as the grade of malignancy increased, no statistical significance was found. CSIC-enhanced MRI allowed a noninvasive evaluation of the intranodular reticuloendothelial function. We consider this procedure as a supplementary method for evaluation of the histologic grade of HCC prior to performing invasive procedures such as angiography and biopsy. (author)

Influence of Kupffer cell inactivation on cycloheximide-induced hepatic injury

International Nuclear Information System (INIS)

Kumagai, Kazuyoshi; Kiyosawa, Naoki; Ito, Kazumi; Yamoto, Takashi; Teranishi, Munehiro; Nakayama, Hiroyuki; Manabe, Sunao

2007-01-01

In our previous study, we found that cycloheximide (CHX) induces hepatocellular necrosis as well as hepatocellular apoptosis. This article evaluates the role of Kupffer cells on cycloheximide-induced hepatic injury using gadolinium chloride (GdCl 3 ) for the inhibition of Kupffer cells. One group of rats was treated with CHX (CHX group), and another was treated with GdCl 3 before being treated with the same dose of CHX (GdCl 3 /CHX group). The necrotic change in the GdCl 3 /CHX group was exacerbated under the induction of hepatocellular apoptosis by the CHX treatment. A substantial diminution of the number of ED1- or ED2-positive cells was demonstrated in the GdCl 3 /CHX group compared to the CHX group. In addition, the degree of decrease in ED2-positive cells was more apparent than that in ED1-positive cells. Increases in the mRNA levels of IL-10 and Stat3 were observed in the CHX group, but not in the GdCl 3 /CHX group. On the other hand, the hepatic mRNA levels of chemokines and adhesion molecules such as Ccl20, LOX-1, and E-selectin were significantly increased only in the GdCl 3 /CHX group. Thus, Kupffer cell inactivation by the GdCl 3 treatment leads to a loss of the capacity to produce IL-10, supposedly resulting in the enhancement of pro-inflammatory cytokine activities such as tumor necrosis factor (TNF) signaling. These events are suggested to be a factor of the inflammatory exacerbation in the livers of the GdCl 3 /CHX group. In conclusion, Kupffer cells may play a role in protecting hepatic necroinflammatory changes by releasing anti-inflammatory cytokines following the hepatocellular apoptosis resulting from CHX treatment

Is gut the "motor" for producing hepatocellular dysfunction after trauma and hemorrhagic shock?

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Wang, P; Ba, Z F; Cioffi, W G; Bland, K I; Chaudry, I H

1998-02-01

Although studies suggest that the gut may be the "motor" responsible for producing sepsis and multiple organ failure after injury, it is not known whether enterectomy prior to the onset of hemorrhage alters proinflammatory cytokines TNF and IL-6 and, if so, whether hepatocellular dysfunction and damage are prevented or attenuated under such conditions. Under methoxyflurane anesthesia, an enterectomy in the rat was performed by excision of the duodenum, jejunum, and ileum. The rats were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal shed volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood with Ringer's lactate over 1 h. At 1.5 h after the completion of resuscitation, hepatocellular function [i.e., the maximal velocity (Vmax) and transport efficiency (Km) of indocyanine green (ICG) clearance] was assessed by an in vivo ICG clearance technique. Blood samples were taken for the measurement of TNF, IL-6, and liver enzymes (i.e., SGPT and SGOT). Cardiac output and microvascular blood flow were determined by ICG dilution and laser Doppler flowmetry, respectively. The increase in circulating levels of TNF but not IL-6 was prevented by enterectomy prior to hemorrhage. The reduced Vmax and K(m) and elevated SGPT and SGOT following hemorrhage and resuscitation, however, were not significantly affected by prior enterectomy. Moreover, enterectomy before hemorrhage further reduced hepatic perfusion. Since enterectomy prior to the onset of hemorrhage does not prevent or attenuate the reduced ICG clearance and elevated liver enzymes despite downregulation of TNF production, it appears that the small intestine does not play a significant role in producing hepatocellular dysfunction and injury following trauma and hemorrhagic shock.

Ring-Like Enhancement of Hepatocellular Carcinoma in Gadoxetic Acid-Enhanced Multiphasic Hepatic Arterial Phase Imaging With Differential Subsampling With Cartesian Ordering.

Science.gov (United States)

Ichikawa, Shintaro; Motosugi, Utaroh; Oishi, Naoki; Shimizu, Tatsuya; Wakayama, Tetsuya; Enomoto, Nobuyuki; Matsuda, Masanori; Onishi, Hiroshi

2018-04-01

The aim of this study was to evaluate the efficacy of multiphasic hepatic arterial phase (HAP) imaging using DISCO (differential subsampling with Cartesian ordering) in increasing the confidence of diagnosis of hepatocellular carcinoma (HCC). This retrospective study was approved by the institutional review board, and the requirement for informed patient consent was waived. Consecutive patients (from 2 study periods) with malignant liver nodules were examined by gadoxetic acid-enhanced magnetic resonance imaging using either multiphasic (6 phases; n = 135) or single (n = 230) HAP imaging, which revealed 519 liver nodules other than benign ones (HCC, 497; cholangiocarcinoma, 11; metastases, 10; and malignant lymphoma, 1). All nodules were scored in accordance with the Liver Imaging Reporting and Data System (LI-RADS v2014), with or without consideration of ring-like enhancement in multiphasic HAP images as a major feature. In the multiphasic HAP group, 178 of 191 HCCs were scored as LR-3 to LR-5 (3 [1.69%], 85 [47.8%], and 90 [50.6%], respectively). Upon considering ring-like enhancement in multiphasic HAP images as a major feature, 5 more HCCs were scored as LR-5 (95 [53.4%]), which was a significantly more confident diagnosis than that with single HAP images (295 of 306 HCCs scored as LR-3 to LR-5: 13 [4.41%], 147 [49.8%], and 135 [45.8%], respectively; P = 0.0296). There was no significant difference in false-positive or false-negative diagnoses between the multiphasic and single HAP groups (P = 0.8400 and 0.1043, respectively). Multiphasic HAP imaging can improve the confidence of diagnosis of HCCs in gadoxetic acid-enhanced magnetic resonance imaging.

CT findings of exophytic hepatocellular carcinoma

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Lee, Sang Jin; Cho, June Sik; Kim, Hyung Lyul; Lee, Chung Keun; Kim, Dae Hong; Rhee, Byung Chull [Chungnam National University College of Medicine, Daejeon (Korea, Republic of)

1993-11-15

We retrospectively evaluated the characteristic computed tomographic(CT) findings in nine patients with exohepatic hepatocellular carcinoma(HCC) pathologically prove by surgery(n=2) or percutaneous needle biopsy(n=7). The CT findings of exphepatic HCC were correlated with clinical findings and compared with those of usual HCC. Lesions were in the left lobe(n=7) and right lobe(n=2) of the liver. All lesions showed a well-marginated hypodense mass with capsular enhancement on enhanced CT scan. The patterns of capsular enhancement were complete in five and partial in four case. The portal vein thrombosis was seen only in one case. There was no difference between exohepatic HCC and usual HCC in clinical findings such as increased {alpha}-fetoprotein({alpha}-FP), positive hepatitis B surface antigen(HBsAg), and underlying liver cirrhosis. In conclusion, the CT findings of exohepatic HCC were a well-defined hyperdense mass with complete or partial capsular enhancement and these findings may be useful in differentiation from the tumors of adjacent organs.

Percutaneous cryoablation for hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Kyoung Doo Song

2016-12-01

Full Text Available Local ablation therapy is considered as a conventional treatment option for patients with early stage hepatocellular carcinoma (HCC. Although radiofrequency (RF ablation is widely used for HCC, the use of cryoablation has been increasing as newer and safer cryoablation systems have developed. The thermodynamic mechanism of freezing and thawing used in cryoablation is the Joule-Thomson effect. Cryoablation destroys tissue via direct tissue destruction and vascular-related injury. A few recent comparative studies have shown that percutaneous cryoablation for HCCs is comparable to percutaneous RF ablation in terms of long term therapeutic outcomes and complications. Cryoablation has several advantages over RF ablation such as well visualization of iceball, no causation of severe pain, and lack of severe damage to great vessels and gallbladder. It is important to know the advantages and disadvantages of cryoablation compared with RF ablation for improvement of therapeutic efficacy and safety.

The evaluation study of helical CT for hepatocellular carcinoma with microwave coagulation treatment

International Nuclear Information System (INIS)

Zheng Keguo; Xu Dasheng; Xie Xiaoyan; Peng Zhenpeng

2002-01-01

Objective: To study the helical CT signs of the hepatocellular carcinoma (HCC) after percutaneous microwave coagulation therapy (PMCT) and to evaluate the correlation between the helical CT signs and the therapeutic effect of HCC. Methods: The helical CT signs were analyzed in 22 cases with 26 lesions of the hepatocellular carcinoma that were treated with PMCT under ultrasonic guidance. Results: In 21 lesions, no enhancement was detected in the lesion border or inside the lesion at hepatic arterial phase (HAP) and portal venous phase (PVP). In 7 lesions, the slight or marked patchy enhancement was revealed in the surrounding liver of the lesions in HAP. In 5 lesions, nodular enhancement was found in the lesion border or inside the lesion in HAP. Conclusion: The dual-phase helical CT might be accurate in judging the therapeutic effect of HCC after PMCT. If no enhancement was showed in the lesions in the dual-phase helical CT, it indicated that no tumor survived. If slight or marked patchy pattern enhancement was revealed in the surrounding liver of the lesions in HAP, it was a normal reaction after PMCT. If nodular enhancement was found in the lesion border or inside the lesion in HAP, it indicated that the tumor partially survived

Correlative Study of Angiogenesis and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Features of Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Wang, B.; Gao, Z.Q.; Yan, X.

2005-01-01

Purpose: To explore the correlation between contrast-enhancement patterns on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and angiogenesis by analyzing microvessel density (MVD), vascular endothelial growth factor (VEGF), and P53 protein expression in hepatocellular carcinoma (HCC). Material and Methods: MRI was performed with a GE Signa 5T MR scanner using SE and FMPSPGR sequences in 30 patients (38 lesions) during the period October 1998 to March 2000. All had histopathologically proven HCC. MR images were reviewed/analyzed retrospectively. The 30 patients were between 35 and 65 years of age. SE T1WI, PDWI, and T2WI were acquired initially. The FMPSPGR sequence was acquired in the same position. The DCE-MRI was performed in the arterial, portal vein, and delay phase after a bolus injection of Gd-DTPA. The specimens were stained immunohistochemically for CD34, VEGF, and P53. MVD was highlighted by anti-CD34 antibody staining. The enhancement features of HCC lesions were studied correlatively with the tumor MVD, VEGF, and P53 expression at protein level. Results: In the arterial phase, the results showed that MVD of HCC in the high-enhancement group (229.76±80.96) was higher than that in the equal-enhancement (173.09±61.38) and low-enhancement groups (153.00±108.58) (P <0.01, respectively). VEGF expression of HCC in the high-enhancement group (68.42%) was higher than that in the equal-enhancement (36.36%) and low-enhancement groups (38.89%) (P <0.05, respectively). In the portal vein phase, MVD of HCC in the enhancement group (259.80±93.30) was higher than that in the non-enhancement group (178.64±92.65) (P <0.05). No significant correlation was found between VEGF expression and the enhancement feature in the portal vein phase. In the delay phase, MVD of HCC in the ring-enhancement group (269.06±57.89) was significantly higher than that in the non-ring-enhancement group (144.10±88.90) (P <0.01). There was a significant difference in VEGF

Viral hepatitis and hepatocellular carcinoma

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Juei-Low, Sung [ed.; National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Department of Internal Medicine; Ding-Shinn, Chen [ed.; National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Hepatitis Research Center National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Graduate Institute of Clinical Medicine

1990-01-01

Two papers in this volume are in INIS scope, respectively dealing with MRI in the study of viral hepatitis and hepatocellular carcinoma, and The use of {sup 131}I-labeled Lipidol in the diagnosis of hepato-cellular carcinoma. (H.W.). refs.; figs.; tabs.

Viral hepatitis and hepatocellular carcinoma

International Nuclear Information System (INIS)

Sung Juei-Low; Chen Ding-Shinn

1990-01-01

Two papers in this volume are in INIS scope, respectively dealing with MRI in the study of viral hepatitis and hepatocellular carcinoma, and The use of 131 I-labeled Lipidol in the diagnosis of hepato-cellular carcinoma. (H.W.). refs.; figs.; tabs

Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

Directory of Open Access Journals (Sweden)

Eric J. Neuberger

2017-09-01

Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

Elevated renin levels in patients with liver cirrhosis and hepatocellular carcinoma.

Science.gov (United States)

Lotfy, Mahmoud; El-Kenawy, Ayman El-Meghawry; Abdel-Aziz, Mohamed M; El-Kady, Ibrahim; Talaat, Ayman

2010-01-01

Liver fibrosis is the common consequence of chronic liver injury of any etiology, disrupting the normal architecture,and causing hepatocellular dysfunction and portal hypertension. Since the renin-angiotensin system (RAS) may be involved in chronic liver diseases, in the present study we assayed renin levels using ELISA in groups of Egyptian patients with liver cirrhosis (N=32) and hepatocellular carcinoma (HCC) (N=67), for comparison with twenty five healthy controls. The results showed significant differences between the control and liver cirrhosis patients (P<0.001) and also the controls and HCC patients (P<0.001), without significant variation between the patient groups. Furthermore, in HCC patients, it was found that the renin levels negatively correlated with serum albumin and prothrombin time (P=0.003 for each) and positively with α-fetoprotein (P=0.04). Thus, it is concluded that renin levels are elevated in patients with liver cirrhosis and HCC and suitable medical intervention should be placed for management of such alteration. Moreover, further studies are warranted to explore its prognostic significance.

Computed tomographic findings of hepatocellular carcinoma

International Nuclear Information System (INIS)

Jo, In Su; Jong, Woo Yung; Lee, Jong Yul; Choi, Han Yong; Kim, Bong Ki

1987-01-01

With Development of Computed Tomography, detection of the Hepatocellular Carcinoma are easily performed and frequently used in the world. During 15 months, from December 1985 to February 1987, 59 patients with hepatocellular carcinoma were evaluated with computed tomography in department of radiology at Wallace Memorial Baptist Hospital. The results were as follow: 1. The most prevalent age group was 5th to 7th decades, male to female ratio was 4.9:1. 2. Classification with incidence of computed tomographic appearance of the hepatocellular carcinoma were solitary type 28 cases (48%), multinodular type 24 cases (40%), and diffuse type 7 cases (12%), Association with liver cirrhosis was noted in 22 cases (38%). 3. Inhomogenous internal consistency of hepatocellular carcinoma due to central necrosis were 35 cases (60%). Portal vein invasion by hepatocellular carcinoma was noted in 15 cases (25%), and particularly most common in diffuse type 4 cases (55%). 4. On precontrast scan, all hepatocellular carcinoma were seen as area of low density except for 3 cases(0.5%) of near isodensity which turned out to be remarkable low density on postcontrast scan. 5. In solitary type, posterior segment of right lobe was most common site of involvement 12 cases (43%). In diffuse type, bilobar involvement was most common, 6 cases (85%)

Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment.

Science.gov (United States)

Chen, Aiping; Zhang, Yonghui; Meng, Gang; Jiang, Dengxu; Zhang, Hailin; Zheng, Meihong; Xia, Mao; Jiang, Aiqin; Wu, Junhua; Beltinger, Christian; Wei, Jiwu

2017-07-12

There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8 + NKG2D + cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8 + NKG2D + cells, mediated by at least three distinct mechanisms. First, MV-Edm infection compelled HCC cells to express the specific NKG2D ligands MICA/B, which may contribute to the activation of CD8 + NKG2D + cells. Second, MV-Edm-infected HCC cells stimulated CD8 + NKG2D + cells to express high level of FasL resulting in enhanced induction of apoptosis. Third, intratumoural administration of MV-Edm enhanced infiltration of intravenously injected CD8 + NKG2D + cells. Moreover, we found that MV-Edm and adoptive CD8 + NKG2D + cells, either administered alone or combined, upregulated the immune suppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in HCC. Elimination of IDO1 by fludarabine enhanced antitumour responses. Taken together, our data provide a novel and clinically relevant strategy for treatment of HCC.

Gd-EOB-DTPA-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading and portal blood flow

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Kogita, Sachiyo; Imai, Yasuharu; Fukuda, Kazuto; Igura, Takumi; Sawai, Yoshiyuki [Ikeda Municipal Hospital, Department of Gastroenterology, Osaka (Japan); Okada, Masahiro; Murakami, Takamichi [Kinki University, School of Medicine, Department of Radiology, Osaka (Japan); Kim, Tonsok; Onishi, Hiromitsu; Hori, Masatoshi [Osaka University, Graduate School of Medicine, Department of Radiology, Osaka (Japan); Takamura, Manabu [Ikeda Municipal Hospital, Department of Radiology, Osaka (Japan); Morimoto, Osakuni [Ikeda Municipal Hospital, Department of Surgery, Osaka (Japan); Nagano, Hiroaki [Osaka University, Graduate School of Medicine, Department of Surgery, Osaka (Japan); Wakasa, Kenichi [Osaka City University, Graduate School of Medicine, Department of Diagnostic Pathology, Osaka (Japan); Hayashi, Norio [Osaka University, Graduate School of Medicine, Department of Gastroenterology and Hepatology, Osaka (Japan)

2010-10-15

To retrospectively investigate enhancement patterns of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI in relation to histological grading and portal blood flow. Sixty-nine consecutive patients with 83 histologically proven HCCs and DNs were studied. To assess Gd-EOB-DTPA uptake, we calculated the EOB enhancement ratio, which is the ratio of the relative intensity of tumorous lesion to surrounding nontumorous area on hepatobiliary phase images (post-contrast EOB ratio) to that on unenhanced images (pre-contrast EOB ratio). Portal blood flow was evaluated by CT during arterial portography. Post-contrast EOB ratios significantly decreased as the degree of differentiation declined in DNs (1.00 {+-} 0.14) and well, moderately and poorly differentiated HCCs (0.79 {+-} 0.19, 0.60 {+-} 0.27, 0.49 {+-} 0.10 respectively). Gd-EOB-DTPA uptake, assessed by EOB enhancement ratios, deceased slightly in DNs and still more in HCCs, while there was no statistical difference in the decrease between different histological grades of HCC. Reductions in portal blood flow were observed less frequently than decreases in Gd-EOB-DTPA uptake in DNs and well-differentiated HCCs. Reduced Gd-EOB-DTPA uptake might be an early event of hepatocarcinogenesis, preceding portal blood flow reduction. The hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI may help estimate histological grading, although difficulties exist in differentiating HCCs from DNs. (orig.)

Drug-induced lung injury associated with sorafenib: analysis of all-patient post-marketing surveillance in Japan.

Science.gov (United States)

Horiuchi-Yamamoto, Yuka; Gemma, Akihiko; Taniguchi, Hiroyuki; Inoue, Yoshikazu; Sakai, Fumikazu; Johkoh, Takeshi; Fujimoto, Kiminori; Kudoh, Shoji

2013-08-01

Sorafenib is a multi-kinase inhibitor currently approved in Japan for unresectable and/or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma. Although drug-induced lung injury has recently been the focus of interest in Japanese patients treated with molecular targeting agents, the clinical features of patients receiving sorafenib remain to be completely investigated. All-patient post-marketing surveillance data was obtained within the frame of Special Drug Use Investigation; between April 2008 and March 2011, we summarized the clinical information of 62 cases with drug-induced lung injury among approximately 13,600 sorafenib-treated patients in Japan. In addition, we summarized the results of evaluation by a safety board of Japanese experts in 34 patients in whom pulmonary images were available. For the calculation of reporting frequency, interim results of Special Drug Use Investigation were used. In the sets of completed reports (2,407 in renal cell carcinoma and 647 in hepatocellular carcinoma), the reporting frequency was 0.33 % (8 patients; fatal, 4/8) and 0.62 % (4 patients; fatal, 2/4), respectively. Major clinical symptoms included dyspnea, cough, and fever. Evaluation of the images showed that 18 cases out of 34 patients had a pattern of diffuse alveolar damage. The patients with hepatocellular carcinoma showed a greater incidence and earlier onset of lung injury than those with renal cell carcinoma. Although the overall reporting frequency of sorafenib-induced lung injury is not considered high, the radiological diffuse alveolar damage pattern led to a fatal outcome. Therefore, early recognition of sorafenib-induced lung injury is crucial for physicians and patients.

Imaging of hepatocellular carcinoma; Bildgebung des hepatozellulaeren Karzinoms

Energy Technology Data Exchange (ETDEWEB)

Lincke, Therese; Zech, Christoph [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Boll, Daniel

2016-12-15

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Besides the improvement in diagnostics and therapy the quantity of new cases and fatalities per year are equal. The main risk factors for HCC developing are liver cirrhosis (causing 90% of HCCs), non-alcoholic fatty liver disease and chronic hepatitis B infection. Therefore, it is recommended to perform an ultrasound screening on patients at risk every 6 month to detect HCC-lesions early. HCC can be definitely diagnosed by imaging techniques using contrast agent such as contrast-enhanced-ultrasound (CEUS), contrast-enhanced-MRI (CE-MRI) and contrast-enhanced-CT (CE-CT). MRI has several advantages compared to the other modalities due to the multi-parametric approach and a higher sensitivity for tumor detection.

Patterns of Gene Expression Associated with Recovery and Injury in Heat-stressed Rats

Science.gov (United States)

2014-12-03

renal failure, acute respiratory distress syndrome, myocardial in- jury, hepatocellular injury, intestinal ischemia, pancreatic injury, and hemorrhagic...pathways are involved in the observed cardiomyopathy. Results and discussion To induce the pathophysiological effects of heat stress, we placed conscious...Table S2). The incidence and severity of lesions, such as car- diomyopathy and chronic progressive nephropathy, were generally minimal and consistent

Grp78 promotes the invasion of hepatocellular carcinoma

International Nuclear Information System (INIS)

Su, Rongjian; Li, Zhen; Li, Hongdan; Song, Huijuan; Bao, Cuifen; Wei, Jia; Cheng, Liufang

2010-01-01

A-GTP level in Grp78 overexpressing cells, indicating Grp78 inhibited RhoA activity in hepatocellular carcinoma cells. Furthermore, overexpression of Grp78 in SMMC7721 cells increased phospho-p190RhoGAP level. FAK siRNA knockdown in Grp78 overexpressing cells reversed phospho-p190RhoGAP level. These data suggested that Grp78 inhibited RhoA activity by up-regulated phospho-p190RhoGAP level and Grp78 mediated p190RhoGAP phosphorylation is FAK dependent. Grp78 promoted the invasion of hepatocellular carcinoma both in vitro and in vivo. Overexpression of Grp78 in hepatocellular carcinoma cells enhanced the activation and activity of FAK which negatively regulated Rock kinase activity by promoting the phosphorylation of p190RhoGAP

Grp78 promotes the invasion of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Li Hongdan

2010-01-01

RhoA-GTP level, and Grp78 siRNA knockdown rescued RhoA-GTP level in Grp78 overexpressing cells, indicating Grp78 inhibited RhoA activity in hepatocellular carcinoma cells. Furthermore, overexpression of Grp78 in SMMC7721 cells increased phospho-p190RhoGAP level. FAK siRNA knockdown in Grp78 overexpressing cells reversed phospho-p190RhoGAP level. These data suggested that Grp78 inhibited RhoA activity by up-regulated phospho-p190RhoGAP level and Grp78 mediated p190RhoGAP phosphorylation is FAK dependent. Conclusion Grp78 promoted the invasion of hepatocellular carcinoma both in vitro and in vivo. Overexpression of Grp78 in hepatocellular carcinoma cells enhanced the activation and activity of FAK which negatively regulated Rock kinase activity by promoting the phosphorylation of p190RhoGAP.

Hepatic protection and anticancer activity of curcuma: A potential chemopreventive strategy against hepatocellular carcinoma

OpenAIRE

LI, YAN; SHI, XUE; ZHANG, JINGWEN; ZHANG, XIANG; MARTIN, ROBERT C.G.

2013-01-01

Malignant transformation of hepatocellular carcinoma (HCC) occurs through repetitive liver injury in a context of inflammation and oxidative DNA damage. A spectrum of natural sesquiterpenoids from curcuma oil has displayed anti-oxidant, anti-inflammatory and anti-carcinogenic properties. The aim of the study was to investigate the hepatoprotective and anti-HCC effects of curcuma oil in vivo and in vitro. Mice were pretreated with curcuma oil (100 mg/kg) for 3 days, then treated with Concanava...

Therapeutic response assessment of percutaneous radiofrequency ablation for hepatocellular carcinoma: Utility of contrast-enhanced agent detection imaging

International Nuclear Information System (INIS)

Kim, Chan Kyo; Choi, Dongil; Lim, Hyo K.; Kim, Seung Hoon; Lee, Won Jae; Kim, Min Ju; Lee, Ji Yeon; Jeon, Yong Hwan; Lee, Jongmee; Lee, Soon Jin; Lim, Jae Hoon

2005-01-01

Purpose: To assess the utility of contrast-enhanced agent detection imaging (ADI) in the assessment of the therapeutic response to percutaneous radiofrequency (RF) ablation in patients with hepatocellular carcinoma (HCC). Materials and methods: Ninety patients with a total of 97 nodular HCCs (mean, 2.1 ± 1.3 cm; range, 1.0-5.0 cm) treated with percutaneous RF ablation under the ultrasound guidance were evaluated with contrast-enhanced ADI after receiving an intravenous bolus injection of a microbubble contrast agent (SH U 508A). We obtained serial contrast-enhanced ADI images during the time period from 15 to 90 s after the initiation of the bolus contrast injection. All of the patients underwent a follow-up four-phase helical CT at 1 month after RF ablation, which was then repeated at 2-4 month intervals during a period of at least 12 months. The results of the contrast-enhanced ADI were compared with those of the follow-up CT in terms of the presence or absence of residual unablated tumor and local tumor progression in the treated lesions. Results: On contrast-enhanced ADI, technical success was obtained in 94 (97%) of the 97 HCCs, while residual unablated tumors were found in three HCCs (3%). Two of the three tumors that were suspicious (was not proven) for incomplete ablation were subjected to additional RF ablation. The remaining one enhancing lesion that was suspicious of a residual tumor on contrast-enhanced ADI was revealed to be reactive hyperemia at the 1-month follow-up CT. Therefore; the diagnostic concordance between the contrast-enhanced ADI and 1-month follow-up CT was 99%. Of the 94 ablated HCCs without residual tumors on both the contrast-enhanced ADI and 1-month follow-up CT after the initial RF ablation, five (5%) had CT findings of local tumor progression at a subsequent follow-up CT. Conclusion: Despite its limitations in predicting local tumor progression in the treated tumors, contrast-enhanced ADI is potentially useful for evaluating the

Chemoembolization through intercostal arteries in hepatocellular carcinoma: Report of a case of transient spinal cord injury

International Nuclear Information System (INIS)

Moon, Tae Yong; Hwang, In Tae; Kim, Byung Soo; Ko, Hyun Yoon; Yang, Ung Suk; Kim, Hak Jin

1994-01-01

Liver has a dual blood supply from portal vein and hepatic artery. Hepatocellular carcinoma receive their blood supply almost exclusively from hepatic artery. Thus, the concept of treating hepatocellular carcinoma by chemoembolization through these arteries is very effective . However, there may be several collateral or parasitic vessels feeding them in case of huge tumor or previous chemoembolization. We experienced a case of huge tumor involving right upper posterior portion of liver fed by 9th, 10th, 11th right posterior intercostal arteries and an anomalous hepatic artery. We tried chemoembolization with Adriamycin-Lipiodol suspension and Gelfoam material through the right posterior intercostal arteries to treat the lesion. After the procedure, the patient(55 years old female) became paraplegic with voiding and defecation difficulty which could be due to spinal cord infarction by anterior spinal arterial occlusion caused by embolic material through the artery of Adamkiewicz from a posterior intercostal artery. She recovered completely after 20 days of treatment

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

Science.gov (United States)

Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

2013-12-01

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts--we designate this variant as 'chromophobe hepatocellular carcinoma with abrupt anaplasia'. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P=0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of

Subcentimeter hypervascular nodules with typical imaging findings of hepatocellular carcinoma on gadoxetic acid-enhanced MRI: Outcomes of early treatment and watchful waiting

Energy Technology Data Exchange (ETDEWEB)

Woo, Jung Han; Song, Kyoung Doo; Kim, Seong Hyun [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, 81 Irwon-Ro, Gangnam-Gu, Seoul (Korea, Republic of)

2017-10-15

To compare treatment outcomes of subcentimeter hypervascular nodules at high risk for developing into hepatocellular carcinomas (SHNHR) between early treatment and watchful waiting until progression to overt hepatocellular carcinoma (HCC) groups. SHNHRs were defined as subcentimeter hypervascular nodules with the usual imaging features of HCC on gadoxetic acid-enhanced magnetic resonance imaging (MRI). Among 63 patients with 74 SHNHRs, 27 (37 SHNHRs) received early treatment (treatment of < 1 cm nodules), and 36 (37 SHNHRs) underwent watchful waiting until progression to overt HCC. Risk factor analysis was performed for recurrence-free and local recurrence-free survival. Among the 36 patients who adopted watchful waiting, 33 eventually underwent treatment because their SHNHRs progressed to overt HCC. For recurrence-free survival, significant risk factors included number of previous treatments (HR, 1.181; p < 0.001), tumour number (HR, 1.943; p = 0.009), and α-feto protein level (HR, 1.005; p = 0.037) in the multivariate analyses. Treatment strategy was not a significant risk factor for recurrence-free survival. For local recurrence-free survival from the date of treatment, only treatment modality (transarterial chemoembolization) (HR, 6.879; p = 0.002) was a significant risk factor. Recurrence-free survival was not significantly different between early treatment and watchful waiting for SHNHRs. (orig.)

The antifibrinolytic drug tranexamic acid reduces liver injury and fibrosis in a mouse model of chronic bile duct injury.

Science.gov (United States)

Joshi, Nikita; Kopec, Anna K; Towery, Keara; Williams, Kurt J; Luyendyk, James P

2014-06-01

Hepatic fibrin deposition has been shown to inhibit hepatocellular injury in mice exposed to the bile duct toxicant α-naphthylisothiocyanate (ANIT). Degradation of fibrin clots by fibrinolysis controls the duration and extent of tissue fibrin deposition. Thus, we sought to determine the effect of treatment with the antifibrinolytic drug tranexamic acid (TA) and plasminogen activator inhibitor-1 (PAI-1) deficiency on ANIT-induced liver injury and fibrosis in mice. Plasmin-dependent lysis of fibrin clots was impaired in plasma from mice treated with TA (1200 mg/kg i.p., administered twice daily). Prophylactic TA administration reduced hepatic inflammation and hepatocellular necrosis in mice fed a diet containing 0.025% ANIT for 2 weeks. Hepatic type 1 collagen mRNA expression and deposition increased markedly in livers of mice fed ANIT diet for 4 weeks. To determine whether TA treatment could inhibit this progression of liver fibrosis, mice were fed ANIT diet for 4 weeks and treated with TA for the last 2 weeks. Interestingly, TA treatment largely prevented increased deposition of type 1 collagen in livers of mice fed ANIT diet for 4 weeks. In contrast, biliary hyperplasia/inflammation and liver fibrosis were significantly increased in PAI-1(-/-) mice fed ANIT diet for 4 weeks. Overall, the results indicate that fibrinolytic activity contributes to ANIT diet-induced liver injury and fibrosis in mice. In addition, these proof-of-principle studies suggest the possibility that therapeutic intervention with an antifibrinolytic drug could form a novel strategy to prevent or reduce liver injury and fibrosis in patients with liver disease.

Stress Hormone Cortisol Enhances Bcl2 Like-12 Expression to Inhibit p53 in Hepatocellular Carcinoma Cells.

Science.gov (United States)

Wu, Weizhong; Liu, Sanguang; Liang, Yunfei; Zhou, Zegao; Bian, Wei; Liu, Xueqing

2017-12-01

The pathogenesis of hepatocellular carcinoma (HC) is unclear. It is suggested that psychological stress associates with the pathogenesis of liver cancer. Bcl2-like protein 12 (Bcl2L12) suppresses p53 protein. This study tests a hypothesis that the major stress hormone, cortisol, inhibits the expression of p53 in HC cells (HCC) via up regulating the expression of Bcl2L12. Peripheral blood samples were collected from patients with HC to be analyzed for the levels of cortisol. HCC were cultured to assess the role of cortisol in the regulation of the expression of Bcl2L12 and p53 in HCC. We observed that the serum cortisol levels were higher in HC patients. Expression of Bcl2L12 in HCC was correlated with serum cortisol. Cortisol enhanced the Bcl2L12 expression in HCC. Bcl2L12 binding to the TP53 promoter was correlated with p53 expression in HCC. Cortisol increased the Bcl2L12 expression in HCC to inhibit p53 expression. Stress hormone cortisol suppresses p53 in HCC via enhancing Bcl2L12 expression in HCC. The results suggest that cortisol may be a therapeutic target for the treatment of HC.

Contrast-enhanced ultrasonography of hepatocellular carcinoma: Correlation between quantitative parameters and arteries in neoangiogenesis or sinusoidal capillarization

International Nuclear Information System (INIS)

Pei Xiaoqing; Liu Longzhong; Zheng Wei; Cai Muyan; Han Feng; He Jiehua; Li Anhua; Chen Minshan

2012-01-01

Objective: The quantitative parameters in contrast-enhanced ultrasonography-time–intensity curve of hepatocellular carcinoma (HCC) were studied to explore their potential importance in monitoring the effects of anti-angiogenic therapy for HCC. Methods: 115 HCC patients were studied with contrast-enhanced ultrasonography-time–intensity curve (CEUS-TIC) and with immunohistochemical analysis of tissue sections. The CEUS images were analyzed off-line to obtained quantitative parameters including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), mean transit time (mTT), rise slope (RS), and washout time (WT). Monoclonal antibodies specific for smooth muscle actin and anti-CD34 were used to observe unpaired arteries (UAs) and microvessel area (MVA) of sinusoidal capillarization, respectively. The UAs and MVA of 82 HCC cases were successfully stained. Results: The number of UAs had moderate correlation with RT (r = −0.446), TTP (r = −0.432), and RS (r = 0.431) (P < 0.05), and it had mild correlation with IMAX (r = 0.303) and WT (r = 0.285) (P < 0.05). MVA of sinusoidal capillarization had no correlation with perfusion parameters. Conclusion: Quantitative CEUS-TIC parameters reflecting hemodynamics of tumors are correlated with UAs, but not with MVA, and they might be used to monitor the effects of anti-angiogenic therapy on HCC.

Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

Science.gov (United States)

Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

2016-03-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Therapeutic evaluation of sorafenib for hepatocellular carcinoma using contrast-enhanced ultrasonography: Preliminary result.

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Shiozawa, Kazue; Watanabe, Manabu; Ikehara, Takashi; Kogame, Michio; Kikuchi, Yoshinori; Igarashi, Yoshinori; Sumino, Yasukiyo

2016-07-01

The present study aimed to determine the usefulness of contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating the therapeutic response to sorafenib for hepatocellular carcinoma (HCC). In total, 26 patients with advanced HCC who received sorafenib and were followed up by CEUS were enrolled in the present study. CEUS was performed prior to and within 2-4 weeks of treatment, and the images of the target lesion in the post-vascular phase with a re-injection method were analyzed. The presence (+) or absence (-) of intratumoral necrosis and the intratumoral vascular architecture on micro-flow imaging (MFI) were compared prior to and subsequent to treatment. Target lesions that exhibited non-enhancement after re-injection were considered to indicate intratumoral necrosis. The intratumoral vascular architecture was classified into three groups, as follows: Vd, the intratumoral vessels visually narrowed or decreased; Vnc, the vessels remained unchanged; and Vi, the vessels were thickened or increased. Survival curves were estimated using the Kaplan-Meier method and compared using the log rank test between the intratumoral necrosis (+) and (-) groups, and among the Vd, Vnc and Vi groups. PVnc group and 5 patients in the Vi group. The MSTs in the Vd, Vnc and Vi groups were 15.6 months (95% CI, 5.0-23.3), 11.0 months (95% CI, 3.5-17.6) and 3.6 months (95% CI: 1.2-6.0), respectively. The P-value for the differences between the Vd and Vnc groups, Vd and Vi groups, and Vnc and Vi groups were 0.78, 0.016 and 0.047, respectively, which indicated that the survival time decreased significantly in the Vi group. Evaluation of intratumoral vascular architecture using MFI demonstrates promise for assessing the therapeutic response to sorafenib in patients with HCC.

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features

OpenAIRE

Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

2013-01-01

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independen...

Elevated serum levels of Chromogranin A in hepatocellular carcinoma.

Science.gov (United States)

Biondi, Antonio; Malaguarnera, Giulia; Vacante, Marco; Berretta, Massimiliano; D'Agata, Velia; Malaguarnera, Michele; Basile, Francesco; Drago, Filippo; Bertino, Gaetano

2012-01-01

During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.

Microvascular injury of the peribiliary plexus associated with transarterial chemoembolization: a study of surgical specimens

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Park, Won Kyu; Bae, Young Kyung; Hwang, Tae Yoon; Cho, Jae Ho; Chang, Jay Chun; Kim, Jae Woon; Jang, Han Won [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

2006-11-15

We attempted to evaluate the relationship between transarteiral chemoembolization (TACE) and injury to the peribiliary plexus by evaluating the number of microvessels in peribiliary plexus of surgical specimen. Surgical specimens were obtained from 78 hepatocellular carcinoma patients and 22 patients with liver metastases. They were divided into 4 groups (Group 1; hepatocellular carcinoma without TACE [n=30], Group 2; hepatocellular carcinoma receiving preoperative TACE once [n=37], Group 3; hepatocellular carcinoma receiving preoperative TACE more than two times [n=11] and Group 4; metastatic carcinoma of the liver patients without a history of liver disease [n=22]). Immunohistochemical staining for factor VIII-related antigen was performed in all the specimens and the number of microvessels in the inner capillary layer and the outer venous layer of the bile duct (> 200 {mu} m in diameter) was counted. The mean numbers of microvessels in the inner capillary layer were 4.50, 4.08, 1.64 and 2.05, and those in the outer venous layer were 25.23, 20.00, 18.36 and 12.32 for the 4 groups, respectively. The number of microvessels in group 4 was statistically fewer than that of group 1 ({rho} < 0.01). In the hepatocellular carcinoma patients, the number of microvessels was decreased as the number of TACE sessions was increased. The number of microvessels in the peribiliary plexus is increased in chronic liver disease patients. It may be from the increased portal pressure and flow stagnation in the sinusoidal and portal venules. TACE can have an effect on microvascular injury of the peibiliary plexus, and this can be a cause of bile duct necrosis and biloma.

Metastases of Hepatocellular Carcinoma Misdiagnosed as Isolated Hypertrophic Cardiomyopathy.

Science.gov (United States)

Greco, Assunta; De Masi, Roberto; Orlando, Stefania; Metrangolo, Antonio; Zecca, Vittorio; Morciano, Giancarlo; De Donno, Antonella; Bagordo, Francesco; Piccinni, Giancarlo

At present, cardiac metastasis of hepatocellular carcinoma is rarely mentioned in the literature. We report a hepatocellular carcinoma patient with cardiac metastasis misdiagnosed as hypertrophic cardiomyopathy in 2011. Two years later, on presentation of syncope, an abnormal ventricular septal size was recorded by ultrasound scan, and was subsequently shown by magnetic resonance imaging to be a tumour lesion. A myocardial biopsy confirmed infiltration of hepatocellular carcinoma. This observation underlines the risk of hepatocellular carcinoma cardiac metastasis, manifested in its infiltrative form as hypertrophic cardiomyopathy. In conclusion, we suggest that the ultrasound appearance of hypertrophic cardiomyopathy in hepatocellular carcinoma patients should be seen as a "red flag" and recommend the introduction of magnetic resonance imaging assessment of transplant candidates.

Imaging characteristics of hepatocellular adenoma compared with pathologic findings

International Nuclear Information System (INIS)

Zhao Jing; Zhao Xinming; Ouyang Han; Huang Wenting; Zhou Chunwu

2012-01-01

Objective: To retrospectively compare CT and MR features of hepatocellular adenoma with pathologic findings. Methods: Twelve patients with histopathologically proved hepatocellular adenoma were classified on the basis of pathologic and genotype phenotype findings into four groups: steatotic type, cytological abnormality type, telangiectatic adenoma with inflammatory infiltrates type and atypical adenoma type. The CT and MR features of each type were reviewed retrospectively compared with the pathological results. Results: In this retrospective study, 12 patients were examined with CT (8 patients) and MR (8 patients). Among 12 patients, 4 patients showed a steatotic type. One patient showed hypo-density on the non-enhanced CT and 3 patients demonstrated hypo-density on all phases of the post-contrast scans. Two lesions showed iso-intense signal on the in-phase T 1 WI with signal dropout on the out-of-phase T 1 WI, and hypo-intense signal on the T 2 WI with fat suppression sequences. One lesion demonstrated moderate hypointense signal on all phases of the post-contrast MRI scans. Two patients with the telangiectatic adenoma inflammatory infiltrates type were found. One patient showed hypo-density on the non-enhanced CT scans and hyper-density on all phases of the post-contrast CT scans. One patient demonstrated iso-intense signal and the other hypo-intense signal on the T 1 WI, and both displayed moderate hyper-intense signal on the T 2 WI with fat suppression sequences and hyper-intense signal with gradual enhancement on all phases of post-contrast MR scans. There were 3 patients with a cytological abnormality type. One patient appeared hypo-density and 1 patient showed uniform iso-density on non-enhanced CT scans. All patients who had undergone contrast-enhanced CT scans were found to have hyper-density on the hepatic arterial-dominant phase and became slightly lower on the portal venous phase. On the delay phase the density reduced further. One mass showed iso

Hepatocellular calcification

DEFF Research Database (Denmark)

Ladefoged, Claus; Frifelt, J J

1987-01-01

Autopsy of a twenty year old girl dying from complications of renal and cardiac failure demonstrated severe hepatocellular calcification, a rare finding. The pathogenesis is thought to be a combination of dystrophic calcification caused by severe centrilobular necrosis and metastatic calcificatio...

Lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma

Science.gov (United States)

Tsend-Ayush, Altansukh; Zhu, Xiumei; Ding, Yu; Yao, Jianxu; Yin, Lifang; Zhou, Jianping; Yao, Jing

2017-05-01

Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. The main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after being prepared using the nanoprecipitation method and characterized by dynamic light scattering (DLS). According to the results, smaller (˜141.43 nm), positively charged ETO-loaded TPGS-LA NPs were more suitable for providing efficient delivery to hepatoma cells by avoiding the clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs were noticeably able to enhance the cytotoxicity of ETO in HepG2 cells. Besides this, markedly higher internalization by the ASGPR-overexpressed HepG2 cells and efficient accumulation at the tumor site in vivo were revealed in the TPGS-LA NP group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to the ETO-loaded TPGS NPs. These results suggest that TPGS-LA NPs could be used as a potential ETO delivery system against HCC.

Quantification of traumatic meningeal injury using dynamic contrast enhanced (DCE) fluid-attenuated inversion recovery (FLAIR) imaging

Science.gov (United States)

Castro, Marcelo A.; Williford, Joshua P.; Cota, Martin R.; MacLaren, Judy M.; Dardzinski, Bernard J.; Latour, Lawrence L.; Pham, Dzung L.; Butman, John A.

2016-03-01

Traumatic meningeal injury is a novel imaging marker of traumatic brain injury, which appears as enhancement of the dura on post-contrast T2-weighted FLAIR images, and is likely associated with inflammation of the meninges. Dynamic Contrast Enhanced MRI provides a better discrimination of abnormally perfused regions. A method to properly identify those regions is presented. Images of seventeen patients scanned within 96 hours of head injury with positive traumatic meningeal injury were normalized and aligned. The difference between the pre- and last post-contrast acquisitions was segmented and voxels in the higher class were spatially clustered. Spatial and morphological descriptors were used to identify the regions of enhancement: a) centroid; b) distance to the brain mask from external voxels; c) distance from internal voxels; d) size; e) shape. The method properly identified thirteen regions among all patients. The method failed in one case due to the presence of a large brain lesion that altered the mask boundaries. Most false detections were correctly rejected resulting in a sensitivity and specificity of 92.9% and 93.6%, respectively.

Diagnostic Approaches to Metastatic Hepatocellular Carcinoma of the Orbit.

Science.gov (United States)

Geske, Michael J; Bloomer, Michele M; Kersten, Robert C; Vagefi, M Reza

Orbital metastasis of hepatocellular carcinoma is exceedingly rare and caries a grave prognosis. Three cases of metastatic orbital hepatocellular carcinoma in which the primary tumor was initially unknown and the diagnostic challenges encountered are presented. With hepatocellular carcinoma, open biopsy and palliative tumor debulking has an increased bleeding risk due to the highly vascular nature of the tumor and coagulopathy associated with chronic liver disease. As an alternative, fine needle aspiration biopsy should be considered for hepatocellular carcinoma with a readily accessible mass and the availability of an experienced cytopathologist.

Findings in multidetector computed tomography in the diagnosis of hepatocellular carcinoma in patients with cirrhosis and correlation with pathology of liver explants

International Nuclear Information System (INIS)

Haberman, D.; Castignola, M.; Mela, M.; Paladini, H.; Santilli, J.P.; Gruz, F.; Gondolesi, G.

2013-01-01

Objectives: To describe the imagenological behavior of hepatocellular carcinoma in cirrhotic patients using a dynamic multidetector computed tomography (MDCT) technique, and correlate these findings with histological tumor grades. Materials and methods: A retrospective, descriptive observational study was conducted to evaluate 51 nodules in 32 liver transplant patients diagnosed with liver cirrhosis. The pathology of liver explants was used as a reference. Nodules with hepatocellular carcinoma histopathology were retrospectively analyzed by computed tomography scans performed pre-transplant. Using a dynamic multidetector computed tomography technique, we evaluated the most common imagenological behavior reported in the literature: arterial enhancement, washout, capsule, and intratumoral arterial vessels. Results: Forty-six of 51 (90%) tumors showed arterial enhancement. Of the 46 tumors with arterial enhancement, 39 (85%) had washout in portal-late phase. Five of 51 (10%) were hypovascular. Twenty-two of 51 (43%) had capsule and 12 of 51 (24%) showed intratumoral arterial vessels. The more frequent image combination was the combination of arterial enhancement and washout (39 of 51 tumors or 76%). The most frequent histological grade was II (35 of 51 tumors or 69%). Statistically significant relationships were found between histological grade tumors and imagenological behavior: arterial enhancement and hypovascular. Conclusion: In our population, arterial enhancement with washout in portal-late phases was observed in most of the tumors. Our results are consistent with previously reported studies, demonstrating the high reliability of this imaging pattern for the diagnosis of hepatocellular carcinoma. (authors) [es

Radiological imagings of small hepatocellular carcinomas

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Miyake, Hidetoshi; Hayashi, Kuniaki; Futagawa, Sakae; Matsunaga, Naofumi; Maeda, Tohru [Nagasaki Univ. (Japan). School of Medicine

1984-08-01

Forty three cases of small hepatocellular carcinoma (measuring less than 3 cm in diameter on imaging modalities) were detected during a period of four years and two months. There were two cases in which hepatoma measured 1 cm in diameter, twenty four cases between 1 and 2 cm, and seventeen cases between 2 and 3 cm. The relative role of each modality and AFP value in the detection of these tumors was evaluated. The detection rate of small hepatocellular carcinoma by liver scintigraphy, ultrasonography (US), computed tomography (CT) and angiography was 8%, 74%, 70% and 95%, respectively. The sensitivity of serum AFP value was 67% (either measuring more than 200ng/ml or showing a tendency of steady rising even if below the level of 200ng/ml). Most hepatomas less than 2 cm in size were hypoechoic on US, and those above 2 cm in size were hyperechoic with peripheral sonolucency (halo). Almost all cases were described as low density area on both plain and enhancement CT. Angiography was the best method for detecting small hepatomas. It may be recommended to perform angiography on every patient with liver cirrhosis at the time of diagnosis of this disease. Periodic examinations by AFP, US and CT should be done if the angiography was negative. Evaluation by US in every three months and by CT in every twelve months may be appropriate.

Hepatocellular carcinoma: clinical significance of signal heterogeneity in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging

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Fujita, Nobuhiro; Nishie, Akihiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Moirta, Koichiro; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Fukuoka (Japan); Kubo, Yuichiro; Aishima, Shinichi [Kyushu University, Department of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka (Japan); Takayama, Yukihisa [Kyushu University, Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences, Fukuoka (Japan); Shirabe, Ken [Kyushu University, Department of Surgery and Science, Graduate School of Medical Sciences, Fukuoka (Japan)

2015-01-15

To clarify the relationship between the biological behaviour of hepatocellular carcinomas (HCCs) and their signal intensity in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging with a special focus on the signal heterogeneity. A total of 68 patients with 70 pathologically proven HCCs were enrolled. On the basis of the signal intensity in the hepatobiliary phase, the lesions were classified into three groups: group 1, homogeneous hypointensity (n = 44); group 2, heterogeneous hyperintensity (n = 20); and group 3, homogeneous hyperintensity (n = 6). The clinicopathological findings were compared among the three groups. The tumour size and the serum level of protein induced by vitamin K absence or antagonist-II (PIVKA-II) were significantly higher in group 2 compared to group 1 (p = 0.0155, p = 0.0215, respectively) and compared to group 3 (p = 0.0330, p = 0.0220, respectively). The organic anion transporting polypeptide 8 (OATP8) expression in group 2 and group 3 was significantly higher than in group 1 (p < 0.0001, p < 0.0001, respectively). Group 2 showed a significantly lower disease-free survival rate compared to group 1 (p = 0.0125), and group 2 was an independent prognostic factor for disease-free survival (p = 0.0308). HCCs in the hepatobiliary phase that are heterogeneously hyperintense on gadoxetic acid-enhanced MR imaging have more malignant potential than other types of HCCs. (orig.)

Mammalian-enabled (MENA) protein enhances oncogenic potential and cancer stem cell-like phenotype in hepatocellular carcinoma cells.

Science.gov (United States)

Hu, Kunpeng; Huang, Pinzhu; Luo, Hui; Yao, Zhicheng; Wang, Qingliang; Xiong, Zhiyong; Lin, Jizong; Huang, He; Xu, Shilei; Zhang, Peng; Liu, Bo

2017-08-01

Mammalian-enabled (MENA) protein is an actin-regulatory protein that influences cell motility and adhesion. It is known to play a role in tumorigenicity of hepatocellular carcinoma (HCC) but the underlying molecular mechanism remains unknown. This study aimed to investigate the oncogenic potential of MENA and its capacity to regulate cancer stem cell (CSC)-like phenotypes in HCC cells. Real-time-PCR and western blot were used to assess mRNA and protein levels of target genes in human HCC tissue specimens and HCC cell lines, respectively. Stable MENA-overexpressing HCC cells were generated from HCC cell lines. Transwell cell migration and colony formation assays were employed to evaluate tumorigenicity. Ectopic expression of MENA significantly enhanced cell migration and colony-forming ability in HCC cells. Overexpression of MENA upregulated several hepatic progenitor/stem cell markers in HCC cells. A high MENA protein level was associated with high mRNA levels of MENA, CD133, cytokeratin 19 (CK19), and epithelial cell adhesion molecule (EpCAM) in human HCC tissues. Overexpression of MENA enhanced epithelial-to-mesenchymal transition (EMT) markers, extracellular signal-regulated kinases (ERK) phosphorylation, and the level of β-catenin in HCC cells. This study demonstrated that overexpression of MENA in HCC cells promoted stem cell markers, EMT markers, and tumorigenicity. These effects may involve, at least partially, the ERK and β-catenin signaling pathways.

Morphologic Subtypes of Hepatocellular Carcinoma.

Science.gov (United States)

Torbenson, Michael S

2017-06-01

Hepatocellular carcinomas can be further divided into distinct subtypes that provide important clinical information and biological insights. These subtypes are distinct from growth patterns and are on based on morphologic and molecular findings. There are 12 reasonably well-defined subtypes as well as 6 provisional subtypes, together making up 35% of all hepatocellular carcinomas. These subtypes are discussed, with an emphasis on their definitions and the key morphologic findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma.

Science.gov (United States)

Sun, Xu; Zhang, Qi; Chen, Wei; Hu, Qida; Lou, Yu; Fu, Qi-Han; Zhang, Jing-Ying; Chen, Yi-Wen; Ye, Long-Yun; Wang, Yi; Xie, Shang-Zhi; Hu, Li-Qiang; Liang, Ting-Bo; Bai, Xue-Li

2017-07-01

Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-β-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-β-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.

Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

International Nuclear Information System (INIS)

Seo, J.M.; Lee, S.J.; Kim, S.H.; Park, C.K.; Ha, S.Y.

2012-01-01

Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

Energy Technology Data Exchange (ETDEWEB)

Seo, J.M. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, S.J., E-mail: lucia@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, S.H. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, C.K.; Ha, S.Y. [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2012-04-15

Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

Contrast-enhanced Harmonic power Doppler ultrasonography: Improved depiction of vascularity and characterization of flow pattern in hepatocellular carcinoma

International Nuclear Information System (INIS)

Baek, Hyung Chul; Yoon, Kwon Ha; Kim, Chang Guhn; Park, Ki Han; Won, Jong Jin

2000-01-01

To evaluate the value of contrast-enhanced harmonic power Doppler ultrasonography (PDUS) in depiction and characterization of tumoral vascularity in hepatocellular carcinoma (HCC). Thirty-three patients with HCC were prospectively evaluated with harmonic PDUS before and after injection of the contrast agent SH U 508A (2.5g, 300 mg/ml ). Unenhanced and serial dynamic scans at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 seconds after injection of contrast agents were obtained using a tissue harmonic technique with power Doppler imaging. The tumoral vascularity was expressed as percentage of power Doppler area, which was measured quantitatively by a computerized program (Ultrasonic Imaging Tool; Soongsil University, Seoul, Korea). The grade (0, no signal; 1, less than 5%; 2, 5-25%; 3, more than 25%) and flow pattern (intratumoral, detour, basket, and mixed) of tumoral vascularity were analyzed. Peak time of contrast-enhancement was measured on each tumor. After injection of contrast agent, tumoral flow signals increased in all lesions (100%). At unenhanced harmonic PDUS, flow signals were detected in 17 HCCs (52%); 15 tumors (46%) demonstrated grade 1 vascularity; and two (6%), grade 2. At contrast-enhanced harmonic PDUS, all tumors were detected vascularity; five (15%) were grade 1; eight (24%), grade 2; and 20 (61%), grade 3. Flow patterns were demonstated as follows at unenhanced harmonic PDUS; intratumoral pattern in 13 tumors (76%), detour in 2 (12%), and basket in 2 (12%). After injection of contrast agent, intratumoral pattern in 7 tumors (21%), detour 0 (0%), basket in 3 (9%) and mixed in 23 (70%) were demonstrated. Peak time of enhancement after injection of contrast agent was 30- 90 seconds in majority of the patients. Contrast-enhanced harmonic PDUS would be valuable in depiction of vascularity and characterization of flow pattern in HCC.

Contrast-enhanced Harmonic power Doppler ultrasonography: Improved depiction of vascularity and characterization of flow pattern in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Baek, Hyung Chul; Yoon, Kwon Ha; Kim, Chang Guhn; Park, Ki Han; Won, Jong Jin [Wonkwang University School of Medicine, Iksa (Korea, Republic of)

2000-12-15

To evaluate the value of contrast-enhanced harmonic power Doppler ultrasonography (PDUS) in depiction and characterization of tumoral vascularity in hepatocellular carcinoma (HCC). Thirty-three patients with HCC were prospectively evaluated with harmonic PDUS before and after injection of the contrast agent SH U 508A (2.5g, 300 mg/ml ). Unenhanced and serial dynamic scans at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 seconds after injection of contrast agents were obtained using a tissue harmonic technique with power Doppler imaging. The tumoral vascularity was expressed as percentage of power Doppler area, which was measured quantitatively by a computerized program (Ultrasonic Imaging Tool; Soongsil University, Seoul, Korea). The grade (0, no signal; 1, less than 5%; 2, 5-25%; 3, more than 25%) and flow pattern (intratumoral, detour, basket, and mixed) of tumoral vascularity were analyzed. Peak time of contrast-enhancement was measured on each tumor. After injection of contrast agent, tumoral flow signals increased in all lesions (100%). At unenhanced harmonic PDUS, flow signals were detected in 17 HCCs (52%); 15 tumors (46%) demonstrated grade 1 vascularity; and two (6%), grade 2. At contrast-enhanced harmonic PDUS, all tumors were detected vascularity; five (15%) were grade 1; eight (24%), grade 2; and 20 (61%), grade 3. Flow patterns were demonstated as follows at unenhanced harmonic PDUS; intratumoral pattern in 13 tumors (76%), detour in 2 (12%), and basket in 2 (12%). After injection of contrast agent, intratumoral pattern in 7 tumors (21%), detour 0 (0%), basket in 3 (9%) and mixed in 23 (70%) were demonstrated. Peak time of enhancement after injection of contrast agent was 30- 90 seconds in majority of the patients. Contrast-enhanced harmonic PDUS would be valuable in depiction of vascularity and characterization of flow pattern in HCC.

Evaluation of CT in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Nakao, Norio; Miura, Yukio; Ohnishi, Mitsunori; Kamikon-ya, Norihiko; Sakamoto, Yoshisato; Miura, Takashi; Sakamoto, Kiyoshi; Takayasu, Yoshio

1985-06-01

In order to evaluate the diagnostic ability of CT in hepatocellular carcinoma, four kinds of CT images were comparatively studied by the accuracy and ROC (receiver operating characteristic) curve analysis. As a result, it was clarified that CT images were evaluated more objectively by ROC curve analysis than by accuracy. The diagnostic ability of existence and differentiation of tumor in the liver were higher in order of plain CT, contrast enhanced CT (CECT), bolus CT and CT arteriography (CTA). Therefore, in an usual CT examination intended to make differential diagnosis in space occupying liver disease, bolus CT seems to be indispensable, and also CTA is essential where diagnosis is difficult even by bolus CT.

Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

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Costello Joseph F

2008-07-01

Full Text Available Abstract Background Hypertonic saline (HTS reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury. Methods Adult male Sprague Dawley rats were used in all experiments. Series 1 examined the potential for HTS to reduce the severity of evolving oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12 or hypertonic saline (HTS, n = 12, and the extent of lung injury assessed after 6 hours. Series 2 examined the potential for HTS to enhance the resolution of oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6 or hypertonic saline (HTS, n = 6, and the extent of lung injury assessed after 6 hours. Results In Series I, HTS significantly reduced bronchoalveolar lavage (BAL neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 103 cells.ml-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in Series 2, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 103 cells.ml-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml-1]. Conclusion These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.

Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

DEFF Research Database (Denmark)

Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs

2009-01-01

of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

A qualitative signature for early diagnosis of hepatocellular carcinoma based on relative expression orderings.

Science.gov (United States)

Ao, Lu; Zhang, Zimei; Guan, Qingzhou; Guo, Yating; Guo, You; Zhang, Jiahui; Lv, Xingwei; Huang, Haiyan; Zhang, Huarong; Wang, Xianlong; Guo, Zheng

2018-04-23

Currently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate. Based on the within-sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non-tumour tissues from cirrhosis tissues of non-hepatocellular carcinoma patients. A signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non-hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non-hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long-lasting cirrhosis could have already gained hepatocellular carcinoma characteristics. The signature can distinguish both hepatocellular carcinoma tissues and tumour-adjacent tissues from cirrhosis tissues of non-hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early

Implantation of Neuronal Stem Cells Enhances Object Recognition without Increasing Neurogenesis after Lateral Fluid Percussion Injury in Mice

Directory of Open Access Journals (Sweden)

Laura B. Ngwenya

2018-01-01

Full Text Available Cognitive deficits after traumatic brain injury (TBI are debilitating and contribute to the morbidity and loss of productivity of over 10 million people worldwide. Cell transplantation has been linked to enhanced cognitive function after experimental traumatic brain injury, yet the mechanism of recovery is poorly understood. Since the hippocampus is a critical structure for learning and memory, supports adult neurogenesis, and is particularly vulnerable after TBI, we hypothesized that stem cell transplantation after TBI enhances cognitive recovery by modulation of endogenous hippocampal neurogenesis. We performed lateral fluid percussion injury (LFPI in adult mice and transplanted embryonic stem cell-derived neural progenitor cells (NPC. Our data confirm an injury-induced cognitive deficit in novel object recognition, a hippocampal-dependent learning task, which is reversed one week after NPC transplantation. While LFPI alone promotes hippocampal neurogenesis, as revealed by doublecortin immunolabeling of immature neurons, subsequent NPC transplantation prevents increased neurogenesis and is not associated with morphological maturation of endogenous injury-induced immature neurons. Thus, NPC transplantation enhances cognitive recovery early after LFPI without a concomitant increase in neuron numbers or maturation.

Small hepatocellular carcinoma versus small cavernous hemangioma

International Nuclear Information System (INIS)

Choi, B.I.; Park, H.W.; Kim, S.H.; Han, M.C.; Kim, C.W.

1989-01-01

To determine the optimal pulse sequence for detection and differential diagnosis of small hepatocellular carcinomas and cavernous hemangiomas less than 5 cm in diameter, the authors have analyzed spin-echo (SE) images of 15 small hepatocellular carcinomas and 31 small cavernous hemangiomas obtained at 2.0 T. Pulse sequences used included repetition times (TRs) of 500 and 2,000 msec and echo times (TEs) of 30,60,90,120,150, and 180 msec. Mean tumor-liver contrast-to-noise ratios on the SE 2,000/60 (TR msec/TE msec) sequence were 23.90 ± 16.33 and 62.10 ± 25.94 for small hepatocellular carcinomas and hemangiomas, respectively, and were significantly greater than for all other pulse sequences. Mean tumor-liver signal intensity ratios on the SE 2,000/150 sequence were 2.34 ± 1.72 and 6.04 ± 2.72 for small hepatocellular carcinomas and hemangiomas, respectively, and were significantly greater than for all other pulse sequences in hemangiomas

Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation in rhesus monkey with spinal cord injury.

Science.gov (United States)

Huang, Lin; Chen, Keng; Chen, Fu-Chao; Shen, Hui-Yong; Ye, Ji-Chao; Cai, Zhao-Peng; Lin, Xi

2017-06-20

This study tried to quantify spinal cord perfusion by using contrast-enhanced ultrasound (CEUS) in rhesus monkey models with acute spinal cord injury. Acute spinal cord perfusion after injury was detected by CEUS, coupling with conventional ultrasound (US) and Color Doppler US (CDFI). Time-intensity curves and perfusion parameters were obtained by autotracking contrast quantification (ACQ) software in the epicenter and adjacent regions of injury, respectively. Neurological and histological examinations were performed to confirm the severity of injury. US revealed spinal cords were hypoechoic and homogeneous, whereas dura maters, pia maters, and cerebral aqueducts were hyperechoic. After spinal cord contusion, the injured spinal cord was hyperechoic on US, and intramedullary vessels of adjacent region of injury were increased and dilated on CDFI. On CEUS hypoperfusion were found in the epicenter of injury, while hyperperfusion in its adjacent region. Quantitative analysis showed that peak intensity (PI) decreased in epicenters of injury but significantly increased in adjacent regions at all time points (p spinal cord injury in overall views and real-time.

Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma

OpenAIRE

Narita, Masato; Hatano, Etsuro; Arizono, Shigeki; Miyagawa-Hayashino, Aya; Isoda, Hiroyoshi; Kitamura, Koji; Yasuchika, Kentaro; Nitta, Takashi; Uemoto, Shinji

2009-01-01

Background: Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is an MRI contrast agent with perfusion and hepatoselective properties. The purpose of the study was to examine uptake of Gd-EOB-DTPA in the hepatobiliary phase in hepatocellular carcinoma (HCC). Methods: A retrospective analysis of 22 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI was performed. Enhancement ratios (ERs) and expression levels of the organic anion transporter (OATP) 1B3...

New Insights Into the Relationships Among Alcohol Consumption, Hepatocellular Carcinoma and Hepatitis C Virus Infection

Directory of Open Access Journals (Sweden)

Sabouri Ghannad

2014-04-01

Full Text Available Context Viral hepatitis and the consumption of alcohol are recognized as important reasons for the development of liver disease throughout the world. It would also seem that chronic alcoholism causes more severe and rapid progression of liver disease in patients with chronic hepatitis C, leading to more frequent liver cirrhosis and hepatocellular carcinoma. Evidence Acquisition The data for this article were obtained through an initial Medline search and from the references of relevant articles, and used to provide updated information on the relationship between alcohol consumption and the hepatitis C virus. Results Excessive alcohol consumption among patients with chronic hepatitis C is likely to result in more severe hepatic injuries, promote pathologic progression to cirrhosis, and increase the risk of developing hepatocellular carcinoma. Although the exact mechanisms involved in the progression of chronic hepatitis C in alcoholic patients have not been definitely established, possible alcohol-induced enhancement of viral replication, iron overload, immunologic suppression, the role of NF-kappa B, and the signaling pathways involved in its activation, have been suggested. Significant correlations have been reported between hepatitis C virus RNA levels and the amount of alcohol consumed by an individual. Interferon therapy is less effective for alcohol patients, than non-alcoholic patients, even after a period of abstinence. The obtained data suggest that a hepatitis C virus infection is an important cofactor in the pathogenesis of liver disease among patients with an alcohol problem. Conclusions In light of a possible synergistic effect between alcohol and hepatitis C virus replication, total abstention ought to be recommended, and due to alcohol's inhibitory effect on interferon therapy, patients with alcohol problems should not be treated until they stop drinking.

Value of gadoxetic acid-enhanced and diffusion-weighted MR imaging in evaluation of hepatocellular carcinomas with atypical enhancement pattern on contrast-enhanced multiphasic MDCT in patients with chronic liver disease

International Nuclear Information System (INIS)

Kim, Hyun Su; Kim, Seong Hyun; Kang, Tae Wook; Song, Kyoung Doo; Choi, Dongil; Park, Cheol Keun

2015-01-01

Highlights: •We investigated imaging findings on gadoxetic acid-enhanced MRI of HCCs without the typical enhancement pattern on multiphasic MDCT. •Most HCCs showed ancillary MR findings of typical HCC. •Considerable number of HCCs showed MR enhancement pattern of typical HCC. -- Abstract: Objective: The purpose of this study was to investigate the value of enhancement kinetics and ancillary imaging findings on gadoxetic acid-enhanced and diffusion-weighted (DW) MR imaging for diagnosing hepatocellular carcinomas (HCCs) without the typical enhancement pattern on contrast-enhanced multiphasic MDCT in patients with chronic liver disease. Materials and methods: Eighty-two surgically confirmed HCCs without the typical enhancement pattern (hypervascular in the arterial phase, followed by washout on the portal or equilibrium phases) on triple-phase MDCT were enrolled in this study. The patients were classified into four categories based on the CT density pattern of arterial and equilibrium phases (isodense–isodense, hypodense–hypodense, isodense–hypodense, and hyperdense–isodense) compared to liver parenchyma. Signal intensity of HCCs on T2-weighted images (T2WI), arterial phase, 3 min late-phase, hepatobiliary phase (HBP) and DW images with a b value of 800 s/mm 2 were qualitatively evaluated, and ADC values were measured. Fisher's exact test and Chi-square test were used to compare the frequency and trend of hyperintensity on T2WI, hypointensity on HBP images, hyperintensity on DW images, and histopathologic grades between groups with different CT density patterns. Kruskal–Wallis test was used to compare the ADC value between groups. Results: Thirty and 52 HCCs were categorized as hypervascular (hyperdense–isodense) and non-hypervascular HCCs (3, isodense–isodense; 37, hypodense–hypodense; 12, isodense–hypodense), respectively. Most HCCs showed hyperintensity on T2WI (77/82, 93.9%) and DW images (81/82, 98.8%) and hypointensity on HBP images

Value of gadoxetic acid-enhanced and diffusion-weighted MR imaging in evaluation of hepatocellular carcinomas with atypical enhancement pattern on contrast-enhanced multiphasic MDCT in patients with chronic liver disease

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyun Su [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul (Korea, Republic of); Kim, Seong Hyun, E-mail: kshyun@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul (Korea, Republic of); Kang, Tae Wook; Song, Kyoung Doo; Choi, Dongil [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul (Korea, Republic of); Park, Cheol Keun [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of)

2015-04-15

Highlights: •We investigated imaging findings on gadoxetic acid-enhanced MRI of HCCs without the typical enhancement pattern on multiphasic MDCT. •Most HCCs showed ancillary MR findings of typical HCC. •Considerable number of HCCs showed MR enhancement pattern of typical HCC. -- Abstract: Objective: The purpose of this study was to investigate the value of enhancement kinetics and ancillary imaging findings on gadoxetic acid-enhanced and diffusion-weighted (DW) MR imaging for diagnosing hepatocellular carcinomas (HCCs) without the typical enhancement pattern on contrast-enhanced multiphasic MDCT in patients with chronic liver disease. Materials and methods: Eighty-two surgically confirmed HCCs without the typical enhancement pattern (hypervascular in the arterial phase, followed by washout on the portal or equilibrium phases) on triple-phase MDCT were enrolled in this study. The patients were classified into four categories based on the CT density pattern of arterial and equilibrium phases (isodense–isodense, hypodense–hypodense, isodense–hypodense, and hyperdense–isodense) compared to liver parenchyma. Signal intensity of HCCs on T2-weighted images (T2WI), arterial phase, 3 min late-phase, hepatobiliary phase (HBP) and DW images with a b value of 800 s/mm{sup 2} were qualitatively evaluated, and ADC values were measured. Fisher's exact test and Chi-square test were used to compare the frequency and trend of hyperintensity on T2WI, hypointensity on HBP images, hyperintensity on DW images, and histopathologic grades between groups with different CT density patterns. Kruskal–Wallis test was used to compare the ADC value between groups. Results: Thirty and 52 HCCs were categorized as hypervascular (hyperdense–isodense) and non-hypervascular HCCs (3, isodense–isodense; 37, hypodense–hypodense; 12, isodense–hypodense), respectively. Most HCCs showed hyperintensity on T2WI (77/82, 93.9%) and DW images (81/82, 98.8%) and hypointensity on HBP

Dual-energy CT with iodine quantification in distinguishing between bland and neoplastic portal vein thrombosis in patients with hepatocellular carcinoma.

Science.gov (United States)

Ascenti, G; Sofia, C; Mazziotti, S; Silipigni, S; D'Angelo, T; Pergolizzi, S; Scribano, E

2016-09-01

To investigate the diagnostic accuracy of dual-energy multidetector computed tomography (MDCT) with iodine quantification compared to conventional enhancement measurements in distinguishing bland from neoplastic portal vein thrombosis in patients with hepatocellular carcinoma. Thirty-four patients (26 men, eight women; mean age, 62 years) with hepatocellular carcinoma and portal vein thrombosis underwent contrast-enhanced dual-energy MDCT during the late hepatic arterial phase for the assessment of portal thrombosis (bland, n=21; neoplastic, n=13). Datasets were analysed separately by two different readers. Interobserver correlation and variability were calculated and compared with the Bland-Altman method. Diagnostic accuracy of conventional enhancement measurements and iodine quantification was calculated by setting either histopathology (n=7) or a reference standard based on MDCT imaging criteria and thrombus evolutionary characteristics compared to a previous MDCT examination (n=27). For iodine quantification threshold determination receiver operating characteristic (ROC) curves were drawn. p-Values <0.05 were considered significant. For conventional enhancement measurements and iodine quantification interobserver correlation was 98% and 96%. Enhancement measurement resulted in a sensitivity of 92.3%, specificity of 85.7%, positive predictive value (PPV) of 80%, and negative predictive value (NPV) of 94.7%. An iodine concentration of 0.9 mg/ml optimised discrimination between neoplastic and bland thrombi (area under the ROC [AUC] 0.993) resulting in a sensitivity of 100%, specificity of 95.2%, PPV of 92.9%, and NPV of 100%. The overall diagnostic accuracy of iodine quantification (97%) was significantly better than conventional enhancement measurements (88.2%; p<0.001). Compared to conventional enhancement measurements, iodine quantification improves the characterisation of portal vein thrombi during the late hepatic arterial phase in patients with

Preoperative detection of hepatocellular carcinoma: comparison of combined constrast-enhanced MR imaging and combined CT during arterial portography and CT hepatic arteriography

International Nuclear Information System (INIS)

Kwak, H.S.; Kim, C.S.; Lee, J.M.; Seoul National University Medical Research Center

2004-01-01

The aim of this study was to compare Gd-DTPA-enhanced dynamic MR images, superparamagnetic iron oxide (SPIO)-enhanced MR images, combined Gd-DTPA-enhanced dynamic and SPIO-enhanced MR images, vs combined CT arterial portography (CTAP) and CT hepatic arteriography (CTHA), in the detection of hepatocellular carcinoma (HCC) using receiver operating characteristic (ROC) analysis. Twenty-four patients with 38 nodular HCCs (5-60 mm, mean 23.0 mm) were retrospectively analyzed. Image reviews were conducted on a liver segment-by-segment basis. A total of 192 segments, including 36 segments with 38 HCC, were reviewed independently by three radiologists. Each radiologist read four sets of images (set 1, unenhanced and Gd-DTPA-enhanced dynamic MR images; set 2, unenhanced and SPIO-enhanced MR images; set 3, combined Gd-DTPA-enhanced dynamic and SPIO-enhanced MR images; set 4, combined CTAP and CTHA). To minimize any possible learning bias, the reviewing order was randomized and the reviewing procedure was performed in four sessions at 2-week intervals. The diagnostic accuracy (Az values) for HCCs of combined CTAP and CTHA, combined Gd-DTPA-enhanced dynamic and SPIO-enhanced MR images, Gd-DTPA-enhanced dynamic MR images, and SPIO-enhanced MR images for all observers were 0.934, 0.963, 0.878, and 0.869, respectively. The diagnostic accuracy of combined CTAP and CTHA and combined Gd-DTPA-enhanced dynamic and SPIO-enhanced MR images was significantly higher than Gd-DTPA-enhanced dynamic MR images or SPIO-enhanced MR images (p<0.005). The mean specificity of combined CTAP and CTHA (93%) and combined Gd-DTPA-enhanced dynamic and SPIO-enhanced MR images (95%) was significantly higher than Gd-DTPA-enhanced dynamic MR images (87%) or SPIO-enhanced MR images (88%; p<0.05). Combined Gd-DTPA-enhanced dynamic and SPIO-enhanced MR images may obviate the need for more invasive combined CTAP and CTHA for the preoperative evaluation of patients with HCC

Peritoneal carcinomatosis: an unusual presentation of fibrolamellar hepatocellular carcinoma

International Nuclear Information System (INIS)

Vicente, R.; Garcia-Gutierrez, J. A.; Fernandez, A.; Santalla, F.

2001-01-01

Fibrolamellar hepatocellular carcinoma is an uncommon malignant tumor with characteristic clinical, radiological and histopathological features that is usually associated with a more favorable natural course and greater survival than more common variants of hepatocellular carcinoma. We describe an atypical case of a fibrolamellar hepatocellular carcinomas sowing aggressive behaviour in a 20-year-old woman. The lesion presented with massive ascites, and imaging studies revealed extensive peritoneal metastatic spread. (Author) 8 refs

[Expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma].

Science.gov (United States)

Gu, C J; Ni, Q C; Ni, K; Zhang, S; Qian, H X

2018-05-29

Objective: To investigate the expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma. Methods: A total of 136 cases of primary hepatocellular carcinoma tissues and paired adjacent tissues were collected. Immunohistochemistry and Western blot were used to detect the expression of KIAA1199 in primary hepatocellular carcinoma tissues and paired adjacent tissues. The relationship between KIAA1199 and clinicopathological parameter of primary hepatocellular carcinoma was analyzed. Results: The positive rate of KIAA1199 in primary hepatocellular carcinoma was 82.3% (112/136), which was higher than that in paired para-cancerous tissues (14.7%, 20/136). High expression of KIAA1199 was significantly correlated with age, cirrhosis history, tumor size, tumor number, degree of differentiation, TNM staging and microvenous invasion (MVI) ( P 0.05). The Kaplan-Meier survival curves indicated that high KIAA1199 expression was associated with poor survival ( P hepatocellular carcinoma, which is significantly correlated with the clinicopathological features and prognosis, high expression of KIAA1199 increased the risk of death in patients with primary hepatocellular carcinoma.

Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Tomoki; Aikata, Hiroshi; Hatooka, Masahiro; Morio, Kei; Morio, Reona; Kan, Hiromi; Fujino, Hatsue; Fukuhara, Takayuki; Masaki, Keiichi; Ohno, Atsushi; Naeshiro, Noriaki; Nakahara, Takashi; Honda, Yohji; Murakami, Eisuke; Kawaoka, Tomokazu; Tsuge, Masataka; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Hyogo, Hideyuki; Takahashi, Shoichi [Hiroshima University Hospital, Department of Gastroenterology and Metabolism, Hiroshima (Japan); Chayama, Kazuaki [Hiroshima University Hospital, Department of Gastroenterology and Metabolism, Hiroshima (Japan); Hiroshima University, Liver Research Project Center, Hiroshima (Japan)

2015-11-15

Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs. A total of 85 surgically resected nodules (≤30 mm) were analyzed. HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared. Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95 % confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682-0.890): CEUS, 0.784 (0.679-0.889), in combination, 0.876 (0.792-0.959). The sensitivity, specificity, and accuracy were 64.1 %, 95.7 %, and 81.2 % in EOB-MRI, 56.4 %, 97.8 %, and 78.8 % in CEUS, and 84.6 %, 95.7 %, and 90.6 % in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS. Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs. (orig.)

Liver injury from Herbals and Dietary Supplements in the US Drug Induced Liver Injury Network

Science.gov (United States)

Navarro, Victor J.; Barnhart, Huiman; Bonkovsky, Herbert L.; Davern, Timothy; Fontana, Robert J.; Grant, Lafaine; Reddy, K. Rajender; Seeff, Leonard B.; Serrano, Jose; Sherker, Averell H.; Stolz, Andrew; Talwalkar, Jayant; Vega, Maricruz; Vuppalanchi, Raj

2014-01-01

Background The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity due to conventional medications as well as herbals and dietary supplements (HDS). Rationale To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight US referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury due to HDS. Hepatotoxicity due to HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments including death and liver transplantation were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury due to bodybuilding HDS, 85 due to non-bodybuilding HDS, and 709 due to medications. Main Results Liver injury due to HDS increased from 7% to 20% (p Bodybuilding HDS caused prolonged jaundice (median 91 days) in young men but did not result in any fatalities or liver transplantation. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women and more frequently led to death or transplantation compared to injury from medications (13% vs. 3%, p bodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes; death and transplantation. PMID:25043597

Hepatocellular carcinoma detected by iodized oil

International Nuclear Information System (INIS)

Yumoto, Y.; Jinno, K.; Tokuyama, K.

1985-01-01

This study assesses the diagnostic value of Lipiodol (iodized oil) and computed tomography (CT) in detecting hepatocellular carcinoma (HCC). Twenty-four patients who were suspected of having HCC received injections of a small amount of Lipiodol, along with an antitumor agent, in the hepatic artery following routine celiac angiography. CT scans obtained 7-10 days after Lipiodol administration demonstrated HCC in distinct contrast to the surrounding noncancerous parenchyma. In particular, the CT-Lipiodol procedure disclosed many small HCC lesions that were not shown by celiac angiography, scintigraphy, CT with an without contrast medium enhancement, and ultrasonography. Although this procedure may miss very small or highly fibrotic lesions, it is recommended for patients suspected of having HCC and for patients for whom hepatic resection is being considered

Refeeding with a high-protein diet after a 48 h fast causes acute hepatocellular injury in mice.

Science.gov (United States)

Oarada, Motoko; Tsuzuki, Tsuyoshi; Nikawa, Takeshi; Kohno, Shohei; Hirasaka, Katsuya; Gonoi, Tohru

2012-05-01

Elucidating the effects of refeeding a high-protein diet after fasting on disease development is of interest in relation to excessive protein ingestion and irregular eating habits in developed countries. The objective of the present study was to address the hepatic effects of refeeding a high-protein diet after fasting. Mice were fasted for 48 h and then refed with a test diet containing 3, 15, 35, 40, 45 or 50 % casein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and liver immediate-early gene expression levels were sequentially measured for the first 24 h after initiation of refeeding. Refeeding with a 50 % casein diet after 48 h of fasting led to a rapid (within 2-3 h) and abnormal elevation in serum ALT (P = 0·006) and AST (P = 0·001) activities and a marked increase in liver Finkel-Biskis-Jinkins (FBJ) osteosarcoma oncogene (P = 0·007) and nuclear receptor subfamily 4, group A, member 1 (P = 0·002) mRNA levels. In contrast, refeeding of the 3, 15 or 35 % casein diets produced no substantial increases in serum ALT and AST activities in mice. Refeeding of 40, 45 or 50 % casein increased serum ALT and AST activities in proportion to this dietary casein content. In mice refed the 3, 15 or 35, but not 50 %, casein diets, liver heat shock protein 72 transcript levels greatly increased. We conclude from these data that the consumption of a high-protein diet after fasting causes acute hepatocellular injury in healthy animals, and propose that careful attention should be paid to the use of such diets.

Evaluation of pathological features of hepatocellular carcinoma by contrast-enhanced ultrasonography: Comparison with pathology on resected specimen

International Nuclear Information System (INIS)

Ogawa, Sadanobu; Kumada, Takashi; Toyoda, Hidenori; Ichikawa, Hideo; Kawachi, Toshiaki; Otobe, Katsuhiko; Hibi, Toshio; Takeshima, Kenji; Kiriyama, Seiki; Sone, Yasuhiro; Tanikawa, Makoto; Hisanaga, Yasuhiro; Yamaguchi, Akihiro; Isogai, Masatoshi; Kaneoka, Yuji; Washizu, Junji

2006-01-01

Features of hepatocellular carcinoma (HCC) observed by contrast-enhanced ultrasonography (CEUS) were compared to pathological features of corresponding resected HCC specimens, to evaluate the ability of CEUS to depict the pathological features of HCC. We investigated 50 HCC nodules that were treated by surgical resection. All nodules had been examined by CEUS with intravenous contrast agent (Levovist) before surgery. CEUS findings were divided into three phases for evaluation and classification of enhancement patterns: two vascular phases (arterial phase and portal venous phase) and the delayed phase. Pathological examination focused on differentiation and on the presence or absence of a tumor capsule, intratumoral septum, and intratumoral necrosis. All 21 nodules that showed a linear or annular vessel around the tumor margin in the arterial phase had capsular formation. Of the 27 nodules that showed heterogeneous perfusion in the portal venous phase, 21 (77.8%) had an intratumoral septum and 23 (85.2%) showed intratumoral necrosis. All nodules that were depicted as a defect with an unclear margin in the delayed phase were well-differentiated HCCs, whereas all nodules that were depicted as a defect with a clear margin were moderately or poorly differentiated HCCs. From our observations, the arterial, portal venous, and delayed phases of CEUS could reflect different pathological aspects of HCC. Some pathological characteristics of HCC might be evaluated preoperatively and non-invasively, by means of combined analysis of three phases of CEUS findings

Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma

DEFF Research Database (Denmark)

Oliveri, Roberto S; Wetterslev, Jørn; Gluud, Christian

2011-01-01

Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC.......Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC....

Research progress of vascular change after TACE in hepatocellular carcinoma

International Nuclear Information System (INIS)

Kang Zhen; Xiao Enhua

2013-01-01

Mortality rate of hepatocellular carcinoma is high. The majority of the patients are diagnosed in advanced stage and lose surgical opportunities. Many studies have reported transcatheter arterial chemoembolization (TACE) is an effective treatment for unresectable hepatocellular carcinoma, and recommended TACE as a standard treatment for hepatocellular carcinoma of Barcelona Clinical Liver Cancer staging (BCLC staging) B. However, TACE can hardly fully embolize tumor blood supply, TACE postoperative hemodynamics and angiogenesis can induce tumor recurrence and metastasis. This paper reviewed characteristics of vascular changes, mechanisms, diagnosis and treatment methods, new progress in the field of hepatocellular carcinoma after TACE. (authors)

Significance of detecting circulating hepatocellular carcinoma cells in peripheral blood of hepatocellular carcinoma patients by nested reverse transcription-polymerase chain reaction and its clinical value: a retrospective study.

Science.gov (United States)

Liu, Yang; Wang, Yue-ru; Wang, Long; Song, Rui-mei; Zhou, Bo; Song, Zhen-shun

2014-01-01

Circulating hepatocellular carcinoma cells may be detected by reverse transcription-polymerase chain reaction. We investigated the relationship between circulating hepatocellular carcinoma cells and hepatoma patient survival after different managements and survival periods. Peripheral vein blood (5 ml) samples were obtained from 113 patients with hepatocellular carcinoma and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 healthy individuals) between January 1, 2009, and December 31, 2013. To detect circulating hepatocellular carcinoma cells in peripheral blood, alpha-fetoprotein messenger RNA was amplified from total RNA extracted from whole blood by reverse transcription-polymerase chain reaction. Alpha-fetoprotein messenger RNA was detected in 59 blood samples from the hepatocellular carcinoma patients (59/113, 52.2%). In contrast, there were no clinical control subjects whose samples showed detectable alpha-fetoprotein messenger RNA. The presence of alpha-fetoprotein messenger RNA in blood seemed to be correlated with the stage (by TNM classification) of hepatocellular carcinoma, serum alpha-fetoprotein value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. In addition, alpha-fetoprotein messenger RNA was detected in the blood of 25 patients showing distant metastasis at extrahepatic organs (100%), in contrast to 32 of 88 cases without metastasis (36.4%). All the patients with hepatocellular carcinoma were followed. Seventeen patients with resection of a T 2 stage hepatocellular carcinoma had a survival of 3.2 years after surgical management, 38 cases with resection of a T3 stage hepatocellular carcinoma had a 1.3-year survival, and only 37 cases with T4 stage disease after different treatments except surgery survived for 0.6 years (P <0.01). The presence of alpha-fetoprotein messenger RNA in peripheral blood may be an indicator of circulating

Usage of adenovirus expressing thymidine kinase mediated hepatocellular damage for enabling mouse liver repopulation with allogenic or xenogenic hepatocytes.

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Daniel Moreno

Full Text Available It has been shown that the liver of immunodeficient mice can be efficiently repopulated with human hepatocytes when subjected to chronic hepatocellular damage. Mice with such chimeric livers represent useful reagents for medical and clinical studies. However all previously reported models of humanized livers are difficult to implement as they involve cross-breeding of immunodeficient mice with mice exhibiting genetic alterations causing sustained hepatic injury. In this paper we attempted to create chimeric livers by inducing persistent hepatocellular damage in immunodeficient Rag2(-/- γc(-/- mice using an adenovirus encoding herpes virus thymidine kinase (AdTk and two consecutive doses of ganciclovir (GCV. We found that this treatment resulted in hepatocellular damage persisting for at least 10 weeks and enabled efficient engraftment and proliferation within the liver of either human or allogenic hepatocytes. Interestingly, while the nodules generated from the transplanted mouse hepatocytes were well vascularized, the human hepatocytes experienced progressive depolarization and exhibited reduced numbers of murine endothelial cells inside the nodules. In conclusion, AdTk/GCV-induced liver damage licenses the liver of immunodeficient mice for allogenic and xenogenic hepatocyte repopulation. This approach represents a simple alternative strategy for chimeric liver generation using immunodeficient mice without additional genetic manipulation of the germ line.

Surgical management of spontaneous ruptured hepatocellular adenoma

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Marcelo Augusto Fontenelle Ribeiro Junior

2009-01-01

Full Text Available AIMS: Spontaneous ruptured hepatocellular adenoma (SRHA is a rare life-threatening condition that may require surgical treatment to control hemorrhaging and also stabilize the patient. We report a series of emergency surgeries performed at our institution for this condition. METHODS: We reviewed medical records and radiology files of 28 patients (from 1989 to 2006 with a proven diagnosis of hepatocellular adenoma (HA. Three (10.7% of 28 patients had spontaneous ruptured hepatocellular adenoma, two of which were associated with intrahepatic hemorrhage while one had intraperitoneal bleeding. Two patients were female and one was male. Both female patients had a background history of oral contraceptive use. Sudden abdominal pain associated with hemodynamic instability occurred in all patients who suffered from spontaneous ruptured hepatocellular adenoma. The mean age was 41.6 years old. The preoperative assessment included liver function tests, ultrasonography and computed tomography. RESULTS: The surgical approaches were as follows: right hemihepatectomy for controlling intraperitoneal bleeding, and right extended hepatectomy and non-anatomic resection of the liver for intrahepatic hemorrhage. There were no deaths, and the postoperative complications were bile leakage and wound infection (re-operation, as well as intraperitoneal abscess (re-operation and pleural effusion. CONCLUSION: Spontaneous ruptured hepatocellular adenoma may be treated by surgery for controlling hemorrhages and stabilizing the patient, and the decision to operate depends upon both the patient's condition and the expertise of the surgical team.

Hydroxychloroquine Protects against Cardiac Ischaemia/Reperfusion Injury In Vivo via Enhancement of ERK1/2 Phosphorylation.

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Lauren Bourke

Full Text Available An increasing number of investigations including human studies demonstrate that pharmacological ischaemic preconditioning is a viable way to protect the heart from myocardial ischaemia/reperfusion (I/R injury. This study investigated the role of hydroxychloroquine (HCQ in the heart during I/R injury. In vitro and in vivo models of myocardial I/R injury were used to assess the effects of HCQ. It was found that HCQ was protective in neonatal rat cardiomyocytes through inhibition of apoptosis, measured by TUNEL and cleaved caspase-3. This protection in vitro was mediated through enhancement of ERK1/2 phosphorylation mediated by HCQ in a dose-dependent fashion. A decrease in infarct size was observed in an in vivo model of myocardial I/R injury in HCQ treated animals and furthermore this protection was blocked in the presence of the ERK1/2 inhibitor U0126. For the first time, we have shown that HCQ promotes a preconditioning like protection in an in vivo simulated rat myocardial I/R injury model. Moreover, it was shown that HCQ is protective via enhanced phosphorylation of the pro-survival kinase ERK1/2.

Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

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Lin, Tao; Qiu, Shuai; Yan, Liwei; Zhu, Shuang; Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin

2018-05-01

Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. © 2017 Wiley Periodicals, Inc.

Presence of non-hypervascular hypointense nodules on Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in patients with hepatocellular carcinoma.

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Inoue, Masanori; Ogasawara, Sadahisa; Chiba, Tetsuhiro; Ooka, Yoshihiko; Wakamatsu, Toru; Kobayashi, Kazufumi; Suzuki, Eiichiro; Tawada, Akinobu; Yokosuka, Osamu

2017-04-01

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) performed before curative therapy for hepatocellular carcinoma (HCC) can distinguish between intrahepatic distant recurrence and hypervascularization. This study aimed to retrospectively evaluate the presence of non-hypervascular hypointense nodules on hepatobiliary phase images from Gd-EOB-DTPA-enhanced MRI as a risk factor of the intrahepatic distant recurrence of early stage HCC following radiofrequency ablation (RFA). A total of 132 patients who underwent preprocedural Gd-EOB-DTPA-enhanced MRI followed by initial RFA were retrospectively analyzed. Post-RFA intrahepatic distant recurrence, which excluded the hypervascularization of non-hypervascular hypointense nodules detected by preprocedural Gd-EOB-DTPA-enhanced MRI, was evaluated according to the presence of non-hypervascular hypointense nodules on preprocedural Gd-EOB-DTPA-enhanced MRI. Intrahepatic distant recurrence rates following RFA were higher in patients with non-hypervascular hypointense nodules (1-year: 22.5%, 2-year: 52.1%, 5-year: 89.1%) compared with in patients without non-hypervascular hypointense nodules (1-year: 7.0%, 2-year: 28.8%, 5-year: 48.7%). The presence of non-hypervascular hypointense nodules was associated with markedly increased cumulative recurrence rates of both identical and different subsegment intrahepatic distant recurrence, being an independent risk factor for post-RFA identical and different subsegment intrahepatic distant recurrence (identical: HR = 2.365, P = 0.027; different: HR = 3.276, P DTPA-enhanced MRI obtained prior to RFA is an important predictive factor of intrahepatic distant recurrence following RFA of HCC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Resected Hepatocellular Carcinoma in a Patient with Crohn's Disease on Azathioprine

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Heron, Valérie; Fortinsky, Kyle Joshua; Spiegle, Gillian; Hilzenrat, Nir; Szilagyi, Andrew

2016-01-01

Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn's disease. The patient is a 61-year-old with longstanding Crohn's disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn's disease who present with elevated liver enzymes, especially those on azathioprine therapy. PMID:27403102

Models of Hepatocellular Carcinoma and Biomarker Strategy

Energy Technology Data Exchange (ETDEWEB)

Bagi, Cedo M., E-mail: cedo.bagi@pfizer.com; Andresen, Catharine J. [Global Science & Technology, PGRD, Pfizer Inc, Groton, CT 06340 (United States)

2010-07-07

The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients.

Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network.

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Navarro, Victor J; Barnhart, Huiman; Bonkovsky, Herbert L; Davern, Timothy; Fontana, Robert J; Grant, Lafaine; Reddy, K Rajender; Seeff, Leonard B; Serrano, Jose; Sherker, Averell H; Stolz, Andrew; Talwalkar, Jayant; Vega, Maricruz; Vuppalanchi, Raj

2014-10-01

The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity caused by conventional medications as well as herbals and dietary supplements (HDS). To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight U.S. referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury caused by HDS. Hepatotoxicity caused by HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments, including death and liver transplantation (LT), were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury caused by bodybuilding HDS, 85 by nonbodybuilding HDS, and 709 by medications. Liver injury caused by HDS increased from 7% to 20% (P Bodybuilding HDS caused prolonged jaundice (median, 91 days) in young men, but did not result in any fatalities or LT. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women, and, more frequently, led to death or transplantation, compared to injury from medications (13% vs. 3%; P bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes (death and transplantation). (Hepatology 2014;60:1399-1408). © 2014 by the American Association for the Study of Liver Diseases.

Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

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Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

2018-02-09

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

Hepatocellular carcinoma: a clinico pathological study

International Nuclear Information System (INIS)

Abbasi, A.; Butt, N.; Bhutto, A.R.; Gulzar, K.; Munir, S.M.

2010-01-01

To describe the clinico-pathological and radiological profile of hepatocellular carcinoma. All consecutive patients suspected of having hepatocellular carcinoma (HCC), were admitted and included in this study. Diagnosis of HCC was established by clinical, biochemical, ultrasonographic and histopathologic findings. Patients with primary carcinoma elsewhere in the body, metastatic in the liver, fibrolamellar carcinoma and benign tumours were excluded from the study. At ultrasonography, the details of tumour size and number, portal vein thrombosis and presence of ascites were recorded. Patients were staged according to Okuda staging system. Results were described in mean and percentage values. There were 82 patients with hepatocellular carcinoma including 58 males and 24 females, with male to female ratio of 2.8:1. The mean age of patients was 56.24 +- 13.65 years. Right hypochondrial pain was the main symptom in 52 (63.4%) patients. The duration of symptoms varied from 1 month to 2 years. Tumour size was larger than 50% of liver size in 42 (51.2%) with portal vein thrombosis in 10 (12.19%). Anti HCV was positive in 44 (53.7%), HBsAg in 26 (31.7%) and both were found positive in 2 (2.44%) patients. Ten patients (12.2/%) found negative both for anti-HCV and HBsAg. According to Okuda staging system 18 patients had stage 1, 50 had stage 2 and 14 had stage 3 hepatocellular carcinoma. The mean age of presentation of hepatocellular carcinoma was younger as compared to western countries with potentially large non-resectable lesions. Chronic hepatitis C and B was found to be the major known factors. Patients with chronic hepatitis C and B should undergo vigorous HCC surveillance to detect early, potentially respectable HCC. (author)

PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

Science.gov (United States)

Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

2014-01-01

Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

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Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma.

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Nooron, Nattakarn; Ohba, Koji; Takeda, Kazuhisa; Shibahara, Shigeki; Chiabchalard, Anchalee

2017-08-01

Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array. MITF immunoreactivity was detected in subsets of hepatocellular carcinoma (6 out of 38 specimens; 16%) and cholangiocarcinoma (2/7 specimens; 29%). Moreover, immunoreactivity for glioma-associated oncogene 1 (GLI1), a transcription factor of the Hedgehog signaling pathway, was detected in 55% of hepatocellular carcinoma (21/38 specimens) and 86% of cholangiocarcinoma (6/7 specimens). Importantly, MITF was detectable only in the GLI1-positive hepatocellular carcinoma and cholangiocarcinoma, and MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. Subsequently, the effect of mahanine was analyzed in HepG2 human hepatocellular carcinoma and HuCCT1 and KKU-100 human cholangiocarcinoma cells. Mahanine (25 µM) showed the potent cytotoxicity in these hepatic cancer cell lines, which was associated with increased expression levels of MITF, as judged by Western blot analysis. MITF is over-expressed in subsets of hepatocellular carcinoma and cholangiocarcinoma, and detectable MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. MITF expression levels may be determined in hepatic cancer cells by the balance between the Hedgehog signaling and the cellular stress.

A new apatinib microcrystal formulation enhances the effect of radiofrequency ablation treatment on hepatocellular carcinoma

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Xie H

2018-05-01

Full Text Available Hui Xie,1,2 Shengtao Tian,2 Haipeng Yu,1 Xueling Yang,1 Jia Liu,3 Huaming Wang,2 Fan Feng,2 Zhi Guo1 1Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Interventional Therapy, 302nd Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 3Department of Blood Transfusion, 302nd Hospital of People’s Liberation Army, Beijing, People’s Republic of China Introduction: Radiofrequency ablation (RFA is the foremost treatment option for advanced hepatocellular carcinoma (HCC, however, rapid and aggressive recurrence of HCC often occurs after RFA due to epithelial–mesenchymal transition process. Although combination of RFA with sorafenib, a molecular targeted agent, could attenuate the recurrence of HCC, application of this molecular targeted agent poses a heavy medical burden and oral administration of sorafenib also brings severe side effects. Materials and methods: In this study, we prepared an apatinib microcrystal formulation (Apa-MS that sustainably releases apatinib, a novel molecular targeted agent, for advanced HCC treatment. We injected apatinib solution or Apa-MS into subcutaneous HCC tumors. Results: It was found that Apa-MS exhibited slow apatinib release in vivo and in turn inhibited the epithelial–mesenchymal transition of HCC cells for extended time. Moreover, in rodent HCC model, Apa-MS enhanced the antitumor effect of RFA treatment. Conclusion: Based on these results, we conclude that Apa-MS, a slow releasing system of apatinib, allows apatinib to remain effective in tumor tissues for a long time and could enhance the antitumor effect of RFA on HCC. Keywords: apatinib microcrystals, radiofrequency ablation, sustained releasing behavior, long-acting efficiency

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Dual-energy CT with iodine quantification in distinguishing between bland and neoplastic portal vein thrombosis in patients with hepatocellular carcinoma

International Nuclear Information System (INIS)

Ascenti, G.; Sofia, C.; Mazziotti, S.; Silipigni, S.; D'Angelo, T.; Pergolizzi, S.; Scribano, E.

2016-01-01

Aim: To investigate the diagnostic accuracy of dual-energy multidetector computed tomography (MDCT) with iodine quantification compared to conventional enhancement measurements in distinguishing bland from neoplastic portal vein thrombosis in patients with hepatocellular carcinoma. Material and methods: Thirty-four patients (26 men, eight women; mean age, 62 years) with hepatocellular carcinoma and portal vein thrombosis underwent contrast-enhanced dual-energy MDCT during the late hepatic arterial phase for the assessment of portal thrombosis (bland, n=21; neoplastic, n=13). Datasets were analysed separately by two different readers. Interobserver correlation and variability were calculated and compared with the Bland–Altman method. Diagnostic accuracy of conventional enhancement measurements and iodine quantification was calculated by setting either histopathology (n=7) or a reference standard based on MDCT imaging criteria and thrombus evolutionary characteristics compared to a previous MDCT examination (n=27). For iodine quantification threshold determination receiver operating characteristic (ROC) curves were drawn. p-Values <0.05 were considered significant. Results: For conventional enhancement measurements and iodine quantification interobserver correlation was 98% and 96%. Enhancement measurement resulted in a sensitivity of 92.3%, specificity of 85.7%, positive predictive value (PPV) of 80%, and negative predictive value (NPV) of 94.7%. An iodine concentration of 0.9 mg/ml optimised discrimination between neoplastic and bland thrombi (area under the ROC [AUC] 0.993) resulting in a sensitivity of 100%, specificity of 95.2%, PPV of 92.9%, and NPV of 100%. The overall diagnostic accuracy of iodine quantification (97%) was significantly better than conventional enhancement measurements (88.2%; p<0.001). Conclusion: Compared to conventional enhancement measurements, iodine quantification improves the characterisation of portal vein thrombi during the late

Lymph node enhancement at MRI with MnDPDP in primary hepatic carcinoma. Technical report

International Nuclear Information System (INIS)

Burkill, Guy J.C.; Mannion, Ethna M.; Healy, Jeremiah C.

2001-01-01

AIMS: To report two cases of lymph node enhancement in primary hepatic carcinoma following the administration of Mangafodipir trisodium (MnDPDP, Teslascan[reg ], Nycomed Amersham U.K.), an hepatocyte specific magnetic resonance imaging (MRI) contrast agent. To review our experience with this contrast agent and the literature to establish if such enhancement occurs in normal lymph nodes or has been previously described in hepatocellular carcinoma (HCC) or other lesions. MATERIALS AND METHODS: The radiological reports of all MnDPDP enhanced abdominal MRI examinations were reviewed for lymph node enlargement. The MR images from examinations with reported nodal enlargement were re-evaluated for evidence of nodal enhancement and the hospital notes and histological reports were reviewed. Nodal enhancement was considered present if lymph node signal intensity was greater than that of the spleen following MnDPDP. Literature searches were performed on Medline and PubMed for previous descriptions of lymph node enhancement following MnDPDP. RESULTS: The reports of 90 MnDPDP abdominal MRI examinations were reviewed. Of 18 cases of lymph node enlargement, two had evidence of lymph node enhancement following MnDPDP. These two cases had hepatocellular carcinoma and fibrolamellar hepatocellular carcinoma, respectively, confirmed on liver biopsy. No reports of lymph node enhancement following MnDPDP were identified in the literature. CONCLUSION: Two cases of lymph node enhancement following MnDPDP have been presented. Although histological confirmation of the lymph nodes was not obtained, the authors propose that the lymph node enhancement was due to functioning hepatocytes in lymph node metastases from the patients' histologically confirmed hepatocellular carcinomas. Burkill, G.J.C., Mannion, E.M. and Healy, J.C. (2001)

The evolutionary scenario of hepatocellular carcinoma in Italy: an update.

Science.gov (United States)

Bucci, Laura; Garuti, Francesca; Lenzi, Barbara; Pecorelli, Anna; Farinati, Fabio; Giannini, Edoardo G; Granito, Alessandro; Ciccarese, Francesca; Rapaccini, Gian Lodovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Sacco, Rodolfo; Cammà, Calogero; Virdone, Roberto; Marra, Fabio; Felder, Martina; Morisco, Filomena; Benvegnù, Luisa; Gasbarrini, Antonio; Svegliati-Baroni, Gianluca; Foschi, Francesco Giuseppe; Missale, Gabriele; Masotto, Alberto; Nardone, Gerardo; Colecchia, Antonio; Bernardi, Mauro; Trevisani, Franco

2017-02-01

Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of aetiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centres from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000-2004, 2005-2009 and 2010-2014). The main results were as follows: (i) progressive patient aging; (ii) progressive expansion of non-viral cases and, namely, of "metabolic" hepatocellular carcinomas; (iii) increasing proportion of hepatocellular carcinoma diagnosed during a correct (semi-annual) surveillance programme; (iv) favourable cancer stage migration; (v) increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) improved overall survival (adjusted for the lead time in surveyed patients), particularly after 2009, of both viral and non-viral patients presenting with an early- or intermediate-stage hepatocellular carcinoma. During the last 15 years several aetiological and clinical features of hepatocellular carcinoma patients have changed, as their management. The observed improvement of overall survival was owing both to the wider use of semi-annual surveillance, expanding the proportion of tumours that qualified for curative treatments, and to the improved outcome of loco-regional treatments. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sustained multiple organ ischaemia after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma.

Science.gov (United States)

Kim, Young Woon; Kwon, Jung Hyun; Nam, Soon Woo; Jang, Jeong Won; Jung, Hyun Suk; Shin, Yu Ri; Park, Eun Su; Shim, Dong Jae

2018-02-01

Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads) may enhance drug delivery to tumours and reduce systemic toxicity. TACE with DC beads leads to significantly fewer serious side-effects compared with conventional TACE. A 66-year-old man with hepatocellular carcinoma (HCC) complained of continuous abdominal pain 1 month after TACE with DC beads. At the time of TACE, angiography revealed severe stenosis of both hepatic arteries. The diagnostic work up on admission suggested severe bile duct injury with regional bile duct dilatation, segmental liver and spleen infarction, necrotizing pancreatitis, as well as gastric and duodenal ulcers. The pathology specimens of the duodenum contained DC beads that had passed through small vessels in the connective tissue. The patient's condition appeared to improve after 2 weeks of antibiotic treatment and supportive care, but new multifocal liver and spleen infarction subsequently developed. After 2 months, he was well enough to be discharged. His HCC partially responded to the TACE with DC beads but eventually progressed and he died after 11 months. The present case report highlights unexpected ongoing multiple organ ischaemia in a 66-year-old man treated for HCC using TACE with DC beads. The use of TACE with DC beads should be carefully considered in patients with vascular strictures or aberrant blood supply.

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File list: Oth.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

Traditional Chinese Medicine and Herb-induced Liver Injury: Comparison with Drug-induced Liver Injury.

Science.gov (United States)

Jing, Jing; Teschke, Rolf

2018-03-28

Cases of suspected herb-induced liver injury (HILI) caused by herbal Traditional Chinese Medicines (TCMs) and of drug-induced liver injury (DILI) are commonly published in the scientific literature worldwide. As opposed to the multiplicity of botanical chemicals in herbal TCM products, which are often mixtures of several herbs, conventional Western drugs contain only a single synthetic chemical. It is therefore of interest to study how HILI by TCM and DILI compare with each other, and to what extent results from each liver injury type can be transferred to the other. China is among the few countries with a large population using synthetic Western drugs as well as herbal TCM. Therefore, China is well suited to studies of liver injury comparing drugs with TCM herbs. Despite some concordance, recent analyses of liver injury cases with verified causality, using the Roussel Uclaf Causality Assessment Method, revealed major differences in HILI caused by TCMs as compared to DILI with respect to the following features: HILI cases are less frequently observed as compared to DILI, have a smaller proportion of females and less unintentional rechallenge events, and present a higher rate of hepatocellular injury features. Since many results were obtained among Chinese residents who had access to and had used Western drugs and TCM herbs, such ethnic homogeneity supports the contention that the observed differences of HILI and DILI in the assessed population are well founded.

Orbital Metastasis of Hepatocellular Carcinoma: A Case Report ...

African Journals Online (AJOL)

Background: Hepatocellular carcinoma is one of the commonest malignancies in Nigeria, however metastasis to the orbit is a rare presentation. Objective: To present a rare case of orbital metastasis of hepatocellular carcinoma. Case Report: A 25-year-old man presented with a 3-month history of pain, progressive swelling ...

File list: ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 All antigens Liver Carcinoma, Hepato...cellular SRX467209,SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.

Science.gov (United States)

Kim, Soo Ryang; Kanda, Fumio; Kobessho, Hiroshi; Sugimoto, Koji; Matsuoka, Toshiyuki; Kudo, Masatoshi; Hayashi, Yoshitake

2006-11-07

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves

Institute of Scientific and Technical Information of China (English)

Soo Ryang Kim; Fumio Kanda; Hiroshi Kobessho; Koji Sugimoto; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

2006-01-01

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-yearold woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI)disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement.The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Metastatic hepatocellular carcinoma on the mandible: a case report

International Nuclear Information System (INIS)

Kim, Jin Soo; Kim, Jae Duk

2005-01-01

Hepatocellular carcinoma is one of the most common cancer worldwide, primarily affecting those in regions with a high prevalence of viral hepatitis. However, the metastasis of hepatocellular carcinoma to the oral cavity is a rare phenomenon. This report presents a case of metastatic hepatocellular carcinoma in the left mandibular angle and ramus region of a 62-year-old man. Panoramic radiograph revealed an ill-defined radiolucent lesion extending from the retained root of the mandibular left second molar into the ascending ramus. The lesion had irregular and ill-defined margins.

Radio-embolization for hepatocellular carcinoma

International Nuclear Information System (INIS)

Raoul, J.L.; Edeline, J.; Pracht, M.; Boucher, E.; Rolland, Y.; Garin, E.

2011-01-01

Hepatocellular carcinoma is now a major public health concern. In intermediate stages (one third of hepatocellular carcinoma patients), chemo-embolization is the standard of care despite a poor tolerance and a moderate efficacy. Moreover, despite recent improvements, this technique seems in a dead end. Radio-embolization could be an excellent tool for such patients. Currently 131 I-Lipiodol, 188 Re-Lipiodol, 90 Y-glass or resin microspheres are available. More recent and promising data come from microspheres, but phase II and III studies are needed before drawing any conclusion. In the future, the combination of radio-embolization with systemic chemotherapy or targeted agents (particularly anti-angiogenic drugs) seems very promising. (authors)

Experimental study of Gadofluorine M enhancement in early diagnosis of radiation brain injury by MRI in rats

International Nuclear Information System (INIS)

Bai Shoumin; Liao Chengde; Guo Ruomi; Huang Ying; Liang Biling; Shen Jun; Lu Taixiang

2011-01-01

Objective: To explore the value of Gadofluorine M, a novel MRI enhancement agent,in the diagnosis the early radiation brain injury. Methods: Seventy-two Wistar rats were randomly divided into 5 equal groups. To establish the radiation injury model, the rat's posterior brain was irradiated with 0 (blank controls), 25, 35, 45, 55, and 65 Gy, respectively. After irradiation MR plain scanning and Gadofluorine M enhancement scanning (after the T1WI and T2WI scanning Gf at the dosage of 0.1 mmol/kg was injected intravenously and scanning was performed again 12 h later) were performed once a week for 8 weeks. Another 12 rats were randomly divided into 2 equal groups to exposure to 55 and 65 Gy, respectively, and MR scanning was performed once a week for 8 weeks since the third week after MR. After T1WI and T2WI scanning Gd-DTPA was injected intravenously, MR was conducted again 30 min later, and Gf was injected intravenously (Gd-DTPA enhancement and Gf enhancement contrast). The MR image and the pixel count were compared. Since the third week 2 rats from the Gf enhancement scanning group and 1 rat from the Gd-DTPA enhancement and Gf enhancement contrast were killed after MR with their brains taken out to undergo pathological examination. Results: No abnormal signal changes were found in MRI in 25 and 35 Gy groups within 2 months after irradiation. A high signal in the Gf enhancement T1WI image was found in 45, 55, and 65 Gy groups within the period of 4-6 weeks after radiation. The signal intensity was significantly higher than that of the control, 25, and 35 Gy groups (F=2.15, P<0.05). The emerge time of this signal was negatively correlated with the dose of radiation (r =-0.62, P<0.05). When there was no obvious change was found by Gd-DTPA enhancement, a high signal representing change of injury could be found in Gf enhancement in the same rat. The signal intensity was significantly enhanced in Gf enhancement compared to the Gd-DTPA enhancement (F=2.74, P<0

Spiral CT dual-phase scanning for hepatocellular carcinoma: comparison study on the peripheral enhancement and pathology

International Nuclear Information System (INIS)

Chen Wenxia; Min Pengqiu; Zhou Xiangping; Song Bin; Liu Yan; Shen Mingen; Li Zhenlin; Yang Min

2002-01-01

Objective: To compare the peripheral enhancement features of hepatocellular carcinoma (HCC) lesions in arterial and portal venous phases with histopathology, and to study the histopathologic bases of peripheral enhancement of the HCC lesions and how it affects the biologic behavior and prognosis. Methods: Forty-two histopathologically proven HCC patients were included. First, an unenhanced scanning covering the whole liver was done, and followed by arterial and portal venous phase scanning. The delay time was 20 sec and 60 sec after the injecting of contrast media. the slides of 5 μm thickness were stained with HE and the standard immunoperoxidase method using the polyclonal antibody of factor VIII-related antigen (F8RA). The pseudo capsule of the lesion, tumor invasion of the pseudo capsule, and the number of positive stained tumor vessels in the pseudo capsule were evaluated. Results: Among the 42 cases, in arterial phase, the pseudo capsule of the HCC lesions was demonstrated as hyper-or hypo-attenuation in 13 and 8 cases, respectively, and no marked pseudo capsule was perceived in 21 cases. In portal venous phase, hyper-attenuated pseudo capsule was shown in 27 cases, hypo-attenuated pseudo capsule in 2 cases, and no pseudo capsule in 13 cases. On CT scans, daughter foci were showed in 14 cases, in which 9 cases were single and 5 of 42 patients, and tumor cells invaded the pseudo capsule in 16 caes among these cases. F8RA immunohistochemical staining showed that the pseudo capsule contained rich positive staining neo-vascular structure in 15 of 25 cases, and the other 10 cases had thick pseudo capsule but few neo-vascular structure. HE staining showed no marked pseudo capsule in 17 cases, in which 8 cases exhibited no clear border between the tumor tissue and liver parenchyma. Conclusion: The peripheral enhancement features of HCC on spiral CT dural-phase scanning could reflect the histopathologic characteristics and predict the biologic behavior and prognosis

Tumor vessels and contrast enhancement of hepatocellular carcinoma demonstrated by percutaneous transhepatic portography. Report of a case

Energy Technology Data Exchange (ETDEWEB)

Fujisawa, I.; Minami, S.; Tsutsui, K.; Imura, T.; Asano, M.; Kitamura, O.; Matsumoto, M.; Ozawa, K.; Torizuka, K.

A patient with an Edmondson type I-II hepatocellular carcinoma had, at celiac angiography, a poor arterial supply but a rich portal supply as observed at percutaneous transhepatic portography, an observation not previously reported in this disease. The importance of demonstrating the vascular supply of the tumor previous to planned intravascular treatment is obvious.

Changes in signal-to-noise ratios and contrast-to-noise ratios of hypervascular hepatocellular carcinomas on ferucarbotran-enhanced dynamic MR imaging

International Nuclear Information System (INIS)

Park, Yulri; Choi, Dongil; Kim, Seong Hyun; Kim, Seung Hoon; Kim, Min Ju; Lee, Jongmee; Lim, Jae Hoon; Lee, Won Jae; Lim, Hyo K.

2006-01-01

Purpose: To verify changes in the signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of hypervascular hepatocellular carcinomas (HCCs) on ferucarbotran-enhanced dynamic T1-weighted MR imaging. Materials and methods: Fifty-two patients with 61 hypervascular HCCs underwent ferucarbotran-enhanced dynamic MR imaging, and then hepatic resection. Hypervascular HCCs were identified when definite enhancement was noted during the arterial dominant phase of three-phase MDCT. Dynamic MR Images with T1-weighted fast multiplanar spoiled gradient-recalled echo sequence (TR200/TE4.2) were obtained before and 20 s, and 1, 3, 5, and 10 min, after bolus injection of ferucarbotran. We estimated the signal intensities of tumors and livers, and calculated the SNRs and CNRs of the tumors. Results: On ferucarbotran-enhanced dynamic MR imaging, SNR measurements showed a fluctuating pattern, namely, an increase in SNR followed by a decrease and a subsequent increase (or a decrease in SNR followed by a increase and a subsequent decrease) in 50 (82.0%) of 61 tumors, a single-peak SNR pattern (highest SNR on 20 s, 1, 3, or 5 min delayed images followed by a decrease) in seven (11.5%), and a decrease in SNR followed by an increase in four (6.6%). Maximum absolute CNRs with positive value were noted on 10 min delayed images in 41 (67.2%) tumors, and maximum absolute CNRs with negative value were observed on 20 s delayed images in 12 (19.7%) and on 1 min delayed images in eight (13.1%). Conclusion: Despite showing various SNR and CNR changes, the majority of hypervascular HCCs demonstrated a fluctuating SNR pattern on ferucarbotran-enhanced dynamic MR imaging and a highest CNR on 10 min delayed image, which differed from the classic enhancement pattern on multiphasic CT

Caveolin-1 enhances resveratrol-mediated cytotoxicity and transport in a hepatocellular carcinoma model

Directory of Open Access Journals (Sweden)

Yang Hui-ling

2009-03-01

Full Text Available Abstract Background Resveratrol (RES, an estrogen analog, is considered as a potential cancer chemo-preventive agent. However, it remains unclear how RES is transported into cells. In this study, we observed that Caveolin-1(CAV1 expression can increase the cytotoxic and pro-apoptotic activity of RES in a dose- and time-dependent manner both in vitro and in vivo in a Hepatocellular Carcinoma animal model. Methods High performance liquid chromatography (HPLC demonstrated that RES intra-cellular concentration is increased about 2-fold in cells stably expressing CAV1 or CAVM1 (a scaffolding domain (81-101AA-defective CAV1 mutant compared to the untransduced human Hepatoblastoma cell line (HepG2 or after transduction with the green fluorescent protein (GFP control vector. The increased intra-cellular transport of RES was abolished in cells stably expressing CAVM2 (a cholesterol shuttle domain (143-156AA-defective CAV1 mutant or CAVRNAi. In order to further characterize CAV1-dependent RES transport, we synthesized RES-dansyl chloride derivatives as fluorescent probes to visualize the transport process, which demonstrated a distribution consistent with that of CAV1 in HepG2 cells. Results In addition, RES endocytosis was not mediated by estrogen receptor (ER α and β, as suggested by lack of competitive inhibition by estrogen or Tamoxifen. Pathway analysis showed that RES can up-regulate the expression of endogenous CAV1; this activates further the MAPK pathway and caspase-3 expression. Discussion This study provides novel insights about the role played by CAV1 in modulating cellular sensitivity to RES through enhancement of its internalization and trafficking.

Rottlerin upregulates DDX3 expression in hepatocellular carcinoma.

Science.gov (United States)

Wang, Zhong; Shen, Gen-Hai; Xie, Jia-Ming; Li, Bin; Gao, Quan-Gen

2018-01-01

Rottlerin has been reported to exert its anti-tumor activity in various types of human cancers. However, the underlying molecular mechanism has not been fully elucidated. In the current study, we explored whether rottlerin exhibits its tumor suppressive function in hepatocellular carcinoma cells. Our MTT assay results showed that rottlerin inhibited cell growth in hepatocellular carcinoma cells. Moreover, we found that rottlerin induced cell apoptosis and caused cell cycle arrest at G1 phase. Furthermore, our wound healing assay result demonstrated that rottlerin retarded cell migration in hepatocellular carcinoma cells. Additionally, rottlerin suppressed cell migration and invasion. Notably, we found that rottlerin upregulated DDX3 expression and subsequently downregulated Cyclin D1 expression and increased p21 level. Importantly, down-regulation of DDX3 abrogated the rottlerin-mediated tumor suppressive function, whereas overexpression of DDX3 promoted the anti-tumor activity of rottlerin. Our study suggests that rottlerin exhibits its anti-cancer activity partly due to upregulation of DDX3 in hepatocellular carcinoma cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Roomi, M. Waheed; Roomi, Nusrath W.; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra, E-mail: a.niedz@drrath.com; Rath, Matthias [Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050 (United States)

2012-03-23

The incidence of hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N-acetylcysteine, selenium, copper and zinc (NM) synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay), MMPs secretion (by gelatinase zymography), cell invasion (through Matrigel) and induction of apoptosis (by live green caspase). In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography) and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography) in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13-acetate (PMA) induction and inhibited by NM. In previous studies, NM inhibited Sk-Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and progression

Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Roomi, M. Waheed; Roomi, Nusrath W.; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

2012-01-01

The incidence of hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N-acetylcysteine, selenium, copper and zinc (NM) synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay), MMPs secretion (by gelatinase zymography), cell invasion (through Matrigel) and induction of apoptosis (by live green caspase). In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography) and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography) in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13-acetate (PMA) induction and inhibited by NM. In previous studies, NM inhibited Sk-Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and progression

Dysregulation of protein degradation pathways may mediate the liver injury and phospholipidosis associated with a cationic amphiphilic antibiotic drug

International Nuclear Information System (INIS)

Mosedale, Merrie; Wu, Hong; Kurtz, C. Lisa; Schmidt, Stephen P.; Adkins, Karissa; Harrill, Alison H.

2014-01-01

A large number of antibiotics are known to cause drug-induced liver injury in the clinic; however, interpreting clinical risk is not straightforward owing to a lack of predictivity of the toxicity by standard preclinical species and a poor understanding of the mechanisms of toxicity. An example is PF-04287881, a novel ketolide antibiotic that caused elevations in liver function tests in Phase I clinical studies. In this study, a mouse diversity panel (MDP), comprised of 34 genetically diverse, inbred mouse strains, was utilized to model the toxicity observed with PF-04287881 treatment and investigate potential mechanisms that may mediate the liver response. Significant elevations in serum alanine aminotransferase (ALT) levels in PF-04287881-treated animals relative to vehicle-treated controls were observed in the majority (88%) of strains tested following a seven day exposure. The average fold elevation in ALT varied by genetic background and correlated with microscopic findings of hepatocellular hypertrophy, hepatocellular single cell necrosis, and Kupffer cell vacuolation (confirmed as phospholipidosis) in the liver. Global liver mRNA expression was evaluated in a subset of four strains to identify transcript and pathway differences that distinguish susceptible mice from resistant mice in the context of PF-04287881 treatment. The protein ubiquitination pathway was highly enriched among genes associated with PF-04287881-induced hepatocellular necrosis. Expression changes associated with PF-04287881-induced phospholipidosis included genes involved in drug transport, phospholipid metabolism, and lysosomal function. The findings suggest that perturbations in genes involved in protein degradation leading to accumulation of oxidized proteins may mediate the liver injury induced by this drug. - Highlights: • Identified susceptible and resistant mouse strains to liver injury induced by a CAD • Liver injury characterized by single cell necrosis, and phospholipidosis �

Dysregulation of protein degradation pathways may mediate the liver injury and phospholipidosis associated with a cationic amphiphilic antibiotic drug

Energy Technology Data Exchange (ETDEWEB)

Mosedale, Merrie [Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Wu, Hong [Drug Safety Research and Development, Pfizer Global Research and Development, Groton, CT06340 (United States); Kurtz, C. Lisa [Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Schmidt, Stephen P. [Drug Safety Research and Development, Pfizer Global Research and Development, Groton, CT06340 (United States); Adkins, Karissa, E-mail: Karissa.Adkins@pfizer.com [Drug Safety Research and Development, Pfizer Global Research and Development, Groton, CT06340 (United States); Harrill, Alison H. [Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); University of Arkansas for Medical Sciences, Little Rock, AR72205 (United States)

2014-10-01

A large number of antibiotics are known to cause drug-induced liver injury in the clinic; however, interpreting clinical risk is not straightforward owing to a lack of predictivity of the toxicity by standard preclinical species and a poor understanding of the mechanisms of toxicity. An example is PF-04287881, a novel ketolide antibiotic that caused elevations in liver function tests in Phase I clinical studies. In this study, a mouse diversity panel (MDP), comprised of 34 genetically diverse, inbred mouse strains, was utilized to model the toxicity observed with PF-04287881 treatment and investigate potential mechanisms that may mediate the liver response. Significant elevations in serum alanine aminotransferase (ALT) levels in PF-04287881-treated animals relative to vehicle-treated controls were observed in the majority (88%) of strains tested following a seven day exposure. The average fold elevation in ALT varied by genetic background and correlated with microscopic findings of hepatocellular hypertrophy, hepatocellular single cell necrosis, and Kupffer cell vacuolation (confirmed as phospholipidosis) in the liver. Global liver mRNA expression was evaluated in a subset of four strains to identify transcript and pathway differences that distinguish susceptible mice from resistant mice in the context of PF-04287881 treatment. The protein ubiquitination pathway was highly enriched among genes associated with PF-04287881-induced hepatocellular necrosis. Expression changes associated with PF-04287881-induced phospholipidosis included genes involved in drug transport, phospholipid metabolism, and lysosomal function. The findings suggest that perturbations in genes involved in protein degradation leading to accumulation of oxidized proteins may mediate the liver injury induced by this drug. - Highlights: • Identified susceptible and resistant mouse strains to liver injury induced by a CAD • Liver injury characterized by single cell necrosis, and phospholipidosis �

Usefulness of computed tomography in diagnosis of hepatocellular carcinoma with special reference to visualization of its capsule

Energy Technology Data Exchange (ETDEWEB)

Kubo, Y; Hirai, K; Nagasaki, Y [Kurume Univ., Fukuoka (Japan). School of Medicine; Sakami, T; Motokawa, M

1981-05-01

Diagnostic significance of computed tomography was studied in 45 cases with hepatocellular carcinoma. The diagnosis was correct in 95.6%, and in 66.6% of 21 cases with encapsulated hepatoma which shows expanding growth, its capsules were demonstrated by simple or contrast enhanced CT. Capsules surrounding tumor nodules were showed characteristic features; low density area by plain CT, and markedly enhanced high density or iso-density area around tumor nodules (called ''corona sign'') by contrast medium injection.

BIOCHEMICAL NUTRITIONAL PROFILE OF LIVER CIRRHOSIS PATIENTS WITH HEPATOCELLULAR CARCINOMA

Directory of Open Access Journals (Sweden)

Gabriela Zanatta PORT

2014-03-01

Full Text Available Context Liver cirrhosis patients with hepatocellular carcinoma present nutritional alterations and metabolic disorders that negatively impact the prognosis. Objective The objective is to identify alterations in the metabolism of macro and micronutrients among liver cirrhosis patients with and without hepatocellular carcinoma and their relation to the Child-Turcote-Pugh score and Barcelona Clinic Liver Cancer staging. Methods Analytical transversal study, with 31 hepatocellular carcinoma patients and 48 liver cirrhosis patients. Laboratorial exams were carried out. The existence of an association between the biochemical parameters and the disease severity as well as the presence of hepatocellular carcinoma was assessed. Results The metabolic-nutritional profile of liver cirrhosis patients caused by the hepatitis C virus and hepatocellular carcinoma showed alterations, specifically the lipid (total cholesterol, HDL and triglycerides, protein (albumin, creatinine and uric acid, iron (transferrin, iron and ferritin saturation, hematocrit and hemoglobin, zinc and B12 vitamin profiles. There is a relation between nutritional biochemical markers and the Child-Turcote-Pugh, as well as Barcelona Clinic Liver Cancer staging. Conclusions Considering the existence of alterations in the metabolism of nutrients in liver cirrhosis patients with and without hepatocellular carcinoma, and also that conventional nutritional assessment methods present limitations for this population, the biochemical laboratorial exams are valid to complement the diagnosis of the nutritional state in a quick and practical manner.

Use of Ultrasmall Superparamagnetic Iron Oxide Enhanced Susceptibility Weighted Imaging and Mean Vessel Density Imaging to Monitor Antiangiogenic Effects of Sorafenib on Experimental Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Shuohui Yang

2017-01-01

Full Text Available We investigated effectiveness of ultrasmall superparamagnetic iron oxide enhanced susceptibility weighted imaging (USPIO-enhanced SWI and mean vessel density imaging (Q in monitoring antiangiogenic effects of Sorafenib on orthotopic hepatocellular carcinoma (HCC. Thirty-five HCC xenografts were established. USPIO-enhanced SWI and Q were performed on a 1.5 T MR scanner at baseline, 7, 14, and 21 days after Sorafenib treatment. Intratumoral susceptibility signal intensity (ITSS and Q were serially measured and compared between the treated (n = 15 and control groups (n = 15. Both ITSS and Q were significantly lower in the treated group at each time point (P < 0.05. Measurements in the treated group showed that ITSS persisted at 7 days (P = 0.669 and increased at 14 and 21 days (P < 0.05, while Q significantly declined at 7 days (P = 0.028 and gradually increased at 14 and 21 days. In the treated group, significant correlation was found between Q and histologic microvessel density (MVD (r = 0.753, P < 0.001, and ITSS correlated well with MVD (r = 0.742, P = 0.002 after excluding the data from baseline. This study demonstrated that USPIO-enhanced SWI and Q could provide novel biomarkers for evaluating antiangiogenic effects of Sorafenib on HCC.

File list: NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

Imaging and embolization of hepatocellular carcinoma supplied by gonadal artery

International Nuclear Information System (INIS)

Wu Hongping; Wang Junjie; Lu Yang; You Kaizhi

2010-01-01

Objective: To evaluate radiology and embolization for hepatocellular carcinoma supplied by gonadal artery. Methods: The medical records of 3 patients with hepatocellular carcinoma supplied by gonadal artery from August 2002 to September 2008 were reviewed. The demography, gonadal artery location, modus operandi, imaging features of liver cancer and prognosis were retrospectively analyzed. Results: Anatomic variation of gonadal artery occurred with the gonadal artery arising from the upper abdominal aorta in 1 patient and from the middle suprarenal artery in 2 patients. The blood supply of the hepatocellular carcinoma derived from the gonadal artery in all 3 patients. No complications occurred in the 6-month follow-up after embolization. Conclusion: Hepatocellular carcinoma may be supplied by gonadal artery with anomalous origin. This anatomic variant can be readily demonstrated by imaging to guide embolization. (authors)

Intraoperative ultrasound for prediction of hepatocellular carcinoma biological behaviour: Prospective comparison with pathology.

Science.gov (United States)

Santambrogio, Roberto; Cigala, Claudia; Barabino, Matteo; Maggioni, Marco; Scifo, Giovanna; Bruno, Savino; Bertolini, Emanuela; Opocher, Enrico; Bulfamante, Gaetano

2018-02-01

Preoperative prediction of both microinvasive hepatocellular carcinoma and histological grade of hepatocellular carcinoma is pivotal to treatment planning and prognostication. The aim of this study was to evaluate whether some intraoperative ultrasound features correlate with both the presence of same histological patterns and differentiation grade of hepatocellular carcinoma on the histological features of the primary resected tumour. All patients with single, small hepatocellular carcinoma that underwent hepatic resection were included in this prospective double-blind study: the intraoperative ultrasound patterns of nodule were registered and compared with similar histological features. A total of 179 patients were enclosed in this study: 97 (54%) patients (34% in HCC ≤2 cm) had a microinvasive hepatocellular carcinoma at ultrasound examination, while 82 (46%) patients (41% in HCC ≤2 cm) at histological evaluation. Statistical analysis showed that diameters ≤2 cm, presence of satellites and microinvasive hepatocellular carcinoma at ultrasound examination were the variables with the strongest association with the histological findings. In the multivariate analysis, the vascular microinfiltration and infiltrative hepatocellular carcinoma aspect were independent predictors for grading. In patients with cirrhosis and hepatocellular carcinoma, the prevalence of microinvasive hepatocellular carcinoma is high, even in cases of HCC ≤2 cm. Intraoperative ultrasound findings strongly correlated with histopathological criteria in detecting microinvasive patterns and are useful to predict neoplastic differentiation. The knowledge of these features prior to treatment are highly desired (this can be obtained by an intraoperative ultrasound examination), as they could help in providing optimal management of patients with hepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Resected Hepatocellular Carcinoma in a Patient with Crohn’s Disease on Azathioprine

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Valérie Heron

2016-05-01

Full Text Available Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn’s disease. The patient is a 61-year-old with longstanding Crohn’s disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn’s disease who present with elevated liver enzymes, especially those on azathioprine therapy.

File list: InP.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

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Exposure to Experimental Preeclampsia in Mice Enhances the Vascular Response to Future Injury

Science.gov (United States)

Pruthi, Dafina; Khankin, Eliyahu V.; Blanton, Robert M.; Aronovitz, Mark; Burke, Suzanne D.; McCurley, Amy; Karumanchi, S. Ananth; Jaffe, Iris Z.

2015-01-01

Cardiovascular disease (CVD) remains the leading killer of women in developed nations. One gender-specific risk factor is preeclampsia (PE), a syndrome of hypertension and proteinuria that complicates 5% of pregnancies. Although PE resolves after delivery, exposed women are at increased long term risk of premature CVD and mortality. Preexisting CVD risk factors are associated with increased risk of developing PE but whether PE merely uncovers risk or contributes directly to future CVD remains a critical unanswered question. A mouse PE model was used to test the hypothesis that PE causes an enhanced vascular response to future vessel injury. A PE-like state was induced in pregnant CD1 mice by overexpressing soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein that induces hypertension and glomerular disease resembling human PE. Two months post-partum, sFlt-1 levels and blood pressure normalized and cardiac size and function by echocardiography and renal histology were indistinguishable in PE-exposed compared to control mice. Mice were then challenged with unilateral carotid injury. PE-exposed mice had significantly enhanced vascular remodeling with increased vascular smooth muscle cell proliferation (180% increase, P<0.01) and vessel fibrosis (216% increase, P<0.001) compared to control pregnancy. In the contralateral uninjured vessel, there was no difference in remodeling after exposure to PE. These data support a new model in which vessels exposed to PE retain a persistently enhanced vascular response to injury despite resolution of PE after delivery. This new paradigm may contribute to the substantially increased risk of CVD in woman exposed to PE. PMID:25712723

Sharps injury reduction using a sharps container with enhanced engineering: a 28 hospital nonrandomized intervention and cohort study.

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Grimmond, Terry; Bylund, Suzann; Anglea, Candace; Beeke, Lou; Callahan, Angela; Christiansen, Erik; Flewelling, Kelly; McIntosh, Kathleen; Richter, Kay; Vitale, Monica

2010-12-01

The decrease in reported sharps injuries (SI) in the United States has markedly slowed. Additional devices and strategies need investigation. Sharps containers are associated with SI, and more than 90% of these injuries are related to container design. This study addresses the hypothesis that containers with enhanced engineering can reduce SI. In a before/after intervention study from 2006 to 2008, we examined the impact of conversion to a sharps container with enhanced engineering (the Device) on SI categories in 14 Ascension Health hospitals (study group). The Device's safety features included large horizontal aperture, sensitive counterbalanced door, large atrium, and passive overfill prevention. Study group results were also compared with a control cohort of 14 contemporaneous size-matched, Ascension Health hospitals (control group). The Device was associated with significant reductions in after-procedure (-30%), disposal-related (-57%), and container-associated (-81%) SI in the study group. No significant reductions occurred in container-associated sharps injuries in the control group. Hospitals using the Device had significantly fewer total SI than control hospitals. Enhanced aperture design can significantly reduce container-associated sharps injuries. Other factors contributing to reduced injuries may include 1-hand deposit, safe closure, hand restriction, and preassembly. These results, from a country where sharps safety devices are widespread, are particularly applicable to countries where safety devices are not extensively used. Copyright © 2010 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Contrast-Enhanced Ultrasound in the Diagnosis of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Controversy over the ASSLD Guideline

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Le-Hang Guo

2015-01-01

Full Text Available Hepatocellular carcinoma (HCC and intrahepatic cholangiocarcinoma (ICC are both regarded as primary liver cancers, having different biological behaviors and prognoses. Correct differentiation between them is essential for surgical planning and prognosis assessment. In 2005, the American Association for the Study of Liver Diseases (AASLD recommended that noninvasive diagnosis of HCC is achievable by a single dynamic technique (including contrast-enhanced ultrasound (CEUS showing intense arterial uptake followed by washout of contrast in the venous-delayed phases. However, CEUS has been dropped from the diagnostic techniques in the latest AASLD guideline according to the opinion of some authors from Europe that CEUS may offer false positive HCC diagnosis in patients with ICC. Since the update of AASLD guideline has been released, increased attention has been paid to this interesting topic. Remarkable controversy over this issue is present and this removal was not well received in Europe and Asia. This commentary summarized the opinions for the role of CUES in differentiation between HCC and ICC in recent years. It is concluded that prospective studies with strict design and large case series are mandatory to solve the controversies and stratification of ICC in terms of tumor size and liver background is also essential.

Detection of hepatocellular carcinoma in gadoxetic acid-enhanced MRI and diffusion-weighted MRI with respect to the severity of liver cirrhosis

International Nuclear Information System (INIS)

Kim, Ah Yeong; Kim, Young Kon; Lee, Min Woo; Park, Min Jung; Hwang, Jiyoung; Lee, Mi Hee; Lee, Jae Won

2012-01-01

Background As gadoxetic acid-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) have been widely used for the evaluation of hepatocellular carcinoma (HCC), it is clinically relevant to determine the diagnostic efficacy of gadoxetic acid-enhanced MRI and DWI for detection of HCCs with respect to the severity of liver cirrhosis. Purpose To compare the diagnostic accuracy and sensitivity of gadoxetic acid-enhanced MRI and DWI for detection of HCCs with respect to the severity of liver cirrhosis. Material and Methods A total of 189 patients with 240 HCCs (≤3.0 cm) (Child-Pugh A, 81 patients with 90 HCCs; Child-Pugh B, 65 patients with 85 HCCs; Child-Pugh C, 43 patients with 65 HCCs) underwent DWI and gadoxetic acid-enhanced MRI at 3.0 T. A gadoxetic acid set (dynamic and hepatobiliary phase plus T2-weighted image) and DWI set (DWI plus unenhanced MRIs) for each Child-Pugh class were analyzed independently by two observers for detecting HCCs using receiver-operating characteristic analysis. The diagnostic accuracy and sensitivity were calculated. Results There was a trend toward decreased diagnostic accuracy for gadoxetic acid and DWI set with respect to the severity of cirrhosis (Child-Pugh A [mean 0.974, 0.961], B [mean 0.904, 0.863], C [mean 0.779, 0.760]). For both observers, the sensitivities of both image sets were highest in Child-Pugh class A (mean 95.6%, 93.9%), followed by class B (mean 83.0%, 77.1%), and class C (mean 60.6%, 60.0%) (P < 0.05). Conclusion In HCC detection, the diagnostic accuracy and sensitivity for gadoxetic acid-enhanced MRI and DWI were highest in Child-Pugh class A, followed by Child-Pugh class B, and Child-Pugh class C, indicating a tendency toward decreased diagnostic capability with the severity of cirrhosis

Effect of smoking on survival of patients with hepatocellular carcinoma.

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Kolly, Philippe; Knöpfli, Marina; Dufour, Jean-François

2017-11-01

Lifestyle factors such as smoking, obesity and physical activity have gained interest in the field of hepatocellular carcinoma. These factors play a significant role in the development of hepatocellular carcinoma. Several studies revealed the impact of tobacco consumption on the development of hepatocellular carcinoma and its synergistic effects with viral etiologies (hepatitis B and C). The effects of smoking on survival in patients with a diagnosed hepatocellular carcinoma have not yet been investigated in a Western cohort where hepatitis C infection is a major risk factor. Using data from a prospective cohort of patients with hepatocellular carcinoma who were followed at the University Hospital of Bern, Switzerland, survival was compared by Kaplan-Meier analysis in smokers and nonsmokers, and multivariate Cox regression was applied to control for confounding variables. Of 238 eligible hepatocellular carcinoma patients, 64 were smokers at the time of inclusion and 174 were nonsmokers. Smokers had a significant worse overall survival than nonsmokers (hazard ratio 1.77, 95% confidence interval: 1.22-2.58, P=.003). Analysis of patients according to their underlying liver disease, revealed that smoking, and not nonsmoking, affected survival of hepatitis B virus and C virus-infected patients only. In this subgroup, smoking was an independent predictor for survival (hazard ratio 2.99, 95% confidence interval: 1.7-5.23, Phepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhancement pattern of small hepatocellular carcinoma (HCC) at contrast-enhanced US (CEUS), MDCT, and MRI: Intermodality agreement and comparison of diagnostic sensitivity between 2005 and 2010 American Association for the Study of Liver Diseases (AASLD) guidelines

International Nuclear Information System (INIS)

Furlan, Alessandro; Marin, Daniele; Cabassa, Paolo; Taibbi, Adele; Brunelli, Elena; Agnello, Francesco; Lagalla, Roberto; Brancatelli, Giuseppe

2012-01-01

Objective: To evaluate agreement between contrast-enhanced ultrasound (CEUS), multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI) for the assessment of typical and atypical enhancement patterns of small hepatocellular carcinoma (HCC); and to compare diagnostic sensitivity of 2005 and 2010 American Association for the Study of Liver Diseases (AASLD) guidelines. Materials and methods: Between January 2008 and December 2009, we included cirrhotic patients with newly diagnosed 10–20 mm HCC imaged at two contrast-enhanced imaging techniques among CEUS, MDCT, and MRI. Dynamic studies were reviewed by two radiologists to assess enhancement pattern. Percentage of cases with concordant findings and Cohen coefficient (k) were calculated. McNemar's test was used to compare sensitivity between 2005 and 2010 AASLD guidelines. Results: There were 91 patients (69 M; 22 F; mean age, 68 years) with 96 HCCs, studied with a combination of CEUS and MDCT (n = 59), CEUS and MRI (n = 26), or MDCT and MRI (n = 11). Intermodality agreement for assessment of tumor enhancement pattern was 67% (k = 0.294, P = 0.001). Typical enhancement pattern was detected coincidentally at two imaging modalities in 50 (52%) HCCs. Sensitivity for the diagnosis of HCC increased significantly using the 2010 AASLD (81/96 (84%) vs. 50/96 (52%), P < 0.001). Conclusions: Agreement between two imaging modalities for the detection of typical tumor enhancement pattern was reached in 52% of cases. The 2010 AASLD guidelines significantly increased the sensitivity for the diagnosis of HCC

Computed tomographic findings of hepatocellular carcinoma

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Eun, Chung Kie [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

1982-09-15

It is well known that CT is very useful in the evaluation of hepatocellular carcinoma. The computed tomographic findings of 56 patients diagnosed as hepatocellular carcinoma were reviewed and analyzed. The results were as follows: 1. The male to female ratio was 3 : 1 and the age ranged from 31 to 73 years with average age of 54 years. 2. Alpha-fetoprotein was positive in 19 out of 38 cases (50%). HBsAg was positive in 8 out of 33 cases (24%). 3. All lesions were seen as areas of low density except 1 case (0%) of isodensity, and 40 cases (72%) appeared to be solitary while 15 (26%) were multifocal. The low density was homogenous in 13 cases (24%) and inhomogenous in 42 cases (76%), and 18 cases out of 42 cases inhomogenous low density showed peripheal and/or central nodular enhancement. The additional findings were contour changes in 37 cases (66%), metastasis in 35 cases (63%), splenomegaly in 23 cases (42%) and ascities in 22 cases (39%). 4. In postcontrast scans, 41 cases (80%) out of 51 cases showed the change of density after contrast infusion. The presence and extent of tumors were better seen after contrast infusion in 30 cases (59%), better seen before contrast infusion in 11 cases (21%) and no significant difference before and after contrast infusion in 10 cases (20%). 5. The sites of involved lobe were right lobe in 38 cases (68%), left lobe in 5 cases (9%) and both lobes in 13 cases (23%). 6. 35 cases (63%) showed evidence of metastasis to regional lymph nodes, organ or tissues.

Exploiting bilosomes for delivering bioactive polysaccharide isolated from Enteromorpha intestinalis for hacking hepatocellular carcinoma.

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Matloub, Azza Abdelmageed; Salama, Alaa Hamed; Aglan, Hadeer Ahmed; AbouSamra, Mona Mahmoud; ElSouda, Sahar Salah Mohamed; Ahmed, Hanaa Hamdy

2018-04-01

Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing rats with EH-Bilo-2 experienced significant decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.

Hepatocellular carcinomas supplied by inferior phrenic arteries.

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Tanabe, N; Iwasaki, T; Chida, N; Suzuki, S; Akahane, T; Kobayashi, N; Ishii, M; Toyota, T

1998-07-01

To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). A total of 126 consecutive cases of HCC were studied by contract-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 1, 1, and 4. HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography.

Hepatocellular carcinomas supplied by inferior phrenic arteries

International Nuclear Information System (INIS)

Tanabe, N.; Iwasaki, T.; Akahane, T.; Kobayashi, N.; Ishii, M.; Toyota, T.; Chida, N.; Suzuki, S.

1998-01-01

Purpose: To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). Material and Methods: A total of 126 consecutive cases of HCC were studied by contrast-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. Results: In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 7, 1, and 4. Conclusion: HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography. (orig.)

Hepatocellular carcinomas supplied by inferior phrenic arteries

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Tanabe, N.; Iwasaki, T.; Akahane, T.; Kobayashi, N.; Ishii, M.; Toyota, T. [Tohoku Univ. School of Medicine (Japan). Third Dept. of Internal Medicine; Chida, N.; Suzuki, S. [National Sendai Hospital (Japan). Dept. of Gastroenterology

1998-07-01

Purpose: To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). Material and Methods: A total of 126 consecutive cases of HCC were studied by contrast-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. Results: In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 7, 1, and 4. Conclusion: HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography. (orig.)

Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.

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Huang, Shujing; Jiang, Feifei; Wang, Ying; Yu, Yanhua; Ren, Siqian; Wang, Xiaowei; Yin, Peng; Lou, Jinli

2017-06-01

Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better

Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells

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Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

2015-01-01

Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased γ-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity.Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively

Cerebrovascular Accidents Associated with Sorafenib in Hepatocellular Carcinoma

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Saif, Muhammad W.; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N.

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. La...

Giant ectopic liver, hepatocellular carcinoma and pachydermia-a rare genetic syndrome?

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Miny Peter

2011-08-01

Full Text Available Abstract Ectopic liver is a very uncommon developmental anomaly that predisposes to the development of hepatocellular carcinoma. We describe the second documented case of a hepatocellular carcinoma developing in the primary liver of a patient with a rare and uncharacterized genetic symptom complex. Also present was the largest ectopic liver ever reported, measuring 12 cm in diameter which contained a solitary focus of metastatic hepatocellular carcinoma. The primary hepatocellular carcinoma is believed to have arisen in the native liver from a hepatic adenoma that was diagnosed 15 years earlier. The patient's uncharacterised condition featured prominent thick, yellow skin over the dorsum of the fingers, and was associated with follicular hyperkeratosis, abnormal plantar creases, digital clubbing, misshaped ears, a lingua plicata and an angioleiomyolipoma of the right kidney. This unique case of hepatocellular carcinoma arising from liver cell adenoma in a patient with an uncharacterised condition featuring a large ectopic liver invites discussion of the role of local factors in carcinogenesis in the parent liver but not the ectopic liver. It also underlines the imperative ongoing need for clinical autopsies.

Dual energy spectral CT imaging for the evaluation of small hepatocellular carcinoma microvascular invasion.

Science.gov (United States)

Yang, Chuang-Bo; Zhang, Shuang; Jia, Yong-Jun; Yu, Yong; Duan, Hai-Feng; Zhang, Xi-Rong; Ma, Guang-Ming; Ren, Chenglong; Yu, Nan

2017-10-01

To study the clinical value of dual-energy spectral CT in the quantitative assessment of microvascular invasion of small hepatocellular carcinoma. This study was approved by our ethics committee. 50 patients with small hepatocellular carcinoma who underwent contrast enhanced spectral CT in arterial phase (AP) and portal venous phase (VP) were enrolled. Tumour CT value and iodine concentration (IC) were measured from spectral CT images. The slope of spectral curve, normalized iodine concentration (NIC, to abdominal aorta) and ratio of IC difference between AP and VP (RIC AP-VP : [RIC AP-VP =(IC AP -IC VP )/IC AP ]) were calculated. Tumours were identified as either with or without microvascular invasion based on pathological results. Measurements were statistically compared using independent samples t test. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of tumours microvascular invasion assessment. The 70keV images were used to simulate the results of conventional CT scans for comparison. 56 small hepatocellular carcinomas were detected with 37 lesions (Group A) with microvascular invasion and 19 (Group B) without. There were significant differences in IC, NIC and slope in AP and RIC AP-VP between Group A (2.48±0.70mg/ml, 0.23±0.05, 3.39±1.01 and 0.28±0.16) and Group B (1.65±0.47mg/ml, 0.15±0.05, 2.22±0.64 and 0.03±0.24) (all phepatocellular carcinoma with and without microvascular invasion. Quantitative iodine concentration measurement in spectral CT may be used to provide a new method to improve the evaluation for small hepatocellular carcinoma microvascular invasion. Copyright © 2017 Elsevier B.V. All rights reserved.

Current radiologic interventions in hepatocellular carcinoma

International Nuclear Information System (INIS)

Masoud, I.; Naeem, M.Q.T.; Saeed, F.; Mirza, S.A.M.; Khan, A.; Bhatti, M.A.

2006-01-01

With the rising incidence of chronic liver disease caused by viral hepatitis, hepatocellular carcinoma is showing a corresponding rise worldwide. Surgery remains the mainstay of treatment, but patients unfit for surgery or liver transplantation form the bulk of those presenting with this disease. Palliative treatments are being used to treat those and radiological modalities form the mainstay of the treatment. Radiology plays a major role in the diagnosis, treatment and follow-up of hepatocellular carcinoma. Current radiological treatment modalities include percutaneous ethanol ablation, radiofrequency ablation and trans-arterial chemoembolization. This update highlights the recent advancements in the field and compares their relative merits and demerits. (author)

Inhibition of galactosamine cytotoxicity in an in vivo/in vitro hepatocellular toxicity model

International Nuclear Information System (INIS)

MacDonald, J.R.; Thayer, K.J.; White, C.

1987-01-01

A combined in vivo/in vitro model of galactosamine hepatotoxicity was employed to test whether previously reported cytoprotective actions of cystamine administration on galactosamine-induced hepatic injury in vivo could be attributed to a direct action of cystamine on toxicant-challenged hepatocytes. In this model, male Sprague-Dawley rats received a 400 mg/kg galactosamine challenge via intraperitoneal injection 1 hr prior to portal vein cannulation for hepatocyte isolation. Isolated cells are established in monolayer culture and galactosamine-induced cellular injury is then expressed over the ensuing 24-48 hr in culture. Consistent with the biochemical basis of galactosamine-induced hepatocellular injury in vivo, cytotoxicity could be prevented by in vitro uridine treatments within 3 hr of the in vivo galactosamine challenge, but not when added 12 hr later. Cystamine, in contrast, exhibited a cytoprotective effect even when added to cultures 12 hr after the in vivo toxicant challenge. Post-toxicant cytoprotection by cystamine in vitro was concentration dependent and did not produce an alteration of hepatocyte nonprotein sulfhydryl content. Post-toxicant cytoprotection by uridine and cystamine in this in vivo/in vitro model of toxicity were fully consistent with in vivo protection from galactosamine-induced necrosis by these agents. This model eliminates potential extrahepatic mechanisms for cystamine's hepatoprotective effect and demonstrates a direct cytoprotective action on galactosamine-challenged hepatocytes

Changing incidence patterns of hepatocellular carcinoma among age groups in Taiwan.

Science.gov (United States)

Hung, Giun-Yi; Horng, Jiun-Lin; Yen, Hsiu-Ju; Lee, Chih-Ying; Lin, Li-Yih

2015-12-01

This study examined and compared the incidence patterns of hepatocellular carcinoma among age groups in Taiwan, 30 years after a universal hepatitis B virus immunization program was launched. Data for hepatocellular carcinoma diagnosed in 2003-2011 were collected from the population-based Taiwan Cancer Registry. Age-standardized incidence rates were calculated to analyze and compare the changes in incidence rates and trends. More specific analyses were performed on four age groups separated by sex. A total of 82,856 patients were diagnosed with hepatocellular carcinoma in 2003-2011 in Taiwan, yielding an age-standardized incidence rate of 32.97 per 100,000 person-years. Hepatocellular carcinoma was predominantly diagnosed in middle-aged adults (50.1%) and elderly people (49.1%), in contrast to the low incidences in children (0.04%) and adolescents and young adults (0.8%). Striking variations in trends were found for children (annual percent change: -16.6%, 2003-2010) and adolescents and young adults (annual percent change: -7.9%, 2003-2011). The incidence rate of hepatocellular carcinoma in children decreased to zero in 2011; only a slight decline in trends occurred for the middle-aged group (annual percent change: -2%, 2003-2011), and a slight upward trend was observed for elderly people (1.3%), specifically in women (1.7%). In Taiwan, hepatitis B virus-related hepatocellular carcinoma was nearly eradicated in children in 2011. The findings on age-specific incidence patterns and trends of hepatocellular carcinoma suggest that different control strategies for treating this devastating disease in the future be made according to age. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C

DEFF Research Database (Denmark)

Kimer, Nina; Dahl, Emilie Kristine; Gluud, Lise Lotte

2012-01-01

To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C.......To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C....

Detection of hepatocellular carcinoma: Comparison of gadoxetic acis-enhanced MIRI, diffusion-weighted imaging, and combined interpretation at 3 T MIRI

International Nuclear Information System (INIS)

Park, Seung Hyun; Chung, Yong Eun; Kim, Ki Whang; Kim, Myeong Jin; Hong, Hye Suk

2013-01-01

To compare diffusion-weighted imaging (DWI) and gadoxetic acid-enhanced (Gdx) magnetic resonance imaging (MRI), whether alone or in combination, for the detection of hepatocellular carcinoma (HCC) by using 3 T. 84 HCCs in 66 patients (57 men, 9 women; mean age 69.2 years) were examined using 3 T MRI. DWI (b values 0, 50, and 800 sec/mm2) and dynamic gadoxetic acid-enhanced MRI as well as hepatobiliary phase were performed. Images were retrospectively reviewed by two radiologists to compare the diagnostic performances of DWI and Gdx MRI alone and in combination for the detection of HCC. Alternative free response receiver operating characteristic analysis and comparison of sensitivities were used for statistical analysis. The sensitivity of Gdx set (73/84, 87%) was significantly higher than that of DWI set (60.5/84, 72%) for both observers. The Az values of DWI and Gdx MRI for the detection of HCC were not statistically significant for either observer (Az for DWI = 0.818 and 0.864, Az for Gdx MR = 0.902 and 0.842, respectively, p = 0.107 for observer 1 and p = 0.738 for observer 2). The combination of both techniques did not increase the sensitivities of detecting HCC in either observer. When lesions smaller than 2 cm were considered, the DWI set yielded a significantly lower sensitivity as compared with either the Gdx set alone or the combination set. Gadoxetic acid-enhanced MRI was better than DWI for detection the HCC by using 3 T MRI. The combination of DWI and Gdx MRI did not contribute to the successful detection of HCC.

Selective angiography in fifty patients with primary hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Shou-Zhong, Wang; Xing-Rong, Chen; Gong-Xian, Wang

1983-06-01

Selective angiography is of great importance in the diagnosis of primary hepatocellular carcinoma. It offers information on the findings, multicentricity, localisation, extension, and type of growth. This paper discusses angiography from the methodical point of view, the findings to be obtained, the types of hepatocellular carcinoma, and the diagnostic efficiency of selective angiography in the evaluation of this type of tumour.

Rupture of hepatocellular carcinoma following transcatheter arterial chemoembolization: A case report

Energy Technology Data Exchange (ETDEWEB)

Kang, Hyo Jin; Lee, Byung Hoon; Hwang, Yoon Joon; Kim, Su Young; Lee, Ji Young [Ilsan Paik Hospital/Inje Univ. School of Medicine, Goyang (Korea, Republic of); Han, Yoon Hee [Seonam Hospital/Ewha Womans Univ. School of Medicine, Seoul (Korea, Republic of)

2012-08-15

Transcatheter arterial chemoembolization (TACE) is known to be an effective palliative treatment for unresectable hepatocellular carcinoma (HCC). Serious complications, such as neutropenic sepsis and hepatic decompensation, are well known. A HCC rupture following TACE is a rare complication; however, it can be life threatening if it occurs. In a 75 year old male patient who subsequently developed capsular rupture of the lipiodol laden mass and several free intraperitoneal chemoembolization agents with hemoperitoneum, we report a case of a ruptured HCC that superficially located arterial enhancing and early wash out mass in the right hepatic dome following TACE.

Enhanced hepatocarcinogenesis in mouse models and human hepatocellular carcinoma by coordinate KLF6 depletion and increased messenger RNA splicing

NARCIS (Netherlands)

Vetter, Diana; Cohen-Naftaly, Michal; Villanueva, Augusto; Lee, Youngmin A.; Kocabayoglu, Peri; Hannivoort, Rebekka; Narla, Goutham; M. Llovet, Josep; Thung, Swan N.; Friedman, Scott L.

2012-01-01

KLF6-SV1 (SV1), the major splice variant of KLF6, antagonizes the KLF6 tumor suppressor by an unknown mechanism. Decreased KLF6 expression in human hepatocellular carcinoma (HCC) correlates with increased mortality, but the contribution of increased SV1 is unknown. We sought to define the impact of

Yttrium 90 microspheres for the treatment of hepatocellular carcinoma.

Science.gov (United States)

Memon, Khairuddin; Lewandowski, Robert J; Riaz, Ahsun; Salem, Riad

2013-01-01

Yttrium-90 microspheres are radioactive particles which are increasingly being employed for treating patients with unresectable hepatocellular carcinoma (HCC). The procedure is called radioembolization. It involves the injection of micron-sized embolic particles loaded with a radioisotope by use of transarterial techniques. Because of the sensitivity of liver parenchyma and relative insensitivity of tumor, external radiation has played a limited role in treating HCC. (90)Y administered via arterial route directs the highly concentrated radiation to the tumor while healthy liver parenchyma is relatively spared due to its preferential blood supply from portal venous blood. This technique has proven useful for the majority of patients with HCC as most of them present in advanced stage, beyond potentially curative options (resection/liver transplantation). (90)Y microspheres can be used in downstaging large tumors to bring within transplantable criteria, in patients with portal venous thrombosis due to tumor invasion and as palliative therapy. There are two available devices for (90)Y administration; TheraSphere® (glass based) and SIR-Spheres® (resin based). The procedure is performed on an outpatient basis. The incidence of complications is comparatively less and may include nausea, fatigue, abdominal pain, hepatic dysfunction, biliary injury, fibrosis, radiation pneumonitis, GI ulcers, and vascular injury; however, these can be avoided by meticulous pretreatment assessment, careful patient selection, and adequate dosimetry. This article explores the technical and clinical aspects of (90)Y radioembolization with keeping emphasis on patient selection, uses, and complications.

Parametric response mapping of contrast-enhanced biphasic CT for evaluating tumour viability of hepatocellular carcinoma after TACE

Energy Technology Data Exchange (ETDEWEB)

Hinrichs, Jan B.; Shin, Hoen-Oh; Kaercher, Daniel; Hasdemir, Davut; Kaireit, Till; Lutat, Carolin; Meyer, Bernhard C.; Wacker, Frank K.; Rodt, Thomas [Hannover Medical School, Department of Diagnostic and Interventional Radiology, Hannover (Germany); Murray, Tim [Beaumont Hospital, Department of Diagnostic and Interventional Radiology, Dublin (Ireland); Vogel, Arndt [Hannover Medical School, Gastroenterology, Hepatology and Endocrinology, Hannover (Germany)

2016-10-15

To determine the feasibility and role of parametric response mapping (PRM) for quantitative assessment of regional contrast-enhancement patterns in hepatocellular carcinoma (HCC). Biphasic CT of 19 patients receiving repetitive conventional transarterial chemoembolisation (cTACE) for intermediate stage HCC were retrospectively analysed at baseline and follow-up at 3, 6, and 9 months. Voxel-based registration of arterial and porto-venous phases, with segmentation of the largest target lesion was performed. Frequency distribution plots of density-pairs of segmented voxels were generated. To differentiate necrotic, hypervascular and non-hypervascular tumour, and lipiodol/calcification, thresholds of 30, 100, and 300 HU were applied. Changes in density frequency plots over time were analysed and compared to response and assessment criteria (WHO, RECIST, EASL, mRECIST) and survival. PRM was feasible in all cases. Tumour volumes and hypervascular/non-hypervascular volume ratio showed significant longitudinal decrease (p < 0.05). Hypervascular volume at baseline was inversely correlated to survival (R = -0.57, p = 0.005). The only predictive parameter following cTACE to show significant survival difference was the change of the viable/non-viable ratio (p = 0.044), whereas common response assessment criteria showed no significant difference in survival. PRM allows a quantitative and more precise assessment of regional tumour vascularisation patterns and may be helpful for TACE treatment planning and response assessment. (orig.)

TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells.

Science.gov (United States)

Li, Yang; Zhu, Danxi; Hou, Lidan; Hu, Bin; Xu, Min; Meng, Xiangjun

2018-01-01

Tribbles homolog 3 (TRB3), a type of pseudokinase that contains a consensus serine/threonine kinase catalytic core structure, is upregulated in hepatocellular carcinoma. However, the effect of TRB3 expression in hepatocellular carcinoma and the molecular mechanisms underlying TRB3-mediated effects on tumorigenesis in hepatocellular carcinoma have not been fully elucidated. The present study focused on the effect of TRB3 expression in MHCC97H hepatocellular carcinoma cells and investigated the underlying molecular mechanisms in MHCC97H cells. In the present study, it was revealed that TRB3 was significantly overexpressed in the MHCC97H hepatocellular carcinoma cell compared with L-02 normal hepatic cells. Under endoplasmic reticulum (ER) stress induced by thapsigargin and tunicamycin, the levels of TRB3, CCAAT/enhancer binding protein homologous protein (CHOP), protein kinase B (AKT) and phosphorylated (p)AKT expression were upregulated. Furthermore, when the expression of TRB3 was silenced by short hairpin (sh)RNA, the survival of MHCC97H hepatocellular carcinoma cells was increased. Notably, following transduction with lentiviral containing TRB3-shRNA, cell survival also increased after treatment with chemotherapy drug cisplatin. The present study demonstrated that knockdown of CHOP by shRNA was able to reduce TRB3 expression, and the knockdown of TRB3 markedly increased the level of pAKT. TRB3 was overexpressed in MHCC97H hepatocellular carcinoma cells, particularly under endoplasmic reticulum stress. Knockdown of TRB3 was able to increase cell survival. Therefore, TRB3 expression may induce apoptosis and reverse resistance to chemotherapy in MHCC97H hepatic carcinoma cells. The present study suggests that TRB3 is a key molecule that mediates the crosstalk between ER stress and AKT signal pathways. Furthermore, the present study may provide further insight into the cancer biology of hepatocellular carcinoma and the development of anticancer drugs targeting the ER

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

Science.gov (United States)

Li, Min; Zhang, Weiyue; Wang, Birong; Gao, Yang; Song, Zifang; Zheng, Qi Chang

2016-01-01

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC. PMID:27920520

Hepatocellular Carcinoma in Tyrosinemia Type 1 Without Clear Increase of AFP

NARCIS (Netherlands)

van Ginkel, Willem G.; Gouw, Annette S. H.; van der Jagt, Eric J.; de Jong, Koert P.; Verkade, Henkjan J.; van Spronsen, Francjan J.

Patients with hereditary tyrosinemia type 1 have an elevated risk of developing hepatocellular carcinoma, especially if initiation of treatment with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione is delayed. Hepatocellular carcinoma can usually be suspected when there are increased

Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Aleksandra Niedzwiecki

2012-03-01

Full Text Available The incidence of hepatocellular carcinoma (HCC, once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs that degrade the extracellular matrix (ECM have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N-acetylcysteine, selenium, copper and zinc (NM synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay, MMPs secretion (by gelatinase zymography, cell invasion (through Matrigel and induction of apoptosis (by live green caspase. In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13-acetate (PMA induction and inhibited by NM. In previous studies, NM inhibited Sk-Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and

Diagnostic accuracy of contrast-enhanced ultrasound for the differential diagnosis of hepatocellular carcinoma: ESCULAP versus CEUS-LI-RADS.

Science.gov (United States)

Schellhaas, Barbara; Görtz, Ruediger S; Pfeifer, Lukas; Kielisch, Christian; Neurath, Markus F; Strobel, Deike

2017-09-01

A comparison is made of two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients: Erlanger Synopsis of Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at Risk (ESCULAP) and American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADSv.2016). Focal liver lesions in 100 high-risk patients were assessed using both CEUS algorithms (ESCULAP and CEUS-LI-RADSv.2016) for a direct comparison. Lesions were categorized according to size and contrast enhancement in the arterial, portal venous and late phases.For the definite diagnosis of HCC, categories ESCULAP-4, ESCULAP-Tr and ESCULAP-V and CEUS-LI-RADS-LR-5, LR-Tr and LR-5-V were compared. In addition, CEUS-LI-RADS-category LR-M (definitely/probably malignant, but not specific for HCC) and ESCULAP-category C [intrahepatic cholangiocellular carcinoma (ICC)] were compared.Histology, CE-computed tomography and CE-MRI served as reference standards. The reference standard among 100 lesions included 87 HCCs, six ICCs and seven non-HCC-non-ICC-lesions. For the diagnosis of HCC, the diagnostic accuracy of CEUS was significantly higher with ESCULAP versus CEUS-LI-RADS (94.3%/72.4%; pdiagnostic accuracy for ICC (LR-M/ESCULAP-C) was identical with both algorithms (50%), with higher PPV for ESCULAP-C versus LR-M (75 vs. 50%). CEUS-based algorithms contribute toward standardized assessment and reporting of HCC-suspect lesions in high-risk patients. ESCULAP shows significantly higher diagnostic accuracy, sensitivity and negative predictive value with no loss of specificity compared with CEUS-LI-RADS. Both algorithms have an excellent PPV. Arterial hyperenhancement is the key feature for the diagnosis of HCC with CEUS. Washout should not be a necessary prerequisite for the diagnosis of definite HCC. CEUS-LI-RADS in its current version is inferior to ESCULAP for the noninvasive diagnosis of HCC

Chitosan nanoparticles from marine squid protect liver cells against N-diethylnitrosoamine-induced hepatocellular carcinoma.

Science.gov (United States)

Subhapradha, Namasivayam; Shanmugam, Vairamani; Shanmugam, Annaian

2017-09-01

Rationale of this study was framed to investigate the protective effect and anti-cancer property of nanoparticles based on chitosan isolated from squid, Sepioteuthis lessoniana, on hepatic cells in N-Nitrosodiethylamine-induced hepatocellular carcinoma in rats. The results conferred that the chitosan nanoparticle supplementation had a protective effect on liver cells by reducing the levels of marker enzymes and bilirubin and thus increasing the albumin levels. The level of reduced glutathione, ascorbic acid and α-tocopherol significantly increased in both post- and pre-treatment with chitosan nanoparticles. The levels of antioxidant enzymes were enhanced and lipid peroxidation products were diminished while treating nitrosodiethylamine-induced hepatocellular carcinoma with chitosan nanoparticles. Supplementation of chitosan nanoparticles had potent anti-hyperlipidemic property that was evidenced by monitoring the serum lipid levels and its components. Animals pre-treated with chitosan nanoparticles along with nitrosodiethylamine showed a significant reduction in the total cholesterol and triglycerides levels with increase in the levels of phospholipids and free fatty acids. Chitosan nanoparticles treated rats showed significant increment in high-density lipoprotein cholesterol and reduction in low-density lipoprotein and very low-density lipoprotein cholesterol when compared with levels in nitrosodiethylamine-induced hepatocellular carcinoma. Nitrosodiethylamine-induced carcinoma changes on circulation and hepatic antioxidant defense mechanism were regulated by chitosan nanoparticles, concluding that the chitosan nanoparticles have a potent protective effect on liver cells which might be due to its robust antioxidant and anti-lipidemic property. Copyright © 2017 Elsevier Ltd. All rights reserved.

The clinical significance and biological function of lncRNA RGMB-AS1 in hepatocellular carcinoma.

Science.gov (United States)

Sheng, Nan; Li, Yannan; Qian, Ruikun; Li, Yichun

2018-02-01

LncRNA RGMB-AS1 has been suggested to play significant roles in lung cancer progression. However, it remains unknown whether lncRNA RGMB-AS1 is involved in the development and progression of hepatocellular carcinoma. In our results, lncRNA RGMB-AS1 was low-expressed in hepatocellular carcinoma tissues and cell lines, and associated with clinical stage, tumor size and metastasis. Survival analysis indicated that lncRNA RGMB-AS1 high was an independent favorable prognostic factor for hepatocellular carcinoma patients. Gain-of-function studies showed up-regulated lncRNA RGMB-AS1 expression suppressed hepatocellular carcinoma cells proliferation, migration and invasion, and promoted cells apoptosis. There was a positively association between lncRNA RGMB-AS1 and RGMB in hepatocellular carcinoma tissues, and up-regulated lncRNA RGMB-AS1 expression increased RGMB mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, lncRNA RGMB-AS1 serves an anti-oncogenic role in hepatocellular carcinoma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Using the marker CD34 as tool to discriminate adenoma versus hepatocellular

International Nuclear Information System (INIS)

Mohs Alfaro, Monica

2011-01-01

The CD34 marker is used as immunohistochemistry technique to detect and differentiate between the hepatocellular adenoma of the hepatocellular carcinoma. The liver lesions are described. The hepatic angiogenesis is explained [es

Hepatocellular carcinoma

International Nuclear Information System (INIS)

Farooqi, J.I.; Farooqi, R.J.

2001-01-01

Hepatocellular carcinoma (HCC) is a common cause of cancer mortality. Hepatitis B and C viruses, aflatoxin and alga toxin in the contaminated drinking water are the major etiological factors. Rapidly progressing medical imaging has resulted in the improved treatment results. Surgical resection has a major role for influencing prognosis of HCC. Local cancer therapies based on the advances in early diagnosis are progressing rapidly. Multimodality combination and sequential treatment has proved effective, unfortunately systemic chemotherapy for HCC remains disappointed. All of these have resulted in the improved prognosis of HCC. (author)

Silencing glypican-3 expression induces apoptosis in human hepatocellular carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Liu, Shiyuan [The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu (China); Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou 730030, Gansu (China); Li, Yumin, E-mail: liym@lzu.edu.cn [The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu (China); Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou 730030, Gansu (China); Chen, Wei [Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Lanzhou University, Lanzhou 730000, Gansu (China); Zheng, Pengfei [The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu (China); Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou 730030, Gansu (China); Liu, Tao; He, Wenting; Zhang, Junqiang; Zeng, Xiangting [Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou 730030, Gansu (China)

2012-03-23

Highlights: Black-Right-Pointing-Pointer RNA interference GPC3 induces apoptosis in human hepatocellular carcinoma cell. Black-Right-Pointing-Pointer Silencing GPC3 resulted in the release of cytochrome c and activation of caspase-3. Black-Right-Pointing-Pointer GPC3 modulates the Bax/Bcl-2/cytochrome c/caspase-3 apoptotic signaling pathway. Black-Right-Pointing-Pointer Knockdown of GPC3 is a novel approach to HCC treatment. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common internal malignant tumors. Glypican-3 (GPC3) is involved in the biological and molecular events in the tumorigenesis of HCC. We used RNA interference to evaluate the molecular effects of GPC3 suppression at the translational level and demonstrated for the first time that GPC3 silencing results in a significant elevation of the Bax/Bcl-2 ratio, the release of cytochrome c from mitochondria and the activation of caspase-3. The results suggest that GPC3 regulates cell proliferation by enhancing the resistance to apoptosis through the dysfunction of the Bax/Bcl-2/cytochrome c/caspase-3 signaling pathway and therefore plays a critical role in the tumorigenesis of HCC. Thus, the knockdown of GPC3 should be further investigated as an attractive novel approach for the targeted gene therapy of HCC.

Vorinostat enhances the anticancer effect of oxaliplatin on hepatocellular carcinoma cells.

Science.gov (United States)

Liao, Bo; Zhang, Yingying; Sun, Quan; Jiang, Ping

2018-01-01

Oxaliplatin-based systemic chemotherapy has been proposed to have efficacy in hepatocellular carcinoma (HCC). We investigated the combination of vorinostat and oxaliplatin for possible synergism in HCC cells. SMMC7721, BEL7402, and HepG2 cells were treated with vorinostat and oxaliplatin. Cytotoxicity assay, tumorigenicity assay in vitro, cell cycle analysis, apoptosis analysis, western blot analysis, animal model study, immunohistochemistry, and quantitative PCR were performed. We found that vorinostat and oxaliplatin inhibited the proliferation of SMMC7721, BEL7402, and HepG2 cells. The combination index (CI) values were all vorinostat and oxaliplatin induced G2/M phase arrest, triggered caspase-dependent apoptosis, and decreased tumorigenicity both in vitro and in vivo. Vorinostat suppressed the expression of BRCA1 induced by oxaliplatin. In conclusion, cotreatment with vorinostat and oxaliplatin exhibited synergism in HCC cells. The combination inhibited cell proliferation and tumorigenicity both in vitro and in vivo through induction of cell cycle arrest and apoptosis. Our results predict that a combination of vorinostat and oxaliplatin may be useful in the treatment of advanced HCC. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

DEFF Research Database (Denmark)

Thiele, Maja; Wiest, Reiner; Gluud, Lise Lotte

2013-01-01

Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular...... and growth of hepatocellular carcinoma. Rodent and in vitro studies support the hypothesis, but clinical verification is needed. Different study designs may be considered. The feasibility of a randomized controlled trial is limited due to the necessary large number of patients and long follow......-up. Observational studies carry a high risk of bias. The meta-analytic approach may be used if the incidence and mortality of hepatocellular carcinoma can be extracted from trials on variceal bleeding and if the combined sample size and follow up is sufficient....

Hepatocellular carcinoma in Danish patients

DEFF Research Database (Denmark)

Stefansdottir, Jenna; Christensen, Erik; Schiødt, Frank Vinholt

2017-01-01

OBJECTIVE: Hepatocellular carcinoma (HCC) is a common cause of cancer, and most HCC patients have underlying cirrhosis. Retrospectively, we aimed to characterize patients with newly diagnosed HCC at a Danish hospital and to investigate survival and identify predictive factors for survival. METHODS...

Non-transplant therapies for patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B cirrhosis.

Science.gov (United States)

Granito, Alessandro; Bolondi, Luigi

2017-02-01

Underlying liver cirrhosis is present in most patients with hepatocellular carcinoma, and liver transplantation is the only treatment strategy to cure both diseases. All other hepatocellular carcinoma treatment strategies have to take into account residual liver function that concurs with the patient's prognosis and might limit their feasibility. In patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B (CPT-B), owing to borderline liver function, any intervention might be offset by liver function deterioration. In this setting, the decision for hepatocellular carcinoma treatment requires a comprehensive assessment of liver function, not restricted to the CPT classification, in addition to a careful evaluation of the prognostic effect of hepatocellular carcinoma compared with cirrhosis. In this Review, we provide an overview of the literature regarding the benefits and harms of non-transplant therapies in patients with hepatocellular carcinoma and CPT-B cirrhosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatocellular carcinoma with bile duct involvement : computed Tomographic (CT) findings

International Nuclear Information System (INIS)

Lee, Joon Woo; Han, Joon Koo; Kim, Tae Kyoung; And others

2000-01-01

To describe the radiologic features of computed tomography (CT) in hepatocellular carcinoma (HCC) with bile duct involvement. We retrospectively analyzed the two phase spiral CT findings of 31 patients in whom HCC with bile duct invasion (n=3D28) or compression (n=3D3), was diagnosed. Eight of these underwent follow up CT after transarterial chemoembolization. We analyzed the size, type, location, enhancement pattern, and lipiodol retention of parenchymal and intraductal masses, as well as their lymphadenopathy. In all patients with bile duct invasion, single or multiple masses were demonstrated in the bile ducts. Intraductal masses showed the same enhancement characteristics as the parenchymal mass (kappa 0.550, p less than 0.001), and were contiguous to this mass. In 14 of 28 patients, intraductal masses filled the peripheral intrahepatic bile ducts and extended to the common bile ducts. In the other 14, the parenchymal mass extended to the area of the porta hepatis and then directly invaded the large ducts. In nine of the 28 patients, there was a hypoattenuated cleft between the intraductal mass and ductal wall. In six, a parenchymal mass was not apparent (n=3D2), or was smaller than 2cm (n=3D4). In five of eight patients (62.5%), follow-up CT after transarterial chemoembolization showed compact or partial lipiodol retention within the intraductal mass. In patients with bile duct compression, perihilar lymph nodes were noted along with the dilated intrahepatic duct but no intra ductal mass was demonstrated in the duct. Hepatocellular carcinomas cause bile duct dilatation either by direct invasion or by extrinsic compression of the bile duct with surrounding enlarged nodes. For the diagnosis of this condition, CT is helpful. (author)

Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma.

Science.gov (United States)

Yahagi, Naoya; Shimano, Hitoshi; Hasegawa, Kiyoshi; Ohashi, Kenichi; Matsuzaka, Takashi; Najima, Yuho; Sekiya, Motohiro; Tomita, Sachiko; Okazaki, Hiroaki; Tamura, Yoshiaki; Iizuka, Yoko; Ohashi, Ken; Nagai, Ryozo; Ishibashi, Shun; Kadowaki, Takashi; Makuuchi, Masatoshi; Ohnishi, Shin; Osuga, Jun-ichi; Yamada, Nobuhiro

2005-06-01

Hepatocellular carcinoma is a very common neoplastic disease in countries where hepatitis viruses B and/or C are prevalent. Small hepatocellular carcinoma lesions detected by ultrasonography at an early stage are often hyperechoic because they are composed of well-differentiated cancer cells that are rich in triglyceride droplets. The triglyceride content of hepatocytes depends in part on the rate of lipogenesis. Key lipogenic enzymes, such as fatty acid synthase, are co-ordinately regulated at the transcriptional level. We therefore examined the mRNA expression of lipogenic enzymes in human hepatocellular carcinoma samples from 10 patients who had undergone surgical resection. All of the samples exhibited marked elevation of expression of mRNA for lipogenic enzymes, such as fatty acid synthase, acetyl-CoA carboxylase and ATP citrate lyase, compared with surrounding non-cancerous liver tissue. In contrast, the changes in mRNA expression of SREBP-1, a transcription factor that regulates a battery of lipogenic enzymes, did not show a consistent trend. In some cases where SREBP-1 was elevated, the main contributing isoform was SREBP-1c rather than SREBP-1a. Thus, lipogenic enzymes are markedly induced in hepatocellular carcinomas, and in some cases SREBP-1c is involved in this activation.

Radiofrequency (thermal) ablation versus no intervention or other interventions for hepatocellular carcinoma

DEFF Research Database (Denmark)

Weis, Sebastian; Franke, Annegret; Mössner, Joachim

2013-01-01

Hepatocellular carcinoma is the fifth most common cancer worldwide. Percutaneous interventional therapies, such as radiofrequency (thermal) ablation (RFA), have been developed for early hepatocellular carcinoma. RFA competes with other interventional techniques such as percutaneous ethanol...

Kaempferol induces hepatocellular carcinoma cell death via endoplasmic reticulum stress-CHOP-autophagy signaling pathway.

Science.gov (United States)

Guo, Haiqing; Lin, Wei; Zhang, Xiangying; Zhang, Xiaohui; Hu, Zhongjie; Li, Liying; Duan, Zhongping; Zhang, Jing; Ren, Feng

2017-10-10

Kaempferol is a flavonoid compound that has gained widespread attention due to its antitumor functions. However, the underlying mechanisms are still not clear. The present study investigated the effect of kaempferol on hepatocellular carcinoma and its underlying mechanisms. Kaempferol induced autophagy in a concentration- and time-dependent manner in HepG2 or Huh7 cells, which was evidenced by the significant increase of autophagy-related genes. Inhibition of autophagy pathway, through 3-methyladenine or Atg7 siRNA, strongly diminished kaempferol-induced apoptosis. We further hypothesized that kaempferol can induce autophagy via endoplasmic reticulum (ER) stress pathway. Indeed, blocking ER stress by 4-phenyl butyric acid (4-PBA) or knockdown of CCAAT/enhancer-binding protein homologous protein (CHOP) with siRNA alleviated kaempferol-induced HepG2 or Huh7 cells autophagy; while transfection with plasmid overexpressing CHOP reversed the effect of 4-PBA on kaempferol-induced autophagy. Our results demonstrated that kaempferol induced hepatocarcinoma cell death via ER stress and CHOP-autophagy signaling pathway; kaempferol may be used as a potential chemopreventive agent for patients with hepatocellular carcinoma.

SERUM LEPTIN LEVENS AND HEPATOCELLULAR CARCINOMA: REVIEW ARTICLE.

Science.gov (United States)

Andrighetto, Luiza Vitelo; Poziomyck, Aline Kirjner

2016-01-01

Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported. O carcinoma hepatocelular é um dos tipos mais frequentes de tumores malignos no mundo. Há crescentes evidências da relação entre o seu desenvolvimento e a obesidade. O mecanismo que os relaciona ainda não é completamente entendido. Entretanto é essencial a compreensão do tecido adiposo nas alterações metabólicas relacionadas à obesidade e ao câncer. Revisar a influência dos níveis séricos de leptina em pacientes com carcinoma hepatocelular. Trata-se de revisão bibliográfica baseada na metodologia do Instituto Cochrane; a busca de dados foi realizada na base de dados Science Direct, Scielo, Medline, Lilacs e Pubmed, empregando as seguintes descritores: hepatocellular carcinoma, leptin, adipokine. Após avaliação individual dos artigos selecionaram-se sete estudos

Mitochondrial fission promotes cell migration by Ca2+ /CaMKII/ERK/FAK pathway in hepatocellular carcinoma.

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Sun, Xiacheng; Cao, Haiyan; Zhan, Lei; Yin, Chun; Wang, Gang; Liang, Ping; Li, Jibin; Wang, Zhe; Liu, Bingrong; Huang, Qichao; Xing, Jinliang

2018-07-01

Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma (HCC) cells. However, how they influence the migration of tumour cells remained largely unknown. In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of hepatocellular carcinoma cells. Moreover, the underlying molecular mechanisms and therapeutic application were explored. Our data showed that dynamin-1-like protein expression was strongly increased in distant metastasis of hepatocellular carcinoma when compared to primary hepatocellular carcinoma. In contrast, the mitochondrial fusion protein mitofusin 1 showed an opposite trend. Moreover, the expression of dynamin-1-like protein and mitofusin 1 was significantly associated with the disease-free survival of hepatocellular carcinoma patients. In addition, our data further showed that mitochondrial fission significantly promoted the reprogramming of focal-adhesion dynamics and lamellipodia formation in hepatocellular carcinoma cells mainly by activating typical Ca 2+ /CaMKII/ERK/FAK pathway. Importantly, treatment with mitochondrial division inhibitor-1 significantly decreased calcium signalling in hepatocellular carcinoma cells and had a potential treatment effect for hepatocellular carcinoma metastasis in vivo. Taken together, our findings demonstrate that mitochondrial fission plays a critical role in the regulation of hepatocellular carcinoma cell migration, which provides strong evidence for this process as a drug target in hepatocellular carcinoma metastasis treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High MRPS23 expression contributes to hepatocellular carcinoma proliferation and indicates poor survival outcomes.

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Pu, Meng; Wang, Jianlin; Huang, Qike; Zhao, Ge; Xia, Congcong; Shang, Runze; Zhang, Zhuochao; Bian, Zhenyuan; Yang, Xishegn; Tao, Kaishan

2017-07-01

Hepatocellular carcinoma is one of the most prevalent neoplasms and the leading cause of cancer-related mortality worldwide. Mitochondrial ribosomal protein S23 is encoded by a nuclear gene and participates in mitochondrial protein translation. Mitochondrial ribosomal protein S23 overexpression has been found in many types of cancer. In this study, we explored mitochondrial ribosomal protein S23 expression in primary hepatocellular carcinoma tissues compared with matched adjacent non-tumoral liver tissues using mitochondrial ribosomal protein S23 messenger RNA and protein levels collected from public databases and clinical samples. Immunohistochemistry was performed to analyze the relationship between mitochondrial ribosomal protein S23 and various clinicopathological features. The results indicated that mitochondrial ribosomal protein S23 was significantly overexpressed in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 expression was correlated with the tumor size and tumor-metastasis-node stage. Moreover, patients with high mitochondrial ribosomal protein S23 expression levels presented poorer survival rates. Mitochondrial ribosomal protein S23 was an independent prognostic factor for survival, especially at the early stage of hepatocellular carcinoma. In addition, the downregulation of mitochondrial ribosomal protein S23 decreased the proliferation of hepatocellular carcinoma in vitro and in vivo. In conclusion, we verified for the first time that mitochondrial ribosomal protein S23 expression was upregulated in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 levels can predict poor clinical outcomes in hepatocellular carcinoma, and this protein plays a key role in tumor proliferation. Therefore, mitochondrial ribosomal protein S23 may be a potential therapeutic target for hepatocellular carcinoma.

Magnetic resonance imaging following treatment of advanced hepatocellular carcinoma with sorafenib

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Joon-Il Choi

2014-06-01

Full Text Available Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.

PGE2 suppresses intestinal T cell function in thermal injury: a cause of enhanced bacterial translocation.

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Choudhry, M A; Fazal, N; Namak, S Y; Haque, F; Ravindranath, T; Sayeed, M M

2001-09-01

Increased gut bacterial translocation in burn and trauma patients has been demonstrated in a number of previous studies, however, the mechanism for such an increased gut bacterial translocation in injured patients remains poorly understood. Utilizing a rat model of burn injury, in the present study we examined the role of intestinal immune defense by analyzing the T cell functions. We investigated if intestinal T cells dysfunction contributes to bacterial translocation after burn injury. Also our study determined if burn-mediated alterations in intestinal T cell functions are related to enhanced release of PGE2. Finally, we examined whether or not burn-related alterations in intestinal T cell function are due to inappropriate activation of signaling molecule P59fyn, which is required for T cell activation and proliferation. The results presented here showed an increase in gut bacterial accumulation in mesenteric lymph nodes after thermal injury. This was accompanied by a decrease in the intestinal T cell proliferative responses. Furthermore, the treatments of burn-injured animals with PGE2 synthesis blocker (indomethacin or NS398) prevented both the decrease in intestinal T cell proliferation and enhanced bacterial translocation. Finally, our data suggested that the inhibition of intestinal T cell proliferation could result via PGE2-mediated down-regulation of the T cell activation-signaling molecule P59fyn. These findings support a role of T cell-mediated immune defense against bacterial translocation in burn injury.

Glutathione treatment of hepatocellular carcinoma

DEFF Research Database (Denmark)

Dalhoff, K; Ranek, L; Mantoni, M

1992-01-01

This prospective study was undertaken to substantiate observations that glutathione (GSH) inhibits or reverses tumor growth in humans with hepatocellular carcinoma (HCC), a neoplasm with an extremely poor prognosis. Eight patients with biopsy-proven HCC not amenable to surgery were given 5 g of GSH...

Hydroalcoholic extract of Stevia rebaudiana bert. leaves and stevioside ameliorates lipopolysaccharide induced acute liver injury in rats.

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S, Latha; Chaudhary, Sheetal; R S, Ray

2017-11-01

Oxidative stress and hepatic inflammatory response is primarily implicated in the pathogenesis of LPS induced acute liver injury. Stevioside, a diterpenoidal glycoside isolated from the Stevia rebaudiana leaves, exerts potent anti-oxidant, anti-inflammatory and immunomodulatory activities. The present study was aimed to investigate the hepatoprotective effect of hydroalcoholic extract of Stevia rebaudiana leaves (STE EXT) and its major phytochemical constituent, stevioside (STE) in LPS induced acute liver injury. The hepatoprotective activity of STE EXT (500mg/kg p.o) and STE (250mg/kg p.o) was investigated in lipopolysaccharide (LPS 5mg/kg i.p.) induced acute liver injury in male wistar rats. Our results revealed that both STE EXT and STE treatment ameliorated LPS induced hepatic oxidative stress, evident from altered levels of reduced SOD, Catalase, GSH, MDA, NO. Histopathological observations revealed that both STE EXT and STE attenuated LPS induced structural changes and hepatocellular apoptosis providing additional evidence for its hepatoprotective effect. Further, STE EXT and STE significantly restored the elevated serum and tissue levels of AST and ALT in LPS treated rats. Furthermore, both STE EXT and STE rescued hepatocellular dysfunctions to normal by altering the level of proinflammatory cytokines such as TNF-α, IL-1β and IL-6 exhibiting its anti-inflammatory potential. In conclusion, both STE EXT and STE demonstrated excellent hepatoprotective effects against endotoxemia induced acute liver injury possibly through suppression of hepatic inflammatory response and oxidative stress, attributing to its medicinal importance in treating various liver ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma.

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Kobayashi, Tomoki; Aikata, Hiroshi; Hatooka, Masahiro; Morio, Kei; Morio, Reona; Kan, Hiromi; Fujino, Hatsue; Fukuhara, Takayuki; Masaki, Keiichi; Ohno, Atsushi; Naeshiro, Noriaki; Nakahara, Takashi; Honda, Yohji; Murakami, Eisuke; Kawaoka, Tomokazu; Tsuge, Masataka; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Hyogo, Hideyuki; Takahashi, Shoichi; Chayama, Kazuaki

2015-11-01

Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs. A total of 85 surgically resected nodules (≤30 mm) were analyzed. HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared. Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95% confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682-0.890): CEUS, 0.784 (0.679-0.889), in combination, 0.876 (0.792-0.959). The sensitivity, specificity, and accuracy were 64.1%, 95.7%, and 81.2% in EOB-MRI, 56.4%, 97.8%, and 78.8% in CEUS, and 84.6%, 95.7%, and 90.6% in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS. Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs. • Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN. • Macroscopic classification is useful to choose the treatment strategy for small HCCs. • Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal. • The diagnosis of macroscopic findings by individual modality has limitations. • Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.

Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury.

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Nakamura, Yuka; Fujita, Yuki; Ueno, Masaki; Takai, Toshiyuki; Yamashita, Toshihide

2011-01-21

Myelin components that inhibit axonal regeneration are believed to contribute significantly to the lack of axonal regeneration noted in the adult central nervous system. Three proteins found in myelin, Nogo, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein, inhibit neurite outgrowth in vitro. All of these proteins interact with the same receptors, namely, the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PIR-B). As per previous reports, corticospinal tract (CST) regeneration is not enhanced in NgR-knock-out mice after spinal cord injury. Therefore, we assessed CST regeneration in PIR-B-knock-out mice. We found that hindlimb motor function, as assessed using the Basso mouse scale, footprint test, inclined plane test, and beam walking test, did not differ between the PIR-B-knock-out and wild-type mice after dorsal hemisection of the spinal cord. Further, tracing of the CST fibers after injury did not reveal enhanced axonal regeneration or sprouting in the CST of the PIR-B-knock-out mice. Systemic administration of NEP1-40, a NgR antagonist, to PIR-B knock-out mice did not enhance the regenerative response. These results indicate that PIR-B knock-out is not sufficient to induce extensive axonal regeneration after spinal cord injury.

Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma: comparison between drug-eluting beads and lipiodol emulsion

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Monier, Arnaud; Duran, Rafael; Bize, Pierre; Dunet, Vincent; Denys, Alban [Lausanne University Hospital, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Guiu, Boris [Lausanne University Hospital, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Montpellier University Hospital, Department of Diagnostic and Interventional Radiology, Montpellier (France); Aho, Serge [University Hospital, Department of Epidemiology, Dijon (France); Deltenre, Pierre [Lausanne University Hospital, Department of Gastroenterology, Lausanne (Switzerland)

2017-04-15

To compare transarterial chemoembolization (TACE)-related hepatic toxicities of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with intermediate-stage hepatocellular carcinoma. In this retrospective study, 151 consecutive patients undergoing cTACE or DEB-TACE and MRI 3-6 weeks before and after therapy were included. Toxicity was assessed on imaging (global hepatic damages (GHD), overall biliary injuries, biliary cast, bile duct dilatation, intrahepatic biloma, portal thrombosis), and clinico-biological follow-ups. Tumour response, time to progression (TTP), and overall survival were assessed. Factors influencing complication rate were identified by generalized equation logistic regression model. Biliary injuries and intrahepatic biloma incidence were significantly higher following DEB-TACE (p < 0.001). DEB-TACE showed a significant increased risk of GHD (OR: 3.13 [1.74-5.63], p < 0.001) and biliary injuries (OR: 4.53 [2.37-8.67], p < 0.001). A significant relationship was found between baseline prothrombin value and GHD, biliary injuries and intrahepatic biloma (all p < 0.01), and between the dose of chemotherapy and intrahepatic biloma (p = 0.001). Only TTP was significantly shorter following DEB-TACE compared to cTACE (p = 0.025). DEB-TACE was associated with increased hepatic toxicities compared to cTACE. GHD, biliary injuries, and intrahepatic biloma were more frequently observed with high baseline prothrombin value, suggesting that cTACE might be more appropriate than DEB-TACE in patients with less advanced cirrhosis. (orig.)

Risks of Liver (Hepatocellular) Cancer Screening

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... cancer. Having hepatitis or cirrhosis can increase the risk of developing liver cancer. Anything that increases the ... clinical trials is available from the NCI website . Risks of Liver (Hepatocellular) Cancer Screening Key Points Screening ...

Contrast-enhanced ultrasonography and spiral computed tomography in the detection and characterization of portal vein thrombosis complicating hepatocellular carcinoma

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Rossi, Sandro; Ghittoni, Giorgia; Ravetta, Valentina; Torello Viera, Francesca; Rosa, Laura [Policlinico ' S. Matteo' Foundation, IRCCS, VI Department of Internal Medicine and Interventional Ultrasonography, Pavia (Italy); Serassi, Martina; Scabini, Mara; Vercelli, Alessandro; Calliada, Fabrizio [IRCCS Policlinico ' S. Matteo' , Department of Radiology, P.le Golgi n. 19, Pavia (Italy); Tinelli, Carmine [Biometrics Unit, IRCCS Policlinico ' S. Matteo' , Pavia (Italy); Dal Bello, Barbara [IRCCS Policlinico ' S. Matteo' , Department of Human Pathology, Pavia (Italy); Burns, Peter N. [University of Toronto, Department of Medical Biophysics, Toronto, ON (Canada); Imaging Research S660, Sunnybrook Health Science Centre, Toronto, ON (Canada)

2008-08-15

The aim was to compare the performances of contrast-enhanced (CE) ultrasonography (US) and spiral computed tomography (CT) in the detection and characterization of portal vein thrombosis complicating hepatocellular carcinoma (HCC). We studied 50 patients with HCC who had biopsy-proven portal vein thrombi that had been detected with US and color Doppler US. Thirteen of the thrombi involved the main portal trunk and 37 the segmental branches. CEUS and CT were performed within a week of thrombus biopsies. For each imaging technique, diagnoses of thrombosis (present/absent) and thrombus nature (malignancy/benignancy) were made by experienced readers under blinded conditions and compared with pathological findings to determine accuracy rates for thrombus detection and characterization. Forty-four of the 50 thrombi were pathologically diagnosed as malignant and the remaining six were benign. CEUS detected 50/50 (100%) thrombi and correctly characterized 49/50 (98%). CT detected 34/50 (68%) thrombi and correctly characterized 23 of these 34 (68%). CEUS outperformed CT in terms of both thrombus detection (P < 0.0001) and characterization (P = 0.0001). CEUS appears to be significantly superior to CT for detection and characterization of portal vein thrombosis complicating HCC, and it should be considered in the staging of these tumors. (orig.)

Diagnostic and prognostic potential of serum miR-132/212 cluster in patients with hepatocellular carcinoma.

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Wang, Feng; Wang, Jun; Ju, Linlin; Chen, Lin; Cai, Weihua; Yang, Jialin

2018-01-01

Background It has been reported that both of the miR-132/212 (micro-RNA) cluster members, miR-132 and miR-212, are downregulated in hepatocellular carcinoma. Nevertheless, the expression pattern and clinical utility of serum miR-132/212 in hepatocellular carcinoma are still unknown. Methods In this study, serum concentrations of miR-132 and miR-212 were measured in 80 hepatocellular carcinoma patients, 51 controls with chronic liver diseases and 42 healthy volunteers by using quantitative real-time polymerase chain reaction. Results In hepatocellular carcinoma patients, serum concentrations of miR-132 and miR-212 were significantly reduced and strongly correlated (r = 0.603, p hepatocellular carcinoma. Moreover, the combination of serum miR-132, miR-212 and alpha-fetoprotein improved the diagnostic efficiency for hepatocellular carcinoma, especially in sensitivity and negative predictive value. Serum miR-132 was associated with tumour differentiation degree ( p = 0.021) and tumour-node-metastasis stage ( p = 0.002); serum miR-212 correlated with tumour size ( p = 0.023) and tumour-node-metastasis stage ( p = 0.007). Kaplan-Meier analyses indicated poorer overall survival in hepatocellular carcinoma patients with lower serum concentrations of miR-132 ( p hepatocellular carcinoma.

Acute liver injury associated with a newer formulation of the herbal weight loss supplement Hydroxycut.

Science.gov (United States)

Araujo, James L; Worman, Howard J

2015-05-06

Despite the widespread use of herbal and dietary supplements (HDS), serious cases of hepatotoxicity have been reported. The popular herbal weight loss supplement, Hydroxycut, has previously been implicated in acute liver injury. Since its introduction, Hydroxycut has undergone successive transformations in its formulation; yet, cases of liver injury have remained an ongoing problem. We report a case of a 41-year-old Hispanic man who developed acute hepatocellular liver injury with associated nausea, vomiting, jaundice, fatigue and asterixis attributed to the use of a newer formulation of Hydroxycut, SX-7 Clean Sensory. The patient required hospitalisation and improved with supportive therapy. Despite successive transformations in its formulation, potential liver injury appears to remain an ongoing problem with Hydroxycut. Our case illustrates the importance of obtaining a thorough medication history, including HDS, regardless of new or reformulated product marketing efforts. 2015 BMJ Publishing Group Ltd.

Intra-abdominal solid organ injuries: an enhanced management algorithm.

Science.gov (United States)

Kokabi, Nima; Shuaib, Waqas; Xing, Minzhi; Harmouche, Elie; Wilson, Kenneth; Johnson, Jamlik-Omari; Khosa, Faisal

2014-11-01

The organ injury scale grading system proposed by the American Association for the Surgery of Trauma provides guidelines for operative versus nonoperative management in solid organ injuries; however, major shortcomings of the American Association for the Surgery of Trauma injury scale may become apparent with low-grade injuries, in which conservative management may fail. Nonoperative management of common intra-abdominal solid organ injuries relies increasingly on computed tomographic findings and other clinical factors, including patient age, presence of concurrent injuries, and serial clinical assessments. Familiarity with characteristic imaging features is essential for the prompt diagnosis and appropriate treatment of blunt abdominal trauma. In this pictorial essay, the spectrum of the American Association for the Surgery of Trauma organ injury scale grading system is illustrated, and a multidisciplinary management algorithm for common intra-abdominal solid organ injuries is proposed. Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Evaluation of hepatocellular carcinoma tumor vascularity using contrast-enhanced ultrasonography as a predictor for local recurrence following radiofrequency ablation

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Ishii, Tomohiro [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Numata, Kazushi, E-mail: kz-numa@urahp.yokohama-cu.ac.jp [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Hao, Yoshiteru; Doba, Nobutaka; Hara, Koji [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Kondo, Masaaki [Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004 (Japan); Tanaka, Katsuaki [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Maeda, Shin [Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004 (Japan)

2017-04-15

Purpose: The purpose of this study was to evaluate whether the hypervascularity of hepatocellular carcinomas (HCCs) on contrast-enhanced ultrasonography (CEUS) prior to radiofrequency ablation (RFA) is a significant risk factor for local recurrence after RFA. Materials and methods: Institutional review board approval and informed consent were obtained. Overall, 208 patients (mean age, 71.7 years; range, 50–87 years; 137 men, 71 women) with 282 HCCs treated with RFA were analyzed retrospectively. The mean maximum tumor diameter was 15.7 mm. We compared the abilities of CEUS and contrast-enhanced computed tomography (CECT) to detect hypervascularity in HCCs. We then classified the HCCs into two groups according to the arterial-phase CEUS findings: a “hypervascular group” with whole or partial hypervascular areas within the lesions compared with the surrounding liver parenchyma, and a “non-hypervascular group” with isovascular or hypovascular areas within the lesions. We assessed the cumulative rate of local recurrence after RFA, and we also evaluated the risk factors for local recurrence using a univariate analysis. Results: The detection rate for hypervascular HCCs was significantly higher using CEUS (78%, 221/282) than that using CECT (66%, 186/282) (P < 0.001). Using the CEUS findings, the cumulative rate of local recurrence was significantly higher in the hypervascular group (41.2%, 56/221) than in the non-hypervascular group (18.4%, 6/61) (P = 0.007). A univariate analysis revealed that hypervascularity on CEUS was an independent risk factor for local recurrence (P = 0.010). Conclusion: Hypervascularity in HCCs as observed using CEUS is a significant risk factor for local recurrence after RFA.

Specific diagnosis of hepatocellular carcinoma by delayed hepatobiliary imaging

International Nuclear Information System (INIS)

Hasegawa, Y.; Nakano, S.; Ibuka, K.

1986-01-01

For assessment of the value of delayed hepatobiliary imaging with technetium 99m (/sup 99m/Tc)-(Sn)-N-pyridoxyl-5-methyltryptophan (/sup 99m/Tc-PMT) for specific diagnosis of hepatocellular carcinoma, 88 patients with various malignant and benign liver diseases (49 with hepatocellular carcinoma, 4 with cholangiocellular carcinoma, 10 with metastatic liver carcinoma, 2 with liver cysts, 2 with liver hemangioma, 1 with liver abscess, 2 with intrahepatic lithiasis, 12 with liver cirrhosis, and 6 with chronic hepatitis) were studied. In 20 (41%) of the 49 patients with hepatocellular carcinoma, greater uptake of /sup 99m/Tc-PMT by the tumor than by the surrounding liver tissue was seen in delayed hepatobiliary images, whereas in eight patients (16%), equilibrated uptake was seen. No increased uptake of the radioisotope by hepatic lesions was seen in 21 patients with localized liver diseases other than hepatoma. Moreover, in 18 patients with diffuse liver diseases, no focal accumulation of the radioisotope was seen in delayed /sup 99m/Tc-PMT images. In addition, of 28 patients with hepatocellular carcinoma in whom the serum alpha-fetoprotein level showed little or no increase, 12 showed increased uptake of /sup 99m/Tc-PMT by the tumor. In assessing delayed /sup 99m/Tc-PMT images, however, it was necessary to consider following complications: accumulation of tracer in obstructed and dilated biliary trees; retention of radioactivity in nonneoplastic liver tissues; difficulties in evaluating /sup 99m/Tc-PMT uptake by small hepatic tumors; overlapping of radioactivity in the gut and gallbladder in delayed /sup 99m/Tc-PMT images of tumors. This study indicates that delayed /sup 99m/Tc-PMT images can be useful in the diagnosis of hepatocellular carcinoma

Tocilizumab-Induced Acute Liver Injury in Adult Onset Still’s Disease

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Michael Drepper

2013-01-01

Full Text Available Background. Tocilizumab, a monoclonal humanized anti-IL-6 receptor antibody, is used in treatment of refractory adult onset Still’s disease (AOSD. Mild to moderate liver enzyme elevation is a well-known side effect, but severe liver injury has only been reported in 3 cases in the literature. Case. A young female suffering from corticoid and methotrexate refractory AOSD was treated by tocilizumab. After 19 months of consecutive treatment, she developed acute severe liver injury. Liver biopsy showed extensive hepatocellular necrosis with ballooned hepatocytes, highly suggestive of drug-induced liver injury. No other relevant drug exposure beside tocilizumab was recorded. She recovered totally after treatment discontinuation and an initial 3-day course of intravenous N-acetylcysteine with normalization of liver function tests after 6 weeks. Conclusion. Acute severe hepatitis can be associated with tocilizumab as documented in this case. Careful monitoring of liver function tests is warranted during tocilizumab treatment.

Herbal Medicine and Hepatocellular Carcinoma: Applications and Challenges

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Yan Li

2011-01-01

Full Text Available Use of herbal medicine in the treatment of liver cancer has a long tradition. The compounds derived from the herb and herbal composites are of considerable interest among oncologists. In the past, certain herbal compounds and herbal composite formulas have been studied through in vitro and in vivo as an anti-hepatocellular carcinoma (HCC agent, enhancing our knowledge about their biologic functions and targets. However there is a significant distinction between the herbal medicine and the herbal production even though both are the plant-based remedies used in the practice. In this article, for the sake of clarity, the effective herbal compounds and herbal composite formulas against HCC are discussed, with emphasizing the basic conceptions of herbal medicine in order to have a better understanding of the prevention and treatment of HCC by herbal active compounds and herbal composite formulas.

Diagnostic imaging and interventional radiology of hepatocellular carcinoma: A multicenter study on 290 cases

International Nuclear Information System (INIS)

Dalla Palma, Ludovico; Puzzi Mucelli, Roberto; Sponza, Massimo; De Santis, Mario; Gandini, Giovanni; Matricardi, Luigi; Rossi, Cristina

1997-01-01

The authors report of a multicenter study on the diagnosis and interventional therapy of hepatocellular carcinoma (HCC).The first aim -diagnostic - was to evaluate the sensitivity of 4 imaging techniques, namely ultrasonography (US), Computed Tomography (CT), digital arteriography (DSA) and Lipiodol CT (LCT), in hepatocellular carcinoma detection. The accuracy of these techniques was also investigated in tumor staging, which is important for treatment planning.The second aim - treatment - consisted in assessing the therapeutic efficacy of intraarterial chemoembolization (CEAT) versus percutaneous ethanol injection (PEI) in non advanced hepatocellular carcinoma and of intraarterial chemoembolization versus no treatment (NT) in advanced hepatocellular carcinoma. Treatment efficacy was evaluated with the following randomized protocols

Lipid-coated iron oxide nanoparticles for dual-modal imaging of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Liang J

2017-03-01

Full Text Available Jinying Liang,1–3 Xinxin Zhang,2 Yunqiu Miao,2 Juan Li,1 Yong Gan2 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 3School of Pharmacy, Xinxiang Medical University, Xinxiang, People’s Republic of China Abstract: The development of noninvasive imaging techniques for the accurate diagnosis of progressive hepatocellular carcinoma (HCC is of great clinical significance and has always been desired. Herein, a hepatocellular carcinoma cell-targeting fluorescent magnetic nanoparticle (NP was obtained by conjugating near-infrared fluorescence to the surface of Fe3O4 (NIRF-Fe3O4 NPs, followed by coating the lipids consisting of tumoral hepatocytes-targeting polymer (Gal-P123. This magnetic NP (GPC@NIRF-Fe3O4 with superparamagnetic behavior showed high stability and safety in physiological conditions. In addition, GPC@NIRF-Fe3O4 achieved more specific uptake of human liver cancer cells than free Fe3O4 NPs. Importantly, with superparamagnetic iron oxide and strong NIR absorbance, GPC@NIRF-Fe3O4 NPs demonstrate prominent tumor-contrasted imaging performance both on fluorescent and T2-weighted magnetic resonance (MR imaging modalities in a living body. The relative MR signal enhancement of GPC@NIRF-Fe3O4 NPs achieved 5.4-fold improvement compared with NIR-Fe3O4 NPs. Therefore, GPC@NIRF-Fe3O4 NPs may be potentially used as a candidate for dual-modal imaging of tumors with information covalidated and directly compared by combining fluorescence and MR imaging. Keywords: dual-imaging, magnetic resonance imaging, hepatocellular carcinoma, tumor-targeting

Assessment of ablative margin after radiofrequency ablation for hepatocellular carcinoma; comparison between magnetic resonance imaging with ferucarbotran and enhanced CT with iodized oil deposition

International Nuclear Information System (INIS)

Koda, Masahiko; Tokunaga, Shiho; Fujise, Yuki; Kato, Jun; Matono, Tomomitsu; Sugihara, Takaaki; Nagahara, Takakazu; Ueki, Masaru; Murawaki, Yoshikazu; Kakite, Suguru; Yamashita, Eijiro

2012-01-01

Background and purpose: Our aim was to investigate whether magnetic resonance imaging (MRI) with ferucarbotran administered prior to radiofrequency ablation could accurately assess ablative margin when compared with enhanced computed tomography (CT) with iodized oil marking. Materials and methods: We enrolled 27 patients with 32 hepatocellular carcinomas in which iodized oil deposits were visible throughout the nodule after transcatheter arterial chemoembolization. For these nodules, radiofrequency ablation was performed after ferucarbotran administration. We then performed T2-weighted MRI after 1 week and enhanced CT after 1 month. T2-weighted MRI demonstrated the ablative margin as a low-intensity rim. We classified the margin into three grades; margin (+): high-intensity area with a continuous low-intensity rim; margin zero: high-intensity area with a discontinuous low-intensity rim; and margin (−): high-intensity area extending beyond the low-intensity rim. Results: In 28 (86%) of 32 nodules, there was agreement between MRI and CT. The overall agreement between for the two modalities in the assessment of ablative margin was good (κ = 0.759, 95% confidence interval: 0.480–1.000, p < 0.001). In four nodules, ablative margins on MRI were underestimated by one grade compared with CT. Conclusion: MRI using ferucarbotran is less invasive and allows earlier assessment than CT. The MRI technique performed similarly to enhanced CT with iodized oil marking in evaluating the ablative margin after radiofrequency ablation.

Comparison of the multi-drug resistant human hepatocellular carcinoma cell line Bel-7402/ADM model established by three methods

Directory of Open Access Journals (Sweden)

Zhong Xingguo

2010-08-01

Full Text Available Abstract Background To compare the biological characteristics of three types of human hepatocellular carcinoma multi-drug resistant cell sub-lines Bel-7402/ADM models established by three methods. Methods Established human hepatocellular carcinoma adriamycin (ADM multi-drug resistant cell sub-lines models Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS by three methods of in vitro concentration gradient increased induction, nude mice liver-implanted induction and subcutaneous-implanted induction respectively. Phase contrast microscopy was used to observe the cells and the MTT (methyl thiazolyl tetrazolium method was used to detect drug resistance of the three different sub-lines of cells. Results The three groups of drug resistant cells, Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS generated cross-resistance to ADM and CDDP (cis-Diaminedichloroplatinum, but showed a significant difference in resistance to Bel-7402 IC50 value (P V, 46 h (Bel-7402/ADML, and 45 h (Bel-7402/ADMS. The excretion rates of ADM were significantly increased compared with the parent cell (34.14% line and were 81.06% (Bel-7402/ADMV, 66.56% (Bel-7402/ADML and 61.56% (Bel-7402/ADMS. Expression of P-gp and MRP in the three groups of resistant cells was significantly enhanced (P P > 0.05. Conclusions Stable resistance was involved in the resistant cell line model established by the above three methods. Liver implantation was a good simulation of human hepatocellular and proved to be an ideal model with characteristics similar to human hepatocellular biology and the pharmacokinetics of anticancer drugs.

Small (≤ 2 cm) hepatocellular carcinoma in patients with chronic liver disease: comparison of gadoxetic acid-enhanced 3.0 T MRI and multiphasic 64-multirow detector CT.

Science.gov (United States)

Hwang, J; Kim, S H; Lee, M W; Lee, J Y

2012-07-01

To compare the diagnostic performance of gadoxetic acid-enhanced MRI using 3.0 T with that of multiphasic 64-multirow detector CT (MDCT) for the detection of small (≤2 cm) hepatocellular carcinoma (HCC) in patients with chronic liver disease. A total of 54 patients (44 men, 10 women; age range, 33-81 years) with 59 HCCs (≤2 cm in diameter) who underwent both multiphasic (arterial, portal venous, equilibrium) 64-MDCT and gadoxetic acid-enhanced 3.0 T MRI were enrolled in this study. Two observers independently and randomly reviewed the MR and CT images on a lesion-by-lesion basis. The diagnostic performance of these techniques for the detection of HCC was assessed by alternative free-response receiver operating characteristic (ROC) analysis, in addition to evaluating the sensitivity and positive predictive value. For each observer, the areas under the ROC curve were 0.874 and 0.863 for MRI, respectively, as opposed to 0.660 and 0.687 for CT, respectively. The differences between the two techniques were statistically significant for each observer (p0.05). Gadoxetic acid-enhanced 3.0 T MRI shows a better diagnostic performance than that of 64-MDCT for the detection of small (≤2 cm) HCCs in patients with chronic liver disease.

Hospital- and community-based interventions enhancing (re) employment for people with spinal cord injury : a systematic review

NARCIS (Netherlands)

Roels, E. H.; Aertgeerts, B.; Ramaekers, D.; Peers, K.

Study design: Systematic Review. Objectives: To investigate the effect of interventions enhancing (re) employment following spinal cord injury (SCI). Setting: Studies from multiple countries were included. Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL,

Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

Science.gov (United States)

Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

2017-11-01

Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dysregulation of serum microRNA-574-3p and its clinical significance in hepatocellular carcinoma.

Science.gov (United States)

Shen, Xianjuan; Xue, Yajing; Cong, Hui; Wang, Xudong; Ju, Shaoqing

2018-07-01

Objectives To explore microRNA-574-3p expression in serum of patients with hepatocellular carcinoma and investigate correlations between serum microRNA-574-3p expression and the development and prognosis of hepatocellular carcinoma. Design and methods Serum samples were collected from 70 patients with primary hepatocellular carcinoma, 40 patients with cirrhosis and 45 healthy controls. Serum microRNA-574-3p expression levels were detected by real-time quantitative polymerase chain reaction. The linearity, specificity and reproducibility were evaluated. In addition, the diagnostic value of microRNA-574-3p and its correlations with clinicopathologic features were assessed. Results The relative expression of microRNA-574-3p in hepatocellular carcinoma patients, cirrhosis patients and healthy controls was 2.306 (1.801-3.130), 1.362 (0.994-1.665) and 1.263 (0.765-1.723), respectively, indicating that it was significantly higher in hepatocellular carcinoma patients than that in the other two groups ( U = 439.5, 514.5, both P hepatocellular carcinoma patients, the relative expression of microRNA-574-3p was significantly correlated with hepatitis B virus DNA concentration ( r = 0.348, P = 0.022). Compared with healthy control group, AUC ROC of serum microRNA-574-3p in hepatocellular carcinoma group was 0.837 with 95% CI: 0.763-0.910. Combining microRNA-574-3p, AFU and alpha-fetoprotein together, the sensitivity was highest compared with other markers alone or combined. Conclusions The relative expression of serum microRNA-574-3p in hepatocellular carcinoma patients was significantly higher than that in cirrhosis patients and healthy controls, and it may be an important biomarker in the auxiliary diagnosis of hepatocellular carcinoma.

Hepatocellular Carcinoma: An Unusual Complication of Longstanding Wilson Disease.

Science.gov (United States)

Gunjan, Deepak; Shalimar; Nadda, Neeti; Kedia, Saurabh; Nayak, Baibaswata; Paul, Shashi B; Gamanagatti, Shivanand Ramachandra; Acharya, Subrat K

2017-06-01

Wilson disease is caused by the accumulation of copper in the liver, brain or other organs, due to the mutation in ATP7B gene, which encodes protein that helps in excretion of copper in the bile canaliculus. Clinical presentation varies from asymptomatic elevation of transaminases to cirrhosis with decompensation. Hepatocellular carcinoma is a known complication of cirrhosis, but a rare occurrence in Wilson disease. We present a case of neurological Wilson disease, who later developed decompensated cirrhosis and hepatocellular carcinoma.

ANGIOGENESIS INHIBITORS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA

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Massimiliano Berretta

2016-11-01

Full Text Available Background: Angiogenesis inhibitors have become an important therapeutic approach in the treatment of hepatocellular carcinoma (HCC patients. The achievement of Sorafenib in prolonging overall survival of patients with HCC makes therapeutic inhibition of angiogenesis a fundamental element of the treatment of HCC. Considering the heterogeneous aspects of HCC and to enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, the combination of antiangiogenic drugs with antiblastic chemotherapy (AC, radiotherapy or other targeted drugs have been evaluated. The issue is further complicated by the combination of antiangiogenesis with other AC or biologic drugs. To date, there is no planned approach to determine which patients are more responsive to a given type of antiangiogenic treatment. Conclusion: Large investments in the clinical research are essential to improve treatment response and minimize toxicities for patients with HCC. Future investigations will need to focus on utilizing patterns of genetic information to classify HCC into groups that display similar prognosis and treatment sensitivity, and combining targeted therapies with AC producing enhanced anti-tumor effect. In this review the current panel of available antiangiogenic therapies for the treatment of HCC have been analyzed. In addition current clinical trials are also reported herein.

Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

International Nuclear Information System (INIS)

Dugard, J.; Kew, M.C.; Da Fonseca, M.; Levin, J.

1982-01-01

Having found raised serum calcitonin concentrations is 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1 650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35,5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2 179 pg/ml). If 1 000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma

Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Dugard, J; Kew, M C; Da Fonseca, M; Levin, J [University of the Witwatersrand, Johannesburg (South Africa)

1982-08-21

Having found raised serum calcitonin concentrations in 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1,650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35.5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2,179 pg/ml). If 1,000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma.

Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

Science.gov (United States)

2015-12-01

Hepatocellular Carcinoma; Hepatoma; Liver Cancer, Adult; Liver Cell Carcinoma; Liver Cell Carcinoma, Adult; Cancer of Liver; Cancer of the Liver; Cancer, Hepatocellular; Hepatic Cancer; Hepatic Neoplasms; Hepatocellular Cancer; Liver Cancer; Neoplasms, Hepatic; Neoplasms, Liver

Pengaruh Pemberian Madu Terhadap Fungsi Hati Tikus Wistar Jantan Yang Diinduksi Monosodium Glutamat

OpenAIRE

Aliftiyo, Widi Taufik; Tjahjono DK, Kusmiyati; Johan, Andrew

2015-01-01

Background: Consuming high dose of MSG may damage liver. MSG increases oxidative stress and causing hepatocellular injury. Hepatocellular injury marked by increased transaminases serum. Honey has antioxidant properties. Honey may attenuate MSG induced hepatocellular injury.Aim: Study the effect of honey on Wistar rats's liver function which induced by MSG.Methods: This study was a true experimental study with post test randomized controlled group design. 31 samples assigned into 4 groups. K1 ...

Brain Injury Expands the Numbers of Neural Stem Cells and Progenitors in the SVZ by Enhancing Their Responsiveness to EGF

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Dhivyaa Alagappan

2009-04-01

Full Text Available There is an increase in the numbers of neural precursors in the SVZ (subventricular zone after moderate ischaemic injuries, but the extent of stem cell expansion and the resultant cell regeneration is modest. Therefore our studies have focused on understanding the signals that regulate these processes towards achieving a more robust amplification of the stem/progenitor cell pool. The goal of the present study was to evaluate the role of the EGFR [EGF (epidermal growth factor receptor] in the regenerative response of the neonatal SVZ to hypoxic/ischaemic injury. We show that injury recruits quiescent cells in the SVZ to proliferate, that they divide more rapidly and that there is increased EGFR expression on both putative stem cells and progenitors. With the amplification of the precursors in the SVZ after injury there is enhanced sensitivity to EGF, but not to FGF (fibroblast growth factor-2. EGF-dependent SVZ precursor expansion, as measured using the neurosphere assay, is lost when the EGFR is pharmacologically inhibited, and forced expression of a constitutively active EGFR is sufficient to recapitulate the exaggerated proliferation of the neural stem/progenitors that is induced by hypoxic/ischaemic brain injury. Cumulatively, our results reveal that increased EGFR signalling precedes that increase in the abundance of the putative neural stem cells and our studies implicate the EGFR as a key regulator of the expansion of SVZ precursors in response to brain injury. Thus modulating EGFR signalling represents a potential target for therapies to enhance brain repair from endogenous neural precursors following hypoxic/ischaemic and other brain injuries.

Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

DEFF Research Database (Denmark)

Lildballe, Dorte Launholt; Nguyen, Khoa Tran; Poulsen, Steen Seier

2011-01-01

No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker.......No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker....

Experimental assessment of the role of the blood flow inhibition in hyperglycemia-enhanced radiation injury to tumor

International Nuclear Information System (INIS)

Kozin, S.V.; Sevast'yanov, A.I.; Yarmonenko, S.P.

1986-01-01

Experimental assessment of the role of the blood flow inhibition in enhancement of radiation injury to tumors using short-term hyperglycemia was provided. Experiments on mice with Ehrlich solid carcinoma showed the dependence of a rise of the antitumor effect of preceding radiation induced by glucose and glucose combined with mexamin on a degree of the blood flow inhibition under the influence of these modifying agents. It was established that a considerable enhancement of radiation injury occured but in such tumors where short-term hyperglycemia and mexamin decreased the blood flow level not less than 5-10 fold as estimated by 133 Xe clearance. The results of the above experiments showed that the noticeable inhibition of the blood flow in tumors was a necessary tough, probably, not the only condition for a high efficacy of short-term hyperglycemia used an ajuvant to radiotherapy

Radiation-induced liver injury showing low intensity on T2-weighted images noted in Budd-Chiari syndrome

Energy Technology Data Exchange (ETDEWEB)

Mori, Harushi [Tokyo Univ. (Japan). Graduate School of Medicine; Yoshioka, Hiroshi; Saida, Yukihisa; Itai, Yuji [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Mori, Kensaku [Tsukuba Univ., Ibaraki (Japan). Hospital; Ahmadi, T. [Shahid Beheshti Univ. of Medical Sciences, Teheran (Iran, Islamic Republic of); Okumura, Toshiyuki [Ibaraki Prefectural Central Hospital, Tomobe (Japan)

2002-04-01

Although it is documented that radiation can cause density or intensity changes on computed tomography or MR imaging in the irradiated hepatic parenchyma, few researchers have reported or understood the MR presentation of changes in hepatic parenchyma following radiotherapy in the patient with Budd-Chiari syndrome. The purpose of this study was to investigate the MR appearance of hepatic radiation injury in Budd-Chiari syndrome and to consider the underlying pathophysiology. The MR examinations of two patients with Budd-Chiari syndrome was compared with those of 11 patients without Budd-Chiari syndrome. The two groups, both of which suffered from hepatocellular carcinoma, underwent 50-72 Gy of proton-beam irradiation during a period of 14-43 days. Examinations including T1- and T2-weighted imaging, superparamagnetic iron oxide-enhanced imaging, and dynamic study were performed 3-10 weeks after the end of irradiation. Radiation-induced hepatic injury was observed as a low-intensity area on T2-weighted images and on delayed phase images of dynamic study in the Budd-Chiari patients, and as iso- or high-intensity areas on both images in the patients without Budd-Chiari syndrome. US-guided needle biopsy from the irradiated area in one patient with Budd-Chiari syndrome revealed mostly necrotic tissue and fibrous tissue. These MR features of hepatic radiation injury in Budd-Chiari syndrome were considered to be due to severe hepatic fibrosis. (author)

Diagnostic accuracy of gadoxetic acid-enhanced MR for small hypervascular hepatocellular carcinoma and the concordance rate of Liver Imaging Reporting and Data System (LI-RADS).

Science.gov (United States)

Bae, Jae Seok; Kim, Jung Hoon; Yu, Mi Hye; Lee, Dong Ho; Kim, Hyo-Cheol; Chung, Jin Wook; Han, Joon Koo

2017-01-01

To assess diagnostic accuracy of gadoxetic acid-enhanced MR for small hypervascular hepatocellular carcinoma (HCC) detected by C-arm CT and concordance rate of Liver Imaging Reporting and Data System (LI-RADS). In this retrospective study, we recruited 4,544 patients suspected of having HCC underwent C-arm CT from November 2008 to May 2013. Among these patients, gadoxetic acid-enhanced MR was performed in 167 patients with HCC (n = 379; 257 > 1 cm, 122 ≤ 1 cm). HCC was confirmed by MR, CT, or follow-up images. Two radiologists graded likelihood of HCC and assessed MR features. Jackknife alternative free-response receiver operating characteristic (JAFROC) analysis was performed. All HCCs were evaluated concordance rate of LI-RADS. Mean JAFROC figure of merit for large (>1-cm) HCC was 0.948, while that for small HCC was 0.787 with fair agreement (κ = 0.409). Mean sensitivity and positive predictive value (PPV) were 91% and 90% for large HCC versus 63.0% and 79% for small HCC, respectively. Seventeen of 122 small HCCs (13.9%) were not visible on MR. Among 379 HCCs, 99 met LR-5, and 259 met LR-4. Common features for small HCC included arterial enhancement (81.9%), hepatobiliary phase hypointensity (80.3%), and delayed washout (72.9%). Diagnostic accuracy of gadoxetic acid-enhanced MR imaging for small, hypervascular HCCs (Mean figure of merit = 0.787) was still low compared with large HCC (Mean figure of merit = 0.948). LR-5 and LR-4 covered 94% (358/379) of the HCCs.

One stage resection of spontaneous rupture of hepatocellular carcinoma in the triangular ligament with diaphragm invasion: case report and review of the literature

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Park Kwang-Kuk

2012-09-01

Full Text Available Abstract A spontaneous rupture of hepatocellular carcinoma (HCC can lead to extensive hemorrhage and is a rare but life-threatening event. A 58-year-old male patient with no history of trauma presented at our institution with severe epigastric pain and abdominal distension for 6 h. His blood pressure was a 60/40 mmHg, and pulse rate was 132/min. Abdominal contrast enhanced computed tomography (CT imaging revealed a ruptured mass under the left diaphragm and fluid collection in the upper abdomen, flanks and pelvic cavity. Exploratory laparotomy confirmed the presence of an active bleeding tumor in the triangular ligament invading into the diaphragm. The tumor was resected with an appropriate diaphragm margin. The resected tumor was 5 cm in diameter and pathologically identified as hepatocellular carcinoma with a negative surgical margin. This case report shows that ruptured hepatocellular carcinoma should be considered in the differential diagnosis of non-traumatic hemoperitoneum. And it is necessary to set a surgical plan for unpredictable HCC rupture with direct diaphragm invasion.

Clinical significance of computed tomographic arteriography for minute hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Itoh, H; Matsui, O; Suzuki, M; Ida, M; Kitagawa, K [Kanazawa Univ. (Japan). School of Medicine

1982-03-01

Computed tomographic arteriography (CTA) can clearly demonstrate minute hepatocellular carcinoma (H.C.C.) more than 2 cm in diameter as an enhanced mass lesion. In this case the precise localization of H.C.C. becomes so obvious that CTA plays an important role to evaluate its resectability. However, H.C.C. of the size from 2 cm to 1 cm indiameter, which is visualized with celiac and infusion hepatic angiography, becomes more difficult in detection, and particularly H.C.C. of less than 1 cm in diameter can hardly be recognized, nor be diagnosed as a malignant nodule by CTA, therefore it appears that in these sizes of H.C.C. the detectability of CTA is not superior to the hepatic angiography.

MR imaging with Gd-DTPA enhancement in experimental acute injury of the spinal cord

International Nuclear Information System (INIS)

Hackney, D.B.; Asato, R.; Joseph, P.M.; McGrath, J.T.; Grossman, R.I.; Shetty, A.

1986-01-01

The authors performed MR imaging with Gd-DTPA enhancement in adult male Sprague-Dawley rats, with experimentally induced acute spinal cored injuries. After epidural compression of the spinal cored the pathologic changes of acute cord contusion were allowed to develop for 30 minutes to 4 hours. MR imaging was then performed at 1.4 T. Both short spin-echo (TR = 400 msec, TE = 15-20 msec) and long spin-echo (TR = 2,000 msec, TE = 100 msec) images were obtained. After the initial imaging, Gd-DTPA (0.1 mmol/kg) and Evans blue dye were administered intravenously and imaging was repeated. Enhancement of normal central gray matter was consistently observed. However, neither pathologic enhancement on MR images nor extravasation of Evans blue dye on histologic inspection were identified

Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

Energy Technology Data Exchange (ETDEWEB)

Gang, QiangQiang, E-mail: rousikang@163.com; Zhang, Jianing, E-mail: 1325916060@qq.com; Hao, Peng, E-mail: 1043600590@qq.com; Xu, Yikai, E-mail: yikaivip@163.com

2013-11-01

Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy.

Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

International Nuclear Information System (INIS)

Gang, QiangQiang; Zhang, Jianing; Hao, Peng; Xu, Yikai

2013-01-01

Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy

Ultrasonographic detection of hepatocellular carcinoma: correlation of preoperative ultrasonography and resected liver pathology

International Nuclear Information System (INIS)

Lim, J.H.; Kim, S.H.; Lee, W.J.; Choi, D.; Kim, S.H.; Lim, H.K.

2006-01-01

AIM: The aim of this study was to determine the sensitivity of ultrasonography for detecting hepatocellular carcinoma in patients who underwent surgical liver resection. MATERIALS AND METHODS: The preoperative ultrasonography reports of 103 patients who underwent hepatic resection surgery were retrospectively reviewed. The patients had chronic liver disease with good liver function and a relatively normal liver echotexture. The presence of a mass or masses in the resected part of the liver segments on preoperative ultrasonography was regarded as possible hepatocellular carcinoma, and these results were compared with the surgically resected hepatic lobes or segments. Accuracy for detection was assessed on a lesion-by-lesion basis, on a segment-by-segment basis, and on a patient basis. RESULTS: One hundred and fifty-seven hepatocellular carcinomas were found in 244 hepatic segments of 103 patients. One hundred and one of 157 hepatocellular carcinomas were detected using ultrasonography in 97 patients resulting in a sensitivity of 64%. In six patients, a solitary hepatocellular carcinoma was missed in each patient, a patient sensitivity being 94%. Using ultrasonography, 87 of 100 (87%) hepatocellular carcinomas larger than 2 cm in diameter, and 14 of 57 (25%) hepatocellular carcinomas 2 cm or smaller in diameter were revealed. On the basis of segment-by-segment analysis, the sensitivity was 78% (99 of 127 segments), specificity was 97% (114 of 117 segments), accuracy was 87% (213 of 244 segments), positive predictive value was 97% (99 of 102 segments), and negative predictive value was 80% (114 of 142 segments). CONCLUSION: In patients with chronic liver disease and good hepatic function, ultrasonography has a sensitivity of 94% in the identification of affected patients, but for individual lesions, the sensitivity is only 64%

Evaluation of iron colloid-enhanced T{sub 2}-weighted fast MR imaging of hepatocellular carcinoma. Comparison of SE, TSE and TGSE sequences

Energy Technology Data Exchange (ETDEWEB)

Sugihara, Shuji; Suto, Yuji; Kamba, Masayuki; Yoshida, Kotarou; Ohta, Yoshio [Tottori Univ., Yonago (Japan). Faculty of Medicine

1996-06-01

We have applied chondroitin sulfate iron colloid (CSIC) as a contrast agent for MRI in detecting hepatocellular carcinoma (HCC) on conventional spin-echo sequences (SE). In this report, we evaluated CSIC-enhanced T{sub 2}-weighted fast MR imaging of HCC. MR imaging were performed before and after i.v. administration of CSIC in 15 patients with 46 HCCs. T{sub 2}-weighted SE (1800/80/2, 210 x 256 matrix), T{sub 2}-weighted turbo spin-echo (TSE1800) (1800/90/5, echo train length=7, 252 x 256 matrix), TSE (3500/90/5, echo train length=7, 252 x 256 matrix) (TSE7), TSE (3500/99/5, echo train length=11, 242 x 256 matrix) (TSE11) and T{sub 2}-weighted turbo-gradient spine-echo (TGSE) (4500/108/4, echo train length=33, 252 x 256 matrix) images were compared quantitatively and qualitatively. In all sequences, liver signal-to-noise ratio (SNR) was significantly decreased and lesion-to-liver contrast-to-noise ratio (CNR) was significantly increased after CSIC administration. Although decreased ratio in liver and tumor SNR caused by CSIC was smaller on TSE sequences compared with SE and TGSE, increased ratio in lesion-to-liver CNR was largest on TSE7. Either before or after i.v. administration of CSIC, the number of detectable lesions was largest on TSE7. TSE with used longer TR, TE and decreased echo factor was useful method for CSIC-enhanced abdominal MR imaging. (author)

Acoustic Radiation Force Impulse Elastography for Efficacy Evaluation after Hepatocellular Carcinoma Radiofrequency Ablation: A Comparative Study with Contrast-Enhanced Ultrasound

Directory of Open Access Journals (Sweden)

Xiaohong Xu

2014-01-01

Full Text Available Aim. To explore acoustic radiation force impulse (ARFI elastography in assessing residual tumors of hepatocellular carcinoma (HCC after radiofrequency ablation (RFA. Materials and Methods. There were 83 HCC lesions among 72 patients. All patients were examined with ARFI, contrast enhanced ultrasound (CEUS, and CT or MRI. Tumor brightness on virtual touch tissue imaging (VTI and shear wave velocity (SWV were assessed before and approximately one month after RFA. Results. There were 14 residual tumors after RFA. VTI showed that all the tumors were darker after RFA. VTI was not able to distinguish the ablated lesions and the residual tumors. 13 residual tumor lesions were detected by CEUS. All completely ablated nodules had SWV demonstration of x.xx., while with those residual nodules, 6 tumors had x.xx measurement and 8 tumors had measurable SWV. nine lesions with residual tumors occurred in cirrhosis subjects and 5 lesions with residual tumors occurred in fibrosis subjects; there was no residual tumor in the normal liver subjects. Conclusion. VTI technique cannot demonstrate residual tumor post RFA. While SWV measurement of less than x.xx is likely associated with residual tumors, measurement of less than x.xx cannot exclude residual tumors. Liver cirrhosis is associated with decreased chance of a complete ablation.

Acoustic Radiation Force Impulse Elastography for Efficacy Evaluation after Hepatocellular Carcinoma Radiofrequency Ablation: A Comparative Study with Contrast-Enhanced Ultrasound

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Xu, Xiaohong; Luo, Liangping; Chen, Jiexin; Wang, Jiexin; Zhou, Honglian; Li, Mingyi; Jin, Zhanqiang; Chen, Nianping; Miao, Huilai; Lin, Manzhou; Dai, Wei; Ahuja, Anil T.; Wang, Yi-Xiang J.

2014-01-01

Aim. To explore acoustic radiation force impulse (ARFI) elastography in assessing residual tumors of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). Materials and Methods. There were 83 HCC lesions among 72 patients. All patients were examined with ARFI, contrast enhanced ultrasound (CEUS), and CT or MRI. Tumor brightness on virtual touch tissue imaging (VTI) and shear wave velocity (SWV) were assessed before and approximately one month after RFA. Results. There were 14 residual tumors after RFA. VTI showed that all the tumors were darker after RFA. VTI was not able to distinguish the ablated lesions and the residual tumors. 13 residual tumor lesions were detected by CEUS. All completely ablated nodules had SWV demonstration of x.xx., while with those residual nodules, 6 tumors had x.xx measurement and 8 tumors had measurable SWV. nine lesions with residual tumors occurred in cirrhosis subjects and 5 lesions with residual tumors occurred in fibrosis subjects; there was no residual tumor in the normal liver subjects. Conclusion. VTI technique cannot demonstrate residual tumor post RFA. While SWV measurement of less than x.xx is likely associated with residual tumors, measurement of less than x.xx cannot exclude residual tumors. Liver cirrhosis is associated with decreased chance of a complete ablation. PMID:24895624

Hepatocellular carcinoma: Implications for Asia-Pacific Oncology Nurses

Directory of Open Access Journals (Sweden)

Deborah A Boyle

2017-01-01

Full Text Available Hepatocellular carcinoma (HCC is a prominent malignancy in the Asia-Pacific region. Despite considerable knowledge about it's scope and nature this malignancy remains incurable. This manuscript reviews the epidemiology of this cancer, its pathogenesis, risk factors, potential prevention, surveillance, treatment, and the oncology nurses' role relative to this malignancy. A literature search from the past decade was performed using the PubMed and CINAHL databases using the search terms “hepatocellular carcinoma,” “Asia,” and “nursing issues”. Themes such as etiology, prevention, treatment, and prognosis were included in this synthesis which has particular relevance to oncology nurses within the Asia-Pacific region.

Knockdown of long noncoding RNA linc-ITGB1 suppresses migration, invasion of hepatocellular carcinoma via regulating ZEB1.

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Yu, W-W; Wang, K; Liao, G-J

2017-11-01

This research focuses on the influence of linc-ITGB1 on the metastasis of hepatocellular carcinoma and further explores its underlying mechanism. A total of 70 hepatocellular carcinoma patients were chosen for our study. RT-qPCR was used for detecting the expression level of linc-ITGB1 in their cancer tissues. Moreover, the expression level of linc-ITGB1 was also detected in hepatocellular carcinoma cell lines. Furthermore, whether linc-ITGB1 could affect the migrated and invaded ability of hepatocellular carcinoma cells was determined by wound healing assay and transwell assay. We further explored the potential mechanism by RT-qPCR and Western blot assay. Linc-ITGB1 expression level in hepatocellular carcinoma tissues was remarkably higher than that in adjacent tissues. Moreover, migrated and invaded ability of hepatocellular carcinoma cells was inhibited through knockdown of linc-ITGB1. Further study revealed that silenced linc-ITGB1 inhibited the expression of ZEB1 and then suppressed epithelial to mesenchymal transition (EMT), which was important during the metastasis of hepatocellular carcinoma. Moreover, the inhibition of cell invasion by silenced linc-ITGB1 could be rescued through overexpression of ZEB1 in hepatocellular carcinoma. The results indicate that linc-ITGB1, a novel oncogene in tumorigenesis, could promote the metastasis and EMT via ZEB1, which may offer a possible therapeutic target in hepatocellular carcinoma.

[Care pathway of patients with hepatocellular carcinoma in France: State of play in 2017].

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Costentin, Charlotte; Ganne-Carrié, Nathalie; Rousseau, Benoit; Gérolami, René; Barbare, Jean-Claude

2017-09-01

Hepatocellular carcinoma is a major public health problem with one of the highest overall mortality compared to other cancers. The median overall survival in France in a hospital population with hepatocellular carcinoma is 9.4 months. Several publications reported a positive impact of hepatocellular carcinoma screening on diagnosis at an early-stage, eligibility for curative treatment and overall survival. However, the identification of patients to be included in a hepatocellular carcinoma screening program and the application of screening recommendations are not optimal. Other studies suggest a potentially negative impact of delayed diagnosis or treatment initiation on the patient's prognosis. Finally, marked variations between French regions and departments have been described in terms of access to curative treatment and overall survival. In this review article, we propose a state of play of the hepatocellular carcinoma patient's care pathway in France with the aim of identifying potential breaking points with negative impact on prognosis and of developing proposals for improvement. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Gallic acid against hepatocellular carcinoma: An integrated scheme of the potential mechanisms of action from in vivo study.

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Aglan, Hadeer A; Ahmed, Hanaa H; El-Toumy, Sayed A; Mahmoud, Nadia S

2017-06-01

The global burden of hepatocellular carcinoma is increasing; actually, it is estimated as 750,000 new cases annually. This study was initiated to emphasize the possibility that gallic acid could alleviate hepatocarcinogenesis in vivo. In this study, 40 rats were enrolled and distributed as follows; group 1 was set as negative control, while all of groups 2, 3, and 4 were orally received N-nitrosodiethylamine for hepatocellular carcinoma induction. Group 2 was left untreated, whereas groups 3 and 4 were orally treated with gallic acid and doxorubicin, respectively. The current data indicated that gallic acid administration in hepatocellular carcinoma bearing rats yielded significant decline in serum levels of alpha-fetoprotein, glypican-3, and signal transducer and activator of transcription 3 along with significant enhancement in serum suppressors of cytokine signaling 3 level. Also, gallic acid-treated group displayed significant downregulation in the gene expression levels of hepatic gamma glutamyl transferase and heat shock protein gp96. Intriguingly, treatment with gallic acid remarkably ameliorated the destabilization of liver tissue architecture caused by N-nitrosodiethylamine intoxication as evidenced by histopathological investigation. In conclusion, this study demonstrates that the hepatocarcinogenic effect of N-nitrosodiethylamine can be abrogated by gallic acid supplementation owing to its affinity to regulate signal transducer and activator of transcription 3 signaling pathway through its outstanding bioactivities including antioxidant, anti-inflammatory, apoptotic, and antitumor effects.

Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report

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Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

2015-01-01

Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism

Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report.

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Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

2015-11-06

Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism.

Contrast-Enhanced Ultrasonography of Hepatocellular Carcinoma After Chemoembolisation Using Drug-Eluting Beads: A Pilot Study Focused on Sustained Tumor Necrosis

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Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina Georgiou; Kornezos, Ioannis; Matsaidonis, Dimitrios

2010-01-01

The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical-index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% ± 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% ± 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.

Hepatic parenchymal atrophy induction for intractable segmental bile duct injury after liver resection.

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Hwang, Shin; Park, Gil-Chun; Ha, Tae-Yong; Ko, Gi-Young; Gwon, Dong-Il; Choi, Young-Il; Song, Gi-Won; Lee, Sung-Gyu

2012-05-01

Liver resection can result in various types of bile duct injuries but their treatment is usually difficult and often leads to intractable clinical course. We present an unusual case of hepatic segment III duct (B3) injury, which occurred after left medial sectionectomy for large hepatocellular carcinoma and was incidentally detected 1 week later due to bile leak. Since the pattern of this B3 injury was not adequate for operative biliary reconstruction, atrophy induction of the involved hepatic parenchyma was attempted. This treatment consisted of embolization of the segment III portal branch to inhibit bile production, induction of heavy adhesion at the bile leak site and clamping of the percutaneous transhepatic biliary drainage (PTBD) tube to accelerate segment III atrophy. This entire procedure, from liver resection to PTBD tube removal took 4 months. This patient has shown no other complication or tumor recurrence for 4 years to date. These findings suggest that percutaneous segmental portal vein embolization, followed by intentional clamping of external biliary drainage, can effectively control intractable bile leak from segmental bile duct injury.

Functional image-guided stereotactic body radiation therapy planning for patients with hepatocellular carcinoma

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Tsegmed, Uranchimeg [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nakashima, Takeo [Division of Radiation Therapy, Hiroshima University Hospital, Hiroshima (Japan); Nakamura, Yuko; Higaki, Toru [Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Imano, Nobuki; Doi, Yoshiko; Kenjo, Masahiro; Ozawa, Shuichi; Murakami, Yuji [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Awai, Kazuo [Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nagata, Yasushi [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan)

2017-07-01

The aim of the current planning study is to evaluate the ability of gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI)–guided stereotactic body radiation therapy (SBRT) planning by using intensity-modulated radiation therapy (IMRT) techniques in sparing the functional liver tissues during SBRT for hepatocellular carcinoma. In this study, 20 patients with hepatocellular carcinoma were enrolled. Functional liver tissues were defined according to quantitative liver-spleen contrast ratios ≥ 1.5 on a hepatobiliary phase scan. Functional images were fused with the planning computed tomography (CT) images; the following 2 SBRT plans were designed using a “step-and-shoot” static IMRT technique for each patient: (1) an anatomical SBRT plan optimization based on the total liver; and (2) a functional SBRT plan based on the functional liver. The total prescribed dose was 48 gray (Gy) in 4 fractions. Dosimetric parameters, including dose to 95% of the planning target volume (PTV D{sub 95%}), percentages of total and functional liver volumes, which received doses from 5 to 30 Gy (V5 to V30 and fV5 to fV30), and mean doses to total and functional liver (MLD and fMLD, respectively) of the 2 plans were compared. Compared with anatomical plans, functional image-guided SBRT plans reduced MLD (mean: plan A, 5.5 Gy; and plan F, 5.1 Gy; p < 0.0001) and fMLD (mean: plan A, 5.4 Gy; and plan F, 4.9 Gy; p < 0.0001), as well as V5 to V30 and fV5 to fV30. No differences were noted in PTV coverage and nonhepatic organs at risk (OARs) doses. In conclusion, EOB-MRI–guided SBRT planning using the IMRT technique may preserve functional liver tissues in patients with hepatocellular carcinoma (HCC).

Silencing of Pokemon enhances caspase-dependent apoptosis via fas- and mitochondria-mediated pathways in hepatocellular carcinoma cells.

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Zhang, Yu-Qin; Xiao, Chuan-Xing; Lin, Bi-Yun; Shi, Ying; Liu, Yun-Peng; Liu, Jing-Jing; Guleng, Bayasi; Ren, Jian-Lin

2013-01-01

The role of Pokemon (POK erythroid myeloid ontogenic actor), a recently identified POK transcription factor with proto-oncogenic activity, in hepatocellular carcinogenesis has only been assessed by a few studies. Our previous study revealed that Pokemon is overexpressed in hepatocellular carcinomas (HCC) and promotes HCC cell proliferation and migration via an AKT- and ERK- dependent manner. In the present study, we used the TUNEL assay and FACS analysis to demonstrate that oxaliplatin induced apoptosis was significantly increased in cells with silenced Pokemon. Western blots showed that p53 expression and phosphorylation were significantly increased in Pokemon defective cells, thereby initiating the mitochondria-mediated and death receptor-mediated apoptotic pathways. In the mitochondria-mediated pathway, expression of pro-apoptotic Bcl-2 family members (including Bad, Bid, Bim and Puma) as well as AIF was increased and decreasing the mitochondrial membrane potential resulted in cytochrome C released from mitochondrial in HepG2 si-Pokemon cells. In addition, upon oxaliplatin treatment of Pokemon-silenced cells, the FAS receptor, FADD and their downstream targets caspase-10 and caspase-8 were activated, causing increased release of caspase-8 active fragments p18 and p10. Increased activated caspase-8-mediated cleavage and activation of downstream effector caspases such as caspase-9 and caspase-3 was observed in HepG2 si-Pokemon cells as compared to control. Therefore, Pokemon might serve as an important mediator of crosstalk between intrinsic and extrinsic apoptotic pathways in HCC cells. Moreover, our findings suggest that Pokemon could be an attractive therapeutic target gene for human cancer therapy.

Silencing of Pokemon enhances caspase-dependent apoptosis via fas- and mitochondria-mediated pathways in hepatocellular carcinoma cells.

Directory of Open Access Journals (Sweden)

Yu-Qin Zhang

Full Text Available The role of Pokemon (POK erythroid myeloid ontogenic actor, a recently identified POK transcription factor with proto-oncogenic activity, in hepatocellular carcinogenesis has only been assessed by a few studies. Our previous study revealed that Pokemon is overexpressed in hepatocellular carcinomas (HCC and promotes HCC cell proliferation and migration via an AKT- and ERK- dependent manner. In the present study, we used the TUNEL assay and FACS analysis to demonstrate that oxaliplatin induced apoptosis was significantly increased in cells with silenced Pokemon. Western blots showed that p53 expression and phosphorylation were significantly increased in Pokemon defective cells, thereby initiating the mitochondria-mediated and death receptor-mediated apoptotic pathways. In the mitochondria-mediated pathway, expression of pro-apoptotic Bcl-2 family members (including Bad, Bid, Bim and Puma as well as AIF was increased and decreasing the mitochondrial membrane potential resulted in cytochrome C released from mitochondrial in HepG2 si-Pokemon cells. In addition, upon oxaliplatin treatment of Pokemon-silenced cells, the FAS receptor, FADD and their downstream targets caspase-10 and caspase-8 were activated, causing increased release of caspase-8 active fragments p18 and p10. Increased activated caspase-8-mediated cleavage and activation of downstream effector caspases such as caspase-9 and caspase-3 was observed in HepG2 si-Pokemon cells as compared to control. Therefore, Pokemon might serve as an important mediator of crosstalk between intrinsic and extrinsic apoptotic pathways in HCC cells. Moreover, our findings suggest that Pokemon could be an attractive therapeutic target gene for human cancer therapy.

Role of microRNA-7 and selenoprotein P in hepatocellular carcinoma.

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Tarek, Marwa; Louka, Manal Louis; Khairy, Eman; Ali-Labib, Randa; Zakaria Zaky, Doaa; Montasser, Iman F

2017-05-01

There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. In this regard, the aim of this study was to evaluate and correlate both relative quantification of microRNA-7 using quantitative real time polymerase chain reaction and quantitative analysis of selenoprotein P using enzyme-linked immunosorbent assay in sera of hepatocellular carcinoma patients, chronic liver disease patients, as well as normal healthy subjects in order to establish a new diagnostic biomarker with a valid non-invasive technique. In addition, this study aimed to investigate whether changes in selenium supply affect microRNA-7 expression and selenoprotein P levels in human hepatocarcinoma cell line (HepG2). The results showed a highly significant decrease in serum microRNA-7 relative quantification values and selenoprotein P levels in malignant group in comparison with benign and control groups. The best cutoff for serum microRNA-7 and selenoprotein P to discriminate hepatocellular carcinoma group from benign and control groups was 0.06 and 4.30 mg/L, respectively. Furthermore, this study showed that changes in selenium supply to HepG2 cell line can alter the microRNA-7 profile and are paralleled by changes in the concentration of its target protein (selenoprotein P). Hence, serum microRNA-7 and selenoprotein P appear to be potential non-invasive diagnostic markers for hepatocellular carcinoma. Moreover, the results suggest that selenium could be used as an anticancer therapy for hepatocellular carcinoma by affecting both microRNA-7 and selenoprotein P.

Histopathology of hepatocellular carcinoma.

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Schlageter, Manuel; Terracciano, Luigi Maria; D'Angelo, Salvatore; Sorrentino, Paolo

2014-11-21

Hepatocellular carcinoma (HCC) is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide. Its etiology is usually linked to environmental, dietary or life-style factors. HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed. Although this process is yet to be completely understood, this changing scenario also has impact on the material seen by pathologists, presenting them with new diagnostic dilemmas. Histopathologic criteria for diagnosing classical, progressed HCC are well established and known, but with an increase in detection of small and early HCCs due to routine screening programs, the diagnosis of these small lesions in core needle biopsies poses a difficult challenge. These lesions can be far more difficult to distinguish from one another than progressed HCC, which is usually a clear cut hematoxylin and eosin diagnosis. Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO. This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification. Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.

Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10 production in HBV-induced hepatocellular carcinoma

International Nuclear Information System (INIS)

Shi, Yang; Song, Qingwei; Hu, Dianhe; Zhuang, Xiaohu; Yu, Shengcai

2015-01-01

Hepatocellular carcinoma (HCC) is one of the most common cancers and can be induced by chronic HBV infection. The role of HBV-specific immune responses in mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here, we examined resected tumor tissue from 36 patients with HBV-induced HCC. We categorized study cohort based on ex vivo IL-10 secretion by tumor cells into high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10 group contained higher frequencies of HBV-specific IFN-g-producing cells and total IFN-g-producing cells, and possessed higher proliferative capacity. Moreover, the proliferative capacity of TILs from the Hi10 group was negatively correlated with IL-10 secretion from tumor cells. Together, our data demonstrated that low IL-10-producing capacity in HBV-induced HCC tumors is associated with enhanced TIL activity. - Highlights: • We examined intratumoral IL-10 production in HBV-induced HCC. • We grouped HCC tumors into Hi10 and Lo10 groups based on their IL-10 production. • Lo10 groups had better IFN-g response by TILs. • Lo10 groups had better TIL proliferative capacity. • Lo10 group tumor cells were refractory to TLR ligand stimulation

Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10 production in HBV-induced hepatocellular carcinoma

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Shi, Yang, E-mail: yangshi_xz@126.com; Song, Qingwei; Hu, Dianhe; Zhuang, Xiaohu; Yu, Shengcai

2015-05-22

Hepatocellular carcinoma (HCC) is one of the most common cancers and can be induced by chronic HBV infection. The role of HBV-specific immune responses in mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here, we examined resected tumor tissue from 36 patients with HBV-induced HCC. We categorized study cohort based on ex vivo IL-10 secretion by tumor cells into high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10 group contained higher frequencies of HBV-specific IFN-g-producing cells and total IFN-g-producing cells, and possessed higher proliferative capacity. Moreover, the proliferative capacity of TILs from the Hi10 group was negatively correlated with IL-10 secretion from tumor cells. Together, our data demonstrated that low IL-10-producing capacity in HBV-induced HCC tumors is associated with enhanced TIL activity. - Highlights: • We examined intratumoral IL-10 production in HBV-induced HCC. • We grouped HCC tumors into Hi10 and Lo10 groups based on their IL-10 production. • Lo10 groups had better IFN-g response by TILs. • Lo10 groups had better TIL proliferative capacity. • Lo10 group tumor cells were refractory to TLR ligand stimulation.

Synergistic effect of oral corticosteroids use on risk of hepatocellular carcinoma in high risk populations.

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Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

2018-06-01

Little evidence is available on the relationship between oral corticosteroids use and hepatocellular carcinoma. The objective of this study was to investigate whether oral corticosteroids use correlates with the risk of hepatocellular carcinoma in high risk populations in Taiwan. Using representative claims database established from the Taiwan National Health Insurance Program with a population coverage rate of 99.6%, we identified 102,182 subjects aged 20-84 years with newly diagnosed hepatocellular carcinoma in 2000-2011 as the cases and 102,182 randomly selected subjects aged 20-84 years without hepatocellular carcinoma as the matched controls. In subjects with any one of comorbidities including alcohol-related disease, chronic liver disease, and diabetes mellitus, the adjusted OR of hepatocellular carcinoma was 29.9 (95% CI 28.7, 31.1) for subjects with never use of oral corticosteroids, and the adjusted OR would increase to 33.7 (95% CI 32.3, 35.3) for those with ever use of oral corticosteroids. The adjusted OR of hepatocellular carcinoma was 1.03 for subjects with increasing cumulative duration of oral corticosteroids use for every one year (95% CI 1.01, 1.06), with a duration-dependent effect. The largest OR occurred in subjects with ever use of oral corticosteroids and concurrently comorbid with alcohol-related disease, chronic liver disease, and diabetes mellitus (adjusted OR 122.7, 95% CI 108.5, 138.8). There is a synergistic effect between oral corticosteroids use and the traditional risk factors on the risk of hepatocellular carcinoma. People with risk factors for hepatocellular carcinoma should receive regular ultrasound surveillance, particularly when they currently use oral corticosteroids. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats.

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Shiotani, Satoko; Shimada, Mitsuo; Suehiro, Taketoshi; Soejima, Yuji; Yosizumi, Tomoharu; Shimokawa, Hiroaki; Maehara, Yoshihiko

2004-08-15

Reperfusion of ischemic tissues is known to cause the generation of reactive oxygen species (ROS) with resultant tissue damage. However, the sources of ROS in reperfused tissues are not fully characterized. We hypothesized that the small GTPase Rho and its target effector Rho-kinase/ROK/ROCK are involved in the oxidative burst in reperfused tissue with resultant reperfusion injury. In an in vivo rat model of liver transplantation using cold ischemia for 12 hr followed by reperfusion, a specific Rho-kinase inhibitor, fasudil (30 mg/kg), was administered orally 1 hr before the transplantation. Fasudil suppressed the ischemia-reperfusion (I/R)-induced generation of ROS after reperfusion (P<0.01) and also suppressed the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) 3 hr after reperfusion, resulting in a significant reduction of I/R-induced hepatocellular injury (P<0.05), necrosis, apoptosis (P<0.01), and neutrophil infiltration (P<0.0001) 12 hr after reperfusion. All animals receiving a graft without fasudil died within 3 days, whereas 40% of those receiving fasudil survived (P<0.001). The present study demonstrates that Rho-kinase-mediated production of ROS and inflammatory cytokines are substantially involved in the pathogenesis of hepatocellular necrosis and apoptosis induced by cold I/R in vivo and that Rho-kinase may be regarded as a novel therapeutic target for the disorder.

The application of Fasudil in treating vascular spasm occurred in interventional treatment for hepatocellular carcinomas

International Nuclear Information System (INIS)

Fan Xiaoqiang; Shen Jie; Zhang Xuena; Liu Qiuru; Ma Aiying

2011-01-01

Objective: To explore an effective way to treat the vascular spasm occurred during TACE for hepatocellular carcinomas. Methods: During interventional chemoembolization for hepatocellular carcinomas, Fasudil of 2.5 mg was injected via the catheter if vessel spasm occurred, which was followed by DSA to determine the dilatation of the arteries. Adverse effect was observed and recorded. Results: After the injection of Fasudil the vascular spasm was completely relieved in all the 30 cases. The interventional procedure for hepatocellular carcinomas was successfully accomplished in all patients. No obvious side effect occurred. Conclusion: The injection of Fasudil via the catheter is an effective and safe method to eliminate vessel spasm occurred during TACE for hepatocellular carcinomas. (authors)

MicroRNA-mediated Th2 bias in methimazole-induced acute liver injury in mice

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Uematsu, Yasuaki; Akai, Sho; Tochitani, Tomoaki; Oda, Shingo; Yamada, Toru; Yokoi, Tsuyoshi

2016-01-01

MicroRNA (miRNA) is a class of small non-coding RNAs containing approximately 20 nucleotides that negatively regulate target gene expression. Little is known about the role of individual miRNAs and their targets in immune- and inflammation-related responses in drug-induced liver injury. In the present study, involvement of miRNAs in the T helper (Th) 2-type immune response was investigated using a methimazole (MTZ)-induced liver injury mouse model. Co-administration of L-buthionine-S,R-sulfoximine and MTZ induced acute hepatocellular necrosis and elevated plasma levels of alanine aminotransferase (ALT) from 4 h onward in female Balb/c mice. The hepatic mRNA expression of Th2 promotive factors was significantly increased concomitantly with plasma ALT levels. In contrast, the hepatic mRNA expression of Th2 suppressive factors was significantly decreased during the early phase of liver injury. Comprehensive profiling of hepatic miRNA expression was analyzed before the onset of MTZ-induced liver injury. Using in silico prediction of miRNAs that possibly regulate Th2-related genes and subsequent quantification, we identified up-regulation of expression of miR-29b-1-5p and miR-449a-5p. Among targets of these miRNAs, down-regulation of Th2 suppressive transcription factors, such as SRY-related HMG-box 4 (SOX4) and lymphoid enhancer factor-1 (LEF1), were observed from the early phase of liver injury. In conclusion, negative regulation of the expression of SOX4 by miR-29b-1-5p and that of LEF1 by miR-449a-5p is suggested to play an important role in the development of Th2 bias in MTZ-induced liver injury. - Highlights: • Methimazole induced hepatic Th2 bias in the pathogenesis of liver injury in mice. • Rapid down-regulation of SOX4 and LEF1 may initiate and/or maintain hepatic Th2 bias. • Negative regulation of SOX4 by miR-29b-1-5p and LEF1 by miR-449a-5p was suggested.

MicroRNA-mediated Th2 bias in methimazole-induced acute liver injury in mice

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Uematsu, Yasuaki, E-mail: yasuaki-uematsu@ds-pharma.co.jp [Department of Drug Safety Sciences, Division of Clinical Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 1-98 Kasugade-naka, 3-chome, Konohana-ku, Osaka (Japan); Akai, Sho [Department of Drug Safety Sciences, Division of Clinical Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Tochitani, Tomoaki [Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 1-98 Kasugade-naka, 3-chome, Konohana-ku, Osaka (Japan); Oda, Shingo [Department of Drug Safety Sciences, Division of Clinical Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Yamada, Toru [Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 1-98 Kasugade-naka, 3-chome, Konohana-ku, Osaka (Japan); Yokoi, Tsuyoshi [Department of Drug Safety Sciences, Division of Clinical Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

2016-09-15

MicroRNA (miRNA) is a class of small non-coding RNAs containing approximately 20 nucleotides that negatively regulate target gene expression. Little is known about the role of individual miRNAs and their targets in immune- and inflammation-related responses in drug-induced liver injury. In the present study, involvement of miRNAs in the T helper (Th) 2-type immune response was investigated using a methimazole (MTZ)-induced liver injury mouse model. Co-administration of L-buthionine-S,R-sulfoximine and MTZ induced acute hepatocellular necrosis and elevated plasma levels of alanine aminotransferase (ALT) from 4 h onward in female Balb/c mice. The hepatic mRNA expression of Th2 promotive factors was significantly increased concomitantly with plasma ALT levels. In contrast, the hepatic mRNA expression of Th2 suppressive factors was significantly decreased during the early phase of liver injury. Comprehensive profiling of hepatic miRNA expression was analyzed before the onset of MTZ-induced liver injury. Using in silico prediction of miRNAs that possibly regulate Th2-related genes and subsequent quantification, we identified up-regulation of expression of miR-29b-1-5p and miR-449a-5p. Among targets of these miRNAs, down-regulation of Th2 suppressive transcription factors, such as SRY-related HMG-box 4 (SOX4) and lymphoid enhancer factor-1 (LEF1), were observed from the early phase of liver injury. In conclusion, negative regulation of the expression of SOX4 by miR-29b-1-5p and that of LEF1 by miR-449a-5p is suggested to play an important role in the development of Th2 bias in MTZ-induced liver injury. - Highlights: • Methimazole induced hepatic Th2 bias in the pathogenesis of liver injury in mice. • Rapid down-regulation of SOX4 and LEF1 may initiate and/or maintain hepatic Th2 bias. • Negative regulation of SOX4 by miR-29b-1-5p and LEF1 by miR-449a-5p was suggested.

Increased accumulation of 4-hydroxynonenal adducts in female GSTA4/PPAR alpha double knockout mice enhance steatosis and inflammation in a model of pediatric nonalcoholic fatty liver disease

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Hepatocellular injury resulting from increased lipid peroxidation products and oxidative stress is considered a potential mechanism driving the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitsis (NASH). To test the significance of lipid peroxidation and protein...

Computed tomography of hepatocellular carcinoma: Usefulness of dynamic CT

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Takemoto, Kazumasa; Inoue, Yuichi; Matsuoka, Toshiyuki; Nakatsuka, Haruki; Oda, Junro [Osaka City Univ. (Japan). Faculty of Medicine

1983-04-01

Dynamic computed tomography (CT) scans in 65 hepatocellular carcinomas were analyzed and compared to plain and drip infusion contrast CT scans of those. Scans were obtained before, 10, 30, and 50 seconds after an intravenous bolus injection of 50ml 65% Angiografin. By this method, 49 hepatomas had moderate to marked enhancement at the arterial phase while the enhancement of normal liver parenchyma was only slight at the arterial phase and peaked at the portal phase. Compared to a drip infusion contrast CT, a dynamic CT had advantages to detect an isodense hepatoma in 4 and daughter tumors in 16 both of which were not appreciated by a plain and a drip infusion contrast CT. The tumor extension was also better delineated by a dynamic CT because a part of hepatoma had an isodense area. An arterio-portal shunt was visualized in one. Tumor thrombus in the portal vein was clearly demonstrated in 6 at the portal phase of a dynamic CT. Since a dynamic CT is convenient to perform without any special program or soft wear and gives us very useful information, we believe that it should be routinely employed as a part of a liver CT examination.

Value of infusion-DSA (Digital Subtraction Angiography) in diagnosis of primary hepatocellular carcinoma

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Kwon, Jeong Mi; Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk

1991-01-01

In order to evaluate diagnostic effectiveness of the infusion-study, the authors prospectively evaluated hepatic digital subtraction angiography of bolus and infusion studies in 71 patients with hepatocellular carcinoma. In contrast to Bolus-DSA, which involves a 2 second injection of 10cc of contrast medium, the Infusion-DSA uses a protracted (10sec) injection, a lower injection rate, and larger total dose of contrast medium (20cc). The information yield of arterial and capillary phases of Infusion-DSA was compared with that of Bolus-DSA and graded as 'improved(+)', 'equivalent( ± )', or 'poor(-)'. Also, the contribution of Infusion-DSA to the diagnosis was classified into one of five in a graded system. In 29 hepatocellular patients, the Infusion-DSA was helpful in detecting daughter nodules, fibrous capsule and arteriovenous shunt. Infusion-DSA is a useful complementary technique in the diagnosis of hepatocellular carcinoma and was also helpful in determining the selection of the therapeutic modality of hepatocellular carcinoma

Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.

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Li, Yichun; Li, Yannan; Wang, Dan; Meng, Qingdong

2018-06-12

Linc-POU3F3 showed an up-regulated tendency and functioned as tumor promoter in glioma, esophageal cancer and colorectal cancer. There was no report about the expression pattern and clinical value of linc-POU3F3 in hepatocellular carcinoma. Thus, the purpose of our study is to explore the clinical significance and biological role of linc-POU3F3 in hepatocellular carcinoma. Our results suggested that levels of linc-POU3F3 were dramatically increased in hepatocellular carcinoma tissues and cell lines compared with paired normal hepatic tissues and normal hepatic cell line, respectively. Levels of linc-POU3F3 were positively correlated with clinical stage, tumor size, vascular invasion and metastasis. Moreover, high-expression of linc-POU3F3 was an independent prognostic factor for hepatocellular carcinoma patients. The gain- and loss-of-function experiments showed that linc-POU3F3 expression significantly promoted tumor cell proliferation, migration and invasion. In addition, linc-POU3F3 expression was negatively correlated with POU3F3 mRNA and protein expressions in hepatocellular carcinoma tissues, and negatively regulated POU3F3 mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, our study supports the first evidence that linc-POU3F3 plays an oncogenic role in hepatocellular carcinoma, and represents a potential therapeutic strategy for hepatocellular carcinoma patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans.

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Gordon, Tessa

2016-04-01

Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

Gd-EOB-DTPA-enhanced MRI for monitoring future liver remnant function after portal vein embolization and extended hemihepatectomy: A prospective trial.

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Geisel, Dominik; Raabe, Philip; Lüdemann, Lutz; Malinowski, Maciej; Stockmann, Martin; Seehofer, Daniel; Pratschke, Johann; Hamm, Bernd; Denecke, Timm

2017-07-01

To evaluate changes in liver function after right portal vein embolization (PVE) and extended right hemihepatectomy using gadolinium ethoxybenzyl-DTPA-enhanced (Gd-EOB-DTPA) MRI. In this prospective trial, 37 patients undergoing PVE were examined before and 14 and 28 days after PVE and 10 days after extended hemihepatectomy using Gd-EOB-DTPA-enhanced MRI. Lobar volume, kinetic growth rate (KGR), relative enhancement (RE) as well as hepatocellular uptake index (HUI) and fat signal fraction (FSF) were calculated for each lobe. RE of the left liver lobe (LLL) was steadily increasing after PVE and decreased to 0.48 ± 0.19 10 days after surgery, which is significantly lower than 14 days and 28 days post PVE (P DTPA-enhanced MRI may be used to monitor the functional increase in the FLR after PVE and to depict the intraoperative liver injury leading to a decrease in liver remnant function. • The most significant FLR volume increase happens within the first 14 days. • No MRI parameter was able to predict the success of FLR growth. • Our data suggest an early resection about 14 days after PVE. • Routine Gd-EOB-DTPA-enhanced MRI might be suitable to replace ICG-test.

Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells

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Li Fan

2010-04-01

Full Text Available Abstract Background In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Methods We constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7. Results CXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo

Hep par-1: a novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma

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Hanif, R.

2014-01-01

To evaluate the diagnostic utility of Hep par-1 in differentiating hepatocellular carcinoma from metastatic carcinoma taking histopathology as a gold standard. Study Design: Comparative cross-sectional study. Place and Duration of Study: Pathology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from April 2007 to February 2008. Methodology: Hep par-1 immunohistochemical stain was performed on 60 cases of liver carcinoma, 30 cases each of metastatic and hepatocellular carcinoma. Information regarding patient age, gender, sign and symptoms, radiographic findings, histological grade of tumour, and expression of Hep par-1 on hepatocellular and metastatic carcinoma were recorded on proforma sheet. Sensitivity, specificity, positive and negative predictive values, and accuracy of Hep par-1 were calculated using the formulas. Results: Hep par-1 expression was noted in 25 out of 30 cases of hepatocellular carcinoma (83%). Out of 30 cases of metastatic carcinoma, only one case expressed staining in < 5% tumour cells and remaining 29 cases showed no reactivity. The age of the patients with hepatocellular carcinoma ranged from 40 to 76 years with a median age of 60.5 years and 40 - 75 years for metastatic carcinomas with a median age of 57.5 years. Conclusion: Hep par-1 is a reliable immunohistochemical marker for cases of hepatocellular carcinoma (HCC). It can be used along with other markers in morphologically difficult cases when differential diagnosis lies between poorly differentiated HCC and metastatic carcinoma of liver. (author)

Differential proteomic and tissue expression analyses identify valuable diagnostic biomarkers of hepatocellular differentiation and hepatoid adenocarcinomas.

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Reis, Henning; Padden, Juliet; Ahrens, Maike; Pütter, Carolin; Bertram, Stefanie; Pott, Leona L; Reis, Anna-Carinna; Weber, Frank; Juntermanns, Benjamin; Hoffmann, Andreas-C; Eisenacher, Martin; Schlaak, Joörg F; Canbay, Ali; Meyer, Helmut E; Sitek, Barbara; Baba, Hideo A

2015-10-01

The exact discrimination of lesions with true hepatocellular differentiation from secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary protein biomarkers by using complementary proteomic techniques (2D-DIGE, label-free MS). The identified candidates were immunohistochemically validated in 14 paired samples of hepatocellular carcinoma (HCC) and non-tumourous liver tissue (NT). The candidates and HepPar1/Arginase1 were afterwards tested for consistency in a large cohort of hepatocellular lesions and NT (n = 290), non-hepatocellular malignancies (n = 383) and HAC (n = 13). Eight non-redundant, differentially expressed proteins were suitable for further immunohistochemical validation and four (ABAT, BHMT, FABP1, HAOX1) for further evaluation. Sensitivity and specificity rates for HCC/HAC were as follows: HepPar1 80.2%, 94.3% / 80.2%, 46.2%; Arginase1 82%, 99.4% / 82%, 69.2%; BHMT 61.4%, 93.8% / 61.4%, 100%; ABAT 84.4%, 33.7% / 84.4%, 30.8%; FABP1 87.2%, 95% / 87.2%, 69.2%; HAOX1 95.5%, 36.3% / 95.5%, 46.2%. The best 2×/3× biomarker panels for the diagnosis of HCC consisted of Arginase1/HAOX1 and BHMT/Arginase1/HAOX1 and for HAC consisted of Arginase1/FABP1 and BHMT/Arginase1/FABP1. In summary, we successfully identified, validated and benchmarked protein biomarker candidates of hepatocellular differentiation. BHMT in particular exhibited superior diagnostic characteristics in hepatocellular lesions and specifically in HAC. BHMT is therefore a promising (panel based) biomarker candidate in the differential diagnostic process of lesions with hepatocellular aspect.

Dynamic Contrast-Enhanced MR Imaging of Renal Ischemia-Reperfusion Injury

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Baik, Jun Hyun; Ahn, Myeong Im; Park, Young Ha; Chung, Soo Kyo [Catholic University, Seoul (Korea, Republic of)

2010-02-15

To evaluate the usefulness of magnetic resonance imaging (MRI) in a renal ischemia-reperfusion injury. Twenty-four rabbits were randomly divided into four groups, including a sham operated group (n=3). Renal ischemia was induced for 30 minutes (group 1), 60 minutes (group 2) and 120 minutes (group 3). MR imaging was performed before ischemia as well as one hour, 24 hours, and 72 hours after reperfusion. A 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy was performed before ischemia, as well as 24 hours and 72 hours after reperfusion. The signal-to-noise ratio (SNR) on the T2WI, time-relative signal intensity (%RSI) curve on dynamic enhanced images, and relative left renal uptake (%) on DMSA scan were obtained and compared to the histologic findings. The SNR of the cortex on the T2WI changed significantly over the course of the reperfusion time (p<0.001), but was not significantly different among the ischemia groups. The area under the time-%RSI curve gradually decreased from cortex to inner medulla before ischemia, which was reversed and gradually increased after reperfusion. The areas under the time-%RSI curve of outer and inner medulla were significantly different among the ischemia groups (p=0.04, p=0.008). The relative renal uptake (%) of left kidney decreased significantly over the reperfusion time (p=0.03), and was also significantly different among the ischemia groups (p=0.005). Tubular cell necrosis was observed in 16 rabbits (76.2%). The histologic grades of group 3 were higher than those of group 1 and group 2 (p=0.002). Even in rabbits without tubular cell necrosis, the areas under the time-%RSI curves of the cortex, outer, and inner medulla after a 72 hour reperfusion time were significantly lower than those before ischemia (p=0.007, p=0.005, p=0.004). The results of this study suggest that dynamic enhanced MR imaging could be a useful tool for the evaluation of renal ischemia and reperfusion injury.

Lineage fate of ductular reactions in liver injury and carcinogenesis.

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Jörs, Simone; Jeliazkova, Petia; Ringelhan, Marc; Thalhammer, Julian; Dürl, Stephanie; Ferrer, Jorge; Sander, Maike; Heikenwalder, Mathias; Schmid, Roland M; Siveke, Jens T; Geisler, Fabian

2015-06-01

Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary differentiation toward the hepatocyte lineage. Further, lineage-labeled DRs did not produce tumors in genetic and chemical HCC mouse models. In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs.

Oxidative stress following traumatic brain injury: enhancement of ...

African Journals Online (AJOL)

neuronal loss following traumatic brain injury and presents experimental and clinical evidence of the role of exogenous antioxidants as neuroprotectants. Method: We reviewed published literature on reactive oxygen species and their role in experimental and clinical brain injuries in journals and the Internet using Yahoo ...

Preparation and Optimization Lipid Nanocapsules to Enhance the Antitumor Efficacy of Cisplatin in Hepatocellular Carcinoma HepG2 Cells.

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Zhai, Qingqing; Li, Hailong; Song, Yanlin; Wu, Ruijiao; Tang, Chuanfang; Ma, Xiaodong; Liu, Zhihao; Peng, Jinyong; Zhang, Jianbin; Tang, Zeyao

2018-04-20

This work aimed to develop and optimize several lipid nanocapsule formulations (LNCs) to encapsulate cisplatin (CDDP) for treatment of hepatocellular carcinoma. By comparing the effect of oil/surfactant ratio, lecithin content, and oil/surfactant type on LNC characteristics, two LNCs were selected as optimal formulations: HS15-LNC (Solutol HS 15/MCT/lecithin, 54.5:42.5:3%, w/w) and EL-LNC (Cremophor EL/MCT/lecithin, 54.5:42.5:3%, w/w). Both LNCs could effectively encapsulate CDDP with the encapsulation efficiency of 73.48 and 78.84%. In vitro release study showed that both LNCs could sustain the release CDDP. Moreover, cellular uptake study showed that C6-labeled LNCs could be effectively internalized by HepG2 cells. Cellular cytotoxicity study revealed that both LNCs showed negligible cellular toxicity when their concentrations were below 313 μg/mL. Importantly, CDDP-loaded LNCs exhibited much stronger cell killing potency than free CDDP, with the IC50 values decreased from 17.93 to 3.53 and 5.16 μM after 72-h incubation. In addition, flow cytometric analysis showed that the percentage of apoptotic cells was significantly increased after treatment with LNCs. Therefore, the prepared LNC formulations exhibited promising anti-hepatocarcinoma effect, which could be beneficial to hepatocellular carcinoma therapy.

Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.

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Xiaofang Yu

Full Text Available Mesenchymal stem cell (MSC administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP. MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC, HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy.

Abdominal lymph node metastases of hepatocellular carcinoma diagnosed by computed tomography and angiography

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Nakamura, Hironobu; Oi, Hiromichi [Osaka Univ. (Japan). Research Inst. for Microbial Diseases; Tanaka, Takeshi; Sai, Soomi; Hori, Shinichi

1984-04-01

CT scans of 164 patients with hepatocellular carcinoma were studied, and abdominal lymph node metastases were detected in 13 cases. Most of these lymph node metastases occured in periportal, peripancreatic and paraaortic lymph nodes. Ten instances of each these metastases were identified by CT. Six of the patients had metastases in all three sites. In 9 of 13 cases, lymph node metastases were demonstrated by angiography and various degrees of contrast material stain were seen. Lymph node metastasis of hepatocellular carcinoma is apt to be hypervascular. Most of hepatocellular carcinoma with lymph node metastasis showed infiltrative growth, and tumor thrombosis in the portal vein was commonly complicated.

Non-Invasive Radiofrequency-Induced Targeted Hyperthermia for the Treatment of Hepatocellular Carcinoma

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Mustafa Raoof

2011-01-01

Full Text Available Targeted biological therapies for hepatocellular cancer have shown minimal improvements in median survival. Multiple pathways to oncogenesis leading to rapid development of resistance to such therapies is a concern. Non-invasive radiofrequency field-induced targeted hyperthermia using nanoparticles is a radical departure from conventional modalities. In this paper we underscore the need for innovative strategies for the treatment of hepatocellular cancer, describe the central paradigm of targeted hyperthermia using non-invasive electromagnetic energy, review the process of characterization and modification of nanoparticles for the task, and summarize data from cell-based and animal-based models of hepatocellular cancer treated with non-invasive RF energy. Finally, future strategies and challenges in bringing this modality from bench to clinic are discussed.

Radiation recall dermatitis triggered by sorafenib after radiation therapy for hepatocellular carcinoma

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Kim, Gwi Eon; Song, Hee Sung; Kim, Young Suk [Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of); Ahn, Ki Jung [Dept. of Radiation Oncology, Inje University Busan Paik Hospital, Inje University of Medicine, Busan (Korea, Republic of)

2017-09-15

Sorafenib is widely used for unresectable and metastatic hepatocellular carcinomas. Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin that occurs after the administration of certain drugs. RRD after sorafenib treatment is rare; five cases have been reported thus far. We describe a 44-year-old man irradiated for chest wall bone metastasis from hepatocellular carcinoma. Eight days after radiotherapy completion, systemic therapy for metastatic hepatocellular carcinoma was initiated with sorafenib treatment. Eleven days after starting sorafenib, the patient complained of erythematous rash with pruritus in the chest wall, in a location consistent with the previous radiation field. Sorafenib was continued at the same dose, despite the RRD. The skin reaction subsided over the next 2 weeks without any medical intervention.

O-GlcNAcylation of RACK1 promotes hepatocellular carcinogenesis.

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Duan, Fangfang; Wu, Hao; Jia, Dongwei; Wu, Weicheng; Ren, Shifang; Wang, Lan; Song, Shushu; Guo, Xinying; Liu, Fenglin; Ruan, Yuanyuan; Gu, Jianxin

2018-06-01

Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis. Nevertheless, whether and how these two pathways are interlinked remain unknown. Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC). The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis. The site(s) of RACK1 for O-GlcNAcylation was mapped by mass spectrometry analysis. HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro. Transgenic knock-in mice were used to detect the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo. The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples. We found that ribosomal RACK1 was highly modified by O-GlcNAc at Ser122. O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells. Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model. Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy. These findings demonstrate that RACK1 acts as key mediator linking O-GlcNAc metabolism to cap-dependent translation during HCC tumorigenesis. Targeting RACK1 O-GlcNAcylation provides promising options for HCC treatment. O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction

Cinnamic Acid Derivatives Enhance the Efficacy of Transarterial Embolization in a Rat Model of Hepatocellular Carcinoma

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Wilkins, Luke R., E-mail: lrw6n@virginia.edu [University of Virginia Health Systems, Department of Radiology and Medical Imaging (United States); Brautigan, David L., E-mail: db8g@virginia.edu [University of Virginia, Department of Microbiology, Immunology, and Cancer Biology (United States); Wu, Hanping, E-mail: hanpingwumd@gmail.com [University Hospitals of Cleveland, Case Western Reserve University, Department of Radiology (United States); Yarmohammadi, Hooman, E-mail: yar.hooman@gmail.com [Memorial Sloan-Kettering Cancer Center, Department of Radiology (United States); Kubicka, Ewa, E-mail: emk6d@virginia.edu [University of Virginia, Department of Microbiology, Immunology, and Cancer Biology (United States); Serbulea, Vlad, E-mail: vs9ck@virginia.edu; Leitinger, Norbert, E-mail: nl2q@virginia.edu [University of Virginia, Department of Pharmacology (United States); Liu, Wendy, E-mail: wendy.liu@uhhospitals.org [University Hospitals of Cleveland, Case Western Reserve University, Department of Pathology (United States); Haaga, John R., E-mail: john.haaga@uhhospitals.org [University Hospitals of Cleveland, Case Western Reserve University, Department of Radiology (United States)

2017-03-15

IntroductionWe hypothesize that the combination of transarterial embolization (TAE) plus inhibition of lactate export will limit anaerobic metabolism and reduce tumor survival compared to TAE alone. The purpose of this study was to test this hypothesis in a rat model of hepatocellular carcinoma (HCC).MethodsRat N1-S1 hepatoma cells were assayed in vitro using the Seahorse XF analyzer to measure extracellular acidification (lactate excretion) comparing effects of the addition of caffeic acid (CA) or ferulic acid (FA) or UK-5099 with control. Monocarboxylate transporter Slc16a3 was knocked down by RNAi. N1S1 tumors were orthotopically implanted in rats and 4 groups evaluated: (1) Control, (2) TAE-only, (3) TAE plus CA, and (4) TAE plus FA. Tumor size was determined by ultrasound and analyzed by repeated measures statistics. Tumors harvested at 4 weeks were examined by microscopy.ResultsSeahorse assays showed that CA and FA caused a significant reduction by >90% in lactate efflux by N1S1 tumor cells (p < 0.01). Knockdown of Slc16a3 prevented inhibition by CA. In vivo tumors grew 30-fold in volume over 4 weeks in untreated controls. By comparison, TAE resulted in near cessation of growth (10% in 4-week time period). However, both TAE + CA and TAE + FA caused a significant reduction of tumor volumes (87 and 72%, respectively) compared to control and TAE (p < 0.05). Pathologic evaluation revealed residual tumor in the TAE group but no residual viable tumor cells in the TAE + CA and TAE + FA groups.ConclusionAddition of CA or FA enhances the effectiveness of TAE therapy for HCC in part by blocking lactate efflux.

Cinnamic Acid Derivatives Enhance the Efficacy of Transarterial Embolization in a Rat Model of Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Wilkins, Luke R.; Brautigan, David L.; Wu, Hanping; Yarmohammadi, Hooman; Kubicka, Ewa; Serbulea, Vlad; Leitinger, Norbert; Liu, Wendy; Haaga, John R.

2017-01-01

IntroductionWe hypothesize that the combination of transarterial embolization (TAE) plus inhibition of lactate export will limit anaerobic metabolism and reduce tumor survival compared to TAE alone. The purpose of this study was to test this hypothesis in a rat model of hepatocellular carcinoma (HCC).MethodsRat N1-S1 hepatoma cells were assayed in vitro using the Seahorse XF analyzer to measure extracellular acidification (lactate excretion) comparing effects of the addition of caffeic acid (CA) or ferulic acid (FA) or UK-5099 with control. Monocarboxylate transporter Slc16a3 was knocked down by RNAi. N1S1 tumors were orthotopically implanted in rats and 4 groups evaluated: (1) Control, (2) TAE-only, (3) TAE plus CA, and (4) TAE plus FA. Tumor size was determined by ultrasound and analyzed by repeated measures statistics. Tumors harvested at 4 weeks were examined by microscopy.ResultsSeahorse assays showed that CA and FA caused a significant reduction by >90% in lactate efflux by N1S1 tumor cells (p < 0.01). Knockdown of Slc16a3 prevented inhibition by CA. In vivo tumors grew 30-fold in volume over 4 weeks in untreated controls. By comparison, TAE resulted in near cessation of growth (10% in 4-week time period). However, both TAE + CA and TAE + FA caused a significant reduction of tumor volumes (87 and 72%, respectively) compared to control and TAE (p < 0.05). Pathologic evaluation revealed residual tumor in the TAE group but no residual viable tumor cells in the TAE + CA and TAE + FA groups.ConclusionAddition of CA or FA enhances the effectiveness of TAE therapy for HCC in part by blocking lactate efflux.

Diagnostic accuracy of C-arm CT during selective transcatheter angiography for hepatocellular carcinoma: comparison with intravenous contrast-enhanced, biphasic, dynamic MDCT

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Higashihara, Hiroki; Osuga, Keigo; Onishi, Hiromitsu; Nakamoto, Atsushi; Tsuboyama, Takahiro; Maeda, Noboru; Hori, Masatoshi; Kim, Tonsok; Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Diagnostic and Interventional Radiology, Suita, Osaka (Japan)

2012-04-15

This study was aimed to compare the accuracy, sensitivity, and positive predictive value of C-arm CT (CACT) during selective transcatheter angiography with those of multidetector CT (MDCT) in the detection of hepatocellular carcinoma (HCC). In this prospective study, 30 patients (mean age, 73 years) with unresectable HCC were examined with CACT before chemoembolisation. Images of a combination of CACT during arterial portography (CACTAP) and dual-phase CACT during hepatic arteriography (CACTHA) was obtained and images of intravenous contrast-enhanced, biphasic, dynamic, MDCT was also obtained beforehand. Three blinded observers independently reviewed CACT and MDCT. Diagnostic accuracy was evaluated by the alternative free-response receiver operating characteristic (AFROC) method. Sensitivities and positive predictive values (PPV) were analyzed with the paired t-test. In the mean area under the AFROC curve (Az), there was no significant difference between MDCT and CACT (MDCT, mean Az value, 0.83; CACT, 0.85, respectively) (P = 0.32). There was also no significant difference between the two techniques in sensitivity (MDCT, mean 0.65; CACT, 0.60) and PPV (MDCT, mean 0.98; CACT, 0.97) (P = 0.40, P = 0.68, respectively). The diagnostic accuracy of CACT was equivalent to that of biphasic CT in the diagnosis of HCC. (orig.)

Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression.

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Sathidpak Nantasanti

Full Text Available The tumor suppressors Retinoblastoma (Rb and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC. DDC is metabolized mainly by cytochrome P450 (Cyp3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC.

α-Hispanolol sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis via death receptor up-regulation

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Mota, Alba, E-mail: amota@iib.uam.es [Unidad de Terapias Farmacológicas, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III, Madrid (Spain); Jiménez-Garcia, Lidia, E-mail: ljimenez@isciii.es [Unidad de Terapias Farmacológicas, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III, Madrid (Spain); Herránz, Sandra, E-mail: sherranz@isciii.es [Unidad de Terapias Farmacológicas, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III, Madrid (Spain); Heras, Beatriz de las, E-mail: lasheras@ucm.es [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), Madrid (Spain); Hortelano, Sonsoles, E-mail: shortelano@isciii.es [Unidad de Terapias Farmacológicas, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III, Madrid (Spain)

2015-08-01

Hispanolone derivatives have been previously described as anti-inflammatory and antitumoral agents. However, their effects on overcoming Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance remain to be elucidated. In this study, we analyzed the cytotoxic effects of the synthetic hispanolone derivative α-hispanolol (α-H) in several tumor cell lines, and we evaluated the induction of apoptosis, as well as the TRAIL-sensitizing potential of α-H in the hepatocellular carcinoma cell line HepG2. Our data show that α-H decreased cell viability in a dose-dependent manner in HeLa, MDA-MB231, U87 and HepG2 cell lines, with a more prominent effect in HepG2 cells. Interestingly, α-H had no effect on non-tumoral cells. α-H induced activation of caspase-8 and caspase-9 and also increased levels of the proapoptotic protein Bax, decreasing antiapoptotic proteins (Bcl-2, X-IAP and IAP-1) in HepG2 cells. Specific inhibition of caspase-8 abrogated the cascade of caspase activation, suggesting that the extrinsic pathway has a critical role in the apoptotic events induced by α-H. Furthermore, combined treatment of α-H with TRAIL enhanced apoptosis in HepG2 cells, activating caspase-8 and caspase-9. This correlated with up-regulation of both the TRAIL death receptor DR4 and DR5. DR4 or DR5 neutralizing antibodies abolished the effect of α-H on TRAIL-induced apoptosis, suggesting that sensitization was mediated through the death receptor pathway. Our results demonstrate that α-H induced apoptosis in the human hepatocellular carcinoma cell line HepG2 through activation of caspases and induction of the death receptor pathway. In addition, we describe a novel function of α-H as a sensitizer on TRAIL-induced apoptotic cell death in HepG2 cells. - Highlights: • α-Hispanolol induced apoptosis in the human hepatocellular carcinoma cell line HepG2. • α-Hispanolol induced activation of caspases and the death receptor pathway. • α-Hispanolol enhanced

α-Hispanolol sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis via death receptor up-regulation

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Mota, Alba; Jiménez-Garcia, Lidia; Herránz, Sandra; Heras, Beatriz de las; Hortelano, Sonsoles

2015-01-01

Hispanolone derivatives have been previously described as anti-inflammatory and antitumoral agents. However, their effects on overcoming Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance remain to be elucidated. In this study, we analyzed the cytotoxic effects of the synthetic hispanolone derivative α-hispanolol (α-H) in several tumor cell lines, and we evaluated the induction of apoptosis, as well as the TRAIL-sensitizing potential of α-H in the hepatocellular carcinoma cell line HepG2. Our data show that α-H decreased cell viability in a dose-dependent manner in HeLa, MDA-MB231, U87 and HepG2 cell lines, with a more prominent effect in HepG2 cells. Interestingly, α-H had no effect on non-tumoral cells. α-H induced activation of caspase-8 and caspase-9 and also increased levels of the proapoptotic protein Bax, decreasing antiapoptotic proteins (Bcl-2, X-IAP and IAP-1) in HepG2 cells. Specific inhibition of caspase-8 abrogated the cascade of caspase activation, suggesting that the extrinsic pathway has a critical role in the apoptotic events induced by α-H. Furthermore, combined treatment of α-H with TRAIL enhanced apoptosis in HepG2 cells, activating caspase-8 and caspase-9. This correlated with up-regulation of both the TRAIL death receptor DR4 and DR5. DR4 or DR5 neutralizing antibodies abolished the effect of α-H on TRAIL-induced apoptosis, suggesting that sensitization was mediated through the death receptor pathway. Our results demonstrate that α-H induced apoptosis in the human hepatocellular carcinoma cell line HepG2 through activation of caspases and induction of the death receptor pathway. In addition, we describe a novel function of α-H as a sensitizer on TRAIL-induced apoptotic cell death in HepG2 cells. - Highlights: • α-Hispanolol induced apoptosis in the human hepatocellular carcinoma cell line HepG2. • α-Hispanolol induced activation of caspases and the death receptor pathway. • α-Hispanolol enhanced

Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery

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Sugihara, Fumie; Murata, Satoru; Ueda, Tatsuo; Yasui, Daisuke; Yamaguchi, Hidenori; Miki, Izumi; Kumita, Shin-ichiro [Nippon Medical School, Department of Radiology, Center for Advanced Medical Technology, Tokyo (Japan); Kawamoto, Chiaki [Nippon Medical School, Department of Internal Medicine, Tokyo (Japan); Uchida, Eiji [Nippon Medical School, Department of Surgery, Tokyo (Japan)

2017-06-15

To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. (orig.)

Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition

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Wu, Xiao-cai; Xiao, Cui-cui; Li, Hua [Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou (China); Tai, Yan; Zhang, Qi [Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou (China); Yang, Yang, E-mail: yysysu2@163.com [Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou (China)

2016-08-19

Background: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC). Methods: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation. Results: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared to matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group. Conclusions: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC. - Highlights: • TLE4 is significantly down-regulated in HCC samples. • Down regulated of TLE4 in HCC cells promotes cell proliferation. • Down regulated of TLE4 in HCC cells promotes epithelial-to-mesenchymal transition.

Combined hepatocellular-cholangiocarcinoma in a Yellow-headed Amazon (Amazona oratrix).

Science.gov (United States)

Tennakoon, Anusha Hemamali; Izawa, Takeshi; Fujita, Daisuke; Denda, Yuki; Seto, Eiko; Sasai, Hiroshi; Kuwamura, Mitsuru; Yamate, Jyoji

2013-11-01

A 9-year-old male Yellow-headed Amazon (Amazona oratrix) with a history of anorexia and vomiting died of a liver tumor. The tumor consisted of neoplastic cells with hepatocellular and cholangiocellular differentiations and their intermingled areas. Neoplastic hepatocytes showed islands or trabecular growth with vacuolated eosinophilic cytoplasm. Cells showing biliary differentiation formed ducts or tubules lined by cytokeratin AE1/AE3-positive epithelia, accompanied by desmoplasia consisting of myofibroblasts reacting to α-smooth muscle actin and desmin. The tumor was diagnosed as a combined hepatocellular-cholangiocarcinoma, which is very rare in the avian.

Serological diagnosis of hepatocellular carcinoma: challenges and opportunities

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LU Fengmin

2017-07-01

Full Text Available Serological markers have the features of noninvasiveness and simple operation and thus have become a research hotspot in the diagnosis of hepatocellular carcinoma. This article briefly introduces the role of the conventional serological marker alpha-fetoprotein (AFP in assisting the diagnosis and predicting the prognosis of HBV-related liver cancer, as well as the clinical value of new markers such as alpha-fetoprotein-L3 and abnormal prothrombin/des-γ-carboxy prothrombin. Based on literature review, the possibility of serum Golgi protein 73 used for laboratory auxiliary diagnosis of hepatocellular carcinoma has been denied. The results of the author′s experiment suggest that serum GP73 measurement can be used as a laboratory diagnostic index for progressive liver fibrosis and liver cirrhosis.

Defining Hepatocellular Carcinoma Subtypes and Treatment Responses in Patient-Derived Tumorgrafts

Science.gov (United States)

2017-10-01

Hepatocellular carcinoma (HCC) is the 6th most common cancer and 3rd leading cause of cancer-related death worldwide. We know that HCC subtypes exist because...italicized descriptions of section contents in your submitted reports. 1. INTRODUCTION: Hepatocellular carcinoma (HCC) is the 6th most common cancer and 3rd...know the results or have not been harvested to assess tumor engraftment in liver. Overall, we have found that there is a good engraftment rate

How to detect hepatocellular carcinoma in cirrhosis

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Ward, Janice; Robinson, Philip J. [Department of Clinical Radiology, St. James' s University Hospital, Beckett Street, Leeds LS9 7TF (United Kingdom)

2002-09-01

Cirrhosis predisposes to hepatocellular carcinoma (HCC) which develops by sequential steps of de-differentiation of hepatocytes from regenerative nodules via borderline (dysplastic) nodules to frankly malignant HCC. Effective treatment depends on early recognition of HCC, so the key tasks for imaging are firstly recognising the presence of a suspicious lesion, and secondly differentiating between benign, borderline and malignant nodules. Screening of high-risk cirrhotic patients with sonography and measurement of alpha fetoprotein (AFP) is helpful but will not reliably differentiate small HCC from benign or dysplastic nodules. Large HCCs can usually be recognised by their characteristic morphology on imaging, but the appearances of smaller benign and malignant nodules show considerable overlap on unenhanced sonography, CT and MRI. Increasing degrees of histological malignancy are associated with increasing arterialisation and loss of portal blood supply, so the recognition of HCC requires the use of dynamic imaging with contrast-enhanced CT or T1-weighted MRI with gadolinium enhancement. Sonography with microbubble contrast media now offers another method for detecting arterialised nodules; however, some non-malignant nodules show arterial hypervascularity and a minority of HCCs are hypovascular, so the assessment of perfusion does not conclusively distinguish benign from malignant lesions. Kupffer cell function is another attribute of liver tissue which can be explored using MRI with superparamagnetic iron oxide particles (SPIO). Experience thus far suggests that uptake of SPIO is an effective discriminator between benign and malignant nodules. The combination of SPIO with gadolinium-enhanced MRI offers the opportunity for imaging characterisation of cirrhotic nodules by cellular function as well as by blood supply, and this approach is now proposed as the examination of choice for detecting HCC in cirrhosis. (orig.)

Ultrasound-guided percutaneous treatment of hepatocellular carcinoma by radiofrequency hyperthermia with a 'cooled-tip needle'. A preliminary clinical experience.

Science.gov (United States)

Francica, G; Marone, G

1999-05-01

Radiofrequency hyperthermia using the newly-developed 'cooled-tip' needle has recently been proposed as a therapeutic modality for hepatocellular carcinoma (HCC). Herein we report our preliminary results on feasibility and effectiveness of the thermal ablation of mono- or pauci-focal hepatocellular carcinoma with the cooled-tip needle. We treated 15 cirrhotic patients (mean age 68.8 years; 12 males; 14 HCV-positive; 13 in Child's Class A and 2 in Class B) with 20 hepatocellular carcinoma nodules (mean diameter 28.1 mm; range 10-43 mm; nine lesions with diameter greater than 3 cm). None of the patients had portal thrombosis and/or extrahepatic spread. We used a radiofrequency generator (100 W of power) connected to a 18 g perfusion electrode needle with an exposed tip of 2-3 cm. The circuit was closed through a dispersive electrode positioned under the patient's thighs. A peristaltic pump infused a chilled (2-5 degrees C) saline solution to guarantee the continuous cooling of the needle tip. The needle was placed into target lesions under US guidance. The interventional procedure was carried out in general anesthesia without intubation. Dynamic helical CT was carried out 15-20 days after thermal ablation to assess therapeutic efficacy. In all, 38 areas of coagulation necrosis (at 1000-1200 mA for 10-15 min) were generated in 24 sessions in the 20 hepatocellular carcinoma nodules (mean 1.9 lesions per nodule and 1.2 sessions per nodule). Complete necrosis as assessed at dynamic CT (lack of enhancement during the arteriographic phase) was achieved in 75% of cases in a single session; after a second RF session success rate was 90% (18 out of 20 nodules). A self-limited pleurisy along with a 5-fold increase in transaminases occurred in one patient; a 3-fold elevation of transaminases was encountered in three other patients. During the follow-up (median 15 months) five patients had recurrent hepatocellular carcinoma with a 1-year disease free interval of 64%. Of the

Design and rationale of the HCC BRIDGE study in China: a longitudinal, multicenter cohort trial in hepatocellular carcinoma

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Qiao You-Lin

2011-05-01

Full Text Available Abstract Background More than 50% of the worldwide cases of hepatocellular carcinoma occur in China, and this malignancy currently represents the country's second leading cause of cancer death in cities and the leading cause in rural areas. Despite recent advances in the control and management of hepatocellular carcinoma within China, this disease remains a major health care issue. The global HCC BRIDGE study, designed to assess patterns of hepatocellular carcinoma therapy use and associated outcomes across real-world clinical practice, has recently been expanded as a national study in China, allowing a detailed analysis of hepatocellular carcinoma in this important country. Methods/Design The global HCC BRIDGE study is a multiregional longitudinal cohort trial including patients newly diagnosed with hepatocellular carcinoma between January 1, 2005, and June 30, 2011, who are receiving treatment for hepatocellular carcinoma via sites in the Asia-Pacific, European, and North American regions. The HCC BRIDGE China national study comprises the portion of the global HCC BRIDGE study conducted within mainland China. Patients will be followed from time of diagnosis of hepatocellular carcinoma (post-January 1, 2005 to time of death or December 31, 2011, whichever comes first. Data will be collected on demographic/clinical characteristics, relevant laboratory values, hepatocellular carcinoma/underlying liver disease treatment, tumor response, adverse events, hospitalizations, and overall survival. The primary study end point is overall survival; secondary end points are disease progression, treatment-limiting adverse events, and treatment failure. Results At the time of writing, 15 sites have selected for participation across all 7 traditional regions of China (North, North-East, East, South, South-West, North-West, and Central. The anticipated study population from the China national study is approximately 9000 patients. Discussion Findings from the

Methyleugenol hepatocellular cancer initiating effects in rat liver.

Science.gov (United States)

Williams, Gary M; Iatropoulos, Michael J; Jeffrey, Alan M; Duan, Jian-Dong

2013-03-01

Methyleugenol (MEG), a constituent of plants used in the human diet, is hepatocarcinogenic in rodents. In an experiment to elucidate its mode of action in rat liver, male F344 rats were administered MEG intragastrically at 3 doses per week for up to 16 weeks in an initiation phase, after which half the rats were fed 500 ppm phenobarbital (PB) in the diet to promote liver neoplasia and the other half were maintained on control diet for 24 weeks. At 8 and 16 week interim terminations, (32)P-nucleotide postlabeling assay revealed 3 adducts in livers of all MEG groups. The hepatocellular replicating fractions, measured by proliferating cell nuclear antigen immunohistochemistry, were doubled or more in all MEG groups. Hepatocellular altered foci, detected by glutathione S-transferase-placental type (π) immunohistochemistry, were present beginning with the high dose group at 8 weeks and extending to all MEG groups at 16 weeks. At the end of maintenance/promotion phase, the incidences, multiplicity and size of foci was similar between control and low dose groups, while those of mid and high dose groups were increased. Hepatocellular adenomas occurred in the mid and high dose groups, attaining higher multiplicity and size with PB. Thus, MEG had rapid initiating activity, reflecting the formation of DNA adducts and possibly cell proliferation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Intra-arterial cis-diamminedichloroplatinum infusion treatment for widespread hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Sung Il; Yang, Hee Chul; Lee, Do Yon; Shim, Yong Woon; Kim, Sang Heum; Kim, Myeong Jin; Lee, Jong Tae; Yoo, Hyung Sik

1997-01-01

The purpose of this study is to evaluate the therapeutic efficacy of intra-arterial infusion of Cis-diamminedichloroplatinum (C-DDP) for the treatment of hepatocellular carcinomas with widespread involvement. We retrospectively analyzed 22 patients who between July 1994 and June 1996 had undergone intra-arterial c-DDP infusion therapy for the treatment of hepatocellular carcinomas with widespread involvement. The hepatomas involved both lobes in ten, portal venous obstructions in fourteen, arterio-portal shunts in nine, and arterio-venous shunts in two. Proper hepatic artery was selected for infusion of 100 mg/BSA of C-DDP. The same procedure was repeated every 3 to 4 weeks, and the total number of infusions was 65. On the basis of WHO criteria, response was classified as complete remission, partial remission, stable, or progression of the disease. Six-month and one-year survival rates were estimated, and adverse reactions were evaluated. Although the response rate is not high, intra-arterial C-DDP infusion therapy can be used as an alternative treatment for hepatocellular carcinomas with widespread involvement; adverse reactions are tolerable. (author). 16 refs., 3 figs

Application of radionuclide imaging to hepatic impact injury in rabbits

Institute of Scientific and Technical Information of China (English)

金榕兵; 麻晓林; 温建良; 唐维佳

2004-01-01

Objective: To investigate the role and clinical value of radionuclide imaging in hepatic impact injuries in rabbits.Methods: Rabbits were experimentally impacted on the liver with BIM-IV bio-impact machine. Liver imaging was performed with 99mTc labeled sodium phytate. Liver blood pool imaging was performed with 99mTc -stannous pyrophosphate labeled red blood cells. The results of radionuclide imaging were compared with the anatomic results.Results: There was significant difference between the images of the injured liver and the control. Radio diminution and defect were shown in the injured liver areas. Various sorts of abnormal radioactivity distribution were observed with hepatic blood pool imaging. The results of the liver imaging and liver blood pool imaging were accorded with the results of the anatomic findings.Conclusions: Radionuclide imaging may well display the changes of hepatocellular structures and functions after injury, which is valuable in locating the concrete injured position and differentiating the injured degrees of liver.

Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells.

Science.gov (United States)

Zhang, Yafei; Zhang, Bicheng; Zhang, Anran; Zhao, Yong; Zhao, Jie; Liu, Jian; Gao, Jianfei; Fang, Dianchun; Rao, Zhiguo

2012-09-01

Sorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in hepatocellular carcinoma, and there is a strong rationale for investigating its use in combination with other agents. Vitamin K2 is nearly non-toxic to humans and has been shown to inhibit the growth of hepatocellular carcinoma. In this study, we evaluated the effects of a combination of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Flow cytometry, 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) and nude mouse xenograft assays were used to examine the effects of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Western blotting was used to elucidate the possible mechanisms underlying these effects. Assays for 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) revealed a strong synergistic growth-inhibitory effect between sorafenib and vitamin K2. Flow cytometry showed an increase in cell cycle arrest and apoptosis after treatment with a combination of these two drugs at low concentrations. Sorafenib-mediated inhibition of extracellular signal-regulated kinase phosphorylation was promoted by vitamin K2, and downregulation of Mcl-1, which is required for sorafenib-induced apoptosis, was observed after combined treatment. Vitamin K2 also attenuated the downregulation of p21 expression induced by sorafenib, which may represent the mechanism by which vitamin K2 promotes the inhibitory effects of sorafenib on cell proliferation. Moreover, the combination of sorafenib and vitamin K2 significantly inhibited the growth of hepatocellular carcinoma xenografts in nude mice. Our results determined that combined treatment with sorafenib and vitamin K2 can work synergistically to inhibit the growth of hepatocellular carcinoma cells. This finding raises the possibility that this combined treatment strategy might be promising as a new therapy against hepatocellular carcinoma, especially for patients

Skeletal metastases from primary hepatocellular carcinoma

International Nuclear Information System (INIS)

Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk; Chang, Hee Kyung; Huh, Man Ha

1988-01-01

In order to detect and to evaluate the frequency, the distribution, and the radiological findings of skeletal metastases from hepatocellular carcinoma, the authors retrospectively analyzed radiographic, scintigraphic, and CT findings of 257 patients with hepatocellular carcinoma. The results were as follows: 1. Skeletal metastases were demonstrated in 21 patients (8.2%). 2. Frequent symptoms were pain, limitation of motion, paralysis, and mass. In nine of them the initial symptoms were due to skeletal metastases. 3. The common sites of metastases were spine (13 cases), ribs (8 cases), pelvis (8 cases) and femur (6 cases). Humerus, skull and sternum were also frequently involved. 4. Plain film findings were purely osteolytic in all cases and pathologic fractures were noted in 5 cases. 5. The lesions appear expansible in 7 cases, and 4 of them showed associated soft tissue masses on CT scans. 6. Bone scans were performed in 13 cases of them and showed increased radiotracer uptake in all. 7. Angiographic studies of 3 cases showed hypervascularity of the metastatic lesions as well as the primary hepatic tumor.

SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis

International Nuclear Information System (INIS)

Srisuttee, Ratakorn; Koh, Sang Seok; Malilas, Waraporn; Moon, Jeong; Cho, Il-Rae; Jhun, Byung Hak; Horio, Yoshiyuki; Chung, Young-Hwa

2012-01-01

Highlights: ► Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. ► Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. ► Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. ► Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of β-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.

SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Srisuttee, Ratakorn [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Koh, Sang Seok [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Malilas, Waraporn; Moon, Jeong; Cho, Il-Rae [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Jhun, Byung Hak [Department of Applied Nanoscience, Pusan National University, Busan 609-735 (Korea, Republic of); Horio, Yoshiyuki [Department of Pharmacology, Sapporo Medical University, Sapporo 060-8556 (Japan); Chung, Young-Hwa, E-mail: younghc@pusan.ac.kr [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of)

2012-12-07

Highlights: Black-Right-Pointing-Pointer Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. Black-Right-Pointing-Pointer Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. Black-Right-Pointing-Pointer Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. Black-Right-Pointing-Pointer Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of {beta}-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.

Three-dimensional contrast-enhanced MRI using an intravascular contrast agent for detection of traumatic intra-abdominal hemorrhage and abdominal parenchymal injuries: an experimental study

International Nuclear Information System (INIS)

Weishaupt, D.; Ruehm, S.G.; Patak, M.A.; Schmidt, M.; Debatin, J.F.; Hetzer, F.H.

2000-01-01

The aim of this study was to compare the performance of 3D MRI in conjunction with an intravascular contrast agent to spiral contrast-enhanced CT, regarding the detection of abdominal parenchymal injuries as well as peritoneal hemorrhage in an animal model. Liver and kidney injuries were created surgically in six female pigs under general anesthesia. All pigs underwent contrast-enhanced spiral CT and 3D MR imaging following administration of an intravascular contrast agent (NC100150 Injection). Two readers rated their confidence independently on MR and CT data sets using a five-point scale for the presence of organ injury and hemoperitoneum. Autopsy findings served as standard of reference. Sensitivity and specificity for MR in detecting hepatic and renal injuries as well as hemoperitoneum was 100 %. Computed tomography was less accurate with sensitivity and specificity values of 90 and 94 %, respectively. Receiver operating characteristics (ROC) analysis revealed a higher confidence when interpretation was based on MR images. In an animal model 3D MR imaging in conjunction with an intravascular contrast agent proved highly accurate in detecting and localizing parenchymal injuries to the upper abdomen as well as in detecting intraperitoneal blood collections. (orig.)

Gd-EOB-DTPA-enhanced MRI for monitoring future liver remnant function after portal vein embolization and extended hemihepatectomy: A prospective trial

Energy Technology Data Exchange (ETDEWEB)

Geisel, Dominik; Raabe, Philip; Hamm, Bernd; Denecke, Timm [Charite Campus Virchow-Klinikum, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Luedemann, Lutz [Essen University Hospital, Department of Medical Physics, Essen (Germany); Malinowski, Maciej; Stockmann, Martin; Seehofer, Daniel; Pratschke, Johann [Charite Campus Virchow-Klinikum, Department of General, Visceral and Transplantation Surgery, Berlin (Germany)

2017-07-15

To evaluate changes in liver function after right portal vein embolization (PVE) and extended right hemihepatectomy using gadolinium ethoxybenzyl-DTPA-enhanced (Gd-EOB-DTPA) MRI. In this prospective trial, 37 patients undergoing PVE were examined before and 14 and 28 days after PVE and 10 days after extended hemihepatectomy using Gd-EOB-DTPA-enhanced MRI. Lobar volume, kinetic growth rate (KGR), relative enhancement (RE) as well as hepatocellular uptake index (HUI) and fat signal fraction (FSF) were calculated for each lobe. RE of the left liver lobe (LLL) was steadily increasing after PVE and decreased to 0.48 ± 0.19 10 days after surgery, which is significantly lower than 14 days and 28 days post PVE (P < 0.05). KGR was 14.06 ± 9.82%/week for the period from PVE to 14 days after PVE. HUI of the LLL increased steadily after PVE and was significantly higher at both 14 and 28 days after PVE compared to pre PVE (P < 0.05). HUI of the residual liver after surgery was lower than before. Gd-EOB-DTPA-enhanced MRI may be used to monitor the functional increase in the FLR after PVE and to depict the intraoperative liver injury leading to a decrease in liver remnant function. (orig.)

Light-induced retinal injury enhanced neurotrophins secretion and neurotrophic effect of mesenchymal stem cells in vitro

Directory of Open Access Journals (Sweden)

Wei Xu

2013-04-01

Full Text Available PURPOSE: To investigate neurotrophins expression and neurotrophic effect change in mesenchymal stem cells (MSCs under different types of stimulation. METHODS: Rats were exposed in 10,000 lux white light to develop light-induced retinal injury. Supernatants of homogenized retina (SHR, either from normal or light-injured retina, were used to stimulate MSCs. Quantitative real time for polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA were conducted for analysis the expression change in basic fibroblast growth factor (bFGF, brain-derived neurotrophic factor (BDNF and ciliary neurotrophic factor (CNTF in MSCs after stimulation. Conditioned medium from SHR-stimulated MSCs and control MSCs were collected for evaluation their effect on retinal explants. RESULTS: Supernatants of homogenized retina from light-injured rats significantly promoted neurotrophins secretion from MSCs (p<0.01. Conditioned medium from mesenchymal stem cells stimulated by light-injured SHR significantly reduced DNA fragmentation (p<0.01, up-regulated bcl-2 (p<0.01 and down-regulated bax (p<0.01 in retinal explants, displaying enhanced protective effect. CONCLUSIONS: Light-induced retinal injury is able to enhance neurotrophins secretion from mesenchymal stem cells and promote the neurotrophic effect of mesenchymal stem cells.

Hepatic protection and anticancer activity of curcuma: a potential chemopreventive strategy against hepatocellular carcinoma.

Science.gov (United States)

Li, Yan; Shi, Xue; Zhang, Jingwen; Zhang, Xiang; Martin, Robert C G

2014-02-01

Malignant transformation of hepatocellular carcinoma (HCC) occurs through repetitive liver injury in a context of inflammation and oxidative DNA damage. A spectrum of natural sesquiterpenoids from curcuma oil has displayed antioxidant, anti-inflammatory and anti-carcinogenic properties. The aim of the study was to investigate the hepatoprotective and anti-HCC effects of curcuma oil in vivo and in vitro. Mice were pretreated with curcuma oil (100 mg/kg) for 3 days, then treated with Concanavalin A (30 mg/kg). The hepatic tissue was evaluated for histology, CD4+ cell, interferon-γ, apoptosis, lipid peroxidation, 8-hydroxy-deoxyguanosine and MnSOD. C57L/J mice were treated with curcuma oil and 107 Hepa1-6 cells directly inoculated into liver lobes. The effects of curcuma oil on cell growth and cell death were evaluated. In addition, MnSOD, HSP60, catalase, NF-κB and caspase-3 were also investigated in the Hepa1-6 cells treated with curcuma oil. Pretreatment with curcuma oil significantly attenuates inflammation and oxidative damage by Concanavalin A. Treatment with curcuma oil can decrease the incidence of HCC. Curcuma oil inhibits cell growth and induces cell death in Hepa1-6 cells. Curcuma protected mice with hepatic injury from inflammatory and oxidative stress. Curcuma oil can inhibit hepatoma cell growth in vivo and in vitro.

Liver transplantation in patients with hepatocellular carcinoma

NARCIS (Netherlands)

Polak, Wojciech G.; Soyama, Akihiko; Slooff, Maarten J. H.

2008-01-01

Liver transplantation has a definitive place in the treatment of patients with hepatocellular carcinoma (HCC) in a cirrhotic liver. Patients with a tumor load within the Milan criteria have excellent survival comparable to survival in patients with benign indications. When tumor load exceeds the

Hyperkalaemia after radiofrequency ablation of hepatocellular carcinoma

NARCIS (Netherlands)

Verhoevena, BH; Haagsma, EB; Appeltans, BMG; Slooff, MJH; de Jong, KP

Radiofrequency ablation of liver tumours is a useful therapy for otherwise unresectable tumours. The complication rate is said to be low. In this case report we describe hyperkalaemia after radiofrequency ablation of a hepatocellular carcinoma in a patient with end-stage renal insufficiency. (C)

Understanding the tumor suppressor PTEN in chronic alcoholism and hepatocellular carcinoma.

Science.gov (United States)

Shearn, Colin T; Petersen, Dennis R

2015-01-01

The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a phosphatidylinositol (PtdIns) phosphatase that regulates Akt activation via PtdIns 3 kinase. Changes in PTEN expression and/or activity have been identified in a variety of chronic hepatocellular disorders including obesity, NAFLD, NASH, and alcoholism. In cancer biology, PTEN is frequently mutated or deleted in a wide variety of tumors. Mutations, decreased promoter activity, and decreased expression in PTEN are frequently identified in patients with hepatocellular carcinoma. While the majority of research on PTEN concerns obesity and NASH, PTEN clearly has a role in hepatic insulin sensitivity and in the development of steatosis during chronic alcoholism. Yet, in chronic alcoholics and HCC, very little is known concerning PTEN mutation/deletion or low PTEN expression. This review is focused on an overview of the current knowledge on molecular mechanisms of dysregulation of PTEN expression/activity in the liver and their relationship to development of ethanol-induced hepatocellular damage and cancer.

Enhanced synthesis and secretion of apolipoprotein E from sciatic nerves of streptozotocin-induced diabetic rats after injury

International Nuclear Information System (INIS)

Ishibashi, S.; Yamada, N.; Oka, Y.

1988-01-01

To elucidate the pathogenesis of diabetic neuropathy, synthesis and secretion of apolipoprotein E (apo E) from sciatic nerves after injury was studied in normal and streptozotocin-induced diabetic rats. Seven, 14, 28, 45 and 59 days after making crush injury on sciatic nerves with concomitant administration of streptozotocin (50 mg/kg body weight), the nerves were taken out and incubated with [ 35 S]methionine. The [ 35 S]labeled apo E was precipitated with specific antiserum. The amounts of apo E secreted into medium by nerves of diabetic rats were 7 times greater than those of non-diabetic rats 7 days after injury. This enhanced secretion of apo E was relatively selective for this protein, since the ratio of the immunoprecipitable apo E to the TCA preciptitable protein in the medium increased in diabetic rats. Intriguing possibility deduced from these results is that the secretion of apo E is involved in the development of diabetic neuropathy

Pigmented hepatocellular adenoma with complete CD34 immunostaining pattern: A diagnostic dilemma

Directory of Open Access Journals (Sweden)

Mukul Vij

2012-01-01

Full Text Available WHO defines hepatocellular adenoma (HCA as a benign tumor composed of cells closely resembling normal hepatocytes, which are arranged in plates separated by sinusoids. It is more common in women. The present concerns a 41 years female who was found to have a mass lesion in liver on ultrasound while undergoing routine evaluation for dyspepsia. Computed tomography scan of abdomen showed 10 × 8 cm lesion in liver. Extended left hepatectomy was performed. Grossly hepatic cut surface showed circumscribed tumor with dark gray or black color. Microscopy revealed hepatocellular adenoma with abundant Dubin Johnson like pigment deposition. CD34 immunostaining showed complete sinusoidal pattern. We labeled the tumor as pigmented hepatic adenoma with complete CD34 staining pattern. To the best of author′s knowledge only eight cases of pigmented hepatocellular adenoma are described in world literature.

Value of MR histogram analyses for prediction of microvascular invasion of hepatocellular carcinoma.

Science.gov (United States)

Huang, Ya-Qin; Liang, He-Yue; Yang, Zhao-Xia; Ding, Ying; Zeng, Meng-Su; Rao, Sheng-Xiang

2016-06-01

The objective is to explore the value of preoperative magnetic resonance (MR) histogram analyses in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Fifty-one patients with histologically confirmed HCC who underwent diffusion-weighted and contrast-enhanced MR imaging were included. Histogram analyses were performed and mean, variance, skewness, kurtosis, 1th, 10th, 50th, 90th, and 99th percentiles were derived. Quantitative histogram parameters were compared between HCCs with and without MVI. Receiver operating characteristics (ROC) analyses were generated to compare the diagnostic performance of tumor size, histogram analyses of apparent diffusion coefficient (ADC) maps, and MR enhancement.The mean, 1th, 10th, and 50th percentiles of ADC maps, and the mean, variance. 1th, 10th, 50th, 90th, and 99th percentiles of the portal venous phase (PVP) images were significantly different between the groups with and without MVI (P histogram analyses-in particular for 1th percentile for PVP images-held promise for prediction of MVI of HCC.

Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular carcinoma in vitro and in vivo.

Science.gov (United States)

Xiang, Jianfeng; Xiang, Yanjie; Lin, Shengming; Xin, Dongwei; Liu, Xiaoyu; Weng, Lingling; Chen, Tao; Zhang, Minguang

2014-04-01

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world whose chemoprevention became increasingly important in HCC treatment. Although the anticancer effects of asparagus constituents have been investigated in several cancers, its effects on hepatocellular carcinoma have not been fully studied. In this study, we investigated the anticancer effects of the deproteinized asparagus polysaccharide on the hepatocellular carcinoma cells using the in vitro and in vivo experimental model. Our data showed that deproteinized asparagus polysaccharide might act as an effective inhibitor on cell growth in vitro and in vivo and exert potent selective cytotoxicity against human hepatocellular carcinoma Hep3B and HepG2 cells. Further study showed that it could potently induce cell apoptosis and G2/M cell cycle arrest in the more sensitive Hep3B and HepG2 cell lines. Moreover, deproteinized asparagus polysaccharide potentiated the effects of mitomycin both in vitro and in vivo. Mechanistic studies revealed that deproteinized asparagus polysaccharide might exert its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. In conclusion, deproteinized asparagus polysaccharide exhibited significant anticancer activity against hepatocellular carcinoma cells and could sensitize the tumoricidal effects of mitomycin, indicating that it is a potential therapeutic agent (or chemosensitizer) for liver cancer therapy.

A hepatectomized case of hepatocellular carcinoma after fast neutron irradiation therapy

International Nuclear Information System (INIS)

Nagashima, Tohru; Ryu, Takamasa; Watanabe, Yoshiji

1985-01-01

A 51-year-old male patient with hepatocellular carcinoma was treated preoperatively by fast neutron radiotherapy (910 rad/7 fractions/15 days) with a field of 8 x 6 cm. Radiation-associated liver function disturbance was scarcely observed. No side effect, such as loss of appetite and general fatigue, was encountered. According to the classification of Ohoshi and Shimosato, histological effect of radiation was graded as II sub(A). There is no preoperative fast neutron radiotherapy for hepatocellular carcinoma in Japan in the literature. (Namekawa, K.)

Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis

Science.gov (United States)

Jiang, Han-Yu; Chen, Jie; Xia, Chun-Chao; Cao, Li-Kun; Duan, Ting; Song, Bin

2018-01-01

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major public health problem worldwide. Hepatocarcinogenesis is a complex multistep process at molecular, cellular, and histologic levels with key alterations that can be revealed by noninvasive imaging modalities. Therefore, imaging techniques play pivotal roles in the detection, characterization, staging, surveillance, and prognosis evaluation of HCC. Currently, ultrasound is the first-line imaging modality for screening and surveillance purposes. While based on conclusive enhancement patterns comprising arterial phase hyperenhancement and portal venous and/or delayed phase wash-out, contrast enhanced dynamic computed tomography and magnetic resonance imaging (MRI) are the diagnostic tools for HCC without requirements for histopathologic confirmation. Functional MRI techniques, including diffusion-weighted imaging, MRI with hepatobiliary contrast agents, perfusion imaging, and magnetic resonance elastography, show promise in providing further important information regarding tumor biological behaviors. In addition, evaluation of tumor imaging characteristics, including nodule size, margin, number, vascular invasion, and growth patterns, allows preoperative prediction of tumor microvascular invasion and patient prognosis. Therefore, the aim of this article is to review the current state-of-the-art and recent advances in the comprehensive noninvasive imaging evaluation of HCC. We also provide the basic key concepts of HCC development and an overview of the current practice guidelines. PMID:29904242

Validity of Alpha Fetoprotein for Diagnosis of Hepatocellular Carcinoma in Cirrhosis

International Nuclear Information System (INIS)

Sarwar, S.; Tarique, S.; Khan, A. A.

2014-01-01

Objective: To determine the accuracy of serum alpha fetoprotein (AFP) for diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. Study Design: Observational study. Place and Duration of Study: Department of Medicine, The King Edward Medical University, Lahore, from November 2007 to August 2011. Methodology: Consecutive patients, diagnosed with HCC by contrast enhanced CT, MRI or biopsy were included as cases. Patients of cirrhosis with no evidence of HCC were enrolled as controls. Demographic, laboratory and radiological data were recorded. Serum AFP was determined in all patients at outset and was analyzed using ROC curve for its accuracy in diagnosing HCC. Results: A total of 275 patients were included; of them 173 had HCC and 102 had cirrhosis. One hundred and thirty nine cases (80.3%) with HCC and 86 (84.3%) without HCC had cirrhosis due to HCV. Stage of liver disease, as determined by Child Turcotte Pugh (CTP) score, was comparable; mean CTP value 7.97 A +- 2.1A +- 2.21 in control group (p 0.41). Area under curve (AUC) for AFP was 0.85 (95%, CI: 0.80 - 0.90) with optimum cut off value of 20.85 ng/ml which showed 72.2% sensitivity, 86.2% specificity, 89.9% positive predictive value, 64.7% negative predictive value and 77.4% overall accuracy in diagnosing patients with HCC. Conclusion: Despite sub-optimal sensitivity, alpha fetoprotein is still a valid screening test for diagnosis of hepatocellular carcinoma till other more sensitive markers are developed. Till then, it should be used in conjunction with ultrasound. (author)

Hepatocellular carcinoma: risk groups, surveillance and outcome

NARCIS (Netherlands)

van Meer, S

2016-01-01

The burden of hepatocellular carcinoma (HCC) has changed in the past few decades. Although the majority of HCC cases develops in East Asia and Sub-Saharan Africa, HCC has become an increasing problem in Western countries such as the Netherlands. Surveillance for HCC is controversial because of

Role of contrast-enhanced helical CT in the evaluation of acute thoracic aortic injuries after blunt chest trauma

International Nuclear Information System (INIS)

Scaglione, M.; Pinto, A.; Pinto, F.; Romano, L.; Ragozzino, A.; Grassi, R.

2001-01-01

The purpose of this retrospective study was to determine the value of contrast-enhanced helical CT for detecting and managing acute thoracic aortic injury (ATAI). Between June 1995 and February 2000, 1419 consecutive chest CT examinations were performed in the setting of major blunt trauma. The following CT findings were considered indicative of ATAI: intimal flap; pseudoaneurysm; contour irregularity; lumen abnormality; and extravasation of contrast material. On the basis of these direct findings no further diagnostic investigations were performed. Isolated mediastinal hematoma on CT scans was considered an indirect sign of ATAI: In these cases, thoracic aortography was performed even if CT indicated normal aorta. Seventy-seven patients had abnormal CT scans: Among the 23 patients with direct CT signs, acute thoracic aortic injuries was confirmed at thoracotomy in 21. Two false-positive cases were observed. The 54 remaining patients had isolated mediastinal hematoma without aortic injuries at CT and corresponding negative angiograms. The 1342 patients with negative CT scans were included in the 8-month follow-up program and did not show any adverse sequela based on clinical and radiographic criteria. Contrast-enhanced helical CT has a critical role in the exclusion of thoracic aortic injuries in patient with major blunt chest trauma and prevents unnecessary thoracic aortography. Direct CT signs of ATAI do not require further diagnostic investigations to confirm the diagnosis: Isolated aortic bands or contour vessel abnormalities should be first considered as possible artifacts or related to non-traumatic etiologies especially when mediastinal hematoma is absent. In cases of isolated mediastinal hematoma other possible sources of bleeding should be considered before directing patients to thoracic aortography. (orig.)

Nuclear receptor CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation in mouse liver.

Science.gov (United States)

Yamazaki, Yuichi; Moore, Rick; Negishi, Masahiko

2011-11-01

The liver is endowed with the ability to regenerate hepatocytes in response to injury. When this regeneration ability is impaired during liver injury, oval cells, which are considered to be postnatal hepatic progenitors, proliferate and differentiate into hepatocytes. Here we have demonstrated that 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) activates the nuclear receptor constitutive active/androstane receptor (CAR), resulting in proliferation of oval cells in mouse liver. Activation of CAR by DDC was shown by hepatic nuclear CAR accumulation and cytochrome P450 (CYP)2B10 mRNA induction after feeding a 0.1% DDC-containing diet to Car(+/+) mice. After being fed the DDC diet, Car(+/+), but not Car(-/-) mice, developed severe liver injury and an A6 antibody-stained ductular reaction in an area around the portal tract. Oval cell proliferation was confirmed by laser capture microdissection and real-time PCR; mRNAs for the two oval cell markers epithelial cell adhesion molecule and TROP2 were specifically induced in the periportal region of DDC diet-fed Car(+/+), but not Car(-/-) mice. Although rates of both hepatocyte growth and death were initially enhanced only in DDC diet-fed Car(+/+) mice, growth was attenuated when oval cells proliferated, whereas death continued unabated. DDC-induced liver injury, which differs from other CAR activators such as phenobarbital, occurred in the periportal region where cells developed hypertrophy, accumulated porphyrin crystals and inflammation developed, all in association with the proliferation of oval cells. Thus, CAR provides an excellent experimental model for further investigations into its roles in liver regeneration, as well as the development of diseases such as hepatocellular carcinoma.

Spontaneous rupture of adrenal metastasis from hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Lim, Chae Hun; Kim, Hyun Jin; Park, Soo Youn; Hwang, Seong Su; Choi, Hyun Joo [St. Vincent Hospital, Suwon (Korea, Republic of)

2007-03-15

Rupture of adrenal tumor from various primary origins is a rather rare event. We report here on a ruptured adrenal metastasis from hepatocellular carcinoma, and this ruptured metastasis was observed at the time of the initial diagnosis.

Regulation of human hepatocellular carcinoma cells by Spred2 and correlative studies on its mechanism

International Nuclear Information System (INIS)

Ma, Xiao-Ni; Liu, Xiao-Yun; Yang, Yue-Feng; Xiao, Feng-Jun; Li, Qing-Fang; Yan, Jun; Zhang, Qun-Wei; Wang, Li-Sheng; Li, Xue-Yan; Wang, Hua

2011-01-01

Highlights: → Hepatocellular carcinoma is inhibited by Spred2 through as yet unclear mechanisms. → We studied the overexpression of Spred2 in cell line and murine tumor models of HCC. → Spred2 inhibited cell proliferation and migration via attenuating ERK signaling. → Spred2 overexpression induced apoptosis via caspase-3 and downregulated Mcl-1. → A Spred2 knockdown markedly induced tumor growth in vivo. -- Abstract: Members of the Spred gene family are negative regulators of the Ras/Raf-1/ERK pathway, which has been associated with several features of the tumor malignancy. However, the effect of Spred genes on hepatocellular carcinoma (HCC) remains uninvestigated. In the present work, we analyzed the in vitro and in vivo effects of Spred2 expression on the hepatic carcinoma cell line, SMMC-7721. In addition to attenuated ERK activation, which inhibited the proliferation and migration of unstimulated and HGF-stimulated SMMC-7721 cells. Adenovirus-mediated Spred2 overexpression induced the activation of caspase-3 and apoptosis, as well as reduced the expression level of Mcl-1. Most importantly, the knockdown of Spred2 markedly enhanced tumor growth in vivo. In conclusion, these results suggest that Spred2 could qualify as a potential therapeutic target in HCC.

Soluble ICAM-1 activates lung macrophages and enhances lung injury

DEFF Research Database (Denmark)

Schmal, H; Czermak, B J; Lentsch, A B

1998-01-01

production of TNF-alpha and the CXC chemokine, macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages exhibited cytokine responses to both sICAM-1 and immobilized sICAM-1, while rat PBMCs failed to demonstrate similar responses. Exposure of alveolar macrophages to sICAM-1 resulted in NFkappa......B activation (which was blocked by the presence of the aldehyde peptide inhibitor of 28S proteosome and by genistein, a tyrosine kinase inhibitor). As expected, cross-linking of CD18 on macrophages with Ab resulted in generation of TNF-alpha and MIP-2. This response was also inhibited in the presence...... of TNF-alpha and MIP-2 and increased neutrophil recruitment. Therefore, through engagement of beta2 integrins, sICAM-1 enhances alveolar macrophage production of MIP-2 and TNF-alpha, the result of which is intensified lung injury after intrapulmonary disposition of immune complexes....

Radiofrequency ablation of hepatocellular carcinoma: Mono or multipolar?

Science.gov (United States)

Cartier, Victoire; Boursier, Jérôme; Lebigot, Jérôme; Oberti, Frédéric; Fouchard-Hubert, Isabelle; Aubé, Christophe

2016-03-01

Thermo-ablation by radiofrequency is recognized as a curative treatment for early-stage hepatocellular carcinoma. However, local recurrence may occur because of incomplete peripheral tumor destruction. Multipolar radiofrequency has been developed to increase the size of the maximal ablation zone. We aimed to compare the efficacy of monopolar and multipolar radiofrequency for the treatment of hepatocellular carcinoma and determine factors predicting failure. A total of 171 consecutive patients with 214 hepatocellular carcinomas were retrospectively included. One hundred fifty-eight tumors were treated with an expandable monopolar electrode and 56 with a multipolar technique using several linear bipolar electrodes. Imaging studies at 6 weeks after treatment, then every 3 months, assessed local effectiveness. Radiofrequency failure was defined as persistent residual tumor after two sessions (primary radiofrequency failure) or local tumor recurrence during follow-up. This study received institutional review board approval (number 2014/77). Imaging showed complete tumor ablation in 207 of 214 lesions after the first session of radiofrequency. After a second session, only two cases of residual viable tumor were observed. During follow-up, there were 46 local tumor recurrences. Thus, radiofrequency failure occurred in 48/214 (22.4%) cases. By multivariate analysis, technique (P radiofrequency failure. Failure rate was lower with the multipolar technique for tumors radiofrequency, multipolar radiofrequency improves tumor ablation with a subsequent lower rate of local tumor recurrence. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Delayed presentation and diagnosis of metastatic hepatocellular ...

African Journals Online (AJOL)

Hepatocellular carcinoma (HCC) is rarely diagnosed in women of reproductive age. ... an adverse effect on HCC, and that high levels of oestrogen associated with pregnancy may ... A 30-year-old pregnant woman presented at 23 weeks' gestation and was diagnosed as HIV-infected, with anaemia. She was initiated on.

The role of contrast-enhanced ultrasonography in image-guided liver ablations

International Nuclear Information System (INIS)

Pescatori, Lorenzo Carlo; Sconfienza, Luca Maria; Mauri, Giovanni

2016-01-01

We read with great interest the paper by Kim et al. entitled “Local ablation therapy with contrast enhanced ultrasonography for hepatocellular carcinoma: a practical review,” recently published in Ultrasonography. We think that contrast-enhanced ultrasonography (CEUS), together with the development of reliable navigation systems, is likely to represent one of the most important advances in image-guided ablations in recent years. Thus, we offer some considerations on the topic

Correlations of matrix metalloproteinase content and expression with invasion and metastasis of hepatocellular carcinoma

International Nuclear Information System (INIS)

Zhang Zhichao; Jia Mingku; Sun Yaxin

2006-01-01

Objective: To investigate the correlations of serum matrix metalloproteinase-2, -9 (MMP-2, MMP-9) contents and tissue expressions in hepatocellular carcinoma with tumor invasion and metastasis. Methods: Serum MMP-2, MMP-9 contents were detected in 40 patient with hepatocellular carcinoma and 20 healthy controls by ELISA; the expressions and distributions of MMP-2 and MMP-9 in 40 patients and 10 normal tissues were detected by immunohistochemical method. Results: Serum MMP-2, MMP-9 contents were significantly elevated in cancer samples compared with normal serum (P<0.01), the significant difference was found between contents in the presence and the absence of lymph node metastasis (P<0.05). In hepatocellular carcinoma, the expressions of MMP-2, MMP-9 were increased significantly compared with normal tissue. The expressions of MMP-2, MMP-9 were correlated with histological grade and lymph node metastasis (P<0.05). Conclusion: The serum of MMP-2 and MMP-9 contents and their expressions may provide reliable information for hepatocellular carcinoma prognosis. (authors)

Intravenous miR-144 inhibits tumor growth in diethylnitrosamine-induced hepatocellular carcinoma in mice.

Science.gov (United States)

He, Quan; Wang, Fangfei; Honda, Takashi; Lindquist, Diana M; Dillman, Jonathan R; Timchenko, Nikolai A; Redington, Andrew N

2017-10-01

Previous in vitro studies have demonstrated that miR-144 inhibits hepatocellular carcinoma cell proliferation, invasion, and migration. We have shown that miR-144, injected intravenously, is taken up by the liver and induces endogenous hepatic synthesis of miR-144. We hypothesized that administered miR-144 has tumor-suppressive effects on liver tumor development in vivo. The effects of miR-144 on tumorigenesis and tumor growth were tested in a diethylnitrosamine-induced hepatocellular carcinoma mouse model. MiR-144 injection had no effect on body weight but significantly reduced diethylnitrosamine-induced liver enlargement compared with scrambled microRNA. MiR-144 had no effect on diethylnitrosamine-induced liver tumor number but reduced the tumor size above 50%, as evaluated by magnetic resonance imaging (scrambled microRNA 23.07 ± 5.67 vs miR-144 10.38 ± 2.62, p hepatocellular carcinoma tumorigenesis. Exogenously delivered miR-144 may be a therapeutic strategy to suppress tumor growth in hepatocellular carcinoma.

Dynamic contrast enhanced MR imaging for evaluation of angiogenesis of hepatocellular nodules in liver cirrhosis in N-nitrosodiethylamine induced rat model

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wei; Chen, Hui Juan; Huang, Wei; Zhang, Long Jiang [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Wang, Zhen J. [University of California, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

2017-05-15

To investigate whether dynamic contrast -enhanced MRI (DCE-MRI) can distinguish the type of liver nodules in a rat model with N-nitrosodiethylamine- induced cirrhosis. Liver nodules in cirrhosis were induced in 60 male Wistar rats via 0.01 % N-nitrosodiethylamine in the drinking water for 35-100 days. The nodules were divided into three groups: regenerative nodule (RN), dysplastic nodule (DN), and hepatocellular carcinoma (HCC). DCE-MRI was performed, and parameters including transfer constant (K{sup trans}), rate constant (K{sub ep}), extravascular extracellular space volume fraction (V{sub e}), and initial area under the contrast concentration versus time curve (iAUC) were measured and compared. The highest K{sup trans} and iAUC values were seen in HCC, followed by DN and RN (all P < 0.05). The area under the receiver operating characteristic curve (AUROC) for DN and HCC were 0.738 and 0.728 for K{sup trans} and iAUC, respectively. The AUROC for HCC were 0.850 and 0.840 for K{sup trans} and iAUC, respectively. Ordinal logistic regression analysis showed that K{sup trans} had a high goodness of fit (0.970, 95 % confidence interval, 13.751-24.958). DCE-MRI is a promising method to differentiate of liver nodules. Elevated K{sup trans} suggested that the nodules may be transformed into HCC. (orig.)

Upregulation of MiR-212 Inhibits Migration and Tumorigenicity and Inactivates Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma.

Science.gov (United States)

Jia, Pengbo; Wei, Guangbing; Zhou, Cancan; Gao, Qi; Wu, Yunhua; Sun, Xuejun; Li, Xuqi

2018-01-01

MicroRNAs are involved in hepatocellular carcinoma metastasis, a principal cause of hepatocellular carcinoma-related death in patients worldwide. MiR-212 is a microRNA that has been identified in several types of cancers and is postulated to influence cell signaling and subsequent malignant pathogenesis. Despite emerging reports suggesting that miR-212 plays a significant role in the onset, progression, and migration of these types of malignant tumors, its involvement in the development of hepatocellular carcinoma has not been fully elucidated. Quantitative reverse transcription polymerase chain reaction, wound healing, transwell migration and invasion assays, Western blotting, and xenograft tumor growth models were performed to test the expression levels and functions of miR-212 in hepatocellular carcinoma. Luciferase reporter assay, quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry were used to identify and verify the target of miR-212. In this study, we identify significant repression of miR-212 in hepatocellular carcinoma and demonstrate that overexpression of miR-212 inhibits the migration of hepatocellular carcinoma cells in vitro and in vivo. Furthermore, we identify forkhead box M1, whose expression is inversely related to that of miR-212, as a direct target of miR-212. Additionally, reexpression of forkhead box M1 rescues the miR-212-mediated inhibition of cell migration. We observed that inhibition of miR-212 activates forkhead box M1 but inhibits the Wnt/β-catenin pathway by suppressing Wnt, LEF-1, c-Myc, and nuclear β-catenin. Finally, in vivo studies confirmed the inhibitory effect of miR-212 on hepatocellular carcinoma growth. Our present findings indicate that miR-212 is a potential prognostic biomarker of hepatocellular carcinoma and that the miR-212/forkhead box M1 regulatory axis may represent a new therapeutic objective for hepatocellular carcinoma treatment.

Cerebrovascular accidents associated with sorafenib in hepatocellular carcinoma.

Science.gov (United States)

Saif, Muhammad W; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. Laboratory data were noncontributory. The head CT scan did not reveal acute abnormalities. No hemodynamically significant stenosis was visible in the carotid ultrasound, and the echocardiogram showed normal size of the heart chambers and normal systolic function of the left ventricle. Sorafenib was discontinued in both cases. Physicians should monitor patients receiving sorafenib for neurologic symptoms, and in the absence of other etiology, prompt discontinuation of this drug should be considered.

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria.

Science.gov (United States)

Kim, Young; Stahl, Christopher C; Makramalla, Abouelmagd; Olowokure, Olugbenga O; Ristagno, Ross L; Dhar, Vikrom K; Schoech, Michael R; Chadalavada, Seetharam; Latif, Tahir; Kharofa, Jordan; Bari, Khurram; Shah, Shimul A

2017-12-01

Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N = 214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400 ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17 months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for

Fibrolamellar Hepatocellular Carcinoma Presenting as Obstructive Jaundice: Uncommon Presentation of a Rare Entity

International Nuclear Information System (INIS)

Arora, Richa

2015-01-01

Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor, significantly different from generic hepatocellular carcinoma with distinct demographics, risk factors, imaging features, histopathology and prognosis. Unlike conventional hepatocellular carcinoma, it presents in young individuals with no preexisting hepatitis or cirrhosis and does not cause elevation of serum alpha feto proteins in most cases. This paper presents a case report of this rare tumor in a young female with an unusual clinical manifestation of obstructive jaundice (which has not been reported so far) along with a review of its imaging and pathological features, with treatment options. Fibrolamellar HCC is a rare variant of classic HCC with different epidemiology, risk factors, clinical manifestations, radiological, pathological and prognostic features. Therefore, it is important to be familiar with the entity for its early diagnosis and management

Efficacy of intrahepatic absolute alcohol in unrespectable hepatocellular carcinoma

International Nuclear Information System (INIS)

Farooqi, J.I.; Hameed, K.; Khan, I.U.; Shah, S.

2001-01-01

To determine efficacy of intrahepatic absolute alcohol injection in researchable hepatocellular carcinoma. A randomized, controlled, experimental and interventional clinical trial. Gastroenterology Department, PGMI, Hayatabad Medical Complex, Peshawar during the period from June, 1998 to June, 2000. Thirty patients were treated by percutaneous, intrahepatic absolute alcohol injection sin repeated sessions, 33 patients were not given or treated with alcohol to serve as control. Both the groups were comparable for age, sex and other baseline characteristics. Absolute alcohol therapy significantly improved quality of life of patients, reduced the tumor size and mortality as well as showed significantly better results regarding survival (P< 0.05) than the patients of control group. We conclude that absolute alcohol is a beneficial and safe palliative treatment measure in advanced hepatocellular carcinoma (HCC). (author)

Case report combined hepatocellular and cholangiocarcinoma with sarcomatous transformation.

Science.gov (United States)

Boonsakan, Paisarn; Thangnapakorn, Orathai; Tapaneeyakorn, Jiemjit; Kositchaiwat, Sawit; Bunyaratvej, Sukhum

2007-03-01

Combined hepatocellular and cholangiocarcinoma with sarcomatous transformation was first recognized in Ramathibodi Hospital in 2005. This variant of carcinoma has been increasingly reported particularly from Asian countries. Dedifferentiation of the epithelial component to various sarcomatous components is likely the underlying mechanism. The causative factors of hepatocarcinogenesis in Thailand include chronic viral hepatitis B or C, exposures to aflatoxin B1 and nitrosamine(s) and occasionally some certain nodular hepatocellular lesions due to arterial hyperperfusion. It is suggested that the recent change of the Thai peoples' life style to an increased consumption of fast foods containing food preservatives especially nitrate or nitrite, the nitrosamine precursor may allow heavy exposure(s) to the chemical carcinogen(s) i.e. nitrosamine(s) leading to sarcomatous transformation of the carcinoma.

[A single metastasis in the carpal bones as the first clinical manifestation of a hepatocellular carcinoma].

Science.gov (United States)

Corrales Pinzón, R; Alonso Sánchez, J M; de la Mano González, S; El Karzazi Tarazona, K

2014-01-01

Hepatocellular carcinoma is the most common primary tumor of the liver. Spreading outside the liver usually takes place in advanced stages of the disease, and bone is the third most common site of metastases. We present a case of hepatocellular carcinoma in which the first clinical manifestation was a single metastasis to the carpal bones. The interest of this case lies in the way this hepatocellular carcinoma manifested as well as in the unusual site of the metastasis. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Pretreatment Evaluation with Contrast-Enhanced Ultrasonography for Percutaneous Radiofrequency Ablation of Hepatocellular Carcinomas with Poor Conspicuity on Conventional Ultrasonography

International Nuclear Information System (INIS)

Kim, Ah Yeong; Lee, Min Woo; Rhim, Hyunchul; Cha, Dong Ik; Choi, Dongil; Kim, Young-sun; Lim, Hyo Keun; Cho, Seong Whi

2013-01-01

To determine whether pretreatment evaluation with contrast-enhanced ultrasonography (CEUS) is effective for percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) with poor conspicuity on conventional ultrasonography (US). This retrospective study was approved by the institutional review board and informed consent was waived. From June 2008 to July 2011, 82 patients having HCCs (1.2 ± 0.4 cm) with poor conspicuity on planning US for RFA were evaluated with CEUS prior to percutaneous RFA. We analyzed our database, radiologic reports, and US images in order to determine whether the location of HCC candidates on planning US coincide with that on CEUS. To avoid incomplete ablation, percutaneous RFA was performed only when HCC nodules were identified on CEUS. The rate of technical success was assessed. The cumulative rate of local tumor progression was estimated with the use of the Kaplan-Meier method (mean follow-up: 24.0 ± 13.0 months). Among 82 patients, 73 (89%) HCCs were identified on CEUS, whereas 9 (11%) were not. Of 73 identifiable HCCs on CEUS, the location of HCC on planning US corresponded with that on CEUS in 64 (87.7%), whereas the location did not correspond in 9 (12.3%) HCCs. Technical success was achieved for all 73 identifiable HCCs on CEUS in a single (n = 72) or two (n = 1) RFA sessions. Cumulative rates of local tumor progression were estimated as 1.9% and 15.4% at 1 and 3 years, respectively. Pretreatment evaluation with CEUS is effective for percutaneous RFA of HCCs with poor conspicuity on conventional US

Diagnostic and therapeutic management of hepatocellular carcinoma

Science.gov (United States)

Bellissimo, Francesco; Pinzone, Marilia Rita; Cacopardo, Bruno; Nunnari, Giuseppe

2015-01-01

Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemo-embolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines. PMID:26576088

Prognosis of small hepatocellular nodules detected only at the hepatobiliary phase of Gd-EOB-DTPA-enhanced MR imaging as hypointensity in cirrhosis or chronic hepatitis

Energy Technology Data Exchange (ETDEWEB)

Higaki, Atsushi; Ito, Katsuyoshi; Tamada, Tsutomu; Sone, Teruki; Kanki, Akihiko; Noda, Yasufumi; Yasokawa, Kazuya; Yamamoto, Akira [Kawasaki Medical School, Department of Radiology, Kurashiki City, Okayama (Japan)

2014-10-15

To evaluate the prognosis of ''strict'' high-risk nodules (small hepatocellular nodules detected only in the hepatobiliary phase of initial Gd-EOB-DTPA-enhanced MR examination) in patients with cirrhosis or chronic hepatitis. The study included thirty-three patients with 60 ''strict'' high-risk nodules showing hypointensity at the hepatobiliary phase that was undetectable at the vascular phase and other conventional sequences of initial Gd-EOB-DTPA-enhanced MR imaging. These nodules were observed on follow-up MR examinations until hypervascularity was detected. The potential predictive factors for hypervascular transformation were compared between two groups (group A showing hypervascular transformation, group B not showing hypervascularization). Ten (16.7 %) of 60 ''strict'' high-risk nodules showed hypervascular transformation during follow-up periods (group A). The growth rates of the nodules in group A (6.3 ± 4.5 mm/year) were significantly higher than those in group B (3.4 ± 7.2 mm/year) (p = 0.003). Additionally, the median observation period in group A (177.5 ± 189.5 day) was significantly shorter than in group B (419 ± 372.2 day) (p = 0.045). The other predictive factors were not significantly correlated with hypervascularization. Subsets of ''strict'' high-risk nodules showed hypervascular transformation during follow-up periods in association with increased growth rates, indicating that nodule growth rate is an important predictive factor for hypervascularization. (orig.)

An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas.

Science.gov (United States)

Cicalese, Luca; Raun, Loren; Shirafkan, Ali; Campos, Laura; Zorzi, Daria; Montalbano, Mauro; Rhoads, Colin; Gazis, Valia; Ensor, Katherine; Rastellini, Cristiana

2017-11-01

Primary liver cancer is a significant cause of cancer-related death in both the United States and the world at large. Hepatocellular carcinoma comprises 90% of these primary liver cancers and has numerous known etiologies. Evaluation of these identified etiologies and other traditional risk factors cannot explain the high incidence rates of hepatocellular carcinoma in Texas. Texas is home to the second largest petrochemical industry and agricultural industry in the nation; industrial activity and exposure to pathogenic chemicals have never been assessed as potential links to the state's increased incidence rate of hepatocellular carcinoma. The association between the county-level concentrations of 4 air pollutants known to be linked to liver cancer, vinyl chloride, arsenic, benzene, and 1,3-butadiene, and hepatocellular carcinoma rates was evaluated using nonparametric generalized additive logistic regression and gamma regression models. Hepatocellular carcinoma incidence rates for 2000-2013 were evaluated in comparison to 1996 and 1999 pollution concentrations and hepatocellular carcinoma rates for the subset of 2006-2013 were evaluated in comparison to 2002 and 2005 pollution concentrations, respectively. The analysis indicates that the relationship between the incidence of liver cancer and air pollution and risk factors is nonlinear. There is a consistent significant positive association between the incidence of liver cancer and hepatitis C prevalence rates (gamma all years, p < 0.05) and vinyl chloride concentrations (logistic 2002 and 2005, p < 0.0001; gamma 2002 and 2005, p < 0.05). This study suggests that vinyl chloride is a significant contributor to the incidence of liver cancer in Texas. The relationship is notably nonlinear. Further, the study supports the association between incidence of liver cancer and prevalence of hepatitis B.

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

Energy Technology Data Exchange (ETDEWEB)

Lee, Edward Wolfgang; Alanis, Lourdes [Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Cho, Sung-Ki [Division of Interventional Radiology, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351 (Korea, Republic of); Saab, Sammy [Division of Hepatology, Department of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles, CA 90024 (United States)

2016-11-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: Current and updated literature review

International Nuclear Information System (INIS)

Lee, Edward Wolfgang; Alanic, Lourdes; Cho, Sung Ki; Saab, Sammy

2016-01-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma

Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor prognosis in hepatocellular carcinoma.

Science.gov (United States)

An, Jun; Liu, Zhiyong; Liang, Qiong; Pan, Yuhang; Li, Haifeng; Wang, Ruizhi; Jin, Yi

2017-09-01

The expression of Rabl3 and Cullin7 is relevant to the carcinogenesis of certain cancers. However, the relationship of this expression with hepatocellular carcinoma remains unclear. To study the protein expression of Rabl3 and Cullin7 and to evaluate their role in hepatocarcinogenesis, in 162 cases of hepatocellular carcinoma, we used immunohistochemistry to investigate the expression of Rabl3 and Cullin7 in both the cancer tissues and the normal hepatic tissues around the hepatocellular carcinoma. The results demonstrated that the rates of positive Rabl3 and Cullin7 expression were 80.2% and 69.1%, respectively, in hepatocellular carcinoma tissues. However, the rates of positive Rabl3 and Cullin7 expression were 31.5% and 29.0%, respectively, in adjacent normal hepatic tissues. Rabl3 and Cullin7 were expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent normal hepatic tissues (Phepatocellular carcinoma tissues of patients with lymph node metastasis, tumor thrombi in the portal vein and an advanced clinical stage (Phepatocellular carcinoma cohort. Moreover, patients with positive expression for both Rabl3 and Cullin7 had a remarkably shorter survival time compared with patients with negative expression for both proteins (Phepatocellular carcinoma and could be used as a prognostic indicator in patients with hepatocellular carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

International Nuclear Information System (INIS)

Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

2016-01-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma

Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: Current and updated literature review

Energy Technology Data Exchange (ETDEWEB)

Lee, Edward Wolfgang; Alanic, Lourdes [Div. of Interventional Radiology, Dept. of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles (United States); Cho, Sung Ki [Div. of Interventional Radiology, Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Saab, Sammy [Div. of Hepatology, Dept. of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles (United States)

2016-07-15

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review.

Science.gov (United States)

Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

2016-01-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma

Science.gov (United States)

Wilson, C. L.; Jurk, D.; Fullard, N.; Banks, P.; Page, A.; Luli, S.; Elsharkawy, A. M.; Gieling, R. G.; Chakraborty, J. Bagchi; Fox, C.; Richardson, C.; Callaghan, K.; Blair, G. E.; Fox, N.; Lagnado, A.; Passos, J. F.; Moore, A. J.; Smith, G. R.; Tiniakos, D. G.; Mann, J.; Oakley, F.; Mann, D. A.

2015-04-01

Hepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dimers and the co-repressor HDAC1. These anti-inflammatory proteins combine to transcriptionally repress hepatic expression of a S100A8/9, CXCL1 and CXCL2 neutrophil chemokine network. Loss of nfkb1 promotes ageing-associated chronic liver disease (CLD), characterized by steatosis, neutrophillia, fibrosis, hepatocyte telomere damage and HCC. Nfkb1S340A/S340Amice carrying a mutation designed to selectively disrupt p50:p50:HDAC1 complexes are more susceptible to HCC; by contrast, mice lacking S100A9 express reduced neutrophil chemokines and are protected from HCC. Inhibiting neutrophil accumulation in CLD or targeting their tumour-promoting activities may offer therapeutic opportunities in HCC.

Serologic and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation

DEFF Research Database (Denmark)

Pommergaard, Hans-Christian; Burcharth, Jakob Hornstrup Frølunde; Rosenberg, Jacob

2016-01-01

INTRODUCTION: Recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC) is a major cause of mortality. Knowledge on biomarkers may contribute to better surveillance based on the patients' risk of recurrence. Reviewing the literature, we aimed to identify serological...... and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation. METHODS: A literature search was performed in the databases PubMed and Scopus to identify observational studies evaluating serological or molecular biomarkers for recurrence of HCC after LT using adjusted analysis...

Hepatitis B virus induces cell proliferation via HBx-induced microRNA-21 in hepatocellular carcinoma by targeting programmed cell death protein4 (PDCD4 and phosphatase and tensin homologue (PTEN.

Directory of Open Access Journals (Sweden)

Preeti Damania

Full Text Available Hepatitis B viral infection-induced hepatocellular carcinoma is one of the major problems in the developing countries. One of the HBV proteins, HBx, modulates the host cell machinery via several mechanisms. In this study we hypothesized that HBV enhances cell proliferation via HBx-induced microRNA-21 in hepatocellular carcinoma. HBx gene was over-expressed, and miRNA-21 expression and cell proliferation were measured in Huh 7 and Hep G2 cells. miRNA-21 was over-expressed in these cells, cell proliferation and the target proteins were analyzed. To confirm the role of miRNA-21 in HBx-induced proliferation, Hep G 2.2.1.5 cells (a cell line that expresses HBV stably were used for miRNA-21 inhibition studies. HBx over-expression enhanced proliferation (3.7- and 4.5-fold increase; n = 3; p<0.01 and miRNA-21 expression (24- and 36-fold increase, normalized with 5S rRNA; p<0.001 in Huh 7 and Hep G2 cells respectively. HBx also resulted in the inhibition of miRNA-21 target proteins, PDCD4 and PTEN. miRNA-21 resulted in a significant increase in proliferation (2- and 2.3-fold increase over control cells; p<0.05 in Huh 7 and Hep G2 cells respectively and decreased target proteins, PDCD4 and PTEN expression. Anti-miR-21 resulted in a significant decrease in proliferation (p<0.05 and increased miRNA-21 target protein expression. We conclude that HBV infection enhances cell proliferation, at least in part, via HBx-induced miRNA-21 expression during hepatocellular carcinoma progression.

Knockdown of TMEM16A suppressed MAPK and inhibited cell proliferation and migration in hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Deng L

2016-01-01

Full Text Available Liang Deng,1,* Jihong Yang,2,* Hongwu Chen,3 Bo Ma,4 Kangming Pan,1 Caikun Su,1 Fengfeng Xu,1 Jihong Zhang1 1Department of Hepatobiliary Surgery, The Eastern Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 2Department of General Surgery, The Affiliated Hospital of Hebei University, Baoding, 3Department of Emergency, 4Department of Gastroenterology, The Eastern Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: TMEM16A plays an important role in cell proliferation in various cancers. However, less was known about the expression and role of TMEM16A in hepatocellular carcinoma. We screened the expression of TMEM16A in patients’ hepatocellular carcinoma tissues, and also analyzed the biological function of hepatocellular carcinoma cells by knockdown of TMEM16A, as well as the expression of MAPK signaling proteins, including p38, p-p38, ERK1/2, p-ERK1/2, JNK, and p-JNK, and cell cycle regulatory protein cyclin D1 in TMEM16A siRNA-transfected SMMC-7721 cells by Western blot. Our results showed that TMEM16A was overexpressed in hepatocellular carcinoma tissues. Inhibition of TMEM16A suppressed the cell proliferation, migration, and invasion, and cell cycle progression but did not influence the cell apoptosis. TMEM16A siRNA-suppressed cancer cell proliferation and tumor growth were accompanied by a reduction of p38 and ERK1/2 activation and cyclin D1 induction, and were not influenced by other tested MAPK signaling proteins. In addition, inhibition of TMEM16A suppressed tumorigenicity in vivo. TMEM16A is overexpressed in hepatocellular carcinoma, and that inhibition of TMEM16A suppressed MAPK and growth of hepatocellular carcinoma. TMEM16A could be a potentially novel therapeutic target for human cancers, including hepatocellular carcinoma.Keywords: TMEM16A, cell cycle, proliferation, apoptosis

Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.

Science.gov (United States)

Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

2014-10-01

Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial

Leptomeningeal metastasis from hepatocellular carcinoma with other unusual metastases: a case report

International Nuclear Information System (INIS)

Pan, Zhenyu; Yang, Guozi; Yuan, Tingting; Pang, Xiaochuan; Wang, Yongxiang; Qu, Limei; Dong, Lihua

2014-01-01

Leptomeningeal metastasis, which results from metastasis of tumors to the arachnoid and pia mater, can lead to the dissemination of tumor cells throughout the subarachnoid space via the cerebral spinal fluid, and frequently with a poor prognosis. The primary tumor in adults is most often breast cancer, lung cancer, or melanoma. Although leptomeningeal metastasis due to cholangiocarcinoma has been reported, to the best of our knowledge there is no cytologically confirmed report of leptomeningeal metastasis from hepatocellular carcinoma. We herein report a case of leptomeningeal metastasis from hepatocellular carcinoma in a 53-year-old woman with concomitant systemic metastases to the lung, bone, brain, kidney, adrenal gland, subcutaneous tissues, and abdominal pelvis. The neurological symptoms of the patient were relieved after treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy. To our knowledge this is the first report of leptomeningeal metastasis from hepatocellular carcinoma confirmed by cytology. Treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy was effective

Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma

International Nuclear Information System (INIS)

Leung, Henry W. C.; Liu, Chung-Feng; Chan, Agnes L. F.

2016-01-01

Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO’s guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan

Ultrasonographic finding of hepatocellular carcinoma

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Ryu, Han Soo; Woo, Seong Ku; Lim, Jae Hoon; Ko, Young Tae; Kim, Ho Kyun; Kim, Soon Yong [Kyung Hee University Hospital, Seoul (Korea, Republic of)

1983-12-15

With the development of gray scale ultrasonography, detection and evaluation of hepatic parenchymal disease including space occupying lesion are easily performed and frequently used in the world. Thrity five cases of histopathologically proven and ultrasonographically suggested hepatocellular carcinoma are retrospectively studied. The results were as follows; 1. Ultrasonographic findings of hepatocellular carcinoma show hyperechoic pattern in 22 cases (63%), hypoechoic pattern in 2 cases (6%), and mixed pattern in 11 cases (31%). 2. The margin of tumor is ill-defined in 19 cases (54%) and well defined in16 cases (46%). 3. The size of tumor by sonographic measurement was large than 5 cm in diameter in 33 cases (94%). 4. The number of tumor is solitary in 19 cases and multiple in 16 cases. The sites of involved lobe were right lobe in 22 cases (63%), left lobe in 2 cases (6%), and both lobes in 11 cases (31%). 5. Associated sonographic findings were hepatomegaly with focal contour change in 25 cases (71%), splenomegaly in 16 cases (46%), cirrhosis of liver in 15 cases (43%), ascites in 11 cases (31%) and tumoral thrombosis in portal vein in 8 cases (23%). 6. The sex ratio is 6 : 1 male predominence and the age ranges from 32 to 76 years with highest incidence in 5th and 6th decades.

Magnetic Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy

DEFF Research Database (Denmark)

Ungureanu, Bogdan Silviu; Teodorescu, Cristian-Mihail; Săftoiu, Adrian

2016-01-01

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver, ranking as the second most common cause of death from cancer worldwide. Magnetic nanoparticles (MNPs) have been used so far in tumor diagnosis and treatment, demonstrating great potential and promising results...

Histological heterogeneity in primary and metastatic classic combined hepatocellular-cholangiocarcinoma: a case series.

Science.gov (United States)

De Vito, Claudio; Sarker, Debashis; Ross, Paul; Heaton, Nigel; Quaglia, Alberto

2017-11-01

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare and aggressive primary liver cancer with both hepatocellular and cholangiocellular differentiation. Due to its bi-phenotypic component, cHCC-CC is a heterogeneous tumour and histopathological analysis of metastatic deposits is poorly characterized. In this retrospective study, we describe four patients in whom the histology from resected specimens of both primary and recurrent and/or metastatic tumour was available for comparison and immunohistochemical characterization. Our study shows that recurrent or metastatic deposits replicate the heterogeneity of the primary cHCC-CC, that even originally small foci of divergent differentiation can become predominant later on and that hepatocellular and cholangiocellular components can show different tropism in distant organs. In our experience, the behaviour of recurrent/metastatic cHCC-CC is unpredictable and histological examination is necessary to guide treatment options at present.

Added value of smooth hypointense rim in the hepatobiliary phase of gadoxetic acid-enhanced MRI in identifying tumour capsule and diagnosing hepatocellular carcinoma

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An, Chansik; Han, Kyunghwa; Choi, Jin-Young; Park, Mi-Suk; Kim, Myeong-Jin [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Rhee, Hyungjin [Yonsei University College of Medicine, Department of Pathology, Brain Korea 21 PLUS Project for Medical Science, Integrated Genomic Research Center for Metabolic Regulation, Seoul (Korea, Republic of); Park, Young-Nyun [Yonsei University College of Medicine, Department of Pathology, Brain Korea 21 PLUS Project for Medical Science, Integrated Genomic Research Center for Metabolic Regulation, Seoul (Korea, Republic of); Yonsei University College of Medicine, Severance Biomedical Science Institute, Seoul (Korea, Republic of); Park, Sumi [National Health Insurance Service Ilsan Hospital, Department of Radiology, Goyang (Korea, Republic of)

2017-06-15

To examine the added value of considering smooth hypointense rim in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI as capsule appearance for diagnosing tumour capsules and hepatocellular carcinoma (HCC). A total of 377 hepatic lesions (330 HCCs, 35 non-HCC malignancies and 12 benign) were included from 345 patients who underwent resection after MRI between January 2008 and December 2011. Two radiologists assessed the presence or absence of conventional capsule appearance and smooth hypointense rim in the HBP, and categorized each hepatic lesion according to the Liver Imaging Reporting and Data System. Difference in diagnostic performance was evaluated using the generalized estimating equation method. For identifying capsule, the sensitivity and accuracy of HBP hypointense rim were significantly higher than those of conventional capsule appearance (81.5 % vs. 57.8 % and 76.1 % vs. 59.4 %, respectively; P < 0.001). For diagnosing HCC, the sensitivity and accuracy of LR-5 or LR-5 V were significantly higher when the HBP hypointense rim was also considered capsule appearance (83 % vs. 72.7 % and 84.1 % vs. 75.1 %, respectively; P < 0.001), with the same specificity (91.5 %). Regarding smooth hypointense rim in the HBP as capsule appearance could improve the detection of tumour capsule and the diagnosis of HCC. (orig.)

Dose response relationship in local radiotherapy for hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok

2001-01-01

In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2±7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver

Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis.

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Lewis, Anthony J; Zhang, Xianghong; Griepentrog, John E; Yuan, Du; Collage, Richard D; Waltz, Paul K; Angus, Derek C; Zuckerbraun, Brian S; Rosengart, Matthew R

2018-05-04

The physiology of nearly all mammalian organisms are entrained by light and exhibit circadian rhythm. The data derived from animal studies show that light influences immunity, and these neurophysiologic pathways are maximally entrained by the blue spectrum. Here, we hypothesize that bright blue light reduces acute kidney injury by comparison with either bright red or standard, white fluorescent light in mice subjected to sepsis. To further translational relevance, we performed a pilot clinical trial of blue light therapy in human subjects with appendicitis. Laboratory animal research, pilot human feasibility trial. University basic science laboratory and tertiary care hospital. Male C57BL/6J mice, adult (> 17 yr) patients with acute appendicitis. Mice underwent cecal ligation and puncture and were randomly assigned to a 24-hour photoperiod of bright blue, bright red, or ambient white fluorescent light. Subjects with appendicitis were randomized to receive postoperatively standard care or standard care plus high-illuminance blue light. Exposure to bright blue light enhanced bacterial clearance from the peritoneum, reduced bacteremia and systemic inflammation, and attenuated the degree of acute kidney injury. The mechanism involved an elevation in cholinergic tone that augmented tissue expression of the nuclear orphan receptor REV-ERBα and occurred independent of alterations in melatonin or corticosterone concentrations. Clinically, exposure to blue light after appendectomy was feasible and reduced serum interleukin-6 and interleukin-10 concentrations. Modifying the spectrum of light may offer therapeutic utility in sepsis.

A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury

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Marta Koch

2018-02-01

Full Text Available Injury to the adult central nervous systems (CNS can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducted a gain-of-function genetic screen in Drosophila to identify strong inducers of axonal growth after injury. We focus on a novel axis the Down Syndrome Cell Adhesion Molecule (Dscam1, the de-ubiquitinating enzyme Fat Facets (Faf/Usp9x and the Jun N-Terminal Kinase (JNK pathway transcription factor Kayak (Kay/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3′-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism.

Radioembolisation for treatment of pediatric hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Hawkins, Clifford Matthew; Kukreja, Kamlesh [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Geller, James I. [Cincinnati Children' s Hospital Medical Center, Department of Hematology/Oncology, Cincinnati, OH (United States); Schatzman, Carmen; Ristagno, Ross [University of Cincinnati, UC Health, Department of Radiology, Division of Interventional Radiology, Cincinnati, OH (United States)

2013-07-15

Transarterial radioembolisation with yttrium-90 (TARE-Y90), a catheter-directed therapy, has been used extensively in adults to treat primary and secondary hepatic malignancies. To our knowledge, the use of this palliative technique has not been described in children. We present two children with unresectable hepatocellular carcinoma (HCC) treated with TARE-Y90. (orig.)

CTP synthase forms the cytoophidium in human hepatocellular carcinoma.

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Chang, Chia-Chun; Jeng, Yung-Ming; Peng, Min; Keppeke, Gerson Dierley; Sung, Li-Ying; Liu, Ji-Long

2017-12-15

CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma. Copyright © 2017. Published by Elsevier Inc.

Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma.

Science.gov (United States)

Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

2016-07-21

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.

Chemopreventive effect of corosolic acid in human hepatocellular ...

African Journals Online (AJOL)

Anticancer effects of corosolic acid have been demonstrated earlier in human cervix adenocarcinoma and osteosarcoma cells, but the exact underlying molecular mechanisms have not been studied. Hence, an attempt was made to identify the anticancer mechanism of corosolic acid in human hepatocellular carcinoma cells ...

Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid (Gd-EOB-DTPA)-Enhanced Magnetic Resonance Imaging and Multidetector-Row Computed Tomography for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

Science.gov (United States)

Ye, Feng; Liu, Jun; Ouyang, Han

2015-08-01

The purpose of this meta-analysis was to compare the diagnostic accuracy of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and multidetector-row computed tomography (MDCT) for hepatocellular carcinoma (HCC).Medline, Cochrane, EMBASE, and Google Scholar databases were searched until July 4, 2014, using combinations of the following terms: gadoxetic acid disodium, Gd-EOB-DTPA, multidetector CT, contrast-enhanced computed tomography, and magnetic resonance imaging. Inclusion criteria were as follows: confirmed diagnosis of primary HCC by histopathological examination of a biopsy specimen; comparative study of MRI using Gd-EOB-DTPA and MDCT for diagnosis of HCC; and studies that provided quantitative outcome data. The pooled sensitivity and specificity of the 2 methods were compared, and diagnostic accuracy was assessed with alternative-free response receiver-operating characteristic analysis.Nine studies were included in the meta-analysis, and a total of 1439 lesions were examined. The pooled sensitivity and specificity for 1.5T MRI were 0.95 and 0.96, respectively, for 3.0T MRI were 0.91 and 0.96, respectively, and for MDCT were 0.74 and 0.93, respectively. The pooled diagnostic odds ratio for 1.5T and 3.0T MRI was 242.96, respectively, and that of MDCT was 33.47. To summarize, Gd-EOB-DTPA-enhanced MRI (1.5T and 3.0T) has better diagnostic accuracy for HCC than MDCT.

Comparison of AMI-25 enhanced MRI and helical dynamic CT in the detection of hepatic lesions

International Nuclear Information System (INIS)

Saitou, Kazuhiro; Matsuda, Hiromichi; Fukushima, Hiroaki; Kanzaki, Hiroshi; Hirose, Takashi; Karizaki, Dai; Abe, Kimihiko; Amino, Saburou

1994-01-01

We performed AMI-25 enhanced MRI and helical dynamic CT in 12 cases of hepatic lesions. Nine of these were hepatocellular carcinomas. Two cases were metastatic liver tumors (the primary lesion was gastric in one and the other was gallbladder cancer). One case was suspected to be adenomatous hyperplasia. Thirty-two lesions were detected in T2-weighted SE images before AMI-25 administration, while 46 lesions were detected in AMI-25 enhanced MRI images. In particular, AMI-25 enhanced MRI was superior to plain MRI in lesions less than 10 mm in size. A total of 48 lesions were detected in helical dynamic CT. Although AMI-25 enhanced MRI almost equaled helical dynamic CT in the detection of liver tumors, helical dynamic CT was slightly superior to AMI-25 enhanced MRI in the detection of subphrenic lesions. It was possible to know the hemodynamics in each hepatic lesion by helical dynamic CT. AMI-25 enhanced MRI was useful to know the inclusion of reticuloendothelial system, and that yielded different diagnoses in adenomatous hyperplasia and well differentiated hepatocellular carcinoma. Helical dynamic CT was useful for qualitative diagnosis. Both AMI-25 enhanced MRI and helical dynamic CT contributed to the detection of liver tumor and qualitative diagnosis. (author)

FBX8 Acts as an Invasion and Metastasis Suppressor and Correlates with Poor Survival in Hepatocellular Carcinoma.

Directory of Open Access Journals (Sweden)

Feifei Wang

Full Text Available F-box only protein 8 (FBX8, a novel component of F-box proteins, is lost in several cancers and has been associated with invasiveness of cancer cells. However, its expression pattern and role in the progression of hepatocellular carcinoma remain unclear. This study investigated the prognostic significance of FBX8 in hepatocellular carcinoma samples and analyzed FBX8 function in hepatocellular carcinoma cells by gene manipulation.The expression of FBX8 was detected in 120 cases of clinical paraffin-embedded hepatocellular carcinoma tissues, 20 matched pairs of fresh tissues and five hepatocellular carcinoma cell lines by immunohistochemistry with clinicopathological analyses, real-time RT-PCR or Western blot. The correlation of FBX8 expression with cell proliferation and invasion in five HCC cell lines was analyzed. Moreover, loss of function and gain of function assays were performed to evaluate the effect of FBX8 on cell proliferation, motility, invasion in vitro and metastasis in vivo.We found that FBX8 was obviously down-regulated in HCC tissues and cell lines (P<0.05. The FBX8 down-regulation correlated significantly with poor prognosis, and FBX8 status was identified as an independent significant prognostic factor. Over-expression of FBX8 decreased proliferation, migration and invasion in HepG2 and 97H cells, while knock-down of FBX8 in 7721 cells showed the opposite effect. FBX8 negatively correlated with cell proliferation and invasion in 7701, M3, HepG2 and 97H cell lines. In vivo functional assays showed FBX8 suppressed tumor growth and pulmonary metastatic potential in mice. Our results indicate that down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma treatment.

A discussion of serum albumin level in advanced-stage hepatocellular carcinoma: a medical oncologist's perspective.

Science.gov (United States)

Tanriverdi, Ozgur

2014-11-01

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and it is particularly prevalent in East and Southeast Asia. With surgical and/or local interventional treatment methods, survival rates for early-stage hepatocellular cancers have increased. However, it is not yet clear which staging systems are more applicable in hepatocellular carcinoma. Serum albumin level is already being used as a criterion in most staging systems. Albumin is an important serum protein in human bodily functions, but only 5 % of the daily amount needed is synthesized by the liver. The serum albumin level is affected by multifactorial situations, including capillary permeability, drugs, liver insufficiency, inflammation and/or infections, dehydration or overhydration, protein loosing disorders, and decreased nutrition intake in anorexia-malnutrition syndrome and cancer cachexia. Because of this complex situation, serum albumin level may affect many staging systems for hepatocellular carcinoma by leading to false-negative results. In this paper, the statuses of current staging systems are reviewed, and possible negative events regarding the serum albumin levels found in these staging systems are discussed.

An investigation into the effects of temporal resolution on hepatic dynamic contrast-enhanced MRI in volunteers and in patients with hepatocellular carcinoma

International Nuclear Information System (INIS)

Gill, Andrew B; Graves, Martin J; Lomas, David J; Black, Richard T; Bowden, David J; Priest, Andrew N

2014-01-01

This study investigated the effect of temporal resolution on the dual-input pharmacokinetic (PK) modelling of dynamic contrast-enhanced MRI (DCE-MRI) data from normal volunteer livers and from patients with hepatocellular carcinoma. Eleven volunteers and five patients were examined at 3 T. Two sections, one optimized for the vascular input functions (VIF) and one for the tissue, were imaged within a single heart-beat (HB) using a saturation-recovery fast gradient echo sequence. The data was analysed using a dual-input single-compartment PK model. The VIFs and/or uptake curves were then temporally sub-sampled (at interval ▵t = [2–20] s) before being subject to the same PK analysis. Statistical comparisons of tumour and normal tissue PK parameter values using a 5% significance level gave rise to the same study results when temporally sub-sampling the VIFs to HB < ▵t <4 s. However, sub-sampling to ▵t > 4 s did adversely affect the statistical comparisons. Temporal sub-sampling of just the liver/tumour tissue uptake curves at ▵t ≤ 20 s, whilst using high temporal resolution VIFs, did not substantially affect PK parameter statistical comparisons. In conclusion, there is no practical advantage to be gained from acquiring very high temporal resolution hepatic DCE-MRI data. Instead the high temporal resolution could be usefully traded for increased spatial resolution or SNR. (paper)

MicroRNA gene polymorphisms and environmental factors increase patient susceptibility to hepatocellular carcinoma.

Directory of Open Access Journals (Sweden)

Yin-Hung Chu

Full Text Available BACKGROUND: Micro RNAs (miRNAs are small RNA fragments that naturally exist in the human body. Through various physiological mechanisms, miRNAs can generate different functions for regulating RNA protein levels and balancing abnormalities. Abnormal miRNA expression has been reported to be highly related to several diseases and cancers. Single-nucleotide polymorphisms (SNPs in miRNAs have been reported to increase patient susceptibility and affect patient prognosis and survival. We adopted a case-control research design to verify the relationship between miRNAs and hepatocellular carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: A total of 525 subjects, including 377 controls and 188 hepatocellular carcinoma patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and real-time PCR were used to analyze miRNA146a (rs2910164, miRNA149 (rs2292832, miRNA196 (rs11614913, and miRNA499 (rs3746444 genetic polymorphisms between the control group and the case group. The results indicate that people who carry the rs3746444 CT or CC genotypes may have a significantly increased susceptibility to hepatocellular carcinoma (adjusted odds ratio [AOR] = 2.84, 95% confidence interval [CI] = 1.88-4.30. In addition, when combined with environmental risk factors, such as smoking and alcohol consumption, interaction effects were observed between gene polymorphisms and environmental factors (odds ratio [OR] = 4.69, 95% CI = 2.52-8.70; AOR = 3.38, 95% CI = 1.68-6.80. CONCLUSIONS: These results suggest that a significant association exists between miRNA499 SNPs and hepatocellular carcinoma. Gene-environment interactions of miRNA499 polymorphisms, smoking, and alcohol consumption might alter hepatocellular carcinoma susceptibility.

Peritoneal carcinomatosis: an unusual presentation of fibrolamellar hepatocellular carcinoma; Carcinomatosis peritoneal como forma de presentacion infrecuente del hepatocarcinoma fibrolamelar

Energy Technology Data Exchange (ETDEWEB)

Vicente, R; Garcia-Gutierrez, J A; Fernandez, A; Santalla, F [Hospital Comarcal de la Axarquia. Malaga (Spain)

2001-07-01

Fibrolamellar hepatocellular carcinoma is an uncommon malignant tumor with characteristic clinical, radiological and histopahtological features that is usually associated with a more favorable natural course and greater survival than more common variants of hepatocellular carcinoma. We describe an atypical case of a fibrolamellar hepatocellular carcinomas sowing aggressive behaviour in a 20-year-old woman. The lesion presented with massive ascites, and imaging studies revealed extensive peritoneal metastatic spread. (Author) 8 refs.

Deubiquitinase inhibitor b-AP15 activates endoplasmic reticulum (ER) stress and inhibits Wnt/Notch1 signaling pathway leading to the reduction of cell survival in hepatocellular carcinoma cells.

Science.gov (United States)

Ding, Youming; Chen, Xiaoyan; Wang, Bin; Yu, Bin; Ge, Jianhui

2018-04-15

b-AP15, a potent and selective inhibitor of the ubiquitin-specific peptidase 14 (USP14), displays in vitro and in vivo antitumor abilities on some types of cancer cells. However, the mechanism underlying its action is not well elucidated. The purposes of the present study are to observe the potential impacts of b-AP15 on cell survival of hepatocellular carcinoma cells and to investigate whether and how this compound inhibits some survival-promoting signaling pathways. We found that b-AP15 significantly decreased cell viability and increased cell apoptosis in a dose-dependent manner in hepatocellular carcinoma cells, along with the perturbation of cell cycle and the decreased expressions of cell cycle-related proteins. We also demonstrated that the endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) were enhanced by b-AP15 supplementation. The inhibition of ER stress/UPR only partly attenuated the cytotoxicity of b-AP15 on hepatocellular carcinoma cells. In addition, b-AP15 treatment inhibited Wnt/β-catenin and Notch1 signaling pathways, and suppressed phosphorylation of STAT3, Akt, and Erk1/2, which were not restored by the inhibition of ER stress/UPR. Furthermore, the expression levels of signaling molecules in Notch1 were reduced by specific inhibitor of Wnt/β-catenin pathway. Notably, either Wnt or Notch1 signaling inhibitor mitigated phosphorylation of STAT3, Akt, and Erk1/2, and mimicked the cytotoxicity of b-AP15 on hepatocellular carcinoma cells. These results clearly indicate that b-AP15 induced cytotoxic response to hepatocellular carcinoma cells by augmenting ER stress/UPR and inhibiting Wnt/Notch1 signaling pathways. This new finding provides a novel mechanism by which b-AP15 produces its antitumor therapeutic effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Combined polymer-curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery.

Science.gov (United States)

Requejo-Aguilar, Raquel; Alastrue-Agudo, Ana; Cases-Villar, Marta; Lopez-Mocholi, Eric; England, Richard; Vicent, María J; Moreno-Manzano, Victoria

2017-01-01

Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. Animal models of acute SCI have provided evidence that transplantation of ependymal stem/progenitor cells of the spinal cord (epSPCs) induces functional recovery, while systemic administration of the anti-inflammatory curcumin provides neuroprotection. However, functional recovery from chronic stage SCI requires additional enhancements in available therapeutic strategies. Herein, we report on a combination treatment for SCI using epSPCs and a pH-responsive polymer-curcumin conjugate. The incorporation of curcumin in a pH-responsive polymeric carrier mainchain, a polyacetal (PA), enhances blood bioavailability, stability, and provides a means for highly localized delivery. We find that PA-curcumin enhances neuroprotection, increases axonal growth, and can improve functional recovery in acute SCI. However, when combined with epSPCs, PA-curcumin also enhances functional recovery in a rodent model of chronic SCI. This suggests that combination therapy may be an exciting new therapeutic option for the treatment of chronic SCI in humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using peer mentoring for people with spinal cord injury to enhance self-efficacy beliefs and prevent medical complications.

Science.gov (United States)

Ljungberg, Inger; Kroll, Thilo; Libin, Alexander; Gordon, Samuel

2011-02-01

Individuals with spinal cord injury/disease are faced with a myriad of psychosocial adjustment challenges. This article describes the implementation of a peer-mentoring programme designed to support this adjustment process for people with SCI/disease and the programme's believed impact on self-efficacy and prevention of medical complications. With shorter length of stay in acute inpatient rehabilitation after spinal cord injury/disease, peer mentor programmes are becoming an important component to assist with education and community re-integration. Quasi-experimental non-controlled pretest/post-test. Patients with newly acquired spinal cord injury/disease participated in a one-year spinal cord injury peer-mentoring programme. Peer mentors met with their assigned participants regularly during inpatient care and on discharge to track medical complications and assist with adjusting to life after spinal cord injury/disease. In all, of 37 mentees enrolled, 24 successfully completed the programme. Sixty-seven per cent showed improved self-efficacy score between the two time points. Medical complications and doctor visits all decreased significantly between 0-6 months and 7-12 months. Our findings indicate that the older an individual is, the lower the likelihood of having a urinary tract infection (p = 0.006). The programme was well received by all mentees who felt they could connect well with their peer mentor. Peer mentoring in a rehabilitation setting enhances the understanding of challenges that patients and medical staff deal with on a day-to-day basis. Our findings suggest it is important to monitor and educate individuals with spinal cord injury/disease at the acute stage to improve medical outcomes. Caution is advised in the interpretation of these results as they were obtained in a small non-random sample using self-report data. Peer mentors play an increasingly important role in nurse-delivered education in the spinal cord injury/disease population. © 2011

Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

DEFF Research Database (Denmark)

Chaisaingmongkol, Jittiporn; Budhu, Anuradha; Dang, Hien

2017-01-01

Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integratio...

Preclinical evaluation of transcriptional targeting strategy for human hepatocellular carcinoma in an orthotopic xenograft mouse model.

Science.gov (United States)

Sia, Kian Chuan; Huynh, Hung; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Hui, Kam Man; Lam, Paula Yeng Po

2013-08-01

Gene regulation of many key cell-cycle players in S-, G(2) phase, and mitosis results from transcriptional repression in their respective promoter regions during the G(0) and G(1) phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma.

Transhemangioma Ablation of Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Pua, Uei

2012-01-01

Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

Current management of hepatocellular carcinoma

Science.gov (United States)

Tabrizian, Parissa; Roayaie, Sasan; Schwartz, Myron E

2014-01-01

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis. Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system. The choice among therapeutic options that include liver resection, liver transplantation, locoregional, and systemic treatments must be individualized for each patient. The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice. PMID:25132740

Transhemangioma Ablation of Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Pua, Uei, E-mail: druei@yahoo.com [Tan Tock Seng Hospital, Department of Diagnostic Radiology (Singapore)

2012-12-15

Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

Emerging role of microRNAs in the treatment of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Callegari E

2015-05-01

Full Text Available Elisa Callegari,1 Marco Domenicali,2 Laura Gramantieri,3 Massimo Negrini,1 Silvia Sabbioni4 1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 2Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 3Center for Applied Biomedical Research, S Orsola-Malpighi University Hospital, Bologna, 4Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy Abstract: Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide. Currently available curative options, such as surgery and transplantation, are not available to patients with advanced stages of disease. Among the potential new treatments being investigated are microRNA (miRNA-based therapies. A number of preclinical studies have reported antitumor activities of miRNA mimics or anti-miRNA molecules. Optimal in vivo delivery of miRNA molecules is crucial to their action. To this end, significant progress has been made in the development of nanoparticles for in vivo delivery of miRNA molecules. Delivery of these molecules, alone or in combination with other drugs, promises to open new possibilities for therapeutic approaches to hepatocellular carcinoma. Keywords: hepatocellular carcinoma, microRNA, nanocarriers, therapy 

Association between hepatitis B virus/hepatitis C virus infection and primary hepatocellular carcinoma risk: A meta-analysis based on Chinese population.

Science.gov (United States)

Li, Libo; Lan, Xiaolin

2016-12-01

To assess the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), and HBV/HCV double infection and hepatocellular carcinoma risk in Chinese population. The databases of PubMed and CNKI were electronic searched by reviewers according to the searching words of HBV, HCV, and hepatocellular carcinoma. The related case-control studies or cohort studies were included. The association between virus infection and hepatocellular carcinoma risk was demonstrated by odds ratio (OR) and 95% confidence interval (95% CI). The data were pooled by fixed or random effects model according to the statistical heterogeneity. The publication bias was assessed by Begg's funnel plot and Egger's linear regression test. Finally, 13 publications were included in this meta-analysis. For significant statistical heterogeneity (I2 = 99.8%,P = 0.00), the OR was pooled by random effects model. The pooled results showed that HBV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 58.01, 95% CI: 44.27-71.75); statistical heterogeneity analysis showed that significant heterogeneity existed in evaluation of HCV infection and hepatocellular carcinoma risk across the included 13 studies I2 = 77.78%, P = 0.00). The OR was pooled by random effects model. The pooled results showed that HCV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 2.34, 95% CI: 1.20-3.47); significant heterogeneity did not exist in evaluation HBV/HCV double infection and hepatocellular carcinoma risk for the included 13 studies (I2 = 0.00%,P = 0.80). The OR was pooled by fixed effects model. The pooled results showed that HBV/HCV double infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 11.39, 95% CI: 4.58-18.20). No publication bias was found in the aspects of HBV, HCV, and HBV/HCV double infection and hepatocellular carcinoma. For Chinese population, HBV, HCV or HBV/HCV double infection can

Mutant woodchuck hepatitis virus genomes from virions resemble rearranged hepadnaviral integrants in hepatocellular carcinoma.

OpenAIRE

Kew, M C; Miller, R H; Chen, H S; Tennant, B C; Purcell, R H

1993-01-01

Although hepadnaviruses are implicated in the etiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence DR1, less often DR2, or in the cohesive overlap region. Integrants invariab...

Potent efficacy signals from systemically administered oncolytic herpes simplex virus (HSV1716 in hepatocellular carcinoma xenograft models

Directory of Open Access Journals (Sweden)

Braidwood L

2014-10-01

Full Text Available Lynne Braidwood, Kirsty Learmonth, Alex Graham, Joe Conner Virttu Biologics Ltd, Department of Neurology, Southern General Hospital, Glasgow, UK Abstract: Oncolytic herpes simplex virus (HSV1716, lacking the neurovirulence factor ICP34.5, has highly selective replication competence for cancer cells and has been used in clinical studies of glioma, melanoma, head and neck squamous cell carcinoma, pediatric non-central nervous system solid tumors, and malignant pleural mesothelioma. To date, 88 patients have received HSV1716 and the virus is well tolerated, with selective replication in tumor cells and no spread to surrounding normal tissue. We assessed the potential value of HSV1716 in preclinical studies with two human hepatocellular carcinoma cell lines, HuH7 and HepG2-luc. HSV1716 displayed excellent replication kinetics in vitro in HepG2-luc cells, a cell line engineered to express luciferase, and virus-mediated cell killing correlated with loss of light emissions from the cells. In vivo, the HepG2-luc cells readily formed light-emitting xenografts that were easily visualized by an in vivo imaging system and efficiently eliminated by HSV1716 oncolysis after intratumoral injection. HSV1716 also demonstrated strong efficacy signals in subcutaneous HuH7 xenografts in nude mice after intravenous administration of virus. In the HuH7 model, the intravenously injected virus replicated prolifically immediately after efficient tumor localization, resulting in highly significant reductions in tumor growth and enhanced survival. Our preclinical results demonstrate excellent tumor uptake of HSV1716, with prolific replication and potent oncolysis. These observations warrant a clinical study of HSV1716 in hepatocellular carcinoma. Keywords: oncolytic herpes simplex virus, HSV1716, hepatocellular carcinoma, xenografts, efficacy 

Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

Directory of Open Access Journals (Sweden)

Behl Susanne

2008-03-01

Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0 with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01, a low score in the Okuda- and CLIP-classification (p Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. Trial registration Current Controlled Trials ISRCTN29319366.

Glycogen metabolism in radiation induced hepatocellular carcinoma in Swiss albino mice

International Nuclear Information System (INIS)

Gupta, N.K.; Kumar, Ashok

1988-01-01

Glycogen content and the activities of phosphorylase, glycogen sythetase (GS), glucose 6-phosphatase (G6Pase), phosphohexose isomerase (PHI), glucose 6-phosphodehydrogenase were biochemically determined in the heparocellular carcinoma induced in swiss albino mice following radiocalcium internal irradiation. The content glycogen and the activities of phosphorylase, glycogen synthetase, G6Pase, PHI, GPT and GOT are considerably reduced in the hepatocellular carcinoma compared to that in control liver. However, the activity of G6PDH shows an increased activity. Results indicate that the decreas ed glycogen content in the hepatocellular carcinoma is due to the reduced glycogen synthetase activity and utilization of glucose by HMP pathway. (author). 2 tabs., 24 refs

Two cases of Budd-Chiari syndrome complicated by hepatocellular carcinoma. Hemodynamic study with computed tomography and venacavography

Energy Technology Data Exchange (ETDEWEB)

Takayasu, Kenichi; Moriyama, Noriyuki; Suzuki, Masao [National Cancer Center, Tokyo (Japan). Hospital

1982-12-01

Two patients with Budd-Chiari syndrome complicated by hepatocellular carcinoma in whom CT and inferior venacavography were carried out are described. The imaging study with CT disclosed: 1) calcified inferior vena cava (IVC) at the level of the diaphragm and lack of enhancement of the IVC and hepatic veins after contrast enhancement, 2) markedly dilated inferior right hepatic vein, 3) marked compensatory enlargement of the caudate lobe, 4) icile-like thrombus extending caudally in the IVC and dilatation of that portion of the IVC, and 5) enlarged and dilated azygos, hemiazygos and anterior longitudinal venous trunk of the internal vertebral venous plexus, and with cavography, 1) the inferior right hepatic vein as a venous outlet to maintain the liver functions, and 2) occlusion of the right and left hepatic vein openings and a communicating vein between the left hepatic and caudate lobe vein.

Hepatitis viruses and hepatocellular carcinoma | Kew | South African ...

African Journals Online (AJOL)

Animal models - other members of the hepadnavirus family (to which HBV belongs) that also cause HCC in their respective animal hosts, and transgenic mice into which sequences of HBV DNA have been inserted - are proving useful in elucidating putative mechanisms of HBV-related hepatocellular carcinogenesis, but no ...

Tumoural portal vein thrombosis. Enhancement with MnDPDP

International Nuclear Information System (INIS)

Marti-Bonmati, L.; Lonjedo, E.; Mathieu, D.; Coffin, C.; Poyatos, C.; Anglade, M.C.

1997-01-01