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Sample records for hepatocellular tumor thrombus

  1. Computed tomographic and ultrasonographic diagnosis of portal vein tumor thrombus in hepatocellular carcinoma

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    Mori, H; Futagawa, S; Hayashi, K; Amagasaki, Y; Ochi, M [Nagasaki Univ. (Japan). School of Medicine

    1982-04-01

    Nine cases of hepatocellular carcinoma which have invaded the intra- and extrahepatic portal vein were evaluated by computed tomography (CT) and ultrasonography (US). The outstanding CT and sonographic features of the portal vein tumor thrombus were described. In CT, contrast opacification of normal portal vein and its major tributaries were not observed, and they were replaced by a soft tissue density mass representing the tumor thrombus. The thrombus measured 35 - 45 Hounsfield units (HU) in precontrast scans and 60 - 80 HU in postcontrast scans. The portal vein tumor thrombus showed a branched pattern of low density in porta hepatis and intrahepatic region due to differences in attenuation coefficients of the thrombus and adjacent noncancerous hepatic parenchyma on postcontrast scans. In ultrasound study, tumor thrombus was recognized as an echogenic solid mass in the porta hepatis obliterating the normal portal venous structures, or as an intraluminal solid mass in the dilated portal vein and its branches. Numerous collateral venous channels surrounding the thrombosed portal vein were also demonstrated on both CT and US. Particular emphasis was placed on the clinical implications of these non-invasive detection of the portal vein tumor thrombosis in patients with hepatocellular carcinoma.

  2. Long-term survival after liver transplant for recurrent hepatocellular carcinoma with bile duct tumor thrombus: case report.

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    Liu, Chao; Wang, Jie

    2012-12-01

    Hepatocellular carcinoma with bile duct tumor thrombus is considered an aggressive malignancy, and the prognosis of liver transplant for it remains obscure. A 42-year-old man with recurrent hepatocellular carcinoma and a history of surgical resection was admitted to our hospital with a 10-day history of yellowish urine and itchy skin. There were 3 lesions in the right lobe with the diameter of 2 cm each. A mass was found in the upper part of common bile duct, and the intrahepatic bile duct was dilated. His serum alpha-fetoprotein level was 2476 μg/L, total bilirubin level was 327 μmol/L, direct bilirubin level was 261 μmol/L, and alanine aminotransferase was 714 U/L. There was no main portal vein thrombus or extrahepatic metastases. Because of his poor liver function, he was listed for a liver transplant. During the wait (30 d), he underwent 9 episodes of plasmapheresis to decrease the serum level of bilirubin. He had an orthotopic liver transplant with the graft from a deceased donor. After the liver transplant, he received 5 cycles of chemotherapy with the regimen of oxaliplatin and 5-fluorouracil. This patient has survived without recurrence of hepatocellular carcinoma for more than 82 months and remains in good condition. Liver transplant may have a favorable result for hepatocellular carcinoma patient with a bile duct tumor thrombus, within the Milan criteria.

  3. Transarterial chemoembolization combined with sorafenib for the treatment of hepatocellular carcinoma with hepatic vein tumor thrombus

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    Zhang YF

    2016-07-01

    Full Text Available Yong-Fa Zhang,1–3,* Wei Wei,1–3,* Jia-Hong Wang,1–3,* Li Xu,1–3 Pei-En Jian,1–3 Cheng-Zuo Xiao,4 Xiao-Ping Zhong,1–3 Ming Shi,1–3 Rong-Ping Guo1–3 1Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 2State Key Laboratory of Oncology in South China, 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, 4Department of General Surgery, Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University, Shenzhen, People’s Republic of China *These authors contributed equally to this work Objective: To compare the treatment outcomes of sorafenib plus transarterial chemoembolization (TACE vs TACE alone in patients with hepatocellular carcinoma (HCC and hepatic vein tumor thrombus (HVTT.Methods: Twenty patients who were initially diagnosed with HCC and HVTT and received TACE combined with sorafenib during February 2009 to October 2013 were included in the study. To minimize selection bias, these patients were compared with 60 case-matched controls selected from a pool of 81 patients (in a 1:3 ratio who received TACE alone during the same period. The primary end point was overall survival (OS. The secondary end points were time to progression, disease control rate, and adverse events.Results: After a median follow-up period of 12.5 months (range, 1.03–44.23 months, the OS of the combined group was found to be significantly higher compared with the monotherapy group (14.9 vs 6.1 months, P=0.010. The time to progression was found to be significantly longer in the combined group (4.9 vs 2.4 months, P=0.016. Univariate and multivariate analyses revealed that the treatment allocation was an independent predictor of OS.Conclusion: Sorafenib plus TACE was well tolerated and was more effective in treating patients with advanced HCC and HVTT. Future trials with prospective larger samples are required to validate these results. Keywords: hepatocellular carcinoma, hepatic vein tumor thrombus, prognosis

  4. Hepatectomy for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus, Including Cases with Obstructive Jaundice.

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    Orimo, Tatsuya; Kamiyama, Toshiya; Yokoo, Hideki; Wakayama, Kenji; Shimada, Shingo; Tsuruga, Yosuke; Kamachi, Hirofumi; Taketomi, Akinobu

    2016-08-01

    This study aimed to evaluate the short- and long-term outcomes of hepatectomy for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT), including cases with obstructive jaundice. The study reviewed 42 HCC patients with BDTT, including six patients who needed preoperative biliary drainage due to obstructive jaundice, and 732 HCC patients without BDTT. The authors analyzed the impact of BDTT on the surgical outcomes and assessed the outcomes of hepatectomy for patients presenting with obstructive jaundice. The HCC patients with BDTT, almost all with stage 3 or 4 disease, had increased alpha-fetoprotein expression, larger tumors, and more portal vein invasion status. The survival of the HCC patients with BDTT was significantly inferior to that of the patients without BDTT (p = 0.0003). Survival did not differ significantly between the HCC patients with BDTT and those without BDTT when the two groups were matched by stage (p = 0.3366). The HCC patients with BDTT who presented with obstructive jaundice demonstrated outcomes similar to those for the HCC patients with BDTT who did not present with obstructive jaundice in terms of the overall survival rate (p = 0.5469). The perioperative outcomes for the HCC patients with BDTT did not depend on the presence or absence of preoperative jaundice. No patients in either BDTT group demonstrated 90-day mortality in this study. Hepatectomy should be considered for HCC patients with BDTT, even for patients with obstructive jaundice, because the surgical outcomes equivalent to those for HCC without BDTT can be achieved.

  5. Transjugular Intrahepatic Portosystemic Shunt for Portal Hypertension in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

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    Qiu, Bin; Li, Kai; Dong, Xiaoqun; Liu, Fu-Quan

    2017-09-01

    In patients with hepatocellular carcinoma (HCC), limited therapeutic options are available for portal hypertension resulted from portal vein tumor thrombus (PVTT). We aimed to determine safety and efficacy of TIPS for treatment of symptomatic portal hypertension in HCC with PVTT. We evaluated clinical characteristics of 95 patients with HCC and PVTT out of 992 patients who underwent TIPS. The primary endpoints included success rate, procedural mortality, serious complications, decrease in portosystemic pressure gradient, and symptom relief. The secondary endpoints included recurrence of portal hypertension, overall survival, adverse events related to treatments for HCC, and quality of life measured by Karnofsky Performance Status Scale (KPS). Success rate of TIPS was 95.8% (91/95), with procedural mortality of 1.1%. Serious complications related to TIPS procedure occurred in 2.1% (2/95) of patients. The symptoms of portal hypertension were well relieved. Variceal bleeding was successfully controlled and terminated in 100% of patients, with a recurrence rate of 39.2% in 12 months. Refractory ascites/hydrothorax was controlled partially or completely in 92.9% of patients during 1 month after TIPS, with a recurrence rate of 17.9% in 12 months. Survival rate at 6, 12, 24, and 36 months was 75.8, 52.7, 26.4, and 3.3%, respectively. No unexpected adverse event related to treatments for HCC was observed. The KPS score was 49 ± 4.5 and 63 ± 4.7 before and 1 month after TIPS, respectively (p portal hypertension in HCC with PVTT.

  6. Particle radiotherapy, a novel external radiation therapy, versus liver resection for hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus: A matched-pair analysis.

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    Komatsu, Shohei; Kido, Masahiro; Asari, Sadaki; Toyama, Hirochika; Ajiki, Tetsuo; Demizu, Yusuke; Terashima, Kazuki; Okimoto, Tomoaki; Sasaki, Ryohei; Fukumoto, Takumi

    2017-12-01

    Hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus carries a dismal prognosis, and the feasibility of local treatment has remained controversial. The present study aimed to compare the outcomes of particle radiotherapy and liver resection in patients with hepatocellular carcinoma with inferior vena cava tumor thrombus. Thirty-one and 19 patients, respectively, underwent particle radiotherapy and liver resection for hepatocellular carcinoma with inferior vena cava tumor thrombus. A matched-pair analysis was undertaken to compare the short- and long-term outcomes according to tumor stage determined using the tumor-node-metastasis classification. Both stages IIIB and IV (IVA and IVB) patients were well-matched for 12 factors, including treatment policy and patient and tumor characteristics. The median survival time of matched patients with stage IIIB tumors in the particle radiotherapy group was greater than that in the liver resection group (748 vs 272 days, P = .029), whereas no significant difference was observed in the median survival times of patients with stage IV tumors (239 vs 311 days, respectively). There were significantly fewer treatment-related complications of grade 3 or greater in the particle radiotherapy group (0%) than in the liver resection group (26%). Particle radiotherapy is potentially preferable in hepatocellular carcinoma patients with stage IIIB inferior vena cava tumor thrombus and at least equal in efficiency to liver resection in those with stage IV disease, while causing significantly fewer complications. Considering the relatively high survival and low invasiveness of particle radiotherapy when compared to liver resection, this approach may represent a novel treatment modality for hepatocellular carcinoma with inferior vena cava tumor thrombus. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Extensive tumor thrombus of hepatocellular carcinoma in the entire portal venous system detected on fluorodeoxyglucose positron emission tomography computed tomography

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    Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Puranik, Ameya; Rangarajan, Venkatesh

    2013-01-01

    Detection of thrombus is usually an incidental finding on fluorodeoxyglucose positron emission tomography/computed tomography studies. Nevertheless this is an important finding in terms of disease prognostication and in planning the treatment strategy. We herein report a case of a 50-years-old male, a diagnosed case of hepatocellular carcinoma with extensive hypermetabolic thrombus involving the entire portal venous system. (author)

  8. Endovascular treatment of intrahepatic inferior vena cava obstruction from malignant hepatocellular tumor thrombus utilizing Luminexx self-expanding nitinol stents

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    Stambo, Glenn W.; Leto, John; George, Christopher; Van Epps, Kelly; Woeste, Troy; Berlet, Mathew

    2008-01-01

    Inferior vena cava (IVC) obstruction is a well-described clinical entity. Most IVC obstructions from malignant neoplasms are a direct result of tumor compression [Oviedo J, Cerda S. Vascular invasion by hepatocellular carcinoma. Arch Pathol Lab Med 2001;125: 454-5; Furui S, Sawada S, et al. Gianturco stent placement in malignant caval obstruction: analysis of factors for predicting the outcome. Radiology 1995;195:147-52; Fletcher WS, Lakin PC, et al. Results of treatment of inferior vena cava syndrome with expandable metallic stents. Arch Surg 1998;133:935-8]. The symptoms of IVC obstruction include progressive ascites, scrotal edema and lower body edema. These constellations of symptoms are described as IVC syndrome and are devastating to a patient with end-stage cancer. We describe a palliative therapy utilizing Luminexx nitinol self-expanding stents to treat intracaval hepatoma thrombus obstructing the IVC. The procedure is rapidly performed, technically reliable, and has essentially no morbidity or mortality. This procedure can be performed in the interventional radiology suite with excellent results resolving the IVC syndrome soon after placement of the stents. We believe endovascular stenting as an excellent palliative therapy for patients with IVC syndrome and should be the treatment of choice for caval obstructions due to intraluminal tumor thrombus

  9. Endovascular treatment of intrahepatic inferior vena cava obstruction from malignant hepatocellular tumor thrombus utilizing Luminexx self-expanding nitinol stents

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    Stambo, Glenn W. [Division of Vascular and Interventional Radiology, Department of Radiology, St. Joseph' s Hospital and Medical Center, 4516 North Armenia Avenue, Tampa, FL 33603 (United States)], E-mail: xraydoc2@yahoo.com; Leto, John [Division of Vascular and Interventional Radiology, Department of Radiology, St. Joseph' s Hospital and Medical Center, 3001 W. Dr. Martin Luther King Jr. Blvd., Tampa, FL 33607 (United States); George, Christopher [Department of Hematology and Oncology, St. Joseph' s Hospital and Medical Center, 4301 W. Habana Avenue, Suite 1, Tampa, FL 33607 (United States); Van Epps, Kelly; Woeste, Troy; Berlet, Mathew [Division of Vascular and Interventional Radiology, Department of Radiology, St. Joseph' s Hospital and Medical Center, 4516 North Armenia Avenue, Tampa, FL 33603 (United States)

    2008-05-15

    Inferior vena cava (IVC) obstruction is a well-described clinical entity. Most IVC obstructions from malignant neoplasms are a direct result of tumor compression [Oviedo J, Cerda S. Vascular invasion by hepatocellular carcinoma. Arch Pathol Lab Med 2001;125: 454-5; Furui S, Sawada S, et al. Gianturco stent placement in malignant caval obstruction: analysis of factors for predicting the outcome. Radiology 1995;195:147-52; Fletcher WS, Lakin PC, et al. Results of treatment of inferior vena cava syndrome with expandable metallic stents. Arch Surg 1998;133:935-8]. The symptoms of IVC obstruction include progressive ascites, scrotal edema and lower body edema. These constellations of symptoms are described as IVC syndrome and are devastating to a patient with end-stage cancer. We describe a palliative therapy utilizing Luminexx nitinol self-expanding stents to treat intracaval hepatoma thrombus obstructing the IVC. The procedure is rapidly performed, technically reliable, and has essentially no morbidity or mortality. This procedure can be performed in the interventional radiology suite with excellent results resolving the IVC syndrome soon after placement of the stents. We believe endovascular stenting as an excellent palliative therapy for patients with IVC syndrome and should be the treatment of choice for caval obstructions due to intraluminal tumor thrombus.

  10. Hepatic vein tumor thrombus as a risk factor for excessive pulmonary deposition of microspheres during TheraSphere therapy for unresectable hepatocellular carcinoma.

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    Fleming, Chad J; Andrews, James C; Wiseman, Gregory A; Gansen, Denise N; Roberts, Lewis R

    2009-11-01

    To evaluate the impact of identifiable hepatic vein tumor thrombus on the ability to safely deliver TheraSphere (yttrium 90-containing glass microspheres) for the treatment of hepatocellular carcinoma (HCC). A retrospective review was performed of 87 patients (71 men, 16 women; mean age, 64.5 years; age range, 25-83 y) referred for TheraSphere therapy for HCC during a 2-year period between April 2005 and May 2007. Evaluation included contrast-enhanced computed tomography or magnetic resonance imaging, selective mesenteric angiography, and radionuclide perfusion scintigraphy to measure the arteriovenous shunting through the tumor. Of the 87 patients, 83 underwent angiography and perfusion scintigraphy; 53 were ultimately treated with 65 glass microsphere infusions. Twelve of 83 were identified as having tumor thrombus in a hepatic vein or extending into the inferior vena cava. The mean lung shunt for the patients with hepatic vein tumor thrombus was 30% (range, 11%-60%), compared with 8.2% (range, 3%-23%) for patients without identifiable tumor thrombus. Two of the 12 patients were treated with reduced doses of glass microspheres, and the remaining 10 were offered alternative therapies. The presence of hepatic vein tumor thrombus is a risk factor for an increased lung shunt that may prohibit delivery of a therapeutic dose of TheraSphere to hepatic tumor.

  11. Combination of Transarterial Chemoembolization and Three-Dimensional Conformal Radiotherapy for Hepatocellular Carcinoma With Inferior Vena Cava Tumor Thrombus

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    Koo, Ja Eun; Kim, Jong Hoon; Lim, Young-Suk

    2010-01-01

    Purpose: To evaluate the effects of transarterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (CRT) in patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT). Methods and Materials: A total of 42 consecutive patients who underwent TACE and CRT (TACE+CRT group) for the treatment of HCC with IVCTT were prospectively enrolled from July 2004 to October 2006. As historical controls, 29 HCC patients with IVCTT who received TACE alone (TACE group) between July 2003 and June 2004 were included. CRT was designed to target only the IVCTT and to deliver a median total dose of 45 Gy (range, 28-50 Gy). Results: Most baseline characteristics of the two groups were similar (p > 0.05). The response and progression-free rates of IVCTT were significantly higher in the TACE+CRT group than in the TACE group (42.9% and 71.4% vs. 13.8% and 37.9%, respectively; p < 0.01 for both rates). Overall, patient survival was significantly higher in the TACE+CRT group than in the TACE group (p < 0.01), with a median survival time of 11.7 months and 4.7 months, respectively. Treatment with TACE+CRT (hazard ratio [HR] = 0.38; 95% confidence interval [CI], 0.20-0.71), progression of IVCTT (HR = 4.05; 95% CI, 2.00-8.21), Child-Pugh class B (HR = 3.44; 95% CI, 1.79-6.61), and portal vein invasion (HR = 2.31; 95% CI, 1.19-4.50) were identified as independent predictors of mortality by multivariable analysis. Conclusions: The combination of TACE and CRT is more effective in the control of IVCTT associated with HCC and improves patient survival compared with TACE alone.

  12. Therapeutic effect and prognostic analysis of intensity-modulated radiotherapy for primary hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombus

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    HUANG Long

    2015-06-01

    Full Text Available ObjectiveTo determine the efficacy and prognostic factors of intensity-modulated radiotherapy (IMRT for primary hepatocellular carcinoma (HCC with portal vein and/or inferior vena cava tumor thrombus. MethodsTwenty-three HCC patients with portal vein and/or inferior vena cava tumor thrombus received IMRT with an 8 MV linear accelerator at the Cancer Center of General Hospital of Armed Police Forces, Anhui Medical University, from April 2008 to August 2011. A single dose of 3 to 6 Gy was delivered at five fractions per week, with a total dose of 56 to 96 Gy and a median dose of 60 Gy. Survival time was recorded, and adverse reactions were evaluated. Survival rate calculation and survival analysis were performed using the Kaplan-Meier method. Comparison of categorical between two groups was made by chi-square test. ResultsOne patient did not complete radiotherapy due to upper gastrointestinal bleeding. Of 22 patients who completed IMRT, 4 achieved complete remission and 10 achieved partial remission, with an overall response rate of 63.7%. Our analysis showed that the type of tumor thrombus and tumor size were associated with tumor response rate and were significant prognostic factors (P<0.05. The median survival time was 13.4 months. The 1-, 2-, and 3-year survival rates were 59%, 27%, and 18%, respectively. The 22 patients who completed radiotherapy did not experience acute radiation injury or late adverse outcomes such as radiation-induced liver disease. ConclusionThis study suggests IMRT is a safe and effective treatment option for HCC patients with portal vein and/or inferior vena cava tumor thrombus.

  13. Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion

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    Hou Jiazhou [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Zeng Zhaochong, E-mail: zeng.zhaochong@zs-hospital.sh.cn [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Zhang Jianying [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Fan Jia; Zhou Jian [Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Zeng Mengsu [Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)

    2012-10-01

    Purpose: The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Methods and Materials: We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. Results: The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher {alpha}-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better response to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). Conclusions: In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.

  14. Propensity Score Matching Analysis of Changes in Alpha-Fetoprotein Levels after Combined Radiotherapy and Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

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    Yuri Jeong

    Full Text Available To investigate the value of changes in alpha-fetoprotein (AFP levels for the prediction of radiologic response and survival outcomes in hepatocellular carcinoma (HCC patients with portal vein tumor thrombus (PVTT who received combined treatment of 3-dimensional conformal radiotherapy (3D-CRT and transarterial chemoembolization (TACE.A database of 154 HCC patients with PVTT and elevated AFP levels (>20 ng/mL treated with 3D-CRT and TACE as an initial treatment between August 2002 and August 2008 was retrospectively reviewed. AFP levels were determined 1 month after radiotherapy, and AFP response was defined as an AFP level reduction of >20% from the initial level. Radiologic response, overall survival (OS, and progression-free survival (PFS rates were compared between AFP responders and non-responders. Propensity-score based matching analysis was performed to minimize the effect of potential confounding bias.The median follow-up period was 11.1 months (range, 3.1-82.7 months. In the propensity-score matching cohort (92 pairs, a best radiologic response of CR or PR occurred in more AFP responders than AFP non-responders (41.3% vs. 10.9%, p < 0.001. OS and PFS were also longer in AFP responders than in non-responders (median OS 13.2 months vs. 5.6 months, p < 0.001; median PFS 8.7 months vs. 3.5 months, p < 0.001.AFP response is a significant predictive factor for radiologic response. Furthermore, AFP response is significant for OS and PFS outcomes. AFP evaluation after combined radiotherapy and TACE appears to be a useful predictor of clinical outcomes in HCC patients with PVTT.

  15. Novel Percutaneous Radiofrequency Ablation of Portal Vein Tumor Thrombus: Safety and Feasibility

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    Mizandari, Malkhaz [High Technology Medical Center, Tbilisi State Medical University (Georgia); Ao, Guokun [The 309 Hospital of People' s Liberation Army, Department on Oncology (China); Zhang Yaojun; Feng Xi [Imperial College London, Department of Surgery and Cancer (United Kingdom); Shen Qiang [The First Minimally Invasive Department of Eastern Hepatobiliary Surgery Hospital (China); Chen Minshan [Cancer Centre of Sun Yat-Sen University, Department of Hepatobiliary Surgery (China); Lau, Wan Yee [Chinese University of Hong Kong, Department of Surgery, Faculty of Medicine (Hong Kong); Nicholls, Joanna; Jiao Long; Habib, Nagy, E-mail: nagy.habib@imperial.ac.uk [Imperial College London, Department of Surgery and Cancer (United Kingdom)

    2013-02-15

    We report our experience of the safety of partial recanalization of the portal vein using a novel endovascular radiofrequency (RF) catheter for portal vein tumor thrombosis. Six patients with liver cancer and tumor thrombus in the portal vein underwent percutaneous intravascular radiofrequency ablation (RFA) using an endovascular bipolar RF device. A 0.035-inch guidewire was introduced into a tributary of the portal vein and through which a 5G guide catheter was introduced into the main portal vein. After manipulation of the guide catheter over the thrombus under digital subtraction angiography, the endovascular RF device was inserted and activated around the thrombus. There were no observed technique specific complications, such as hemorrhage, vessel perforation, or infection. Post-RFA portography showed partial recanalization of portal vein. RFA of portal vein tumor thrombus in patients with hepatocellular carcinoma is technically feasible and warrants further investigation to assess efficacy compared with current recanalization techniques.

  16. Distribution of Functional Liver Volume in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus in the 1st Branch and Main Trunk Using Single Photon Emission Computed Tomography—Application to Radiation Therapy

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    Akira Ikoma

    2011-10-01

    Full Text Available Purpose: To analyze the distribution of functional liver volume (FLV in the margin volume (MV surrounding hepatocellular carcinoma (HCC with portal vein tumor thrombus (PVTT before radiation therapy (RT and to verify the safety of single photon emission computed tomography-based three-dimensional conformal radiotherapy (SPECT-B3DCRT by exploring the relation of FLV in MV to radiation-induced liver disease (RILD. Methods and Materials: Clinical target volume (CTV included main tumor and PVTT, and planning target volume (PTV included CTV with a 10 mm margin. MV was defined as PTV–CTV. FLV ratio in MV was calculated as FLV in MV/MV × 100 (%. The two high-dose beams were planned to irradiate FLV as little as possible. Fifty-seven cases of HCC (26/57, 46%; Child–Pugh grade B with PVTT underwent SPECT-B3DCRT which targeted the CTV to a total dose of 45 Gy/18 fractions. The destructive ratio was defined as radiation induced dysfunctional volume/FLV × 100 (%. Results: We observed a significant negative correlation between FLV ratio in MV and CTV (p < 0.001. Three cases with CTVs of 287, 587 and 1184 cm3 experienced transient RILD. The FLV ratio in MV was highest in patients with RILD: nine patients with CTV of 200–300 cm3, three with CTV of 500–600 cm3, and two with CTV of 1100–1200 cm3. The destructive ratio yielded a mean value of 24.2 ± 1.5%. Conclusions: Radiation planning that takes into account the distribution of FLV appears to result in the least possible RILD.

  17. Giant tumor thrombus in the right atrium clearly detected by /sup 111/In-oxine labeled platelet scintigraphy

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    Takeda, T; Ishikawa, N; Satoh, A; Masuda, Y; Hiramatsu, Y; Akisada, M; Sakakibara, Y

    1985-07-01

    A 54-year-old man was admitted to hospital with a 3-month history of progressive dyspnea with coughing. A giant right atrial mass, originating from a hepatocellular carcinoma, was visualized by computed tomography, and digital subtraction angiography. The volume if the right atrial mass was increasing rapidly. It was therefore essential to determine whether this giant mass was a tumor thrombus or a multiplication of the hepatocellular carcinoma. /sup 111/In-oxine labeled platelet scintigraphy revealed active accumulation in the right atrium caused by the presence of active platelet deposition, and slight accumulation in the lung fields probably due to embolic showers originating from the tumor thrombus in the right atrium. This is the first case report showing that /sup 111/In-oxine labeled platelet scintigraphy can aid in confirming the nature of a giant tumor thrombus in the right atrium and can clarify the pathogenesis of the respiratory symptoms.

  18. Metastatic Adenocarcinoma Presenting as Extensive Cavoatrial Tumor Thrombus

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    Johari, Bushra; Abdul Aziz, Yang Faridah; Krishnasamy, Sivakumar; Looi, Lai Meng; Hashim, Shahrul Amry; Raja Mokhtar, Raja Amin

    2015-01-01

    The presence of tumor thrombus in the right atrium is frequently the result of direct intraluminal extension of infra-diaphragmatic malignancy into the inferior vena cava (IVC) or supradiaphragmatic carcinoma into the superior vena cava (SVC). Right atrial tumor thrombus with extension into both SVC and IVC has not been reported in the literature. We present a patient who presented with symptoms of right atrial and SVC obstruction. Imaging revealed presence of a thrombus in the right atrium, extending to the SVC and IVC, with the additional findings of a left adrenal mass and multiple liver lesions. The histopathological examination of the right atrial mass revealed metastatic adenocarcinoma cells. The patient was given a presumptive diagnosis of metastatic adenocarcinoma, most likely adrenal in origin, with multiple hepatic lesions suspicious for metastasis. The clinical outcome of the patient was not favorable; the patient succumbed before the adrenal mass could be confirmed to be the primary tumor. This case highlights that in patients manifesting with extensive cavoatrial thrombus as, the existence of primary carcinoma should be considered especially in the adrenal cortex or in the lung

  19. Interobserver Variability in Target Definition for Hepatocellular Carcinoma With and Without Portal Vein Thrombus: Radiation Therapy Oncology Group Consensus Guidelines

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    Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Bosch, Walter R. [Department of Radiation Oncology, Washington University in St. Louis School of Medicine, St. Louis, Missouri (United States); Krishnan, Sunil [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kim, Tae K. [Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women' s College Hospital, University of Toronto, Toronto, Ontario (Canada); Mamon, Harvey J. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Shyn, Paul [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (United States); Seong, Jinsil [Department of Radiation Oncology, Yonsei University Medical College, Seoul (Korea, Republic of); Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Cheng, Jason C. [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Feng, Mary U. [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan (United States); Stephans, Kevin L. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Roberge, David [Department of Radiation Oncology, Montreal General Hospital/McGill University Health Centre, Montreal, Quebec (Canada); Crane, Christopher [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); and others

    2014-07-15

    Purpose: Defining hepatocellular carcinoma (HCC) gross tumor volume (GTV) requires multimodal imaging, acquired in different perfusion phases. The purposes of this study were to evaluate the variability in contouring and to establish guidelines and educational recommendations for reproducible HCC contouring for treatment planning. Methods and Materials: Anonymous, multiphasic planning computed tomography scans obtained from 3 patients with HCC were identified and distributed to a panel of 11 gastrointestinal radiation oncologists. Panelists were asked the number of HCC cases they treated in the past year. Case 1 had no vascular involvement, case 2 had extensive portal vein involvement, and case 3 had minor branched portal vein involvement. The agreement between the contoured total GTVs (primary + vascular GTV) was assessed using the generalized kappa statistic. Agreement interpretation was evaluated using Landis and Koch's interpretation of strength of agreement. The S95 contour, defined using the simultaneous truth and performance level estimation (STAPLE) algorithm consensus at the 95% confidence level, was created for each case. Results: Of the 11 panelists, 3 had treated >25 cases in the past year, 2 had treated 10 to 25 cases, 2 had treated 5 to 10 cases, 2 had treated 1 to 5 cases, 1 had treated 0 cases, and 1 did not respond. Near perfect agreement was seen for case 1, and substantial agreement was seen for cases 2 and 3. For case 2, there was significant heterogeneity in the volume identified as tumor thrombus (range 0.58-40.45 cc). For case 3, 2 panelists did not include the branched portal vein thrombus, and 7 panelists contoured thrombus separately from the primary tumor, also showing significant heterogeneity in volume of tumor thrombus (range 4.52-34.27 cc). Conclusions: In a group of experts, excellent agreement was seen in contouring total GTV. Heterogeneity exists in the definition of portal vein thrombus that may impact treatment

  20. Tumor thrombus formation in two dogs with insulinomas.

    Science.gov (United States)

    Hambrook, Lydia E; Kudnig, Simon T

    2012-10-15

    A 9-year-old sexually intact male Staffordshire Bull Terrier and a 9-year-old neutered male Boxer were evaluated for intermittent neurologic signs including muscle tremors, ataxia, episodic collapse, disorientation, and seizures. Both dogs had low blood glucose and high serum insulin concentrations. Results of abdominal ultrasonography were unremarkable for both dogs. Exploratory laparotomy revealed a mass that extended from the body of the pancreas into the pancreaticoduodenal vein in each dog. Marginal resection of pancreatic masses was performed, and tumor thrombi were removed via venotomy in both dogs. Histologic evaluation indicated the masses were pancreatic islet cell tumors with tumor thrombi. Clinical signs resolved following surgical resection of tumors and tumor thrombi, and the dogs were euglycemic during the follow-up period (17 and 45 months after surgery). Although gross tumor thrombus formation has been identified in humans with insulinomas, tumor thrombi have not been previously reported for dogs with insulinomas. Surgical removal of tumor thrombi via venotomy seemed to be well tolerated by the dogs. Tumor thrombus formation did not seem to adversely affect prognosis for the 2 dogs of this report.

  1. Portal Vein Tumor Thrombus of Liver Metastasis from Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ryoko Ogawa

    2009-01-01

    Full Text Available We report a case of liver metastasis of lung carcinoma with portal vein tumor thrombus (PVTT. Although the primary lesion of lung tumor remained unchanged, the patient rapidly developed wide-spread metastases and formed PVTT of liver metastasis. The primary lesion showed features of mixed Clara and bronchial surface epithelial cell component type adenocarcinoma with small foci of micropapillary pattern. Micropapillary pattern was observed in the metastatic lesions in the liver and PVTT. Micropapillary pattern lung adenocarcinoma may develop rapid metastases and cause PVTT associated with liver metastasis. We should perform a detailed examination to establish correct diagnosis.

  2. Resectable hepatoblastoma with tumor thrombus extending into the right atrium after chemotherapy: A case report

    Directory of Open Access Journals (Sweden)

    Kosuke Endo

    2016-04-01

    Full Text Available Hepatoblastoma with intraatrial tumor thrombus is relatively rare. We report a case of hepatoblastoma with tumor thrombus extending into the right atrium, which responded well to chemotherapy and was resected using extracorporeal circulation. A 4-year-old girl was referred to our hospital because of abdominal distention and tenderness. A computed tomography (CT scan showed a large tumor occupying the left 3 segments of the liver with tumor thrombus extending into the right atrium. There was also a small intrahepatic metastasis in the right lobe of the liver. She was diagnosed with hepatoblastoma on the basis of the results of open biopsy. Neoadjuvant chemotherapy with an intense CDDP-based regimen was performed. The tumor responded well to chemotherapy, and intrahepatic metastasis became undetectable on CT scan, although the tumor thrombus remained in the right atrium. After 7 courses of chemotherapy, we performed resection using extracorporeal circulation. The postoperative course was uneventful, and adjuvant chemotherapy was started 10 days after the operation. Her serum alpha-fetoprotein (AFP level decreased to the normal range, and she was free of disease for 1 year after the operation. Tumor resection using extracorporeal circulation can be performed safely and is justified in patients with intraatrial tumor thrombus.

  3. CT diagnosis of tumor thrombus of the renal vein and inferior vena cava

    International Nuclear Information System (INIS)

    Masuda, Fujio; Chen, Zuicho; Oishi, Yukihiko; Machida, Toyohei

    1980-01-01

    We used computed tomography (CT) for diagnosis in 4 cases of renal tumor associated with tumor thrombus of the renal vein and inferior vana cava. The results obtained are described below: A total of 4 cases consisting of 3 cases of renal cell carcinoma and one case of squamous cell carcinoma of the renal pelvis, treated at the Jikei University Hospital during the six months period from January to June of 1979, were studied. The affected side was right in 3 cases and left in one case. In all of the former cases the tumor thrombus was extending from the renal vein to the inferior vena cava, while in the latter case it was confined in the renal vein. All these 4 cases received CT together with renal arteriography and inferior venacavography, followed by nephrectomy, and were confirmed of the presence of tumor thrombus in the renal vein and inferior vena cava operatively. CT findings revealed a pronounced enlargement of the renal vein, and tumor thrombus of the renal vein was diagnosed in all of the 4 cases. In 2 of 3 cases in which tumor thrombus extended to the inferior vena cava, the dilated renal vein was found to be connected to the slightly dilated inferior vena cava, while in the remaining one case the outline of the inferior vena cava was obscure, showing no clear dilatation. After contrast enhancement, a filling defect was seen in the inferior vena cava. CT findings of tumor thrombus in the vein indicated a dilatation of the renal vein and inferior vena cava. In addition, a filling defect was found after contrast enhancement, suggesting that CT is helpful as a diagnostic aid. (author)

  4. Radiodiagnostic methods in determining the structure of tumor thrombus in the inferior vena cava in kidney cancer

    Directory of Open Access Journals (Sweden)

    N. B. Vikhrova

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC is the most common primary tumor of the renal parenchyma. Venous involvement is one of the most important anatomic characteristics of tumor. It is known that venous spread influences the survival of patients with RCC. Tumor thrombosis of IVC in patients with renal cell carcinoma has been reported in 4–10 %. The reference standard for RCC with tumor thrombus remains surgical resection. The structure of thrombus determines some technical difficulties in the management of tumor. Spongeous thrombus correlate with higher risk of thrombus detachment during surgery resulting in PE. Therefore determination of IVC thrombus consistency is very important part of preoperative radiologic assessment of tumor in patients with RCC.

  5. Safety and efficacy of transarterial chemoembolization plus sorafenib for hepatocellular carcinoma with portal venous tumour thrombus

    International Nuclear Information System (INIS)

    Pan, T.; Li, X.-S.; Xie, Q.-K.; Wang, J.-P.; Li, W.; Wu, P.-H.; Zhao, M.

    2014-01-01

    Aim: To evaluate the safety and efficacy of combined therapy with transarterial chemoembolization (TACE) and sorafenib for hepatocellular carcinoma (HCC) with portal venous tumour thrombus (PVTT). Materials and methods: This study was approved by the institutional review board. From May 2009 to May 2012, 170 consecutive patients were newly diagnosed with advanced-stage HCC and treated with TACE plus sorafenib. Among them, 41 patients with PVTT were retrospectively enrolled in the study. The adverse events (AEs), overall survival (OS), time to progression (TTP), and prognostic factors were analysed. Statistical analysis was performed with the Kaplan–Meier method using the log-rank test and Cox regression models. Results: The most common AEs were hand–foot skin reaction related to sorafenib and fever related to TACE. Procedure-related mortality and grade 4 AEs were not observed. Grade 3 AEs were observed in five patients. During the median follow-up period of 13.5 months (range 1.4–45 months), the 6-month and 1-year survival rates were 87.7% and 53.6%, respectively. The median OS was 13 months (range 1.4–44.8 months), and the median TTP was 7 months (range 1–18.6 months). The Child–Pugh class (p = 0.022), extrahepatic metastasis (p = 0.009), and gross morphological type (nodular type versus diffuse type; p = 0.008) were prognostic factors related to OS in the multivariate analysis. Conclusion: TACE plus sorafenib in an interrupted therapeutic scheme was well tolerated and might improve OS for HCC patients with PVTT, especially in those with Child–Pugh class A, no extrahepatic metastasis, or nodular-type HCC. - Highlights: • We introduce the safety of TACE plus sorafenib for patients with advanced HCC and PVTT. • We suggest that the combined therapy might prolong the TTP and OS than sorafenib alone. • Clinic benefit determinations with the Child-Pugh class, extrahepatic metastasis or gross type

  6. CT Findings of Intrarenal Yolk Sac Tumor with Tumor Thrombus Extending into the Inferior Vena Cava: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Shao Chun; Li, Xue Hua; Sun, Can Hui; Feng, Shi Ting; Peng, Zhen Peng; Huang, Si Yun; Li, Zi Ping [Dept. of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)

    2014-10-15

    Yolk sac tumor (YST) is a rare germ cell neoplasm of childhood that usually arises from the testis or ovary. The rare cases of YST in various extragonadal locations have been reported, but the primary intrarenal YST is even more uncommon. Here, we report a case of a primary intrarenal YST with tumor thrombus of the inferior vena cava and left renal vein in a 2-year-old boy, with an emphasis on the CT features. To our knowledge, this is the first reported case of an intrarenal YST with intravascular involvement.

  7. Organizing Thrombus Mimicking a Cardiac Tumor Located at the Mitral-Aortic Intervalvular Fibrosa

    Directory of Open Access Journals (Sweden)

    Ji Seong Lee

    2016-02-01

    Full Text Available Thrombosis at the left ventricular outflow tract occurs without any detectable heart disease or predisposing factors only extremely rarely. A 48-year-old male visited Konkuk University Medical Center with loss of consciousness one month prior to presentation. Before he visited our hospital, he had been diagnosed with a cardiac tumor, which was located between the left atrium and posterior aortic root, and which was adjacent to both the aortic and mitral valves. Cardiac transplantation was recommended at the other hospital because of the high risk of cardiac dysfunction induced by both aortic and mitral valvular dysfunction after surgical resection. Based on preoperative transthoracic echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging, and intraoperative transesophageal echocardiography, we considered it to be a benign tumor. Complete resection was achieved and the pathology confirmed organizing thrombus. We report a case of organizing thrombus mimicking a cardiac tumor, which was located at the mitral-aortic intervalvular fibrosa of the left ventricular outflow tract without any heart disease.

  8. Tumor thrombus

    DEFF Research Database (Denmark)

    Ravina, Mudalsha; Hess, Søren; Chauhan, Mahesh Singh

    2014-01-01

    period at the Army Hospital Research and Referral in New Delhi, India, and included all oncology cases with FDG-avid thrombosis in the report. The diagnosis of TT was based on FDG-avid solid masses inside the vessels in patients with known malignancy. The SUVmax was calculated. RESULTS: Twenty...

  9. A Novel Technique for Endovascular Removal of Large Volume Right Atrial Tumor Thrombus

    Energy Technology Data Exchange (ETDEWEB)

    Nickel, Barbara, E-mail: nickel.ba@gmail.com [US Teleradiology and Quantum Medical Radiology Group (United States); McClure, Timothy, E-mail: tmcclure@gmail.com; Moriarty, John, E-mail: jmoriarty@mednet.ucla.edu [UCLA Medical Center, Department of Interventional Radiology (United States)

    2015-08-15

    Venous thromboembolic disease is a significant cause of morbidity and mortality, particularly in the setting of large volume pulmonary embolism. Thrombolytic therapy has been shown to be a successful treatment modality; however, its use somewhat limited due to the risk of hemorrhage and potential for distal embolization in the setting of large mobile thrombi. In patients where either thrombolysis is contraindicated or unsuccessful, and conventional therapies prove inadequate, surgical thrombectomy may be considered. We present a case of percutaneous endovascular extraction of a large mobile mass extending from the inferior vena cava into the right atrium using the Angiovac device, a venovenous bypass system designed for high-volume aspiration of undesired endovascular material. Standard endovascular methods for removal of cancer-associated thrombus, such as catheter-directed lysis, maceration, and exclusion, may prove inadequate in the setting of underlying tumor thrombus. Where conventional endovascular methods either fail or are unsuitable, endovascular thrombectomy with the Angiovac device may be a useful and safe minimally invasive alternative to open resection.

  10. A Novel Technique for Endovascular Removal of Large Volume Right Atrial Tumor Thrombus

    International Nuclear Information System (INIS)

    Nickel, Barbara; McClure, Timothy; Moriarty, John

    2015-01-01

    Venous thromboembolic disease is a significant cause of morbidity and mortality, particularly in the setting of large volume pulmonary embolism. Thrombolytic therapy has been shown to be a successful treatment modality; however, its use somewhat limited due to the risk of hemorrhage and potential for distal embolization in the setting of large mobile thrombi. In patients where either thrombolysis is contraindicated or unsuccessful, and conventional therapies prove inadequate, surgical thrombectomy may be considered. We present a case of percutaneous endovascular extraction of a large mobile mass extending from the inferior vena cava into the right atrium using the Angiovac device, a venovenous bypass system designed for high-volume aspiration of undesired endovascular material. Standard endovascular methods for removal of cancer-associated thrombus, such as catheter-directed lysis, maceration, and exclusion, may prove inadequate in the setting of underlying tumor thrombus. Where conventional endovascular methods either fail or are unsuitable, endovascular thrombectomy with the Angiovac device may be a useful and safe minimally invasive alternative to open resection

  11. Pancreatic endocrine tumor with neoplastic venous thrombus and bilobar liver metastasis. A case report.

    Science.gov (United States)

    Barbier, L; Turrini, O; Sarran, A; Delpero, J-R

    2010-02-01

    We report the case of an asymptomatic 56-year-old woman with a metastatic pancreatic endocrine tumor, fortuitously discovered by abdominal imaging. A CT-scan showed a large mass in the pancreatic tail invading the spleen and stomach; in addition, there was neoplastic thrombus within the spleno-mesentericoportal venous confluence and bilobar liver metastases. Surgical resection was performed in two stages. The first procedure was an extended left pancreatectomy with venous thrombectomy and "clearance" of the left hepatic lobe. During the interval, embolization of the right portal vein was carried out. Right hepatectomy and radiofrequency destruction of residual metastases was then performed. On the basis of completeness of the resection and the histopathological data, the patient did not undergo any adjuvant therapy, in accordance with French guidelines. At 1 year of follow-up, there was no evidence of recurrence. (c) 2010 Elsevier Masson SAS. All rights reserved.

  12. Benign and malignant hepatocellular tumors: evaluation of tumoral enhancement after mangafodipir trisodium injection on MR imaging

    International Nuclear Information System (INIS)

    Coffin, C.M.; Diche, T.; Mahfouz, A.E.; Alexandre, M.; Caseiro-Alves, F.; Rahmouni, A.; Vasile, N.; Mathieu, D.

    1999-01-01

    The aim of this work was to study the ability of mangafodipir trisodium (Mn-DPDP)-enhanced MR imaging in differentiating malignant from benign hepatocellular tumors. Eleven patients with pathologically proved hepatocellular carcinomas, six with focal nodular hyperplasias, and one with a single hepatocellular adenoma were examined by spin-echo and gradient-echo T1-weighted sequences before, 1 h after, and 24 h after intravenous injection of Mn-DPDP (5 μmol/kg). Quantitative analysis including enhancement and lesion-to-liver contrast-to-noise ratio, and qualitative analysis including the presence of a central area and a capsule were done on pre- and post-Mn-DPDP-enhanced images. Enhancement was observed in all the tumors with significant improvement (p < 0.05) in contrast-to-noise ratio 1 h after, and 24 h after intravenous injection of Mn-DPDP. There were no significant differences in the mean enhancement and the mean contrast-to-noise ratio (CNR) between benign and malignant tumors. No enhancement was seen within internal areas observed in 7 hepatocellular carcinomas, and in 5 focal nodular hyperplasias, and within capsules which were observed in 9 hepatocellular carcinomas. In our study, Mn-DPDP increased CNR of both benign and malignant tumors but did not enable differentiation between benign and malignant tumors of hepatocellular nature. (orig.)

  13. 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.

  14. Role of presurgical targeted molecular therapy in renal cell carcinoma with an inferior vena cava tumor thrombus

    Directory of Open Access Journals (Sweden)

    Peng C

    2018-04-01

    Full Text Available Cheng Peng,1,* Liangyou Gu,1,* Lei Wang,2 Qingbo Huang,1 Baojun Wang,1 Gang Guo,1 Yang Fan,1 Yu Gao,1 Xin Ma,1 Xu Zhang1 1Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing, People’s Republic of China; 2Department of Urology, Chinese PLA 534 Hospital, Luoyang, People’s Republic of China *These authors contributed equally to this work Purpose: The clinical benefit of targeted molecular therapy (TMT in renal cell carcinoma (RCC with an inferior vena cava (IVC tumor thrombus remains controversial. The aim of this study was to investigate the effects of presurgical TMT on the heights and levels of IVC thrombi, and to assess its impact on surgical strategy. Patients and methods: We retrospectively reviewed data from 18 patients with RCC involving IVC tumor thrombi who were treated at our hospital with presurgical TMT followed by an IVC thrombectomy. The changes in heights and levels of the IVC thrombi were compared using computed tomography or magnetic resonance imaging. Clinicopathological factors were also evaluated to assess their association with TMT efficacy. Results: The tumor thrombus levels before TMT were stage I in 1 patient (5.6%, II in 12 patients (66.7%, III in 4 patients (22.2%, and IV in 1 patient (5.6%. After a median of two treatment cycles (range: 1–3, the thrombus height decreased measurably in 11 patients (61.1% with an average shrinkage of 17.7%. The thrombus height remained stable in five patients (27.8% and was enlarged in two (11.1%. Downstaging of the thrombus level occurred in four patients (22.2%; the surgical strategy was modified in three patients (16.7% to avoid cardiopulmonary bypass and complicated liver mobilization under robot-assisted laparoscopy. Furthermore, a higher neutrophil count tended to be associated with a worse clinical TMT-associated outcome (P=0.056. Conclusion: Our data suggest a limited influence of presurgical TMT

  15. Adult Wilms tumor with inferior vena cava thrombus and distal deep vein thrombosis - a case report and literature review.

    Science.gov (United States)

    Ratajczyk, Krzysztof; Czekaj, Adrian; Rogala, Joanna; Kowal, Pawel

    2018-02-23

    Adult Wilms tumor (WT, nephroblastoma) is a rare, but well-described renal neoplasm. Although inferior vena cava tumor thrombosis is present in up to 10% of Wilms tumors in childhood, only few cases of this clinical manifestation in adults have been reported. To the best of our knowledge, this is the first case of adult WT infiltrating into inferior vena cava (IVC) with concomitant distal deep vein thrombosis. A 28-year-old male patient with gross hematuria and right flank pain was diagnosed with right kidney tumor penetrating to IVC. Preoperatively, acute distal thrombosis in inferior vena cava and lower extremities veins occurred. Right radical nephrectomy with tumor thrombectomy via cavotomy was performed. In order to prevent pulmonary embolism, IVC was ligated below left renal vein level. Histopathological examination revealed a triphasic nephroblastoma without anaplastic features. Postoperatively, patient was diagnosed with metastatic liver disease, which was treated with two lines of chemotherapy followed by radiotherapy with achievement of complete response. Adult WT occurs usually in young patients, under 40 years of age. Neoadjuvant chemotherapy proved to be effective in children, resulting with tumor shrinkage and venous tumor thrombus regression. Therefore, percutaneous biopsy should be always considered in young patients presenting with renal tumor invading venous system. IVC ligation is a safe treatment option in the event of complete inferior vena cava occlusion due to distal thrombosis concomitant to tumor thrombus, provided collateral venous pathways are well-developed.

  16. Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: A feasibility study.

    Science.gov (United States)

    Tarantino, Luciano; Busto, Giuseppina; Nasto, Aurelio; Fristachi, Raffaele; Cacace, Luigi; Talamo, Maria; Accardo, Catello; Bortone, Sara; Gallo, Paolo; Tarantino, Paolo; Nasto, Riccardo Aurelio; Di Minno, Matteo Nicola Dario; Ambrosino, Pasquale

    2017-02-07

    To treated with electrochemotherapy (ECT) a prospective case series of patients with liver cirrhosis and Vp3-Vp4- portal vein tumor thrombus (PVTT) from hepatocellular carcinoma (HCC), in order to evaluate the feasibility, safety and efficacy of this new non thermal ablative technique in those patients. Six patients (5 males and 1 female), aged 61-85 years (mean age, 70 years), four in Child-Pugh A and two in Child-Pugh B class, entered our study series. All patients were studied with three-phase computed tomography (CT), contrast enhanced ultrasound (CEUS) and ultrasound-guided percutaneous biopsy of the thrombus before ECT. All patients underwent ECT treatment (Cliniporator Vitae ® , IGEA SpA, Carpi, Modena, Italy) of Vp3-Vp4 PVTT in a single session. At the end of the procedure a post-treatment biopsy of the thrombus was performed. Scheduled follow-up in all patients entailed: CEUS within 24 h after treatment; triphasic contrast-enhanced CT and CEUS at 3 mo after treatment and every six months thereafter. Post-treatment CEUS showed complete absence of enhancement of the treated thrombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranged from 9 to 20 mo (median, 14 mo). In 2 patients, the follow-up CT and CEUS demonstrated complete patency of the treated portal vein. Other 3 patients showed a persistent avascular non-tumoral shrinked thrombus at CEUS and CT during follow-up. No local recurrence was observed at follow-up CT and CEUS in 5/6 patients. One patient was lost to follow-up because of death from gastrointestinal hemorrage 5 wk after ECT. In patients with cirrhosis, ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.

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

    Directory of Open Access Journals (Sweden)

    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

  18. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  19. Robotic partial nephrectomy for renal cell carcinomas with venous tumor thrombus.

    Science.gov (United States)

    Abaza, Ronney; Angell, Jordan

    2013-06-01

    To describe the first report of robotic partial nephrectomies (RPNs) for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). Partial nephrectomy for RCC extending into the renal vein has been described in limited fashion, but such a complex procedure has not previously been reported in minimally-invasive fashion. We demonstrate the feasibility of robotic nephron-sparing surgery despite vein thrombi and the results of the initial four highly-selected patients to have undergone this novel procedure. Two patients underwent RPN for RCC with VTT involving intraparenchymal vein branches, and 2 others had VTT involving the main renal vein. Mean patient age was 65 years (range 50-74 years). Mean tumor size was 7.75 cm (range 4.3-12.8 cm) with mean RENAL (radius, exophytic/endophytic, nearness to collecting system, anterior/posterior, and location) nephrometry score of 9.75 (range 8-12). Mean warm ischemia time was 24.2 minutes (range 19-27 minutes) and mean estimated blood loss was 168.8 mL (range 100-300 mL). No patients required transfusion, and there were no intraoperative complications. No patients required conversion to open or standard laparoscopic surgery. All 4 patients were discharged home on the first postoperative day. A single postoperative complication occurred in 1 patient who was readmitted with an ileus that resolved spontaneously. All patients had negative surgical margins. Two patients developed metastatic disease on surveillance imaging. RPN in patients with VTT is safe and feasible in selected patients. Given the risk of metastatic disease in patients with pathologic stage T3a RCC, the role of nephron sparing requires further evaluation such that radical nephrectomy remains the standard of care. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Factors associated with tumor size of hepatocellular carcinoma

    Science.gov (United States)

    Siregar, G. A.; Buulolo, B. A.

    2018-03-01

    Determining the association of age and laboratory parameters with tumor size of hepatocellular carcinoma (HCC). The study was at Adam Malik Hospital Medan from June- December 2016. 100 HCC patients were enrolled; those with excluding liver metastatic. Baseline characteristics of gender, age, obtaining etiology of HCC. Liver function tests, viral marker, and INR were done. Based on tumor size from abdomen CT, patients were three groups: tumor size below 3 cm, 3-5 cm, and above 5 cm size. Patients were also divided based on Child-Pugh class. Correlation of age and laboratory results with tumor size of HCC patients were analyzed. Age have negative correlation with tumor size in HCC patients (r=-0.297, p=0.032) while AFP have positive correlation with tumor size (r0.446, p=<0.001). Total bilirubin, AST, and ALT have negative correlation but non-significant (r=-0.045, -0.078, - 0.126 respectively). Albumin and INR have positive correlation but non-significant (r=0.021, 0.112 respectively). Our study suggests that older age correlates with smaller tumor size, while AFP level has a significant correlation with tumor size in HCC patients. AFP level may be a useful marker for determining the prognosis of HCC patients.

  1. Imaging manifestation of hepatocellular carcinoma with bile duct tumor thrombi

    International Nuclear Information System (INIS)

    Liu Qingyu; Chen Jianyu; Liang Biling; Hu Tao

    2008-01-01

    Objective: To analyze the imaging features of hepatocellular carcinoma(HCC) with bile duct tumor thrombi. Methods: Thirteen patients with bile duct tumor thrombi proved pathologically underwent imaging examination. MR and CT were performed in 3 cases, and 2 cases had CT only and 8 cases had MRI only. Ultrasonography(US) was performed in all 13 patients. The accuracy of bile duct tumor thrombi detection was compared between US, CT and MRI with Fisher test. Results: Liver tumors and bile duct tumor thrombi were demonstrated in all patients on CT or MRI. Presence of intraluminal soft tissue mass was found in four of five cases on CT, and mild enhancement of the intraluminal mass in the arterial phase was noted, dilated bile duct distal to tumor thrombi was detected in all five patients. Eleven Tumor thrombi showed slight low signal intensity on T 1 WI, slight high signal intensity on T 2 WI, and mild to moderate contrast enhancement on the contrast-enhanced MR images. The MRCP findings of tumor thrombi were as follows: interruption, stricture of the bile ducts or irregular filling defect in the bile ducts with dilated intrahepatic ducts, bile duet was abruptly interrupted or showed a 'rat-tail' stricture (n=5); the common bile duct was filled with tumor thrombi, intrahepatic bile duct dilatation and missing common bile duct was noted on MRCP (n=2). Bile duct tumor thrombi were correctly diagnosed in 7 cases on US, and 12 cases on CT or MRI. Six cases were misdiagnosed or miss-diagnosed on US, and 4 cases were misdiagnosed on CT or MRI. There was no significant difference between US and CT/MRI in diagnosis of bile duct tumor thrombi (P=0.270). Conclusion: CT or MR imaging is useful for the diagnosis of HCC with biliary tumor thrombi and for evaluating the extension of thrombi. (authors)

  2. Expression and role of VEGFA and miR-381 in portal vein tumor thrombi in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Jing; Wu, Shuzhi; Huang, Tianren

    2018-06-01

    The aim of the present study was to examine the expression and role of vascular endothelial growth factor A (VEGFA) and microRNA (miRNA or miR)-381 in tumor thrombi from patients with hepatocellular carcinoma and portal vein tumor thrombus (PVTT). Tumor thrombi and adjacent paired tissues were collected from 39 patients with hepatocellular carcinoma with PVTT. VEGFA expression levels were assessed using reverse transcription-quantitative polymerase chain reaction and western blotting. miRNAs that may regulate VEGFA expression were predicted using bioinformatics analysis and confirmed via a dual luciferase reporter assay. The effects of VEGFA and its upstream miRNA on proliferation of the proliferation of EAhy926 human venous endothelial cells were analyzed using an MTT assay. Compared with the paired adjacent tissues, VEGFA was significantly upregulated at both the mRNA and protein level in tumor thrombi (P<0.05). VEGFA was predicted to be a target of miR-381 and this was confirmed experimentally. miR-381 expression was significantly downregulated in tumor thrombi from patients with PVTT compared with paired adjacent tissues (P<0.05). In addition, transfection with antagomirs against miR-381 or short interfering RNA against VEGFA significantly inhibited EAhy926 cell proliferation (P<0.05). In conclusion, the results of the present study indicate that VEGFA is upregulated in tumor thrombi whereas miR-381 is downregulated. VEGFA is regulated by miR-381 and both may be associated with the development of PVTT.

  3. Computed tomographic diagnosis of calcified inferior vena cava thrombus in a child with Wilm's tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kirks, D R; Ponzi, J W; Korobkin, M

    1980-01-01

    A calcified thrombus in the inferior vena cava of infants and children may be imaged by computed tomography. The precise location of the calcification within the inferior vena cava may be confirmed by computed tomographic scanning during injection of intravenous contrast material.

  4. Radiotherapy for hepatocellular carcinoma. Regarding solitary tumor on radiologic examinations

    International Nuclear Information System (INIS)

    Kawashima, Mitsuhiko; Tokuuye, Koichi; Sumi, Minako; Kagami, Yashikazu; Murayama, Shigeyuki; Nakayama, Hidetsugu; Imai, Atsushi; Ando, Kou; Ikeda, Hiroshi

    1997-01-01

    To evaluate the effect of radiotherapy (RT) on hepatocellular carcinoma (HCC) that appears as a solitary nodule on radiologic studies. We irradiated 17 patients with solitary HCC lesions (25-150 mm in diameter) with approximately 60 Gy (range 50-70 Gy). Patients underwent dynamic CT and/or ultrasound imaging at 3-month intervals after treatment. Patients were classified based on lesion size, degree of cirrhosis (Child A. 6; Child B, 6; Child C, 5), and whether they had received other therapy such as transarterial chemoembolization (TACE). The responses were classified as complete, partial, no change, or progression. The median survival was 12.8 months for all 17 patients, with 1-, 2-, and 3-year cumulative survival rates of 59%, 35% and 24%, respectively. Patients classified as Child A showed significantly longer survival than those classified as either Child B (p<0.04) or C (p<0.01). Four of the five Child C patients died of liver failure within 6 months after RT despite the absence of tumor recurrence. The initial tumor diameter, concurrent treatment with TACE, and radiation dose showed no significant effect on survival. Survival in patients with solitary HCC lesions appears to be affected mainly by the degree of liver dysfunction, and not the initial tumor diameter, radiation dose, or concurrent use of TACE. (author)

  5. Tumor thrombus of inferior vena cava in patients with renal cell carcinoma – clinical and oncological outcome of 50 patients after surgery

    Directory of Open Access Journals (Sweden)

    Kocot Arkadius

    2012-06-01

    Full Text Available Abstract Background To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC and tumor thrombus involving inferior vena cava (IVC treated with nephrectomy and thrombectomy. Methods We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome. Results The median follow-up was 26 months. In 21 patients (42% distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30%, thoracoabdominal (14 patients/28% or midline abdominal approach (21 patients/42%, depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB was performed in 10 patients (20% with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1%. Survival for the patients without distant metastasis at 5 years was 50.7%, whereas survival rate in the metastatic group at 5 years was 7.4%. Median survival of patients with metastatic disease was 16.4 months. On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10 even had a better outcome (overall survival at 5 years of 58.33% than the entire cohort. Conclusions An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal

  6. A massive hepatic tumor demonstrating hepatocellular, cholangiocarcinoma and neuroendocrine lineages: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Rachel E. Beard

    2017-01-01

    Conclusion: This is one of the only reports of a hepatic tumor arising from hepatocellular carcinoma, cholangiocarcinoma and neuroendocrine lineages. Increased awareness of this tumor type may optimize improve future management.

  7. 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.

  8. Iodine-125 Seeds Strand for Treatment of Tumor Thrombus in Inferior Vena Cava: An Experimental Study in a Rabbit Model

    International Nuclear Information System (INIS)

    Zhang, Wen; Yan, Zhiping; Luo, Jianjun; Fang, Zhuting; Wu, Linlin; Liu, QingXin; Qu, Xudong; Liu, Lingxiao; Wang, Jianhua

    2013-01-01

    Objective: The purpose of this study was to establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate the effect of linear iodine-125 seeds strand in treating implanted IVCTT. Methods: Tumor cell line VX 2 was inoculated subcutaneously into New Zealand rabbit to develop the parent tumor. The tumor strip was inoculated into inferior vena cava (IVC) to establish the IVCTT model. The IVCTT was confirmed by multidetector computed tomography (MDCT) after 2 weeks. Twelve rabbits with IVCTT were randomly divided into two groups. Treatment group (group T; n = 6) underwent Iodine-125 seeds brachytherapy, and the control group (group C; n = 6) underwent blank seeds strand. The blood laboratory examination (including blood routine examination, hepatic and renal function), body weight, survival time, and IVCTT volume by MDCT were monitored. All rabbits were dissected postmortem, and the therapeutic effects were evaluated on the basis of histopathology. The proliferating cell nuclear antigen index (PI) and apoptosis index (AI) of IVCTT were compared between two groups. T test, Wilcoxon rank test, and Kaplan–Meier survival curve analysis were used. Results: The success rate of establishing IVCTT was 100 %. The body weight loss and cachexia of rabbits in group C appeared earlier than in group T. Body weight in the third week, the mean survival time, PI, AI in groups T and C were 2.23 ± 0.12 kg, 57.83 ± 8.68 days, (16.73 ± 5.18 %), (29.47 ± 7.18 %), and 2.03 ± 0.13 kg, 43.67 ± 5.28 days, (63.01 ± 2.01 %), (6.02 ± 2.93 %), respectively. There were statistically significant differences between group T and group C (P < 0.05). The IVCTT volume of group T was remarkably smaller than that of group C. Conclusions: Injecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish IVCTT animal model. The linear Iodine-125 seeds strand brachytherapy was a safe and effective method for treating IVCTT in rabbit model

  9. Iodine-125 Seeds Strand for Treatment of Tumor Thrombus in Inferior Vena Cava: An Experimental Study in a Rabbit Model

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wen; Yan, Zhiping; Luo, Jianjun; Fang, Zhuting; Wu, Linlin; Liu, QingXin; Qu, Xudong; Liu, Lingxiao; Wang, Jianhua [Fudan University, Department of Interventional Radiology, Zhongshan Hospital (China)

    2013-10-15

    Objective: The purpose of this study was to establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate the effect of linear iodine-125 seeds strand in treating implanted IVCTT. Methods: Tumor cell line VX{sub 2} was inoculated subcutaneously into New Zealand rabbit to develop the parent tumor. The tumor strip was inoculated into inferior vena cava (IVC) to establish the IVCTT model. The IVCTT was confirmed by multidetector computed tomography (MDCT) after 2 weeks. Twelve rabbits with IVCTT were randomly divided into two groups. Treatment group (group T; n = 6) underwent Iodine-125 seeds brachytherapy, and the control group (group C; n = 6) underwent blank seeds strand. The blood laboratory examination (including blood routine examination, hepatic and renal function), body weight, survival time, and IVCTT volume by MDCT were monitored. All rabbits were dissected postmortem, and the therapeutic effects were evaluated on the basis of histopathology. The proliferating cell nuclear antigen index (PI) and apoptosis index (AI) of IVCTT were compared between two groups. T test, Wilcoxon rank test, and Kaplan-Meier survival curve analysis were used. Results: The success rate of establishing IVCTT was 100 %. The body weight loss and cachexia of rabbits in group C appeared earlier than in group T. Body weight in the third week, the mean survival time, PI, AI in groups T and C were 2.23 {+-} 0.12 kg, 57.83 {+-} 8.68 days, (16.73 {+-} 5.18 %), (29.47 {+-} 7.18 %), and 2.03 {+-} 0.13 kg, 43.67 {+-} 5.28 days, (63.01 {+-} 2.01 %), (6.02 {+-} 2.93 %), respectively. There were statistically significant differences between group T and group C (P < 0.05). The IVCTT volume of group T was remarkably smaller than that of group C. Conclusions: Injecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish IVCTT animal model. The linear Iodine-125 seeds strand brachytherapy was a safe and effective method for treating IVCTT

  10. Research advances in tumor markers for the diagnosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    YANG Guimin

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a malignant tumor with a high fatality rate in the world, and alpha-fetoprotein (AFP is the most commonly used tumor marker for HCC diagnosis. However, AFP does not have a satisfactory sensitivity or specificity and may lead to missed diagnosis when the tumor is small in the early stage of HCC. This article summarizes the clinical value of new tumor markers in the diagnosis, treatment monitoring, and prognosis judgment of HCC and analyzes the future prospects of the measurement of tumor markers for HCC. It is pointed out that combined determination of several tumor markers helps to improve the sensitivity and specificity of HCC diagnosis, and the screening and optimization of combined determination of tumor markers, noninvasive and efficient tumor markers, and individualized treatment are research hotspots in future.

  11. Rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases following combined loco-regional therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei [Dept. of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore (Singapore)

    2013-08-15

    This manuscript describes an unusual case of rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases occurring 1 month after combined chemoembolization and radiofrequency ablation. Inferior vena cava and portal vein invasion tumor thrombus was also detected, possibly accounting for the mechanism of disease dissemination route of disease.

  12. Rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases following combined loco-regional therapy

    International Nuclear Information System (INIS)

    Pua, Uei

    2013-01-01

    This manuscript describes an unusual case of rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases occurring 1 month after combined chemoembolization and radiofrequency ablation. Inferior vena cava and portal vein invasion tumor thrombus was also detected, possibly accounting for the mechanism of disease dissemination route of disease.

  13. Cone-Beam Computed Tomography (CBCT) Hepatic Arteriography in Chemoembolization for Hepatocellular Carcinoma: Performance Depicting Tumors and Tumor Feeders

    Energy Technology Data Exchange (ETDEWEB)

    Lee, In Joon [National Cancer Center, Department of Radiology (Korea, Republic of); Chung, Jin Wook, E-mail: chungjw@snu.ac.kr; Yin, Yong Hu; Kim, Hyo-Cheol; Kim, Young Il; Jae, Hwan Jun; Park, Jae Hyung [Seoul National University College of Medicine, Seoul National University Hospital, Department of Radiology (Korea, Republic of)

    2015-10-15

    PurposeThis study was designed to analyze retrospectively the performance of cone-beam computed tomography (CBCT) hepatic arteriography in depicting tumors and their feeders and to investigate the related determining factors in chemoembolization for hepatocellular carcinoma (HCC).MethodsEighty-six patients with 142 tumors satisfying the imaging diagnosis criteria of HCC were included in this study. The performance of CBCT hepatic arteriography for chemoembolization per tumor and per patient was evaluated using maximum intensity projection images alone (MIP analysis) or MIP combined with multiplanar reformation images (MIP + MPR analysis) regarding the following three aspects: tumor depiction, confidence of tumor feeder detection, and trackability of tumor feeders. Tumor size, tumor enhancement, tumor location, number of feeders, diaphragmatic motion, portal vein enhancement, and hepatic artery to parenchyma enhancement ratio were regarded as potential determining factors.ResultsTumors were depicted in 125 (88.0 %) and 142 tumors (100 %) on MIP and MIP + MPR analysis, respectively. Imaging performances on MIP and MIP + MPR analysis were good enough to perform subsegmental chemoembolization without additional angiographic investigation in 88 (62.0 %) and 128 tumors (90.1 %) on per-tumor basis and in 43 (50 %) and 73 (84.9 %) on per-patient basis, respectively. Significant determining factors for performance in MIP + MPR analysis on per tumor basis were tumor size (p = 0.030), tumor enhancement (0.005), tumor location (p = 0.001), and diaphragmatic motion (p < 0.001).ConclusionsCBCT hepatic arteriography provided sufficient information for subsegmental chemoembolization by depicting tumors and their feeders in the vast majority of patients. Combined analysis of MIP and MPR images was essential to enhance the performance of CBCT hepatic arteriography.

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

    Directory of Open Access Journals (Sweden)

    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

  15. Massive tumor pulmonary embolism following transcatheter arterial chemoembolization of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kim, Jeong Ho; Ko, Gi Young; Yoon, Hyun Ki; Sung, Kyu Bo

    2002-01-01

    Pulmonary embolism complicated by transcatheter arterial chemoembolization (TACE) in known to be due to the use of large amount of lipiodol as an embolic agent. To our knowledge, massive tumoral pulmonary embolism following TACE and confirmed by surgery has not been described in the literature. In this report, we detail the cas of a 49-year-old man in whom cyanosis and hypotension developed abruptly on the day of TACE.. Chest CT revealed diffuse low-attenuated lesions in both pulmonary arteries. Histopathological specimens after emergent pulmonary arterial embolectomy confirmed the presence of massive tumor emboli of hepatocellular carcinoma

  16. Massive tumor pulmonary embolism following transcatheter arterial chemoembolization of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kim, Jeong Ho; Ko, Gi Young; Yoon, Hyun Ki; Sung, Kyu Bo

    2002-01-01

    Pulmonary embolism complicated by transcatheter arterial chemoembolization (TACE) is known to be due to the use of large amount of lipiodol as an embolic agent. To our knowledge, massive tumoral pulmonary embolism following TACE and confirmed by surgery has not been described in the literature. In this report, we detail the case of a 49-year-old man in whom cyanosis and hypotension developed abruptly on the day of TACE. Chest CT revealed diffuse low-attenuated lesions in both pulmonary arteries. Histopathological specimens after emergent pulmonary arterial embolectomy confirmed the presence of massive tumor emboli of hepatocellular carcinoma

  17. CT of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. A metastatic adrenal tumor from a hepatocellular carcinoma: combination therapy with transarterial chemoembolization and radiofrequency ablation

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyun Jin; Cho, Yun Ku; Ahn, Yong Sik; Kim, Mi Young [Seoul Veterans Hospital, Seoul (Korea, Republic of)

    2007-07-15

    The adrenal gland is the second most common site of metastasis from a hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) for these tumors has been reported to be a potentially effective alternative to an adrenalectomy, especially for inoperable patients. However, for intermediate or large adrenal tumors, combination therapy of transarterial chemoembolization (TACE) and RFA can be attempted as it may reduce the heat sink effect. A 74-year-old patient presented with abdominal discomfort. Abdominal CT images revealed a 5.0 cm sized right adrenal mass. A percutaneous biopsy of the adrenal mass revealed a metastatic hepatocellular carcinoma. TACE was performed on the adrenal mass. However, a one-month follow-up CT image revealed a residual viable tumor. RFA was performed for the adrenal tumor six weeks after the TACE. No procedure-related major complications were noted. The serum alpha-fetoprotein level had also been normalized after the treatment, and 10-month follow-up CT images showed no definite evidence of viable adrenal tumor.

  19. Baseline Tumor Lipiodol Uptake after Transarterial Chemoembolization for Hepatocellular Carcinoma: Identification of a Threshold Value Predicting Tumor Recurrence.

    Science.gov (United States)

    Matsui, Yusuke; Horikawa, Masahiro; Jahangiri Noudeh, Younes; Kaufman, John A; Kolbeck, Kenneth J; Farsad, Khashayar

    2017-12-01

    The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response. A single-institution retrospective database of HCC treated with Lipiodol-TACE was reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy emulsion and no additional particle embolization were included. Baseline Lipiodol uptake was measured as the mean Hounsfield units (HU) on a CT within one week after TACE. Washout rate was calculated dividing the difference in HU between the baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models were used to correlate baseline Lipiodol uptake and other variables with tumor response. A receiver operating characteristic (ROC) curve was used to identify the optimal threshold for baseline Lipiodol uptake predicting tumor response. During the follow-up period (mean 5.6 months), 19 (41.3%) tumors recurred (mean time to recurrence = 3.6 months). In a multivariate model, low baseline Lipiodol uptake and higher washout rate were significant predictors of early tumor recurrence ( P = 0.001 and Baseline Lipiodol uptake and washout rate on follow-up were independent predictors of early tumor recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly sensitive and specific for tumor response. These findings may prove useful for determining subsequent treatment strategies after Lipiodol TACE.

  20. 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.

  1. [Cellular adhesion signal transduction network of tumor necrosis factor-alpha induced hepatocellular carcinoma cells].

    Science.gov (United States)

    Zheng, Yongchang; Du, Shunda; Xu, Haifeng; Xu, Yiyao; Zhao, Haitao; Chi, Tianyi; Lu, Xin; Sang, Xinting; Mao, Yilei

    2014-11-18

    To systemically explore the cellular adhesion signal transduction network of tumor necrosis factor-alpha (TNF-α)-induced hepatocellular carcinoma cells with bioinformatics tools. Published microarray dataset of TNF-α-induced HepG2, human transcription factor database HTRI and human protein-protein interaction database HPRD were used to construct and analyze the signal transduction network. In the signal transduction network, MYC and SP1 were the key nodes of signaling transduction. Several genes from the network were closely related with cellular adhesion.Epidermal growth factor receptor (EGFR) is a possible key gene of effectively regulating cellular adhesion during the induction of TNF-α. EGFR is a possible key gene for TNF-α-induced metastasis of hepatocellular carcinoma.

  2. Mechanism and Natural Course of Tumor Involution in Hepatocellular Carcinoma Following Transarterial Ethanol Ablation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Simon Chun Ho, E-mail: simonyu@cuhk.edu.hk; Lau, Tiffany Wing Wa; Tang, Peggy; Chan, Stephen Ka Chi; Chu, Charmant Cheuk Man; Hui, Joyce Wai Yi [The Chinese University of Hong Kong, Department of Imaging and Interventional Radiology, Prince of Wales Hospital (Hong Kong); Lee, Kit Fai [Prince of Wales Hospital, Department of Surgery (Hong Kong); Chan, Anthony [The Chinese University of Hong Kong, Department of Anatomical and Cellular Pathology (Hong Kong)

    2016-08-15

    PurposeTo evaluate the microvascular distribution of lipiodol–ethanol, the histological change of the tumor lesion, and the status of tumor involution over time in hepatocellular carcinoma (HCC) following transarterial ethanol ablation (TEA), in lesions that showed CT evidence of complete tumor response.Materials and methodsPatients with unresectable HCC were treated (183 patients, 242 lesions) with TEA using lipiodol–ethanol mixture (LEM) mixed in 2:1 ratio by volume and followed with CT at 3-month intervals for a median of 14.1 months. Liver tumors (n = 131) that showed CT evidence of complete tumor response, defined as the absence of any enhancing tumor throughout the follow-up period, were included. The surgical specimens of five patients who subsequently received partial hepatectomy were available for histological assessment. The microvascular distribution of LEM and the degree of tumor necrosis were analyzed. Tumor involution over time was assessed with CT in lesions that showed complete response.ResultsLipid stain revealed lipiodol infiltration throughout arterioles, intratumoral sinusoidal spaces, tumor capsule, and peritumoral portal venules. Complete tumor necrosis (100 %) occurred in all 5 surgical specimens. The median (IQR) percentage tumor volume compared to baseline volumes at 12, 36, and 60 months was 32 % (23.5–52.5 %), 22 % (8–31 %), and 13.5 % (6–21.5 %), respectively.ConclusionIntrahepatic HCC lesion that showed CT evidence of complete tumor response following TEA is associated with histological evidence of LEM infiltration throughout the intratumoral and peritumoral vasculature and complete tumor necrosis, as well as sustained reduction in tumor volume over time.

  3. MicroRNA-regulated non-viral vectors with improved tumor specificity in an orthotopic rat model of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ronald, J A; Katzenberg, R; Nielsen, Carsten Haagen

    2013-01-01

    In hepatocellular carcinoma (HCC), tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs (miRNAs) are powerful negative regulators of gene expression and many are downregulated in human HCC. We identified seven miRNAs that are also downregulated in tumors...

  4. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. A case of huge colon carcinoma and right renal angiomyolipoma accompanied by proximal deep venous thrombosis, pulmonary embolism and tumor thrombus in the renal vein.

    Science.gov (United States)

    Ban, Daisuke; Yamamoto, Seiichiro; Kuno, Hirofumi; Fujimoto, Hiroyuki; Fujita, Shin; Akasu, Takayuki; Moriya, Yoshihiro

    2008-10-01

    A preoperative inferior vena cava (IVC) filter is reported to be effective in surgical cases with proximal deep venous thrombosis (DVT) or in which pulmonary embolism (PE) has already developed, and considered to be at high risk of developing secondary fatal PE during or after surgery. However, guidelines for using an IVC filter have yet to be established. The patient in the present report had two huge tumors, ascending colon cancer and renal angiomyolipoma, which occupied the entire right half of the abdomen, coexisting PE, DVT and tumor thrombus in the right renal vein. Secondary PE is fatal in the perioperative period, therefore, the vena cava filters were preoperatively inserted into the supra- and the infrarenal IVC. We successfully removed the tumors without complications. The patient is alive without tumor recurrence and PE or recurrent DVT 1 year and 6 months after surgery. The coexistence of two huge abdominal tumors as potential causes of PE and DVT is extremely rare, and we could have safely undergone the operation, using two vena cava filters in the supra- and infrarenal IVC.

  7. 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

  8. Single-level dynamic spiral CT of hepatocellular carcinoma: correlation between imaging features and tumor angiogenesis

    International Nuclear Information System (INIS)

    Chen Weixia; Min Pengqiu; Song Bin; Xiao Bangliang; Liu Yan; Wang Wendong; Chen Xian; Xu Jianying

    2001-01-01

    Objective: To investigate the correlation of the enhancement imaging features of hepatocellular carcinoma (HCC) and relevant parameters revealed by single-level dynamic spiral CT scanning with tumor microvessel counting (MVC). Methods: The study included 26 histopathologically proven HCC patients. Target-slice dynamic scanning and portal venous phase scanning were performed for all patients. The time-density curves were generated with measurement of relevant parameters including: peak value (PV) and contrast enhancement ratio (CER), and the gross enhancement morphology analyzed. Histopathological slides were carefully prepared for the standard F8RA and VEGF immunohistochemical staining and tumor microvessel counting and calculation of VEGF expression percentage of tumor cells. The enhancement imaging features of HCC lesions were correlatively studied with tumor MVC and VEGF expression. Results: Peak value of HCC lesions were 7.9 to 75.2 HU, CER were 3.8% to 36.0%. MVC were 6 to 91, and the VEGF expression percentage were 32.1% to 78.3%. The PV and CER were significantly correlated with tumor tissue MVC (r = 0.508 and 0.423, P < 0.01 and 0.05 respectively). There were no correlations between PV and CER and VEGF expression percentage. Both the patterns of time-density curve and the gross enhancement morphology of HCC lesions were also correlated with tumor MVC, and reflected the distribution characteristics of tumor microvessels within HCC lesions. A close association was found between the likelihood of intrahepatic metastasis of HCC lesions with densely enhanced pseudo capsules and the presence of rich tumor microvessels within these pseudo capsules. Conclusion: The parameters and the enhancement imaging features of HCC lesions on target-slice dynamic scanning are correlated with tumor MVC, and can reflect the distribution characteristics of tumor microvessels within HCC lesions. Dynamic spiral CT scanning is a valuable means to assess the angiogenic activity and

  9. Multi-slice CT three dimensional volume measurement of tumors and livers in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Yu Yuanlong; Li Liangcai; Tang Binghang; Hu Zemin

    2004-01-01

    Objective: To examine the accuracy of multi-slice CT (MSCT) three dimensional (3D) volume measurement of tumors and livers in hepatocellular carcinoma cases by using immersion method as the standard. Methods: (1) The volume of 25 porkling livers was measured using immersion method in experiment group in vitro. Then the models were built according to Matsumoto's method and CT scanning and special software were used to measure the volume of the livers. (2) The volume of the tumors in 25 cases of hepatocellular carcinoma was measured using diameter measurement method and special volume measurement software (tissue measurements). Two tumors of them were measured respectively using MSCT 3D measurement, diameter measurement before the operation and immersion method after the operation. The data of the two groups were examined using pairing t test. Results: (1) The volume range of 25 porkling livers was 68.50-1150.10 ml using immersion method and 69.78-1069.97 ml using MSCT 3D measurement. There was no significant difference of the data in these two groups using t-test (t=1.427, P>0.05). (2) The volume range of 25 hepatocellular tumors was 395.16-2747.7 ml using diameter measurement and 203.10-1463.19 ml using MSCT 3D measurement before the operation. There was significant difference of the data in these two groups using t-test (t=7.689, P<0.001). In 2 ablated tumors, 1 case's volume was (21.75±0.60) ml using MSCT 3D measurement and 33.73 ml using diameter measurement before the operation and 21.50 ml using immersion measurement after the operation. The other case's volume was (696.13±5.30) ml using MSCT 3D measurement and 1323.51 ml using diameter measurement before the operation and 685.50 ml using immersion measurement after the operation. Conclusion: MSCT 3D volume measurement can accurately measure the volume of tumor and liver and has important clinical application value. There is no significant difference between MSCT 3D volume measurement and immersion method

  10. Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma.

    Science.gov (United States)

    Markowitz, Geoffrey J; Michelotti, Gregory A; Diehl, Anna Mae; Wang, Xiao-Fan

    2015-04-01

    Initiation and progression of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue. This diseased liver tissue background is a drastically different microenvironment from the healthy liver, especially with regard to immune cell prevalence and presence of mediators of immune function. To better understand the consequences of liver disease on tumor growth and the interplay with its microenvironment, we utilized two standard methods of fibrosis induction and orthotopic implantation of tumors into the inflamed and fibrotic liver to mimic the liver condition in human HCC patients. Compared to non-diseased controls, tumor growth was significantly enhanced under fibrotic conditions. The immune cells that infiltrated the tumors were also drastically different, with decreased numbers of natural killer cells but greatly increased numbers of immune-suppressive CD11b + Gr1 hi myeloid cells in both models of fibrosis. In addition, there were model-specific differences: Increased numbers of CD11b + myeloid cells and CD4 + CD25 + T cells were found in tumors in the bile duct ligation model but not in the carbon tetrachloride model. Induction of fibrosis altered the cytokine production of implanted tumor cells, which could have farreaching consequences on the immune infiltrate and its functionality. Taken together, this work demonstrates that the combination of fibrosis induction with orthotopic tumor implantation results in a markedly different tumor microenvironment and tumor growth kinetics, emphasizing the necessity for more accurate modeling of HCC progression in mice, which takes into account the drastic changes in the tissue caused by chronic liver disease.

  11. Clinical value of 18F-FDG PET/CT in detecting viable tumor, recurrence and metastases of hepato-cellular carcinoma after transcatheter arterial chemoembolization

    International Nuclear Information System (INIS)

    Hu Silong; Zhang Yingjian; Zhu Beiling; Shi Wei; Men Zhiqiang; Li Peilen; Jiang Guoliang

    2009-01-01

    Objective: Accurate evaluation of treatment result of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) by conventional imaging is difficult. The objective of this study was to investigate the clinical value of 18 F-fluorodeoxyglucose (FDG) PET/CT for detecting residual viable tumor, recurrence and metastases in patients with HCC after TACE. Methods: Twenty-two patients with HCC after TACE were investigated with 18 F-FDG PET/CT. The accuracy of FDG PET/CT was determined by the histopathological results or evidences of clinical follow-up. Results: Of all 22 HCC patients after TACE, 18 had intra- and (or) extrahepatic lesions, detected by FDG PET/CT. Six-teen patients had intrahepatic FDG-avid lesion(s). Of the 16 patients, five had intrahepatic FDG-avid lesions located at both lipiodol-rich and -deprive regions, 13 had associated extrahepatic metastases. Of the two HCC patients who had no intrahepatic FDG-avid lesion, there were extrahepatic FDG-avid lesions at the retroperitoneal lymph nodes. In all, 15 HCC had extrahepatic lesions identified by FDG PET/CT. There were lung and lymph nodes (n = 9), bone (n = 2), tumor thrombus at portal vein (n - 1) and diaphragm crus (n = 1). Two patients were false negative. The sensitivity, specificity, accuracy of FDG PET/CT in detecting intra- and (or) extrahepatic lesions after TACE were 88.9% (16/18) vs 94.7 % (18/19), 4/4 vs 3/3, and 90.9% (20/22) vs 95.5% (21/22), respectively. Conclusion: 18 F-FDG PET/CT is potential useful for detection both intra- and (or) extrahepatic lesions in HCC patients after TACE. (authors)

  12. 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.

  13. Histological assessment of the efficacy of drug-eluting beads in portal tumor thrombosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yusuke Imai, MD

    2017-03-01

    Full Text Available A 58-year-old man was diagnosed with advanced hepatocellular carcinoma with portal vein tumor thrombosis (PVTT. The tumors were multiple and existed in both lobes. Drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE was performed for the tumors in the left lobe. Embosphere and Hepasphere were selected for embolization of the arterioportal shunt, followed by loaded epirubicin infusion into the left hepatic artery. Computed tomography showed reduction of PVTT. However, liver failure progressed, and the patient died 67 days after DEB-TACE. Autopsy showed that the beads reached the tumor thrombosis in the portal vein. The prognosis of hepatocellular carcinoma with PVTT is poor. Although there are no established treatments for unresectable PVTT, DEB-TACE might be a useful option for such cases.

  14. Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.

    Science.gov (United States)

    Markowitz, Geoffrey J; Yang, Pengyuan; Fu, Jing; Michelotti, Gregory A; Chen, Rui; Sui, Jianhua; Yang, Bin; Qin, Wen-Hao; Zhang, Zheng; Wang, Fu-Sheng; Diehl, Anna Mae; Li, Qi-Jing; Wang, Hongyang; Wang, Xiao-Fan

    2016-04-15

    Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results have been reported for IL18 in hepatocellular carcinoma development and progression. In this study, we used tissue specimens from hepatocellular carcinoma patients and clinically relevant mouse models of hepatocellular carcinoma to evaluate IL18 expression and function. In a mouse model of liver fibrosis that recapitulates a tumor-promoting microenvironment, global deletion of the IL18 receptor IL18R1 enhanced tumor growth and burden. Similarly, in a carcinogen-induced model of liver tumorigenesis, IL18R1 deletion increased tumor burden. Mechanistically, we found that IL18 exerted inflammation-dependent tumor-suppressive effects largely by promoting the differentiation, activity, and survival of tumor-infiltrating T cells. Finally, differences in the expression of IL18 in tumor tissue versus nontumor tissue were more predictive of patient outcome than overall tissue expression. Taken together, our findings resolve a long-standing contradiction regarding a tumor-suppressive role for IL18 in established hepatocellular carcinoma and provide a mechanistic explanation for the complex relationship between its expression pattern and hepatocellular carcinoma prognosis. Cancer Res; 76(8); 2394-405. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. Hepatocellular carcinoma with bile duct tumor thrombi: Correlation of magnetic resonance imaging features to histopathologic manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Liu Qingyu, E-mail: liu.qingyu@163.co [Department of Radiology, Second Affiliated Hospital of Sun Yat-sen University, 107 Yan Jiang Xi Road, Guangzhou, 510120, Guangdong Province (China); Chen Jianyu, E-mail: chenjianyu5562@sina.co [Department of Radiology, The Second Affiliated Hospital of Sun Yat-sen University, 107 Yan Jiang Xi Road, Guangzhou, 510120, Guangdong Province (China); Li Haigang, E-mail: lhg00433@yahoo.com.c [Department of Pathology, Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province (China); Liang Biling, E-mail: liangbl@163.ne [Department of Radiology, Second Affiliated Hospital of Sun Yat-sen University, 107 Yan Jiang Xi Road, Guangzhou, 510120, Guangdong Province (China); Zhang Lei, E-mail: zhanglei646@126.co [Department of Hepatobiliary Surgery, Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province (China); Hu Tao, E-mail: htwuaini@hotmail.co [Department of Radiology, Second Affiliated Hospital of Sun Yat-sen University, 107 Yan Jiang Xi Road, Guangzhou, 510120, Guangdong Province (China)

    2010-10-15

    Purpose: This study was to analyze the magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) with bile duct tumor thrombi, and explore their correlations to histopathology to improve the accuracy of diagnosis. Materials and methods: 21 patients with pathologically confirmed HCC with bile duct tumor thrombi was performed with a superconducting 1.5-T MR imager within two weeks before operation. Magnetic resonance cholangiopancreatography (MRCP) was performed on 18 patients. Images were retrospectively assessed for the size, location and MRI manifestations of HCC lesions and associated bile duct tumor thrombi. The differentiation of HCC lesions and the pathologic changes of bile duct tumor thrombi were retrospectively analyzed under microscope. Results: The average diameter of HCC lesions was 5.8 {+-} 2.8 cm, and {<=}5.0 cm in nine cases. Capsule formation was observed on MRI or pathology in 4 cases of HCC (19%). Of the 21 cases with bile duct tumor thrombi, 20 were clearly presented on MRI as cord-like or columnar masses in the bile duct with proximal cholangiectasis. The tumor thrombi showed slightly hypointense on T1WI and slightly hyperintense on T2WI. On enhanced scan, three cases of tumor thrombi, which were mainly consisted of necrotic tissue, did not show enhancement; 17 cases, which were mainly consisted of cancer cells, showed mild or moderate enhancement. On magnetic resonance cholangiopancreatogram (MRCP), 14 cases of tumor thrombi presented as filling defect in the bile duct, abrupt obstruction of the bile duct, and cholangiectasis above the obstruction; four presented as dilated intra-hepatic bile ducts with missing common bile duct. Of the 21 patients, 16 had biliary hemorrhage; three also had tumor thrombi in the portal vein. Seventeen of the 21 HCC with biliary thrombi were poorly differentiated, unencapsulated and with an invasive growth. Nineteen of 21 bile duct tumor thrombi did not invade the bile duct wall and could be

  16. Hepatocellular carcinoma with bile duct tumor thrombi: Correlation of magnetic resonance imaging features to histopathologic manifestations

    International Nuclear Information System (INIS)

    Liu Qingyu; Chen Jianyu; Li Haigang; Liang Biling; Zhang Lei; Hu Tao

    2010-01-01

    Purpose: This study was to analyze the magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) with bile duct tumor thrombi, and explore their correlations to histopathology to improve the accuracy of diagnosis. Materials and methods: 21 patients with pathologically confirmed HCC with bile duct tumor thrombi was performed with a superconducting 1.5-T MR imager within two weeks before operation. Magnetic resonance cholangiopancreatography (MRCP) was performed on 18 patients. Images were retrospectively assessed for the size, location and MRI manifestations of HCC lesions and associated bile duct tumor thrombi. The differentiation of HCC lesions and the pathologic changes of bile duct tumor thrombi were retrospectively analyzed under microscope. Results: The average diameter of HCC lesions was 5.8 ± 2.8 cm, and ≤5.0 cm in nine cases. Capsule formation was observed on MRI or pathology in 4 cases of HCC (19%). Of the 21 cases with bile duct tumor thrombi, 20 were clearly presented on MRI as cord-like or columnar masses in the bile duct with proximal cholangiectasis. The tumor thrombi showed slightly hypointense on T1WI and slightly hyperintense on T2WI. On enhanced scan, three cases of tumor thrombi, which were mainly consisted of necrotic tissue, did not show enhancement; 17 cases, which were mainly consisted of cancer cells, showed mild or moderate enhancement. On magnetic resonance cholangiopancreatogram (MRCP), 14 cases of tumor thrombi presented as filling defect in the bile duct, abrupt obstruction of the bile duct, and cholangiectasis above the obstruction; four presented as dilated intra-hepatic bile ducts with missing common bile duct. Of the 21 patients, 16 had biliary hemorrhage; three also had tumor thrombi in the portal vein. Seventeen of the 21 HCC with biliary thrombi were poorly differentiated, unencapsulated and with an invasive growth. Nineteen of 21 bile duct tumor thrombi did not invade the bile duct wall and could be easily

  17. Microarray profiling shows distinct differences between primary tumors and commonly used preclinical models in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wang, Weining; Iyer, N. Gopalakrishna; Tay, Hsien Ts’ung; Wu, Yonghui; Lim, Tony K. H.; Zheng, Lin; Song, In Chin; Kwoh, Chee Keong; Huynh, Hung; Tan, Patrick O. B.; Chow, Pierce K. H.

    2015-01-01

    Despite advances in therapeutics, outcomes for hepatocellular carcinoma (HCC) remain poor and there is an urgent need for efficacious systemic therapy. Unfortunately, drugs that are successful in preclinical studies often fail in the clinical setting, and we hypothesize that this is due to functional differences between primary tumors and commonly used preclinical models. In this study, we attempt to answer this question by comparing tumor morphology and gene expression profiles between primary tumors, xenografts and HCC cell lines. Hep G2 cell lines and tumor cells from patient tumor explants were subcutaneously (ectopically) injected into the flank and orthotopically into liver parenchyma of Mus Musculus SCID mice. The mice were euthanized after two weeks. RNA was extracted from the tumors, and gene expression profiling was performed using the Gene Chip Human Genome U133 Plus 2.0. Principal component analyses (PCA) and construction of dendrograms were conducted using Partek genomics suite. PCA showed that the commonly used HepG2 cell line model and its xenograft counterparts were vastly different from all fresh primary tumors. Expression profiles of primary tumors were also significantly divergent from their counterpart patient-derived xenograft (PDX) models, regardless of the site of implantation. Xenografts from the same primary tumors were more likely to cluster together regardless of site of implantation, although heat maps showed distinct differences in gene expression profiles between orthotopic and ectopic models. The data presented here challenges the utility of routinely used preclinical models. Models using HepG2 were vastly different from primary tumors and PDXs, suggesting that this is not clinically representative. Surprisingly, site of implantation (orthotopic versus ectopic) resulted in limited impact on gene expression profiles, and in both scenarios xenografts differed significantly from the original primary tumors, challenging the long

  18. [Value of R2(*) in evaluating the biological behavior of primary hepatocellular carcinoma].

    Science.gov (United States)

    Tian, S F; Liu, A L; Liu, J H; Li, Y; Liu, X D; Huang, K; Song, Q W; Xu, M Z; Guo, W Y

    2016-04-19

    To investigate the correlation between R2(*) value of enhanced T2 star-weighted angiography (ESWAN) sequence and primary hepatocellular carcinoma infiltration and tumor thrombus, and investigate the biological behavior of HCC. A total of 221 cases of patients' imaging data with MRI examination(including ESWAN sequence) diagnosed as primary HCC were retrospectively analyzed.All the patients were collected from January 2014 to September 2015 in the First Affiliated Hospital of Dalian Medical University.The differences of R2(*) values in different MR types of HCC were analyzed.All patients were divided into infiltration group and non-infiltration group, tumor thrombus group and non-tumor thrombus group, the R2(*) values of the paired groups were compared.The diagnostic efficiency of R2(*) in HCC infiltration and tumor thrombus were evaluated by ROC curve, and to find out the threshold values. The MR types of 221 patients included 90 cases of nodular type, 62 cases of massive type, 69 cases of diffuse type.70 patients had tumor thrombus.The R2(*) values of different MR types were (21.82±8.52), (24.17±8.84)and (34.45±11.73) Hz, respectively.There was no statistically significant difference between the nodular and the massive types (P=0.144), while the difference between the nodular and diffuse type, the massive and diffuse types were statistically significant(P=0.000). The R2(*) values of infiltration group and non-infiltration group were (34.45±11.73) and (22.78±8.70) Hz , the R2(*) values of tumor thrombus group and non-tumor thrombus group were (31.20±12.17) and (24.21±9.90) Hz, the difference also had statistically significant(t=7.397 and 4.534, P=0.000 and 0.000). The AUC of R2(*) values for infiltration and tumor thrombus were 0.804, 0.681. R2(*) ≥24.68 Hz was the threshold value to diagnose the infiltration and tumor thrombus. R2(*) value can be used as a MR non-enhancement quantitative index to evaluate the biological behavior of HCC.

  19. Cyclin-dependent kinase inhibitor 3 is overexpressed in hepatocellular carcinoma and promotes tumor cell proliferation

    International Nuclear Information System (INIS)

    Xing, Chunyang; Xie, Haiyang; Zhou, Lin; Zhou, Wuhua; Zhang, Wu; Ding, Songming; Wei, Bajin; Yu, Xiaobo; Su, Rong; Zheng, Shusen

    2012-01-01

    Highlights: ► CDKN3 is commonly overexpressed in HCC and is associated with poor clinical outcome. ► Overexpression of CDKN3 could stimulate the proliferation of HCC cells by promoting G1/S transition. ► CDKN3 could inhibit the expression of p21 in HCC cells. ► Overexpression of CDKN3 has no effect on apoptosis and invasion of HCC cells. ► We identified 61 genes co-expressed with CDKN3, and BIRC5 was located at the center of the co-expression network. -- Abstract: Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the protein phosphatases family and has a dual function in cell cycling. The function of this gene has been studied in several kinds of cancers, but its role in human hepatocellular carcinoma (HCC) remains to be elucidated. In this study, we found that CDKN3 was frequently overexpressed in both HCC cell lines and clinical samples, and this overexpression was correlated with poor tumor differentiation and advanced tumor stage. Functional studies showed that overexpression of CDKN3 could promote cell proliferation by stimulating G1-S transition but has no impact on cell apoptosis and invasion. Microarray-based co-expression analysis identified a total of 61 genes co-expressed with CDKN3, with most of them involved in cell proliferation, and BIRC5 was located at the center of CDKN3 co-expression network. These results suggest that CDKN3 acts as an oncogene in human hepatocellular carcinoma and antagonism of CDKN3 may be of interest for the treatment of HCC.

  20. Anti-tumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Qin JM

    2012-01-01

    Full Text Available Jian-Min Qin1, Pei-Hao Yin1, Qi Li1, Zhong-Qiu Sa1, Xia Sheng1, Lin Yang1, Tao Huang1, Min Zhang1, Ke-Pan Gao2, Qing-Hua Chen2, Jing-Wei Ma3, He-Bai Shen31Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 2National Pharmaceutical Engineering Research Center; Shanghai Institute of Pharmaceutical Industry, 3Department of Physical Chemistry, Shanghai Normal University, Shanghai, People's Republic of ChinaBackground: Hepatocellular carcinoma is difficult to diagnose early, and most patients are already in the late stages of the disease when they are admitted to hospital. The total 5-year survival rate is less than 5%. Recent studies have showed that brucine has a good anti-tumor effect, but high toxicity, poor water solubility, short half-life, narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study evaluated the effects of brucine immuno-nanoparticles (BIN on hepatocellular carcinoma.Materials and methods: Anionic polymerization, chemical modification technology, and phacoemulsification technology were used to prepare a carboxylated polyethylene glycol-polylactic acid copolymer carrier material. Chemical coupling technology was utilized to develop anti-human AFP McAb-polyethylene glycol-polylactic acid copolymer BIN. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these immune-nanoparticles were studied in vitro. The targeting, and growth, invasion, and metastasis inhibitory effects of this treatment on liver cancer SMMC-7721 cells were tested.Results: BIN were of uniform size with an average particle size of 249 ± 77 nm and zeta potential of -18.7 ± 4.19 mV. The encapsulation efficiency was 76.0% ± 2.3% and the drug load was 5.6% ± 0.2%. Complete uptake and even distribution around the liver cancer cell membrane were observed.Conclusion: BIN had even size distribution, was

  1. Tumor stroma with senescence-associated secretory phenotype in steatohepatitic hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Jee San Lee

    Full Text Available Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC, a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs. The expression of α-smooth muscle actin (α-SMA, p21Waf1/Cif1, γ-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P <0.05, all. The numbers of α-SMA-positive cancer-associated fibroblasts (CAFs (P = 0.049 and α-SMA-positive CAFs co-expressing p21Waf1/Cif1 (P = 0.038, γ-H2AX (P = 0.065, and IL-6 (P = 0.048 were greater for SH-HCCs than C-HCCs. Additionally, non-tumoral liver from SH-HCCs showed a higher incidence of non-alcoholic fatty liver disease and a higher number of α-SMA-positive stellate cells expressing γ-H2AX and p21Waf1/Cif1 than that from C-HCCs (P <0.05, all. In conclusion, SH-HCCs are considered to occur more frequently in metabolic syndrome patients. Therein, senescent and damaged CAFs, as well as non-tumoral stellate cells, expressing SASP including IL-6 may contribute to the development of SH-HCC.

  2. Tolerability and efficacy of gamma knife radiosurgery on hepatocellular carcinoma with portal vein tumor thrombosis

    Science.gov (United States)

    Lu, Xiao-Jie; Dong, Jing; Ji, Li-Juan; Xiao, Li-Xin; Ling, Chang-Quan; Zhou, Jun

    2016-01-01

    This is a retrospective study on the safety and efficacy of gamma knife radiosurgery (GKR) in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Patients with confirmed HCC and PVTT were allocated into two groups based on the treatments they received (palliative or GKR). A total of 138 patients were included (74 in the palliative group, 64 in GKR group). No significant differences in baseline characteristics existed between the two groups. Treatment-related adverse events (AEs) were recorded and compared between groups. The majority of AEs were mild to moderate and subsided naturally or after medication. There was no AE-induced death. The influences of baseline characteristics and treatment options on patients' OS were analyzed. The median OS of patients in the palliative and GKR group were 3.0 months (95% CI: 2.719-3.281) and 6.1 months (95% CI: 4.706-7.494) respectively (p = 0.003). Multivariate analysis revealed that GKR treatment, performance status 0-1, Child A, smaller tumor diameter and monolobar distribution were significant favorable prognosticators. Subgroup analyses showed OS benefit of GKR regardless of PVTT location (main or branch of PVTT). In conclusion, GKR is well tolerated in selected HCC-PVTT patients and can confer OS benefit, which needs validation in future prospective studies. PMID:26473291

  3. Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study.

    Science.gov (United States)

    Carr, Brian I; Pancoska, Petr; Branch, Robert A

    2009-12-24

    967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end point. We found that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated AFP or bilirubin, or alkaline phosphatase, were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, even in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient sub groups based on liver function and tumor characteristics and found clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant factors. We also used a purely mathematical approach to derive subgroups and a prognostic model for individual patients. Interestingly, the two approaches gave similar predictive information, which opens the possibility of a more detailed mathematical analysis in the future. The results of this large dataset show that amongst non-surgical HCC patients, there are clear subsets with longer survival. The data supports the concept of heterogeneity of HCC. The three factors, bilirubin, AFP, and PVT predominate in prognosis.

  4. Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a case cohort study.

    Science.gov (United States)

    Carr, Brian I; Buch, Shama C; Kondragunta, Venkateswarlu; Pancoska, Petr; Branch, Robert A

    2008-08-01

    A total of 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end-point for all analyses. We found in our overall analysis, that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated alpha-fetoprotein (AFP) or bilirubin or alkaline phosphatases were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient subgroups based on poor liver function and aggressive tumor characteristics. In subgroup analysis based on these subsets, there was clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant, independent but modest risk factors. The results of this large dataset show that amongst nonsurgical HCC patients, there are clear subsets with longer survival than other subsets. This data also supports the concept of heterogeneity of HCC.

  5. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Rui; Zhang, Haiyang; Zhang, Yan; Li, Shuang; Wang, Xinyi; Wang, Xia; Wang, Cheng; Liu, Bin; Zen, Ke; Zhang, Chen-Yu; Zhang, Chunni; Ba, Yi

    2017-04-01

    Peroxisome proliferator-activated receptor gamma coactivator-1 alpha plays a crucial role in regulating the biosynthesis of mitochondria, which is closely linked to the energy metabolism in various tumors. This study investigated the regulatory role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha in the pathogenesis of hepatocellular carcinoma. In this study, the changes of peroxisome proliferator-activated receptor gamma coactivator-1 alpha messenger RNA levels between normal human liver and hepatocellular carcinoma tissue were examined by quantitative reverse transcription polymerase chain reaction. Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by RNA interference in the human liver cell line L02, while overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha complementary DNA in the human hepatocarcinoma cell line HepG2. Cellular morphological changes were observed via optical and electron microscopy. Cellular apoptosis was determined by Hoechst 33258 staining. In addition, the expression levels of 21,400 genes in tissues and cells were detected by microarray. It was shown that peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression was significantly downregulated in hepatocellular carcinoma compared with normal liver tissues. After knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression in L02 cells, cells reverted to immature and dedifferentiated morphology exhibiting cancerous tendency. Apoptosis occurred in the HepG2 cells after transfection by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Microarray analysis showed consistent results. The results suggest that peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor

  6. What effects performance status of patients with hepatocellular carcinoma: stage of tumor versus underlying liver status

    International Nuclear Information System (INIS)

    Sarwar, S.; Tarique, S.

    2015-01-01

    Objective: To identify variables associated with poor performance status of hepatocellular carcinoma (HCC) patients and to compare impact of stage of liver disease and that of hepatoma on functional status of patient. Patients and Methods: We included 254 confirmed cases of liver cancer in a crosssectional analytical study carried out at Doctors Hospital Lahore. Patient's clinical, biochemical and radiological variables were correlated with Karnofsky's performance status (KPS) using pearson correlation. Model for End stage Liver Disease (MELD) and Cancer of Liver Italian Program (CLIP) were evaluated for predicting performance status using Receiver Operating Characteristic (ROC) curve. Results: Mean age of patients was 56.69 (±10.34) and male to female ratio was 2.47: 1 (181/73). On KPS evaluation 84 (33.1%) patients scored between 80-100, 147 (57.9%) had score of 50-70 while in 23 (9.1%) KPS score was between 0-40. Variables associated with poor performance status were bilirubin> 3mg/dl (p value 0.00), albumin< 2.5 g/dl (p value 0.00), creatinine > 1.2mg/dl (p 0.00), prothrombin time> 16seconds (p value 0.00), size of tumor >7cm (p value 0.02), tumor involving > 50% of liver mass (p value 0.00) and vascular invasion (p value 0.00). Both stage of liver disease as determined by MELD and stage of liver cancer as per CLIP scores had strong correlation (p value 0.00) with poor performance status of patient. Area under ROC curve was 0.764 for MELD score and 0.785 for CLIP score. Conclusion: Performance status of liver cancer patients is affected by both stage of liver disease and that of liver tumor. Patients with MELD score above 16 and CLIP score above 4 have poor performance status. (author)

  7. Tumor necrosis factor-α attenuates starvation-induced apoptosis through upregulation of ferritin heavy chain in hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    Kou, Xingrui; Zhao, Qiudong; Zhao, Xue; Li, Rong; Wei, Lixin; Wu, Mengchao; Jing, Yingying; Deng, Weijie; Sun, Kai; Han, Zhipeng; Ye, Fei; Yu, Guofeng; Fan, Qingmin; Gao, Lu

    2013-01-01

    Tumor microenviroment is characteristic of inflammation, ischemia and starvation of nutrient. TNF-α, which is an extraordinarily pleiotropic cytokine, could be an endogenous tumor promoter in some tumor types. The basic objective of this study was to investigate the effects of TNF-α on the cell viability and apoptosis of hepatocellular carcinoma cells under serum starvation, and to identify the molecular mechanisms involved. For this purpose, five different concentrations of TNF-α and two different serum settings (serum-cultured and serum-deprived) were used to investigate the effects of TNF-α on the cell viability and apoptosis of Hep3B and SMMC-7721 cells. TNF-α (10 ng/ml) attenuated serum starvation-induced apoptosis of hepatocellular carcinoma cells, and autophagy conferred this process. BAY11-7082, a specific inhibitor of NF-κB, reversed the suppression of serum starvation-induced apoptosis by TNF-α. Moreover, TNF-α-induced NF-κB transactivation was suppressed by autophagy inhibitor 3-MA. In addition, TNF-α up-regulated Ferritin heavy chain (FHC) transiently by NF-κB activation and FHC levels were correlated with the TNF-α-induced protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells. Furthermore, FHC-mediated inhibition of apoptosis depended on suppressing ROS accumulation. Our findings suggested that autophagy conferred the TNF-α protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells, the mechanism involved with the activation of the TNF-α/ NF-κB /FHC signaling pathway

  8. Whole-tumor MRI histogram analyses of hepatocellular carcinoma: Correlations with Ki-67 labeling index.

    Science.gov (United States)

    Hu, Xin-Xing; Yang, Zhao-Xia; Liang, He-Yue; Ding, Ying; Grimm, Robert; Fu, Cai-Xia; Liu, Hui; Yan, Xu; Ji, Yuan; Zeng, Meng-Su; Rao, Sheng-Xiang

    2017-08-01

    To evaluate whether whole-tumor histogram-derived parameters for an apparent diffusion coefficient (ADC) map and contrast-enhanced magnetic resonance imaging (MRI) could aid in assessing Ki-67 labeling index (LI) of hepatocellular carcinoma (HCC). In all, 57 patients with HCC who underwent pretreatment MRI with a 3T MR scanner were included retrospectively. Histogram parameters including mean, median, standard deviation, skewness, kurtosis, and percentiles (5 th , 25 th , 75 th , 95 th ) were derived from the ADC map and MR enhancement. Correlations between histogram parameters and Ki-67 LI were evaluated and differences between low Ki-67 (≤10%) and high Ki-67 (>10%) groups were assessed. Mean, median, 5 th , 25 th , 75 th percentiles of ADC, and mean, median, 25 th , 75 th , 95 th percentiles of enhancement of arterial phase (AP) demonstrated significant inverse correlations with Ki-67 LI (rho up to -0.48 for ADC, -0.43 for AP) and showed significant differences between low and high Ki-67 groups (P Histogram-derived parameters of ADC and AP were potentially helpful for predicting Ki-67 LI of HCC. 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:383-392. © 2016 International Society for Magnetic Resonance in Medicine.

  9. Low levels of tumor suppressor candidate 3 predict poor prognosis of patients with hepatocellular carcinoma

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    Sheng XR

    2018-02-01

    Full Text Available Xu-Ren Sheng,1,2,* Song-Ge Xing,2,3,* Run-Dong Wang,2 Kang Chen,2 Wei-Dong Jia1,2 1Department of Liver Surgery, Affiliated Provincial Hospital, Anhui Medical University, 2Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, 3CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, People’s Republic of China *These authors contributed equally to this work Purpose: The tumor suppressor candidate 3 (TUSC3 has been considered to be closely associated with the occurrence, development and invasion of various malignant tumors. However, the expression of TUSC3 in hepatocellular carcinoma (HCC tissues remains ambiguous. The purpose of this research was to investigate the expression of TUSC3 in HCC tissues and analyze the relationship between TUSC3 levels and clinicopathological characteristics and prognosis of HCC patients. Materials and methods: Immunohistochemistry was used to detect the expression of TUSC3 in HCC and the corresponding para-cancerous tissues from 92 samples of HCC patients. mRNA and protein expression levels of TUSC3 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR and Western blot assays in 25 paired HCC and corresponding adjacent nontumor tissues. Furthermore, statistical analysis was applied to evaluate the correlation between TUSC3 level and the clinicopathological features and prognosis of HCC patients. Results: Immunohistochemical assay indicated that the expression of TUSC3 was significantly lower in HCC tissues when compared with the corresponding para-cancerous tissues (χ2=11.512, P=0.001. The analysis of clinicopathological characteristics showed that low expression of TUSC3 in HCC tissues was significantly associated with Edmondson grade, Barcelona Clinic Liver Cancer stage and tumor size (P=0.008, 0.009 and 0.020, respectively. Univariate analysis showed

  10. Detection of mycoplasma infection in circulating tumor cells in patients with hepatocellular carcinoma

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    Choi, Hong Seo; Lee, Hyun Min; Kim, Won-Tae; Kim, Min Kyu [Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul (Korea, Republic of); Chang, Hee Jin [Center for Colorectal Cancer, Research Institute and Hospital of National Cancer Center, Goyang-si (Korea, Republic of); Lee, Hye Ran [Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang-si (Korea, Republic of); Joh, Jae-Won [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Dae Shick, E-mail: oncorkim@skku.edu [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ryu, Chun Jeih, E-mail: cjryu@sejong.ac.kr [Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul (Korea, Republic of)

    2014-04-04

    Highlights: • This study generates a monoclonal antibody CA27 against the mycoplasmal p37 protein. • CA27 isolates circulating tumor cells (CTCs) from the blood of liver cancer patients. • Results show the first evidence for mycoplasma infected-CTCs in cancer patients. - Abstract: Many studies have shown that persistent infections of bacteria promote carcinogenesis and metastasis. Infectious agents and their products can modulate cancer progression through the induction of host inflammatory and immune responses. The presence of circulating tumor cells (CTCs) is considered as an important indicator in the metastatic cascade. We unintentionally produced a monoclonal antibody (MAb) CA27 against the mycoplasmal p37 protein in mycoplasma-infected cancer cells during the searching process of novel surface markers of CTCs. Mycoplasma-infected cells were enriched by CA27-conjugated magnetic beads in the peripheral blood mononuclear cells in patients with hepatocellular carcinoma (HCC) and analyzed by confocal microscopy with anti-CD45 and CA27 antibodies. CD45-negative and CA27-positive cells were readily detected in three out of seven patients (range 12–30/8.5 ml blood), indicating that they are mycoplasma-infected circulating epithelial cells. CA27-positive cells had larger size than CD45-positive hematological lineage cells, high nuclear to cytoplasmic ratios and irregular nuclear morphology, which identified them as CTCs. The results show for the first time the existence of mycoplasma-infected CTCs in patients with HCC and suggest a possible correlation between mycoplasma infection and the development of cancer metastasis.

  11. Establishment and characterization of 7 novel hepatocellular carcinoma cell lines from patient-derived tumor xenografts.

    Directory of Open Access Journals (Sweden)

    Hong Xin

    Full Text Available Hepatocellular carcinoma (HCC is a common cancer with poor prognosis worldwide and the molecular mechanism is not well understood. This study aimed to establish a collection of human HCC cell lines from patient-derived xenograft (PDX models. From the 20 surgical HCC sample collections, 7 tumors were successfully developed in immunodeficient mice and further established 7 novel HCC cell lines (LIXC002, LIXC003, LIXC004, LIXC006, LIXC011, LIXC012 and CPL0903 by primary culture. The characterization of cell lines was defined by morphology, growth kinetics, cell cycle, chromosome analysis, short tandem repeat (STR analysis, molecular profile, and tumorigenicity. Additionally, response to clinical chemotherapeutics was validated both in vitro and in vivo. STR analysis indicated that all cell lines were unique cells different from known cell lines and free of contamination by bacteria or mycoplasma. The other findings were quite heterogeneous between individual lines. Chromosome aberration could be found in all cell lines. Alpha-fetoprotein was overexpressed only in 3 out of 7 cell lines. 4 cell lines expressed high level of vimentin. Ki67 was strongly stained in all cell lines. mRNA level of retinoic acid induced protein 3 (RAI3 was decreased in all cell lines. The 7 novel cell lines showed variable sensitivity to 8 tested compounds. LIXC011 and CPL0903 possessed multiple drug resistance property. Sorafenib inhibited xenograft tumor growth of LIXC006, but not of LIXC012. Our results indicated that the 7 novel cell lines with low passage maintaining their clinical and pathological characters could be good tools for further exploring the molecular mechanism of HCC and anti-cancer drug screening.

  12. Tumor-Suppressing Effect of MiR-4458 on Human Hepatocellular Carcinoma

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    Dan Tang

    2015-03-01

    Full Text Available Background: Besides multiple genetic and epigenetic changes of protein coding genes in hepatocellular carcinoma (HCC, growing evidence indicate that deregulation of miRNAs contribute to HCC development by influencing cell growth, apoptosis, migration, or invasion. IKBKE is amplified and over-expressed in a large percentage of human breast tumors and identified as an oncogene of human breast tumor. Microarray analysis showed that miR-4458 was down-regulated in HCC tissues. Methods: The level of miR-4458 was up-regulated by miR-4458 mimics transfection, or down-regulated by miR-4458 ASO transfection. Cell proliferation was assayed by MTT analysis. MiRNAs and mRNA expression were assayed by qRT-PCR. These potential targeted genes of miR-4458 were predicted by bioinformatic algorithms. Dual luciferase reporter assay system was used to analyze the interaction between miR-4458 and IKBKE. IKBKE protein level was assayed by Western blot. The role of miR-4458 or IKBKE in the survival of HCC patients were revealed by Kaplan-Meier plot of overall survival. Results: Lower miR-4458 expression level or higher IKBKE level in HCC tissues correlated with worse prognosis of HCC patients. Overexpression of miR-4458 inhibited the HCC cells growth and vice versa. MiR-4458 played its role via targeting 3'UTR of IKBKE. Conclusions: MiR-4458 or IKBKE may be potential predictors of HCC prognosis. Restoration of miR-4458 or inhibition of IKBKE could be a prospective therapeutic approach for HCC.

  13. Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells

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    Grepper Susan

    2009-09-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is an aggressive cancer, and is the third leading cause of cancer death worldwide. Standard therapy is ineffective partly because HCC is intrinsically resistant to conventional chemotherapy. Its poor prognosis and limited treatment options make it critical to develop novel and selective chemotherapeutic agents. Since the Wnt/β-catenin pathway is essential in HCC carcinogenesis, we studied the inhibition of Wnt-1-mediated signaling as a potential molecular target in HCC. Results We demonstrated that Wnt-1 is highly expressed in human hepatoma cell lines and a subgroup of human HCC tissues compared to paired adjacent non-tumor tissues. An anti-Wnt-1 antibody dose-dependently decreased viability and proliferation of Huh7 and Hep40 cells over-expressing Wnt-1 and harboring wild type β-catenin, but did not affect normal hepatocytes with undetectable Wnt-1 expression. Apoptosis was also observed in Huh7 and Hep40 cells after treatment with anti-Wnt-1 antibody. In these two cell lines, the anti-Wnt-1 antibody decreased β-catenin/Tcf4 transcriptional activities, which were associated with down-regulation of the endogenous β-catenin/Tcf4 target genes c-Myc, cyclin D1, and survivin. Intratumoral injection of anti-Wnt-1 antibody suppressed in vivo tumor growth in a Huh7 xenograft model, which was also associated with apoptosis and reduced c-Myc, cyclin D1, and survivin expressions. Conclusion Our results suggest that Wnt-1 is a survival factor for HCC cells, and that the blockade of Wnt-1-mediated signaling may offer a potential pathway-specific therapeutic strategy for the treatment of a subgroup of HCC that over-expresses Wnt-1.

  14. Novel synergistic antitumor effects of rapamycin with bortezomib on hepatocellular carcinoma cells and orthotopic tumor model

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    Wang Cun

    2012-05-01

    Full Text Available Abstract Background Despite recent advances in the treatment of hepatocellular carcinoma (HCC, the chemotherapy efficacy against HCC is still unsatisfactory. The mammalian target of rapamycin (mTOR has been emerged as an important cancer therapeutic target. However, HCC cells often resistant to rapamycin because of the paradoxical activation of Akt by rapamycin. In this study, we investigated whether bortezomib could enhance the antitumor effects of rapamycin. Methods The effects of rapamycin and bortezomib on HCC proliferation, apoptosis, migration, and invasiveness in vitro were assessed by CCK-8 analysis, flow cytometry, Hoechst 33342 staining and transwell assays, respectively. Total and phosphorylated protein levels of Akt were detected by Western blotting. The effects of rapamycin and/or bortezomib on the mRNA expression levels of p53, p27, p21 and Bcl-2 family in HCCLM3 cells were evaluated by RT-PCR. The roles of rapamycin and bortezomib on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. The effects of rapamycin and bortezomib on cell proliferation and apoptosis in vivo were test by PCNA and TUNEL staining. Results Bortezomib synergized with rapamycin to reduce cell growth, induce apoptosis, and inhibit cell mobility in vitro. Further mechanistic studies showed that bortezomib inhibited rapamycin-induced phosphorylated Akt, which in turn enhanced apoptosis of HCC cell lines. The alteration of the mRNA expression of cell cycle inhibitors p53, p27, p21 and apoptosis associated genes Bcl-2, Bax were also involved in the synergistic antitumor effects of rapamycin and bortezomib. P53 inhibitor PFT-α significantly attenuate the effect of rapamycin and bortezomib on cell apoptosis, which indicated that the pro-apoptotic effect of rapamycin and bortezomib may be p53-dependent. Treatment of HCCLM3-R bearing nude mice with rapamycin and bortezomib significantly enhanced tumor growth

  15. The human LIS1 is downregulated in hepatocellular carcinoma and plays a tumor suppressor function

    International Nuclear Information System (INIS)

    Xing, Zhen; Tang, Xin; Gao, Yuan; Da, Liang; Song, Hai; Wang, Suiquan; Tiollais, Pierre; Li, Tsaiping; Zhao, Mujun

    2011-01-01

    Highlights: → LIS1 mRNA and protein levels are decreased in 70% HCC tissues. → Downregulation of LIS1 expression induces oncogenic transformation of QSG7701 and NIH3T3 cells in vitro and in vivo. → LIS1 downregulation leads to mitotic errors including spindle and chromosome defects. → Ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. → Our results suggest that LIS1 plays a potential tumor suppressor role in the development and progression of HCC. -- Abstract: The human lissencephaly-1 gene (LIS1) is a disease gene responsible for Miller-Dieker lissencephaly syndrome (MDL). LIS1 gene is located in the region of chromosome 17p13.3 that is frequency deleted in MDL patients and in human liver cancer cells. However, the expression and significance of LIS1 in liver cancer remain unknown. Here, we investigated the expression of LIS1 in hepatocellular carcinoma (HCC) tissues by real-time PCR, Western blot, and immunohistochemistry. The results indicated that the mRNA and protein levels of LIS1 were downregulated in about 70% of HCC tissues, and this downregulation was significantly associated with tumor progression. Functional studies showed that the reduction of LIS1 expression in the normal human liver cell line QSG7701 or the mouse fibroblast cell line NIH3T3 by shRNA resulted in colony formation in soft agar and xenograft tumor formation in nude mice, demonstrating that a decrease in the LIS1 level can promote the oncogenic transformation of cells. We also observed that the phenotypes of LIS1-knockdown cells displayed various defective mitotic structures, suggesting that the mechanism by which reduced LIS1 levels results in tumorigenesis is associated with its role in mitosis. Furthermore, we demonstrated that ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. Our results suggest that LIS1 plays a potential tumor suppressor role in the development and

  16. The human LIS1 is downregulated in hepatocellular carcinoma and plays a tumor suppressor function

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    Xing, Zhen; Tang, Xin; Gao, Yuan; Da, Liang; Song, Hai; Wang, Suiquan [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Tiollais, Pierre [Unite' d' Organisation Nucleaire et Oncogenese, INSERM U.579, Institut Pasteur, Paris (France); Li, Tsaiping [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Zhao, Mujun, E-mail: mjzhao@sibs.ac.cn [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China)

    2011-06-03

    Highlights: {yields} LIS1 mRNA and protein levels are decreased in 70% HCC tissues. {yields} Downregulation of LIS1 expression induces oncogenic transformation of QSG7701 and NIH3T3 cells in vitro and in vivo. {yields} LIS1 downregulation leads to mitotic errors including spindle and chromosome defects. {yields} Ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. {yields} Our results suggest that LIS1 plays a potential tumor suppressor role in the development and progression of HCC. -- Abstract: The human lissencephaly-1 gene (LIS1) is a disease gene responsible for Miller-Dieker lissencephaly syndrome (MDL). LIS1 gene is located in the region of chromosome 17p13.3 that is frequency deleted in MDL patients and in human liver cancer cells. However, the expression and significance of LIS1 in liver cancer remain unknown. Here, we investigated the expression of LIS1 in hepatocellular carcinoma (HCC) tissues by real-time PCR, Western blot, and immunohistochemistry. The results indicated that the mRNA and protein levels of LIS1 were downregulated in about 70% of HCC tissues, and this downregulation was significantly associated with tumor progression. Functional studies showed that the reduction of LIS1 expression in the normal human liver cell line QSG7701 or the mouse fibroblast cell line NIH3T3 by shRNA resulted in colony formation in soft agar and xenograft tumor formation in nude mice, demonstrating that a decrease in the LIS1 level can promote the oncogenic transformation of cells. We also observed that the phenotypes of LIS1-knockdown cells displayed various defective mitotic structures, suggesting that the mechanism by which reduced LIS1 levels results in tumorigenesis is associated with its role in mitosis. Furthermore, we demonstrated that ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. Our results suggest that LIS1 plays a potential tumor suppressor role in the

  17. Occult left atrial ball-like thrombus in a patient referred for surgical removal of suspected cerebellum tumor

    International Nuclear Information System (INIS)

    Możeńska, Olga; Kalińska, Irena; Brodowski, Karol; Walecki, Jerzy; Kosior, Dariusz A.

    2014-01-01

    Atrial fibrillation and related cardio-embolic cerebrovascular accidents are two well-defined major healthcare problems worldwide. It has been approximated that 2.2 million people in America and 4.5 million in European Union have paroxysmal or persistent atrial fibrillation. And atrial fibrillation itself is an independent long-term risk factor of stroke. We present a case of patient referred to our center for surgical removal of suspected cerebellum tumor, a case that had a rather unexpected ending. A 58-year-old male patient with a history of atrial fibrillation, congestive heart failure (NYHA II/III), stable coronary artery disease, diabetes type 2 and hyperlipidemia presented with vertigo, headaches, mainly during physical activity and increased tiredness. Performed computer tomography revealed two lesions in the cerebellum and in the left lateral chamber. The diagnosis of a proliferative disease of the cerebellum was established and patient was referred to the Neurosurgical Department. Fortunately, before the operation the echocardiography was performed, which revealed two lesions in left atrium. The decision of the Heart Team was to refer the patient for an open-heart surgery, in which two thrombi were removed. Neurosurgeons decided to withdraw from further surgery and proceed with head MRI and conservative treatment, deciding that the lesion in the cerebellum was most likely an ischemic area. Looking at the brain lesion should always be done from the whole patient’s perspective. And using mutlimodality imaging may lead to appropriate diagnosis, correct course of therapeutic action and unexpected ending of a rather non-extraordinary case

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

    Science.gov (United States)

    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

  19. Outcomes of Locoregional Tumor Therapy for Patients with Hepatocellular Carcinoma and Transjugular Intrahepatic Portosystemic Shunts

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    Padia, Siddharth A., E-mail: spadia@uw.edu; Chewning, Rush H., E-mail: rchewnin@uw.edu; Kogut, Matthew J., E-mail: kogutm@uw.edu; Ingraham, Christopher R., E-mail: cringa@uw.edu; Johnson, Guy E., E-mail: gej@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Bhattacharya, Renuka, E-mail: renuka@uw.edu [University of Washington Medical Center, Division of Gastroenterology and Hepatology, Department of Medicine (United States); Kwan, Sharon W., E-mail: shakwan@uw.edu; Monsky, Wayne L., E-mail: wmonsky@uw.edu; Vaidya, Sandeep, E-mail: svaidya@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Hippe, Daniel S., E-mail: dhippe@uw.edu [University of Washington Medical Center, Department of Radiology (United States); Valji, Karim, E-mail: kvalji@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States)

    2015-08-15

    PurposeLocoregional therapy for hepatocellular carcinoma (HCC) can be challenging in patients with a transjugular intrahepatic portosystemic shunt (TIPS). This study compares safety and imaging response of ablation, chemoembolization, radioembolization, and supportive care in patients with both TIPS and HCC.MethodsThis retrospective study included 48 patients who had both a TIPS and a diagnosis of HCC. Twenty-nine of 48 (60 %) underwent treatment for HCC, and 19/48 (40 %) received best supportive care (i.e., symptomatic management only). While etiology of cirrhosis and indication for TIPS were similar between the two groups, treated patients had better baseline liver function (34 vs. 67 % Child-Pugh class C). Tumor characteristics were similar between the two groups. A total of 39 ablations, 17 chemoembolizations, and 10 yttrium-90 radioembolizations were performed on 29 patients.ResultsAblation procedures resulted in low rates of hepatotoxicity and clinical toxicity. Post-embolization/ablation syndrome occurred more frequently in patients undergoing chemoembolization than ablation (47 vs. 15 %). Significant hepatic dysfunction occurred more frequently in the chemoembolization group than the ablation group. Follow-up imaging response showed objective response in 100 % of ablation procedures, 67 % of radioembolization procedures, and 50 % of chemoembolization procedures (p = 0.001). When censored for OLT, patients undergoing treatment survived longer than patients receiving supportive care (2273 v. 439 days, p = 0.001).ConclusionsAblation appears to be safe and efficacious for HCC in patients with TIPS. Catheter-based approaches are associated with potential increased toxicity in this patient population. Chemoembolization appears to be associated with increased toxicity compared to radioembolization.

  20. Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient.

    Directory of Open Access Journals (Sweden)

    Ling Ye

    Full Text Available BACKGROUND: Sorafenib, the drug used as first line treatment for hepatocellular carcinoma (HCC, is metabolized by cytochrome P450 (CYP 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT 1A9-mediated glucuronidation. Liver diseases are associated with reduced CYP and UGT activities, which can considerably affect drug metabolism, leading to drug toxicity. Thus, understanding the metabolism of therapeutic compounds in patients with liver diseases is necessary. However, the metabolism characteristic of sorafenib has not been systematically determined in HCC patients. METHODS: Sorafenib metabolism was tested in the pooled and individual tumor hepatic microsomes (THLMs and adjacent normal hepatic microsomes (NHLMs of HCC patients (n = 18. Commercial hepatic microsomes (CHLMs were used as a control. In addition, CYP3A4 and UGT1A9 protein expression in different tissues were measured by Western blotting. RESULTS: The mean rates of oxidation and glucuronidation of sorafenib were significantly decreased in the pooled THLMs compared with those in NHLMs and CHLMs. The maximal velocity (Vmax of sorafenib oxidation and glucuronidation were approximately 25-fold and 2-fold decreased in the pooled THLMs, respectively, with unchanged Km values. The oxidation of sorafenib in individual THLMs sample was significantly decreased (ranging from 7 to 67-fold than that in corresponding NHLMs sample. The reduction of glucuronidation in THLMs was observed in 15 out of 18 patients' samples. Additionally, the level of CYP3A4 and UGT1A9 expression were both notably decreased in the pooled THLMs. CONCLUSIONS: Sorafenib metabolism was remarkably decreased in THLMs. This result was associated with the down regulation of the protein expression of CYP3A4 and UGT1A9.

  1. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival.

    Science.gov (United States)

    Salem, Riad; Lewandowski, Robert J; Atassi, Bassel; Gordon, Stuart C; Gates, Vanessa L; Barakat, Omar; Sergie, Ziad; Wong, Ching-Yee O; Thurston, Kenneth G

    2005-12-01

    To present safety and efficacy results obtained in treatment of a cohort of patients with unresectable hepatocellular carcinoma (HCC) with use of 90Y microspheres (TheraSphere). Forty-three consecutive patients with HCC were treated with 90Y microspheres over a 4-year period. Patients were treated by liver segment or lobe on one or more occasions based on tumor distribution, liver function, and vascular flow dynamics. Patients were followed for adverse events, objective tumor response, and survival. Patients were stratified into three risk groups according to method of treatment and risk stratification (group 0, segmental; group 1, lobar low-risk; group 2, lobar high-risk) and Okuda and Child-Pugh scoring systems. Based on follow-up data from 43 treated patients, 20 patients (47%) had an objective tumor response based on percent reduction in tumor size and 34 patients (79%) had a tumor response when percent reduction and/or tumor necrosis were used as a composite measure of tumor response. There was no statistical difference among the three risk groups with respect to tumor response. Survival times from date of diagnosis were different among the risk groups (P TheraSpheres) provides a safe and effective method of treatment for a broad spectrum of patients presenting with unresectable HCC. Further investigation is warranted.

  2. Asparagus polysaccharide and gum with hepatic artery embolization induces tumor growth and inhibits angiogenesis in an orthotopic hepatocellular carcinoma model.

    Science.gov (United States)

    Weng, Ling-Ling; Xiang, Jian-Feng; Lin, Jin-Bo; Yi, Shang-Hui; Yang, Li-Tao; Li, Yi-Sheng; Zeng, Hao-Tao; Lin, Sheng-Ming; Xin, Dong-Wei; Zhao, Hai-Liang; Qiu, Shu-Qi; Chen, Tao; Zhang, Min-Guang

    2014-01-01

    Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy.

  3. Isomalto oligosaccharide sulfate inhibits tumor growth and metastasis of hepatocellular carcinoma in nude mice

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    Tang Zhao-You

    2011-04-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC usually has a dismal prognosis because of its limited response to current pharmacotherapy and high metastatic rate. Sulfated oligosaccharide has been confirmed as having potent antitumor activities against solid tumors. Here, we explored the preclinical effects and molecular mechanisms of isomalto oligosaccharide sulfate (IMOS, another novel sulfated oligosaccharide, in HCC cell lines and a xenograft model. Methods The effects of IMOS on HCC proliferation, apoptosis, adhesion, migration, and invasiveness in vitro were assessed by cell counting, flow cytometry, adhesion, wound healing, and transwell assays, respectively. The roles of IMOS on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. Total and phosphorylated protein levels of AKT, ERK, and JNK as well as total levels of c-MET were detected by Western blotting. IMOS-regulated genes were screened by quantitative reverse-transcription PCR (qRT-PCR array in HCCLM3-red fluorescent protein (RFP xenograft tissues and then confirmed by qRT-PCR in HepG2 and Hep3B cells. Results IMOS markedly inhibited cell proliferation and induced cell apoptosis of HCCLM3, HepG2, and Bel-7402 cells and also significantly suppressed cell adhesion, migration, and invasion of HCCLM3 in vitro. At doses of 60 and 90 mg/kg/d, IMOS displayed robust inhibitory effects on HCC growth and metastasis without obvious side effects in vivo. The levels of pERK, tERK, and pJNK as well as c-MET were significantly down-regulated after treatment with 16 mg/mL IMOS. No obvious changes were found in the levels of pAkt, tAkt, and tJNK. Ten differentially expressed genes were screened from HCCLM3-RFP xenograft tissues after treatment with IMOS at a dose of 90 mg/kg/d. Similar gene expression profiles were confirmed in HepG2 and Hep3B cells after treatment with 16 mg/mL IMOS. Conclusions IMOS is a potential anti-HCC candidate through

  4. Hepatocellular carcinoma with cavernous transformation of the protal vein

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Heung Suk; Lee, Seung Ro; Hahm, Chang Kok [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    1985-10-15

    Twenty cases of hepatocellular carcinoma were examined by selective celiac and superior mesenteric arteriography. Obstruction of the main portal vein due to tumor thrombus was revealed in 7 cases and 3 of these cases had cavernous transformation of the portal vein (CTPV). The authors intended in this study to evaluate CTPV group and non-CTPV group clinically and radiologically. The results obtained are as follows: 1. The duration of illness was shorter in CTPV group than non- CTPV group. 2. There was no significant difference in tumor size between two groups ,and main portion of tumor was located in the right lobe in both groups. 3. Arterio portal shunt was present in 2 of 4 cases in non-CTPV group, but was no present at all in CRPV groups. 5. There wa no significant difference in blood chemistry between two groups. 6. CTPV may play an important role maintain the hepatic blood flow.

  5. Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Uk; Park, Joong-Won; Kim, Tae Hyun; Kim, Yeon-Joo; Woo, Sang Myung; Koh, Young-Hwan; Lee, Woo Jin; Park, Sang-Jae; Kim, Dae Yong; Kim, Chang-Min [National Cancer Center, Center for Liver Cancer, Research Institute and Hospital, Goyang-si, Gyeonggi-do (Korea, Republic of)

    2014-09-15

    To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50-66 GyE) in 20-22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor. Overall, treatment was well tolerated, with no toxicity of grade ≥ 3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0 %) patients, partial response in 15 (55.6 %), stable disease in 10 (37 %), and progressive disease in 2 (7.4 %) patients, with an objective response rate of 55.6 %. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6 % vs. 51.3 %), relapse-free survival (RFS; 20 % vs. 0 %) and OS (80 % vs. 25 %) rates than nonresponders (p < 0.05 each). Multivariate analysis showed that PVTT response and mUICC stage were independent prognostic factors for OS. Our data suggest that PBT could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is feasible and safe for these patients. (orig.) [German] In der vorliegenden Arbeit wurde versucht, die klinische Wirksamkeit und Sicherheit der Protonenstrahltherapie (PBT) fuer Patienten mit fortgeschrittenem Leberzellkarzinom (HCC) in Verbindung mit Portadertumorthrombosen (PVTT) zu bewerten. Ausgefuehrt wurde die PBT fuer 27 HCC-Patienten mit PVTT, einschliesslich 22 Patienten im mUICC-Stadium (''International Union Against Cancer'') IVA sowie 5 Patienten mit Primaertumor im Stadium IVB und 16 Patienten mit PVTT im primaeren Stadium nach der geaenderten UICC-Klassifikation. Eine

  6. Genetic alterations of hepatocellular carcinoma by random amplified polymorphic DNA analysis and cloning sequencing of tumor differential DNA fragment

    Science.gov (United States)

    Xian, Zhi-Hong; Cong, Wen-Ming; Zhang, Shu-Hui; Wu, Meng-Chao

    2005-01-01

    AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated, purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data. RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcin-ogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis. PMID:15996039

  7. Regorafenib inhibits tumor progression through suppression of ERK/NF-κB activation in hepatocellular carcinoma bearing mice.

    Science.gov (United States)

    Weng, Mao-Chi; Wang, Mei-Hui; Tsai, Jai-Jen; Kuo, Yu-Cheng; Liu, Yu-Chang; Hsu, Fei-Ting; Wang, Hsin-Ell

    2018-03-13

    Regorafenib has been demonstrated in our previous study to trigger apoptosis through suppression of extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) activation in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro However, the effect of regorafenib on NF-κB-modulated tumor progression in HCC in vivo is ambiguous. The aim of the present study is to investigate the effect of regorafenib on NF-κB-modulated tumor progression in HCC bearing mouse model. pGL4.50 luciferase reporter vector transfected SK-Hep1 (SK-Hep1/ luc2 ) and Hep3B 2.1-7 tumor bearing mice were established and used for this study. Mice were treated with vehicle or regorafenib (20 mg/kg/day by gavage) for 14 days. Effects of regorafenib on tumor growth and protein expression together with toxicity of regorafenib were evaluated with digital caliper and bioluminescence imaging (BLI), ex vivo Western blotting immunohistochemistry (IHC) staining, and measurement of body weight and pathological examination of liver tissue, respectively, in SK-Hep1/ luc2 and Hep3B 2.1-7 tumor bearing mice. The results indicated regorafenib significantly reduced tumor growth and expression of phosphorylated ERK, NF-κB p65 (Ser536), phosphorylated AKT and tumor progression-associated proteins. In addition, we found regorafenib induced both extrinsic and intrinsic apoptotic pathways. Body weight and liver morphology were not affected by regorafenib treatment. Our findings present the mechanism of tumor progression inhibition by regorafenib is linked to suppression of ERK/NF-κB signaling in SK-Hep1/ luc2 and Hep3B 2.1-7 tumor-bearing mice. ©2018 The Author(s).

  8. Inhibition of Tumor Growth of Human Hepatocellular Carcinoma HepG2 Cells in a Nude Mouse Xenograft Model by the Total Flavonoids from Arachniodes exilis

    Directory of Open Access Journals (Sweden)

    Huimin Li

    2017-01-01

    Full Text Available A tumor growth model of human hepatocellular carcinoma HepG2 cells in nude mice was employed to investigate the antitumor activity of the total flavonoids extracted from Arachniodes exilis (TFAE in vivo. Several biochemical assays including hematoxylin-eosin (HE staining, immunohistochemistry, and Western blot were performed to elucidate the mechanism of action of total flavonoids extracted from Arachniodes exilis (TFAE. The results showed that TFAE effectively inhibited the tumor growth of hepatocellular carcinoma in nude mice and had no significant effect on body weight, blood system, and functions of liver and kidney. Expression levels of proapoptotic proteins Bax and cleaved caspase-3 remarkably increased while the expressions of Bcl-2, HIF-1α, and VEGF were suppressed by TFAE. These results suggested that the antitumor potential of TFEA was implied by the apoptosis of tumor cells and the inhibition of angiogenesis in tumor tissue.

  9. Tumor Molecular Profiling for an Individualized Approach to the Treatment of Hepatocellular Carcinoma: A Patient Case Study

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    Kristine Posadas

    2018-04-01

    Full Text Available Hepatocellular carcinoma (HCC is increasing in incidence, and the associated mortality rate remains among the highest. For advanced HCC, sorafenib has been shown to slightly prolong survival, and regorafenib and nivolumab, both recently approved by the United States Food and Drug Administration (FDA, may produce clinical benefits to a limited extent. Systemic chemotherapy has been shown to produce a modest response, but there is no clinically valid biomarker that can be used to predict which patients may benefit. In this case study, we present two patients with metastatic HCC, they received systemic treatment using capecitabine, oxaliplatin, and either bevacizumab or sorafenib. The tumor response to treatment was determined by the progression-free survival (PFS. Molecular profiling of the tumors showed differential expression of biochemical markers and different mutational status of the TP53 and β-catenin (CTNNB1 genes. We hypothesize that the PFS correlates with the tumor molecular profiles, which may be predictive of the therapeutic response to systemic chemotherapy. Further investigation is indicated to correlate tumor biomarkers and treatment responses, with the objective of personalizing the therapies for patients with advanced HCC.

  10. Homeobox B9 is overexpressed in hepatocellular carcinomas and promotes tumor cell proliferation both in vitro and in vivo

    International Nuclear Information System (INIS)

    Li, Fangyi; Dong, Lei; Xing, Rong; Wang, Li; Luan, Fengming; Yao, Chenhui; Ji, Xuening; Bai, Lizhi

    2014-01-01

    Highlights: • HOXB9 is overexpressed in human HCC samples. • HOXB9 over expression had shorter survival time than down expression. • HOXB9 stimulated the proliferation of HCC cells. • Activation of TGF-β1 contributes to HOXB9-induced proliferation in HCC cells. - Abstract: HomeoboxB9 (HOXB9), a nontransforming transcription factor that is overexpressed in multiple tumor types, alters tumor cell fate and promotes tumor progression. However, the role of HOXB9 in hepatocellular carcinoma (HCC) development has not been well studied. In this paper, we found that HOXB9 is overexpressed in human HCC samples. We investigated HOXB9 expression and its prognostic value for HCC. HCC surgical tissue samples were taken from 89 HCC patients. HOXB9 overexpression was observed in 65.2% of the cases, and the survival analysis showed that the HOXB9 overexpression group had significantly shorter overall survival time than the HOXB9 downexpression group. The ectopic expression of HOXB9 stimulated the proliferation of HCC cells; whereas the knockdown of HOXB9 produced an opposite effect. HOXB9 also modulated the tumorigenicity of HCC cells in vivo. Moreover, we found that the activation of TGF-β1 contributes to HOXB9-induced proliferation activities. The results provide the first evidence that HOXB9 is a critical regulator of tumor growth factor in HCC

  11. Homeobox B9 is overexpressed in hepatocellular carcinomas and promotes tumor cell proliferation both in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fangyi [Department of General Surgery, Dalian Municipal Friendship Hospital, No. 8 Sanba Square, Zhongshan District, Dalian 116001 (China); Dong, Lei, E-mail: dlleidong@126.com [Department of Laparoscopic Surgery, First Affiliated Hospital of Dalian Medical University, No. 193 Lianhe Street, Shahekou District, Dalian 116001 (China); Xing, Rong [Department of Pathology and Pathophysiology, Dalian Medical University, No. 9 Lvshunnan Road, Lvshunkou District, Dalian 116044 (China); Wang, Li; Luan, Fengming; Yao, Chenhui [Department of General Surgery, Dalian Municipal Friendship Hospital, No. 8 Sanba Square, Zhongshan District, Dalian 116001 (China); Ji, Xuening [Department of Oncology, Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian 116001 (China); Bai, Lizhi, E-mail: dllizhibai@126.com [Department of Emergency, Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian 116001 (China)

    2014-02-07

    Highlights: • HOXB9 is overexpressed in human HCC samples. • HOXB9 over expression had shorter survival time than down expression. • HOXB9 stimulated the proliferation of HCC cells. • Activation of TGF-β1 contributes to HOXB9-induced proliferation in HCC cells. - Abstract: HomeoboxB9 (HOXB9), a nontransforming transcription factor that is overexpressed in multiple tumor types, alters tumor cell fate and promotes tumor progression. However, the role of HOXB9 in hepatocellular carcinoma (HCC) development has not been well studied. In this paper, we found that HOXB9 is overexpressed in human HCC samples. We investigated HOXB9 expression and its prognostic value for HCC. HCC surgical tissue samples were taken from 89 HCC patients. HOXB9 overexpression was observed in 65.2% of the cases, and the survival analysis showed that the HOXB9 overexpression group had significantly shorter overall survival time than the HOXB9 downexpression group. The ectopic expression of HOXB9 stimulated the proliferation of HCC cells; whereas the knockdown of HOXB9 produced an opposite effect. HOXB9 also modulated the tumorigenicity of HCC cells in vivo. Moreover, we found that the activation of TGF-β1 contributes to HOXB9-induced proliferation activities. The results provide the first evidence that HOXB9 is a critical regulator of tumor growth factor in HCC.

  12. Differential metabonomic profiles of primary hepatocellular carcinoma tumors from alcoholic liver disease, HBV-infected, and HCV-infected cirrhotic patients

    OpenAIRE

    Cao, Ding; Cai, Can; Ye, Mingxin; Gong, Junhua; Wang, Menghao; Li, Jinzheng; Gong, Jianping

    2017-01-01

    Our objective was to comparatively profile the metabolite composition of primary hepatocellular carcinoma (HCC) tumors from alcoholic liver disease (ALD), hepatitis B virus (HBV)-infected, and hepatitis C virus (HCV)-infected cirrhotic patients. Primary HCC tumors were collected from ALD, HBV-infected, and HCV-infected cirrhotic patients (n=20 each). High-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and metabonomic data analysis were performed to compare HCC ...

  13. Clinical trial of combination therapy using systemic interleukin-2 infusion and low-dose tumor irradiation for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Tsuchida, Tetsuo; Hiragushi, Junji; Asano, Yoshihide

    1995-01-01

    Although recent progress in surgical techniques and interventional radiology enables patients with hepatocellular carcinoma (HCC) to survive longer, there are still many who cannot receive them due to disease progression. We are currently investigating the therapeutic efficacy of the combination of systemic recombinant interleukin-2 (IL-2) administration and local tumor irradiation for HCC patients in the advanced stage. First, the results of the basic experiment to analyze the optimal dose and timing of IL-2 infusion were demonstrated. Intensive administration of high-dose IL-2 caused acute death, whereas intermittent low-dose IL-2 administration resulted in complete tumor regression followed by the acquisition of tumor-specific immunity. Our data suggested that the tumor-bearing state increased the responsiveness to IL-2 treatment, and that an excessively high-dose regimen is not prerequisite for the optimal IL-2 treatment. With regard to the effectiveness of radiotherapy for HCC, human hepatoma cells exhibited apoptotic death when hepatoma cells were cocultured with LAK cells, or were irradiated in vitro with relatively low-dose irradiation. These results suggested the possible synergistic effect of killer cells and low-dose irradiation. Finally, we presented six eligible cases of advanced HCC treated by combination therapy of IL-2 infusion and local low-dose tumor irradiation. Direct anti-tumor effects were one CR, one MR, two NC, and two PD. One CR case and a NC case have survived now for longer than 40 months. In all cases, NK cell activity increased prominently, and side effects wee mild flu-like symptoms except macroscopic hematuria and moderate VLS-like symptoms in two cases in which therapy was continued for longer than 2 years. Hepatic reserve function like prothrombin time or hepaplastic time improved. The apparent clinical effectiveness of the combination therapy presented here might give promising hints for a new therapeutic strategy for HCC. (author)

  14. Liver stem/progenitor cells in the canals of Hering: cellular origin of hepatocellular carcinoma with bile duct tumor thrombi?

    Science.gov (United States)

    Peng, Ningfu; Li, Lequn; Cai, Xiang; Tan, Shaozao; Wu, Ting

    2010-12-01

    It is generally believed that the invasion of hepatocellular carcinoma (HCC) into the biliary tree ultimately leads to the formation of bile duct tumor thrombi (BDTT). However, recent studies revealed that primary tumor might be small, even undetectable, and there was no histopathologic evidence of direct tumor invasion into bile duct wall in some patients. During the last decade, efforts on stem cell biology may shed light on the pathogenesis of BDTT. Presently, accumulating evidence supports the following notions: (1) the canals of Hering (CoH) are the most likely origin of liver stem/progenitor cells (LSPCs) in adult livers; (2) similar signalling pathways may regulate self-renewal in LSPCs and liver cancer cells, and a substantial proportion of liver tumors may often originate from the transformation of LSPCs; and (3) liver cancer contains rare cells with stem cell-like properties, which could derive from malignant transformation of LSPCs. Herein, we propose that HCC with BDTT, especially with small or undetectable primary lesion and/or no histopathologic evidence for bile duct invasion, might arise from LSPCs residing in the CoH and, possibly, some primary lesions are formed firstly within the intrahepatic biliary tree. When "tumor thrombi" extends mainly along bile duct, there might be "BDTT" alone; when it invades into surrounding parenchyma, there might often be small "primary tumor" with "BDTT". If this holds true, the putative type may be a particular subset of HCC, and most importantly it would facilitate our understanding of stem-cell origin of HCC.

  15. Bloom syndrome in sibs: first reports of hepatocellular carcinoma and Wilms tumor with documented anaplasia and nephrogenic rests.

    Science.gov (United States)

    Jain, D; Hui, P; McNamara, J; Schwartz, D; German, J; Reyes-Múgica, M

    2001-01-01

    The triad of small body size, immunodeficiency, and sun-sensitive facial erythema characterizes the phenotype Bloom syndrome (BS), a rare autosomal recessive disorder with a striking predisposition to multiple types of cancers that arise earlier than expected in the general population. Here we report two sibs with BS. The older, a 15-year-old-girl, developed a hepatocellular carcinoma, a neoplasm not yet reported in association with BS. Her younger brother developed an anaplastic Wilms tumor (WT) associated with nephrogenic rests at the age of 31/2 years, and this was followed by a myelodysplastic syndrome. Complex cytogenetic abnormalities were identified in all three neoplasms. These examples expand the spectrum of malignancies occurring in BS to include liver cell neoplasms, and confirm the association of nephrogenic rests with WT, even in the setting of BS.

  16. Biliary obstruction caused by intra-biliary tumor growth from recurred hepatocellular carcinoma after radiofrequency ablation: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Ji Hyun; Kim, Jae Won [Dept. of Radiology, Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2014-04-15

    A 59-year-old man with a known central hepatocellular carcinoma (HCC) underwent a trans-arterial-chemo-embolization (TACE) and a post-TACE percutaneous radiofrequency ablation (PRFA). Two months after the PRFA, the patient presented jaundice and an abdominal computed tomography was obtained. An arterial enhancing mass adjacent to the ablated necrotic lesion with a continuously coexisting mass inside the right hepatic duct, suggestive of a HCC recurrence with a direct extension to the biliary tract was found. Finally a biliary tumor obstruction has been developed and a percutaneous transhepatic biliary drainage was performed. This case of biliary obstruction caused by directly invaded recurred HCC after PRFA will be reported because of its rare occurrence.

  17. Overexpression of cathepsin Z contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Jian Wang

    Full Text Available The aim of this study was to characterize the oncogenic function and mechanism of Cathepsin Z (CTSZ at 20q13.3, a frequently amplified region in hepatocellular carcinoma (HCC. Real-time PCR were used to compare CTSZ expression between paired HCC tumor and non-tumor specimens. CTSZ gene was stably transfected into HCC line QGY-7703 cells and its role in tumorigenicity and cell motility was characterized by soft agar, wound-healing, transwell invasion and cell adhesion assay, and tumor xenograft mouse model. Western blot analysis was used to study expression of proteins associated with epithelial-mesenchymal transition (EMT.Upregulation of CTSZ was detected in 59/137 (43% of primary HCCs, which was significantly associated with advanced clinical stage (P = 0.000. Functional study found that CTSZ could increase colony formation in soft agar and promote cell motility. Further study found that the metastatic effect of CTSZ was associated with its role in inducing epithelial-mesenchymal transition (EMT by upregulating mesenchymal markers (fibronectin and vimentin and downregulating epithelial markers (E-cadherin and α-catenin. In addition, CTSZ could also upregulate proteins associated with extracellular matrix remodeling such as MMP2, MMP3 and MMP9. Taken together, our data suggested that CTSZ was a candidate oncogene within the 20q13 amplicon and it played an important role in HCC metastasis.

  18. Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis.

    Directory of Open Access Journals (Sweden)

    Mian Xi

    Full Text Available BACKGROUND: To report the feasibility, efficacy, and toxicity of stereotactic body radiotherapy (SBRT for the treatment of portal vein tumor thrombosis (PVTT and/or inferior vena cava tumor thrombosis (IVCTT in patients with advanced hepatocellular carcinoma (HCC. MATERIALS AND METHODS: Forty-one patients treated with SBRT using volumetric modulated arc therapy (VMAT for HCC with PVTT/IVCTT between July 2010 and May 2012 were analyzed. Of these, 33 had PVTT and 8 had IVCTT. SBRT was designed to target the tumor thrombosis and deliver a median total dose of 36 Gy (range, 30-48 Gy in six fractions during two weeks. RESULTS: The median follow-up was 10.0 months. At the time of analysis, 15 (36.6% achieved complete response, 16 (39.0% achieved partial response, 7 (17.1% patients were stable, and three (7.3% patients showed progressive disease. No treatment-related Grade 4/5 toxicity was seen within three months after SBRT. One patient had Grade 3 elevation of bilirubin. The one-year overall survival rate was 50.3%, with a median survival of 13.0 months. The only independent predictive factor associated with better survival was response to radiotherapy. CONCLUSIONS: VMAT-based SBRT is a safe and effective treatment option for PVTT/IVCTT in HCC. Prospective randomized controlled trials are warranted to validate the role of SBRT in these patients.

  19. Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment.

    Science.gov (United States)

    Reiner, Caecilia S; Gordic, Sonja; Puippe, Gilbert; Morsbach, Fabian; Wurnig, Moritz; Schaefer, Niklaus; Veit-Haibach, Patrick; Pfammatter, Thomas; Alkadhi, Hatem

    2016-03-01

    To evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE). Sixteen patients (15 male; mean age 65 years; age range 47-80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters' ability to discriminate responders from non-responders. According to mRECIST, 8 patients (50%) were responders and 8 (50%) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min(-1) 100 mL(-1)); p 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min(-1) 100 mL(-1), therapy response could be predicted with a sensitivity of 88% (7/8) and specificity of 75% (6/8). Voxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE.

  20. Optimized performance of flight Plan during chemoembolization for hepatocellular carcinoma: Importance of the proportion of segmented tumor area

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Seung Moon; Kim, Yong Pyo; Yum, Tae Jun; Eun, Na Lae; Lee, Da Hye; Lee, Kwang Hun [Dept. of Radiology, Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-09-15

    To evaluate retrospectively the clinical effectiveness of Flight Plan for Liver (FPFL), an automated tumor-feeding artery detection software in cone-beam CT angiography (CBCTA), in identifying tumor-feeding arteries for the treatment of hepatocellular carcinoma (HCC) using three different segmentation sensitivities. The study included 50 patients with 80 HCC nodules who received transarterial chemoembolization. Standard digital subtracted angiography (DSA) and CBCTA were systematically performed and analyzed. Three settings of the FPFL software for vascular tree segmentation were tested for each tumor: the default, Group D; adjusting the proportion of segmented tumor area between 30 to 50%, Group L; and between 50 to 80%, Group H. In total, 109 feeder vessels supplying 80 HCC nodules were identified. The negative predictive value of DSA, FPFL in groups D, L, and H was 56.8%, 87.7%, 94.2%, 98.5%, respectively. The accuracy of DSA, FPFL in groups D, L, and H was 62.6%, 86.8%, 93.4%, 95.6%, respectively. The sensitivity, negative predictive value (NPV), and accuracy of FPFL were higher in Group H than in Group D (p = 0.041, 0.034, 0.005). All three segmentation sensitivity groups showed higher specificity, positive predictive value, NPV, and accuracy of FPFL, as compared to DSA. FlightPlan for Liver is a valuable tool for increasing detection of HCC tumor feeding vessels, as compared to standard DSA analysis, particularly in small HCC. Manual adjustment of segmentation sensitivity improves the accuracy of FPFL.

  1. Optimized Performance of FlightPlan during Chemoembolization for Hepatocellular Carcinoma: Importance of the Proportion of Segmented Tumor Area

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Seung-Moon; Kim, Yong Pyo; Yum, Tae Jun; Eun, Na Lae; Lee, Dahye; Lee, Kwang-Hun [Department of Radiology, Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273 (Korea, Republic of)

    2016-11-01

    To evaluate retrospectively the clinical effectiveness of FlightPlan for Liver (FPFL), an automated tumor-feeding artery detection software in cone-beam CT angiography (CBCTA), in identifying tumor-feeding arteries for the treatment of hepatocellular carcinoma (HCC) using three different segmentation sensitivities. The study included 50 patients with 80 HCC nodules who received transarterial chemoembolization. Standard digital subtracted angiography (DSA) and CBCTA were systematically performed and analyzed. Three settings of the FPFL software for vascular tree segmentation were tested for each tumor: the default, Group D; adjusting the proportion of segmented tumor area between 30 to 50%, Group L; and between 50 to 80%, Group H. In total, 109 feeder vessels supplying 80 HCC nodules were identified. The negative predictive value of DSA, FPFL in groups D, L, and H was 56.8%, 87.7%, 94.2%, 98.5%, respectively. The accuracy of DSA, FPFL in groups D, L, and H was 62.6%, 86.8%, 93.4%, 95.6%, respectively. The sensitivity, negative predictive value (NPV), and accuracy of FPFL were higher in Group H than in Group D (p = 0.041, 0.034, 0.005). All three segmentation sensitivity groups showed higher specificity, positive predictive value, NPV, and accuracy of FPFL, as compared to DSA. FlightPlan for Liver is a valuable tool for increasing detection of HCC tumor feeding vessels, as compared to standard DSA analysis, particularly in small HCC. Manual adjustment of segmentation sensitivity improves the accuracy of FPFL.

  2. Mechanism of endothelial progenitor cell recruitment into neo-vessels in adjacent non-tumor tissues in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Yu, De-cai; Chen, Jun; Sun, Xi-tai; Zhuang, Lin-yuan; Jiang, Chun-ping; Ding, Yi-tao

    2010-01-01

    We investigated the distribution and clinical significance of mobilized endothelial progenitor cells (EPCs) in hepatocellular carcinoma (HCC). We found that many more EPCs were recruited to nonmalignant liver tissue (especially into adjacent non-tumor tissues (AT)) than to tumor vessels. These results suggest that the mechanism underlying the recruitment of EPCs into microvessels in AT merits further investigation Angiogenic factors were detected in three tissue microarrays comprising normal liver, paired tumor tissue (TT) and AT from 105 patients (who had undergone hepatectomy for HCC) using immunohistochemistry. Also, the number of EPCs (positive for Sca-1, Flk-1 and c-Kit) in the blood and liver of cirrhotic mice were determined by flow cytometry and immunohistochemistry. The distribution of these labeled EPCs in tumor and non-tumor tissues was then studied. The results from the tissue microarrays showed that the expression levels of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, and endostatin were significantly higher in AT than in either normal liver or TT (p < 0.05), but no significant difference was found in the expression levels of COX-2 and NOS-2 between AT and TT. The expression of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, endostatin, COX-2, and NOS-2 in normal liver tissue was weaker than that in AT or TT. In cirrhotic mice, the number of circulating endothelial progenitor cells gradually increased, before decreasing again. In this mouse model, increased numbers of EPCs were recruited and homed specifically to the cirrhotic liver. Both liver cirrhosis and HCC led to increased expression of pro-angiogenic factors, which resulted in the recruitment of EPCs into AT. Also, EPCs were mobilized, recruited and homed to cirrhotic liver. The unique pathology of HCC coupled with liver cirrhosis may, therefore, be associated with the distribution and function of EPCs

  3. CT of portal vein tumor thrombosis. Usefulness of dynamic CT

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    Takemoto, Kazumasa; Inoue, Yuichi; Tanaka, Masahiro; Nemoto, Yutaka; Nakamura, Kenji [Osaka City Univ. (Japan). Faculty of Medicine

    1983-08-01

    We evaluated CT findings of portal vein tumor thrombosis in 16 hepatomas by plain, contrast and dynamic CT. Plain and contrast CT findings were an enlargement of the portal vein (81%), intraluminal low density area (63%). Dynamic CT enhanced the diagnostic capability of the tumor thrombus as a relatively low density area because of the marked enhancement of the portal vein. In addition, dynamic CT newly demonstrated hyperdense peripheral ring (35%) and arterio portal shunt (35%). It is advisable to select the scan level to include the portal vein when dynamic CT is performed in the patient of hepatocellular carcinoma.

  4. Venom from Cuban Blue Scorpion has tumor activating effect in hepatocellular carcinoma.

    Science.gov (United States)

    Giovannini, Catia; Baglioni, Michele; Baron Toaldo, Marco; Cescon, Matteo; Bolondi, Luigi; Gramantieri, Laura

    2017-03-21

    Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.

  5. Renal angiomyolipoma with inferior vena caval thrombus in a 32-year-old male

    Directory of Open Access Journals (Sweden)

    Matthew W Christian

    2009-01-01

    Full Text Available Renal angiomyolipoma (AML rarely presents with evidence of extension into the renal vein, inferior vena cava (IVC or atrium. We report a case of a renal AML with a tumor thrombus to the IVC in a 32-year-old male. The patient subsequently underwent a right radical nephrectomy with IVC tumor thrombectomy. To our knowledge, there are four published cases of renal AML presenting with tumor thrombus in males. This case report describes the management of the youngest male ever to develop a renal AML with IVC tumor thrombus.

  6. Tumor pHe-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment

    Science.gov (United States)

    Chen, Fengqian; Zhang, Jinming; Wang, Lu; Wang, Yitao; Chen, Meiwan

    2015-09-01

    The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano-medicine therapy. Because of the slightly acidic extracellular environment (pHe ~ 6.5) and a higher glutathione (GSH) concentration (approximately 10 mM) in tumor tissue/cells, we firstly designed a novel d-α-tocopheryl polyethylene glycol 1000-poly(β-amino ester) block copolymer containing disulfide linkages (TPSS). TPSS nanoparticles (NPs) with pH- and redox-sensitive behaviors were developed for on-demand delivery of docetaxel (DTX) in hepatocellular carcinoma. DTX/TPSS NPs exhibited sensitive surface charge reversal from -47.6 +/- 2.5 mV to +22.5 +/- 3.2 mV when the pH decreased from 7.4 to 6.5, to simulate the pHe. Meanwhile, anabatic drug release of DTX/TPSS NPs was observed in PBS buffer (pH 6.5, 10 mM GSH). Due to the synergism between the pHe-triggered charge reversal and the redox-triggered drug release, enhanced drug uptake and anticancer efficacy were observed in HepG2 and SMMC 7721 cells treated with DTX/TPSS NPs. The positively charged NPs exhibited a stronger inhibitory effect on cell proliferation, promoted cell cycle arrest in the G2/M phase, and increased the rate of apoptosis. More importantly, based on the higher tumor accumulation of TPSS vehicles in vivo, a significant suppression of tumor growth, but without side-effects, was observed when DTX/TPSS NPs were injected intravenously into HepG2 xenograft tumor-bearing mice. Collectively, these results demonstrate that the newly developed dual-functional TPSS copolymer may be utilized as a drug delivery system for anticancer therapy.The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano-medicine therapy. Because of the slightly acidic extracellular environment (pHe ~ 6.5) and a higher glutathione (GSH) concentration (approximately 10 m

  7. Variation of stemness markers expression in tumor nodules from synchronous multi-focal hepatocellular carcinoma - an immunohistochemical study.

    Science.gov (United States)

    Lo, Regina Cheuk-Lam; Leung, Carmen Oi-Ning; Chok, Kenneth Siu-Ho; Ng, Irene Oi-Lin

    2017-08-01

    Advancing knowledge in molecular pathogenesis of hepatocellular carcinoma (HCC) opens up new horizons in the diagnostic, prognostic and therapeutic perspectives. Assessing the expression of molecular targets prior to definitive treatment is gaining importance in clinical practice. In this study, we investigated the variation in expression pattern of stemness markers in synchronous multi-focal HCC. In the first cohort, 21 liver explants with multi-focal HCC were examined for expression of stemness markers EpCAM, Sox9 and CK19 by immunohistochemistry (IHC). Expression data of 50 tumor nodules were analyzed to determine the concordance of expression among nodules in the same livers. In the second cohort, 14 tumor nodules from 6 multi-focal HCC cases proven as intra-hepatic metastasis were examined for Soc9 immunoexpression. In the first cohort, thirty nodules from 16 cases expressed one or more markers, with Sox9 being most frequently expressed. Complete concordance of expression pattern for all 3 markers was observed in 6 cases. Discrepancy of staining degree was noted in 4 cases for EpCAM, 14 cases for Sox9, and 6 cases for CK19. A two-tier or three-tier difference in staining scores was noted in 5 cases for Sox9 and one case for CK19. With Sox9, identical tumor morphology in terms of Edmondson grading and growth pattern did not infer the same degree of immunoexpression; and the largest tumor nodule was not representative of highest IHC score. In the second cohort of intra-hepatic metastasis, complete concordance of Sox9 expression level was observed in 5 out of 6 cases; while the remaining case showed a 1-tier difference of positive staining. Our findings suggested that clonality of tumor nodules is apparently an important factor to infer immunoexpression pattern. When there is limited information to discern multiple primaries versus intra-hepatic metastasis in multi-focal HCC, discordant degree of stemness markers expression among tumor nodules was commonly

  8. Measurement of tumor volumes of hepatocellular carcinoma (HCC) by computed tomography (CT). Correlation with several tumor markers

    Energy Technology Data Exchange (ETDEWEB)

    Yoneshima, Manabu; Sawabu, Norio; Toya, Daishu

    1984-09-01

    Tumor volumes of HCC were measured by CT using planimeter and the clinical value of this measurement was evaluated by comparing several tumor markers. Tumor volumes measured by CT roughly agreed with those measured by angiography. In some cases, volumes from ultrasonography were smaller than those from CT and angiography. Tumor volumes measured by CT correlated significantly with the levels of ..cap alpha..-fetoprotein (AFP) but didn't relate to the presence of hepatoma specific ..gamma..-GTP isoenzyme (novel ..gamma..-GTP) nor to the values and positivities of LAI assay. In small HCCs (<=30 cm/sup 3/), the presence of novel ..gamma..-GTP and the levels of AFP were significantly lower than for larger tumors of HCC, but LAI assay wasn't lower. The non-tumorous volumes and the ratio of the non-tumorous volume to the whole liver volume didn't relate to the tests of liver function except for the presence of ascites.

  9. GIANT PROSTHETIC VALVE THROMBUS

    Directory of Open Access Journals (Sweden)

    Prashanth Kumar

    2015-04-01

    Full Text Available Mechanical prosthetic valves are predisposed to bleeding, thrombosis & thromboembolic complications. Overall incidence of thromboembolic complications is 1% per year who are on oral anticoagulants, whereas bleeding complications incidence is 0.5% to 6.6% per year. 1, 2 Minimization of Scylla of thromboembolic & Charybdis of bleeding complication needs a balancing act of optimal antithrombotic therapy. We are reporting a case of middle aged male patient with prosthetic mitral valve presenting in heart failure. Patient had discontinued anticoagulants, as he had subdural hematoma in the past. He presented to our institute with a giant prosthetic valve thrombus.

  10. Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results

    Science.gov (United States)

    Łukasiewicz, Adam; Garkowski, Adam; Rutka, Katarzyna; Janica, Jacek; Łebkowska, Urszula

    2016-09-01

    It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  12. Laparoscopic liver resection for hepatocellular carcinoma in cirrhotic patients. Feasibility of nonanatomic resection in difficult tumor locations

    Directory of Open Access Journals (Sweden)

    Marco Casaccia

    2011-01-01

    Full Text Available Background: Surgical resection for hepatocellular carcinoma (HCC in cirrhotic patients remains controversial because of high morbidity and recurrence rates. Laparoscopic resection of liver tumors has recently been developed and could reduce morbidity. The aim of this study was to evaluate retrospectively our results for laparoscopic liver resection (LLR for HCC including lesions in the posterosuperior segments of the liver in terms of feasibility, outcome, recurrence and survival. Materials and Methods: Between June 2005 and February 2009, we performed 20 LLR for HCC. Median age of the patients was 66 years. The underlying cirrhosis was staged as Child A in 17 cases and Child B in 3. Results: LLR included anatomic resection in six cases and nonanatomic resection in 14. Eleven procedures were associated in nine (45% patients. Median tumor size and surgical margins were 3.1 cm and 15 mm, respectively. A conversion to laparotomy occurred in one (5% patient for hemorrhage. Mortality and morbidity rates were 0% and 15% (3/20. Median hospital stay was 8 days (range: 5-16 days. Over a mean follow-up period of 26 months (range: 19-62 months, 10 (50% patients presented recurrence, mainly at distance from the surgical site. Treatment of recurrence was possible in all the patients, including orthotopic liver transplantation in three cases. Conclusions: LLR for HCC in selected patients is a safe procedure with good short-term results. It can also be proposed in tumor locations with a difficult surgical access maintaining a low morbidity rate and good oncological adequacy. This approach could have an impact on the therapeutic strategy of HCC complicating cirrhosis as a treatment with curative intent or as a bridge to liver transplantation.

  13. Anti-tumor effects of metformin in animal models of hepatocellular carcinoma: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Juan Li

    Full Text Available Several studies have reported that metformin can reduce the risk of hepatocellular carcinoma (HCC in diabetes patients. However, the direct anti-HCC effects of metformin have hardly been studied in patients, but have been extensively investigated in animal models of HCC. We therefore performed a systematic review and meta-analysis of animal studies evaluating the effects of metformin on HCC.We collected the relevant studies by searching EMBASE, Medline (OvidSP, Web of Science, Scopus, PubMed Publisher, and Google Scholar. Studies were included according to the following inclusion criteria: HCC, animal study, and metformin intervention. Study quality was assessed using SYRCLE's risk of bias tool. A meta-analysis was performed for the outcome measures: tumor growth (tumor volume, weight and size, tumor number and incidence.The search resulted in 573 references, of which 13 could be included in the review and 12 included in the meta-analysis. The study characteristics of the included studies varied considerably. Two studies used rats, while the others used mice. Only one study used female animals, nine used male, and three studies didn't mention the gender of animals in their experiments. The quality of the included studies was low to moderate based on the assessment of their risk of bias. The meta-analysis showed that metformin significantly inhibited the growth of HCC tumour (SMD -2.20[-2.96,-1.43]; n=16, but no significant effect on the number of tumors (SMD-1.05[-2.13,0.03]; n=5 or the incidence of HCC was observed (RR 0.62[0.33,1.16]; n=6. To investigate the potential sources of significant heterogeneities found in outcome of tumor growth (I2=81%, subgroup analyses of scales of growth measures and of types of animal models used were performed.Metformin appears to have a direct anti-HCC effect in animal models. Although the intrinsic limitations of animal studies, this systematic review could provide an important reference for future

  14. Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment

    International Nuclear Information System (INIS)

    Reiner, Caecilia S.; Gordic, Sonja; Puippe, Gilbert; Morsbach, Fabian; Wurnig, Moritz; Schaefer, Niklaus; Veit-Haibach, Patrick; Pfammatter, Thomas; Alkadhi, Hatem

    2016-01-01

    PurposeTo evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE).Materials and MethodsSixteen patients (15 male; mean age 65 years; age range 47–80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters’ ability to discriminate responders from non-responders.ResultsAccording to mRECIST, 8 patients (50 %) were responders and 8 (50 %) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min −1  100 mL −1 ); p < 0.05], while the mean AP of HCCs (43.5 vs. 27.9 mL min −1  100 mL −1 ; p > 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min −1  100 mL −1 , therapy response could be predicted with a sensitivity of 88 % (7/8) and specificity of 75 % (6/8).ConclusionVoxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE

  15. Application of tumor-node-metastasis staging 2002 version in locally advanced hepatocellular carcinoma: is it predictive of surgical outcome?

    International Nuclear Information System (INIS)

    Li, Binkui; Yuan, Yunfei; Chen, Guihua; He, Liru; Zhang, Yaqi; Li, Jinqing; Li, Guohui; Lau, Wan Yee

    2010-01-01

    Locally advanced (pT3-4N0M0) hepatocellular carcinoma (HCC) is a heterogeneous group of tumors, which consists of four different categories, including HCC with 'multiple tumors more than 5 cm', 'major vascular invasion', 'invasion of adjacent organs', and 'perforation of visceral peritoneum'. The aim of our study was to verify whether the 2002 version of the Tumor-Node-Metastasis staging system could predict surgical outcomes in patients with locally advanced HCC. We retrospectively reviewed 298 patients with pT3-4N0M0 HCC who underwent hepatic resection from 1993 to 2000 in an academic tertiary hospital. Overall survival (OS) and cumulative recurrence rate (CRR) of the four categories of locally advanced HCC patients were compared. In multivariate analysis, major vascular invasion was identified as the most significant factor (HR = 3.291, 95% CI 2.362-4.584, P < 0.001) followed by cirrhosis status on OS, and was found to be the only independent factor of CRR (HR = 2.242, 95% CI 1.811-3.358, P < 0.001) in patients with locally advanced HCC. Among the four categories of locally advanced HCC, OS was significantly worse, and CRR was significantly higher in patients with HCC with major vascular invasion (pT3) than with multiple tumors more than 5 cm (pT3); or tumor invasion of adjacent organs (pT4); or perforation of visceral peritoneum (pT4). No significant differences were observed in OS or CRR between the latter three groups of patients. HCC with major vascular invasion, which are classified as pT3 under the current TNM staging, have the worst prognosis when compared with the other categories of pT3-4 disease. There is a need to redefine the T classification and to stratify locally advanced HCC

  16. Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Reiner, Caecilia S., E-mail: caecilia.reiner@usz.ch; Gordic, Sonja; Puippe, Gilbert; Morsbach, Fabian; Wurnig, Moritz [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology (Switzerland); Schaefer, Niklaus; Veit-Haibach, Patrick [University Hospital Zurich, Division of Nuclear Medicine (Switzerland); Pfammatter, Thomas; Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology (Switzerland)

    2016-03-15

    PurposeTo evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE).Materials and MethodsSixteen patients (15 male; mean age 65 years; age range 47–80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters’ ability to discriminate responders from non-responders.ResultsAccording to mRECIST, 8 patients (50 %) were responders and 8 (50 %) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min{sup −1} 100 mL{sup −1}); p < 0.05], while the mean AP of HCCs (43.5 vs. 27.9 mL min{sup −1} 100 mL{sup −1}; p > 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min{sup −1} 100 mL{sup −1}, therapy response could be predicted with a sensitivity of 88 % (7/8) and specificity of 75 % (6/8).ConclusionVoxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE.

  17. A Therapeutic Challenge: Management of Atrial Thrombus

    Directory of Open Access Journals (Sweden)

    Serkan Burc Deser

    2016-09-01

    Full Text Available Introduction: Primary cause of atrial thrombi include atrial fibrillation, foreign bodies inside the atrium such as catheters and pacemaker leads, emboli of deep venous thrombus and primary or metastatic tumors of the heart. We review the clinical features, epidemiology, diagnosis and treatment of nine intriguing cases with atrial thrombus. Methods: This is a retrospective study of nine patients (seven female (78%, two male (33% who were diagnosed with atrial thrombi (average age of 50 ± 12 years and were treated at the Ondokuz Mayis University, Department of Cardiovascular Surgery from February 2014 to January 2015. Among them, six patients had atrial fibrillation (one male, five female, seven patients were suffering from dispne and orthopnoea, five patients were suffering from leg swelling, seven patients had a history of hypertension and three patients had a history of mitral valve replacement surgery. Results: All patients underwent surgery except one. Four patients recovered uneventfully and discharged with oral anticoagulation (warfarin therapy (adjusted to maintain an international normalized ratio of INR between two and three times. Five of nine patients (55% died after surgery. Conclusion: The response to the thrombolytic therapy is poor, mostly ineffective and unsafe so it is often recommended as a bridge to surgery. In patients diagnosed with mechanical mitral valve thrombosis, medical therapy has the possibility of end organ emboli and also fail to resolve the organised thrombus on the stuck valve. On the other hand surgery does not always give satisfactory results. J Clin Exp Invest 2016; 7(4: 278-282

  18. Squamous Cell Carcinoma Antigen: A Novel Tumor Marker for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Abdel Messeih, Ph.L.

    2009-01-01

    Serum Squamous Cell Carcinoma Antigen (SCC-Ag) by ELISA technique and Alpha-fetoprotein (AFP) by IRMA technique were measured in 65 patients with hepatic focal lesion. 49 patients suffered from proved hepatocellular carcinoma and 16 patients were having cirrhosis and 20 normal controls. Median levels of serum AFP and SCC-Ag in HCC patients was significantly higher when compared with both cirrhotic patients and controls. On using receiver operator characteristic curve to improve sensitivity and specificity of AFP and SCC-Ag for detection of HCC, the best chosen cut-off values were 40 IU/mL for AFP and 2.55 ng/L for SCC-Ag, these yielded a sensitivity of 67.2% and 61.2% respectively and specificity 100%. The diagnostic sensitivity of them increased to 87.7% when they was combiendly calculated. It was found that the combined use of AFP and SCC-Ag is useful in screening patients with hepatic focal lesion to increase the chance of early diagnosis of HCC patients.

  19. Changes in tumor vascularity precede microbubble contrast accumulation deficit in the process of dedifferentiation of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Maruyama, Hitoshi; Takahashi, Masanori; Ishibashi, Hiroyuki; Okabe, Shinichiro; Yoshikawa, Masaharu; Yokosuka, Osamu

    2010-01-01

    Purpose: To elucidate the changes in tumor vascularity and microbubble accumulation on contrast-enhanced sonograms, in relation to the dedifferentiation of hepatocellular carcinoma (HCC). Materials and methods: This prospective study enrolled 10 patients with histologically proven HCC (14.4-39.0 mm, 26.1 ± 7.4) showing nodule-in-nodule appearance upon contrast-enhanced computed tomography. Contrast-enhanced ultrasound was performed by harmonic imaging under a low mechanical index (0.22-0.25) during the vascular phase (agent injection to 1 min) and late phase (15 min) following the injection of Sonazoid TM (0.0075 ml/kg). Contrast enhancement in the inner and outer nodules was assessed in comparison with that in adjacent liver parenchyma as hyper-, iso-, or hypo-enhanced. Results: Vascular-phase enhancement of all 10 inner nodules was hyper-enhanced, and that of outer nodules was hyper-enhanced in 3, iso-enhanced in 2, and hypo-enhanced in 5. Late-phase enhancement of inner nodules was hypo-enhanced in 8 and iso-enhanced in 2. Furthermore, late-phase enhancement of outer nodules was iso-enhanced in the 7 lesions that showed iso- or hypo-enhancement in the vascular phase, and hypo-enhanced in the 3 with hyper-enhancement in the vascular phase. Late-phase hypo-enhancement was significantly more frequent in the nodules showing early-phase hyper-enhancement (11/13) than in the nodules showing early-phase iso- or hypo-enhancement (0/7) in both the inner and outer nodules. Conclusion: Dedifferentiation of HCC may be accompanied by changes in tumor vascularity prior to a reduction in microbubble accumulation. Observation of the vascular phase may be more useful than late-phase imaging for the early recognition of HCC dedifferentiation when using contrast-enhanced ultrasound with Sonazoid.

  20. Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma: the second report: relationship with tumor size and cell differentiation.

    Science.gov (United States)

    Kumagai, Arisa; Kondo, Fukuo; Sano, Keiji; Inoue, Masafumi; Fujii, Takeshi; Hashimoto, Masaji; Watanabe, Masato; Soejima, Yurie; Ishida, Tsuyoshi; Tokairin, Takuo; Saito, Koji; Sasajima, Yuko; Takahashi, Yoshihisa; Uozaki, Hiroshi; Fukusato, Toshio

    2016-07-01

    The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression. Ninety-four HCC lesions no larger than 8 cm from 94 patients were immuno-histochemically studied using two hepatocyte markers (Hep par 1 and α-fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c-Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined. The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c-Kit). Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression. © 2016 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  1. Tumoral response factors after radiofrequency ablation of hepatocellular carcinoma in cirrhotic liver Factores de respuesta tumoral tras ablación mediante radiofrecuencia del carcinoma hepatocelular sobre cirrosis

    Directory of Open Access Journals (Sweden)

    J. Calleja Kempin

    2005-10-01

    Full Text Available Objective: hepatocellular carcinoma (HCC ablation by radiofrequency (RFA is a novel technique with a great variety of methods whose efficacy and predictive factors have not been completely studied. Some of the main predictive factors in this type of treatment are analyzed in the present study. Patients and methods: ninety-three patients with hepatocellular carcinoma over cirrhosis, and with no indication for surgical resection were treated by RFA. Two different types of electrodes were used for RFA (refrigerated-"Cool-Tip" and perfusion with saline solution, the approach was percutaneous, by laparoscopy or laparotomy. Results: overall survival at 1, 2 and 3 years was 88, 81, and 76%, with a free-disease survival (FDS of 66, 31 and 17%, respectively. For tumors less than 3 cm, FDS at 1,2 and 3 years was 74, 44 and 30%, while for more than 3 cm in size FDS was 55, 12 and 0% (p = 0.02. FDS for HCC with one nodule was 70, 36 and 22%, and for more than one nodule it decreased to 50, 17 and 0% at 1, 2 and 3 years, respectively (p = 0.07. Surprisingly, the method employed for RFA has a main influence in FDS, with 0% at 3 years for perfusion electrodes and 26% for cool-tip electrodes at the same period. Conclusions: in this series, overall survival at three years was relatively high; however, tumoral size, number of nodules and RFS method were independent variables associated with disease-free survival.Objetivo: la ablación por radiofrecuencia del hepatocarcinoma (ARF es una técnica de reciente adquisición, cuya eficacia y factores predictivos no han sido suficientemente evaluados. El presente estudio fue diseñado para este análisis. Pacientes y métodos: se han tratado 93 pacientes con hepatocarcinoma sobre hígado cirrótico sin criterios de resección ni de trasplante hepático. El tratamiento se realizó mediante abordaje percutáneo, laparoscópico o mediante laparotomía con dos tipos de electrodos de radiofrecuencia, electrodo refrigerado y

  2. HBV-specific CD4+ cytotoxic T cells in hepatocellular carcinoma are less cytolytic toward tumor cells and suppress CD8+ T cell-mediated antitumor immunity.

    Science.gov (United States)

    Meng, Fanzhi; Zhen, Shoumei; Song, Bin

    2017-08-01

    In East Asia and sub-Saharan Africa, chronic infection is the main cause of the development of hepatocellular carcinoma, an aggressive cancer with low survival rate. Cytotoxic T cell-based immunotherapy is a promising treatment strategy. Here, we investigated the possibility of using HBV-specific CD4 + cytotoxic T cells to eliminate tumor cells. The naturally occurring HBV-specific cytotoxic CD4 + and CD8 + T cells were identified by HBV peptide pool stimulation. We found that in HBV-induced hepatocellular carcinoma patients, the HBV-specific cytotoxic CD4 + T cells and cytotoxic CD8 + T cells were present at similar numbers. But compared to the CD8 + cytotoxic T cells, the CD4 + cytotoxic T cells secreted less cytolytic factors granzyme A (GzmA) and granzyme B (GzmB), and were less effective at eliminating tumor cells. In addition, despite being able to secrete cytolytic factors, CD4 + T cells suppressed the cytotoxicity mediated by CD8 + T cells, even when CD4 + CD25 + regulator T cells were absent. Interestingly, we found that interleukin 10 (IL-10)-secreting Tr1 cells were enriched in the cytotoxic CD4 + T cells. Neutralization of IL-10 abrogated the suppression of CD8 + T cells by CD4 + CD25 - T cells. Neither the frequency nor the absolute number of HBV-specific CD4 + cytotoxic T cells were correlated with the clinical outcome of advanced stage hepatocellular carcinoma patients. Together, this study demonstrated that in HBV-related hepatocellular carcinoma, CD4 + T cell-mediated cytotoxicity was present naturally in the host and had the potential to exert antitumor immunity, but its capacity was limited and was associated with immunoregulatory properties. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  3. Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo.

    Directory of Open Access Journals (Sweden)

    Xinhua Chen

    Full Text Available BACKGROUND AND AIM: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. MATERIALS AND METHODS: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. RESULTS: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. CONCLUSION: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo.

  4. PROMOTION BY 17BETA-ESTRADIOL AND BETA-HEXACHLOROCYCLOHEXANE OF HEPATOCELLULAR TUMORS IN MEDAKA, ORYZIAS LATIPES. (R825298)

    Science.gov (United States)

    AbstractA feature common to many laboratory and field studies with various fish species is a higher prevalence of hepatocellular neoplasia in females than in males. During female sexual maturation, endogenous estrogens stimulate substantial increases in synthetic acti...

  5. Pleural and Pulmonary Staining at Inferior Phrenic Arteriography Mimicking a Tumor Staining of Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Lee, Deok Hee; Hwang, Jae Cheol; Lim, Soo Mee; Yoon, Hyun-Ki; Sung, Kyu-Bo; Song, Ho-Young

    2000-01-01

    Purpose: To describe the findings of pleural and pulmonary staining of the inferior phrenic artery, which can be confused with tumor staining during transarterial chemoembolization (TACE) of hepatoma.Methods: Fifteen patients who showed pleural and pulmonary staining without relationship to hepatic masses at inferior phrenic arteriography were enrolled. The staining was noted at initial TACE (n = 8), at successive TACE (n = 5), and after hepatic surgery (n = 2). The angiographic pattern, the presence of pleural change on computed tomography (CT), and clinical history were evaluated.Results: Draining pulmonary veins were seen in all cases. The lower margin of the staining corresponded to the lower margin of the pleura in 10 patients. CT showed pleural and/or pulmonary abnormalities in all cases. After embolization of the inferior phrenic artery, the accumulation of iodized oil in the lung was noted.Conclusion: Understanding the CT and angiographic findings of pleural and pulmonary staining during TACE may help differentiate benign staining from tumor staining

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. 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.

  8. Radiopharmaceuticals for thrombus detection

    International Nuclear Information System (INIS)

    Knight, L.C.

    1990-01-01

    Most of the components of the thrombotic and fibrinolytic systems have at some time been evaluated as a means of carrying a radiolabel specifically to thrombi, although very few have been promising enough to emerge from investigational status to routine clinical use. New approaches are being explored, including improved methods of labeling platelets, chemically modified forms of previously tested plasma proteins, and new biomolecules, including monoclonal antibodies specific for fibrin and platelets. The current goal is to find one or more radiotracers that bind specifically and rapidly to thrombi, and that also have a rapid blood disappearance rate, permitting a clear diagnosis within a few hours after injection. Because this test may be needed to assess the course of therapy in an anticoagulated patient, the ideal radiopharmaceutical should be able to locate thrombi without interference by anticoagulants. Until a suitable thrombus-specific radiopharmaceutical becomes generally available, many hospitals will continue to attempt to make a diagnosis with nonspecific radiopharmaceuticals that can at best provide blood pool images to indicate filling defects. Several of the new approaches seem likely to provide the radiopharmaceutical sought, although clinical trials are at an early stage.137 references

  9. Regulation of tumorigenesis and metastasis of hepatocellular carcinoma tumor endothelial cells by microRNA-3178 and underlying mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wei; Shen, Shiqiang, E-mail: shenshiqiang2014@hotmail.com; Wu, Shanmin; Chen, Zubing; Hu, Chao; Yan, Ruichen

    2015-08-28

    This study explored the effects of microRNA-3178 (miR-3178) on hepatocellular carcinoma (HCC) tumor endothelial cells (TECs) and on the target mRNA. Real-time polymerase chain reaction (PCR) was performed to detect the differential expression of miR-3178 in hepatic sinusoidal endothelial cells (HSECs) and HCC TECs. Furthermore, HCC TECs were transfected with miR-3178 mimic/inhibitor or their respective negative controls. The expression of miR-3178 before and after transfection was confirmed through RT-PCR. The effects of miR-3178 on the proliferation, apoptosis, cell cycle, invasion, migration, and angiogenesis of HCC TECs were also investigated through methyl thiazol tetrazolium assay, flow cytometry, matrigel invasion assay, transwell migration assay, and tube formation assay. Early growth responsive gene 3 (EGR3), as the putative target of miR-3178, was detected through RT-PCR and Western blot. Compared with HSECs, HCC TECs had lower miR-3178 expression levels (P < 0.001). MiR-3178 mimic inhibited proliferation, arrested cell cycle in G1 phase, and increased apoptosis. The numbers of migrated and invaded cells and capillary-like structures were significantly less in the mimic group than in the other groups. MiR-3178 mimic significantly decreased the mRNA and protein expression levels of EGR3. By contrast, miR-3178 inhibitor induced opposite effects. We conclude that miR-3178 was lowly expressed in HCC TECs, and miR-3178 mimic specifically inhibited the proliferation, migration, invasion, and angiogenesis and promoted the apoptosis and G1 phase arrest of HCC TECs in vitro through the inhibition of EGR3 expression. Thus, miR-3178 might be a critical target in HCC therapy. - Highlights: • MiR-3178 is significantly low-expression in HCC TECs. • MiR-3178 acts as a tumor suppressor to inhibit tumorigenesis and metastasis. • MiR-3178 inhibit angiogenesis of HCC TECs. • EGR3 may be a target gene of miR-3178. • MiR-3178 may have therapeutic application for

  10. Down-regulation of SFRP1 as a putative tumor suppressor gene can contribute to human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Huang, Jian; Zhang, Yun-Li; Teng, Xiao-Mei; Lin, Yun; Zheng, Da-Li; Yang, Peng-Yuan; Han, Ze-Guang

    2007-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. SFRP1 (the secreted frizzled-related protein 1), a putative tumor suppressor gene mapped onto chromosome 8p12-p11.1, the frequent loss of heterozygosity (LOH) region in human HCC, encodes a Wingless-type (Wnt) signaling antagonist and is frequently inactivated by promoter methylation in many human cancers. However, whether the down-regulation of SFRP1 can contribute to hepatocarcinogenesis still remains unclear. We investigated the expression of SFRP1 through real time RT-PCR and immunohistochemistry staining. The cell growth and colony formation were observed as the overexpression and knockdown of SFRP1. The DNA methylation status within SFRP1 promoter was analyzed through methylation-specific PCR or bisulphate-treated DNA sequencing assays. Loss of heterozygosity was here detected with microsatellite markers. SFRP1 was significantly down-regulated in 76.1% (35/46) HCC specimens at mRNA level and in 30% (30/100) HCCs indicated by immunohistochemistry staining, as compared to adjacent non-cancerous livers. The overexpression of SFRP1 can significantly inhibit the cell growth and colony formation of YY-8103, SMMC7721, and Hep3B cells. The RNA interference against the constitutional SFRP1 in the offspring SMMC7721 cells, which were stably transfected by ectopic SFRP1, can markedly promote cell growth of these cells. LOH of both microsatellite markers D8S532 and D8SAC016868 flanking the gene locus was found in 13% (6 of 46 HCCs) and 6.5% (3 of 46 HCCs) of the informative cases, respectively, where 5 of 8 HCC specimens with LOH showed the down-regulation of SFRP1. DNA hypermethylation within SFRP1 promoter was identified in two of three HCC specimens without SFRP1 expression. Moreover, the DNA methylation of SFRP1 promoter was significantly reduced, along with the re-expression of the gene, in those HCC cell lines, Bel7404, QGY7701, and MHCC-H, as treated by DAC. Our data suggested that the

  11. Thrombus aspiration catheter is a Dottering balloon

    Directory of Open Access Journals (Sweden)

    D. Sheshagiri Rao

    2016-07-01

    Full Text Available Coronary angiogram in a young man with history of STEMI with delayed presentation revealed subtotal occlusion of left anterior descending artery (LAD with large thrombotic filling defect distal to the critical lesion. PCI was preferred without delay because of ongoing chest pain. Several runs of thrombus aspiration failed to detect any visible thrombus. However, the immediate angiogram after thrombus aspiration showed complete distal embolization of the thrombus which could have been achieved by Dottering or balloon dilatation. In contrary to the general perception, does thrombus aspiration push more thrombus than it can aspirate?

  12. Thrombus aspiration catheter is a Dottering balloon.

    Science.gov (United States)

    Sheshagiri Rao, D; Barik, Ramachandra; Prasad, Akula Siva

    2016-01-01

    Coronary angiogram in a young man with history of STEMI with delayed presentation revealed subtotal occlusion of left anterior descending artery (LAD) with large thrombotic filling defect distal to the critical lesion. PCI was preferred without delay because of ongoing chest pain. Several runs of thrombus aspiration failed to detect any visible thrombus. However, the immediate angiogram after thrombus aspiration showed complete distal embolization of the thrombus which could have been achieved by Dottering or balloon dilatation. In contrary to the general perception, does thrombus aspiration push more thrombus than it can aspirate? Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  13. Cooperation of Indian Hedgehog and Vascular Endothelial Growth Factor in Tumor Angiogenesis and Growth in Human Hepatocellular Carcinomas, an Immunohistochemical Study.

    Science.gov (United States)

    Li, Yang; Liu, Yang; Wang, Guangxi; Wang, Yuxiang; Guo, Limei

    2018-04-07

    The Hedgehog pathway was recently shown to be involved in vascular development and neovascularization in human embryogenesis and disease. However, the role of Hedgehog pathway in modulating tumor angiogenesis is still unexplored. In the current study, we investigated the expression of Indian Hedgehog (Ihh) and vascular endothelial cell growth factor (VEGF) in human hepatocellular carcinomas (HCCs) with immunohistochemical staining and compared the immunoreaction data with various clinicopathologic characteristics. Immunoreactivity of Ihh and VEGF proteins was observed in 61.5% (56/91) and 64.5% (59/91) cases of HCC tumor tissues, respectively, which was considerably higher than the adjacent nonmalignant tissues. Ihh protein was observed predominantly in the cytoplasm of the tumor cells with a staining pattern of which was sparse and dot-like, or circular around the cell membrane. VEGF protein was expressed heterogenously in the cytoplasm in tumor cells and was negative in peritumoral areas in all cases. CD34 showed diffuse staining in the tumor parenchyma in most HCC specimens. The association of expression of Ihh and VEGF with tumor size was statistically significant (PIhh and VEGF proteins in HCC (r=0.6, PIhh and CD34 staining (r=0.261, P=0.012). Our findings suggest that Ihh is involved in the development of HCC. These findings are also consistent with the concept that cooperation of Ihh and VEGF modulate HCC tumor angiogenesis and growth.

  14. Enhancement pattern analysis of hypervascular hepatocellular carcinoma on dynamic MR imaging with histopathological correlation: Validity of portal phase imaging for predicting tumor grade

    International Nuclear Information System (INIS)

    Okamoto, Daisuke; Yoshimitsu, Kengo; Nishie, Akihiro; Tajima, Tsuyoshi; Asayama, Yoshiki; Ishigami, Kousei; Hirakawa, Masakazu; Ushijima, Yasuhiro; Kakihara, Daisuke; Nakayama, Tomohiro; Nishihara, Yunosuke; Aishima, Shinichi; Taketomi, Akinobu; Kishimoto, Junji; Honda, Hiroshi

    2012-01-01

    Purpose: To elucidate the correlation between hypervascular hepatocellular carcinoma (HCC) enhancement patterns on dynamic MR imaging and histological findings. Materials and methods: Surgically proven 46 hypervascular HCCs of forty-one patients were enrolled. For each HCC, the signal intensity in the portal phase (SIPP) was evaluated. In this study, high, iso-, or low intensity in the portal phase was hypothesized as late, moderate, or early washout pattern, respectively. The SIPP of each HCC was correlated to histological grade and architectural subtypes that represent degrees of trabecular structure. For the trabecular HCCs, the thickness of tumor plate was also correlated for indirect estimation of tumor sinusoid. Results: There was a significant correlation between the SIPP vs. histological grade and also vs. architectural subtypes, namely the degree of trabecular structure. Washout of hypervascular HCC occurred earlier as the histological grade advanced and the histological architecture got closer to pure trabecular HCC. For the trabecular HCCs, the thickness of tumor plate correlated significantly with SIPP or histological grade. Hypervascular HCCs with thicker tumor plates showed worse histological grade and earlier washout pattern. Conclusions: Histological grade of hypervascular HCC may be predicted using SIPP. The thickness of tumor plate, resultantly the size of sinusoid between tumor plates, can account for the relationship between washout pattern and histological grade in the trabecular HCCs.

  15. Carcinogen-Induced Hepatic Tumors in KLF6+/- Mice Recapitulate Aggressive Human Hepatocellular Carcinoma Associated with p53 Pathway Deregulation

    NARCIS (Netherlands)

    Tarocchi, Mirko; Hannivoort, Rebekka; Hoshida, Yujin; Lee, Ursula E.; Vetter, Diana; Narla, Goutham; Villanueva, Augusto; Oren, Moshe; Llovet, Josep M.; Friedman, Scott L.

    Inactivation of KLF6 is common in hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection, thereby abrogating its normal antiproliferative activity in liver cells. The aim of the study was to evaluate the impact of KLF6 depletion on human HCC and experimental

  16. Interobserver variability in gross tumor volume delineation for hepatocellular carcinoma. Results of Korean Radiation Oncology Group 1207 study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Suk [Jeju National University School of Medicine, Department of Radiation Oncology, Jeju National University Hospital, Jeju (Korea, Republic of); Kim, Jun Won; Lee, Ik Jae [Yonsei University College of Medicine, Department of Radiation Oncology, Gangnam Severance Hospital, Seoul (Korea, Republic of); Yoon, Won Sup [Korea University Medical Center, Department of Radiation Oncology, Ansan Hospital, Ansan (Korea, Republic of); Kang, Min Kyu [Kyungpook National University School of Medicine, Department of Radiation Oncology, Daegu (Korea, Republic of); Kim, Tae Hyun [National Cancer Center, Center for Liver Cancer, Goyang (Korea, Republic of); Kim, Jin Hee [Keimyung University School of Medicine, Department of Radiation Oncology, Dongsan Medical Center, Daegu (Korea, Republic of); Lee, Hyung-Sik [Dong-A University College of Medicine, Department of Radiation Oncology, Busan (Korea, Republic of); Park, Hee Chul [Sungkyunkwan University School of Medicine, Department of Radiation Oncology, Samsung Medical Center, Seoul (Korea, Republic of); Jang, Hong Seok; Kay, Chul Seung [The Catholic University of Korea College of Medicine, Department of Radiation Oncology, Seoul (Korea, Republic of); Yoon, Sang Min [University of Ulsan College of Medicine, Department of Radiation Oncology, Asan Medical Center, Seoul (Korea, Republic of); Kim, Mi-Sook [Korea Institute of Radiological and Medical Sciences, Department of Radiation Oncology, Seoul (Korea, Republic of); Seong, Jinsil [Yonsei University College of Medicine, Department of Radiation Oncology, Severance Hospital, Seodaemun-gu, Seoul (Korea, Republic of)

    2016-10-15

    There has been increasing use of external beam radiotherapy for localized treatment of hepatocellular carcinoma (HCC) with both palliative and curative intent. Quality control of target delineation in primary HCC is essential to deliver adequate doses of radiation to the primary tumor while preserving adjacent healthy organs. We analyzed interobserver variability in gross tumor volume (GTV) delineation for HCC. Twelve radiation oncologists specializing in liver malignancy participated in a multi-institutional contouring dummy-run study of nine HCC cases and independently delineated GTV on the same set of provided computed tomography images. Quantitative analysis was performed using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE) with kappa statistics calculating agreement between physicians. To quantify the interobserver variability of GTV delineations, the ratio of the actual delineated volume to the estimated consensus volume (STAPLE), the ratio of the common and encompassing volumes, and the coefficient of variation were calculated. The median kappa agreement level was 0.71 (range 0.28-0.86). The ratio of the actual delineated volume to the estimated consensus volume ranged from 0.19 to 1.93 (median 0.94) for all cases. The ratio of the common and encompassing volumes ranged from 0.001 to 0.56 (median 0.25). The coefficient of variation for GTV delineation ranged from 8 to 57 % (median 26 %). The interobserver variability in target delineation of HCC GTV in this study is noteworthy. Multi-institution studies involving radiotherapy for HCC require appropriate quality assurance programs for target delineation. (orig.) [German] Die externe kurative Strahlentherapie ist zunehmend bei der lokalisierten Behandlung hepatozellulaerer Karzinome (HCC) in palliativer und kurativer Absicht in Gebrauch. Eine Qualitaetskontrolle der Zielabgrenzung beim primaeren HCC ist entscheidend, um die passende Dosis fuer die

  17. Pre-treatment double- or triple-positive tumor markers are predictive of a poor outcome for patients undergoing radiofrequency ablation for hepatocellular carcinoma.

    Science.gov (United States)

    Nitta, Hidetoshi; Nakagawa, Shigeki; Kaida, Takayoshi; Arima, Kota; Higashi, Takaaki; Taki, Katsunobu; Okabe, Hirohisa; Hayashi, Hiromitsu; Hashimoto, Daisuke; Chikamoto, Akira; Ishiko, Takatoshi; Beppu, Toru; Baba, Hideo

    2017-03-01

    We evaluated the therapeutic effect of radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC) according to the number of positive tumor markers. The subjects of this study were 160 patients who underwent percutaneous and surgical RFA for HCC. Patients were divided into negative (n = 51), single- (n = 69), double- (n = 31), and triple-positive (n = 9) tumor marker groups according to the pre-treatment expression of these markers. We looked for any relationships among clinical parameters, outcomes, and tumor markers. The 3-year recurrence-free and overall survival rates of the negative, single-, double-, and triple-positive groups were 30, 19, 16, and 11 % (P = 0.02), and 94, 88, 67, and 37 % (P tumor marker profile was independently associated with local recurrence [hazard ratio (HR) 5.48, 95 % confidence interval (CI) 2.44-12.33, P tumor markers.

  18. Rosmarinic acid inhibits inflammation and angiogenesis of hepatocellular carcinoma by suppression of NF-κB signaling in H22 tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Wen Cao

    2016-10-01

    Full Text Available The aim of this study was to explore the anti-tumor effect and therapeutic potential of rosmarinic acid (RA in the treatment of hepatocellular carcinoma (HCC. RA at 75, 150 and 300 mg/kg was given to H22 tumor-bearing mice by intragastric administration once daily for 10 consecutive days. Levels of inflammatory and angiogenic factors, including interleukin-1β (IL-1β, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, vascular endothelial growth factor (VEGF, and transforming growth factor-β (TGF-β were measured by enzyme linked immunosorbent assays (ELISA. Protein levels of phosphorylated NF-κB p65 and p65 were detected by western blot. mRNA level of NF-κB p65 was analyzed by qRT-PCR. The results showed that RA could effectively suppress tumor growth with fewer toxic effects by regulating the secretion of cytokines associated with inflammation and angiogenesis, and suppressing the expression of NF-κB p65 in the xenograft microenvironment. Our findings unveil the possible anti-tumor mechanisms of RA and support RA as a potential drug for the treatment of HCC.

  19. Evaluation of the human relevance of the constitutive androstane receptor-mediated mode of action for rat hepatocellular tumor formation by the synthetic pyrethroid momfluorothrin.

    Science.gov (United States)

    Okuda, Yu; Kushida, Masahiko; Kikumoto, Hiroko; Nakamura, Yoshimasa; Higuchi, Hashihiro; Kawamura, Satoshi; Cohen, Samuel M; Lake, Brian G; Yamada, Tomoya

    2017-01-01

    High dietary levels of the non-genotoxic synthetic pyrethroid momfluorothrin increased the incidence of hepatocellular tumors in male and female Wistar rats. Mechanistic studies have demonstrated that the mode of action (MOA) for momfluorothrin-induced hepatocellular tumors is constitutive androstane receptor (CAR)-mediated. In the present study, to evaluate the potential human carcinogenic risk of momfluorothrin, the effects of momfluorothrin (1-1,000 µM) and a major metabolite Z-CMCA (5-1,000 µM) on hepatocyte replicative DNA synthesis and CYP2B mRNA expression were examined in cultured rat and human hepatocyte preparations. The effect of sodium phenobarbital (NaPB), a prototypic rodent hepatocarcinogen with a CAR-mediated MOA, was also investigated. Human hepatocyte growth factor (hHGF) produced a concentration-dependent increase in replicative DNA synthesis in rat and human hepatocytes. However, while NaPB and momfluorothrin increased replicative DNA synthesis in rat hepatocytes, NaPB, momfluorothrin and Z-CMCA did not increase replicative DNA synthesis in human hepatocytes. NaPB, momfluorothrin and Z-CMCA increased CYP2B1/2 mRNA levels in rat hepatocytes. NaPB and momfluorothrin also increased CYP2B6 mRNA levels in human hepatocytes. Overall, while momfluorothrin and NaPB activated CAR in cultured human hepatocytes, neither chemical increased replicative DNA synthesis. Furthermore, to confirm whether the findings observed in vitro were also observed in vivo, a humanized chimeric mouse study was conducted. Replicative DNA synthesis was not increased in human hepatocytes of chimeric mice treated with momfluorothrin or its close structural analogue metofluthrin. As human hepatocytes are refractory to the mitogenic effects of momfluorothrin, in contrast to rat hepatocytes, the data support the hypothesis that the MOA for momfluorothrin-induced rat liver tumor formation is not relevant for humans.

  20. 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.

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

    International Nuclear Information System (INIS)

    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.

  2. Prognostic Factors for Tumor Recurrence after a 12-Year, Single-Center Experience of Liver Transplantations in Patients with Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Matteo Cescon

    2010-01-01

    Full Text Available Background. Factors affecting outcomes after orthotopic liver transplantation (OLT for hepatocellular carcinoma (HCC have been extensively studied, but some of them have only recently been discovered or reassessed. Methods. We analyzed classical and more recently emerging variables with a hypothetical impact on recurrence-free survival (RFS in a single-center series of 283 patients transplanted for HCC between 1997 and 2009. Results. Five-year patient survival and RFS were 75% and 86%, respectively. Thirty-four (12% patients had HCC recurrence. Elevated preoperative alpha-fetoprotein (AFP levels, preoperative treatments of HCC, unfulfilled Milan and up-to-seven criteria at final histology, poor tumor differentiation, and tumor microvascular invasion negatively affected RFS by univariate analysis. Milan and up-to-seven criteria applied preoperatively, and the use of m-TOR inhibitors did not reach statistical significance. Cox's proportional hazard model showed that only elevated AFP levels (Odds Ratio=2.88; 95% C.I.=1.43–5.80; =.003, preoperative tumor treatments (Odds Ratio=4.84; 95% C.I.=1.42–16.42; =.01, and microvascular invasion (Odds Ratio=4.82; 95% C.I.=1.87–12.41; =.001 were predictors of lower RFS. Conclusions. Biological aggressiveness and preoperative tumor treatment, rather than traditional and expanded dimensional criteria, conditioned the outcomes in patients transplanted for HCC.

  3. Down-regulation of connective tissue growth factor by inhibition of transforming growth factor beta blocks the tumor-stroma cross-talk and tumor progression in hepatocellular carcinoma.

    Science.gov (United States)

    Mazzocca, Antonio; Fransvea, Emilia; Dituri, Francesco; Lupo, Luigi; Antonaci, Salvatore; Giannelli, Gianluigi

    2010-02-01

    Tumor-stroma interactions in hepatocellular carcinoma (HCC) are of key importance to tumor progression. In this study, we show that HCC invasive cells produce high levels of connective tissue growth factor (CTGF) and generate tumors with a high stromal component in a xenograft model. A transforming growth factor beta (TGF-beta) receptor inhibitor, LY2109761, inhibited the synthesis and release of CTGF, as well as reducing the stromal component of the tumors. In addition, the TGF-beta-dependent down-regulation of CTGF diminished tumor growth, intravasation, and metastatic dissemination of HCC cells by inhibiting cancer-associated fibroblast proliferation. By contrast, noninvasive HCC cells were found to produce low levels of CTGF. Upon TGF-beta1 stimulation, noninvasive HCC cells form tumors with a high stromal content and CTGF expression, which is inhibited by treatment with LY2109761. In addition, the acquired intravasation and metastatic spread of noninvasive HCC cells after TGF-beta1 stimulation was blocked by LY2109761. LY2109761 interrupts the cross-talk between cancer cells and cancer-associated fibroblasts, leading to a significant reduction of HCC growth and dissemination. Interestingly, patients with high CTGF expression had poor prognosis, suggesting that treatment aimed at reducing TGF-beta-dependent CTGF expression may offer clinical benefits. Taken together, our preclinical results indicate that LY2109761 targets the cross-talk between HCC and the stroma and provide a rationale for future clinical trials.

  4. Impact of hydrodynamic injection and phiC31 integrase on tumor latency in a mouse model of MYC-induced hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Lauren E Woodard

    2010-06-01

    Full Text Available Hydrodynamic injection is an effective method for DNA delivery in mouse liver and is being translated to larger animals for possible clinical use. Similarly, phiC31 integrase has proven effective in mediating long-term gene therapy in mice when delivered by hydrodynamic injection and is being considered for clinical gene therapy applications. However, chromosomal aberrations have been associated with phiC31 integrase expression in tissue culture, leading to questions about safety.To study whether hydrodynamic delivery alone, or in conjunction with delivery of phiC31 integrase for long-term transgene expression, could facilitate tumor formation, we used a transgenic mouse model in which sustained induction of the human C-MYC oncogene in the liver was followed by hydrodynamic injection. Without injection, mice had a median tumor latency of 154 days. With hydrodynamic injection of saline alone, the median tumor latency was significantly reduced, to 105 days. The median tumor latency was similar, 106 days, when a luciferase donor plasmid and backbone plasmid without integrase were administered. In contrast, when active or inactive phiC31 integrase and donor plasmid were supplied to the mouse liver, the median tumor latency was 153 days, similar to mice receiving no injection.Our data suggest that phiC31 integrase does not facilitate tumor formation in this C-MYC transgenic mouse model. However, in groups lacking phiC31 integrase, hydrodynamic injection appeared to contribute to C-MYC-induced hepatocellular carcinoma in adult mice. Although it remains to be seen to what extent these findings may be extrapolated to catheter-mediated hydrodynamic delivery in larger species, they suggest that caution should be used during translation of hydrodynamic injection to clinical applications.

  5. Editor's Highlight: Mode of Action Analysis for Rat Hepatocellular Tumors Produced by the Synthetic Pyrethroid Momfluorothrin: Evidence for Activation of the Constitutive Androstane Receptor and Mitogenicity in Rat Hepatocytes.

    Science.gov (United States)

    Okuda, Yu; Kushida, Masahiko; Sumida, Kayo; Nagahori, Hirohisa; Nakamura, Yoshimasa; Higuchi, Hashihiro; Kawamura, Satoshi; Lake, Brian G; Cohen, Samuel M; Yamada, Tomoya

    2017-08-01

    High dietary levels of momfluorothrin, a nongenotoxic synthetic pyrethroid, induced hepatocellular tumors in male and female Wistar rats in a 2-year bioassay. The mode of action (MOA) for rat hepatocellular tumors was postulated to occur via activation of the constitutive androstane receptor (CAR), as momfluorothrin is a close structural analogue of the pyrethroid metofluthrin, which is known to produce rat liver tumors through a CAR-mediated MOA. To elucidate the MOA for rat hepatocellular tumor formation by momfluorothrin, this study was conducted to examine effects on key and associative events of the CAR-mediated MOA for phenobarbital based on the International Programme on Chemical Safety framework. A 2-week in vivo study in Wistar rats revealed that momfluorothrin induced CYP2B activities, increased liver weights, produced hepatocyte hypertrophy and increased hepatocyte replicative DNA synthesis. These effects correlated with the dose-response relationship for liver tumor formation and also showed reversibility upon cessation of treatment. Moreover, momfluorothrin did not increase CYP2B1/2 mRNA expression and hepatocyte replicative DNA synthesis in CAR knockout rats. Using cultured Wistar rat hepatocytes and the RNA interference technique, knockdown of CAR resulted in a suppression of induction of CYP2B1/2 mRNA levels by momfluorothrin. Alternative MOAs for liver tumor formation were excluded. A global gene expression profile analysis of the liver of male Wistar rats treated with momfluorothrin for 2 weeks also showed similarity to the prototypic CAR activator phenobarbital. Overall, these data strongly support that the postulated MOA for momfluorothrin-induced rat hepatocellular tumors as being mediated by CAR activation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Sarcopenia Impairs Prognosis of Patients with Hepatocellular Carcinoma: The Role of Liver Functional Reserve and Tumor-Related Factors in Loss of Skeletal Muscle Volume.

    Science.gov (United States)

    Imai, Kenji; Takai, Koji; Watanabe, Satoshi; Hanai, Tatsunori; Suetsugu, Atsushi; Shiraki, Makoto; Shimizu, Masahito

    2017-09-22

    Sarcopenia impairs survival in patients with hepatocellular carcinoma (HCC). This study aimed to clarify the factors that contribute to decreased skeletal muscle volume in patients with HCC. The third lumbar vertebra skeletal muscle index (L3 SMI) in 351 consecutive patients with HCC was calculated to identify sarcopenia. Sarcopenia was defined as an L3 SMI value ≤ 29.0 cm²/m² for women and ≤ 36.0 cm²/m² for men. The factors affecting L3 SMI were analyzed by multiple linear regression analysis and tree-based models. Of the 351 HCC patients, 33 were diagnosed as having sarcopenia and showed poor prognosis compared with non-sarcopenia patients ( p = 0.007). However, this significant difference disappeared after the adjustments for age, sex, Child-Pugh score, maximum tumor size, tumor number, and the degree of portal vein invasion by propensity score matching analysis. Multiple linear regression analysis showed that age ( p = 0.015) and sex ( p < 0.0001) were significantly correlated with a decrease in L3 SMI. Tree-based models revealed that sex (female) is the most significant factor that affects L3 SMI. In male patients, L3 SMI was decreased by aging, increased Child-Pugh score (≥56 years), and enlarged tumor size (<56 years). Maintaining liver functional reserve and early diagnosis and therapy for HCC are vital to prevent skeletal muscle depletion and improve the prognosis of patients with HCC.

  7. Measurement of Thrombus Flux Using Transesophageal Echocardiography

    Science.gov (United States)

    Yamaguchi, Tadashi; Hirai, Kazuki; Aoki, Masami; Miyagi, Jin; Suzuki, Masahiko; Moriya, Hideshige; Hachiya, Hiroyuki

    2006-05-01

    Deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) are serious problem of total knee replacement (TKR). These diseases may be caused by a thrombus formed during the TKR operation. Therefore, understanding the flow volume of thrombus is important for curing and preventing PTE. In this paper, we tried to understanding the situation of the flow of thrombus by using transesophageal echocardiography movies. We applied the signal processing technique the FSET to extract the anomalous information from ultrasonic echo image. As a result of processing, the time change of the flow volume of thrombus was confirmed.

  8. Measurement of thrombus flux using transesophageal Echocardiography

    International Nuclear Information System (INIS)

    Yamaguchi, Tadashi; Hirai, Kazuki; Aoki, Masami; Miyagi, Jin; Suzuki, Masahiko; Moriya, Hideshige; Hachiya Hiroyuki

    2006-01-01

    Deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) are serious problem of total knee replacement (TKR). These diseases may be caused by a thrombus formed during the TKR operation. Therefore, understanding the flow volume of thrombus is important for curing and preventing PTE. In this paper, we tried to understanding the situation of the flow of thrombus by using transesophageal echocardiography movies. We applied the signal processing technique the fiber structure extraction technique (FSET) to extract the anomalous information from ultrasonic echo image. As a result of processing, the time change of the flow volume of thrombus was confirmed. (author)

  9. Evaluation of radiocolloids as thrombus imaging agents. Effect of particle size on thrombus uptake

    Energy Technology Data Exchange (ETDEWEB)

    Rosenthal, S.N.; Bardfeld, P.A.

    1985-01-01

    Thrombus uptake values of several /sup 99m/Tc labeled radiocolloids determined using an experimental rodent model of deep venous thrombosis were correlated with particle size distributions. The thrombus uptake values increased with increasing mean particle size. The /sup 99m/Tc-tin colloid had the highest thrombus uptake value of any of the colloids used in this study.

  10. Superparamagnetic iron oxide nanoparticles mediated 131I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice

    International Nuclear Information System (INIS)

    Chen, Jing; Zhu, Shu; Tong, Liangqian; Li, Jiansha; Chen, Fei; Han, Yunfeng; Zhao, Ming; Xiong, Wei

    2014-01-01

    Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 ( 131 I) against the human vascular endothelial growth factor (hVEGF). hVEGF siRNA was labeled with 131 I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131 I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131 I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment. 131 I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131 I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131 I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131 I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control. EMF-guided 131 I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131 I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging

  11. Effect of the pringle maneuver on tumor recurrence of hepatocellular carcinoma after curative resection (EPTRH): a randomized, prospective, controlled multicenter trial

    International Nuclear Information System (INIS)

    Xiaobin, Feng; Shuguang, Wang; Ping, Bie; Jiahong, Dong; Shuguo, Zheng; Jian, Zhou; Yudong, Qiu; Lijian, Liang; Kuansheng, Ma; Xiaowu, Li; Feng, Xia; Dong, Yi

    2012-01-01

    Hepatic resection is currently still the best choice of therapeutic strategies for liver cancer, but the long-term survival rate after surgery is unsatisfactory. Most patients develop intra- and/or extrahepatic recurrence. The reasons for this high recurrence rate are not entirely clear. Recent studies have indicated that ischemia-reperfusion injury to the liver may be a significant factor promoting tumor recurrence and metastasis in animal models. If this is also true in humans, the effects of the Pringle maneuver, which has been widely used in hepatectomy for the past century, should be examined. To date, there are no reported data or randomized controlled studies examining the relationship between use of the Pringle maneuver and local tumor recurrence. We hypothesize that the long-term prognosis of patients with liver cancer could be worsened by use of the Pringle maneuver due to an increase in the rate of tumor recurrence in the liver remnant. We designed a multicenter, prospective, randomized surgical trial to test this hypothesis. At least 498 eligible patients from five participating centers will be enrolled and randomized into either the Pringle group or the non-Pringle group in a ratio of 1:1 using a permuted-blocks randomization protocol. After the completion of surgical intervention, patients will be included in a 3-year follow-up program. This multicenter surgical trial will examine whether the Pringle maneuver has a negative effect on the long-term outcome of hepatocellular carcinoma patients. The trial will also provide information about prognostic differences, safety, advantages and disadvantages between Pringle and non-Pringle surgical procedures. Ultimately, the results will increase the available information about the effects of ischemia-reperfusion injury on tumor recurrence, which will be of immense benefit to general surgery.

  12. 6-Shogaol induces apoptosis in human hepatocellular carcinoma cells and exhibits anti-tumor activity in vivo through endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Rong Hu

    Full Text Available 6-Shogaol is an active compound isolated from Ginger (Zingiber officinale Rosc. In this work, we demonstrated that 6-shogaol induces apoptosis in human hepatocellular carcinoma cells in relation to caspase activation and endoplasmic reticulum (ER stress signaling. Proteomic analysis revealed that ER stress was accompanied by 6-shogaol-induced apoptosis in hepatocellular carcinoma cells. 6-shogaol affected the ER stress signaling by regulating unfolded protein response (UPR sensor PERK and its downstream target eIF2α. However, the effect on the other two UPR sensors IRE1 and ATF6 was not obvious. In prolonged ER stress, 6-shogaol inhibited the phosphorylation of eIF2α and triggered apoptosis in SMMC-7721 cells. Salubrinal, an activator of the PERK/eIF2α pathway, strikingly enhanced the phosphorylation of eIF2α in SMMC-7721 cells with no toxicity. However, combined treatment with 6-shogaol and salubrinal resulted in significantly increase of apoptosis and dephosphorylation of eIF2α. Overexpression of eIF2α prevented 6-shogaol-mediated apoptosis in SMMC-7721 cells, whereas inhibition of eIF2α by small interfering RNA markedly enhanced 6-shogaol-mediated cell death. Furthermore, 6-shogaol-mediated inhibition of tumor growth of mouse SMMC-7721 xenograft was associated with induction of apoptosis, activation of caspase-3, and inactivation of eIF2α. Altogether our results indicate that the PERK/eIF2α pathway plays an important role in 6-shogaol-mediated ER stress and apoptosis in SMMC-7721 cells in vitro and in vivo.

  13. In vivo prediction of anti-tumor effect of 3-bromopyruvate in hepatocellular carcinoma using Tc-99m labeled annexin-v imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won; Yoon, Jung Hwan; Kim, Chung Yang [Seoul National University College of Medicine, Seoul (Korea, Republic of); Cheon, Gi Jeoog; Lee, Tae Sup; Woo, Kwang Sun; Chung, Wee Sup [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2005-07-01

    We have recently demonstrated that hypoxia stimulates hepatocellular carcinoma (HCC) cell growth through hexokinase II induction, and its inhibition induces apoptotic cell death through activating mitochondrial apoptotic signaling cascades. In this study, we were apt to evaluate the antitumoral effect of 3-bromopyruvate (3-BP) on in vivo model of HCC by apoptotic imaging using Tc-99m labeled annexin V. In vivo model of HCC was established in C3H mice intradermally implanted with MH134 cells, a mouse HCC cell line, and 3-BP (0, 5, 10 mg/kg) was subsequently administered intraperitoneally. Tc-99m-HYNIC-annexin V (185 KBq) was injected via tail vein at one and three days after the 3-BP treatment, planar scan was acquired at a hour after the injection using gamma camera. The anti-tumor effect was evaluated by measuring tumor volumes and quantification of apoptotic cells using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Tumor volume was significantly reduced in mice treated with 3-BP in a dose-dependent manner (mean tumor volume 1.07 vs. 0.58 vs. 0.39 cm{sup 3} in 3-BP 0, 5, 10 mg/kg, respectively: p=0.047). The percentage of TUNEL staining-positive cells was significantly increased in 3-BP-treated mice (0.53 vs. 1.40 vs. 1.84% in 3-BP 0, 5, 10 mg/kg, respectively; p=0.018). On Tc-99m-HYNIC annexin V imaging, tumor-to-background uptake ratio (UR) was 1.92 at one day and 4.23 at three days after 3-BP treatment of 5 mg/kg (non-treated tumor showed UR of 2.93). Apoptosis-inducing anti-tumor effect of 3-BP was able to be demonstrated in in vivo model of HCC by apoptotic in vivo imaging using Tc-99m-HYNIC annexin V.

  14. In vivo prediction of anti-tumor effect of 3-bromopyruvate in hepatocellular carcinoma using Tc-99m labeled annexin-v imaging

    International Nuclear Information System (INIS)

    Kim, Won; Yoon, Jung Hwan; Kim, Chung Yang; Cheon, Gi Jeoog; Lee, Tae Sup; Woo, Kwang Sun; Chung, Wee Sup

    2005-01-01

    We have recently demonstrated that hypoxia stimulates hepatocellular carcinoma (HCC) cell growth through hexokinase II induction, and its inhibition induces apoptotic cell death through activating mitochondrial apoptotic signaling cascades. In this study, we were apt to evaluate the antitumoral effect of 3-bromopyruvate (3-BP) on in vivo model of HCC by apoptotic imaging using Tc-99m labeled annexin V. In vivo model of HCC was established in C3H mice intradermally implanted with MH134 cells, a mouse HCC cell line, and 3-BP (0, 5, 10 mg/kg) was subsequently administered intraperitoneally. Tc-99m-HYNIC-annexin V (185 KBq) was injected via tail vein at one and three days after the 3-BP treatment, planar scan was acquired at a hour after the injection using gamma camera. The anti-tumor effect was evaluated by measuring tumor volumes and quantification of apoptotic cells using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Tumor volume was significantly reduced in mice treated with 3-BP in a dose-dependent manner (mean tumor volume 1.07 vs. 0.58 vs. 0.39 cm 3 in 3-BP 0, 5, 10 mg/kg, respectively: p=0.047). The percentage of TUNEL staining-positive cells was significantly increased in 3-BP-treated mice (0.53 vs. 1.40 vs. 1.84% in 3-BP 0, 5, 10 mg/kg, respectively; p=0.018). On Tc-99m-HYNIC annexin V imaging, tumor-to-background uptake ratio (UR) was 1.92 at one day and 4.23 at three days after 3-BP treatment of 5 mg/kg (non-treated tumor showed UR of 2.93). Apoptosis-inducing anti-tumor effect of 3-BP was able to be demonstrated in in vivo model of HCC by apoptotic in vivo imaging using Tc-99m-HYNIC annexin V

  15. Blocking Tim-3 or/and PD-1 reverses dysfunction of tumor-infiltrating lymphocytes in HBV-related hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Furong; Zeng, Gucheng; Zhou, Shaotang; He, Xiaoshun; Sun, Nianfeng; Zhu, Xiaofeng; Hu, Anbin

    2018-03-22

    The immunosuppression of tumor-infiltrating lymphocytes (TILs) is associated with rapid progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3) and programmed cell death 1 (PD-1) are important inhibitory molecules expressed on the surface of T cells, but their roles in the function of TILs in HBV-HCC are poorly understood. We aimed to study the roles of these two markers in HBV-HCC. Ninety patients with pathologically confirmed HBV-associated HCC were enrolled in our study. Blood samples, paired fresh tumor tissues and adjacent tissues were collected, and isolating peripheral blood mononuclear cells, TILs and adjacent-infiltrating lymphocytes were isolated from these samples. The patients were followed-up to allow survival analysis. Tim-3 or/and PD-1 was up-regulated expressed on CD4 + and CD8 + TILs in HBV-HCC patients and a higher proportion of TILs expressed PD-1 alone. Tim-3 + and PD-1 + TILs greatly decreased secretion of IFN-γ and TNF-α. Expression of Tim-3 and PD-1 on TILs negatively correlated with disease-free survival of HCC patients. Direct blockade of Tim-3 and PD-1 in vitro significantly enhanced TILs proliferation and secretion of IFN-γ and TNF-α. Expression of Tim-3 and/or PD-1 on TILs impairs their function and correlates negatively with disease-free survival in HBV-HCC. Direct blockade of Tim-3 and PD-1 restores anti-tumor effects of TILs, which suggests a potential target for novel immunotherapy in HBV-HCC. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  16. A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Abei, Masato; Mizumoto, Masashi; Sakae, Takeji; Sakurai, Hideyuki; Zenkoh, Junko; Ariungerel, Gerelchuluun; Sogo, Yu; Ito, Atsuo; Ohno, Tadao; Tsuboi, Koji; Okumura, Toshiyuki; Fukuda, Kuniaki; Hashimoto, Takayuki; Araki, Masahiro; Ishige, Kazunori; Hyodo, Ichinosuke; Kanemoto, Ayae; Numajiri, Haruko

    2013-01-01

    Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored. To prevent the HCC recurrence, we here report on a prospective phase I study of ‘in situ’ tumor vaccination using CalTUMP, a newly developed immunoadjuvant consisting of BCG extract bound to hydroxyapatite and microparticulated tuberculin, following local PBT for HCC. Patients with locally advanced recurrent HCC, which had been heavily pretreated with various treatments, were enrolled. PBT was performed with the conventional method to the target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and 1/1) were administered to 3 patients each. Vital signs, blood samples, ultrasound, and computed tomographic scans were monitored to evaluate the safety. Three intratumoral injections of CalTUMP following PBT (median dose: 72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor laboratory changes were observed in 7 patients after CalTUMP injections. No other treatment-related adverse events were observed. Median progression-free survival was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more than 1 year. Intratumoral injection of CalTUMP following PBT was feasible and safe in patients with heavily pre-treated HCC. Further clinical studies to evaluate the efficacy of this in situ tumor vaccination are warranted

  17. Preoperative Chemoembolization in Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation: Influence of Emergent Versus Elective Procedures on Patient Survival and Tumor Recurrence Rate

    International Nuclear Information System (INIS)

    Stockland, A. H.; Walser, E. M.; Paz-Fumagalli, R.; McKinney, J. M.; May, G. R.

    2007-01-01

    Our purpose was to compare the recurrence rate and survival in patients with hepatocellular carcinoma (HCC) who had elective transarterial chemoembolization (TACE), immediate preoperative TACE, or no treatment prior to orthotopic liver transplantation (OLT). A total of 132 patients with HCC had TACE prior to OLT. Eighteen patients had no TACE before OLT and functioned as a control group. The urgent group included 35 patients embolized less than 24 h before OLT and the elective group included 97 patients embolized greater than 1 day before transplantation. These groups were compared with regard to tumor staging, hepatic synthetic function, and post-TACE tumor necrosis and survival and recurrence rates.Patients were followed for a mean of 780 days post OLT (1-2912 days). The tumor staging was similar between groups but the Childs-Pugh score in the urgent and untreated group was significantly higher than that of the other groups. The degree of necrosis at explant was also significantly different between the two treated groups, with an average 35% necrosis in the patients embolized less than 24 h before OLT vs 77% in the elective group (p < 0.002). Recurrence rate in the urgent group was 8 of 35 (23%) in a median of 580 days, 20 of 97 (21%) in a median of 539 days in the elective group, and 2 of 18 (11%) in a median of 331 days in the no-TACE group. Survival at 1, 3, and 5 years was 91%, 80%, and 72% in the elective group, 79%, 58%, and 39% in the urgent group, and 69%, 61%, and 41% in the no-TACE group, respectively. The urgent and no-TACE groups had significantly worse survival compared with the other groups; however, the tumor recurrence rates were statistically the same among all three groups. TACE within 24 h of OLT causes an average of 35% necrosis and elective TACE increases necrosis further to 77%. Despite this difference, the tumor recurrence rate in the three groups is equivalent and no different from that in the group that received no treatment before OLT

  18. Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available It has been reported that Annexin A2 (ANXA2 is up-regulated in hepatocellular carcinoma (HCC, but the roles of ANXA2 in the migration and invasion of HCC cells have not been determined. In this study, we found that ANXA2-specific siRNA (si-ANXA2 significantly inhibited the migration and invasion of HCC cells co-cultured with fibroblasts in vitro. In addition, the production of MMP-2 by fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells was notably down-regulated. ANXA2 was also found to be co-localized and co-immunoprecipitated with CD147. Further investigation revealed that the expression of ANXA2 in HCC cells affected the shedding of CD147-harboring membrane microvesicles, acting as a vehicle for CD147 in tumor-stromal interactions and thereby regulating the production of MMP-2 by fibroblasts. Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulating the trafficking of CD147-harboring membrane microvesicles.

  19. CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1–Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma

    DEFF Research Database (Denmark)

    Engelholm, Lars H.; Riaz, Anjum; Serra, Denise

    2017-01-01

    Background & Aims Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects children and young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene...... (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1–PRKACA gene fusion has not been shown to induce liver tumorigenesis. We used the CRISPR/Cas9 technique to delete in mice the syntenic region...... on chromosome 8 to create a Dnajb1–Prkaca fusion and monitored the mice for liver tumor development. Methods We delivered CRISPR/Cas9 vectors designed to juxtapose exon 1 of Dnajb1 with exon 2 of Prkaca to create the Dnajb1–Prkaca gene fusion associated with FL-HCC, or control Cas9 vector, via hydrodynamic tail...

  20. Superior Venacava Thrombus-A Case Report

    Directory of Open Access Journals (Sweden)

    Bijay Sah

    2016-03-01

    Full Text Available Superior venacava (SVC thrombus is a condition requiring immediate diagnosis and treatment. SVC thrombus causes obstruction of blood flow through the SVC resulting in severe decrease in venous return from the head, neck and upper extremity to the heart. The presenting symptoms of SVC obstruction include headache, hoarseness of voice, dyspnea, and laryngeal edema, dizziness, swelling of face, neck, and upper extremity. We hereby present a case of SVC thrombus who presented to the casualty department of COMS-TH with features of SVC syndrome which was diagnosed and managed promptly.JCMS Nepal. 2016;12(1:33-5.

  1. The value of emergency CT studies in spontaneous rupture of hepatocellular carcinoma. Analysis for tumor protrusion and hemorrhagic ascites

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, Makiko; Kobayashi, Hisashi; Ichikawa, Taro; Cho, Keiichi; Gemma, Kazuhito; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan)

    1997-12-01

    CT characteristics of spontaneous rupture of HCC (n=13) were reviewed retrospectively, and the value of emergency CT studies in this disease was evaluated. Especially, tumor protrusion ratio (TPR) and ascitic CT numbers were measured to for comparison with the data for unruptured HCCs and ordinary, (e.g., non-hemorrhagic) ascites (n=13). As a result, except for diffuse type HCCs, the TPR was significantly higher than for the unruptured HCCs. Nine cases had intraperitoneal HDAs, and the laterality of the HDAs corresponded with that of the ruptured tumors in 8 cases. Also, the ascitic CT numbers apart from the HDA were still higher than the ordinary ascites. Therefore, a high TPR, HDAs adjacent to the tumor, and elevated ascitic CT numbers are important CT manifestations indicating HCC rupture. Diffuse HCCs, however, require careful clinical evaluation. (author)

  2. The value of emergency CT studies in spontaneous rupture of hepatocellular carcinoma. Analysis for tumor protrusion and hemorrhagic ascites

    International Nuclear Information System (INIS)

    Ishihara, Makiko; Kobayashi, Hisashi; Ichikawa, Taro; Cho, Keiichi; Gemma, Kazuhito; Kumazaki, Tatsuo

    1997-01-01

    CT characteristics of spontaneous rupture of HCC (n=13) were reviewed retrospectively, and the value of emergency CT studies in this disease was evaluated. Especially, tumor protrusion ratio (TPR) and ascitic CT numbers were measured to for comparison with the data for unruptured HCCs and ordinary, (e.g., non-hemorrhagic) ascites (n=13). As a result, except for diffuse type HCCs, the TPR was significantly higher than for the unruptured HCCs. Nine cases had intraperitoneal HDAs, and the laterality of the HDAs corresponded with that of the ruptured tumors in 8 cases. Also, the ascitic CT numbers apart from the HDA were still higher than the ordinary ascites. Therefore, a high TPR, HDAs adjacent to the tumor, and elevated ascitic CT numbers are important CT manifestations indicating HCC rupture. Diffuse HCCs, however, require careful clinical evaluation. (author)

  3. Branched-Chain Amino Acids Ameliorate Fibrosis and Suppress Tumor Growth in a Rat Model of Hepatocellular Carcinoma with Liver Cirrhosis

    Science.gov (United States)

    Cha, Jung Hoon; Bae, Si Hyun; Kim, Hye Lim; Park, Na Ri; Choi, Eun Suk; Jung, Eun Sun; Choi, Jong Young; Yoon, Seung Kew

    2013-01-01

    Purpose Recent studies have revealed that branched-chain amino acids (BCAA) reduce the development of hepatocellular carcinoma (HCC) in patients with obesity and hepatitis C virus infection by improving insulin resistance (IR). The aim of this study was to examine the anti-cancer and anti-fibrotic effects of BCAA on the development of diethylnitrosamine (DEN)-induced HCC and liver cirrhosis in a rat model. Methods Male SD rats received weekly intraperitoneal injections of DEN (50 mg/kg of body weight) for 16 weeks to induce HCC. They were fed a diet containing 3% casein, 3% or 6% BCAA for 13 weeks beginning 6 weeks after DEN administration. DEN was used to induce HCC through stepwise development from cirrhosis to HCC. The effect of BCAA was evaluated in tumor tissues by histopathologic analyses, reverse transcription-polymerase chain reaction, and Western blotting. Results The mean area and number of dysplastic nodules (DNs) and tumors in the casein group tended to be larger than those in the BCAA group 16 weeks after DEN administration. The mean fibrotic area in the BCAA group was smaller than that in the casein group. The BCAA group showed decreased mRNA levels for markers of fibrosis, angiogenesis, and apoptosis inhibition. Compared with the casein group, the BCAA group had lower levels of α-smooth muscle actin, vascular endothelial growth factor, p-β-catenin, p-p38 mitogen-activated protein kinase, proliferating cell nuclear antigen, and caspase-3 protein expression, as well as a higher level of cleaved caspase-3 protein expression. Conclusions BCAA supplementation of the diet ameliorated liver fibrosis and HCC development in a DEN-induced rat model of HCC with liver cirrhosis, but not in the IR model. These results provide a rationale for anti-fibrosis and chemoprevention using BCAA treatment for HCC with liver cirrhosis, as well as decreasing the ammonia level. PMID:24223741

  4. Branched-chain amino acids ameliorate fibrosis and suppress tumor growth in a rat model of hepatocellular carcinoma with liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Jung Hoon Cha

    Full Text Available PURPOSE: Recent studies have revealed that branched-chain amino acids (BCAA reduce the development of hepatocellular carcinoma (HCC in patients with obesity and hepatitis C virus infection by improving insulin resistance (IR. The aim of this study was to examine the anti-cancer and anti-fibrotic effects of BCAA on the development of diethylnitrosamine (DEN-induced HCC and liver cirrhosis in a rat model. METHODS: Male SD rats received weekly intraperitoneal injections of DEN (50 mg/kg of body weight for 16 weeks to induce HCC. They were fed a diet containing 3% casein, 3% or 6% BCAA for 13 weeks beginning 6 weeks after DEN administration. DEN was used to induce HCC through stepwise development from cirrhosis to HCC. The effect of BCAA was evaluated in tumor tissues by histopathologic analyses, reverse transcription-polymerase chain reaction, and Western blotting. RESULTS: The mean area and number of dysplastic nodules (DNs and tumors in the casein group tended to be larger than those in the BCAA group 16 weeks after DEN administration. The mean fibrotic area in the BCAA group was smaller than that in the casein group. The BCAA group showed decreased mRNA levels for markers of fibrosis, angiogenesis, and apoptosis inhibition. Compared with the casein group, the BCAA group had lower levels of α-smooth muscle actin, vascular endothelial growth factor, p-β-catenin, p-p38 mitogen-activated protein kinase, proliferating cell nuclear antigen, and caspase-3 protein expression, as well as a higher level of cleaved caspase-3 protein expression. CONCLUSIONS: BCAA supplementation of the diet ameliorated liver fibrosis and HCC development in a DEN-induced rat model of HCC with liver cirrhosis, but not in the IR model. These results provide a rationale for anti-fibrosis and chemoprevention using BCAA treatment for HCC with liver cirrhosis, as well as decreasing the ammonia level.

  5. Higher proliferation of peritumoral endothelial cells to IL-6/sIL-6R than tumoral endothelial cells in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhuang, Peng-Yuan; Wang, Jian-Dong; Tang, Zhao-Hui; Zhou, Xue-Ping; Quan, Zhi-Wei; Liu, Ying-Bin; Shen, Jun

    2015-01-01

    This study aimed to explore the responses to the interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) complex in peritumoral endothelial cells (PECs) and tumor endothelial cells (TECs), as well as determine the signaling pathways in the angiogenesis of hepatocellular carcinoma (HCC). The expression of IL-6, IL-6R, gp130, CD68, HIF-1α, and microvessel density (MVD) were assessed with an orthotopic xenograft model in nude mice. ECs were incubated under hypoxic conditions to detect IL-6 and gp130. The proliferation of PECs and TECs in the presence of IL-6 and sIL-6R, as well as the expression of gp130, JAK2/STAT3, PI3K/AKT in endothelial cells were measured. Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth. Hypoxia could directly induce IL-6 expression, but not gp130 in PECs. The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT. PECs exhibited higher proliferation in response to IL-6/sIL-6R co-treatment compared with TECs in HCC via the up-regulation of gp130 /JAK2/STAT3. PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment. The online version of this article (doi:10.1186/s12885-015-1763-2) contains supplementary material, which is available to authorized users

  6. Evaluation of tumor response to intra-arterial chemoembolization of hepatocellular carcinoma: Comparison of contrast-enhanced ultrasound with multiphase computed tomography.

    Science.gov (United States)

    Paul, S B; Dhamija, E; Gamanagatti, S R; Sreenivas, V; Yadav, D P; Jain, S; Shalimar; Acharya, S K

    2017-03-01

    To compare the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) with that of multiphase computed tomography (CT) in the evaluation of tumor response to transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). Fifty patients (41 men, 9 women; mean age, 53 years±12.5 [SD]) with a total of 70 HCCs (mean size, 5cm±3 [SD]) were evaluated. Post-TACE therapeutic assessment of HCC was done at 4 weeks. Patients with TACE done earlier and reporting with suspicion for recurrence were also included. Patients with hepatic masses seen on ultrasound were enrolled and subjected to CEUS, multiphase CT and magnetic resonance imaging (MRI). Hyperenhancing area at the tumor site on arterial phase of CEUS/multiphase CT/MRI was termed as residual disease (RD), the patterns of which were described on CEUS. Diagnostic accuracies of CEUS and MPCT were compared to that of MRI that was used as the reference standard. CEUS detected RD in 43/70 HCCs (61%). RD had a heterogeneous pattern in 22/43 HCCs (51%). Sensitivities of CEUS and multiphase CT were 94% (34/36; 95% CI: 81-99%) and 50% (18/36; 95% CI: 33-67%) respectively. Significant difference in sensitivity was found between CEUS and multiphase CT (P=0.0001). CEUS and multiphase CT had 100% specificity (95% CI: 83-100%). CEUS is a useful technique for detecting RD in HCC after TACE. For long term surveillance, CEUS should be complemented with multiphase CT/MRI for a comprehensive evaluation. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  7. Transcatheter arterial chemoembolization of hepatocellular carcinoma with portal vein invasion

    International Nuclear Information System (INIS)

    Lee, Young Rahn; Lee, Ki Yeol; Cho, Seong Beom; Cha, In Ho; Chung, Kyoo Byung

    1993-01-01

    Transcatheter arterial chemoembolization(TACE) is an imperative method for the management of inoperable hepatocellular carcinoma(HCC). It is well known that primary HCC frequently invades the portal venous system and forms a tumor thrombus obstructing the portal blood flow which makes unfavorable prognosis of patient. We retrospectively reviewed 58 patients who reviewed TACE(minimum 3 times) of HCC invading into portal venous system. Group 1(n=29) which showed peripheral portal vein invasion had better clinical and laboratory response. Group 2(n=17) which showed first order portal branch invasion had similar response to Group 3(n=12), which had main portal invasion. Group 1 showed no difference in survival time between TAC and TACE, but, in Group 2 and 3, embolization with chemotherapy made longer survival than chemotherapy only. Clinical level of AFP was meaningful in Group 1 and 2 as decreasing value. Our results provides that careful selection of TAE and case by case Coil/Gelfoam embolization can improve the mean survival and clinical response when HCC evidently invades portal venous system

  8. Mir-452-3p: A Potential Tumor Promoter That Targets the CPEB3/EGFR Axis in Human Hepatocellular Carcinoma

    Science.gov (United States)

    Tang, Hui; Zhang, Jianwen; Yu, Zhenyu; Ye, Linsen; Li, Kun; Ding, Fan; Feng, Xiao

    2017-01-01

    Purpose: We proposed to investigate the effects of miR-452-3p on the proliferation and mobility of hepatocellular carcinoma (HCC) cells by targeting cytoplasmic polyadenylation element binding protein 3/estimated glomerular filtration rate (CPEB3/EGFR) axis. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-452-3p expression in 84 pairs of HCC tissues and adjacent tissues. Luciferase reporter assay was employed to examine the relationship between miR-452-3p and CPEB3. Microculture tetrazolium (MTT) assay, colony formation assay, flow cytometry detection, wound healing assay, and transwell assay were used to detect cell proliferation, cycle arrest, apoptosis, and mobility, respectively, in HCC, HepG2, and Huh-7. Western blot was used to detect protein expression levels in EGFR signaling pathway. Kaplan-Meier survival analysis was conducted to analyze the correlation between the miR-452-3p and CPEB3 expression levels and the survival of patients with HCC. Results: MiRNA-452-3p was found significantly upregulated in 84 human HCC sample tissues and cells in comparison with adjacent tissues and normal liver epithelial cells (P < .01). Luciferase reporter assay demonstrated that CPEB3 was a direct target of miR-452-3p. Overexpression of miR-452-3p promoted cell proliferation and mobility and suppressed apoptosis. MiR-452-3p enhanced EGFR and phosphorylated AKT (pAKT) expression but inhibited p21 expression level. Conclusion: MiR-452-3p promoted HCC cell proliferation and mobility by directly targeting the CPEB3/EGFR axis. PMID:29332449

  9. 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.

  10. Thrombus Formation at High Shear Rates.

    Science.gov (United States)

    Casa, Lauren D C; Ku, David N

    2017-06-21

    The final common pathway in myocardial infarction and ischemic stroke is occlusion of blood flow from a thrombus forming under high shear rates in arteries. A high-shear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood. Thrombosis at high shear rates depends primarily on the long protein von Willebrand factor (vWF) and platelets, with hemodynamics playing an important role in each stage of thrombus formation, including vWF binding, platelet adhesion, platelet activation, and rapid thrombus growth. The prediction of high-shear thrombosis is a major area of biofluid mechanics in which point-of-care testing and computational modeling are promising future directions for clinically relevant research. Further research in this area will enable identification of patients at high risk for arterial thrombosis, improve prevention and treatment based on shear-dependent biological mechanisms, and improve blood-contacting device design to reduce thrombosis risk.

  11. 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...

  12. Antibody-targeted thrombus imaging and thrombolysis

    International Nuclear Information System (INIS)

    Wu Guoxin; Ruan Changgeng

    1993-05-01

    In respect of thrombus imaging, the femoral arterial or venous thrombus model was prepared in dogs and imaged with single photon emission computerized tomography (SPECT). After 4 hours of injection of 131 I-SZ-51 the radioactivity ratio between thrombus and blood (T/B) was 18 : 1 and 8 : 1 for arterial and venous thrombus respectively. The result conformed with the T/B ratio of the removed thrombus and blood after 24 hours of injection of radiotracer. It indicates that the McAb SZ-51 has a great potential to bind with thrombus. In respect of thrombolysis, the Fab(fragment, antigen-binding) fragment of McAb SZ-51 was chemically conjugated of urokinase (UK) by the disulfide-linking reagent SPDP and 2-iminothiolane. The resulting conjugate was 3 to 5 times as potent as UK in vitro in human platelet-rich plasma assay. The increase of fibrinolytic potency was accompanied by a decrease of consumption of plasminogen and fibrinogen. It shows that the increase of potency is the result of selectivity increase

  13. Multi-Constituent Simulation of Thrombus Deposition.

    Science.gov (United States)

    Wu, Wei-Tao; Jamiolkowski, Megan A; Wagner, William R; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F

    2017-02-20

    In this paper, we present a spatio-temporal mathematical model for simulating the formation and growth of a thrombus. Blood is treated as a multi-constituent mixture comprised of a linear fluid phase and a thrombus (solid) phase. The transport and reactions of 10 chemical and biological species are incorporated using a system of coupled convection-reaction-diffusion (CRD) equations to represent three processes in thrombus formation: initiation, propagation and stabilization. Computational fluid dynamic (CFD) simulations using the libraries of OpenFOAM were performed for two illustrative benchmark problems: in vivo thrombus growth in an injured blood vessel and in vitro thrombus deposition in micro-channels (1.5 mm × 1.6 mm × 0.1 mm) with small crevices (125 μm × 75 μm and 125 μm × 137 μm). For both problems, the simulated thrombus deposition agreed very well with experimental observations, both spatially and temporally. Based on the success with these two benchmark problems, which have very different flow conditions and biological environments, we believe that the current model will provide useful insight into the genesis of thrombosis in blood-wetted devices, and provide a tool for the design of less thrombogenic devices.

  14. Multi-Constituent Simulation of Thrombus Deposition

    Science.gov (United States)

    Wu, Wei-Tao; Jamiolkowski, Megan A.; Wagner, William R.; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F.

    2017-02-01

    In this paper, we present a spatio-temporal mathematical model for simulating the formation and growth of a thrombus. Blood is treated as a multi-constituent mixture comprised of a linear fluid phase and a thrombus (solid) phase. The transport and reactions of 10 chemical and biological species are incorporated using a system of coupled convection-reaction-diffusion (CRD) equations to represent three processes in thrombus formation: initiation, propagation and stabilization. Computational fluid dynamic (CFD) simulations using the libraries of OpenFOAM were performed for two illustrative benchmark problems: in vivo thrombus growth in an injured blood vessel and in vitro thrombus deposition in micro-channels (1.5 mm × 1.6 mm × 0.1 mm) with small crevices (125 μm × 75 μm and 125 μm × 137 μm). For both problems, the simulated thrombus deposition agreed very well with experimental observations, both spatially and temporally. Based on the success with these two benchmark problems, which have very different flow conditions and biological environments, we believe that the current model will provide useful insight into the genesis of thrombosis in blood-wetted devices, and provide a tool for the design of less thrombogenic devices.

  15. MicroRNA-219-5p Promotes Tumor Growth and Metastasis of Hepatocellular Carcinoma by Regulating Cadherin 1

    Directory of Open Access Journals (Sweden)

    Jing Yang

    2018-01-01

    Full Text Available MicroRNAs play significant roles in the development of cancer and may serve as promising therapeutic targets. In our previous work, miR-219-5p was identified as one of the important metastasis-related microRNAs in HCC. Here we demonstrated that miR-219-5p expression was elevated in HCC tissues and was associated with vascular invasion and dismal prognosis. In multivariate analysis, miR-219-5p was identified as an independent prognostic indicator for HCC patients. Functional mechanism analyses showed that miR-219-5p promoted HCC cell proliferation and invasion in in vitro, as well as in vivo, tumor growth and metastasis in nude mice models bearing human HCC tumors. In addition, cadherin 1 (CDH1 was revealed to be a downstream target of miR-219-5p in HCC cells. In conclusion, miR-219-5p promotes tumor growth and metastasis of HCC by regulating CDH1 and can serve as a prognostic marker for HCC patients.

  16. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hu, Bo; Sun, Ding; Sun, Chao; Sun, Yun-Fan; Sun, Hai-Xiang; Zhu, Qing-Feng; Yang, Xin-Rong; Gao, Ya-Bo; Tang, Wei-Guo; Fan, Jia; Maitra, Anirban

    2015-01-01

    Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. - Highlights: • Polymeric nanoparticle formulation of curcumin not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. • In combination with sorafenib, NanoCurcumin induced HCC cell apoptosis and cell cycle arrest. • NanoCurcumin and

  17. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Bo [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Sun, Ding [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Department of Hepatobiliary Surgery, First Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Sun, Chao; Sun, Yun-Fan; Sun, Hai-Xiang [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Zhu, Qing-Feng [The Johns Hopkins University School of Medicine, Division of Gastrointestinal and Liver Pathology, Baltimore, MD, 21205 (United States); Institute of Biomedical Sciences, Fudan University, Shanghai, 200032 (China); Yang, Xin-Rong [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Gao, Ya-Bo [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032 (China); Tang, Wei-Guo [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Fan, Jia [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Institute of Biomedical Sciences, Fudan University, Shanghai, 200032 (China); Maitra, Anirban [The Sol Goldman Pancreatic Cancer Research Center, Departments of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States); and others

    2015-12-25

    Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. - Highlights: • Polymeric nanoparticle formulation of curcumin not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. • In combination with sorafenib, NanoCurcumin induced HCC cell apoptosis and cell cycle arrest. • NanoCurcumin and

  18. 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...

  19. Preoperative neutrophil-lymphocyte ratio is an independent prognostic factor for hepatocellular carcinoma after radical resection

    Directory of Open Access Journals (Sweden)

    ZHANG Tingting

    2015-06-01

    Full Text Available ObjectiveTo evaluate the effect and predictive value of preoperative neutrophil-lymphocyte ratio (NLR on the prognosis of patients undergoing radical resection for hepatocellular carcinoma (HCC. MethodsThe clinical data of 245 patients who received radical resection for HCC in our hospital from 2004 to 2009 were retrospectively analyzed. The effects of clinicopathological parameters including NLR on overall survival (OS time were assessed by univariate analysis using the log-rank test. The significant variables were further analyzed by multivariate analysis using the Cox regression model. ResultsUsing NLR=1.5, 2, and 3 as cut-off points, the patients were divided into four groups. The median OS time in groups with NLR<1.5, 1.5≤NLR<2, 2≤NLR<3, and NLR≥3 was 39.6, 38.3, 25.4, and 19.9 months, respectively (P=0.003. Multivariate analysis showed that preoperative NLR, levels of alpha-fetoprotein and alanine aminotransferase in peripheral blood, number of tumor nodules, maximum size of tumor, and portal vein tumor thrombus were independent prognostic factors for HCC (P<0.05. ConclusionPreoperative NLR in peripheral blood is a novel prognostic biomarker for HCC after radical resection.

  20. Activity-based cost analysis of hepatic tumor ablation using CT-guided high-dose rate brachytherapy or CT-guided radiofrequency ablation in hepatocellular carcinoma.

    Science.gov (United States)

    Schnapauff, D; Collettini, F; Steffen, I; Wieners, G; Hamm, B; Gebauer, B; Maurer, M H

    2016-02-25

    To analyse and compare the costs of hepatic tumor ablation with computed tomography (CT)-guided high-dose rate brachytherapy (CT-HDRBT) and CT-guided radiofrequency ablation (CT-RFA) as two alternative minimally invasive treatment options of hepatocellular carcinoma (HCC). An activity based process model was created determining working steps and required staff of CT-RFA and CT-HDRBT. Prorated costs of equipment use (purchase, depreciation, and maintenance), costs of staff, and expenditure for disposables were identified in a sample of 20 patients (10 treated by CT-RFA and 10 by CT-HDRBT) and compared. A sensitivity and break even analysis was performed to analyse the dependence of costs on the number of patients treated annually with both methods. Costs of CT-RFA were nearly stable with mean overall costs of approximately 1909 €, 1847 €, 1816 € and 1801 € per patient when treating 25, 50, 100 or 200 patients annually, as the main factor influencing the costs of this procedure was the single-use RFA probe. Mean costs of CT-HDRBT decreased significantly per patient ablation with a rising number of patients treated annually, with prorated costs of 3442 €, 1962 €, 1222 € and 852 € when treating 25, 50, 100 or 200 patients, due to low costs of single-use disposables compared to high annual fix-costs which proportionally decreased per patient with a higher number of patients treated annually. A break-even between both methods was reached when treating at least 55 patients annually. Although CT-HDRBT is a more complex procedure with more staff involved, it can be performed at lower costs per patient from the perspective of the medical provider when treating more than 55 patients compared to CT-RFA, mainly due to lower costs for disposables and a decreasing percentage of fixed costs with an increasing number of treatments.

  1. miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Jian [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Qu, Shuping [Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Li, Xiaowei; Zhong, Jiaming; Chen, Xiaoxia [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Qu, Zengqiang, E-mail: drquzengqiang@163.com [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Wu, Dong, E-mail: wudongstc@126.com [Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China)

    2015-08-14

    Emerging evidence suggests that microRNAs (miRNAs) play important roles in regulating HCC development and progression; however, the mechanisms by which their specific functions and mechanisms remained to be further explored. miR-129 has been reported in gastric cancers, lung cancer and colon cancer. In this study, we disclosed a new tumor suppresser function of miR-129 in HCC. We also found the downregulation of miR-129 occurred in nearly 3/4 of the tumors examined (56/76) compared with adjacent nontumorous tissues, which was more importantly, correlated to the advanced stage and vascular invasion. We then demonstrated that miR-129 overexpression attenuated HCC cells proliferation and invasion, inducing apoptosis in vitro. Moreover, we used miR-129 antagonist and found that anti-miR-129 promoted HCC cells malignant phenotypes. Mechanistically, our further investigations revealed that miR-129 suppressed cell proliferation and invasion by targeting the 3’-untranslated region of PAK5, as well as miR-129 silencing up-regulated PAK5 expression. Moreover, miR-129 expression was inversely correlated with PAK5 expression in 76 cases of HCC samples. RNA interference of PAK5 attenuated anti-miR-129 mediated cell proliferation and invasion in HCC cells. Taken together, these results demonstrated that miR-129 suppressed tumorigenesis and progression by directly targeting PAK5, defining miR-129 as a potential treatment target for HCC. - Highlights: • Decreased of miR-129 is found in HCC and associated with advanced stage and metastasis. • miR-129 suppresses proliferation and invasion of HCC cells. • miR-129 directly targets the 3′ UTR of PAK5 and diminishes PAK5 expression. • PAK5 is involved in miR-129 mediated suppression functions.

  2. Tumor-adjacent tissue co-expression profile analysis reveals pro-oncogenic ribosomal gene signature for prognosis of resectable hepatocellular carcinoma.

    Science.gov (United States)

    Grinchuk, Oleg V; Yenamandra, Surya P; Iyer, Ramakrishnan; Singh, Malay; Lee, Hwee Kuan; Lim, Kiat Hon; Chow, Pierce Kah-Hoe; Kuznetsov, Vladamir A

    2018-01-01

    Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT) and adjacent non-malignant tissues (AT) typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods. We developed a 24-ribosomal gene-based HCC classifier (RGC), which is prognostically significant in both PT and AT. The RGC gene overexpression in PT was associated with a poor prognosis in the training (hazard ratio = 8.2, P = 9.4 × 10 -6 ) and cross-cohort validation (hazard ratio = 2.63, P = 0.004) datasets. The multivariate survival analysis demonstrated the significant and independent prognostic value of the RGC. The RGC displayed a significant prognostic value in AT of the training (hazard ratio = 5.0, P = 0.03) and cross-validation (hazard ratio = 1.9, P = 0.03) HCC groups, confirming the accuracy and robustness of the RGC. Our experimental and bioinformatics analyses suggested a key role for c-MYC in the pro-oncogenic pattern of ribosomal biogenesis co-regulation in PT and AT. Microarray, quantitative RT-PCR and quantitative immunohistochemical studies of the PT showed that DKK1 in PT is the perspective biomarker for poor HCC outcomes. The common co-transcriptional pattern of ribosome biogenesis genes in PT and AT from HCC patients suggests a new scalable prognostic system, as supported by the model of tumor-like metabolic redirection/assimilation in non-malignant AT. The RGC, comprising 24 ribosomal genes, is introduced as a robust and reproducible prognostic model for

  3. 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)

  4. 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

  5. Hypoxia-inducible factor-1α mediates the toll-like receptor 4 signaling pathway leading to anti-tumor effects in human hepatocellular carcinoma cells under hypoxic conditions.

    Science.gov (United States)

    Zhang, Xiaoyu; Li, Shuchen; Li, Mingrong; Huang, Haiying; Li, Jingyuan; Zhou, Changwei

    2016-08-01

    Hypoxia-inducible factor-1α (HIF-1α) and toll-like receptor 4 (TLR4) are involved in numerous mechanisms of cancer biology, including cell proliferation and survival; however the interaction of the two factors under hypoxic conditions remains unclear. The present study investigated the in vitro mechanism that results in the suppression of tumor cell growth and cellular functions when HIF-1α is silenced. In the present study, the human hepatocellular carcinoma HepG2 cell line was transfected with short hairpin RNA (shRNA) against HIF-1α and cultured under hypoxic conditions (1% O 2 for 24 h). The expression of HIF-1α and various growth factors, including epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2), were examined using quantitative polymerase chain reaction and immunoblotting. Tumor growth was measured using a Cell Counting Kit-8 assay and tumor activity was measured using tumor cell invasion and migration assays. Lipopolysaccharide and TAK-242 were used to activate and inhibit TLR4, respectively, to observe the role of TLR4 in the HIF-1α silenced tumor cells. The expression of TLR4 signaling pathway associates, including myeloid differentiation primary response gene 88 (MyD88), apoptosis signal-regulating kinase 1 (ASK1), p38 mitogen-activated protein kinases and HIF-1α, were analyzed by western blot assay. Under hypoxic conditions, silencing of HIF-1α expression suppressed tumor cell growth and regulated the expression of tumor growth-associated genes, including EGF, HGF, VEGF and FG2. Suppression of tumor cell invasion and migration was also observed in the HIF-1α silenced HepG2 cell line. In addition, TLR4 was identified to be involved in HIF-1α and MyD88 accumulation, and activation of ASK1 and p38 were demonstrated to be critical for TLR4-mediated HIF-1α pathway. In conclusion, silencing of HIF-1α expression may induce anti-tumor effects under hypoxic

  6. 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

  7. 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)

  8. 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)

  9. CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma

    DEFF Research Database (Denmark)

    Engelholm, Lars H; Riaz, Anjum; Serra, Denise

    2017-01-01

    BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1...

  10. Histopathology of hepatocellular carcinoma.

    Science.gov (United States)

    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.

  11. Computed tomography of liver tumors, 2

    International Nuclear Information System (INIS)

    Naito, Akira; Fukuoka, Haruhito; Kashiwado, Kouzou; Ichiki, Toshio; Makidono, Yoko

    1984-01-01

    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. (Namekawa, K.)

  12. 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 ...

  13. 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.

  14. Rocaglamide overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase-8 through cellular FLICE-like-inhibitory protein downregulation.

    Science.gov (United States)

    Luan, Zhou; He, Ying; He, Fan; Chen, Zhishui

    2015-01-01

    The enhancement of apoptosis is a therapeutic strategy used in the treatment of cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising antitumor agent. However, hepatocellular carcinoma (HCC) cells exhibit marked resistance to the induction of cell death by TRAIL. The present study investigated whether rocaglamide, a naturally occurring product isolated from the genus Aglaia, is able to sensitize resistant HCC cells to TRAIL-mediated apoptosis. Two HCC cell lines, HepG2 and Huh-7, were treated with rocaglamide and/or TRAIL and the induction of apoptosis and effects on the TRAIL signaling pathway were investigated. The in vivo efficacy of rocaglamide was determined in TRAIL-resistant Huh-7-derived tumor xenografts. Rocaglamide significantly sensitized the TRAIL-resistant HCC cells to apoptosis by TRAIL, which resulted from the rocaglamide-mediated downregulation of cellular FLICE-like inhibitory protein and subsequent caspase-8 activation. Furthermore, rocaglamide markedly inhibited tumor growth from Huh-7 cells propagated in severe combined immunodeficient mice, suggesting that chemosentization also occurred in vivo. These data suggest that rocaglamide acted synergistically with TRAIL against the TRAIL-resistant HCC cells. Thus, it is concluded that rocaglamide as an adjuvant to TRAIL-based therapy may present a promising therapeutic approach for the treatment of HCC.

  15. Ultrasonographic finding of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Incidence of thromboembolism following detection by trans-oesophageal echocardiography of left atrial thrombus

    Directory of Open Access Journals (Sweden)

    Ciara Mahon

    2015-09-01

    Conclusion: This is the only study to date that has looked at the incidence of ischemic stroke following a confirmed LAA thrombus, LA thrombus or pre-thrombus state. This single centre study found low stroke rates over a six month follow-up period in patients with a confirmed LAA thrombus, LA thrombus or pre-thrombus state and optimization of OAC. Larger studies would be required to confirm these findings.

  17. Ultrasound Detection of Superior Vena Cava Thrombus

    Directory of Open Access Journals (Sweden)

    Aaron Birch

    2014-09-01

    Full Text Available Superior vena cava (SVC syndrome is most commonly the insidious result of decreased vascular flow through the SVC due to malignancy, spontaneous thrombus, infections, and iatrogenic etiologies. Clinical suspicion usually leads to computed tomography to confirm the diagnosis. However, when a patient in respiratory distress requires emergent airway management, travel outside the emergency department is not ideal. With the growing implementation of point-of-care ultrasound (POCUS, clinicians may make critical diagnoses rapidly and safely. We present a case of SVC syndrome due to extensive thrombosis of the deep venous system cephalad to the SVC diagnosed by POCUS. [West J Emerg Med. 2014;15(6:715-718

  18. 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.

  19. Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

    Science.gov (United States)

    Yang, Rui; Tang, Qiusha; Miao, Fengqin; An, Yanli; Li, Mengfei; Han, Yong; Wang, Xihui; Wang, Juan; Liu, Peidang; Chen, Rong

    2015-01-01

    Purpose To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice. Methods CD90+ LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90+ LCSCs and the effect of CD90@17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo. Results CD90+ LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9±7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90+ LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90+ LCSCs to magnetic hyperthermia. Conclusion The inhibition of HSP90 could sensitize CD90+ LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo. PMID:26677324

  20. Detection of extracellular genomic DNA scaffold in human thrombus

    DEFF Research Database (Denmark)

    Oklu, Rahmi; Albadawi, Hassan; Watkins, Michael T

    2012-01-01

    into thrombus remodeling. MATERIALS AND METHODS: Ten human thrombus samples were collected during cases of thrombectomy and open surgical repair of abdominal aortic aneurysms (five samples 1 y old). Additionally, an acute murine hindlimb ischemia model was created to evaluate...... thrombus samples in mice. Human sections were immunostained for the H2A/H2B/DNA complex, myeloperoxidase, fibrinogen, and von Willebrand factor. Mouse sections were immunostained with the H2A antibody. All samples were further evaluated after hematoxylin and eosin and Masson trichrome staining. RESULTS......: An extensive network of extracellular histone/DNA complex was demonstrated in the matrix of human ex vivo thrombus. This network is present throughout the highly cellular acute thrombus. However, in chronic thrombi, detection of the histone/DNA network was predominantly in regions of low collagen content...

  1. Covered stent to exclude intravascular thrombus.

    Science.gov (United States)

    Liistro, Francesco; Stankovic, Goran; Di Mario, Carlo; Montorfano, Matteo; Briguori, Carlo; Colombo, Antonio

    2002-04-01

    To describe the utility of stent-graft implantation to avoid distal embolization from a large thrombus-containing lesion. A 67-year-old man was evaluated for recent onset of disabling left leg claudication. Angiography disclosed a mobile lobular mass occluding the left common iliac artery; irregular staining suggested an atherothrombotic lesion. Through a percutaneous ipsilateral access and an 8-F sheath, a balloon-expandable Jostent peripheral stent-graft was positioned with the distal edge immediately proximal to the internal iliac artery ostium. A prominent "waist" at the center of the balloon confirmed entrapment of the thrombotic mass. Completion angiography showed an optimal result with no residual stenosis or evidence of distal embolization. At 6-month follow-up, the patient was asymptomatic with angiographically documented luminal patency and no evidence of in-stent stenosis. Stent-graft implantation appears a viable treatment alternative for thrombus-containing lesions, particularly when the thrombotic material is localized or is in a large vessel.

  2. Long non-coding RNA CCAT2 is associated with poor prognosis in hepatocellular carcinoma and promotes tumor metastasis by regulating Snail2-mediated epithelial–mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Xu Y

    2017-02-01

    Full Text Available Yongfu Xu,* Binfeng Wang,* Fabiao Zhang, Aidong Wang, Xuefeng Du, Peng Hu, Yu Zhu, Zheping Fang Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, People’s Republic of China *These authors contributed equally to this work Abstract: Increasing evidence has demonstrated that aberrant expressions of long non-coding RNAs (lncRNAs are involved in various malignancies, including hepatocellular carcinoma (HCC. This study aimed to investigate the role of lncRNA colon cancer-associated transcript 2 (CCAT2 in the progression of HCC. Quantitative real-time polymerase chain reaction analysis confirmed that CCAT2 was upregulated in HCC cell lines and cancerous tissues compared with normal liver cell line and adjacent normal tissue samples. The level of CCAT2 was positively associated with tumor–node–metastasis stages and vessel invasion. Survival analyses revealed that high CCAT2 expression predicted poor prognostic outcomes, serving as an independent prognostic factor for HCC patients. Patients with high CCAT2 expression had a 1.849-fold increased risk of death compared with those with low CCAT2 expression. Moreover, we also found that knockdown of CCAT2 expression reduced cell migration and invasion in vitro. We further demonstrated that CCAT2 played a key role in enhancing the epithelial–mesenchymal transition (EMT through the regulation of vimentin, E-cadherin and transcription factor snail2 expression. Taken together, our findings showed that high CCAT2 expression is associated with poor survival in HCC patients. CCAT2 promotes HCC progression by regulating Snail2-induced EMT. CCAT2 may be a prognostic biomarker and therapeutic target for HCC. Keywords: long non-coding RNA, CCAT2, hepatocellular carcinoma, epithelial–mesenchymal transition, survival

  3. Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma

    Science.gov (United States)

    Baek, Yang Hyun; Kim, Kyoung Tae; Lee, Sung Wook; Jeong, Jin Sook; Park, Byeong Ho; Nam, Kyung Jin; Cho, Jin Han; Kim, Young Hoon; Roh, Young Hoon; Lee, Hyung Sik; Choi, Young Min; Han, Sang Young

    2012-01-01

    AIM: To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR) in patients with advanced hepatocellular carcinoma (HCC) confined to the liver. METHODS: Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008. Among the 34 patients, 9 patients were classified as Child class C, and 18 patients had portal vein tumor thrombus (PVTT). One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1, 4, 7 and 11), and this treatment was repeated every 28 d. RESULTS: Two patients (5.9%) displayed a complete response, and 12 patients (35.3%) had a partial response. The tumor control rate was 61.8%. The median overall survival times were 15.3 mo, 12.4 mo and 4.3 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0392). The progression-free survival was 12.9 mo, 7.7 mo and 2.6 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0443). The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT. In addition to hepatic reserve capacity and PVTT, the extent of HCC was an independent factor in determining a poor prognosis. The most common adverse reactions to HAIC were mucositis, diarrhea and peptic ulcer disease, but most of these complications were improved by medical treatment and/or a delay of HAIC. CONCLUSION: The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis. PMID:22807613

  4. Categorization of aortic aneurysm thrombus morphology by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Motte, Louise de la, E-mail: louise.de.la.motte@rh.regionh.dk [Department of Vascular Surgery, Rigshospitalet and University of Copenhagen (Denmark); Pedersen, Mads Møller, E-mail: phd@medit.dk [Department of Radiology, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen (Denmark); Thomsen, Carsten, E-mail: carsten.thomsen@rh.regionh.dk [Department of Radiology, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen (Denmark); Vogt, Katja, E-mail: Vogt@dadlnet.dk [Department of Vascular Surgery, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen (Denmark); Schroeder, Torben V., E-mail: Torben.Veith.schroeder@rh.regionh.dk [Department of Vascular Surgery, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen (Denmark); Lonn, Lars, E-mail: lonn.lars@gmail.com [Department of Vascular Surgery and Department of Radiology, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen (Denmark)

    2013-10-01

    Background: Magnetic resonance imaging (MRI) has been proposed for qualitative categorization of intraluminal thrombus morphology. We aimed to correlate the qualitative MRI categorization previously described to quantitative measurements of signal intensity and to compare morphological characteristics of intraluminal thrombus specimens to the appearance on magnetic resonance imaging. Methods: Thirty-four patients undergoing open surgery for abdominal aortic aneurysm had a preoperative MRI obtained with a 1.5 T magnet. Qualitative categorization was performed (blinded and in consensus) and correlated to intraluminal thrombus to muscle signal-intensity ratios. Morphology of intraluminal thrombus specimens collected during surgery were compared to the magnetic resonance imaging categories and specimen weight was correlated to thrombus volume measured on preoperative computer tomography angiography. Results: Blinded MRI categorization resulted in agreement in 22 out of 34 intraluminal thrombi (Kappa value 0.3, p = 0.006). Medians (p = 0.004) and distribution (p = 0.002) of signal-intensity ratios varied significantly across the three MRI categories obtained by consensus. Heterogeneous and homogenous specimen appearance corresponded to similar appearances on MRI in 78% and 55% respectively, resulting in an overall Kappa = 0.4 (p = 0.04). Intraluminal thrombus volume and weight correlated well (r{sub s} 0.831, p < 0.001) with a mean difference of 60 g (95% CI 38–80 g), without proportional bias. Conclusion: Qualitative evaluation of intraluminal thrombus morphology based on MRI can be quantified by measuring signal-intensity ratios. Concurrently a fair agreement to blinded qualitative evaluation of thrombus specimens can be obtained. However, the evaluation is impaired by loss of a large proportion of thrombus during sampling.

  5. Categorization of aortic aneurysm thrombus morphology by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Motte, Louise de la; Pedersen, Mads Møller; Thomsen, Carsten; Vogt, Katja; Schroeder, Torben V.; Lonn, Lars

    2013-01-01

    Background: Magnetic resonance imaging (MRI) has been proposed for qualitative categorization of intraluminal thrombus morphology. We aimed to correlate the qualitative MRI categorization previously described to quantitative measurements of signal intensity and to compare morphological characteristics of intraluminal thrombus specimens to the appearance on magnetic resonance imaging. Methods: Thirty-four patients undergoing open surgery for abdominal aortic aneurysm had a preoperative MRI obtained with a 1.5 T magnet. Qualitative categorization was performed (blinded and in consensus) and correlated to intraluminal thrombus to muscle signal-intensity ratios. Morphology of intraluminal thrombus specimens collected during surgery were compared to the magnetic resonance imaging categories and specimen weight was correlated to thrombus volume measured on preoperative computer tomography angiography. Results: Blinded MRI categorization resulted in agreement in 22 out of 34 intraluminal thrombi (Kappa value 0.3, p = 0.006). Medians (p = 0.004) and distribution (p = 0.002) of signal-intensity ratios varied significantly across the three MRI categories obtained by consensus. Heterogeneous and homogenous specimen appearance corresponded to similar appearances on MRI in 78% and 55% respectively, resulting in an overall Kappa = 0.4 (p = 0.04). Intraluminal thrombus volume and weight correlated well (r s 0.831, p < 0.001) with a mean difference of 60 g (95% CI 38–80 g), without proportional bias. Conclusion: Qualitative evaluation of intraluminal thrombus morphology based on MRI can be quantified by measuring signal-intensity ratios. Concurrently a fair agreement to blinded qualitative evaluation of thrombus specimens can be obtained. However, the evaluation is impaired by loss of a large proportion of thrombus during sampling

  6. Prediction of microvascular invasion of hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging: Impact of intra-tumoral fat detected on chemical-shift images

    Energy Technology Data Exchange (ETDEWEB)

    Min, Ji Hye [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Young Kon, E-mail: jmyr@dreamwiz.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lim, Sanghyeok [Department of Radiology, Guri Hospital, Hanyang University College of Medicine, Guri (Korea, Republic of); Jeong, Woo Kyoung; Choi, Dongil; Lee, Won Jae [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    Highlights: • Intra-tumoral fat detected with MR imaging may suggest lower risk for MVI of HCC. • Alfa-fetoprotein, tumor size, and fat component were associated with MVI of HCC. • Chemical shift MRI should be considered for the evaluation of HCC. - Abstract: Purpose: To investigate the impact of intra-tumoral fat detected by chemical-shift MR imaging in predicting the MVI of HCC. Materials and methods: Gadoxetic acid-enhanced MR imaging of 365 surgically proven HCCs from 365 patients (306 men, 59 women; mean age, 55.6 years) were evaluated. HCCs were classified into two groups, fat-containing and non-fat-containing, based on the presence of fat on chemical-shift images. Fat-containing HCCs were subdivided into diffuse or focal fatty change groups. Logistic regression analyses were used to identify clinical and MR findings associated with MVI. Results: Based on MR imaging, 66 tumors were classified as fat-containing HCCs and 299 as non-fat-containing HCCs. Among the 66 fat-containing HCCs, 38 (57.6%) showed diffuse fatty changes and 28 (42.4%) showed focal fatty changes. MVI was present in 18 (27.3%) fat-containing HCCs and in 117 (39.1%) non-fat-containing HCCs (P = 0.07). Univariate analysis revealed that serum alpha-fetoprotein (AFP) and tumor size were significantly associated with MVI (P < 0.001). A multiple logistic regression analysis showed that log AFP (odds ratio 1.178, P = 0.0016), tumor size (odds ratio 1.809, P < 0.001), and intra-tumoral fat (odds ratio 0.515, P = 0.0387) were independent variables associated with MVI. Conclusion: Intra-tumoral fat detected with MR imaging may suggest lower risk for MVI of HCC and, therefore, a possibly more favorable prognosis, but the clinical value of this finding is uncertain.

  7. Prediction of microvascular invasion of hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging: Impact of intra-tumoral fat detected on chemical-shift images

    International Nuclear Information System (INIS)

    Min, Ji Hye; Kim, Young Kon; Lim, Sanghyeok; Jeong, Woo Kyoung; Choi, Dongil; Lee, Won Jae

    2015-01-01

    Highlights: • Intra-tumoral fat detected with MR imaging may suggest lower risk for MVI of HCC. • Alfa-fetoprotein, tumor size, and fat component were associated with MVI of HCC. • Chemical shift MRI should be considered for the evaluation of HCC. - Abstract: Purpose: To investigate the impact of intra-tumoral fat detected by chemical-shift MR imaging in predicting the MVI of HCC. Materials and methods: Gadoxetic acid-enhanced MR imaging of 365 surgically proven HCCs from 365 patients (306 men, 59 women; mean age, 55.6 years) were evaluated. HCCs were classified into two groups, fat-containing and non-fat-containing, based on the presence of fat on chemical-shift images. Fat-containing HCCs were subdivided into diffuse or focal fatty change groups. Logistic regression analyses were used to identify clinical and MR findings associated with MVI. Results: Based on MR imaging, 66 tumors were classified as fat-containing HCCs and 299 as non-fat-containing HCCs. Among the 66 fat-containing HCCs, 38 (57.6%) showed diffuse fatty changes and 28 (42.4%) showed focal fatty changes. MVI was present in 18 (27.3%) fat-containing HCCs and in 117 (39.1%) non-fat-containing HCCs (P = 0.07). Univariate analysis revealed that serum alpha-fetoprotein (AFP) and tumor size were significantly associated with MVI (P < 0.001). A multiple logistic regression analysis showed that log AFP (odds ratio 1.178, P = 0.0016), tumor size (odds ratio 1.809, P < 0.001), and intra-tumoral fat (odds ratio 0.515, P = 0.0387) were independent variables associated with MVI. Conclusion: Intra-tumoral fat detected with MR imaging may suggest lower risk for MVI of HCC and, therefore, a possibly more favorable prognosis, but the clinical value of this finding is uncertain

  8. An unexpected complication of acute pancreatitis: Intra-cardiac thrombus.

    Science.gov (United States)

    Keskin, Muhammed; Gümüşdağ, Ayça; Börklü, Edibe Betül; Dayı, Şennur Ünal; Avcı, İlhan İlker; Güvenç, Tolga Sinan; Güngör, Barış; Karabay, Can Yücel; Kozan, Ömer

    2017-05-01

    Left atrial thrombus after acute pancreatitis (AP) is a rare clinical statement. Because of induction of systemic prothrombotic process by AP; some patients with underlying risk factors may develop an intra-cardiac thrombus. We present a 53years-old-woman with moderate mitral stenosis and atrial fibrillation. However the patient was under warfarin treatment, she developed a big left atrial big thrombus which was originated from left atrial appendage after she was suffered from AP. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Deep venous thrombus characterization: ultrasonography, elastography and scattering operator

    OpenAIRE

    Thibaud Berthomier; Ali Mansour; Luc Bressollette; Frédéric Le Roy; Dominique Mottier

    2017-01-01

    A thrombus or a blood clot is the result of blood coagulation which is a natural process to prevent bleeding. An inappropriate formation of a thrombus in a deep vein is known as Deep Venous Thrombosis (DVT). The main complication of a DVT is a Pulmonary Embolism (PE) which occurs when a thrombus breaks loose and travels to the lungs. DVT, PE, or both are also known as Venous thromboembolism (VTE). It affects an estimated 300,000–600,000 Individuals just in the United States per year and can c...

  10. Meta-analysis of the prognostic value of abnormally expressed lncRNAs in hepatocellular carcinoma.

    Science.gov (United States)

    Qu, Zhen; Yuan, Chun-Hui; Yin, Chang-Qing; Guan, Qing; Chen, Hao; Wang, Fu-Bing

    2016-01-01

    Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in hepatocellular carcinoma (HCC), and may have the potential to serve as prognostic markers. In this study, a meta-analysis was conducted to systematically evaluate the prognostic value of various lncRNAs in HCC. Eligible literatures were systematically collected from PubMed, Embase, Web of Science, and Cochrane Library (up to December 30, 2015). The main outcomes including overall survival, relapse-free survival, and disease-free survival were analyzed. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. A total of 2,991 patients with HCC in People's Republic of China from 27 studies were included in the analysis. The level of lncRNAs showed a significant association with clinical outcomes. Abnormally elevated lncRNA transcription level predicted poor overall survival (HR: 1.68, 95% CI: 1.20-2.34, P=0.002; I (2)=75.5%, P=0.000) and relapse-free survival (HR: 2.08, 95% CI: 1.65-2.61, Panalysis further showed that lncRNA transcription level was significantly associated with tumor size (relative risk [RR]: 1.19, 95% CI: 1.01-1.39, P=0.035), microvascular invasion (RR: 1.44, 95% CI: 1.10-1.89, P=0.009), and portal vein tumor thrombus (RR: 1.50, 95% CI: 1.03-2.20, P=0.036). Publication bias and sensitivity analysis further confirmed the stability of our results. Our present meta-analysis indicates that abnormal lncRNA transcription level may serve as a promising indicator for prognostic evaluation of patients with HCC in People's Republic of China.

  11. A Novel Risk prediction Model for Patients with Combined Hepatocellular-Cholangiocarcinoma.

    Science.gov (United States)

    Tian, Meng-Xin; He, Wen-Jun; Liu, Wei-Ren; Yin, Jia-Cheng; Jin, Lei; Tang, Zheng; Jiang, Xi-Fei; Wang, Han; Zhou, Pei-Yun; Tao, Chen-Yang; Ding, Zhen-Bin; Peng, Yuan-Fei; Dai, Zhi; Qiu, Shuang-Jian; Zhou, Jian; Fan, Jia; Shi, Ying-Hong

    2018-01-01

    Backgrounds: Regarding the difficulty of CHC diagnosis and potential adverse outcomes or misuse of clinical therapies, an increasing number of patients have undergone liver transplantation, transcatheter arterial chemoembolization (TACE) or other treatments. Objective: To construct a convenient and reliable risk prediction model for identifying high-risk individuals with combined hepatocellular-cholangiocarcinoma (CHC). Methods: 3369 patients who underwent surgical resection for liver cancer at Zhongshan Hospital were enrolled in this study. The epidemiological and clinical characteristics of the patients were collected at the time of tumor diagnosis. Variables ( P model discrimination. Calibration was performed using the Hosmer-Lemeshow test and a calibration curve. Internal validation was performed using a bootstrapping approach. Results: Among the entire study population, 250 patients (7.42%) were pathologically defined with CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and portal vein tumor thrombus (PVTT) were included in the final risk prediction model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77). Bootstrapping validation presented negligible optimism. When the risk threshold of the prediction model was set at 20%, 2.73% of the patients diagnosed with liver cancer would be diagnosed definitely, which could identify CHC patients with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of 33.70%. Conclusions: Herein, the study established a risk prediction model which incorporates the clinical risk predictors and CT/MRI-presented PVTT status that could be adopted to facilitate the diagnosis of CHC patients preoperatively.

  12. CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma.

    Science.gov (United States)

    Engelholm, Lars H; Riaz, Anjum; Serra, Denise; Dagnæs-Hansen, Frederik; Johansen, Jens V; Santoni-Rugiu, Eric; Hansen, Steen H; Niola, Francesco; Frödin, Morten

    2017-12-01

    Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects children and young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis. We used the CRISPR/Cas9 technique to delete in mice the syntenic region on chromosome 8 to create a Dnajb1-Prkaca fusion and monitored the mice for liver tumor development. We delivered CRISPR/Cas9 vectors designed to juxtapose exon 1 of Dnajb1 with exon 2 of Prkaca to create the Dnajb1-Prkaca gene fusion associated with FL-HCC, or control Cas9 vector, via hydrodynamic tail vein injection to livers of 8-week-old female FVB/N mice. These mice did not have any other engineered genetic alterations and were not exposed to liver toxins or carcinogens. Liver tissues were collected 14 months after delivery; genomic DNA was analyzed by PCR to detect the Dnajb1-Prkaca fusion, and tissues were characterized by histology, immunohistochemistry, RNA sequencing, and whole-exome sequencing. Livers from 12 of the 15 mice given the vectors to induce the Dnajb1-Prkaca gene fusion, but none of the 11 mice given the control vector, developed neoplasms. The tumors contained the Dnajb1-Prkaca gene fusion and had histologic and cytologic features of human FL-HCCs: large polygonal cells with granular, eosinophilic, and mitochondria-rich cytoplasm, prominent nucleoli, and markers of hepatocytes and cholangiocytes. In comparing expression levels of genes between the mouse tumor and non-tumor liver cells, we identified changes similar to those detected in human FL-HCC, which included genes that affect cell cycle and mitosis regulation. Genomic analysis of mouse neoplasms induced by

  13. 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

  14. 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...

  15. Predictive value of CpG island methylator phenotype for tumor recurrence in hepatitis B virus-associated hepatocellular carcinoma following liver transplantation

    Directory of Open Access Journals (Sweden)

    Zheng Shu-Sen

    2010-08-01

    Full Text Available Abstract Background CpG island methylator phenotype (CIMP, in which multiple genes concordantly methylated, has been demonstrated to be associated with progression, recurrence, as well as overall survival in some types of cancer. Methods We examined the promoter methylation status of seven genes including P16, CDH1, GSTP1, DAPK, XAF1, SOCS1 and SYK in 65 cases of HCC treated with LT by methylation-specific PCR. CIMP+ was defined as having three or more genes that are concordantly methylated. The relationship between CIMP status and clinicopathological parameters, as well as tumor recurrence was further analyzed. Results CIMP+ was more frequent in HCC with AFP > 400 ng/ml than those with AFP ≤ 400 ng/ml (P = 0.017. In addition, patients with CIMP+ were prone to have multiple tumor numbers than those with CIMP- (P = 0.007. Patients with CIMP+ tumors had significantly worse recurrence-free survival (RFS than patients with CIMP-tumors by Kaplan-Meier estimates (P = 0.004. Multivariate analysis also revealed that CIMP status might be a novel independent prognostic factor of RFS for HCC patients treated with LT (HR: 3.581; 95% CI: 1.473-8.710, P = 0.005. Conclusion Our results suggested that CIMP could serve as a new prognostic biomarker to predict the risk of tumor recurrence in HCC after transplantation.

  16. Predictive value of CpG island methylator phenotype for tumor recurrence in hepatitis B virus-associated hepatocellular carcinoma following liver transplantation

    International Nuclear Information System (INIS)

    Wu, Li-Ming; Zhang, Feng; Zhou, Lin; Yang, Zhe; Xie, Hai-Yang; Zheng, Shu-Sen

    2010-01-01

    CpG island methylator phenotype (CIMP), in which multiple genes concordantly methylated, has been demonstrated to be associated with progression, recurrence, as well as overall survival in some types of cancer. We examined the promoter methylation status of seven genes including P16, CDH1, GSTP1, DAPK, XAF1, SOCS1 and SYK in 65 cases of HCC treated with LT by methylation-specific PCR. CIMP+ was defined as having three or more genes that are concordantly methylated. The relationship between CIMP status and clinicopathological parameters, as well as tumor recurrence was further analyzed. CIMP+ was more frequent in HCC with AFP > 400 ng/ml than those with AFP ≤ 400 ng/ml (P = 0.017). In addition, patients with CIMP+ were prone to have multiple tumor numbers than those with CIMP- (P = 0.007). Patients with CIMP+ tumors had significantly worse recurrence-free survival (RFS) than patients with CIMP-tumors by Kaplan-Meier estimates (P = 0.004). Multivariate analysis also revealed that CIMP status might be a novel independent prognostic factor of RFS for HCC patients treated with LT (HR: 3.581; 95% CI: 1.473-8.710, P = 0.005). Our results suggested that CIMP could serve as a new prognostic biomarker to predict the risk of tumor recurrence in HCC after transplantation

  17. [Radiofrequency ablation of hepatocellular carcinoma].

    Science.gov (United States)

    Widmann, Gerlig; Schullian, Peter; Bale, Reto

    2013-03-01

    Percutaneous radiofrequency ablation (RFA) is well established in the treatment of hepatocellular carcinoma (HCC). Due to its curative potential, it is the method of choice for non resectable BCLC (Barcelona Liver Clinic) 0 and A. RFA challenges surgical resection for small HCC and is the method of choice in bridging for transplantation and recurrence after resection or transplantation. The technical feasibility of RFA depends on the size and location of the HCC and the availability of ablation techniques (one needle techniques, multi-needle techniques). More recently, stereotactic multi-needle techniques with 3D trajectory planning and guided needle placement substantially improve the spectrum of treatable lesions including large volume tumors. Treatment success depends on the realization of ablations with large intentional margins of tumor free tissue (A0 ablation in analogy to R0 resection), which has to be documented by fusion of post- with pre-ablation images, and confirmed during follow-up imaging.

  18. Hepatocellular carcinoma: a review

    Directory of Open Access Journals (Sweden)

    Balogh J

    2016-10-01

    Full Text Available Julius Balogh,1,2 David Victor III,1,3,4 Emad H Asham,1,2 Sherilyn Gordon Burroughs,1,2 Maha Boktour,1,2 Ashish Saharia,1,2 Xian Li,1,2 R Mark Ghobrial,1,2 Howard P Monsour Jr,1,3,4 1Sherrie and Alan Conover Center for Liver Disease and Transplantation, 2Division of Transplantation, Department of Surgery, 3Department of Gastroenterology and Transplant Hepatology, 4Department of Medicine, Houston Methodist Hospital, Houston, TX, USA Abstract: Hepatocellular carcinoma (HCC is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an

  19. Angiographic findings of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Han, Man Chung; Cho, Byung Jae; Huh, Seung Jae; Bae, Sang Hoon; Kim, Ung Jin; Kim, Chung Yong; Kim, Noe Kyeong [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1985-12-15

    From March 1977 to July 1979, 69 cases of angiograms of hepatocellular carcinoma were observed in Seoul National University Hospital. The findings of selective celiac and/or hepatic arteriography in total 69 cases of confirmed hepatocellular carcinoma, with clinical and laboratory findings, were analyzed. The summarized results are as follows; 1. Among 69 cases od hepatoma, 62 were male and 7 were female with sex ratio of 8.9 : 1. Peak incidence is 5th to 7th decades (72.5%). Epigastric pain, indigestion, and palpable mass in right upper quadrant were common symptoms and sign. Laboratory findings showed elevated serum alkaline phosphatase more than 5 Bodansky unit in 75.4%. Alpha-feto protein was positive in 65.2% of all the patients. 2 All 69 cases were classified into 31 cases of massive type, 22 cases of diffuse type, and 16 cases of nodular type, in accordance with angiographic gross anatomy. The frequency of angiographic findings were hypervascularities and tumor vessels (100%), tumor stainings (98.5%), arteriovenous shunt (71.0%), displacement of intrahepatic arteries (66.7%), vascular lakes and channel (59.4%). Encasement of hepatic artery and portal vein regurgitation was respectively 4 cases. Tumor mass in portal vein were 6 cases and tumor mass in hepatic vein was 1 case. 3. Intraarterial infusion of 5-FU was performed in 15 hepatoma patients, and the results were that angiographic improvement was demonstrated in 3 cases, no improvement in 8 cases, and incomplete infusion in 4 cases. 4. The selective celiac and/or hepatic angiograms are excellent diagnostic tools as well as therapeutic management for intraarterial infusion of anticancerous drugs.

  20. Angiographic findings of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Han, Man Chung; Cho, Byung Jae; Huh, Seung Jae; Bae, Sang Hoon; Kim, Ung Jin; Kim, Chung Yong; Kim, Noe Kyeong

    1985-01-01

    From March 1977 to July 1979, 69 cases of angiograms of hepatocellular carcinoma were observed in Seoul National University Hospital. The findings of selective celiac and/or hepatic arteriography in total 69 cases of confirmed hepatocellular carcinoma, with clinical and laboratory findings, were analyzed. The summarized results are as follows; 1. Among 69 cases od hepatoma, 62 were male and 7 were female with sex ratio of 8.9 : 1. Peak incidence is 5th to 7th decades (72.5%). Epigastric pain, indigestion, and palpable mass in right upper quadrant were common symptoms and sign. Laboratory findings showed elevated serum alkaline phosphatase more than 5 Bodansky unit in 75.4%. Alpha-feto protein was positive in 65.2% of all the patients. 2 All 69 cases were classified into 31 cases of massive type, 22 cases of diffuse type, and 16 cases of nodular type, in accordance with angiographic gross anatomy. The frequency of angiographic findings were hypervascularities and tumor vessels (100%), tumor stainings (98.5%), arteriovenous shunt (71.0%), displacement of intrahepatic arteries (66.7%), vascular lakes and channel (59.4%). Encasement of hepatic artery and portal vein regurgitation was respectively 4 cases. Tumor mass in portal vein were 6 cases and tumor mass in hepatic vein was 1 case. 3. Intraarterial infusion of 5-FU was performed in 15 hepatoma patients, and the results were that angiographic improvement was demonstrated in 3 cases, no improvement in 8 cases, and incomplete infusion in 4 cases. 4. The selective celiac and/or hepatic angiograms are excellent diagnostic tools as well as therapeutic management for intraarterial infusion of anticancerous drugs.

  1. Categorization of aortic aneurysm thrombus morphology by magnetic resonance imaging

    DEFF Research Database (Denmark)

    de la Motte, Louise; Pedersen, Mads Møller; Thomsen, Carsten

    2013-01-01

    Magnetic resonance imaging (MRI) has been proposed for qualitative categorization of intraluminal thrombus morphology. We aimed to correlate the qualitative MRI categorization previously described to quantitative measurements of signal intensity and to compare morphological characteristics...

  2. Significance of performing CT after radiofrequency ablation of hepatocellular carcinoma. Relationship between CT findings in areas other than the tumor site and post therapeutic outcome

    International Nuclear Information System (INIS)

    Shimokoube, Kouichi; Saito, Kazuhiro; Kotake, Fumio; Nakamura, Hiroshi; Mizokami, Yuji; Mikami, Ryuji; Matsuoka, Takeshi

    2004-01-01

    The relationships between the CT findings following radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) and the clinical symptoms and laboratory data were examined. The subjects consisted of 31 cases (41 nodules) of HCC that were treated by RFA. The CT findings before and after RFA, particularly the findings in areas other than the treatment site (henceforth, secondary findings), were evaluated by a physician and a radiologist. In addition, the relationships between the CT findings and post-RFA clinical symptoms (fever/pain) and laboratory data were examined. Secondary findings were found in 90.3% (28/31). These findings were broadly classified into changes in the needle tract 51.6% (16/31), retention of effusion 41.9% (13/31), thickening of the gallbladder wall 12.9% (4/31), changes in the retroperitoneal space 9.7% (3/31), and dilatation of the intrahepatic bile duct 3.2% (1/31), in the order of frequency. A relationship was found between changes in the retroperitoneal space and the clinical symptoms (fever: p=0.0366, pain: p=0.0012). Relationships were also found between changes in the needle tract and retention of effusion and aspartate aminotransferase (AST) (p<0.0001), as well as between changes in the needle tract and alanine aminotransferase (ALT) (p=0.0149). The size of the treatment area did not correlate with the presence of clinical symptoms and changes in laboratory data. Diverse classification of CT findings was observed after RFA, and a relationship with clinical symptoms was noted. A relationship was also found between classification of the CT findings following RFA and the post-therapeutic outcome. (authors)

  3. 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.

  4. Deep venous thrombus characterization: ultrasonography, elastography and scattering operator

    Directory of Open Access Journals (Sweden)

    Thibaud Berthomier

    2017-04-01

    Full Text Available A thrombus or a blood clot is the result of blood coagulation which is a natural process to prevent bleeding. An inappropriate formation of a thrombus in a deep vein is known as Deep Venous Thrombosis (DVT. The main complication of a DVT is a Pulmonary Embolism (PE which occurs when a thrombus breaks loose and travels to the lungs. DVT, PE, or both are also known as Venous thromboembolism (VTE. It affects an estimated 300,000–600,000 Individuals just in the United States per year and can cause considerable morbidity and mortality. This multifactorial disease related to advanced age, immobility, surgery or obesity is an important public health issue. Our project is looking to link the VTE epidemiology (risk factors, patient history, PE to the thrombus structure. To reach our goals, we are collecting ultrasonography (echogenicity and elastography (stiffness of human thrombus. This manuscript describes our approach to create and preprocess a database using Toshiba Aplio 500. Our approaches to characterize the thrombus structure with ultrasound images are also described. The feature extraction is made with the scattering operator. Obtained features are then reduced using Principal Component Analysis and are analyzed to evaluate our approach.

  5. Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling

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    Eunice Yuen Ting Lau

    2016-05-01

    Full Text Available Like normal stem cells, tumor-initiating cells (T-ICs are regulated extrinsically within the tumor microenvironment. Because HCC develops primarily in the context of cirrhosis, in which there is an enrichment of activated fibroblasts, we hypothesized that cancer-associated fibroblasts (CAFs would regulate liver T-ICs. We found that the presence of α-SMA(+ CAFs correlates with poor clinical outcome. CAF-derived HGF regulates liver T-ICs via activation of FRA1 in an Erk1,2-dependent manner. Further functional analysis identifies HEY1 as a direct downstream effector of FRA1. Using the STAM NASH-HCC mouse model, we find that HGF-induced FRA1 activation is associated with the fibrosis-dependent development of HCC. Thus, targeting the CAF-derived, HGF-mediated c-Met/FRA1/HEY1 cascade may be a therapeutic strategy for the treatment of HCC.

  6. 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.

  7. 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)

  8. 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...

  9. Study of 99Tcm-annexin V distribution in inferior vena cava thrombus models of rabbits

    International Nuclear Information System (INIS)

    Wu Dayong; Zhang Wenyan; Bian Yanzhu; Hu Yujing

    2013-01-01

    To study 99 Tc m -Annexin V distribution in inferior vena cava thrombus models of rabbits and uptake of 99 Tc m -Annexin V in fresh and old venous thrombus. Rabbits (n=15) were randomly grouped into 3 groups (the fresh thrombus group, old thrombus group, and control group). The rabbits of two thrombus groups developed inferior vena cava thrombus models by operations. The control group received sham operation. The fresh thrombus group and control group rabbits were injected 99 Tc m -Annexin V after operating 1 d; the old thrombus group 14 d. After 1 h all rabbits were killed by injecting overdose pentobarbital sodium. The thrombus (or the inferior vena cava about 3 cm below inferior pole of right kidney level in the control group rabbits), blood, thrombus area inferior vena cava, head lateral inferior vena cava (except the control group), thigh muscle, stomach, myocardium, pulmonary, liver, kidney, spleen, bone and small intestine were obtained from all group rabbits. The ex tissue and blood were weighed and measured by a Well-type detector. The percentage of the injected dose per gram of ex tissue (or blood) was calculated by the above data. The thrombus to blood, thrombus area inferior vena cava, head lateral inferior vena cava and thigh muscle ratios were calculated by percentage of the injected dose per gram of ex tissue (or blood). The test was used to compare the fresh thrombus group and old thrombus group by SPSS 17.0. The percentage of' the injected dose per gram of thrombi (0.01894± 0.002 16% ID/g) in the fresh thrombus group was higher than the old thrombus group (0.00473±0.001 28% ID/g), P<0.05. The thrombus to blood, thrombus area inferior vena cava, head lateral inferior vena cava and muscle ratios (3.42±1.06, 26.32±13.60, 31.23 ±16.00, 111.62±52.23) in the fresh thrombus group were higher than the old thrombus group (0.98±0.09, 5.12±2.01, 6.25±2.38, 21.82±5.93), P<0.05 for all. All the thrombi of the fresh thrombus group were confirmed

  10. 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

  11. PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process.

    Science.gov (United States)

    Xie, Huijun; Tong, Guihui; Zhang, Yupei; Liang, Shu; Tang, Kairui; Yang, Qinhe

    2017-07-27

    During the proliferation and metastasis, the tumor cells prefer glycolysis (Warburg effect), but its exact mechanism remains largely unknown. In this study, we demonstrated that phosphoglycerate kinase 1 (PGK1) is an important enzyme in the pathway of metabolic glycolysis. We observed a significant overexpression of PGK1 in hepatocellular carcinoma tissues, and a correlation between PGK1 expression and poor survival of hepatocellular carcinoma patients. Also, the depletion of PGK1 dramatically reduced cancer cell proliferation and metastasis, indicating an oncogenic role of PGK1 in liver cancer progression. Further experiments showed that PGK1 played an important role in MYC -induced metabolic reprogramming, which led to an enhanced Warburg effect. Our results revealed a new effect of PGK1, which can provide a new treatment strategy for hepatocellular carcinoma, as PGK1 is used to indicate the prognosis of hepatocellular carcinoma (HCC).

  12. Nonbacterial thrombotic endocarditis associated with cancer of unknown origin complicated with thrombus in the left auricular appendage: case report

    Directory of Open Access Journals (Sweden)

    Morinaga Yukiko

    2011-02-01

    Full Text Available Abstract A 63-year-old man was admitted to our hospital with a complaint of right lateroabdominal pain. He was diagnosed with metastatic colon cancer, and then developed multiple brain embolic infarctions 7 days after admission. Transesophageal echocardiography showed that mobile, echo-dense masses were attached to the anterior and posterior mitral valve leaflet. Furthermore, there was a thrombus in the left auricular appendage despite sinus rhythm. These findings led to a diagnosis of suspected infectious endocarditis with subsequent multiple brain infarctions. The patient's general condition worsened and he died 13 days after admission. An autopsy was performed, and, while poorly differentiated cancer was observed in multiple organs, no primary tumor could be identified. Histological analysis showed that the masses of the mitral valve consisted mainly of fibrin without bacteria or oncocytes. This patient was therefore diagnosed with nonbacterial thrombotic endocarditis associated with cancer of unknown origin complicated with thrombus in the left auricular appendage.

  13. Contemporary management of symptomatic primary aortic mural thrombus.

    Science.gov (United States)

    Verma, Himanshu; Meda, Narendranadh; Vora, Simit; George, Robbie K; Tripathi, Ramesh K

    2014-12-01

    Primary aortic mural thrombus (PAMT) is an uncommon condition but an important source of noncardiogenic emboli with a difficult diagnosis and a high rate of complications, including high mortality. We report our experience of thromboembolic disease from PAMT and review its contemporary management. Retrospective analysis of prospectively collected data of all patients who presented with acute occlusion of a limb or visceral vessels between January 2011 and September 2013 was performed. A total of 88 patients presented with acute occlusion of the extremities or visceral arteries. All underwent extensive evaluation for the possible source of the embolism. Of these 88 patients, 19 patients (mean age, 41.2 years; male:female ratio, 1:2.1) were found to have aortic mural thrombus as the source of distal embolism. Thrombus was located in the thoracic aorta in 10 patients, in the perivisceral aorta in three patients, and in the infrarenal aorta in six patients. Thrombus in the thoracic aorta was treated with stent grafts in four patients, bare metal stents in three patients, and anticoagulation alone in two patients. In the suprarenal abdominal aorta, all three patients underwent trapdoor aortic thrombectomy. Infrarenal aortic thrombus was managed by aortobifemoral embolectomy in two patients, aortic stenting in two patients, surgical thrombectomy in one patient, and anticoagulation alone in one patient. Successful treatment, defined as freedom from further embolic events or recurrence of thrombus, was achieved in 14 of 19 patients (76.4%) with a mean follow-up period of 16.2 months (range, 2-28 months). There were four (21%) thrombus-related deaths, all due to primary thromboembolic insults. One patient needed a below-knee amputation because of a recurrent thrombotic episode. Symptomatic PAMT is an uncommon but important source of noncardiogenic embolus. It appears to occur more frequently in young women. Endovascular coverage of the aortic thrombus, when feasible

  14. PKCalpha regulates platelet granule secretion and thrombus formation in mice.

    Science.gov (United States)

    Konopatskaya, Olga; Gilio, Karen; Harper, Matthew T; Zhao, Yan; Cosemans, Judith M E M; Karim, Zubair A; Whiteheart, Sidney W; Molkentin, Jeffery D; Verkade, Paul; Watson, Steve P; Heemskerk, Johan W M; Poole, Alastair W

    2009-02-01

    Platelets are central players in atherothrombosis development in coronary artery disease. The PKC family provides important intracellular mechanisms for regulating platelet activity, and platelets express several members of this family, including the classical isoforms PKCalpha and PKCbeta and novel isoforms PKCdelta and PKCtheta. Here, we used a genetic approach to definitively demonstrate the role played by PKCalpha in regulating thrombus formation and platelet function. Thrombus formation in vivo was attenuated in Prkca-/- mice, and PKCalpha was required for thrombus formation in vitro, although this PKC isoform did not regulate platelet adhesion to collagen. The ablation of in vitro thrombus formation in Prkca-/- platelets was rescued by the addition of ADP, consistent with the key mechanistic finding that dense-granule biogenesis and secretion depend upon PKCalpha expression. Furthermore, defective platelet aggregation in response to either collagen-related peptide or thrombin could be overcome by an increase in agonist concentration. Evidence of overt bleeding, including gastrointestinal and tail bleeding, was not seen in Prkca-/- mice. In summary, the effects of PKCalpha ablation on thrombus formation and granule secretion may implicate PKCalpha as a drug target for antithrombotic therapy.

  15. Traversing boundaries: thrombus in transit with paradoxical embolism

    Directory of Open Access Journals (Sweden)

    Varun Miriyala

    2016-09-01

    Full Text Available A 72-year-old male is diagnosed with paradoxical embolus after he presented with concurrent deep vein thrombosis, stroke, and multiple arterial emboli in the presence of a patent foramen ovale (PFO. Paradoxical embolus requires the passage of a thrombus from the venous into the arterial circulation through a right-to-left shunt leading to systemic embolism. But, despite the high incidence of PFO (27.3% across all age groups by autopsy, paradoxical embolism (PDE is uncommon, representing <2% of all arterial emboli. We present a case report where a thrombus has been directly observed passing through the PFO during an echocardiogram study; thus, clearly delineating the true cause of multiple thromboemboli and stoke in our patient. Subsequent Transesophageal Echocardiography (TEE also interestingly showed the thrombus in transit in the aorta and pulmonary artery.

  16. Left atrial thrombus following bilobectomy: a case report

    Directory of Open Access Journals (Sweden)

    Kaya Ugur

    2010-02-01

    Full Text Available Abstract Introduction Left atrial free floating ball thrombus is a relatively rare event, especially without mitral valve disease. Case presentation A 61-year-old Turkish man was admitted to our hospital with a thrombus mass in his left atrium. Five months earlier, he had undergone right bilobectomy and superior bronchoplasty due to squamous cell carcinoma in the lung. The patient had no evidence of cardiac disease except atrial fibrillation and there were no defined embolizations. The thrombus mass was surgically removed. The patient was discharged from hospital on the sixth postoperative day. Conclusion Surgery with cardiopulmonary bypass is a safe method for treatment. The patient should be medicated with warfarin, especially in the presence of atrial fibrillation.

  17. Relation of Serum Alkaline Phosphatase to liver scintigram in patients with hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, H; Harada, T; Nawata, J; Hayakawa, M; Nishioka, M; Takemoto, T; Yokoyama, T; Takahashi, M

    1982-12-01

    Serum Alkaline Phosphatase (ALP) was studied in relation to liver scintigrams of 54 patients with hepatocellular carcinoma. The ALP activity was higher with larger tumors and in multiple tumors. Within the single tumor group, the activity was higher when the tumor was located in the hilum than in the periphery. The incidence of ALP-1 isoenzyme (bile ALP) roughly paralleled the total ALP activity. These results suggest that the variation of serum ALP seen in each individual patients with hepatocellular carcinoma reflects the volume of cholestatic liver tissue, which is changed by the number, size and localization of the tumor nodules in the liver.

  18. Method of cell transplantation promoting the organization of intraarterial thrombus.

    Science.gov (United States)

    Hirano, Koji; Shimono, Takatsugu; Imanaka-Yoshida, Kyoko; Miyamoto, Keiichi; Fujinaga, Kazuya; Kajimoto, Masaki; Miyake, Yoichiro; Nishikawa, Masakatsu; Yoshida, Toshimichi; Uchida, Atsumasa; Shimpo, Hideto; Yada, Isao; Hirata, Hitoshi

    2005-08-30

    Endovascular aortic repairs have been developed as less invasive treatments for aortic aneurysms. Some aneurismal cavities, however, remain without organization, causing a re-expansion of the aneurysms. We studied cell transplantation into the aneurismal sac to promote the organization of thrombus for the complete healing of aneurysms. Skin fibroblasts and skeletal myoblasts were isolated from rats for cell transplantation. An intraarterial thrombus model was made by ligation of the carotid artery. Culture medium (medium group, n=11), collagen gel (gel group, n=11), fibroblasts with collagen gel (F group, n=15), myoblasts with collagen gel (M group, n=12), or mixture of fibroblasts and myoblasts with collagen gel (F+M group, n=14) were injected into the thrombus. After 28 days, histologically, the arterial lumens of the F and M groups were partly filled with fibrous tissues, whereas in the F+M group organization was almost completed and luminal sizes diminished. Immunohistochemical staining demonstrated that alpha-smooth muscle actin-positive cells were more abundantly contained in the organized area of the F+M group than in the other groups. We also analyzed cellular function in vitro with immunofluorescence; coculture of fibroblasts and myoblasts showed that the fraction of alpha-smooth muscle actin-positive fibroblasts increased. This phenomenon accounts for the rapid organization of thrombus in the F+M group in vivo. Cell transplantation accelerated thrombus organization. Especially, myoblasts enhanced differentiation of fibroblasts into myofibroblasts, contributing to rapid thrombus organization. Cell transplantation into unorganized spaces seems applicable to endovascular treatment of aneurysms.

  19. Floating arterial thrombus related stroke treated by intravenous thrombolysis.

    Science.gov (United States)

    Vanacker, P; Cordier, M; Janbieh, J; Federau, C; Michel, P

    2014-01-01

    The effects of intravenous thrombolysis on floating thrombi in cervical and intracranial arteries of acute ischemic stroke patients are unknown. Similarly, the best prevention methods of early recurrences remain controversial. This study aimed to describe the clinical and radiological outcome of thrombolyzed strokes with floating thrombi. We retrospectively analyzed all thrombolyzed stroke patients in our institution between 2003 and 2010 with floating thrombi on acute CT-angiography before the intravenous thrombolysis. The floating thrombus was diagnosed if an elongated thrombus of at least 5 mm length, completely surrounded by contrast on supra-aortic neck or intracerebral arteries, was present on CT-angiography. Demographics, vascular risk factors, and comorbidities were recorded and stroke etiology was determined after a standardized workup. Repeat arterial imaging was performed by CTA at 24 h or before if clinical worsening was noted and then by Doppler and MRA during the first week and at four months. Of 409 thrombolyzed stroke patients undergoing acute CT Angiography, seven (1.7%) had a floating thrombus; of these seven, six had it in the anterior circulation. Demographics, risk factors and stroke severity of these patients were comparable to the other thrombolyzed patients. After intravenous thrombolysis, the floating thrombi resolved completely at 24 h in four of the patients, whereas one had an early recurrent stroke and one developed progressive worsening. One patient developed early occlusion of the carotid artery with floating thrombus and subsequently a TIA. The two patients with a stable floating thrombus had no clinical recurrences. In the literature, only one of four reported cases were found to have a thrombolysis-related early recurrence. Long-term outcome seemed similar in thrombolyzed patients with floating thrombus, despite a possible increase of very early recurrence. It remains to be established whether acute mechanical thrombectomy could be

  20. Differential expression of OPN, VEGF-A, and HIF-1α and its clinical significance in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHENG Yan

    2013-01-01

    Full Text Available ObjectiveTo investigate the expression patterns of osteopontin (OPN, vascular endothelial growth factor-A (VEGF-A, and hypoxia-inducible factor-1α(HIF-1α in primary hepatocellular carcinoma (HCC and determine the clinical significance of this differential expression profile. MethodsImmunohistochemical staining of OPN, VEGF-A, and HIF-1α was carried out on primary HCC tissues from 90 patients, HCC-adjacent cirrhosis tissues from 20 of those patients, and normal liver tissues from 15 healthy controls. Correlations between expression levels and HCC clinicopathological characteristics were assessed by Spearman's correlation coefficient. ResultsThe majority of HCC tissues showed positive immunostaining for OPN (69/90, 76.67%, VEGF-A (64/90, 71.11%, and HIF-1α (66/90, 73.33%. OPN- and VEGF-A-positivity were significantly higher than the results from the cirrhosis tissues and normal tissues. HIF-1α-positivity was similar between the HCC and cirrhosis tissues, but both were significantly different from the normal tissues. The differential expressions of OPN, VEGF-A, and HIF-1α were significantly correlated with tumor thrombus, capsular integrity, tumor differentiation and stage, and metastasis (P<0.05. ConclusionHCC tissues overexpress OPN, VEGF-A, and HIF-1α and this differential profile may be related to HCC progression. Future investigations of this triad of factors may provide novel insights into the biological characteristics of HCC and reveal important targets of molecular therapy.

  1. A thrombus in transit through a patent foramen ovale.

    Science.gov (United States)

    Ibebuogu, Uzoma N; Khouzam, Rami N; Sharma, Gyanendra; Thornton, John W; Robati, Roshanak; Silverman, David

    2014-10-01

    Patent foramen ovale (PFO) is a congenital heart defect that may first be diagnosed in adulthood and has a prevalence of 25% to 30%. Although many patients with PFO are asymptomatic and do not require treatment, paradoxical embolism can cause stroke or myocardial infarction. The authors report an unusual case of PFO with a transversing thrombus in an 80-year-old man. The patient's initial presentation appeared clinically as acute coronary syndrome, but he was subsequently diagnosed with a massive thrombus in transit via a PFO and pulmonary embolus leading to right-sided heart failure.

  2. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    NARCIS (Netherlands)

    Santos, Emilie M. M.; Yoo, Albert J.; Beenen, Ludo F.; Berkhemer, Olvert A.; den Blanken, Mark D.; Wismans, Carrie; Niessen, Wiro J.; Majoie, Charles B.; Marquering, Henk A.; Fransen, Puck S. S.; Beumer, Debbie; van den Berg, Lucie A.; Lingsma, Hester F.; Schonewille, Wouter J.; Vos, Jan Albert; Nederkoorn, Paul J.; Wermer, Marieke J. H.; van Walderveen, Marianne A. A.; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A.; Lycklama à Nijeholt, Geert J.; Boiten, Jelis; Brouwer, Patrick A.; Emmer, Bart J.; de Bruijn, Sebastiaan F.; van Dijk, Lukas C.; Kappelle, L. Jaap; Lo, Rob H.; van Dijk, Ewoud J.; de Vries, Joost; de Kort, Paul L. M.; van den Berg, Jan S. P.; A A M van Hasselt, Boudewijn; Aerden, Leo A. M.; Dallinga, René J.; Visser, Marieke C.; Bot, Joseph C. J.; Vroomen, Patrick C.; Eshghi, Omid; Schreuder, Tobien H. C. M. L.; Heijboer, Roel J. J.; Keizer, Koos; Tielbeek, Alexander V.; Hertog, Heleen M. Den; Gerrits, Dick G.; van den Berg-Vos, Renske M.; Karas, Giorgos B.; Steyerberg, Ewout W.; Flach, H. Zwenneke; Sprengers, Marieke E. S.; Jenniskens, Sjoerd F. M.; van den Berg, René; Koudstaal, Peter J.; van Zwam, Wim H.; Roos, Yvo B. W. E. M.; van der Lugt, Aad; van Oostenbrugge, Robert J.; Dippel, Diederik W. J.

    2016-01-01

    Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert

  3. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    NARCIS (Netherlands)

    E.M.M. Santos (Emilie M.); A.J. Yoo (Albert J.); L.F.M. Beenen (Ludo); O.A. Berkhemer (Olvert); M.D. Den Blanken (Mark D.); C. Wismans (Carrie); W.J. Niessen (Wiro); C.B. Majoie (Charles); H. Marquering (Henk)

    2016-01-01

    textabstractIntroduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by

  4. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    NARCIS (Netherlands)

    Santos, E.M.; Yoo, A.J.; Beenen, L.F.; Berkhemer, O.A.; Blanken, M.D. den; Wismans, C.; Niessen, W.J.; Majoie, C.B.; Marquering, H.A.; Dijk, E.J. van; et al.,

    2016-01-01

    INTRODUCTION: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and

  5. 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.

  6. 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.

  7. Erythrocyte membrane modified janus polymeric motors for thrombus therapy

    NARCIS (Netherlands)

    Shao, Jingxin; Abdelghani, Mona; Shen, Guizhi; Cao, Shoupeng; Williams, David S.; van Hest, Jan C.M.

    2018-01-01

    We report the construction of erythrocyte membrane-cloaked Janus polymeric motors (EM-JPMs) which are propelled by near-infrared (NIR) laser irradiation and are successfully applied in thrombus ablation. Chitosan (a natural polysaccharide with positive charge, CHI) and heparin (glycosaminoglycan

  8. 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

  9. Added value of multiphase CTA imaging for thrombus perviousness assessment

    Energy Technology Data Exchange (ETDEWEB)

    Santos, E.M.M. [Academic Medical Center, Department of Biomedical Engineering and Physics, Amsterdam (Netherlands); Erasmus Medical Center, Department of Medical Informatics, Rotterdam (Netherlands); D' Esterre, C.D.; Najm, M.; Goyal, M.; Demchuk, A.M.; Menon, B.K. [University of Calgary, Departments of Neurosciences, Radiology and Community Health Sciences, Calgary (Canada); Treurniet, K.M.; Majoie, C.B. [Academic Medical Center, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Niessen, W.J. [Erasmus Medical Center, Department of Medical Informatics, Rotterdam (Netherlands); Delft University of Technology, Faculty of Applied Sciences, Delft (Netherlands); Marquering, H.A. [Academic Medical Center, Department of Biomedical Engineering and Physics, Amsterdam (Netherlands); Academic Medical Center, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Mandzia, Jennifer; Fainardi, Enrico; Rubiera, Marta; Khaw, Alexander V.; Zini, Andrea; Shankar, JJ.; Collaboration: PRove-IT investigators

    2018-01-15

    Thrombus perviousness has been associated with favorable functional outcome in acute ischemic stroke (AIS) patients. Measuring thrombus perviousness on CTA may be suboptimal due to potential delay in contrast agent arrival in occluded arteries at the moment of imaging. Dynamic sequences acquired over time can potentially overcome this issue. We investigate if dynamic CTA has added value in assessing thrombus perviousness. Prospectively collected image data of AIS patients with proven occlusion of the anterior or posterior circulation with thin-slice multi-phase CTA (MCTA) and non-contrast CT were co-registered (n = 221). Thrombus attenuation increase (TAI; a perviousness measure) was measured for the arterial, venous, and delayed phase of the MCTA and time-invariant CTAs (TiCTA). Associations with favorable clinical outcome (90-day mRS ≤ 2) were assessed using univariate and multivariable regressions and calculating areas under receiver operating curves (AUC). TAI determined from the arterial phase CTA was superior in the association with favorable outcome with OR = 1.21 per 10 HU increase (95%CI 1.04-1.41, AUC 0.62, p = 0.014) compared to any other phase (venous 1.14(95%CI 1.01-1.30, AUC 0.58, p = 0.033), delayed 1.046(95%CI 0.919-1.19, AUC 0.53, p = 0.50)), and TiCTA 1.15(95%CI 1.02-1.30, AUC 0.60, p = 0.022). In the multivariable model, only TAI on arterial phase was significantly associated with favorable outcome (aOR 1.59, 95%CI 1.04-2.43, p = 0.032). Association between TAI with functional outcome was optimal on arterial-phase CTA such that dynamic CTA imaging has no additional benefits in current thrombus perviousness assessment, thereby suggesting that the delay of contrast arrival at the clot is a key variable for patient functional outcome. (orig.)

  10. Coronary artery stent mimicking intracardiac thrombus on cardiac magnetic resonance imaging due to signal loss

    DEFF Research Database (Denmark)

    Qayyum, Abbas Ali; Vejlstrup, Niels Grove; Ahtarovski, Kiril Aleksov

    2012-01-01

    Since the introduction of percutaneous coronary intervention for coronary artery disease, thousands of patients have been treated with the implantation of coronary stents. Moreover, several of the patients with coronary stent undergo cardiac magnetic resonance (CMR) imaging every year. This case...... report is of a 77-year-old man who was previously treated with the implantation of a coronary stent in the left circumflex artery. He underwent CMR imaging, which revealed a process 14×21 mm in the left atrium. Cardiac contrast computed tomography did not demonstrate any cardiac pathology. While...... the signal loss on MRI associated with implanted metallic devices is known, we report a case where an implanted coronary stent in the left circumflex artery led to an intracardiac signal loss mimicking intracardiac thrombus/tumor....

  11. Treatment options for hepatocellular carcinoma.

    Science.gov (United States)

    Sandhu, Dalbir S; Tharayil, Vivek S; Lai, Jin-Ping; Roberts, Lewis R

    2008-02-01

    Hepatocellular carcinoma (HCC) is frequently diagnosed at advanced stages and has a high mortality rate. With improved survival of patients with cirrhotic liver disease and increased prevalence of chronic hepatitis C viral infections, a rise in the number of HCC cases is being reported worldwide. Early diagnosis and treatment can significantly improve the prognosis of patients with HCC. Although surgical resection is an important potentially curative therapy for liver tumors, in appropriately selected patients, liver transplantation has been shown to achieve excellent survival rates for a solid tumor. Locally ablative and locoregional therapies in the form of percutaneous ethanol injection, radiofrequency ablation, transcatheter arterial chemoembolization and transcatheter arterial radioembolization (TheraSphere) are viable options in patients with unresectable HCC. Unfortunately, the role of systemic therapy has been very limited in the treatment of these patients. Novel treatment options based on an improved understanding of the molecular pathogenesis of HCC are being explored. These targeted molecular therapies are aimed at growth factors and their receptors, intracellular signal transduction and cell cycle control. A substantial improvement in outcomes of intermediate and advanced stage HCC is expected with the advent of these targeted therapies, used in combination with surgical or locoregional therapies. Recent positive results from a large Phase III study of the receptor tyrosine kinase inhibitor, sorafenib, hold great promise in the treatment of HCC.

  12. 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

  13. Hepatocellular carcinoma: treatment with transcatheter arterial chemoembolization

    International Nuclear Information System (INIS)

    Acunas, Buelent; Rozanes, Izzet

    1999-01-01

    This article presents a review of the literature regarding the use of transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). There have been two different approaches to the treatment: (a) percutaneous tumor ablation methods which can be divided into injectable and thermal methods; percutaneous ethanol injection (PEI) is the most widely used method, and (b) TACE. PEI is the treatment of choice for single HCCs smaller or equal to 3 cm in size. For patients with large HCCs combined TACE and PEI is probably the most effective nonsurgical treatment. In the presence of multiple HCC nodules, TACE remains the treatment of choice

  14. Prediction of thrombus-related mechanical prosthetic valve dysfunction using transesophageal echocardiography

    Science.gov (United States)

    Lin, S. S.; Tiong, I. Y.; Asher, C. R.; Murphy, M. T.; Thomas, J. D.; Griffin, B. P.

    2000-01-01

    Identification of thrombus-related mechanical prosthetic valve dysfunction (MPVD) has important therapeutic implications. We sought to develop an algorithm, combining clinical and echocardiographic parameters, for prediction of thrombus-related MPVD in a series of 53 patients (24 men, age 52 +/- 16 years) who had intraoperative diagnosis of thrombus or pannus from 1992 to 1997. Clinical and echocardiographic parameters were analyzed to identify predictors of thrombus and pannus. Prevalence of thrombus and diagnostic yields relative to the number of predictors were determined. There were 22 patients with thrombus, 19 patients with pannus, and 12 patients with both. Forty-two of 53 masses were visualized using transesophageal echocardiography (TEE), including 29 of 34 thrombi or both thrombi and panni and 13 of 19 isolated panni. Predictors of thrombus or mixed presentation include mobile mass (p = 0.009), attachment to occluder (p = 0.02), elevated gradients (p = 0.04), and an international normalized ratio of or = 1 predictor. The prevalence of thrombus in the presence of or = 3 predictors is 14%, 69%, and 91%, respectively. Thus, TEE is sensitive in the identification of abnormal mass in the setting of MPVD. An algorithm based on clinical and transesophageal echocardiographic predictors may be useful to estimate the likelihood of thrombus in the setting of MPVD. In the presence of > or = 3 predictors, the probability of thrombus is high.

  15. 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.

  16. 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)

  17. 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

  18. Sonographic evolution of hepatocellular carcinoma associated with cirrhosis

    International Nuclear Information System (INIS)

    Mazzola, G.; Virdone, R.; Orlando, A.; Turri, A.; Caltagirone, M.; Fusco, G.; Parisi, P.; Cottone, M.

    1989-01-01

    To study the sonographic (US) evolution of hepatocellular carcinoma, 53 tumors in 45 untreated patients were observed regulary with real-time US for a period of 6 to 56 months. At the beginning, 25 tumors were hypoechoic, 18 isoechoic, 4 hyperechoic, and 6 had mixed hypo/hyper echopatterns. At the follow-up, 7 initially hypoechoic tumors had changed to hyperechoic or to mixed echopatterns; 8 hypoechoic tumors had becom isoechoic; 9 of the 25 initially hypoechoic neoplastic lesions had maintained the same echodensity. Ten of the 15 initially isoechoic tumors had changed to mixed echopatterns and 5 had remained unchanged. Three initially isoechoic lesions and a hypoechoic one had turned into diffuse patterns; 2 initially hyperechoic neoplastic lesions had remained unchanged; 1 had switched into hypoechoic, and 1 changed to mixed echopattern; 4 out of 6 tumors with echopattern had remained unchanged, 1 had become hyperechoic and 1 hypoechoic. The current study has proven variou tumors ≤3 cm in diameter to be isoechoic and most tumors >3 in diameter to have mixed hypo/hyper echopatterns. The echogenicity of small hepatocellular carcinomas increases with the tumor growth and remains unchanged when they do not increase in size

  19. Surgical Treatment for Thrombus Straddling a Patent Foramen Ovale

    Directory of Open Access Journals (Sweden)

    Marcos Aurélio Barboza de Oliveira

    Full Text Available Abstract We present a case of a 41-year-old female with deep vein thrombosis after abdominal surgery. The patient quickly developed severe pulmonary embolism and stroke representative of paradoxical embolism. Echocardiography showed a thrombus straddling a patent foramen ovale, which was confirmed intraoperatively. An accurate diagnosis and rapid treatment decisions are crucial for preventing patient deterioration in the form of new pulmonary embolisms or stroke.

  20. Imaging thrombus with radiolabelled monoclonal antibody to platelets

    International Nuclear Information System (INIS)

    Loutfi, I.; Peters, A.M.; Lavender, J.P.; Epenetos, A.A.

    1988-01-01

    Indium-111-hydroxyquinoline labelled platelets, though useful in the detection of thrombus, have not gained widespread use owing to the time and technical skill required for their preparation. A study was therefore conducted evaluating a new method of imaging thrombus with platelets radiolabelled with a 111 In labelled monoclonal antibody, P 256 , directed to the platelet surface glycoprotein complex IIb/IIIa. When the number of receptors occupied by P 256 was less than 3% of the total available on the platelet surface platelet function, as assessed by platelet aggregometry, was undisturbed. P 256 was radiolabelled with 111 In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo - that is, by direct intravenous injection of P 256 - in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The 111 In kinetics recorded after intravenous P 256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P 256 , three had documented thrombus, tow of whom gave positive results on P 256 platelet scintigraphy. The third subject had chromic deep venous thrombosis and was scintigraphically negative. Imaging thrombus using a radiolabelled monoclonal antibody directed to platelets appears to offer great potential as a simple, non-invasive approach to the diagnosis of thrombosis. 3 refs. (Author)

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

    Science.gov (United States)

    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.

  2. Ultrasound active nanoscaled lipid formulations for thrombus lysis.

    Science.gov (United States)

    Becker, Andreas; Marxer, Elena; Brüssler, Jana; Hoormann, Anne Sophia; Kuhnt, Daniela; Bakowsky, Udo; Nimsky, Christopher

    2011-04-01

    In the present study, we investigated the sonothrombolytic effect of new nanoscaled lipid formulations in human blood clots, using diagnostic ultrasound. Human blood clots of 1 ml were incubated with 1 μl of the different lipid dispersions DPPC/CH, DPPC/PEG40S, DSPC/PEG40S and the commercially available ultrasound contrast agent SonoVue®. Clots were stored for 3 days at 5 °C to obtain maximal clot retraction and lytic resistance. Each clot weight was determined before and after continuous insonation for 1h of insonation at 1.4 MHz. The pressure in the insonation chamber was 80 mm Hg to mimic middle arterial blood pressure. There were no significant differences in thrombus weight before insonation. All nanoscaled formulations and SonoVue® were able to reduce thrombus weight compared to the weight loss of clots that were not insonated but kept under pressure for one hour (p ultrasound enhanced thrombolysis even without thrombolytic drugs. Stable cavitation is a crucial parameter in fragmentation of thrombus architecture. Further studies of physicochemical properties of DSPC/PEG40S are necessary to corroborate our hypothesis. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. 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.

  4. 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.

  5. [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.

  6. Abdominal lymph node metastases of hepatocellular carcinoma diagnosed by computed tomography and angiography

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. [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.

  8. 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.

  9. Associations Between Collateral Status and Thrombus Characteristics and Their Impact in Anterior Circulation Stroke.

    Science.gov (United States)

    Alves, Heitor C; Treurniet, Kilian M; Dutra, Bruna G; Jansen, Ivo G H; Boers, Anna M M; Santos, Emilie M M; Berkhemer, Olvert A; Dippel, Diederik W J; van der Lugt, Aad; van Zwam, Wim H; van Oostenbrugge, Robert J; Lingsma, Hester F; Roos, Yvo B W E M; Yoo, Albert J; Marquering, Henk A; Majoie, Charles B L M

    2018-02-01

    Thrombus characteristics and collateral score are associated with functional outcome in patients with acute ischemic stroke. It has been suggested that they affect each other. The aim of this study is to evaluate the association between clot burden score, thrombus perviousness, and collateral score and to determine whether collateral score influences the association of thrombus characteristics with functional outcome. Patients with baseline thin-slice noncontrast computed tomography and computed tomographic angiography images from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands) were included (n=195). Collateral score and clot burden scores were determined on baseline computed tomographic angiography. Thrombus attenuation increase was determined by comparing thrombus density on noncontrast computed tomography and computed tomographic angiography using a semiautomated method. The association of collateral score with clot burden score and thrombus attenuation increase was evaluated with linear regression. Mediation and effect modification analyses were used to assess the influence of collateral score on the association of clot burden score and thrombus attenuation increase with functional outcome. A higher clot burden score (B=0.063; 95% confidence interval, 0.008-0.118) and a higher thrombus attenuation increase (B=0.014; 95% confidence interval, 0.003-0.026) were associated with higher collateral score. Collateral score mediated the association of clot burden score with functional outcome. The association between thrombus attenuation increase and functional outcome was modified by the collateral score, and this association was stronger in patients with moderate and good collaterals. Patients with lower thrombus burden and higher thrombus perviousness scores had higher collateral score. The positive effect of thrombus perviousness on clinical outcome was only present in patients with

  10. Recent Inferior Myocardial Infarction Complicated with a Right Ventricular Thrombus Detected by Three Cardiac Imaging Modalities.

    Science.gov (United States)

    Kuno, Toshiki; Imaeda, Syohei; Hashimoto, Kenji; Ryuzaki, Toshinobu; Saito, Tetsuya; Yamazaki, Hiroyuki; Tabei, Ryota; Kodaira, Masaki; Hase, Manabu; Numasawa, Yohei

    2018-03-01

    We report the case of a 71-year-old woman diagnosed with recent inferior myocardial infarction complicated with right ventricular infarction and a right ventricular thrombus. Three-dimensional transthoracic echocardiography, contrast-enhanced computed tomography, and cardiac magnetic resonance imaging clearly detected a thrombus. We consider cases with a recent right ventricular infarction to require assessment for thrombus formations in the right ventricle. Fortunately, vigorous anticoagulation therapy resolved the thrombi in both the right ventricle and right coronary artery.

  11. Angioplasty of symptomatic high-grade internal carotid artery stenosis with intraluminal thrombus: therapeutic approach

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, A.; Mayol, A. [Seccion de Neurorradiologia Intervencionista, Servicio de Radiologia, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, Avenida Manuel Siurot s/n, 41013, Sevilla (Spain); Gil-Peralta, A.; Gonzalez-Marcos, J.R. [Servicio de Neurologia, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, 41013, Sevilla (Spain); Boza, F. [Servicio de Neurofisiologia, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, 41013, Sevilla (Spain); Ruano, J. [Unidad de Cuidados Intensivos, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, 41013, Sevilla (Spain)

    2004-04-01

    Intraluminal thrombus in the internal carotid artery (ICA) is usually found in patients with severe atheromatous stenosis. Having reviewed 300 carotid angioplasties for symptomatic >70% ICA stenosis, we found three patients (1%) with intraluminal thrombus. Conservative treatment with anticoagulants and double antiplatelet coverage can result in lysis of the thrombus without severe risks. Percutaneous transluminal angioplasty and stenting, preferably with distal protection, can be an excellent alternative to carotid endarterectomy. (orig.)

  12. Computational Study of Thrombus Formation and Clotting Factor Effects under Venous Flow Conditions

    Science.gov (United States)

    2016-04-26

    domain used in our thrombus formation simulations. Fig. 2 B shows the 3D geometry of the flow-chamber section consisting of two channels measuring 250 60...ArticleComputational Study of Thrombus Formation and Clotting Factor Effects under Venous Flow ConditionsVijay Govindarajan,1 Vineet Rakesh,1 Jaques...understanding of thrombus formation as a physicochemical process that has evolved to protect the integrity of the human vasculature is critical to our ability to

  13. Giant hepatocellular adenoma; case report

    Energy Technology Data Exchange (ETDEWEB)

    Pitella, F.A.; Coutinho, A.M.N.; Coura Filho, G.B.; Costa, P.L.A.; Ono, C.R.; Watanabe, T.; Sapienza, M.T.; Hironaka, F.; Cerri, G.G.; Buchpiguel, C.A. [Universidade de Sao Paulo (FM/USP), SP (Brazil). Inst. de Radiologia. Servico de Medicina Nuclear

    2008-07-01

    Full text: Introduction: Hepatocellular adenoma is a benign hepatic tumor identified mainly in women during fertility age, with estimated incidence of 4/1000 inhabitants. It is usually unique, well circumscribed, with or without a capsule, size varying from 1 to 30 cm, with possible central areas of necrosis and hemorrhage. Case Report: A 37-year-old female patient presenting with no comorbities, use of hormonal birth control pills for 18 years, a condition of reduction in the consistency of feces, increase in number of daily defecations, abdominal cramps, and a stuffed sensation after meals for two years. A palpable abdominal mass extending from the right hypochondriac to the right iliac fossa was noticed four months ago. A computerized tomography (CT) showed an extensive hepatic mass on the right which was considered, within the diagnostic hypotheses, hepatic adenomatosis, without ruling out secondary lesions. A hepatic scintillography with {sup 99m}Tc-DISIDA showed an extensive exophytic area from segment V to the right iliac fossa with arterialized blood flow and hepatocytic activity, as well as a hepatic nodule in segment VII with hepatocytic activity consistent with the hepatic adenomas hypothesis. The biopsy confirmed the hepatic adenoma diagnosis and the patient was submitted to a partial hepatectomy and cholecystectomy with good clinical evolution. Conclusion: Nuclear Medicine may supplement the assessment of hepatic nodules, including giant masses, thus suggesting new hypotheses and direction to therapeutic conduct. (author)

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

    Science.gov (United States)

    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.

  15. A Hepatocellular Carcinoma Case in a Patient Who had Immunity to Hepatitis B Virus Earlier.

    Science.gov (United States)

    Ates, Ihsan; Kaplan, Mustafa; Demirci, Selim; Altiparmak, Emin

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Hepatitis B virus infection is one of the most important etilogical factors of HCC. In this case report, a patient with HCC previously infected and having ongoing immunity against hepatitis B virus will be discussed. Ates I, Kaplan M, Demirci S, Altiparmak E. A Hepatocellular Carcinoma Case in a Patient Who had Immunity to Hepatitis B Virus Earlier. Euroasian J Hepato-Gastroenterol 2016;6(1):82-83.

  16. 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

  17. Viral hepatitis and hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. 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

  19. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    International Nuclear Information System (INIS)

    Santos, Emilie M.M.; Yoo, Albert J.; Beenen, Ludo F.; Majoie, Charles B.; Berkhemer, Olvert A.; Blanken, Mark D. den; Wismans, Carrie; Niessen, Wiro J.; Marquering, Henk A.

    2016-01-01

    Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland-Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs. (orig.)

  20. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Emilie M.M. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, P.O. Box 2040, Rotterdam (Netherlands); Department of Radiology, AMC, Amsterdam (Netherlands); Yoo, Albert J. [Texas Stroke Institute, Plano, TX (United States); Beenen, Ludo F.; Majoie, Charles B. [Department of Radiology, AMC, Amsterdam (Netherlands); Berkhemer, Olvert A. [Department of Radiology, AMC, Amsterdam (Netherlands); Department of Neurology, Erasmus MC, Rotterdam (Netherlands); Blanken, Mark D. den; Wismans, Carrie [AMC, Department of Biomedical Engineering and Physics, Amsterdam (Netherlands); Niessen, Wiro J. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, P.O. Box 2040, Rotterdam (Netherlands); Delft University of Technology, Faculty of Applied Sciences, Delft (Netherlands); Marquering, Henk A. [Department of Radiology, AMC, Amsterdam (Netherlands); AMC, Department of Biomedical Engineering and Physics, Amsterdam (Netherlands); Collaboration: on behalf of the MR CLEAN investigators

    2016-02-15

    Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland-Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs. (orig.)

  1. Thrombus length discrepancy on dual-phase CT can predict clinical outcome in acute ischemic stroke

    International Nuclear Information System (INIS)

    Park, Mina; Kim, Kyung-eun; Lee, Seung-Koo; Shin, Na-Young; Lim, Soo Mee; Song, Dongbeom; Heo, Ji Hoe; Kim, Jin Woo; Oh, Se Won

    2016-01-01

    The thrombus length may be overestimated on early arterial computed tomography angiography (CTA) depending on the collateral status. We evaluated the value of a grading system based on the thrombus length discrepancy on dual-phase CT in outcome prediction. Forty-eight acute ischemic stroke patients with M1 occlusion were included. Dual-phase CT protocol encompassed non-contrast enhanced CT, CTA with a bolus tracking technique, and delayed contrast enhanced CT (CECT) performed 40s after contrast injection. The thrombus length discrepancy between CTA and CECT was graded by using a three-point scale: G0 = no difference; G1 = no difference in thrombus length, but in attenuation distal to thrombus; G2 = difference in thrombus length. Univariate and multivariate analyses were performed to define independent predictors of poor clinical outcome at 3 months. The thrombus discrepancy grade showed significant linear relationships with both the collateral status (P = 0.008) and the presence of antegrade flow on DSA (P = 0.010) with good interobserver agreement (κ = 0.868). In a multivariate model, the presence of thrombus length discrepancy (G2) was an independent predictor of poor clinical outcome [odds ratio = 11.474 (1.350-97.547); P =0.025]. The presence of thrombus length discrepancy on dual-phase CT may be a useful predictor of unfavourable clinical outcome in acute M1 occlusion patients. (orig.)

  2. Embolotherapy in the management of hepatocellular carcinoma.

    Science.gov (United States)

    Mojtahedi, Alireza; Yang, Xiaoming; Goswami, Gaurav K

    2008-09-01

    Hepatocellular carcinoma (HCC) ranks fifth in frequency of cancers worldwide. The incidence of HCC in the United States is rising, primarily due to the number of patients who were infected by hepatitis in the 1960s and 1970s coupled with the rising migrant population from Asia, where hepatitis is widely prevalent. Up to 80% of the patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the option of resection or liver transplantation. The dual blood supply (arterial and portal) to the liver with predominantly arterial supply to the tumor has made embolotherapy a cornerstone in the management of inoperable HCC. The techniques have become refined not only due to the development of microcatheter angiographic capabilities, but also in the ability to deliver a wide variety of therapeutic agents to these tumors. This article reviews the fundamental principles of bland embolization, chemoembolization, and radioembolization in the management of HCC.

  3. 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

  4. Multifocal manifestation does not affect vascular invasion of hepatocellular carcinoma: implications for patient selection in liver transplantation

    NARCIS (Netherlands)

    Löhe, Florian; Angele, Martin K.; Rentsch, Markus; Graeb, Christian; Gerbes, Alexander; Löhrs, Udo; Beuers, Ulrich; Jauch, Karl-Walter

    2008-01-01

    BACKGROUND AND AIMS: Liver transplantation (OLT) for hepatocellular carcinoma (HCC) improves patient survival when tumor size and number are limited according to the Milan criteria. However, the impact of tumor size vs. the number of lesions for tumor recurrence after OLT is unclear. Microvascular

  5. Hepatocellular carcinomas supplied by inferior phrenic arteries.

    Science.gov (United States)

    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.

  6. 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.)

  7. Hepatocellular carcinomas supplied by inferior phrenic arteries

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  8. Enhanced venous thrombus resolution in plasminogen activator inhibitor type-2 deficient mice.

    Science.gov (United States)

    Siefert, S A; Chabasse, C; Mukhopadhyay, S; Hoofnagle, M H; Strickland, D K; Sarkar, R; Antalis, T M

    2014-10-01

    The resolution of deep vein thrombosis requires an inflammatory response and mobilization of proteases, such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), to degrade the thrombus and remodel the injured vein wall. Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor (serpin) with unique immunosuppressive and cell survival properties that was originally identified as an inhibitor of uPA. To investigate the role of PAI-2 in venous thrombus formation and resolution. Venous thrombus resolution was compared in wild-type C57BL/6, PAI-2(-/-) , and PAI-1(-/-) mice using the stasis model of deep vein thrombosis. Formed thrombi were harvested, thrombus weights were recorded, and tissue was analyzed for uPA and MMP activities, PAI-1 expression, and the nature of inflammatory cell infiltration. We found that the absence of PAI-2 enhanced venous thrombus resolution, while thrombus formation was unaffected. Enhanced venous thrombus resolution in PAI-2(-/-) mice was associated with increased uPA activity and reduced levels of PAI-1, with no significant effect on MMP-2 and -9 activities. PAI-1 deficiency resulted in an increase in thrombus resolution similar to PAI-2 deficiency, but additionally reduced venous thrombus formation and altered MMP activity. PAI-2-deficient thrombi had increased levels of the neutrophil chemoattractant CXCL2, which was associated with early enhanced neutrophil recruitment. These data identify PAI-2 as a novel regulator of venous thrombus resolution, which modulates several pathways involving both inflammatory and uPA activity mechanisms, distinct from PAI-1. Further examination of these pathways may lead to potential therapeutic prospects in accelerating thrombus resolution. © 2014 International Society on Thrombosis and Haemostasis.

  9. Matrix Metalloproteinase 9 (MMP-9 Regulates Vein Wall Biomechanics in Murine Thrombus Resolution.

    Directory of Open Access Journals (Sweden)

    Khanh P Nguyen

    Full Text Available Deep venous thrombosis is a common vascular problem with long-term complications including post-thrombotic syndrome. Post-thrombotic syndrome consists of leg pain, swelling and ulceration that is related to incomplete or maladaptive resolution of the venous thrombus as well as loss of compliance of the vein wall. We examine the role of metalloproteinase-9 (MMP-9, a gene important in extracellular remodeling in other vascular diseases, in mediating thrombus resolution and biomechanical changes of the vein wall.The effects of targeted deletion of MMP-9 were studied in an in vivo murine model of thrombus resolution using the FVB strain of mice. MMP-9 expression and activity significantly increased on day 3 after DVT. The lack of MMP-9 impaired thrombus resolution by 27% and this phenotype was rescued by the transplantation of wildtype bone marrow cells. Using novel biomechanical techniques, we demonstrated that the lack of MMP-9 significantly decreased thrombus-induced loss of vein wall compliance. Biomechanical analysis of the contribution of individual structural components showed that MMP-9 affected the elasticity of the extracellular matrix and collagen-elastin fibers. Biochemical and histological analyses correlated with these biomechanical effects as thrombi of mice lacking MMP-9 had significantly fewer macrophages and collagen as compared to those of wildtype mice.MMP-9 mediates thrombus-induced loss of vein wall compliance by increasing stiffness of the extracellular matrix and collagen-elastin fibers during thrombus resolution. MMP-9 also mediates macrophage and collagen content of the resolving thrombus and bone-marrow derived MMP-9 plays a role in resolution of thrombus mass. These disparate effects of MMP-9 on various aspects of thrombus illustrate the complexity of individual protease function on biomechanical and morphometric aspects of thrombus resolution.

  10. Matrix Metalloproteinase 9 (MMP-9) Regulates Vein Wall Biomechanics in Murine Thrombus Resolution

    Science.gov (United States)

    Nguyen, Khanh P.; McGilvray, Kirk C.; Puttlitz, Christian M.; Mukhopadhyay, Subhradip; Chabasse, Christine; Sarkar, Rajabrata

    2015-01-01

    Objective Deep venous thrombosis is a common vascular problem with long-term complications including post-thrombotic syndrome. Post-thrombotic syndrome consists of leg pain, swelling and ulceration that is related to incomplete or maladaptive resolution of the venous thrombus as well as loss of compliance of the vein wall. We examine the role of metalloproteinase-9 (MMP-9), a gene important in extracellular remodeling in other vascular diseases, in mediating thrombus resolution and biomechanical changes of the vein wall. Methods and Results The effects of targeted deletion of MMP-9 were studied in an in vivo murine model of thrombus resolution using the FVB strain of mice. MMP-9 expression and activity significantly increased on day 3 after DVT. The lack of MMP-9 impaired thrombus resolution by 27% and this phenotype was rescued by the transplantation of wildtype bone marrow cells. Using novel biomechanical techniques, we demonstrated that the lack of MMP-9 significantly decreased thrombus-induced loss of vein wall compliance. Biomechanical analysis of the contribution of individual structural components showed that MMP-9 affected the elasticity of the extracellular matrix and collagen-elastin fibers. Biochemical and histological analyses correlated with these biomechanical effects as thrombi of mice lacking MMP-9 had significantly fewer macrophages and collagen as compared to those of wildtype mice. Conclusions MMP-9 mediates thrombus-induced loss of vein wall compliance by increasing stiffness of the extracellular matrix and collagen-elastin fibers during thrombus resolution. MMP-9 also mediates macrophage and collagen content of the resolving thrombus and bone-marrow derived MMP-9 plays a role in resolution of thrombus mass. These disparate effects of MMP-9 on various aspects of thrombus illustrate the complexity of individual protease function on biomechanical and morphometric aspects of thrombus resolution. PMID:26406902

  11. 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.

  12. 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

  13. Computed tomography scans of metastatic hepatic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Takemoto, Kazumasa; Fukuda, Haruyuki; Nemoto, Yutaka [Osaka City Univ. (Japan). Faculty of Medicine

    1984-01-01

    Computed tomography scans of 114 metastatic hepatic tumors were reviewed. Central low density was found in 82 cases (71.9%) and seems to be characteristic to metastatic hepatic tumors. Dynamic CT was performed on 34 cases, and 21 (61.8%) of these had ring enhancement at the arterial phase. Most of metastatic hepatic tumors could be differentiated from hepatocellular carcinoma. However, metastatic hepatic tumors from renal cell carcinoma, renal rhabdomyosarcoma, malignant melanoma and leiomyosarcoma could not be differentiated from hepatocellular carcinoma, even with use of dynamic study.

  14. 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.

  15. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    OpenAIRE

    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 e...

  16. Variable effects of radiological contrast media on thrombus growth in a rabbit jugular vein thrombosis model

    NARCIS (Netherlands)

    Levi, M. [=Marcel M.; Biemond, B. J.; Sturk, A.; Hoek, J.; ten Cate, J. W.

    1991-01-01

    We studied the effect of an ionic high osmolar contrast medium (Ioxitalamate), an ionic low osmolar contrast medium (Ioxaglate) and various nonionic low osmolar contrast media (Iopamidol, Iopromide and Iohexol) on thrombus growth in a rabbit jugular vein thrombosis model. Thrombus growth was

  17. Deep vein thrombus formation induced by flow reduction in mice is determined by venous side branches.

    Science.gov (United States)

    Brandt, Moritz; Schönfelder, Tanja; Schwenk, Melanie; Becker, Christian; Jäckel, Sven; Reinhardt, Christoph; Stark, Konstantin; Massberg, Steffen; Münzel, Thomas; von Brühl, Marie-Luise; Wenzel, Philip

    2014-01-01

    Interaction between vascular wall abnormalities, inflammatory leukocytes, platelets, coagulation factors and hemorheology in the pathogenesis of deep vein thrombosis (DVT) is incompletely understood, requiring well defined animal models of human disease. We subjected male C57BL/6 mice to ligation of the inferior vena cava (IVC) as a flow reduction model to induce DVT. Thrombus size and weight were analyzed macroscopically and sonographically by B-mode, pulse wave (pw) Doppler and power Doppler imaging (PDI) using high frequency ultrasound. Thrombus size varied substantially between individual procedures and mice, irrespective of the flow reduction achieved by the ligature. Interestingly, PDI accurately predicted thrombus size in a very robust fashion (r2 = 0.9734, p thrombus weight (r2 = 0.5597, p thrombus formation. Occlusion of side branches prior to ligation of IVC did not increase thrombus size, probably due to patent side branches inaccessible to surgery. Venous side branches influence thrombus size in experimental DVT and might therefore prevent thrombus formation. This renders vessel anatomy and hemorheology important determinants in mouse models of DVT, which should be controlled for.

  18. Successful catheter directed thrombolysis of IVC and renal vein occlusive thrombus.

    LENUS (Irish Health Repository)

    McCarthy, E

    2011-11-01

    Thrombus formation is a recognised complication of IVC filter placement, however IVC and bilateral renal vein occlusion secondary to thrombus is much less common. We present a case of infrahepatic caval and bilateral renal vein occlusion secondary to thrombosis of a suprarenal IVC filter. With progressive clinical deterioration and failure of conservative medical management the patient underwent successful mechanical disruption and catheter directed thrombolysis.

  19. Successful Treatment of Free-Floating Right Ventricular Thrombus with Acute Pulmonary Embolism

    Directory of Open Access Journals (Sweden)

    Sanjay Singhal

    2015-01-01

    Full Text Available Acute pulmonary embolism with floating right intra-ventricular thrombus is a rare phenomena associated with poor prognosis. Here, we are presenting a case of 35-year-young male with no co-morbid illness diagnosed to have right ventricular thrombus with bilateral pulmonary embolism, which was managed successfully with thrombolytic therapy.

  20. 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.

  1. Fibrin d-dimer concentration, deep vein thrombosis symptom duration, and venous thrombus volume.

    Science.gov (United States)

    Kurklinsky, Andrew K; Kalsi, Henna; Wysokinski, Waldemar E; Mauck, Karen F; Bhagra, Anjali; Havyer, Rachel D; Thompson, Carrie A; Hayes, Sharonne N; McBane, Robert D

    2011-04-01

    To determine the relationship between fibrin D-dimer levels, symptom duration, and thrombus volume, consecutive patients with incident deep venous thrombosis (DVT) were evaluated. In a cross-sectional study design, patient symptom onset was determined by careful patient questioning. Venous thrombosis was confirmed by compression duplex ultrasonography. Thrombus volume was estimated based on patient's femur length using a forensic anthropology method. Fibrin D-dimer was measured by latex immunoassay. 72 consecutive patients with confirmed leg DVT agreed to participate. The median symptom duration at the time of diagnosis was 10 days. The median D-dimer concentration was 1050 ng/dL. The median thrombus volume was 12.92 cm(3). D-Dimer levels correlated with estimated thrombus volume (P venous thrombosis and correlates with thrombus volume.

  2. Imaging thrombus with radiolabelled monoclonal antibody to platelets

    Energy Technology Data Exchange (ETDEWEB)

    Peters, A.M.; Lavender, J.P.; Needham, S.G.; Loutfi, I.; Snook, D.; Epenetos, A.A.; Lumley, P.; Keery, R.J.; Hogg, N.

    1986-12-13

    A study was conducted evaluating a method of imaging thrombus with platelets radiolabelled with a /sup 111/In labelled monoclonal antibody, P256, directed to the platelet surface glycoprotein complex IIb/IIIa. when the number of receptors occupied by P256 was less than 3% of the total available on the platelet surface, platelet function was undisturbed. P256 was radiolabelled with /sup 111/In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The /sup 111/In kinetics recorded after intravenous P256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P256, three had documented thrombus, two of whom gave positive results on P256 platelet scintigraphy. The third had chronic deep venous thrombosis and was scintigraphically negative.

  3. Intracardiac thrombus in Behçet’s disease

    Directory of Open Access Journals (Sweden)

    I. Ben Ghorbel

    2016-12-01

    Full Text Available Behçet’s disease (BD is a multisystem inflammatory disorder. Intracardiac thrombus (ICT formation is an uncommon but important complication of BD. Of the cases of Behçet’s disease, we selected those with ICT. All patients fulfilled the diagnostic criteria of the International Study Group of Behçet’s disease. The ICT in each case was confirmed by ultrasonography, computed tomography and MRI. Clinical features and laboratory parameters were determined. Among our 518 patients with BD, 8 were diagnosed as having intracardiac thrombus (ICT. All were male; the mean age at the time of the ICT diagnosis was 30.8 years. The main presenting symptoms were hemoptysis, chest pain, and dyspnea. It was associated with pulmonary artery aneurysm and vena cava thrombosis in 3 cases each, pulmonary embolism, and lower limbs deep venous thrombosis in 1 case each. The coexistence of other cardiac complications was as follows: pericarditis in 2 cases, myocarditis, endomyocardial fibrosis, and coronary arteritis with consequent myocardial infarction in one case each. In all cases, echocardiography was sufficient to reach the diagnosis. Chest computed tomography performed in all cases led to the diagnosis of associated pulmonary vasculo-Behçet lesions in 4 cases. All patients received colchicine, anticoagulation, and corticosteroids. Seven patients were on immunosuppressant agents (2 patients received azathioprine and 5 cyclophosphamide. Clinical remission with ICT resolution was observed in 5 cases. Combined immunosuppressive therapy with prednisone and cyclophosphamide might be needed to treat ICT due to BD.

  4. Predictors of Liver Toxicity Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Velec, Michael [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Haddad, Carol R. [Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales (Australia); Craig, Tim [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Wang, Lisa [Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Lindsay, Patricia; Brierley, James; Brade, Anthony; Ringash, Jolie; Wong, Rebecca; Kim, John [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Dawson, Laura A., E-mail: Laura.Dawson@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

    2017-04-01

    Purpose: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. Methods and Materials: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression. CP class B patients were analyzed separately. Results: Among CP class A patients, 101 were evaluable, with a baseline score of A5 (72%) or A6 (28%). Fifty-three percent had portal vein thrombus. The median liver volume was 1286 cc (range, 766-3967 cc), and the median prescribed dose was 36 Gy (range, 27-54 Gy). Toxicity was seen in 26 patients (26%). Thrombus, baseline CP of A6, and lower platelet count were associated with toxicity on univariate analysis, as were several liver DVH-based parameters. Absolute and spared liver volumes were not significant. On multivariate analysis for CP class A patients, significant associations were found for baseline CP score of A6 (odds ratio [OR], 4.85), lower platelet count (OR, 0.90; median, 108 × 10{sup 9}/L vs 150 × 10{sup 9}/L), higher mean liver dose (OR, 1.33; median, 16.9 Gy vs 14.7 Gy), and higher dose to 800 cc of liver (OR, 1.11; median, 14.3 Gy vs 6.0 Gy). With 13 CP-B7 patients included or when dose to 800 cc of liver was replaced with other DVH parameters (eg, dose to 700 or 900 cc of liver) in the multivariate analysis, effective volume and portal vein thrombus were associated with an increased risk. Conclusions: Baseline CP scores and higher liver doses (eg, mean dose, effective volume, doses to 700-900 cc) were strongly associated with liver function decline 3 months after SBRT. A lower baseline platelet count and portal vein thrombus were also associated with an

  5. Surgical Treatment of Hepatocellular Carcinoma

    Science.gov (United States)

    Zamora-Valdes, Daniel; Taner, Timucin; Nagorney, David M.

    2017-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach. PMID:28975836

  6. Magnetic resonance imaging following treatment of advanced hepatocellular carcinoma with sorafenib

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Radiological imagings of small hepatocellular carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. 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.

  10. 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

  11. 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.

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

    Science.gov (United States)

    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.

  13. 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.

  14. Laparoscopic RFA with splenectomy for hepatocellular carcinoma.

    Science.gov (United States)

    Hu, Kunpeng; Lei, Purun; Yao, Zhicheng; Wang, Chenhu; Wang, Qingliang; Xu, Shilei; Xiong, Zhiyong; Huang, He; Xu, Ruiyun; Deng, Meihai; Liu, Bo

    2016-07-27

    The treatment of hepatocellular carcinoma (HCC) is complicated and challenging because of the frequent presence of cirrhosis. Therefore, we propose a novel surgical approach to minimize the invasiveness and risk in patients with HCC, hypersplenism, and esophagogastric varices. This was a retrospective study carried out in 25 patients with HCC and hypersplenism and who underwent simultaneous laparoscopic-guided radio-frequency ablation and laparoscopic splenectomy with endoscopic variceal ligation. Tumor size was restricted to a single nodule of splenectomy. Laparoscopic-guided radio-frequency ablation with laparoscopic splenectomy and endoscopic variceal ligation could be an available technique for patients with HCC <3 cm, hypersplenism, and esophagogastric varices. This approach may help to minimize the surgical risks and results in a fast increase in platelet counts with an acceptable rate of complications.

  15. Platelet endothelial cell adhesion molecule 1 deficiency misguides venous thrombus resolution.

    Science.gov (United States)

    Kellermair, Joerg; Redwan, Bassam; Alias, Sherin; Jabkowski, Joerg; Panzenboeck, Adelheid; Kellermair, Lukas; Winter, Max P; Weltermann, Ansgar; Lang, Irene M

    2013-11-07

    Platelet endothelial cell adhesion molecule 1 (PECAM-1) is involved in leukocyte migration and angiogenesis, which are key components of venous thrombus resolution. This study investigated the effect of PECAM-1 deficiency on thrombus resolution in FVB/n mice and the extent to which levels of soluble PECAM-1 (sPECAM-1) correlate with delayed thrombus resolution in humans after acute symptomatic deep vein thrombosis (DVT). In a mouse stagnant flow venous thrombosis model Pecam-1(-/-) thrombi were larger, persisted for longer periods of time, and displayed attenuated macrophage invasion and decreased vessel formation in the presence of increased fibrosis. In humans, higher levels of truncated plasma sPECAM-1 possibly cleaved from cell surfaces, were found in patients with delayed thrombus resolution (assessed via duplex-based thrombus scoring) relative to those whose thrombi resolved (median, 25th/75th percentile): 92.5 (87.7/103.4) ng/mL vs 71.5 (51.1/81.0) ng/mL; P deep vein thrombus specimens stained positively with antibodies specific for the extracellular, but not the cytoplasmic domain of PECAM-1, consistent with accumulation of cleaved PECAM-1. Our data suggest a regulatory role of PECAM-1 in venous thrombus resolution and suggest a predictive value of sPECAM-1 for postthrombotic syndrome (PTS) after acute DVT.

  16. Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

    Science.gov (United States)

    Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

    2013-07-01

    Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

  17. Left ventricular thrombus formation after acute myocardial infarction as assessed by cardiovascular magnetic resonance imaging

    International Nuclear Information System (INIS)

    Delewi, Ronak; Nijveldt, Robin; Hirsch, Alexander; Marcu, Constantin B.; Robbers, Lourens; Hassell, Marriela E.C.J.; Bruin, Rianne H.A. de; Vleugels, Jim; Laan, Anja M. van der; Bouma, Berto J.; Tio, René A.; Tijssen, Jan G.P.; Rossum, Albert C. van; Zijlstra, Felix; Piek, Jan J.

    2012-01-01

    Introduction: Left ventricular (LV) thrombus formation is a feared complication of myocardial infarction (MI). We assessed the prevalence of LV thrombus in ST-segment elevated MI patients treated with percutaneous coronary intervention (PCI) and compared the diagnostic accuracy of transthoracic echocardiography (TTE) to cardiovascular magnetic resonance imaging (CMR). Also, we evaluated the course of LV thrombi in the modern era of primary PCI. Methods: 200 patients with primary PCI underwent TTE and CMR, at baseline and at 4 months follow-up. Studies were analyzed by two blinded examiners. Patients were seen at 1, 4, 12, and 24 months for assessment of clinical status and adverse events. Results: On CMR at baseline, a thrombus was found in 17 of 194 (8.8%) patients. LV thrombus resolution occurred in 15 patients. Two patients had persistence of LV thrombus on follow-up CMR. On CMR at four months, a thrombus was found in an additional 12 patients. In multivariate analysis, thrombus formation on baseline CMR was independently associated with, baseline infarct size (g) (B = 0.02, SE = 0.02, p < 0.001). Routine TTE had a sensitivity of 21–24% and a specificity of 95–98% compared to CMR for the detection of LV thrombi. Intra- and interobserver variation for detection of LV thrombus were lower for CMR (κ = 0.91 and κ = 0.96) compared to TTE (κ = 0.74 and κ = 0.53). Conclusion: LV thrombus still occurs in a substantial amount of patients after PCI-treated MI, especially in larger infarct sizes. Routine TTE had a low sensitivity for the detection of LV thrombi and the interobserver variation of TTE was large.

  18. Left ventricular thrombus formation after acute myocardial infarction as assessed by cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Delewi, Ronak [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Interuniversity Cardiology Institute of the Netherlands (Netherlands); Nijveldt, Robin [Department of Cardiology, VU University Medical Center, Amsterdam (Netherlands); Hirsch, Alexander [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Marcu, Constantin B.; Robbers, Lourens [Department of Cardiology, VU University Medical Center, Amsterdam (Netherlands); Hassell, Marriela E.C.J.; Bruin, Rianne H.A. de; Vleugels, Jim; Laan, Anja M. van der; Bouma, Berto J. [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Tio, René A. [Thorax Center, University Medical Center Groningen, Groningen (Netherlands); Tijssen, Jan G.P. [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Rossum, Albert C. van [Department of Cardiology, VU University Medical Center, Amsterdam (Netherlands); Zijlstra, Felix [Thorax Center, Department of Cardiology, Erasmus University Medical Center, Rotterdam (Netherlands); Piek, Jan J., E-mail: j.j.piek@amc.uva.nl [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

    2012-12-15

    Introduction: Left ventricular (LV) thrombus formation is a feared complication of myocardial infarction (MI). We assessed the prevalence of LV thrombus in ST-segment elevated MI patients treated with percutaneous coronary intervention (PCI) and compared the diagnostic accuracy of transthoracic echocardiography (TTE) to cardiovascular magnetic resonance imaging (CMR). Also, we evaluated the course of LV thrombi in the modern era of primary PCI. Methods: 200 patients with primary PCI underwent TTE and CMR, at baseline and at 4 months follow-up. Studies were analyzed by two blinded examiners. Patients were seen at 1, 4, 12, and 24 months for assessment of clinical status and adverse events. Results: On CMR at baseline, a thrombus was found in 17 of 194 (8.8%) patients. LV thrombus resolution occurred in 15 patients. Two patients had persistence of LV thrombus on follow-up CMR. On CMR at four months, a thrombus was found in an additional 12 patients. In multivariate analysis, thrombus formation on baseline CMR was independently associated with, baseline infarct size (g) (B = 0.02, SE = 0.02, p < 0.001). Routine TTE had a sensitivity of 21–24% and a specificity of 95–98% compared to CMR for the detection of LV thrombi. Intra- and interobserver variation for detection of LV thrombus were lower for CMR (κ = 0.91 and κ = 0.96) compared to TTE (κ = 0.74 and κ = 0.53). Conclusion: LV thrombus still occurs in a substantial amount of patients after PCI-treated MI, especially in larger infarct sizes. Routine TTE had a low sensitivity for the detection of LV thrombi and the interobserver variation of TTE was large.

  19. Diagnosis of small hepatocellular carcinoma by computed tomography. Study in comparison with pathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Tsunetomi, Shigeyuki; Ohto, Masao; Iino, Yasuo [Chiba Univ. (Japan). School of Medicine

    1984-01-01

    The capability of CT in detecting small hepatocellular carcinoma less than 5 cm in size was studied in 48 patients. Changes in the density of the tumors were analyzed in comparison with the pathologic and angiographic findings. Iso-density was the main cause that made the tumors undetectable in either precontrast or post-contrast scan. By combination of precontrast and postcontrast scans, the majority of the tumors larger than 2 cm were detected. In precontrast scan, the density of the tumors was related to bleeding, necrosis and fatty degeneration in the cancer tissue, and fatty degeneration in the non-cancer tissue. In postcontrast scan, it was related to bleeding, necrosis, fatty degeneration and blood spaces in the cancer tissue. Thus, CT can demonstrate accurately the pathological changes of the tumors as images, and it may be useful not only in the diagnosis of small hepatocellular carcinoma, but also in the assessment of the therapeutic effects.

  20. Biventricular thrombus in hypereosinophilic syndrome presenting with shortness of breath

    Directory of Open Access Journals (Sweden)

    Abdul Baqi

    2016-06-01

    Full Text Available A 48 years old male presented to clinic with 12 months of low grade fever with shortness of breath which has progressively worsened with no associated weight loss, night sweats or loss of appetite. There was no prior history of chronic illness before the current illness. Laboratory workup revealed a high white blood cell count with predominant eosinophils. Chest X-ray was normal. Transthoracic echocardiography and Cardiac Magnetic Resonance showed biventricular thrombi. On further extensive workup the findings were consistent with hypereosinophilic syndrome. The patient was started on oral steroids, hydroxyurea, imatanib mesylate and oral anticoagulation. The patient responded to the treatment with complete resolution of his symptoms over the course of few months. The repeat Echocardiogram after a year showed normal left ventricular systolic and diastolic function with complete resolution of biventricular thrombi. Keywords: Hypereosinophilic syndrome, Thrombus

  1. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation.

    Science.gov (United States)

    Gue, Ying X; Gorog, Diana A

    2017-08-25

    The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions.

  2. Incremental value of contrast echocardiography in the evaluation of a cardiac thrombus.

    Science.gov (United States)

    Po, Jose Ricardo F; Tong, Matthew S; Grove, Erica L; Biederman, Robert W W

    2017-02-01

    A 52-year-old man presented with altered mental status and report of prior complaint of chest pain. On electrocardiography, anterolateral ST-segment elevations with Q-waves in the septal leads were seen. Initial echocardiography images demonstrated a thickened anteroseptum. Further imaging showed the presence of a well-attached laminated apical thrombus. Contrast echocardiography images showed that the thrombus had minimal attachment to the endocardial surface. CT head subsequently showed the presence of acute stroke. The case demonstrates the additional value of contrast echocardiography in the evaluation of cardiac masses despite the certainty in the diagnosis of a thrombus. © 2017, Wiley Periodicals, Inc.

  3. Right Ventricular Endomyocardial Fibrosis Presenting With Ventricular Tachycardia And Apical Thrombus - An Interesting Presentation

    Directory of Open Access Journals (Sweden)

    Amitesh Aggarwal

    2009-11-01

    Full Text Available Endomyocardial fibrosis is a progressive disease of unknown origin affecting children and young adults. It involves inflow portion of right and/or left ventricle and apex. It may be associated with thrombus. Literature regarding right ventricular endomyocardial fibrosis with thrombus is scarce. Here we report a rare case of right ventricular endomyocardial fibrosis presenting as ventricular tachycardia and echocardiographic evidence of apical thrombus. Interestingly there was no pulmonary involvement or evidence of deep venous thrombosis. This case also underscores the importance of urgent echocardiography in diagnosis of obscure cases of ventricular tachycardia.

  4. 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.

  5. 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

  6. 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)

  7. 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

  8. Identification of intraluminal thrombus by ultrasonography in emergency department patients with acute deep venous thrombosis.

    Science.gov (United States)

    Mehta, Ninfa; Schecter, Joshua; Stone, Michael

    2012-05-01

    Traditionally, the diagnosis of deep venous thrombosis (DVT) using duplex ultrasonography (DU) has relied on the absence of venous compressibility. Visualization of an intraluminal thrombus is considered an uncommon finding. The purpose of this study is to determine the frequency of intraluminal thrombus in emergency department (ED) patients diagnosed with acute DVT. Retrospective chart review of adult ED patients with DU examinations demonstrating acute DVT. Patients with chronic DVT or patients in whom DU did not demonstrate DVT were excluded from data analysis. Study reports and ultrasound images were reviewed and analyzed for the presence of intraluminal thrombus. There were 189 patients who met inclusion criteria, of which 160 (85%) were found to have intraluminal thrombus. Intraluminal thrombi are present in the majority of patients in our ED in whom acute DVT is identified by DU. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Intracardiac thrombus in Behçet's disease: Two case reports

    Directory of Open Access Journals (Sweden)

    Brahem Radhia

    2005-07-01

    Full Text Available Abstract Intracardiac thrombus in Behçet's disease is an extremely rare manifestation. We report two such cases. A 20-year-old man presented with dyspnoea, cough and haemoptysis. Right heart thrombus associated with pulmonary artery aneurysm and thromboembolism was identified by helical CT and transoesophageal echocardiography. The second case was a 29-year-old male admitted for fever and chest pain. A diagnosis of right atrial thrombosis associated with pulmonary embolism and hyperhomocysteinemia was made. Due to the absence of haemodynamic compromise, medical management consisting of immunosupressive and anticoagulation therapy was adopted which resulted in complete dissolution of the thrombus with dramatic clinical improvement in both cases of clinical status. Conclusion intracardiac thrombus is a rare complication of Behçet's disease. As shown in our patients, medical treatment should be considered as the first line.

  10. The influence of neck thrombus on clinical outcome and aneurysm morphology after endovascular aneurysm repair

    NARCIS (Netherlands)

    F.M.V. Bastos Gonçalves (Frederico); H.J.M. Verhagen (Hence); K. Chinsakchai (Khamin); J.W. van Keulen (Jasper); M.T. Voûte (Michiel); H.J.A. Zandvoort (Herman); F.L. Moll (Frans); J.A. van Herwaarden (Joost)

    2012-01-01

    textabstractObjective: This study investigated the influence of significant aneurysm neck thrombus in clinical and morphologic outcomes after endovascular aneurysm repair (EVAR). Methods: The patient population was derived from a prospective EVAR database from two university institutions in The

  11. Characterization of an experimental venous thrombus model with MRI, phlebography and histology

    International Nuclear Information System (INIS)

    Schmitz, S.A.; Schiffler, S.; Gust, R.; Winterhalter, S.; Wolf, K.J.; Coupland, S.E.

    2005-01-01

    Introduction: Several magnetic resonance (MR) techniques designed to demonstrate the characteristic signal intensity of blood degeneration products of thrombi have been suggested, but the effect of thrombus organization on the MR display, in particular with regard to its temporal evolution, remains to be determined. It is the purpose of this study to develop a stagnation thrombus model in rabbits and to characterize thrombus at different ages with two (MR) imaging techniques, phlebography and histology. Materials and Methods: Venous stagnation thrombi were induced in the external jugular veins of rabbits using a minimally invasive radiological technique to produce artificial embolic vascular occlusion and hypercoagulability. Twenty-five animals were divided into 5 groups of 5 animals, and each group underwent 1.5 T MR imaging at 1, 3, 5, 7 and 9 days after thrombus induction using a T1-weighted magnetization-prepared rapid gradient-echo sequence (MP-RAGE: TR 10.4 msec, TE 4.0 msec, FA 15 ) and a T2-weighted fast low-angle shot sequence (FLASH: TR 54 msec, TE 18 msec, FA15 ). The thrombus length was measured on the T1-weighted images. Thrombus conspicuity, signal intensity, and heterogeneity on T2* weighted images were described using visual scales. Radiographic venography and histology served as reference methods. Results: Thrombi were successfully induced in all animals. The overall thrombus length decreased from 43±9 (day 1 after induction) to 23±4 mm (day 9). On 3D-reconstructions of the T1-weighted images, the visible portion of the true thrombus length relative to the overall thrombus length was 0.16±0.3 (day 1), 0.24±0.3 (day 3),0.38±0.5 (day 5), 0.06±0.1 (day 7) and 0.00 (day 9). Sixteen of 25 thrombi were detectable with the T2*-weighted technique. The overall thrombus signal intensity decreased with the age of the thrombus from day 1 to day 9. The histological evaluation showed that the rabbit thrombi closely resemble human thrombi morphologically

  12. Recanalization and flow regulate venous thrombus resolution and Matrix metalloproteinases expression in vivo

    Science.gov (United States)

    Chabasse, Christine; Siefert, Suzanne A.; Chaudry, Mohammed; Hoofnagle, Mark H.; Lal, Brajesh K.; Sarkar, Rajabrata

    2016-01-01

    Objective We examined the role of thrombus recanalization and ongoing blood flow in the process of thrombus resolution by comparing two murine in vivo models of deep venous thrombosis. Design of study In CD1 mice, we performed surgical inferior vena cava (IVC) ligation (stasis thrombosis), stenosis (thrombosis with recanalization) or sham procedure. We analyzed thrombus weight over time as a measure of thrombus resolution, and quantified the mRNA and protein levels of Membrane-Type Matrix Metalloproteinases (MT-MMPs) as well as effectors of the plasmin complex at day 4, 8 and 12 post-surgery. Results Despite similar initial thrombus size, the presence of ongoing blood flow (stenosis model) was associated with a 45.91% subsequent improvement in thrombus resolution at day 8, and 12.57% at day 12, as compared with stasis thrombosis (ligation model). Immunoblot and real-time PCR demonstrated a difference in MMP-2 and MMP-9 activity at day 8 between the two models (P=.03 and P=.006 respectively), as well as a difference in MT2-MMP gene expression at day 8 (P=.044) and day 12 (P=0.03) and MT1-MMP protein expression at day 4 (P=.021). Histological analyses revealed distinct areas of recanalization in the thrombi of the stenosis model compared to the ligation model, as well as the recruitment of inflammatory cells, especially macrophages, and a focal pattern of localized expression of MT1-MMP and MT3-MMP proteins surrounding the areas of recanalization in the stenosis model. Conclusions Recanalization and ongoing blood flow accelerate deep venous thrombus resolution in vivo, and are associated with distinct patterns of MT1- and MT3-MMP expression and macrophages localization in areas of intra-thrombus recanalization. PMID:26993683

  13. Thrombus Size is Associated with Etiology of Deep Venous Thrombosis – A Cross-Sectional Study

    OpenAIRE

    Vučić, Nikša; Magdić, Tihana; Krnić, Anton; Včev, Aleksandar; Božić, Dubravko

    2005-01-01

    The aim of this study was to evaluate the impact of risk factors for deep vein thrombosis (DVT) on thrombus sizes in lower extremities. The size and extent of thrombus was scored according to International Consensus Committee for venous disease classification. After the diagnosis of DVT was established and its size scored, predominant risk factors for DVT in each patient were identified (malignant disease, thrombophilia, postoperative state, hormonal therapy, heredity, limb trauma, immobiliza...

  14. Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension

    Science.gov (United States)

    Panzenboeck, Adelheid; Winter, Max P; Schubert, Uwe; Voswinckel, Robert; Frey, Maria K; Jakowitsch, Johannes; Alimohammadi, Arman; Hobohm, Lukas; Mangold, Andreas; Bergmeister, Helga; Sibilia, Maria; Wagner, Erwin F; Mayer, Eckhard; Klepetko, Walter; Hoelzenbein, Thomas J; Preissner, Klaus T; Lang, Irene M

    2015-01-01

    Objective Restoration of patency is a natural target of vascular remodeling following venous thrombosis that involves vascular endothelial cells and smooth muscle cells as well as leukocytes. Acute pulmonary emboli usually resolve within six months. However, in some instances, thrombi transform into fibrous vascular obstructions, resulting in occlusion of the deep veins, or in chronic thromboembolic pulmonary hypertension (CTEPH). We proposed that dysregulated thrombus angiogenesis may contribute to thrombus persistence. Approach and Results Mice with an endothelial-cell-specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor (VEGF-R2/Kdr) were utilized in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of non-resolving venous thromboembolism. Endothelial cell-specific deletion of Kdr and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes such as KDR, vascular endothelial cadherin and podoplanin were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by VEGF. Conclusions In the present work, we propose a mechanism of thrombus non-resolution demonstrating that endothelial cell-specific deletion of Kdr abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis. PMID:24526692

  15. Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Kazankov, Konstantin; Rode, Anthony; Simonsen, Kira Schreiner

    2016-01-01

    BACKGROUND: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. METHODS: In a co...

  16. Evaluation of arterial embolization therapy for hepatocellular carcinoma by liver scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Ohishi, Hajime; Ohue, Shoichi; Ide, Khoichi [Nara Medical Univ., Kashihara (Japan)

    1983-02-01

    After arterial embolization therapy, two cases of hepatocellular carcinoma were followed up by RI scintigraphy, and the results were compared with those of angiography. A correlation between changes in /sup 67/Ga-citrate distribution and angiographical picture was found. This suggested that tumor scintigraphy is useful for follow-up observation after arterial embolization therapy.

  17. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Sung, Wing-Kin; Zheng, Hancheng; Li, Shuyu

    2012-01-01

    To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than...

  18. Hepatocellular carcinoma bone metastasis in an 11-year-old boy

    Energy Technology Data Exchange (ETDEWEB)

    Lucarini, Silvia [Schulich School of Medicine and Dentistry, University of Western Ontario, Department of Diagnostic Radiology and Nuclear Medicine, London, ON (Canada); Fortier, Marielle [Children' s Hospital of Western Ontario, Department of Radiology, London, ON (Canada); Leaker, Michael [Children' s Hospital of Western Ontario, Department of Oncology, London, ON (Canada); Chhem, Rethy [Schulich School of Medicine and Dentistry, University of Western Ontario, Department of Diagnostic Radiology and Nuclear Medicine, London, ON (Canada); London Health Sciences Centre, University Hospital of Windermere, Department of Radiology, London, ON (Canada)

    2008-01-15

    Hepatocellular carcinoma (HCC) is the second most common primary hepatic malignant tumor in children older than 4 years. We describe a rare case of an 11-year-old boy with HCC who presented with HCC of the right liver lobe followed by multiple osseous metastases, confirmed by imaging and biopsy. (orig.)

  19. Glucose-regulated protein 78 regulates the expression of mitochondrial genesis proteins in HBV-related hepatocellular carcinoma: a clinical analysis

    Directory of Open Access Journals (Sweden)

    LI Yaping

    2017-10-01

    Full Text Available ObjectiveTo investigate the expression of glucose-regulated protein 78 (GRP78 in HBV-related hepatocellular carcinoma (HBV-HCC and its association with clinicopathological features, as well as its regulatory effect on mitochondrial genesis proteins in hepatoma cells, and to provide a basis for new strategies for the prevention and treatment of HCC. MethodsTissue samples were collected from 54 patients with HBV-HCC, and immunohistochemistry and Western blot were used to measure the expression of GRP78, Lon, TFAM, and cytochrome C oxidase Ⅳ (COXⅣ. The expression of GRP78 in hepatoma cells was interfered by siRNA, and then the expression of GRP78, Lon, mitochondrial transcription factor A (TFAM, and COX Ⅳ was measured. Quantitative real-time PCR was used to measure the level of mitochondrial DNA (mtDNA in clinical specimens and HCC cells after GRP78 expression was interfered with. A statistical analysis was performed for clinical and experimental data. The t-test was used for comparison of continuous data between groups, the Fisher′s exact test was used for comparison of categorical data between groups, and the Kaplan-Meier method was used for survival analysis. Results Compared with the adjacent tissues, HBV-HCC tissues had significantly higher expression of GRP78 and Lon (t=9.135 and 5523, both P<0.0001 and significantly lower expression of the mitochondrial genesis proteins TFAM and COX Ⅳ and mtDNA level (t=2.765, 4260, and 12.280, P=0.011, <0.001, and <0.001. There were significant increases in the expression of the mitochondrial genesis proteins TFAM and COX Ⅳ and mtDNA level after the interference with GRP78 expression in hepatoma cells (all P<0.05. There were significant differences in the expression of GRP78 between patients with different numbers of tumors, patients with and without portal vein tumor thrombus, and patients with different tumor stages (P=0.016, 0.003, and 0.045. The patients with low GRP78

  20. Optical coherence tomography assessment and quantification of intracoronary thrombus: Status and perspectives

    International Nuclear Information System (INIS)

    Porto, Italo; Mattesini, Alessio; Valente, Serafina; Prati, Francesco; Crea, Filippo; Bolognese, Leonardo

    2015-01-01

    Coronary angiography is the “golden standard” imaging technique in interventional cardiology and it is still widely used to guide interventions. A major drawback of this technique, however, is that it is inaccurate in the evaluation and quantification of intracoronary thrombus burden, a critical prognosticator and predictor of intraprocedural complications in acute coronary syndromes. The introduction of optical coherence tomography (OCT) holds the promise of overcoming this important limitation, as near-infrared light is uniquely sensitive to hemoglobin, the pigment of red blood cells trapped in the thrombus. This narrative review will focus on the use of OCT for the assessment, evaluation and quantification of intracoronary thrombosis. - Highlights: • Thrombotic burden in acute coronary syndromes Is not adequately evaluated by standard coronary angiography, whereas Optical Coherence Tomography is exquisitely sensitive to the hemoglobin contained in red blood cells and can be used to precisely quantify thrombus. • Both research and clinical applications have been developed using the OCT-based evaluation of thrombus. In particular, whereas precise quantification scores are useful for comparing antithrombotic therapies in randomized trials, both pharmacological and mechanical, the most important practical applications for OCT-based assessment of thrombus are the individuation of culprit lesions in the context of diffuse atheromata in acute coronary syndromes, and the so-called “delayed stenting” strategies. • Improvements in 3D rendering techniques are on the verge of revolutionizing OCT-based thrombus assessment, allowing extremely precise quantification of the thrombotic burden

  1. Sixty-Four-Section Cardiac Computed Tomography in Mechanical Prosthetic Heart Valve Dysfunction: Thrombus or Pannus.

    Science.gov (United States)

    Gündüz, Sabahattin; Özkan, Mehmet; Kalçik, Macit; Gürsoy, Ozan Mustafa; Astarcioğlu, Mehmet Ali; Karakoyun, Süleyman; Aykan, Ahmet Çağri; Biteker, Murat; Gökdeniz, Tayyar; Kaya, Hasan; Yesin, Mahmut; Duran, Nilüfer Ekşi; Sevinç, Deniz; Güneysu, Tahsin

    2015-12-01

    Distinguishing pannus and thrombus in patients with prosthetic valve dysfunction is essential for the selection of proper treatment. We have investigated the utility of 64-slice multidetector computed tomography (MDCT) in distinguishing between pannus and thrombus, the latter amenable to thrombolysis. Sixty-two (23 men, mean age 44±14 years) patients with suspected mechanical prosthetic valve dysfunction assessed by transesophageal echocardiography were included in this prospective observational trial. Subsequently, MDCT was performed before any treatment was started. Periprosthetic masses were detected by MDCT in 46 patients, and their attenuation values were measured as Hounsfield Units (HU). Patients underwent thrombolysis unless contraindicated, and those with a contraindication or failed thrombolysis underwent surgery. A mass which was completely lysed or surgically detected as a clot was classified as thrombus, whereas a mass which was surgically detected as tissue overgrowth was classified as pannus. A definitive diagnosis could be achieved in 37 patients with 39 MDCT masses (22 thrombus and 17 pannus). The mean attenuation value of 22 thrombotic masses was significantly lower than that in 17 pannus (87±59 versus 322±122; Ppannus from thrombus. Complete lysis was more common for masses with HUpannus overgrowth, whereas a lower value is associated with thrombus formation. A higher attenuation (HU>90) is associated with reduced lysis rates. © 2015 American Heart Association, Inc.

  2. [Clinical analysis of patients with lower extremity deep venous thrombosis complicated with inferior vena cava thrombus].

    Science.gov (United States)

    Dong, Dian-ning; Wu, Xue-jun; Zhang, Shi-yi; Zhong, Zhen-yue; Jin, Xing

    2013-06-04

    To explore the clinical profiles of patients with lower extremity deep venous thrombosis (DVT) complicated with inferior vena cava (IVC) thrombus and summarize their clinical diagnostic and therapeutic experiences. The clinical characteristics, diagnosis and treatment of 20 hospitalized patients with DVT complicated with inferior vena cava thrombus were analyzed retrospectively. All of them were of proximal DVT. There were phlegmasia cerulea dolens (n = 3), pulmonary embolism (n = 3) and completely occlusion of IVC (n = 5). Clinical manifestations were severe. Retrievable inferior vena cava filter (IVCF) was implanted for 17 cases. Catheter-directed thrombolysis (CDT) through ipsilateral popliteal vein was applied for 7 cases and systemic thrombolysis therapy for 8 cases. The effective rate of thrombolysis for fresh IVC thrombus was 100%. Among 5 cases with Cockett Syndrome, 3 cases underwent balloon dilatation angioplasty and endovascular stenting of iliac vein. And 17 IVCFs were retrieved successfully within 3 weeks. IVC thrombus disappeared completely in 15 cases. Systemic or local thrombolysis with protective IVCF is a safe and effective therapy for nonocclusive IVC thrombus in DVT. And CDT is recommended for symptomatic occlusive IVC thrombus.

  3. Slow flow and mural thrombus in aortic diseases: Spin-echo MR findings and their differentiation

    International Nuclear Information System (INIS)

    Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung

    1993-01-01

    In order to evaluate the ability of spin-echo MR imaging to differentiate slow flow from mural thrombus in aortic diseases, we reviewed the spin-echo MR images of 13 patients with intraaortic thrombus documented by CT (N=11) or aortography (N=2). Six patients had aortic aneurysms and seven had aortic dissections. Intraaortic mural thrombi were accompanied by flow-related intraluminal signal of various pattern and extents in all 13 patients. On 10 gated MR studies, slow flow regions showed ever-echo rephasing phenomenon (N=8), interslice variation of signal intensities of the intraluminal signal (N=7) and flow-related ghost artifact (N=2). However, these MR flow phenomena were obscured on two of three non-gated studies. Seven of 13 intraaortic thrombi remained hyperintense on T2-weighted second-echo images. In these circumstance, a hypointense boundary layer between slow flow and mural thrombus, which was caused by either ' boundary layer dephasing phenomenon' of slow flow or 'paramagnetic T2 shortening' of fresh clot at the edge of mural thrombus, was very useful in discriminating the area of slow flow from that of mural thrombus. Proper interpretation of spin-echo MR images may obviate the need for phase display imaging or gradient-echo imaging in differentiating slow flow and mural thrombus

  4. Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

    Science.gov (United States)

    Chesnutt, Jennifer K. W.; Han, Hai-Chao

    2013-10-01

    Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

  5. Optical coherence tomography assessment and quantification of intracoronary thrombus: Status and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Porto, Italo, E-mail: italo.porto@gmail.com [Interventional Cardiology Unit, San Donato Hospital, Arezzo (Italy); Mattesini, Alessio; Valente, Serafina [Interventional Cardiology Unit, Careggi Hospital, Florence (Italy); Prati, Francesco [Interventional Cardiology San Giovanni Hospital, Rome (Italy); CLI foundation (Italy); Crea, Filippo [Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, Rome (Italy); Bolognese, Leonardo [Interventional Cardiology Unit, San Donato Hospital, Arezzo (Italy)

    2015-04-15

    Coronary angiography is the “golden standard” imaging technique in interventional cardiology and it is still widely used to guide interventions. A major drawback of this technique, however, is that it is inaccurate in the evaluation and quantification of intracoronary thrombus burden, a critical prognosticator and predictor of intraprocedural complications in acute coronary syndromes. The introduction of optical coherence tomography (OCT) holds the promise of overcoming this important limitation, as near-infrared light is uniquely sensitive to hemoglobin, the pigment of red blood cells trapped in the thrombus. This narrative review will focus on the use of OCT for the assessment, evaluation and quantification of intracoronary thrombosis. - Highlights: • Thrombotic burden in acute coronary syndromes Is not adequately evaluated by standard coronary angiography, whereas Optical Coherence Tomography is exquisitely sensitive to the hemoglobin contained in red blood cells and can be used to precisely quantify thrombus. • Both research and clinical applications have been developed using the OCT-based evaluation of thrombus. In particular, whereas precise quantification scores are useful for comparing antithrombotic therapies in randomized trials, both pharmacological and mechanical, the most important practical applications for OCT-based assessment of thrombus are the individuation of culprit lesions in the context of diffuse atheromata in acute coronary syndromes, and the so-called “delayed stenting” strategies. • Improvements in 3D rendering techniques are on the verge of revolutionizing OCT-based thrombus assessment, allowing extremely precise quantification of the thrombotic burden.

  6. Analysis of early thrombus dynamics in a humanized mouse laser injury model.

    Science.gov (United States)

    Wang, Weiwei; Lindsey, John P; Chen, Jianchun; Diacovo, Thomas G; King, Michael R

    2014-01-01

    Platelet aggregation and thrombus formation at the site of injury is a dynamic process that involves the continuous addition of new platelets as well as thrombus rupture. In the early stages of hemostasis (within minutes after vessel injury) this process can be visualized by transfusing fluorescently labeled human platelets and observing their deposition and detachment. These two counterbalancing events help the developing thrombus reach a steady-state morphology, where it is large enough to cover the injured vessel surface but not too large to form a severe thrombotic occlusion. In this study, the spatial and temporal aspects of early stage thrombus dynamics which result from laser-induced injury on arterioles of cremaster muscle in the humanized mouse were visualized using fluorescent microscopy. It was found that rolling platelets show preference for the upstream region while tethering/detaching platelets were primarily found downstream. It was also determined that the platelet deposition rate is relatively steady, whereas the effective thrombus coverage area does not increase at a constant rate. By introducing a new method to graphically represent the real time in vivo physiological shear stress environment, we conclude that the thrombus continuously changes shape by regional growth and decay, and neither dominates in the high shear stress region.

  7. Radioembolization of hepatocellular carcinoma.

    Science.gov (United States)

    Van de Wiele, Christophe

    2010-12-01

    In this review paper, available data on radioembolization of unresectable hepatocellular carcinoma (HCC) using commercially available radiopharmaceuticals, respectively (131)I-Lipiodol, Therasphere (glass-microspheres) and SIRspheres (resin-microspheres) are reviewed. In the palliative setting, (131)I-Lipiodol was shown to yield response rates of 17-92% which in patients with portal vein thrombosis (PVT) translate into a survival benefit as evidenced by a phase III randomized trial. Furthermore, in terms of efficacy, (131)I-Lipiodol is as efficacious as trans-arterial chemoembolization (TACE) but far better tolerated. In the adjuvant setting, improved recurrence-free and overall survival when compared to surgery alone have been reported but these results warrant confirmation by randomized prospective trials. Similar to (131)I-Lipiodol, when administered in a palliative setting, radioembolization using (90)Y microspheres was proven effective for selected cases of non-resectable HCC and well tolerated. Available data suggest that Therasphere treatment outperforms TACE both in terms of response as in terms of event-free survival in unresectable HCC. However, this finding needs confirmation by randomized prospective trials. Therasphere treatment was also shown to limit progression of HCC allowing potential candidates for orthotopic liver transplantation (OLT) more time to wait for donor organs as well as to downstage the HCC disease to such an extent that patients that were initially not, as yet become eligible for OLT with a gain in survival. Finally, Therasphere was shown to be safe and efficacious in HCC patients presenting with PVT, reason for which approval was granted for this indication by the FDA.

  8. Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo

    Science.gov (United States)

    Thomas, Grace M.; Panicot-Dubois, Laurence; Lacroix, Romaric; Dignat-George, Françoise; Lombardo, Dominique

    2009-01-01

    Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active TF and P-selectin glycoprotein ligand 1 (PSGL-1). Cancer cell–derived MPs aggregate platelets via a TF-dependent pathway. In vivo, cancer cell–derived MPs, but not their parent cells, infused into a living mouse accumulate at the site of injury and reduce tail bleeding time and the time to occlusion of venules and arterioles. This thrombotic state is also observed in mice developing tumors. In such mice, the amount of circulating platelet-, endothelial cell–, and cancer cell–derived MPs is increased. Endogenous cancer cell–derived MPs shed from the growing tumor are able to accumulate at the site of injury. Infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor. Collectively, our results indicate that cancer cell–derived MPs bearing PSGL-1 and TF play a key role in thrombus formation in vivo. Targeting these MPs could be of clinical interest in the prevention of thrombosis and to limit formation of metastasis in cancer patients. PMID:19667060

  9. Computed tomographic findings of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. 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...

  11. Potentiality of immunotherapy against hepatocellular carcinoma

    Science.gov (United States)

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future. PMID:26420958

  12. Infrequent widespread microsatellite instability in hepatocellular carcinomas.

    Science.gov (United States)

    Yamamoto, H; Itoh, F; Fukushima, H; Kaneto, H; Sasaki, S; Ohmura, T; Satoh, T; Karino, Y; Endo, T; Toyota, J; Imai, K

    2000-03-01

    Widespread or high-frequency microsatellite instability (MSI) due to the defective DNA mismatch repair (MMR) occurs in the majority of hereditary non-polyposis colorectal cancer and a subset of sporadic malignant tumors. The incidence of MSI and underlying DNA MMR defects have been well characterized in gastrointestinal carcinogenesis, but not in hepatocarcinogenesis. To address the issue, we analyzed 55 Japanese hepatocellular carcinomas using several indicators of DNA MMR defects, such as microsatellite analysis, loss of heterozygosity (LOH) and mutation analysis of MMR genes, methylation of hMLH1 promoter, and frameshift mutations of mononucleotide repeat sequences within possible target genes. Mutation of beta2-microglobulin gene, which is presumably involved in MSI-positive tumor cell escape from immune surveillance was also examined. Some of these analyses were also carried out in 9 human liver cancer cell lines. None of the 3 quasi-monomorphic mononucleotide markers sensitive for MSI, BAT26, BAT25, and BAT34C4 presented shortened unstable alleles in any of the carcinoma, cirrhosis, chronic hepatitis tissues, or cell lines. LOH at MMR genes was infrequent (4.4 approximately 7.1%), and no mutations were detected. Neither hMLH1 hypermethylation nor frameshift mutation in the target genes was detected. No mutations were found in beta2-microglobulin. Widespread MSI due to the defective DNA MMR appears to play little if any part in Japanese hepatocarcinogenesis.

  13. Percutaneous CT-guided high frequency induced thermotherapy as a treatment hepatocellular carcinoma and hepatic metastatic lesions

    International Nuclear Information System (INIS)

    Lu Ligong; Luo Pengfei; Chen Xiaoming

    2004-01-01

    Objective: To analyze the efficacy, side effects and complications of percutaneous high frequency induced thermotherapy (HiTT) performed under CT guidance involving 36 patients with hepatocellular carcinomas (HCC) and hepatic metastatic lesions. Methods: HiTT was performed in treatment of 36 patients (24 men and 12 women) with 42 hepatocellular carcinoma and hepatic metastatic carcinoma (six patient out of 36 had two nidi). The diameter of the tumors ranged from 1.6 to 7.8 cm (mean, 3.2 cm). The efficacy of HiTT was evaluated with triphasic spiral CT performed 1 month after the procedure. Results: The post-treatment CT scan showed complete necrosis in 33 nidi (78%) out of 42 nidi of hepatocellular carcinoma and hepatic metastatic carcinoma in 30 patients out of 36. Complete necrosis was obtained in 18 (95%) of 19 tumors no larger than 3 cm in diameter, 13 (72%) of 18 tumors between 3.0 and 5.0 cm in diameter. Eleven tumors showed incomplete necrosis. In our study, none of the patients experienced severe complications. All the patients are alive in the follow-up ranging from 2 to 12 months (mean, 7 months). Conclusion: Our research suggests that HiTT can be a safe and effective treatment of hepatocellular carcinomas and hepatic metastatic carcinoma when the lesion is no larger than 3 cm. The treatment is relatively effective for hepatocellular carcinoma between 3 and 5 cm in size. (authors)

  14. Potential application of labeled antibodies for thrombus detection

    Energy Technology Data Exchange (ETDEWEB)

    Ezekowitz, M.D.; Coller, B.S.; Srivastava, S.C.

    1986-01-01

    Labeling platelets with monoclonal antibodies in whole blood for imaging thrombi is less cumbersome than the established /sup 111/In-oxine method. 7E3, a murine monoclonal antibody directed against glycoprotein IIb and/or IIIa on both human and dog platelets was used to label canine platelets. Thrombi were induced by transcatheter placement of a copper coil followed by electrocoagulation. 7E3 was iodinated with /sup 131/I and labelled with /sup 111/In using 7E3-DTPA conjugate. Whole blood was incubated with 0.5 - 1.0 ..mu..g labeled 7E3/mL blood. In 4/4 dogs, experimental deep vein thrombi were identified using both /sup 131/I-and /sup 111/In-labeled 7E3 within 5-30 min after injection. For both isotopes, 1 h blood clearance was 54 + - 9%. In 1/3 dogs, experimental coronary thrombus could be identified ex vivo at 4 h. Clot to blood ratios ranged between 7 to 13:1. Using the /sup 111/In-oxine method, 0/3 coronary thrombi were seen. Thus, /sup 131/I-and /sup 111/In-labeled 7E3 may be used to readily identify peripheral venous thrombi. For reliable and prompt identification of coronary thrombi, more rapid clearance of the labeled platelets is required.

  15. Interventional treatment for old thrombus in iliofemoral deep veins

    International Nuclear Information System (INIS)

    Qian Jun; Jiang Hong; Yang Yang

    2009-01-01

    Objective: To evaluate interventional management in treating old thrombus in iliofemoral deep veins. Methods: The clinical data and the interventional treatment results of 32 patients with chronic iliofemoral deep venous thrombosis were retrospectively reviewed and analyzed. Results: Technical success was achieved in 30 patients (93.8%). Twenty-nine endovascular stents were successfully placed in 25 patients. Postoperative therapeutic effects were as follows: grade I was obtained in 4 cases (12.5%), grade II in 16 cases (50.0%), grade III in 10 cases (31.3%) and grade IV in 2 cases (6.3%). Twenty-nine patients were followed-up for a mean period of 13.0 ± 6.8 months, and three patients were lost in touch. The follow-up results were as follows: grade I was seen in 3 cases (10.3%), grade II in 14 cases (48.3%) and grade III in 12 cases (41.4%). Conclusion: Interventional management is a minimally-invasive, safe and effective treatment for chronic iliofemoral deep venous thrombosis. (authors)

  16. 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.

  17. CT and angiographic appearances of hepatocellular carcinoma partially fed by right inferior phrenic artery

    Energy Technology Data Exchange (ETDEWEB)

    Ohtomo, Kuni; Furui, Shigeru; Yoshikawa, Hiroki; Yashiro, Naofumi; Araki, Tsutomu [Tokyo Univ. (Japan). Faculty of Medicine

    1983-04-01

    CT and angiographic appearances of 8 hepatocellular carcinomas which were partially fed by right inferior phrenic artery were discussed. CT demonstrated tumor fully occupied posterior segment of right hepatic lobe in 6 cases which were composed of 3 solitary massive, 2 massive nodular and 1 confluent massive angiographically. In the other 2 cases, CT showed encapsulated tumor in posterior inferior portion of posterior segment protruded from the liver. In 6 out of these 8 cases, tumor vessels and tumor stain were chiefly derived from posterior branch of right inferior phrenic artery.

  18. CT and angiographic appearances of hepatocellular carcinoma partially feeded by right inferior phrenic artery

    International Nuclear Information System (INIS)

    Ohtomo, Kuni; Furui, Shigeru; Yoshikawa, Hiroki; Yashiro, Naofumi; Araki, Tsutomu

    1983-01-01

    CT and angiographic appearances of 8 hepatocellular carcinomas which were partially feeded by right inferior phrenic artery were discussed. CT demonstrated tumor fully occupied posterior segment of right hepatic lobe in 6 cases which were composed of 3 solitary massive, 2 massive nodular and 1 confluent massive angiographically. In the other 2 cases, CT showed encapsulated tumor in posterior inferior portion of posterior segment protruded from the liver. In 6 out of these 8 cases, tumor vessels and tumor stain were chiefly derived from posterior branch of right inferior phrenic artery. (author)

  19. Methylation in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    The development of HCC is a complex, multistep, multistage process. The molecular pathogenesis of HCC appears to involve multiple genetic aberrations in the molecular control of hepatocyte proliferation, differentiation and death and the maintenance of genomic integrity. This process is influenced by the cumulative activation and inactivation of oncogenes, tumor suppressor genes and other genes. p53, a tumor suppressor gene, is the most frequently mutated gene in human cancers. There is also a striking sequence specific binding and induction of mutations by AFB1 at codon 249 of p53 in HCC.

    Epigenetic alterations are also involved in cancer development and progression. Methylation of promoter CpG islands is associated with inhibition of transcriptional initiation and permanent silencing of downstream genes.

    It is now known that most important tumor suppressor genes are inactivated, not only by mutations and deletions but also by promoter methylation. Several studies indicated that p16, p15, RASSF1A, MGMT, and GSTP1 promoter hypermethylation are prevalent in HCC. In addition, geographic variation in the methylation status of tumor DNA indicates that environmental factors may influence the frequent and concordant degree of hypermethylation in multiple genes in HCC and that epigeneticenvironmental interactions may be involved in hepatocarcinogenesis. We have found significant relationships between promoter methylation and AFB1-DNA adducts confirming the impact of environmental exposures on gene methylation.

    DNA isolated from serum or plasma of cancer patients frequently contains the same genetic and

  20. Dynamic computed tomography of hepatocellular carcinoma with particular reference to capsule

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Safety of primary percutaneous coronary intervention with and without (selective) thrombus aspiration

    International Nuclear Information System (INIS)

    Farman, M. T.; Saghir, T.; Rizvi, N. H.; Khan, N.; Zaman, K. S.; Sial, J. A.; Malik, A.

    2014-01-01

    Objective: To determine the safety and efficacy of selective thrombus aspiration during Primary Percutaneous Coronary Intervention (PCI). Methods: This observational prospective study was conducted in the catheterization laboratory of a tertiary care cardiovascular centre. A total of 150 consecutive patients who underwent primary PCI were enrolled. Aspiration was done only when thrombus burden was considered significant. After completion of procedure angiographic and electrocardiographic signs were recorded and clinical follow up was documented up to 1 year. Results: No significant difference among the groups was found in age, height, weight and other risk factors like Hypertension, Diabetes Mellitus and Smoking. In general, left anterior descending artery was culprit in 65 % of patients and more than 90 % of culprit vessels had visible thrombus. Multivessel disease was present in 38 % of patients and 22.7% had past history of myocardial infarction. Out of 150 patients 117 (78%) underwent thrombus aspiration. No significant difference was found in ST resolution within 60 minutes (72.6 vs 81.8 %; P<0.285) and myocardial blush grade II and III (41.9 vs 27.3 %; P<0.128). No difference in event free survival was observed among the two groups (80.3 vs 84.8 %; P<0.708) at one year. Conclusion: Selective thrombus aspiration in definite thrombus laden arteries and no aspiration in low or negligible thrombus burden vessels may be a safe and effective strategy in patients undergoing primary PCI. Overall poor risk profile of our patients as compared to western population necessitates further evaluation of this matter in randomized studies. (author)

  7. Frequency of left ventricular thrombus after anterior wall st-segment elevation acute myocardial infarction

    International Nuclear Information System (INIS)

    Iqbal, M.W.; Fayyaz, A.

    2014-01-01

    Left ventricular thrombus (LVT) formation is a well known complication seen in patients presenting with acute anterior wall ST-segment elevation myocardial infarction (STEMI). In previous studies the incidence of this complication, after acute myocardial infarction (AMI) has been reported to be 4% to 60% in large anterior wall STEMI, depending significantly upon the method as well as time of reperfusion therapy after STEMI. Objective: The objective of this descriptive case series study was to evaluate the frequency of left ventricular thrombus formation in patients after acute anterior wall ST-Segment elevation myocardial infarction. Methodology: In this study, 100 patients with anterior wall STEMI presenting to cardiac emergency or coronary care unit (CCU) of Cardiac complex, Gulab Devi Hospital, were selected on non-probability, purposive sampling meeting inclusion criteria, after taking written informed consent. All the patients were treated initially for management of acute STEMI, including use of thrombolytics where indicated. 2-D Transthoracic echocardiography (TTE) was performed during the same admission to assess presence of LV thrombus (LVT). Results: The mean age of the patients was 54.3 +- 11.4 years. There were 84(84%) male patients and 16 (16%) female patients. LVT was present in 28 (28%) patients on TTE. Among those, there were 23 (82.1%) male and 5 (17.9%) female patients. However, out of 84 male patients 27.4% develop LVT and among 16 female patients this ratio was 31.3%. The LV thrombus was independent of age and gender. LV thrombus was significantly less in thrombolytic group as compared to those who were not given this therapy, i.e. p value <0.05. Conclusion: Patients with anterior wall acute STEMI not infrequently develop the complication of development of LV thrombus. In this study the frequency of LV thrombus formation after anterior wall acute STEMI was 28%. (author)

  8. Recanalization and flow regulate venous thrombus resolution and matrix metalloproteinase expression in vivo.

    Science.gov (United States)

    Chabasse, Christine; Siefert, Suzanne A; Chaudry, Mohammed; Hoofnagle, Mark H; Lal, Brajesh K; Sarkar, Rajabrata

    2015-01-01

    We examined the role of thrombus recanalization and ongoing blood flow in the process of thrombus resolution by comparing two murine in vivo models of deep venous thrombosis. In CD1 mice, we performed surgical inferior vena cava ligation (stasis thrombosis), stenosis (thrombosis with recanalization), or sham procedure. We analyzed thrombus weight over time as a measure of thrombus resolution and quantified the messenger RNA and protein levels of membrane-type matrix metalloproteinases (MT-MMPs) as well as effectors of the plasmin complex at days 4, 8, and 12 after surgery. Despite similar initial thrombus size, the presence of ongoing blood flow (stenosis model) was associated with a 45.91% subsequent improvement in thrombus resolution at day 8 and 12.57% at day 12 compared with stasis thrombosis (ligation model). Immunoblot and real-time polymerase chain reaction analysis demonstrated a difference in MMP-2 and MMP-9 activity at day 8 between the two models (P = .03 and P = .006, respectively) as well as a difference in MT2-MMP gene expression at day 8 (P = .044) and day 12 (P = .03) and MT1-MMP protein expression at day 4 (P = .021). Histologic analyses revealed distinct areas of recanalization in the thrombi of the stenosis model compared with the ligation model as well as the recruitment of inflammatory cells, especially macrophages, and a focal pattern of localized expression of MT1-MMP and MT3-MMP proteins surrounding the areas of recanalization in the stenosis model. Recanalization and ongoing blood flow accelerate deep venous thrombus resolution in vivo and are associated with distinct patterns of MT1-MMP and MT3-MMP expression and macrophage localization in areas of intrathrombus recanalization. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  9. Effect of red blood cells on platelet activation and thrombus formation in tortuous arterioles

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    Jennifer K. W. Chesnutt

    2013-12-01

    Full Text Available Thrombosis is a major contributor to cardiovascular disease, which can lead to myocardial infarction and stroke. Thrombosis may form in tortuous microvessels, which are often seen throughout the human body, but the microscale mechanisms and processes are not well understood. In straight vessels, the presence of red blood cells (RBCs is known to push platelets toward walls, which may affect platelet aggregation and thrombus formation. However in tortuous vessels, the effects of RBC interactions with platelets in thrombosis are largely unknown. Accordingly, the objective of this work was to determine the physical effects of RBCs, platelet size, and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A discrete element computational model was used to simulate the transport, collision, adhesion, aggregation, and shear-induced platelet activation of hundreds of individual platelets and RBCs in thrombus formation in tortuous arterioles. Results showed that high shear stress near the inner sides of curved arteriole walls activated platelets to initiate thrombosis. RBCs initially promoted platelet activation, but then collisions of RBCs with mural thrombi reduced the amount of mural thrombus and the size of emboli. In the absence of RBCs, mural thrombus mass was smaller in a highly tortuous arteriole compared to a less tortuous arteriole. In the presence of RBCs however, mural thrombus mass was larger in the highly tortuous arteriole compared to the less tortuous arteriole. As well, smaller platelet size yielded less mural thrombus mass and smaller emboli, either with or without RBCs. This study shed light on microscopic interactions of RBCs and platelets in tortuous microvessels, which have implications in various pathologies associated with thrombosis and bleeding.

  10. High-resolution characterization of a hepatocellular carcinoma genome.

    Science.gov (United States)

    Totoki, Yasushi; Tatsuno, Kenji; Yamamoto, Shogo; Arai, Yasuhito; Hosoda, Fumie; Ishikawa, Shumpei; Tsutsumi, Shuichi; Sonoda, Kohtaro; Totsuka, Hirohiko; Shirakihara, Takuya; Sakamoto, Hiromi; Wang, Linghua; Ojima, Hidenori; Shimada, Kazuaki; Kosuge, Tomoo; Okusaka, Takuji; Kato, Kazuto; Kusuda, Jun; Yoshida, Teruhiko; Aburatani, Hiroyuki; Shibata, Tatsuhiro

    2011-05-01

    Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide. By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins. We further validated 22 chromosomal rearrangements, generating four fusion transcripts that had altered transcriptional regulation (BCORL1-ELF4) or promoter activity. Whole-exome sequencing at a higher sequence depth (>76× coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. This first high-resolution characterization of a virus-associated cancer genome identified previously uncharacterized mutation patterns, intra-chromosomal rearrangements and fusion genes, as well as genetic heterogeneity within the tumor.

  11. Local Recurrence of Hepatocellular Carcinoma after Segmental Transarterial Chemoembolization: Risk Estimates Based on Multiple Prognostic Factors

    International Nuclear Information System (INIS)

    Park, Seung Hyun; Cho, Yun Ku; Ahn, Yong Sik; Park, Yoon Ok; Kim, Jae Kyun; Chung, Jin Wook

    2007-01-01

    To determine the prognostic factors for local recurrence of nodular hepatocellular carcinoma after segmental transarterial chemoembolization. Seventy-four nodular hepatocellular carcinoma tumors ≤5 cm were retrospectively analyzed for local recurrence after segmental transarterial chemoembolization using follow-up CT images (median follow-up of 17 months, 4 77 months in range). The tumors were divided into four groups (IA, IB, IIA, and IIB) according to whether the one-month follow-up CT imaging, after segmental transarterial chemoembolization, showed homogeneous (Group I) or inhomogeneous (Group II) iodized oil accumulation, or whether the tumors were located within the liver segment (Group A) or in a segmental border zone (Group B). Comparison of tumor characteristics between Group IA and the other three groups was performed using the chi-square test. Local recurrence rates were compared among the groups using the Kaplan-Meier estimation and log rank test. Local tumor recurrence occurred in 19 hepatocellular carcinoma tumors (25.7%). There were: 28, 18, 17, and 11 tumors in Group IA, IB, IIA, and IIB, respectively. One of 28 (3.6%) tumors in Group IA, and 18 of 46 (39.1%) tumors in the other three groups showed local recurrence. Comparisons between Group IA and the other three groups showed that the tumor characteristics were similar. One-, two-, and three-year estimated local recurrence rates in Group IA were 0%, 11.1%, and 11.1%, respectively. The difference between Group IA and the other three groups was statistically significant (p 0.000). An acceptably low rate of local recurrence was observed for small or intermediate nodular tumors located within the liver segment with homogeneous iodized oil accumulation

  12. Effect of transcatheter arterial embolization according to angiographic findings in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wang, Chi Hyung; Shim, Hyung Jin; Lee, Jong Ik; Yu, Hyun; Kim, Young Goo; Lee, Jong Beum; Kim, Kun Sang

    1994-01-01

    The purpose of this study is to assess the effect of Transcatheter Arterial Embolization(TAE) according to angiographic findings in hepatocellular carcinoma. We retrospectively reviewed 50 cases who received TAE for unresectable hepatocellular carcinoma. We analyzed the angiographic findings which were correlated with the effect of TAE. The common angiographic findings of the hepatocellular carcinoma were tumor staining, neo vascularity and enlargement of feeding artery. These angiographic findings were classified into grade 0, +1, +2. Effect of TAE were classified into five patterns; good response, partial response, minimal response, no response and more aggravation. In grading of tumor staining, among 50 cases, the grade 0, +1, +2 were seen in 1 case(2%), 14 cases(28%), 35 cases(70%) each. In grading of enlargement of feeding artery, the grade 0, +1, +2 were seen in 7 cases(14%), 19 cases(38%), 24 cases(48%) each. In grading of neo vascularity, the grade 0, +1, +2 were seen in 6 cases(12%), 15 cases(30%), 29 cases(58%) each. This study showed that the higher grade of angiographic finding, the better effect of TAE. A statistically significant difference was found (P<0.005). But the TAE was not effective in some cases (the maximum diameter of mass is over 10cm, portal vein thrombosis or arteriovenous shunt) in spite of high grade. We believe that these angiographic findings (tumor staining, enlargement of feeding artery, neo vascularity) are one of important indices for anticipating the effect of TAE in patients with unresectable hepatocellular carcinoma

  13. Computed tomography of hepatocellular carcinoma. Comparison with scintigraphy and ultrasonography

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    Kaneko, Kuniyuki; Nakata, Hajime; Honda, Hiroshi [University of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

    1983-09-01

    The detectability of hepatocellular carcinoma by computed tomography (CT) was evaluated on 76 cases. The detectability by plain CT was 93% with only slight improvement following a drip infusion of contrast medium. A comparison of scintigraphy, ultrasonography, and CT was also done on 63 cases. From the standpoint of the overall detectability of the tumor, CT was as good as ultrasonography or scintigraphy. Several cases were positive only on either CT or ultrasonography but no case was positive on scintigraphy alone. We believe that the combination of CT and ultrasonography is the most reliable as the screening method.

  14. Research advances in regorafenib in treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    CHEN Weibo

    2017-12-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common malignant liver tumor, and there are limited systemic treatments for patients with advanced HCC. Regorafenib is an oral multi-kinase inhibitor, and phase III clinical trial has shown that regorafenib can significantly extend the median survival of patients with advanced HCC by 2.8 months, which makes it a second-line drug approved by FDA for the treatment of advanced HCC, just after sorafenib. This article reviews the basic and clinical research on regorafenib in the field of HCC.

  15. Research advances in Hedgehog signaling pathway in hepatocellular carcinoma

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    LIU Jia

    2015-02-01

    Full Text Available Hedgehog (Hh signaling pathway is present in many animals and plays an important role in regulating embryonic development and differentiation. Aberrant activation of Hh signaling contributes to the pathogenesis of many malignancies. Recent studies have shown that dysregulated Hh signaling pathway participates in the tumorigenesis, tumor invasion, and metastasis of hepatocellular carcinoma (HCC. Investigation of the relationship between Hh signaling pathway and HCC will help elucidate the molecular mechanism of pathogenesis of HCC and provide a new insight into the development of novel anticancer therapy and therapeutic target.

  16. Extrahepatic spread of hepatocellular carcinoma: a pictorial review

    International Nuclear Information System (INIS)

    Hong, Seong Sook; Kim, Tae Kyoung; Sung, Kyu-Bo; Kim, Pyo Nyun; Ha, Hyun Kwon; Kim, Ah Young; Lee, Moon-Gyu

    2003-01-01

    Although extrahepatic spread of hepatocellular carcinoma (HCC) is uncommon, it can be found anywhere in the body. Most extrahepatic metastases of HCC occur in patients with advanced-stage intrahepatic tumor, but incidental extrahepatic lesions have also occasionally been found in patients with early-stage intrahepatic HCC. The detection of extrahepatic metastatic disease is crucial when planning therapy for patients with HCC and should be used to avoid unnecessary surgical intervention. In this study we illustrate the radiologic findings of extrahepatic metastases of HCC involving various sites. The presumed mechanism of extrahepatic extension of HCC is also discussed. (orig.)

  17. Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.

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    Gokhan Yildiz

    Full Text Available Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal" by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15

  18. Targeting cancer stem cells in hepatocellular carcinoma

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    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  19. Grp78 promotes the invasion of hepatocellular carcinoma

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    Li Hongdan

    2010-01-01

    Full Text Available Abstract Background Glucose regulated protein 78 (Grp78 is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. Methods The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Results Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased

  20. 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

    Glucose regulated protein 78 (Grp78) is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+)-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased RhoA-GTP level, and Grp78 siRNA knockdown rescued Rho

  1. CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3.

    Science.gov (United States)

    Jin, Xiaoxin; Cai, Lifeng; Wang, Changfa; Deng, Xiaofeng; Yi, Shengen; Lei, Zhao; Xiao, Qiangsheng; Xu, Hongbo; Luo, Hongwu; Sun, Jichun

    2018-02-23

    Hepatocellular carcinoma is one of the most common solid tumors in the digestive system. The prognosis of patients with hepatocellular carcinoma is still poor due to the acquisition of multi-drug resistance. TNF Related Apoptosis Inducing Ligand (TRAIL), an attractive anticancer agent, exerts its effect of selectively inducing apoptosis in tumor cells through death receptors and the formation of the downstream death-inducing signaling complex, which activates apical caspases 3/8 and leads to apoptosis. However, hepatocellular carcinoma cells are resistant to TRAIL. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and miRNAs have been regarded as major regulators of normal development and diseases, including cancers. Moreover, lncRNAs and miRNAs have been reported to be associated with multi-drug resistance. In the present study, we investigated the mechanism by which TRAIL resistance of hepatocellular carcinoma is affected from the view of non-coding RNA regulation. We selected and validated candidate miRNAs, miR-24 and miR-221, that regulated caspase 3/8 expression through direct targeting, and thereby affecting TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. In addition, we revealed that CASC2, a well-established tumor suppressive long non-coding RNA, could serve as a "Sponge" of miR-24 and miR-221, thus modulating TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. Taken together, we demonstrated a CASC2/miR-24/miR-221 axis, which can affect the TRAIL resistance of hepatocellular carcinoma through regulating caspase 3/8; through acting as a "Sponge" of miR-24 and miR-221, CASC2 may contribute to improving hepatocellular carcinoma TRAIL resistance, and finally promoting the treatment efficiency of TRAIL-based therapies.

  2. PATHOPHYSIOLOGY STROKE NON-HEMORRHAGIC ET CAUSA THROMBUS

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    Aji Kristianto Wijaya

    2013-10-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Stroke is one of the most common cause of death worldwide and the third leading cause of death in the United States. Stroke composed 90,000 deaths of women and 60,000 men each year. In Indonesia, 8 of 1000 people suffered a stroke. Stroke is divided into two, non-hemorrhagic stroke and hemorrhagic stroke. Most of them (80% is non-hemorrhagic stroke. Non-hemorrhagic stroke can be caused by thrombi or emboli. Understanding the pathophysiology of non-hemorrhagic stroke caused by a thrombus is very important in regard with providing appropriate patient management. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0in; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  3. Chondroitin sulfate iron colloid as MR contrast agent in differentiation between hepatocellular carcinoma and adenomatous hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Suto, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Kato, T. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Matsuo, T. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Kamba, M. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Shimatani, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Ohuchi, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Nakamura, K. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Ohta, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan))

    1993-05-01

    Using a 1.5 T MR imaging unit, T1- and T2-weighted images were obtained before and after i.v. administration of chondroitin sulfate iron colloid (CSIC) in order to differentiate hepatocellular carcinoma (n=20) from adenomatous hyperplasia without atypia (n=16). Differentiation was made from the tumor-liver contrast to noise ratio (CNR) and visual evaluation of the nodule, with reference to signal intensity relative to that of the surrounding liver. The CNR of adenomatous hyperplasia was on T1-weighted images significantly decreased after CSIC administration (p<0.01). On T2-weighted images, there was no significant difference in CNR after CSIC administration. On the other hand, the CNR of hepatocellular carcinoma was significantly increased after CSIC administration on both T1- and T2-weighted images (p<0.01). CSIC reflects intratumor reticuloendothelial cellular functions, and is therefore useful in differentiating hepatocellular carcinoma from adenomatous hyperplasia without atypia. (orig.).

  4. [Recurrent right atrial thrombus in a patient with atrial fibrillation and heart failure].

    Science.gov (United States)

    Elikowski, Waldemar; Wróblewski, Dariusz; Małek-Elikowska, Małgorzata; Mazurek, Andrzej; Foremska-Iciek, Joanna; Łazowski, Stanisław

    2015-11-01

    Atrial fibrillation and heart failure are factors predisposing to locally formed intracardiac thrombosis, which is usually localized in left-sided chambers. A case report. The authors present a case of a 50-year-old male with permanent atrial fibrillation and dilated cardiomyopathy in whom recurrent right atrial thrombus was observed. Initially, the lesion was detected in echocardiography while he was hospitalized due to extensive right-sided pneumonia. The thrombus was successfully treated with heparin, followed by warfarin. Even though the patient continued warfarin use properly, there was recurrence of the thrombus two years later during a new episode of heart failure exacerbation. Because the thrombus was resistant to intensified anticoagulation, cardiac surgery was needed. A large (30 x 25 mm) pedunculated thrombus, as well as two smaller ones (each of 10 x 10 mm) attached closely to the atrial wall and previously not detected either by echocardiography or by magnetic resonance imaging, were excited. A partially organized pattern of the thrombi in histological examination can explain lack of anticoagulation effectiveness. © 2015 MEDPRESS.

  5. CT detection of daughter nodules in hepatocellular carcinoma after lipiodol infusion via the hepatic artery

    Energy Technology Data Exchange (ETDEWEB)

    Ohishi, Hajime; Ohgami, Syoichi; Katsuragi, Masami

    1985-02-01

    The detectability of daughter nodules in 80 hepatocellular carcinomas was compared between CT assisted by Lipiodol Ultra Fluid (Lipiodol) infused via the hepatic artery and IHA (Infusion hepatic angiography). Lipiodol infused via the hepatic artery was selectively accumulated in the tumor vessels and the tumors and small daughter nodules appeared as markedly high density areas by CT. 18 cases in which the daughter nodules were detected were identified only by CT. Furthermore, in 38 cases CT demonstrated superior detectability of the daughthr nodules than IHA. In 15 cases the daughter nodules were newly detected in areas other than the invaded area where the primary tumor existed. This method is very effective in the diagnosis of daughter nodules of hepatocellular carcinoma. (author).

  6. Evaluation of arterial embolization therapy of hepatocellular carcinoma by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ohishi, H; Ohue, S; Ide, K [Nara Medical Univ., Kashihara (Japan)

    1981-11-01

    The therapeutic effect of arterial embolization performed to 18 patients with hepatocellular carcinoma was evaluated by means of computed tomography (CT). 1) After embolization, the tumor was observed to have been reduced in size in all the cases. The relative attenuation coefficients of the tumor region to surrounding liver tissue was decreased at initial stage after arterial embolization, however, it showed a tendency of more elevation than the initial stage in the cases performed follow-up CT. The decrease of the attenuation values at the initial stage suggests the ischemic necrosis, while its elevation is considered attributable to subsequent histologic change and tumor shrinkage. 2) The follow-up CT examination after the arterial embolization on hepatocellular carcinoma provides significant facility for evaluation of its effectiveness and judgement of the time for the repeat arterial embolization.

  7. Comparison of the effect of dabigatran and dalteparin on thrombus stability in a murine model of venous thromboembolism.

    Science.gov (United States)

    Shaya, S A; Saldanha, L J; Vaezzadeh, N; Zhou, J; Ni, R; Gross, P L

    2016-01-01

    ESSENTIALS: Does thrombus stability alter the presentation of venous thromboembolism and do anticoagulants alter this? In a murine model, we imaged a femoral vein thrombus and quantified emboli in the pulmonary arteries. Dabigatran decreases thrombus stability via factor XIII increasing embolization and pulmonary emboli. This cautions against the unapproved use of dabigatran for acute initial treatment of deep vein thrombosis. Venous thromboembolism (VTE) is a collective term for deep vein thrombosis (DVT) and pulmonary embolism (PE). Thrombus instability possibly contributes to progression of DVT to PE, and direct thrombin inhibitors (DTIs) may alter this. To develop a model to assess thrombus stability and its link to PE burden, and identify whether DTIs, in contrast to low-molecular-weight heparin (LMWH), alter this correlation. Twelve minutes after ferric chloride-induced thrombus formation in the femoral vein of female mice, saline, dalteparin (LMWH) or dabigatran (DTI) was administered. Thrombus size and embolic events breaking off from the thrombus were quantified before treatment and at 10-min intervals after treatment for 2 h using intravital videomicroscopy. Lungs were stained for the presence of PE. Thrombus size was similar over time and between treatment groups. Total and large embolic events and pulmonary emboli were highest after treatment with dabigatran. Variations in amounts of pulmonary embolic events were not attributed to variations in thrombus size. Large embolic events correlated with the number of emboli per lung slice independent of treatment. Embolization in factor XIII deficient (FXIII(-/-) ) saline-treated mice was greater than that in wild-type (WT) saline-treated mice, but was similar to WT dabigatran-treated mice. We have developed a mouse model of VTE that can quantify emboli and correlate this with PE burden. Consistent with clinical data, dabigatran, a DTI, acutely decreases thrombus stability and increases PE burden compared with

  8. Iron-Deficiency Anemia Leading to Transient Ischemic Attacks due to Intraluminal Carotid Artery Thrombus

    Directory of Open Access Journals (Sweden)

    H. Z. Batur Caglayan

    2013-01-01

    Full Text Available Reactive thrombocytosis secondary to iron-deficiency anemia (IDA is a rare but recognized cause of stroke. We report the case of a patient with iron-deficiency anemia presenting with multiple transient ischemic attacks (TIA due to intraluminal thrombus of an internal carotid artery. The putative mechanisms underlying anemia and stroke syndromes are not completely understood, and it is believed that iron deficiency may cause ischemic stroke by several potential mechanisms. Thrombocytosis is often associated with iron deficiency, and microcytosis produces a reduction in the red cell deformability and could produce a hypercoagulable state. The platelet count and function observed in iron-deficiency anemia could act synergistically to promote thrombus formation, especially in the setting of an underlying atherosclerotic disease. The presence of floating thrombus in a patient with clinical and MRI evidence of stroke represents a significant therapeutic dilemma and requires immediate decision about treatment.

  9. Mural Thrombus in the Normal-Appearing Descending Thoracic Aorta of a Chronic Smoker

    Science.gov (United States)

    Habib, Habib; Hsu, Judy; Winchell, Patricia Jo; Daoko, Joseph

    2013-01-01

    Thrombus formation in an atherosclerotic or aneurysmal descending thoracic aorta is a well-described, frequently encountered vascular condition. In comparison, thrombus formation in a normal-appearing descending thoracic aorta is reported far less often. We describe the case of a 46-year-old woman who had splenic and renal infarctions secondary to embolic showers from a large, mobile thrombus in a morphologically normal proximal descending thoracic aorta. After the patient underwent anticoagulation, stent-grafting, and surgical bypass to correct an arterial blockage caused by the stent-graft, she resumed a relatively normal life. In contrast with other cases of a thrombotic but normal-appearing descending thoracic aorta, this patient had no known malignancy or systemic coagulative disorders; her sole risk factor was chronic smoking. We discuss our patient's case and review the relevant medical literature, focusing on the effect of smoking on coagulation physiology. PMID:24391341

  10. The accumulation of a platelet protein, thrombospondin, at the site of arterial thrombus formation: Preliminary report

    International Nuclear Information System (INIS)

    Perlman, S.B.; Hammes, R.J.; Besozzi, M.C.; Folts, J.D.; Mosher, D.F.

    1987-01-01

    There are many methods available for the detection of thrombosis, none of which are noninvasive, rapid and accurate. Thrombosponding is a platelet protein that is present in the developing thrombus and may be an effective substance to use for imaging thrombosis. Vascular stenosis and thrombosis were produced in coronary, carotid and femoral arteries in eleven adult mongrel dogs. 131 I labeled thrombosponding was administered to each animal to determine whether the radiotracer accumulated at the site of thrombus formation. The radioactivity per gram of vessels with thrombi was significantly different from the control vessels or whole blood (p=0.0037 and p=0.015, respectively, paired t-test). This preliminary work suggests that iodinated thrombosponding accumulates at the site of thrombus formation. Labeled thrombosponding may be a rapid, safe and accurate method of detecting arterial thrombosis. (orig.)

  11. [Stroke due to infective endocarditis diagnosed by the retrieved thrombus: a case report].

    Science.gov (United States)

    Nakanishi, Kaoru; Kawano, Hiroyuki; Amano, Tatsuo; Omori, Yoshihiko; Kanma, Hiroshi; Hirano, Teruyuki

    2018-01-26

    A 80-years-old woman suddenly presented with aphasia, right hemiparesis, and dysesthesia. MRA showed the left middle cerebral artery occlusion. She was diagnosed as hyperacute ischemic stroke. She was treated with intravenous recombinant tissue plasminogen activator and underwent endovascular thrombectomy. On admission, she had a fever and high C reactive protein, and was treated with antibiotic therapy. The pathological diagnosis of the retrieved thrombus revealed the cluster of the gram positive cocci. The blood culture was negative and thransthoracic echocardiogram did not detect the vegetation. She was finally diagnosed as cardioembolic stroke due to infective endocarditis based on the pathological diagnosis of the retrieved thrombus. The pathological diagnosis of the retrieved thrombus was quite important to clarify the cause of ischemic stroke.

  12. 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

  13. Quantity of residual thrombus after successful catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with recurrence.

    Science.gov (United States)

    Aziz, F; Comerota, A J

    2012-08-01

    Iliofemoral deep venous thrombosis (IFDVT) is an independent risk factor for recurrent DVT. It has been observed that recurrent DVT correlates with residual thrombus. This study evaluates whether risk of recurrence is related to the amount of residual thrombus following catheter-directed thrombolysis (CDT) for IFDVT. Patients who underwent CDT for IFDVT had their degree of lysis quantified by a reader blind to the patients' long-term clinical outcome. Patients were classified into two groups, ≥50% and thrombus. Recurrence was defined as a symptomatic presentation with image verification of new or additional thrombus. A total of 75 patients underwent CDT for IFDVT. Median follow-up was 35.9 months. Sixty-eight patients (91%) had no evidence of recurrence and seven (9%) developed recurrence. Of the patients who had ≥50% (mean 80%) residual thrombus, 50% (4/8) experienced recurrence, but in those with thrombus, only 5% (3/67) had recurrent DVT (P = 0.0014). The burden of residual thrombus at completion of CDT correlates with the risk of DVT recurrence. Patients having CDT for IFDVT had a lower risk of recurrence than expected. Successful clearing of acute clot in IFDVT patients significantly reduces the recurrence risk compared to patients with a large residual thrombus burden. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  14. Severe reversible dilated cardiomyopathy associated with a large left ventricular thrombus in a young child with middle aortic syndrome

    OpenAIRE

    Ponniah, U; Overholt, E

    2014-01-01

    this article reports a case of a seven-year girl who presented with severe dilated cardiomyopathy (DCM) associated with a large thrombus in the left ventricle (LV). She had a long segment stenosis of the lower thoracic descending aorta, possibly due to non-specific aortitis and underwent successful stent angioplasty. The LV thrombus resolved after heparin without sequelae.

  15. Surgical Treatment of Renal Cell Carcinoma with Inferior Vena Cava Thrombus: Using Liver Mobilization Technique to Avoid Cardiopulmonary Bypass

    Directory of Open Access Journals (Sweden)

    Tawatchai Taweemonkongsap

    2008-04-01

    CONCLUSION: These results support the aggressive surgical removal of RCC with IVC thrombus as the initial treatment. Most of the thrombi can be approached and safely controlled by a transabdominal approach without any form of bypass. Tumour thrombus removal provides a high survival chance and offers improvement in quality of life.

  16. Combined Primary Neuroendocrine Carcinoma and Hepatocellular Carcinoma of the Liver

    Directory of Open Access Journals (Sweden)

    Chii-Shuenn Yang

    2009-08-01

    Full Text Available We report a unique case of combined primary neuroendocrine carcinoma (NEC and hepatocellular carcinoma (HCC of the liver in a 65-year-old male patient. The patient underwent segmental resection of the liver and regional lymph node dissection for a tumor mass that measured 7.5 cm in diameter in the right lobe, with regional lymphadenopathy. Histologically, the hepatic tumor was composed of predominantly small-cell NEC, but admixed with a small island of moderately differentiated HCC. We speculate that the NEC originated from a poorly differentiated tumor clone of an HCC that underwent neuroendocrine differentiation, and that this tumor was now at the end stage of the transitional period from HCC to NEC, based on the small amount of disappearing HCC. Ki-67 and p53 expression were higher in the NEC than in the HCC, and the lymph nodes showed only metastatic NEC. Therefore, this kind of tumor had a more aggressive clinical course in accordance with being an NEC rather than a conventional HCC. Three months after operation, the patient had multiple recurrent tumor nodules within the liver, spreading the metastasis to the adrenal glands and para-aortic lymph nodes. The patient died 1 year after operation.

  17. CT findings of exophytic hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Intraarterial digital subtraction angiography applied to diagnosis of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishizawa, Sadahiko; Sano, Akira; Imanaka, Kazufumi; Sasai, Keisuke; Nagae, Toshiyuki; Mizutani, Masaru; Hatabu, Hiroto; Sadatou, Norihiro; Kuroda, Yasumasa

    1985-12-01

    This paper deals with diagnostic values of intraarterial digital subtraction angiography (IADSA) for evaluating hepatocellular carcinoma. The present series consists of 44 patients with hepatocellular carcinoma, who underwent IADSA combined with conventional hepatic angiography 67 times in total. The evaluated vessels by IADSA included 70 hepatic arteries and 36 portal veins. Comparative studies on the image quality of IADSA with conventional angiography were made in referring to the tumor stain for arteriograms and resolution of intrahepatic portal branches for portograms. Diagnostic superiority including equality of DSA image to conventional was noted in arteriograms: 72.7 % in the right lobe and 86 % in the left. Most deteriorated DSA images were caused by misregistration artifacts. IADSA portography revealed basically diagnostic values to demonstrate lobar, segmental or more peripheral branches in about 95 % of cases studied. DSA, characterized by high contrast resolution and real-time subtraction, offered important and effective informations for interventional angiography as well as resectability of the tumors, requiring less contrast medium.

  19. 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.

  20. Intra-arterial injection of iodine-131-labeled lipiodol for treatment of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Boucher, Eveline; Garin, Etienne; Guylligomarc'h, Anne; Olivie, Damien; Boudjema, Karim; Raoul, Jean-Luc

    2007-01-01

    Background/Aim: The therapeutic effect of intra-arterial injection of 131-iodine-labeled lipiodol for treatment of hepatocellular carcinoma in palliative or adjuvant settings has been promising. We report, the results of an open study of this therapy in cirrhotic patients with small hepatocellular carcinoma. Patients and method: Forty patients with hepatocellular carcinoma were given intra-arterial injections of 131-iodine-labeled lipiodol. These injections were repeated if necessary every 3 months. Tumor response (WHO criteria) was determined on CT scans performed after each treatment and every 3 months during the follow-up. Side effects and the cause of death were recorded. Therapeutic response and survival were analyzed. Results: The median number of treatment was 2 (1-4). There was one complete response, 18 partial responses (47.5% response rate); 19 had stable disease and 2 progressions. Overall survival rates (±CI 95%) at 1, 2 and 3 years were: 90 ± 4.7%, 60.3 ± 8%, and 39 ± 8.3%, respectively. Median survival was 27 months; 25 patients have died (4-56 months), 8 of tumor progression with a multifocal spread in the liver. Tolerance was good except for 2 patients who develop a fatal drug-related pulmonary insufficiency. Conclusion: These data suggest that intra-arterial therapeutic injection of 131-iodine-labeled lipiodol for treatment of hepatocellular carcinoma can provide high rate response and long survival for individuals not eligible for surgery or local treatment

  1. Silencing the Girdin gene enhances radio-sensitivity of hepatocellular carcinoma via suppression of glycolytic metabolism.

    Science.gov (United States)

    Yu, Li; Sun, Yifan; Li, Jingjing; Wang, Yan; Zhu, Yuxing; Shi, Yong; Fan, Xiaojun; Zhou, Jianda; Bao, Ying; Xiao, Jie; Cao, Ke; Cao, Peiguo

    2017-08-15

    Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the radio-sensitivity of hepatocellular carcinoma remains unclear. A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression. Then, cell proliferation, colony formation, flow cytometric, scratch, and transwell assays were to examine the influence of Girdin silencing on cellular radiosensitivity. Glycolysis assays were conducted to exam cell glycolysis process. Western blotting was performed to explore the signaling pathway downstream of Girdin. Finally, animal experiments were performed to demonstrate the effect of CCDC88A silencing on the radiosensitivity of hepatoma in vivo. shRNA-induced Girdin silencing suppressed glycolysis and enhanced the radio-sensitivity of hepatic cell lines, HepG2 and Huh-7. Furthermore, silencing of Girdin inhibited the PI3K/AKT/HIF-1α signaling pathway, which is a central regulator of glycolysis. Girdin can regulate glycolysis in hepatocellular carcinoma cells through the PI3K/AKT/HIF-1α signaling pathway, which decreases the sensitivity of tumor cells to radiotherapy.

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    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

  4. 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

  5. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Laura Santangelo

    2017-01-01

    Full Text Available Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA from donor to recipient cells. Notably, tumor-derived exosomes (TDEs appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC, the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined.

  6. Research progress in c-Met and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    WANG Changqing

    2015-06-01

    Full Text Available c-Met plays a pivotal role in the development and progression of hepatocellular carcinoma (HCC, which can lead to proliferation, survival, cytoskeleton reorganization, separation and diffusion, and angiogenesis of tumor cells. Moreover, c-Met is an important prognostic factor for HCC. In HCC, c-Met acts as an activator of a series of signaling pathways, including PI3K/AKT/mTOR, ERK/MAPK, and Rac-Pak. In recent years, it has been reported that small-molecule kinase inhibitors can abolish phosphorylation at the intracellular carboxyl terminal of c-Met, and then inhibit the recruitment of signal convertors and downstream signaling pathways, which finally achieve anti-tumor activities. Based on the carcinogenic activity of c-Met in HCC, this paper points out that selective inhibitors of c-Met hold promise for targeted therapies for HCC.

  7. Y-90 microshperes in the treatment of unresectable hepatocellular carcinoma.

    Science.gov (United States)

    Al-Kalbani, Abdullah; Kamel, Yasser

    2008-04-01

    A small percentage of patients with hepatocellular carcinoma (HCC) are candidates for curative treatment in form of resection or transplantation. There are different treatment options for unresectable HCC-like local ablative therapies and recently systemic therapy with Sorafenib. All of these have variable response rate and had been proven to improve survival. In the last few years, there is a growing interest in TheraSphere radioembolization. It consists of yttrium90 (Y-90) embedded into nonbiodegradable glass microspheres. It is selectively administered by intraarterial hepatic injection giving high doses of radiation to the tumor and sparing the liver parenchyma. It has been shown to improve survival and used as a bridge to transplantation and to downstage tumors for resection. Therasphere seems to have favorable safety profile and has been used in patients with portal vein thrombosis with successful outcome.

  8. CYCLOOXYGENASE-2 AND HEPATOCELLULAR CARCINOMA: THE PROTEOMICS OF ASSOCIATION

    Directory of Open Access Journals (Sweden)

    Jaya Gandhi

    2011-12-01

    Full Text Available Hepatocellular carcinoma represents one of the most common malignancies worldwide with a rising incidence in western countries. Chronic inflammation is recognised as a threat factor for cancer progression. Cyclooxygenase-2 is the major mediator of inflammation. Various studies on Cox-2 suggest its possible association with HCC differentiation. Sufficient genetic and pharmacologic evidences implicate its crucial role in neoplasia and it is also now clear that Cox-2 plays a crucial role in tumor progression. Cox-2 overexpression is associated with maintaining tumor microenvironment and has crucial implication for angiogenesis. Cox-2 operates in multifactorial fashion. Cox-2 selective inhibition has been reported as a successful tool in suppressing angiogenesis and metastasis. The pharmacological suppression of Cox-2 represents a bright future as a therapeutic tool for treatment of various malignancies. This review is an attempt to discuss the critical issue of overexpression of Cox-2 and its role in the development of HCC in particular and cancer in general.

  9. Hemodynamic characteristics of early stage hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kudo, Masatoshi; Tomita, Shusuke; Tochio, Hitoshi

    1992-01-01

    Hemodynamic characteristics were studied by using in vivo vascular imaging techniques in 17 resected early stage hepatocellular carcinoma (e-HCC) by comparing them with 49 resected advanced HCCs (ad-HCC) less than 3 cm in diameter. In this study, e-HCC was defined as the nodule being uniformly composed of well-differentiated HCC or adenomatous hyperplastic nodule containing well-differentiated HCC foci within the nodule. In vivo vascular imaging techniques are as follows; US angiography with intraarterial CO 2 microbubbles were performed to assess the tumor arterial vascularity, and CT during arterial portography (CTAP) was performed to assess the portal perfusion within the nodule. Of 17 e-HCC nodules 5 were hypervascular, 5 were isovascular, 4 were hypovascular, and 3 were vascular spot in hypovascular pattern in contrast to 49 ad-HCC nodules, 43 of which were hypervascular and 6 were isovascular. Of 14 e-HCCs, 9 nodules showed perfusion defect and 5 did not on CTAP, whereas all 37 ad-HCCs on which CTAP was performed, showed perfusion defect. Forty-one percent (7/17) of e-HCC showed fatty metamorphosis in contrast to 8% (4/49) of ad-HCC. In conclusion, hemodynamic characteristics of e-HCC are summarized as follows. (1) Arterial tumor neovascularization is relatively low. (2) Portal perfusion is present in some of e-HCC cases. (3) Hypoperfusion state both from arterial and portal supply is present in some of e-HCC cases. (4) Vascular spot in hypovascular pattern is characteristic arterial pattern in AH containing HCC foci. (5) Fatty metamorphosis may be related with hypoperfusion state of the nodule in e-HCC. (author)

  10. Clinical evaluation of high-resolution CT, 1. CT diagnosis of liver tumors and its limit

    Energy Technology Data Exchange (ETDEWEB)

    Araki, T [Tokyo Univ. (Japan). Faculty of Medicine

    1980-03-01

    To estimate diagnostic accuracy of CT in liver tumors, CT diagnosis in 120 patients with primary hepatocellular carcinoma was discussed. As a result, primary hepatocellular carcinoma less than 2 cm in diameter could not be visualized by CT. Even tumors between 4 and 8 cm in diameter showed false negative caused by isodense tumors on images of 4 patients. To improve the detectability of liver tumors by CT, the higher resolution of low contrast regions on images are required. As a method to improve qualitative diagnosis of liver tumors, rapid intravenous injection of contrast medium was performed on 42 patients with liver tumors, As a result, images reflecting vascularity of tumors were obtained, and the differential diagnosis was possible to some extent by observing the movement of the contrast. Especially, cavernous hemangioma could be distinguished from hepatocellular carcinoma, because cavernous hemangioma showed specific images and could be diagnosed accurately.

  11. CBT-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors

    Science.gov (United States)

    2018-02-07

    Solid Tumor; Advanced Cancer; ColoRectal Cancer; Endometrial Cancer; Gastric Cancer; Hepatocellular Cancer; Nonsmall Cell Lung Cancer; Mesothelioma; Ovarian Cancer; Renal Cancer; Nasopharyngeal Cancer; Esophageal Cancer; Gastroesophageal Junction Adenocarcinoma

  12. 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.

  13. Evaluation of Photoelectron Therapy Effect on Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    bahram Mofid

    2007-10-01

    Full Text Available Mofid B1, Navabpoor M2, Alizadeh Azimi M3 1. Assistant professor, Department of Radiotherapy, Faculty of Para-Medicine, Shahid Beheshti University of medical sciences 2. Instructor, Department of Technology of radiology, Faculty of Para-Medicine, Shahid Beheshti University of medical sciences Abstract Background: Photoelectron therapy method has been usad successfully, on the body phantom, cancer cells culture and animals. In this method, drugs containing x-Ray opaque factors–with high atomic numbers–are injected into the patient’s vein. After appropriate drug accumulation, about at least ten percent of the total injected amounts, 200kev. up to 300kev. of localized x-Ray beams is radiated to the site of the tumor. The Ethic Committee of Shahid Beheshti University of Medical Education and Health Services authorized the implementation of this new cancer treatment method, initially only on the group of patients who suffered from hepato-cellular carcinoma. Hepato cellular carcinoma is one of the most current malignancies of liver. In some cases, in addition to surgery, several approaches exist to come near the aim of predominating hepato-cellular carcinoma such as chemotherapy, current Radiation Therapy, Radio-Frequency application (RF, Trans-Artepical Chemo Embolization, (TACE, and Percutaneous Ethanol Injection (PEI. The effectiveness of the above-mentioned methods is about 10%-47%, applied alone or along side each other. Materials and methods: This study was a clinical-trial one. In this study, first, lipiodol (an x-ray opaque material with a high atomic number was transferred into the main vessel terminating to the tumor by angio-catheterization. Then,200kev. up to 250kev. of localized x-ray was radiated to the site of the tumor in one session. The drug volume was proportionally selected to the volume of the tumor, and the irradiation intensity was between 400 to 600cent.Gy. the beam energy absorption capacity of this drug is as times as

  14. 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.

  15. Contrast-enhanced dynamic magnetic resonance imaging findings of hepatocellular carcinoma and their correlation with histopathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Karahan, Okkes I. [Department of Radiology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey)]. E-mail: oikarahan@yahoo.com; Yikilmaz, Ali [Department of Radiology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey); Artis, Tarik [Department of General Surgery, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey); Canoz, Ozlem [Department of Pathology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey); Coskun, Abdulhakim [Department of Radiology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey); Torun, Edip [Department of Internal Medicine, Division of Gastrenterology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey)

    2006-03-15

    Purpose: To investigate the correlations of contrast-enhanced magnetic resonance (MR) imaging findings of large (>5 cm) hepatocellular carcinomas with tumor size and histopathologic findings. Materials and methods: MR imaging was performed in 30 patients with a histopathologic diagnosis of hepatocellular carcinoma. The imaging protocol included non-contrast, hepatic arterial, portal venous and late phases. The signal intensities relative to the liver, enhancement patterns and the morphologic features of the lesions were evaluated in relation to size and degree of differentiation. Results: On histopathologic examination, 12 of 30 (40%) tumors were well-differentiated (grade 1), 6 of 30 (20%) were moderately differentiated (grades 2 and 3) and 12 of 30 (40%) were poorly differentiated (grade 4). Tumor size, tumor boundary, serum alpha-fetoprotein level and portal vein invasion were found to have statistically significant correlations with the degree of differentiation (p < 0.05). Portal vein invasion, capsule formation and tumor surface characteristics showed statistically significant correlations with tumor size (p < 0.05). Conclusion: MR imaging findings of hepatocellular carcinomas larger than 5 cm are partially dependent on tumor size and degree of differentiation.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

    Science.gov (United States)

    Faltermeier, Claire; Busuttil, Ronald W.; Zarrinpar, Ali

    2015-01-01

    Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC. PMID:28943622

  1. The multifaceted role of podoplanin expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Andreea Cioca

    2017-02-01

    Full Text Available The role of podoplanin in hepatocellular carcinoma (HCC is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD was increased in patients who had vascular invasion at the time of diagnosis (P=0.018 and in those with associated cirrhosis (P=0.006. Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040. Podoplanin-expressing cancer associated fibroblasts (CAFs were correlated with both LVD (P=0.019 and tumor cells (P=0.015. Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation.

  2. The multifaceted role of podoplanin expression in hepatocellular carcinoma.

    Science.gov (United States)

    Cioca, Andreea; Ceausu, Amalia R; Marin, Irina; Raica, Marius; Cimpean, Anca M

    2017-02-13

    The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P=0.006). Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040). Podoplanin-expressing cancer associated fibroblasts (CAFs) were correlated with both LVD (P=0.019) and tumor cells (P=0.015). Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation.

  3. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Claire Faltermeier

    2015-09-01

    Full Text Available Hepatocellular carcinoma (HCC, the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC.

  4. Mechanism and significance of let-7 in diagnosis and treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    HUO Tingting

    2017-07-01

    Full Text Available Abstract:MicroRNA (miRNA play important roles in post-transcriptional gene regulation. In recent years, miRNA has become a hot topic in the research on the development and progression of tumors, and gene targeting therapy for malignant tumors has achieved preliminary progress. As one of the first discovered miRNA, let-7 can regulate the cell cycle and angiogenesis and is involved in the proliferation, differentiation, and apoptosis of various tumor cells. Most members of the let-7 family can act as tumor suppressor gene and have low expression in various tumor tissues and high expression in the serum of patients with malignant tumors. Let-7 is closely associated with the invasion and drug resistance of hepatocellular carcinoma (HCC. The studies above show that let-7 might become a new marker for the early diagnosis of HCC and provide new targets for the treatment of HCC.

  5. Renal Angiomyolipoma Associated with Inferior Vena Cava Thrombus

    Directory of Open Access Journals (Sweden)

    Xavier Durand

    2009-01-01

    Full Text Available A 57-year-old woman was found to have an inferior vena cava involvement of a known sinusal angiomyolipoma incompletely resected three years beforehand. Intravascular extension into the IVC of angiomyolipoma has rarely been reported. We present a new case and reconsider the literature about this uncommon complication of a benign renal tumor.

  6. Thrombus Development on a Transseptal Sheath in the Right Atrium Before Electrical Pulmonary Vein Isolation

    Directory of Open Access Journals (Sweden)

    Nieves Romero-Rodriguez

    2008-02-01

    Full Text Available We describe the case of a patient who developed a thrombus on the transseptal sheath in the right atrium before transseptal puncture for circumferential pulmonary vein isolation for paroxysmal atrial fibrillation treatment. The use of intracardiac echocardiography allowed to its identification and probably prevented the patient from suffering a serious thromboembolic complication.

  7. Large mobile thrombus in non-atherosclerotic thoracic aorta as the source of peripheral arterial embolism

    Directory of Open Access Journals (Sweden)

    Brkovic Zoran

    2005-11-01

    Full Text Available Abstract The presence of thrombi in the atherosclerotic and/or aneurysmatic aorta with peripheral arterial embolism is a common scenario. Thrombus formation in a morphologically normal aorta, however, is a rare event. A 50 years old woman was admitted to the mergency department for pain, coldness, and anesthesia in the the left foot. She had a 25 years history of cigarette smoking, a history of postmenopausal hormone replacement therapy (HRT, hypercholesterolemia and hyperfibrinogenemia. An extensive serologic survey for hypercoagulability, including antiphospholipid antibodies, and vasculitis disorders was negative. Transesophageal echocardiography revealed a large, pedunculated and hypermobile thrombus attached to the aortic wall 5 cm distal of the left subclavian artery. The patient was admitted to the surgery department, where a 15 cm long fresh, parietal thrombus could be removed from the aorta showing no macroscopic wall lesions or any other morphologic abnormalities. This case report demonstrates the possibility of evolving a large, pedunculated thrombus in a morphologically intact aorta in a postmenopausal woman with thrombogenic conditions such as hyperfibrinogenemia, hypercholesterolemia, smoking and HRT. For these patients, profiling the individual risk and weighing the benefits against the potential risks is warranted before prescribing HRT.

  8. Role of newly formed platelets in thrombus formation in rat after clopidogrel treatment

    DEFF Research Database (Denmark)

    Kuijpers, Marijke J E; Megens, Remco T A; Nikookhesal, Elham

    2011-01-01

    Platelet P2Y₁₂ receptors play an important role in arterial thrombosis by stimulating thrombus growth. Both irreversibly (clopidogrel) and reversibly binding (ticagrelor, AZD6140) P2Y₁₂ antagonists are clinically used for restricted periods, but possible differences in platelet function recovery ...

  9. Saphenous vein graft thrombus findings by scanning electron microscopy in a patient with acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Marcela Dias; Aguillera, André Haraguti [Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Brilhante, José Joaquim; Caixeta, Adriano [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

    2013-07-01

    An eighty-year-old male patient with a history of prior (19 years) coronary artery bypass graft surgery was admitted to the hospital with non ST-segment elevation myocardial infarction (NSTEMI). During the hospital stay he was taking acetylsalicylic acid 100mg per day, a loading dose of 600mg clopidogrel, and low molecular weight heparin 1mg/kg twice a day. Twenty-four hours later the patient underwent coronary angiography, which showed a 90% obstruction in the mid portion of the saphenous vein graft to obtuse marginal with signs of degeneration and local thrombus (Figure 1). Thrombus aspiration was performed with a 6-Fr Export{sup ™} catheter (Medtronic, Santa Rosa, CA, USA), which removed small reddish colored fragments. They were fixed in 2,5% glutaraldehyde in a 0.1M sodium cacodilate buffer. The material was processed following the GOTO protocol in which the fragments were washed with osmium tetroxide and titanic acid, after which they were dried in a critical-point device and a golden bath. Scanning electron microscopy and high definition photos (3,000 to 27,221x magnification) were obtained by the FEI Quanta{sup ™} FEG SEM device (FEI Company, Hillsboro, OR, USA). The images showed that the thrombus was rich in activated platelets, with few erythrocytes or inflammatory cells. Many cholesterol crystals were observed (Figures 2 to). The fibrin networks were sparse and thin, which is compatible with a short ischemic time and recent thrombus formation.

  10. Systematic Review of Treatment for Trapped Thrombus in Patent Foramen Ovale.

    Science.gov (United States)

    Seo, Won-Woo; Kim, Sung Eun; Park, Myung-Soo; Lee, Jun-Hee; Park, Dae-Gyun; Han, Kyoo-Rok; Oh, Dong-Jin

    2017-09-01

    Trapped thrombus in patent foramen ovale (PFO) is a rare complication of pulmonary embolism that may lead to tragic clinical events. The aim of this study was to identify the optimal treatment for different clinical situations in patients with trapped thrombus in a PFO by conducting a literature review. A PubMed database search was conducted from 1991 through 2015, and 194 patients (185 articles) with trapped thrombus in a PFO were identified. Patient characteristics, paradoxical embolic events, and factors affecting 60-day mortality were analyzed retrospectively. Among all patients, 112 (57.7%) were treated with surgery, 28 with thrombolysis, and 54 with anticoagulation alone. Dyspnea (79.4%), chest pain (33.0%), and syncope (17.5%) were the most common presenting symptoms. Pretreatment embolism was found in 37.6% of cases, and stroke (24.7%) was the most common event. Surgery was associated with fewer post-treatment embolic events than were other treatment options (p=0.044). In the multivariate analysis, initial shock or arrest, and thrombolysis were independent predictors of 60-day mortality. Thrombolysis was related with higher 60-day mortality compared with surgery in patients who had no initial shock or arrest. This systematic review showed that surgery was associated with a lower overall incidence of post-treatment embolic events and a lower 60-day mortality in patients with trapped thrombus in a PFO. In patients without initial shock or arrest, thrombolysis was related with a higher 60-day mortality compared with surgery.

  11. Early Heparin Administration Reduces Risk for Left Atrial Thrombus Formation during Atrial Fibrillation Ablation Procedures

    Directory of Open Access Journals (Sweden)

    Stefan Asbach

    2011-01-01

    Full Text Available Objective. Despite the use of anticoagulation during left atrial (LA ablation procedures, ischemic cerebrovascular accidents (CVAs are recognized as a serious complication. Heparin is usually given after safe transseptal access has been obtained, resulting in a short unprotected dwell time of catheters within the LA, which may account for CVAs. We investigated the frequency of CVAs and LA thrombus formation as detected by intracardiac ultrasound (ICE depending on the timing of heparin administration. Methods and Results. Sixty LA ablation procedures with the use of ICE were performed in 55 patients. Patients were grouped by heparin administration after (Group I, =13 and before (Group II, =47 transseptal access. Group I patients were younger (56.6±13.7 versus 65.9±9.9 years, =.01; other clinical and echocardiographic characteristics did not differ between groups. Early thrombus formation was observed in 2 (15.4% of group I patients as compared to 0% of group II patients (=.04. One CVA (2.1% occurred in one group II patient without prior thrombus detection, and none occurred in group I patients (=ns. Conclusion. Early administration of heparin reduces the risk of early intracardiac thrombus formation during LA ablation procedures. This did not result in reduced rate of CVAs.

  12. CORONARY EMBOLISM WITH FRAGMENTED THROMBUS FROM THE LEFT VENTRICLE IN PATIENT WITH POSTINFARCTION ANEURYSM

    Directory of Open Access Journals (Sweden)

    Yu. F. Salakhova

    2011-01-01

    Full Text Available The thrombus formation in the left ventricle (LV cavity is a frequent complication of myocardial infarction (MI as well as a risk factor for peripheral arterial embolism. Probability of intraventricular thrombus depends on MI location and its therapy. A case of coronary embolism in a patient with anterior MI and thrombus in the LV aneurysm is considered in details. Successful percutaneous coronary intervention (PCI in the first 90 minutes after admission was performed. Decision to appoint a three-component antithrombotic therapy (acetylsalicylic acid, clopidogrel, warfarin was made on the 4th day of disease onset taking into account the combination of MI, stent placement in the anterior interventricular artery and the presence of left ventricular aneurysm with parietal thrombus. Recurrence of MI developed on the 9th day of disease onset. Aspiration thromboembolectomy was performed taking into account thrombosis of two coronary arteries. Warfarin therapy was discontinued in connection with subsequent clot lysis and development of not intensive nosebleed. Subsequent MI course was uneventful. In conclusion, even in spite of the timely achievement of PCI and early reperfusion, MI course can be complicated by thrombosis of the left ventricle and subsequent development of thromboembolic complications.

  13. Greenfield filter caval perforation causing an aortic mural thrombus and femoral artery occlusion.

    Science.gov (United States)

    Chintalapudi, U B; Gutierrez, O H; Azodo, M V

    1997-05-01

    A 32-year-old woman suffered a right femoral artery embolic occlusion from an abdominal aortic mural thrombus associated with caval perforation by a stainless steel Greenfield Filter. The complication required thrombolytic therapy, surgical revascularization, and long-term anticoagulation.

  14. Saphenous vein graft thrombus findings by scanning electron microscopy in a patient with acute myocardial infarction

    International Nuclear Information System (INIS)

    Borges, Marcela Dias; Aguillera, André Haraguti; Brilhante, José Joaquim; Caixeta, Adriano

    2013-01-01

    An eighty-year-old male patient with a history of prior (19 years) coronary artery bypass graft surgery was admitted to the hospital with non ST-segment elevation myocardial infarction (NSTEMI). During the hospital stay he was taking acetylsalicylic acid 100mg per day, a loading dose of 600mg clopidogrel, and low molecular weight heparin 1mg/kg twice a day. Twenty-four hours later the p